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  1. Bone marrow transplant

    MedlinePlus

    Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical ...

  2. Bone marrow transplant - discharge

    MedlinePlus

    Transplant - bone marrow - discharge; Stem cell transplant - discharge; Hematopoietic stem cell transplant - discharge; Reduced intensity; Non-myeloablative transplant - discharge; Mini transplant - discharge; Allogenic bone marrow transplant - ...

  3. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a person's ...

  4. Bone-marrow transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100112.htm Bone-marrow transplant - series—Normal anatomy To use the sharing ... Go to slide 4 out of 4 Overview Bone-marrow is a soft, fatty tissue found inside of ...

  5. Transplant Outcomes (Bone Marrow and Cord Blood)

    MedlinePlus

    ... reports show patient survival and transplant data of bone marrow and umbilical cord blood transplants in the transplant ... Data by Center Report —View the number of bone marrow and cord blood transplants performed at a specific ...

  6. Bone marrow transplant – children - discharge

    MedlinePlus

    Transplant - bone marrow - children - discharge; Stem cell transplant - children - discharge; Hematopoietic stem cell transplant -children - discharge; Reduced intensity, non-myeloablative transplant - children - discharge; Mini transplant - children - discharge; Allogenic bone ...

  7. Planning for a Bone Marrow Transplant (BMT)

    MedlinePlus

    ... us Digg Facebook Google Bookmarks Planning for a Bone Marrow Transplant (BMT) If you're going to have ... to a friend or family member undergoing a bone marrow or cord blood transplant. Help Your Loved One ...

  8. Allogeneic and Autologous Bone-Marrow Transplantation

    PubMed Central

    Deeg, H. Joachim

    1988-01-01

    The author of this paper presents an overview of the current status of bone marrow transplantation, including indications, pre-transplant considerations, the transplant procedure, acute and delayed transplant-related problems, results currently attainable, and a short discussion of possible future developments. PMID:21253121

  9. Understanding Bone Marrow Transplantation as a Treatment Option

    MedlinePlus

    ... you have had, and your overall health. Transplant Process A bone marrow or cord blood transplant is ... The Transplant Process . For more about the search process, HLA matching, and steps of a transplant, such ...

  10. [Prolonged acute pancreatitis after bone marrow transplantation].

    PubMed

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  11. Bone Marrow Transplantation for Feline Mucopolysaccharidosis I

    PubMed Central

    Ellinwood, N. Matthew; Colle, Marie-Anne; Weil, Margaret A.; Casal, Margret L.; Vite, Charles H.; Wiemelt, Staci; Hasson, Christopher W.; O’Malley, Thomas M.; He, Xingxuan; Prociuk, Ulana; Verot, Lucie; Melniczek, John R.; Lannon, Anne; Aguirre, Gustavo D.; Knox, Van W.; Evans, Sydney M.; Vanier, Marie T.; Schuchman, Edward H.; Walkley, Steven U.; Haskins, Mark E.

    2009-01-01

    Severe mucopolysaccharidosis type I (MPS I) is a fatal neuropathic lysosomal storage disorder with significant skeletal involvement. Treatment involves bone marrow transplantation (BMT), and although effective, is suboptimal, due to treatment sequelae and residual disease. Improved approaches will need to be tested in animal models and compared to BMT. Herein we report on bone marrow transplantation to treat feline mucopolysaccharidosis I (MPS I). Five MPS I stably engrafted kittens, transplanted with unfractionated bone marrow (6.3 × 107 to 1.1 × 109 nucleated bone marrow cells per kilogram) were monitored for 13–37 months post-engraftment. The tissue total glycosaminoglycan (GAG) content was reduced to normal levels in liver, spleen, kidney, heart muscle, lung, and thyroid. Aorta GAG content was between normal and affected levels. Treated cats had a significant decrease in the brain GAG levels relative to untreated MPS I cats and a paradoxical decrease relative to normal cats. The α-L-iduronidase (IDUA) activity in the livers and spleens of transplanted MPS I cats approached heterozygote levels. In kidney cortex, aorta, heart muscle, and cerebrum, there were decreases in GAG without significant increases in detectable IDUA activity. Treated animals had improved mobility and decreased radiographic signs of disease. However, significant pathology remained, especially in the cervical spine. Corneal clouding appeared improved in some animals. Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT. PMID:17482862

  12. Ocular complications of bone marrow transplantation.

    PubMed

    Livesey, S J; Holmes, J A; Whittaker, J A

    1989-01-01

    Thirty-four patients who had undergone bone marrow transplantation (BMT) were examined; 83.3% of those who received single shot and none of those who received fractionated total body irradiation (TBI) developed cataracts. The use of steroids to treat chronic Graft Versus Host Disease (GVHD) produced more severe cataracts in those who had allogeneic transplants after single shot TBI, but follow-up has not been long enough to assess their effect following fractionated TBI. Keratoconjunctivitis sicca (KCS) was seen in 81.8% of patients with chronic GVHD and in 33.3% of patients after autologous BMT. PMID:2693135

  13. Bone marrow transplantation in sickle cell anaemia.

    PubMed Central

    Vermylen, C; Cornu, G; Philippe, M; Ninane, J; Borja, A; Latinne, D; Ferrant, A; Michaux, J L; Sokal, G

    1991-01-01

    Sickle cell anaemia is still responsible for severe crippling and death in young patients living in developing countries. Apart from prophylaxis and treatment of infections, no active treatment can be safely proposed in such areas of the world. Therefore a bone marrow transplantation was performed in 12 patients staying in Belgium and planning to return to Africa. Twelve patients, aged between 11 months and 23 years (median 4 years), underwent a HLA identical bone marrow transplantation. The conditioning regimen included oral busulphan for four consecutive days (4 mg/kg) followed by four days of intravenous cyclophosphamide (50 mg/kg). In 10 patients the engraftment was rapid and sustained. A further patient suffered transient red cell hypoplasia and another underwent a second bone marrow transplantation from the same donor at day 62 because of graft rejection. All patients are alive and well with a follow up ranging from 9-51 months (median 27 months). In all cases a complete cessation of vaso-occlusive episodes and haemolysis was observed as was a change in the haemoglobin pattern in accordance with the donor's electrophoretic pattern. PMID:1953001

  14. Glutamine supplementation in bone marrow transplantation.

    PubMed

    Ziegler, Thomas R

    2002-01-01

    An increasing number of clinical investigations have focused on supplementation of specialized enteral and parenteral nutrition with the amino acid glutamine. This interest derives from strong evidence in animal models and emerging clinical data on the efficacy of glutamine administration following chemotherapy, trauma, sepsis and other catabolic conditions. Glutamine has protein-anabolic effects in stressed patients and, among many key metabolic functions, is used as a major fuel/substrate by cells of the gastrointestinal epithelium and the immune system. These effects may be particularly advantageous in patients undergoing bone marrow transplantation (BMT), who exhibit post-transplant body protein wasting, gut mucosal injury and immunodeficiency. Studies to date indicate that enteral and parenteral glutamine supplementation is well tolerated and potentially efficacious after high-dose chemotherapy or BMT for cancer treatment. Although not all studies demonstrate benefits, sufficient positive data have been published to suggest that this nutrient should be considered as adjunctive metabolic support of some individuals undergoing marrow transplant. However, BMT is a rapidly evolving clinical procedure with regard to the conditioning and supportive protocols utilized. Thus, additional randomized, double-blind, controlled clinical trials are indicated to define the efficacy of glutamine with current BMT regimens.

  15. Functional hyposplenism following allogeneic bone marrow transplantation.

    PubMed Central

    Cuthbert, R J; Iqbal, A; Gates, A; Toghill, P J; Russell, N H

    1995-01-01

    AIMS--To investigate the incidence of functional hyposplenism in a group of patients who had undergone allogeneic bone marrow transplantation (BMT). METHODS--Splenic function was assessed by counting the number of gluteraldehyde fixed red blood cells containing pits or indentations as examined by interference phase microscopy. Normal values are < 2% whereas splenectomy patients have values of 25 to 40%. RESULTS--Twenty eight BMT recipients (17 men, 11 women) were studied at varying periods post-transplant and the results compared with 20 healthy volunteers and 10 patients who had undergone splenectomy or had splenic atrophy because of haematological conditions. Of the 28 BMT recipients, one had undergone a prior splenectomy; of the remaining 27 patients, four (15%) had evidence of functional hyposplenism with between 5.0 and 34.0% pitted cells. Of these four patients, one had active extensive chronic graft versus host disease (GvHD) which has been previously reported to be associated with functional hyposplenism following transplantation. Only one of the four patients had peripheral blood red cell changes typical of hyposplenism. CONCLUSION--These results confirm that extensive chronic GvHD is associated with hyposplenism. Intermediate degrees of functional hyposplenism may also occur following BMT in the absence of chronic GvHD and in the absence of haematological features of hyposplenism on routine blood films. This may be of significance in mediating the susceptibility to infection with encapsulating bacteria seen following allogeneic BMT. PMID:7730489

  16. Late pulmonary sequelae after childhood bone marrow transplantation

    PubMed Central

    Cerveri, I.; Zoia, M.; Fulgoni, P.; Corsico, A.; Casali, L.; Tinelli, C.; Zecca, M.; Giorgiani, G.; Locatelli, F.

    1999-01-01

    BACKGROUND—Respiratory function in transplanted children is important because of the long life expectancy of bone marrow transplant recipients, particularly children. Attention is now being focused on the late sequelae of treatment on organ system function. A few papers have been published but available data are somewhat conflicting.
METHODS—A cross sectional study aimed at evaluating the late effects of transplantation on lung function was performed in a group of 52 young patients who were given autologous or allogeneic bone marrow transplants during childhood for haematological malignancies.
RESULTS—No patients reported chronic respiratory symptoms. The distribution of respiratory function patterns showed that only 62% of patients had respiratory function within the normal limits; 23% had a restrictive pattern and 15% had isolated transfer factor impairment. The percentage of patients with lung function abnormalities was higher in those who (1) received a bone marrow transplant after two or three complete remissions compared with those who were transplanted immediately after the first remission (54% vs 21%; p<0.02), (2) underwent allogeneic bone marrow transplantation rather than an autologous transplantation (45% vs 26%; p = 0.06), and (3) had a pulmonary infection compared with those without (56% vs 26%; p = 0.07).
CONCLUSIONS—In spite of the absence of chronic respiratory symptoms there is a high prevalence of children with late pulmonary sequelae after bone marrow transplantation. Regular testing is recommended after transplantation, in particular in subjects at higher risk of lung injuries, such as those receiving transplants after more than one remission, those receiving allogeneic transplants, and those having suffered from pulmonary infections. When lung function abnormalities become apparent, long term follow up is necessary to see whether they become clinically relevant. All patients should remain non-smokers after transplantation and

  17. Bone marrow processing for transplantation using Cobe Spectra cell separator.

    PubMed

    Veljković, Dobrila; Nonković, Olivera Šerbić; Radonjić, Zorica; Kuzmanović, Miloš; Zečević, Zeljko

    2013-06-01

    Concentration of bone marrow aspirates is an important prerequisite prior to infusion of ABO incompatible allogeneic marrow and prior to cryopreservation and storage of autologous marrow. In this paper we present our experience in processing 15 harvested bone marrow for ABO incompatible allogeneic and autologous bone marrow (BM) transplantation using Cobe Spectra® cell separator. BM processing resulted in the median recovery of 91.5% CD34+ cells, erythrocyte depletion of 91% and volume reduction of 81%. BM processing using cell separator is safe and effective technique providing high rate of erythrocyte depletion and volume reduction, and acceptable recovery of the CD34+ cells.

  18. NIH Blood and Marrow Transplant Late Effects Consensus Conference

    Cancer.gov

    This day and a half symposium will bring together experts in blood and marrow transplantation, late effects, and health care delivery to discuss current evidence and knowledge gaps, develop consensus guidelines, and inform future research in the BMT survivor population.

  19. [T lymphocyte receptors after allogenic bone marrow transplantation].

    PubMed

    Vilmer, E; Schumpp, M; Sigaux, F; Boiron, M; Bensussan, A

    1988-01-01

    Following allogeneic bone marrow transplantation, prominent expansion of peripheral T cells (40%) bearing gamma T cell receptor was observed in some patients. Biochemical, functional and molecular analyses were performed to characterize this T cell receptor and to understand its role in the immunodeficient state after transplantation.

  20. Endocrine complications following pediatric bone marrow transplantation.

    PubMed

    Ho, Josephine; Lewis, Victor; Guilcher, Gregory M T; Stephure, David K; Pacaud, Danièle

    2011-01-01

    Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of <18 years of age at the time of allogeneic or autologous BMT for whom 1-year follow-up through the ACH and a chart were available for review were included in the study. Subjects with a pre-existing endocrine condition were excluded. Of the 194 pediatric BMT procedures performed at the ACH between January 1, 1991 and December 31, 2001, 150 complete charts were available for review. Sixty five subjects received follow-up care at other centers and were excluded. Therefore, a total of 85 subjects were included in the review. The prevalence of endocrine complications identified was: primary hypothyroidism 1.2%, compensated hypothyroidism 7.0%, hyperthyroidism 2.4%, hypergonadotrophic hypogonadism 22.4%, abnormal bone density 2.4%, and secondary diabetes mellitus 1.2%. These findings emphasize the need to screen for endocrine system dysfunction, particularly hypergonadotrophic hypogonadism, in children who have undergone BMT. Children need long-term follow-up so that endocrine complications can be diagnosed and treated promptly. PMID:21823531

  1. Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

    PubMed

    Hudspeth, Michelle; Turner, Amy; Miller, Nicole; Lazarchick, John

    2014-05-01

    Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

  2. What to Expect After a Blood and Marrow Stem Cell Transplant

    MedlinePlus

    ... What To Expect After a Blood and Marrow Stem Cell Transplant You’ll stay in the hospital for ... or even months after your blood and marrow stem cell transplant. Your doctors will want to be sure ...

  3. A marker chromosome in post-transplant bone marrow.

    PubMed

    Morsberger, Laura; Powell, Kerry; Ning, Yi

    2016-01-01

    Detection of small supernumerary marker chromosomes in karyotype analysis represents a diagnostic challenge. While such markers are usually detected during cytogenetic studies of constitutional chromosome abnormalities, they have also been found in specimens submitted from patients with acquired malignancies. We report here the detection of a marker chromosome in a bone marrow specimen from a patient who received a bone marrow transplantation. We discuss the importance of proper characterization and interpretation of marker chromosomes in clinical practice. PMID:27252781

  4. Analyzing the cellular contribution of bone marrow to fracture healing using bone marrow transplantation in mice

    SciTech Connect

    Colnot, C. . E-mail: colnotc@orthosurg.ucsf.edu; Huang, S.; Helms, J.

    2006-11-24

    The bone marrow is believed to play important roles during fracture healing such as providing progenitor cells for inflammation, matrix remodeling, and cartilage and bone formation. Given the complex nature of bone repair, it remains difficult to distinguish the contributions of various cell types. Here we describe a mouse model based on bone marrow transplantation and genetic labeling to track cells originating from bone marrow during fracture healing. Following lethal irradiation and engraftment of bone marrow expressing the LacZ transgene constitutively, wild type mice underwent tibial fracture. Donor bone marrow-derived cells, which originated from the hematopoietic compartment, did not participate in the chondrogenic and osteogenic lineages during fracture healing. Instead, the donor bone marrow contributed to inflammatory and bone resorbing cells. This model can be exploited in the future to investigate the role of inflammation and matrix remodeling during bone repair, independent from osteogenesis and chondrogenesis.

  5. Overview of bone marrow and peripheral blood stem cell transplantation.

    PubMed

    Poliquin, C M

    1997-01-01

    Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are treatments used with increasing frequency for a growing number of cancers. As technology develops, so, too, does the complexity of nursing care. In addition, as the number of patients who receive BMT or PBSCT increases, more and more nurses will be involved in their care. Knowledge of what problems to anticipate, comprehensive assessment, clear patient and family education, and strong emotional support provide the key to successful patient management.

  6. TNF-receptor inhibitor therapy for the treatment of children with idiopathic pneumonia syndrome. A joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521).

    PubMed

    Yanik, Gregory A; Grupp, Stephan A; Pulsipher, Michael A; Levine, John E; Schultz, Kirk R; Wall, Donna A; Langholz, Bryan; Dvorak, Christopher C; Alangaden, Keith; Goyal, Rakesh K; White, Eric S; Collura, Jennifer M; Skeens, Micah A; Eid, Saada; Pierce, Elizabeth M; Cooke, Kenneth R

    2015-01-01

    Idiopathic pneumonia syndrome (IPS) is an acute, noninfectious lung disorder associated with high morbidity and mortality after hematopoietic cell transplantation. Previous studies have suggested a role for TNFα in the pathogenesis of IPS. We report a multicenter phase II trial investigating a soluble TNF-binding protein, etanercept (Enbrel, Amgen, Thousand Oaks, CA), for the treatment of pediatric patients with IPS. Eligible patients were < 18 years old, within 120 days after transplantation, and with radiographic evidence of a diffuse pneumonitis. All patients underwent a pretherapy broncho-alveolor lavage (BAL) to establish the diagnosis of IPS. Systemic corticosteroids (2.0 mg/kg/day) plus etanercept (.4 mg/kg twice weekly × 8 doses) were administered. Response was defined as survival and discontinuation of supplemental oxygen support by day 28 of study. Thirty-nine patients (median age, 11 years; range, 1 to 17) were enrolled, with 11 of 39 patients nonevaluable because of identification of pathogens from their pretherapy BAL. In the remaining 28 patients, the median fraction of inspired oxygen at study entry was 45%, with 17 of 28 requiring mechanical ventilation. Complete responses were seen in 20 (71%) patients, with a median time to response of 10 days (range, 1 to 24). Response rates were higher for patients not requiring mechanical ventilation at study entry (100% versus 53%, P = .01). Overall survival at 28 days and 1 year after therapy were 89% (95% confidence interval [CI], 70% to 96%) and 63% (95% CI, 42% to 79%), respectively. Plasma levels of proinflammatory cytokines were significantly increased at onset of therapy, subsequently decreasing in responding patients. The addition of etanercept to high-dose corticosteroids was associated with high response rates and survival in children with IPS.

  7. Neurological complications of bone marrow transplantation in childhood.

    PubMed

    Wiznitzer, M; Packer, R J; August, C S; Burkey, E D

    1984-11-01

    Bone marrow transplantation, used in the treatment of cancer, aplastic anemia, and metabolic diseases, involves the use of potentially neurotoxic agents to suppress immunity and eradicate malignancy. Fifty-seven patients with a median age of 11 years (age range, 6 months to 24 years) underwent bone marrow transplantation at the Children's Hospital of Philadelphia. Fifty-nine percent developed neurological abnormalities. Twenty-six patients (46%) had central nervous system (CNS) dysfunction, including infection (8), cerebrovascular accident (5), CNS leukemia (7), metabolic encephalopathy (5), and paraparesis with CNS toxoplasmosis (1). Neuropsychological dysfunction was present in 4 of 5 long-term survivors who were tested. Fourteen of 19 patients (74%) on whom postmortem examination was performed were found to have CNS abnormalities, including cerebral atrophy (10), focal cerebral injury (6), leukemia (5), and infection (3). Fourteen patients (24%) had peripheral nervous system dysfunction. CNS dysfunction was more common in patients with lymphoreticular malignancies. Cerebrovascular accidents (in patients with lymphoreticular malignancies) and infections (in our general population and in patients with lymphoreticular malignancies) occurred more often in our patients than in patients with similar illnesses who did not undergo bone marrow transplantation. The combination of prior treatment and preparative therapy for bone marrow transplantation predisposes patients to neurological and neuropsychological sequelae.

  8. Presumptive invasive Chrysosporium infection in a bone marrow transplant recipient.

    PubMed

    Warwick, A; Ferrieri, P; Burke, B; Blazar, B R

    1991-10-01

    Chrysosporium species caused an invasive infection in an 18-year-old patient following allogeneic sibling bone marrow transplant for T lineage acute lymphoblastic leukemia. This infection began as a facial swelling and extended into the central nervous system. Fungal disease spread rapidly despite antifungal agents. An autopsy showed fungal involvement of brain, lungs, liver and kidneys.

  9. Haploidentical bone marrow transplantation without T-cell depletion.

    PubMed

    Chang, Ying-Jun; Huang, Xiao-Jun

    2012-12-01

    Approaches for haploidentical bone marrow transplantation (BMT) without T-cell depletion have been designed using new transplant strategies, including anti-thymocyte globulin (ATG) preparative regimens, granulocyte colony-stimulating factor-primed grafts, post-transplantation rapamycin, or high-dose cyclophosphamide (Cy) in combination with other immunosuppressive agents for graft-versus-host disease (GVHD) prophylaxis. These strategies ensured fast hematologic engraftment across the human leukocyte antigen (HLA) barrier with an acceptable incidence of GVHD. Long-term follow-up results from different transplant centers suggest that unmanipulated transplantation may provide an alternative strategy in the haploidentical setting without requiring the technical expertise and cost of ex vivo T-cell depletion. This review discusses immune reconstitution and factors associated with clinical outcomes following unmanipulated haploidentical hematopoietic stem cell transplantation (HSCT), and compares outcomes between unmanipulated haploidentical transplant versus HLA-matched sibling donor (MSD) transplantation, HLA-matched unrelated donor (MUD) transplantation, or unrelated double umbilical cord blood (dUCB) transplantation. Advantages and disadvantages of unmanipulated haploidentical HSCT and strategies to improve outcome after haploidentical BMT without ex vivo T-cell depletion are discussed. PMID:23206842

  10. Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation.

    PubMed

    Ghavamzadeh, A; Alimoghadam, K; Nasseri, P; Jahani, M; Khodabandeh, A; Ghahremani, G

    1999-02-01

    Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease.

  11. Bone marrow transplantation reverses new-onset immunoinflammatory diabetes in a mouse model.

    PubMed

    Lv, Cheng-Lan; Wang, Jing; Xie, Ting; Ouyang, Jian

    2014-01-01

    Bone marrow transplantation might be an effective method to cure type 1 diabetes mellitus. This study aimed to investigate whether bone marrow transplantation could reverse hyperglycemia in diabetic mice and whether high-dose total body irradiation followed by high-dose bone marrow mononuclear cell infusion could improve the efficiency of bone marrow transplantation in treating diabetic mice. Diabetic mice after multiple low doses of streptozotocin injection were irradiated followed by infusion with approximately 1×10(7) bone marrow mononuclear cells intravenously. Before and after bone marrow transplantation, fasting blood glucose, intraperitoneal glucose tolerance test, serum insulin, pancreatic histology, and the examination of insulin and glucagon in islets were processed. All recipients returned to near euglycemic within 1 week after undergoing bone marrow transplantation. No mice became hyperglycemia again during investigation period. The change of serum insulin, glucose tolerance test, pancreatic histology and the expression of insulin and glucagon in recipient islets after bone marrow transplantation all revealed islets regeneration and significant amelioration when compared respectively with those of diabetic mice without bone marrow transplantation. Bone marrow transplantation contributed to reduce blood glucose, prevent further blood glucose hike in diabetic recipients, and promote islets regeneration. High-dose total body irradiation in combination with high-dose bone marrow monoclear cell infusion could improve the efficiency of bone marrow transplantation in treating streptozotocin-induced diabetes.

  12. A history of bone marrow transplantation.

    PubMed

    de la Morena, M Teresa; Gatti, Richard A

    2010-02-01

    The last 40 years has seen the emergence of hematopoietic stem cell transplantation as a therapeutic modality for fatal diseases and as a curative option for individuals born with inherited disorders that carry limited life expectancy and poor quality of life. Despite the rarity of many primary immunodeficiency diseases, these disorders have led the way toward innovative therapies and further provide insights into mechanisms of immunologic reconstitution applicable to all hematopoietic stem cell transplants. This article represents a historical perspective of the early investigators and their contributions. It also reviews the parallel work that oncologists and immunologists have undertaken to treat both primary immunodeficiencies and hematologic malignancies.

  13. A history of bone marrow transplantation.

    PubMed

    de la Morena, M Teresa; Gatti, Richard A

    2011-02-01

    The last 40 years has seen the emergence of hematopoietic stem cell transplantation as a therapeutic modality for fatal diseases and as a curative option for individuals born with inherited disorders that carry limited life expectancy and poor quality of life. Despite the rarity of many primary immunodeficiency diseases, these disorders have led the way toward innovative therapies and further provide insights into mechanisms of immunologic reconstitution applicable to all hematopoietic stem cell transplants. This article represents a historical perspective of the early investigators and their contributions. It also reviews the parallel work that oncologists and immunologists have undertaken to treat both primary immunodeficiencies and hematologic malignancies.

  14. Haploidentical bone marrow transplantation in Mexico.

    PubMed

    Vázquez-Meraz, José Eugenio; Arellano-Galindo, José; Mendoza-García, Emma; Jiménez-Hernández, Elva; Martínez Avalos, Armando; Velázquez Guadarrama, Norma; Mejía Arangure, Juan Manuel

    2012-11-01

    Haploidentical hematopoietic cell transplantation using CD34(+) cells depleted of T lymphocytes by the CliniMACS is a treatment for hematological malignancy. We report on four Mexican children, three with acute lymphocytic leukemia and one with chronic myelocytic leukemia, who was transplanted with 12 × 10(6) CD34(+) stem cells/kg body weight (98% of purity) with a follow-up of 9½ years. The engraftment was successful in three of the four children. All showed cytomegalovirus reactivation, and one died because of graft rejection and infectious complication. The risk of infections was a major problem.

  15. An alternative model of vascularized bone marrow transplant: partial femur transplantation.

    PubMed

    Chen, Jian-Wu; Chen, Chen; Su, Ying-Jun; Yan, Lun; Wang, Shi-Ping; Guo, Shu-Zhong

    2014-12-01

    The vascularized whole femur transplantation model is one of the commonly used vascularized bone marrow transplant models. It involves technical complexity and morbidities. To optimize this model, we took 2/3 femur as the carrier of bone marrow cells, and developed a vascularized partial femur model. Four experimental groups were carried out, namely, the syngeneic partial femur transplantation, allogeneic partial femur transplantation with or without cyclosporine A, and allogeneic whole femur transplantation with cyclosporine A. The results showed that the partial femur model was technically simpler and shortened the operative and ischemia time compared to the whole femur model. Gross and histologic appearance confirmed the viability of femur, and its bone marrow inside the bone could also maintain normal morphologically at 60-day posttransplant. Besides, donor multilineage chimerism could be continuously detected in immunosuppressed allogeneic partial femur recipients at 1-, 2-, 3-, 4-, and 8-week posttransplant, and it showed no significant differences when compared with whole femur transplantation. Meanwhile, long-term engraftment of donor-origin cells was also confirmed in recipients' bone marrow, lymph nodes, and spleen, but not in thymus. Therefore, the vascularized partial femur can serve as a continuous resource of bone morrow cells and may provide a useful tool for the study of immune tolerance in vascularized composite allotransplantation.

  16. [Kinetic study of splenocytes after allogeneic murine bone marrow transplantation].

    PubMed

    Liu, Jing-Hua; Zhou, Fan; Dou, Li-Ping; Wang, Li-Li; Wang, Xin-Rong; Li, Li; Yu, Li

    2010-08-01

    The study was purposed to understand immunological reconstitution of peripheral immune organs after transplantation, through establishing allogeneic murine bone marrow transplantation model and detecting the kinetic change of splenocytes after transplantation. C57BL/6 mice were donors, BALB/c mice were recipients. Recipient mice were divided into irradiation group (R), irradiation plus inoculating bone marrow mononuclear cells (MNC) group (B), and irradiation plus inoculating bone marrow mononuclear cells and spleno-MNC group (S). After transplantation, the mice were examined daily for the symptoms such as weight, hunched posture, activity, ruffled fur, diarrhea, and survival. Blood routine test was done once a week, splenocyte was counted and CD3, CD4, CD8, B220, CD11c positive cell relative count was detected by FACS on day 2, 7, 14, 27, 60 after transplantation, Liver, skin and intestine were biopsied for histopathological examination before dying. The results indicated that 89% mice in S group died of acute graft-versus-host disease (aGVHD) during day 6 to 78. The spleno-mononuclear cell count quickly decreased and reached to lowest level on day 2, then gradually recovered to level of pretransplantation on day 14; CD8 and B220 positive cells decreased to lowest level on day 12, in which CD8(+) cells quickly recovered and reached to level of pretransplantation, but the B220(+) recovered most slowly and sustained to be with low level, then gradually recovered to level of pretransplantation on day 60; CD3 and CD4 positive cells decreased relatively slowly, and reached to lowest level on day 14, then both gradually recovered to level of pretransplantation on day 60; CD11c positive cell count changed unstrikingly except day 14. It is concluded that when C57BL/6 mice are donors, and BALB/c mice are recipients treated with irradiation of 7.5 Gy and inoculated with 1 x 10⁷ bone marrow MNC and 1 x 10⁷ spleno-MNC, allogeneic murine bone marrow transplantation model

  17. Psychiatric Sequelae in Adolescent Bone Marrow Transplantation Survivors

    PubMed Central

    STUBER, MARGARET L.; NADER, KATHLEEN O.

    1995-01-01

    Survivors of life-threatening pediatric illness and their families present a number of psychotherapeutic challenges. The authors present pilot data evaluating the long-term psychiatric impact of pediatric bone marrow transplantation on 10 adolescent transplantation survivors compared with a matched control group. On a quantitative assessment of posttraumatic stress symptoms, the survivors reported a consistent but low level of symptoms. Their narratives about the experience suggest the need for ongoing mental health assessment in addition to specific interventions with families early in the treatment. PMID:22700211

  18. Autologous bone marrow transplantation by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  19. Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease

    PubMed Central

    Hajifathalian, Kaveh; Humberson, Annette; Hanouneh, Mohamad A; Barnes, David S; Arora, Zubin; Zein, Nizar N; Eghtesad, Bijan; Kelly, Dympna; Hanouneh, Ibrahim A

    2016-01-01

    AIM To evaluate risk of recidivism on a case-by-case basis. METHODS From our center’s liver transplant program, we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium (OSOTC) exception criteria. They were considered to have either a low or medium risk of recidivism, and had at least one or three or more months of abstinence, respectively. They were matched based on gender, age, and Model for End-Stage Liver Disease (MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data. RESULTS Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls. Nineteen patients (53%) with a median [Inter-quartile range (IQR)] MELD score of 24 (13) received transplant and were followed for a median of 3.4 years. They were matched to 38 controls with a median (IQR) MELD score of 25 (9). At one and five years, cumulative survival rates (± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls, respectively (Log-rank test, P = 0.837). Four (21%) patients resumed drinking by last follow-up visit. CONCLUSION Compared to traditional criteria for assessment of risk of recidivism, a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation. PMID:27721920

  20. Ethical issues in bone marrow transplantation in children.

    PubMed

    Bendorf, Aric; Kerridge, Ian H

    2011-09-01

    In the 50 years since the first successful human bone marrow transplant (BMT) was performed in 1959, BMT has become the optimal therapy for a wide variety of life-threatening paediatric haematological, immunological and genetic disorders. Unfortunately, while BMT generally provides the only possibility of cure for such afflicted children, few (25%) have a matched sibling available, and suitably matched unrelated donors are often not identified for many children in need of BMT. And even where BMT is possible, treatment is complex and arduous and associated with significant mortality and morbidity. The issues raised when either or both the donor and recipient are children and lack the capacity to make informed and rational decisions relating to BMT pose great challenges for all involved. This paper examines some of the ethical dilemmas that confront patients, families and medical practitioners when considering bone marrow transplantation in a child. PMID:21951444

  1. Male genital lichen sclerosus in recipients of bone marrow transplants.

    PubMed

    Thomas, L J; Shim, T N; Borysiewicz, C; Dinneen, M; Fawcett, H; Roy, A; Francis, N; Bunker, C B

    2016-07-01

    We describe two patients who received haematopoietic stem cell marrow transplantation, and developed male genital lichen sclerosus (MGLSc), one of whom also had squamous carcinoma in situ (Bowen disease). MGLSc has previously been associated with graft-versus-host disease. Various aetiological factors for LSc have been proposed, including a role for chronic occluded epithelial exposure to urine. A number of factors imply that the risk of malignant transformation in this bone marrow transplant group is likely to be higher than the overall figure of 2-9% cited for MGLSc. It is vital, therefore, that clinicians involved in the care of those with haematological malignancies are adequately prepared to examine the genitals of their patients, and to recognize and refer any suspect penile lesions. PMID:26936088

  2. How I vaccinate blood and marrow transplant recipients.

    PubMed

    Carpenter, Paul A; Englund, Janet A

    2016-06-01

    Vaccination guidelines for recipients of blood and marrow transplantation (BMT) have been published by 3 major societies: American Blood and Marrow Transplantation, European Group of Blood and Marrow Transplantation, and Infectious Disease Society of America. Despite these extensive review articles, clinicians caring for BMT recipients continue to field frequently asked questions (FAQs) regarding the "who, when, and how" of feasible and effective posttransplant vaccination, frequently in the absence of adequate data. This may reflect discomfort with a "one size fits all" policy that makes no adjustments for different posttransplant clinical scenarios. Existing guidelines also lack practical dose clarifications when administering vaccines to patients who differ by age, underlying diagnosis, or amount of immunosuppressive therapy. Frequently, little or conflicting guidance is given regarding age-related schedules for certain vaccines (eg, meningococcal; tetanus toxoid, reduced diphtheria toxoid, and reduced acellular pertussis; and human papillomavirus vaccines) in addition to time posttransplant or other factors. FAQs and their answers form the body of this article and are shared with readers as a concise practical review, with the intent to facilitate good clinical practice. PMID:27048212

  3. Successful renal transplantation following prior bone marrow transplantation in pediatric patients.

    PubMed

    Thomas, Susan E; Hutchinson, Raymond J; DebRoy, Meelie; Magee, John C

    2004-10-01

    Improving survival rates following pediatric bone marrow transplantation (BMT) will likely result in greater numbers of children progressing to end-stage renal disease (ESRD) because of prior chemotherapy, irradiation, sepsis, and exposure to nephrotoxic agents. Renal transplantation remains the treatment of choice for ESRD; however, the safety of renal transplantation in this unique population is not well established. We report our experience with living related renal transplantation in three pediatric patients with ESRD following prior BMT. Two patients with neuroblastoma and ESRD because of BMT nephropathy, and one patient with Schimke immuno-osseous dysplasia and ESRD because of immune complex mediated glomerulonephritis and nephrotic syndrome. Age at time of BMT ranged from 2 to 7 yr. All patients had stable bone marrow function prior to renal transplantation. Age at renal transplant ranged from 8 to 14 yr. All three patients have been managed with conventional immunosuppression, as no patient received a kidney and BMT from the same donor source. These patients are currently 7 months to 6 yr status post-living related transplant. All have functioning bone marrow and kidney transplants, with serum creatinine levels ranging 0.6-1.2 mg/dL. There have been no episodes of rejection. One patient with a history of grade III skin and grade IV gastrointestinal-graft-vs.-host disease (GI-GVHD) prior to transplantation, had a mild flare of GI-GVHD (grade I) post-renal transplant and is currently asymptomatic. The incidence of opportunistic infection has been comparable with our pediatric renal transplant population without prior BMT. One patient was treated for basal cell carcinoma via wide local excision. Renal transplantation is an excellent option for the treatment of pediatric patients with ESRD following BMT. Short-term results in this small population show promising patient and graft survival, however long-term follow-up is needed. Pre-existing immune system

  4. Transplanted Bone Marrow-Derived Cells Contribute to Human Adipogenesis.

    PubMed

    Rydén, Mikael; Uzunel, Mehmet; Hård, Joanna L; Borgström, Erik; Mold, Jeff E; Arner, Erik; Mejhert, Niklas; Andersson, Daniel P; Widlund, Yvonne; Hassan, Moustapha; Jones, Christina V; Spalding, Kirsty L; Svahn, Britt-Marie; Ahmadian, Afshin; Frisén, Jonas; Bernard, Samuel; Mattsson, Jonas; Arner, Peter

    2015-09-01

    Because human white adipocytes display a high turnover throughout adulthood, a continuous supply of precursor cells is required to maintain adipogenesis. Bone marrow (BM)-derived progenitor cells may contribute to mammalian adipogenesis; however, results in animal models are conflicting. Here we demonstrate in 65 subjects who underwent allogeneic BM or peripheral blood stem cell (PBSC) transplantation that, over the entire lifespan, BM/PBSC-derived progenitor cells contribute ∼10% to the subcutaneous adipocyte population. While this is independent of gender, age, and different transplantation-related parameters, body fat mass exerts a strong influence, with up to 2.5-fold increased donor cell contribution in obese individuals. Exome and whole-genome sequencing of single adipocytes suggests that BM/PBSC-derived progenitors contribute to adipose tissue via both differentiation and cell fusion. Thus, at least in the setting of transplantation, BM serves as a reservoir for adipocyte progenitors, particularly in obese subjects. PMID:26190649

  5. Muscle-specific kinase antibody associated myasthenia gravis after bone marrow transplantation.

    PubMed

    Heidarzadeh, Zeinab; Mousavi, Seyyed-Asadollah; Ostovan, Vahid Reza; Nafissi, Shahriar

    2014-02-01

    Myasthenia gravis is a rare complication of bone marrow transplantation and graft versus host disease. We report a 30-year-old woman presented with oculobulbar and proximal limb weakness after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Also, she developed graft versus host disease following bone marrow transplantation. Investigations led to the diagnosis of muscle specific kinase antibody related myasthenia gravis. There have been only two case reports of muscle specific kinase antibody positive myasthenia gravis after bone marrow transplantation in the literature, but none of the previously reported cases had graft versus host disease.

  6. Increasing utilization of bone marrow transplantation. II. Results of the 1985-1987 survey.

    PubMed

    Bortin, M M; Rimm, A A

    1989-09-01

    The International Bone Marrow Transplant REgistry conducts periodic surveys to determine activity in the field of allogeneic and syngeneic bone marrow transplantation. Data were reported to the IBMTR by 258 institutions in 41 countries regarding their patients who received bone marrow transplants during the period 1985-1987. To the best of our knowledge, the data represent essentially all bone marrow transplants (exclusive of autologous transplants) performed in the past 3 years. A total of 10,887 patients received bone marrow transplants; 73% were for leukemia, 11% for other malignant diseases, 9% for severe aplastic anemia and related disorders, 3% for immune deficiency diseases, 2% for thalassemia major, and 2% for genetic, metabolic, and several other rare diseases. 161 (62%) of the 258 institutions performed fewer than one transplant per month. More than 50% of the patients were transplanted in 37 institutions. 46% of the world's bone marrow transplants were performed in North America, 42% in Western Europe, 5% in Asia, 3% in Australia and New Zealand, 2% in the Mideast and Africa, 1% in South and Central America, and 1% in Eastern Europe and the USSR. The data reflect continued growth in utilization of allogeneic and syngeneic bone marrow transplantation and quantify the annual increases in the number of patients receiving transplants.

  7. The Application of Bone Marrow Transplantation to the Treatment of Genetic Diseases

    NASA Astrophysics Data System (ADS)

    Parkman, Robertson

    1986-06-01

    Genetic diseases can be treated by transplantation of either normal allogeneic bone marrow or, potentially, autologous bone marrow into which the normal gene has been inserted in vitro (gene therapy). Histocompatible allogeneic bone marrow transplantation is used for the treatment of genetic diseases whose clinical expression is restricted to lymphoid or hematopoietic cells. The therapeutic role of bone marrow transplantation in the treatment of generalized genetic diseases, especially those affecting the central nervous system, is under investigation. The response of a generalized genetic disease to allogeneic bone marrow transplantation may be predicted by experiments in vitro. Gene therapy can be used only when the gene responsible for the disease has been characterized. Success of gene therapy for a specific genetic disease may be predicted by its clinical response to allogeneic bone marrow transplantation.

  8. Cartilage Repair With Autologous Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Yamasaki, Shinya; Mera, Hisashi; Itokazu, Maki; Hashimoto, Yusuke

    2014-01-01

    Clinical trials of various procedures, including bone marrow stimulation, mosaicplasty, and autologous chondrocyte implantation, have been explored to treat articular cartilage defects. However, all of them have some demerits. We focused on autologous culture-expanded bone marrow mesenchymal stem cells (BMSC), which can proliferate without losing their capacity for differentiation. First, we transplanted BMSC into the defective articular cartilage of rabbit and succeeded in regenerating osteochondral tissue. We then applied this transplantation in humans. Our previous reports showed that treatment with BMSC relieves the clinical symptoms of chondral defects in the knee and elbow joint. We investigated the efficacy of BMSC for osteoarthritic knee treated with high tibial osteotomy, by comparing 12 BMSC-transplanted patients with 12 cell-free patients. At 16-month follow-up, although the difference in clinical improvement between both groups was not significant, the arthroscopic and histological grading score was better in the cell-transplanted group. At the over 10-year follow-up, Hospital for Special Surgery knee scores improved to 76 and 73 in the BMSC-transplanted and cell-free groups, respectively, which were better than preoperative scores. Additionally, neither tumors nor infections were observed in all patients, and in the clinical study, we have never observed hypertrophy of repaired tissue, thereby guaranteeing the clinical safety of this therapy. Although we have never observed calcification above the tidemark in rabbit model and human histologically, the repair cartilage was not completely hyaline cartilage. To elucidate the optimum conditions for cell therapy, other stem cells, culture conditions, growth factors, and gene transfection methods should be explored. PMID:26069698

  9. Unrelated donor marrow transplantation: an update of the experience of the Italian Bone Marrow Transplant Group (GITMO).

    PubMed

    Dini, G; Cancedda, R; Locatelli, F; Bosi, A; Bandini, G; Alessandrino, E P; Porta, F; Uderzo, C; Messina, C; Fagioli, F; Arcese, W; Marenco, P; Fanin, R; Falda, M; Soligo, D; La Nasa, G; Giardini, C; Pession, A; Scimè, R; Di Bartolomeo, P; Bruno, B; Garbarino, L; Lamparelli, T; Giorgiani, G; Lanino, E; Manzitti, C; Bacigalupo, A

    2000-11-01

    Unrelated donor bone marrow transplant (UD-BMT) has become an attractive alternative source of hematopoietic cells for patients lacking a matched sibling. The aim of this paper was to report on results of the 696 UD BMTs performed in 31 Italian institutions during the first 10 years of activity of the Italian Bone Marrow Donor Registry (IBMDR). In 1989 the Italian Bone Marrow Transplant Group (GITMO) established the IBMDR to facilitate donor search and marrow procurement for patients lacking an HLA identical sibling. By end of December 1999, 260,000 HLA-A, B typed volunteer donors had been cumulatively registered and 2,620 searches had been activated for Italian patients. At least one HLA-A, B, DRB1 matched donor was found for 54% of the patients and 696 UD BMTs were performed. In 50% of cases the donor was found in the IBMDR and in 50% in 15 other Registries. The average time from search activation to transplant was 6 months for disease other than CML. For CML it was 14 months. Actuarial 12-month transplant-related mortality (TRM) was 68% in patients grafted between 1979 and 1992 and 44% for patients grafted after 1993. Twenty-eight per cent of patients developed grade III or IV acute GvHD and 24% developed extensive chronic GvHD. The rate of disease free survival at three years was 57% for patients with 1st chronic phase CML, 37% for patients with 1st or 2nd CR ALL, 31% for AML or MDS patients < or = 18 years of age and 54% for patients with inborn errors. We conclude that the IBMDR has benefited a substantial number of patients lacking a matched sibling and has facilitated the recruitment of UDs into the international donor pool. The long time required for the search is the major obstacle to the success of this programme. This suggests that early transplant and a decrease in TRM could further improve these encouraging results.

  10. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient

    PubMed Central

    Siebrasse, Erica A.; Nguyen, Nang L.; Willby, Melisa J.; Erdman, Dean D.; Menegus, Marilyn A.

    2016-01-01

    WU polyomavirus (WUPyV) was detected in a bone marrow transplant recipient with severe acute respiratory distress syndrome who died in 2001. Crystalline lattices of polyomavirus-like particles were observed in the patient’s lung by electron microscopy. WUPyV was detected in the lung and other tissues by real-time quantitative PCR and identified in the lung and trachea by immunohistochemistry. A subset of WUPyV-positive cells in the lung had morphologic features of macrophages. Although the role of WUPyV as a human pathogen remains unclear, these results clearly demonstrate evidence for infection of respiratory tract tissues in this patient. PMID:26691850

  11. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  12. Recovery of hair coat color in Gray Collie (cyclic neutropenia)-normal bone marrow transplant chimeras.

    PubMed Central

    Yang, T. J.

    1978-01-01

    Gray Collie-normal bone marrow transplantation chimeras showed normal coloration of the hair coat on tails and several other areas 2 years after successful transplantation of bone marrow to correct cyclic neutropenia of the Gray Collie syndrome. Images Figures 1-2 PMID:347941

  13. Past and future of providing matched, unrelated donors for marrow transplantation.

    PubMed

    Roeckel, I E; Baker, J

    1997-01-01

    Prior to 1979, bone marrow transplants were only performed with histocompatible sibling donors. Once it was established that histocompatible, unrelated donors could donate marrow for transplantation, the recruitment of such donors needed to be standardized. Blood donor centers had already identified the histocompatibility locus antigen (HLA) typing for donors who could be recruited to donate bone marrow. Recruiting a large number of donors required systematic evaluation and testing according to defined standards which were published in 1988 by the National Marrow Donor Program (NMDP). Peripheral stem cell collection (PBS) has been added as a transplant source. It promises additional therapeutic modalities, such as gene splicing to address other than cancer therapy.

  14. Stress responses after pediatric bone marrow transplantation: preliminary results of a prospective longitudinal study.

    PubMed

    Stuber, M L; Nader, K; Yasuda, P; Pynoos, R S; Cohen, S

    1991-11-01

    This paper reports the preliminary findings of a longitudinal prospective study of young children undergoing bone marrow transplantation. Symptoms of post-traumatic stress were seen in these children up to 12 months after transplant. The bone marrow transplantation survivors demonstrated more denial and avoidance and fewer arousal symptoms than has been noted in children traumatized by a violent life threat, such as a sniper attack. These data suggest the use of post-traumatic stress as a model in understanding some of the symptoms of pediatric bone marrow transplantation survivors and may be applicable to other children exposed to the double life threat of serious illness and intensive medical intervention.

  15. Infection in the bone marrow transplant recipient and role of the microbiology laboratory in clinical transplantation.

    PubMed Central

    LaRocco, M T; Burgert, S J

    1997-01-01

    Over the past quarter century, tremendous technological advances have been made in bone marrow and solid organ transplantation. Despite these advances, an enduring problem for the transplant recipient is infection. As immunosuppressive regimens have become more systematic, it is apparent that different pathogens affect the transplant recipient at different time points in the posttransplantation course, since they are influenced by multiple intrinsic and extrinsic factors. An understanding of this evolving risk for infection is essential to the management of the patient following transplantation and is a key to the early diagnosis and treatment of infection. Likewise, diagnosis of infection is dependent upon the quality of laboratory support, and services provided by the clinical microbiology laboratory play an important role in all phases of clinical transplantation. These include the prescreening of donors and recipients for evidence of active or latent infection, the timely and accurate microbiologic evaluation of the transplant patient with suspected infection, and the surveillance of asymptomatic allograft recipients for infection. Expert services in bacteriology, mycology, parasitology, virology, and serology are needed and communication between the laboratory and the transplantation team is paramount for providing clinically relevant, cost-effective diagnostic testing. PMID:9105755

  16. Allogeneic Marrow Transplantation in Patients With Severe Systemic Sclerosis

    PubMed Central

    Nash, Richard A.; McSweeney, Peter A.; Nelson, J. Lee; Wener, Mark; Georges, George E.; Langston, Amelia A.; Shulman, Howard; Sullivan, Keith M.; Lee, Julie; Henstorf, Gretchen; Storb, Rainer; Furst, Daniel E.

    2010-01-01

    Objective To evaluate the safety and efficacy of allogeneic hematopoietic cell transplantation (HCT) after myeloablative conditioning in patients with severe systemic sclerosis (SSc). Methods Eligibility criteria for the study included SSc patients with features indicative of a poor prognosis. The myeloablative conditioning regimen included busulfan, cyclophosphamide, and antithymocyte globulin. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine and methotrexate. Bone marrow was transplanted from HLA-identical siblings. Results Two patients with diffuse cutaneous SSc and lung involvement who were refractory to conventional immunosuppressive treatment were enrolled in the study. In patient 1, there were no complications related to the conditioning regimen, and GVHD did not develop after transplantation. At 5 years after HCT, there was nearly complete resolution of the scleroderma and marked improvement in physical functioning. Internal organ function improved (lung) or remained stable. On examination of serial skin biopsy samples, there was resolution of the dermal fibrosis. Patient 2 experienced skin toxicity from the conditioning regimen and hypertensive crisis that was likely related to high-dose corticosteroids given for treatment of GVHD. Although this patient experienced an improvement in scleroderma and overall functioning, a fatal opportunistic infection developed 17 months after HCT. Conclusion Allogeneic HCT may result in sustained remission of SSc. GVHD and opportunistic infections are the major risks associated with allogeneic HCT for SSc, as for allogeneic HCT in general. PMID:16732546

  17. NKT cells, Treg, and their interactions in bone marrow transplantation

    PubMed Central

    Kohrt, Holbrook E.; Pillai, Asha B.; Lowsky, Robert; Strober, Samuel

    2010-01-01

    Bone marrow transplantation (BMT) is a potentially curative treatment for patients with leukemia and lymphoma. Tumor eradication is promoted by the anti-tumor activity of donor T cells contained in the transplant; however, donor T cells also mediate the serious side effect of graft-versus-host disease (GVHD). Separation of GVHD from graft anti-tumor activity is an important goal of research in improving transplant outcome. One approach is to take advantage of the immunomodulatory activity of regulatory NKT cells and CD4+ CD25+ Treg of host and/or donor origin. Both host and donor NKT cells and donor Treg are able to prevent GVHD in murine models. In this review, we summarize the mechanisms of NKT cell- and Treg-mediated protection against GVHD in mice while maintaining graft anti-tumor activity. In addition, we also examine the interactions between NKT cells and Treg in the context of BMT, and integrate the data from murine experimental models with the observations made in humans. PMID:20583031

  18. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    PubMed Central

    Maffi, Paola; Balzano, Gianpaolo; Ponzoni, Maurilio; Nano, Rita; Sordi, Valeria; Melzi, Raffaella; Mercalli, Alessia; Scavini, Marina; Esposito, Antonio; Peccatori, Jacopo; Cantarelli, Elisa; Messina, Carlo; Bernardi, Massimo; Del Maschio, Alessandro; Staudacher, Carlo; Doglioni, Claudio; Ciceri, Fabio; Secchi, Antonio; Piemonti, Lorenzo

    2013-01-01

    The liver is the current site of choice for pancreatic islet transplantation, even though it is far from being ideal. We recently have shown in mice that the bone marrow (BM) may be a valid alternative to the liver, and here we report a pilot study to test feasibility and safety of BM as a site for islet transplantation in humans. Four patients who developed diabetes after total pancreatectomy were candidates for the autologous transplantation of pancreatic islet. Because the patients had contraindications for intraportal infusion, islets were infused in the BM. In all recipients, islets engrafted successfully as shown by measurable posttransplantation C-peptide levels and histopathological evidence of insulin-producing cells or molecular markers of endocrine tissue in BM biopsy samples analyzed during follow-up. Thus far, we have recorded no adverse events related to the infusion procedure or the presence of islets in the BM. Islet function was sustained for the maximum follow-up of 944 days. The encouraging results of this pilot study provide new perspectives in identifying alternative sites for islet infusion in patients with type 1 diabetes. Moreover, this is the first unequivocal example of successful engraftment of endocrine tissue in the BM in humans. PMID:23733196

  19. Unrelated bone marrow transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group.

    PubMed

    La Nasa, Giorgio; Argiolu, Franca; Giardini, Claudio; Pession, Andrea; Fagioli, Franca; Caocci, Giovanni; Vacca, Adriana; De Stefano, Piero; Piras, Eugenia; Ledda, Antonio; Piroddi, Antonio; Littera, Roberto; Nesci, Sonia; Locatelli, Franco

    2005-01-01

    Bone marrow transplantation (BMT) remains the only potentially curative treatment for patients with thalassemia major. However, most candidates for BMT do not have a suitable family donor. In order to evaluate whether BMT from an HLA-matched unrelated volunteer donor can offer a probability of cure comparable to that obtained when the donor is a compatible sibling, we carried out a study involving 68 thalassemia patients transplanted in six Italian BMT Centers. Thirty-three males and 35 females (age range, 2-37 years; median age, 15) were transplanted from unrelated volunteer donors, all selected using high-resolution molecular typing of both HLA class I and II loci. Fourteen patients were classified in risk class 1; 16 in risk class 2; and 38 in risk class III of the Pesaro classification system. Nine patients (13%) had either primary or secondary graft failure. Fourteen patients (20%) died from transplant-related causes. Grade II-IV acute graft-versus-host disease (GVHD) developed in 24 cases (40%), and chronic GVHD in 10 cases (18%). Overall survival (OS) in the cohort of 68 patients was 79.3% (CI 67-88%), whereas the Kaplan-Meier estimates of disease-free survival (DFS) with transfusion independence was 65.8% (CI 54-77%). In the group of 30 thalassemic patients in risk classes 1 and 2, the probability of OS and DFS were 96.7% (CI 90-100%) and 80.0% (CI 65-94%), respectively, whereas in the 38 patients in class 3 OS was 65.2% (CI 49-80%) and DFS was 54.5% (CI 38-70%). These data show that when donor selection is based on stringent compatibility criteria, the results of unrelated transplantation in thalassemia patients are comparable to those obtained when the donor is a compatible sibling. PMID:16339665

  20. Combined Bone Marrow and Kidney Transplantation for the Induction of Specific Tolerance

    PubMed Central

    Chen, Yi-Bin; Kawai, Tatsuo; Spitzer, Thomas R.

    2016-01-01

    The induction of specific tolerance, in order to avoid the detrimental effects of lifelong systemic immunosuppressive therapy after organ transplantation, has been considered the “Holy Grail” of transplantation. Experimentally, tolerance has been achieved through clonal deletion, through costimulatory blockade, through the induction or infusion of regulatory T-cells, and through the establishment of hematopoietic chimerism following donor bone marrow transplantation. The focus of this review is how tolerance has been achieved following combined bone marrow and kidney transplantation. Preclinical models of combined bone marrow and kidney transplantation have shown that tolerance can be achieved through either transient or sustained hematopoietic chimerism. Combined transplants for patients with multiple myeloma have shown that organ tolerance and prolonged disease remissions can be accomplished with such an approach. Similarly, multiple clinical strategies for achieving tolerance in patients without an underlying malignancy have been described, in the context of either transient or durable mixed chimerism or sustained full donor hematopoiesis. To expand the chimerism approach to deceased donor transplants, a delayed tolerance approach, which will involve organ transplantation with conventional immunosuppression followed months later by bone marrow transplantation, has been successful in a primate model. As combined bone marrow and organ transplantation become safer and increasingly successful, the achievement of specific tolerance may become more widely applicable. PMID:27239198

  1. Transplanted Bone Marrow Cells Repair Heart Tissue and Reduce Myocarditis in Chronic Chagasic Mice

    PubMed Central

    Soares, Milena B. P.; Lima, Ricardo S.; Rocha, Leonardo L.; Takyia, Christina M.; Pontes-de-Carvalho, Lain; Campos de Carvalho, Antonio C.; Ribeiro-dos-Santos, Ricardo

    2004-01-01

    A progressive destruction of the myocardium occurs in ∼30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy. PMID:14742250

  2. Selection of patients with Hodgkin's disease and non-Hodgkin's lymphoma for bone marrow transplantation.

    PubMed

    Sullivan, K M; Appelbaum, F R; Horning, S J; Rosenberg, S A; Thomas, E D

    1986-01-01

    Despite substantial progress in curative therapy of malignant lymphomas, some patients fail current treatment and die of refractory disease. Although Although high-dose chemotherapy and supralethal total body irradiation followed by bone marrow transplantation may salvage and cure a proportion of these refractory patients, treatment of such end-stage patients with marrow grafting often fails because of resistant disease or transplant-related complications. Using the analogy of transplantation in the early phases of acute and chronic leukemias, results of marrow transplant in Hodgkin's disease and non-Hodgkin's lymphoma might be improved if performed earlier in the course of the malignancy. The following collaborative report by the Seattle and Stanford groups examines current results of conventional lymphoma therapy to define subgroups of patients with "high-risk" lymphoma for whom early marrow transplant might be offered to control otherwise incurable disease. PMID:3528333

  3. Prevention and treatment of fungal infections in bone marrow transplantation.

    PubMed

    Mossad, Sherif B

    2003-07-01

    There has not been as much success in the prevention and treatment of invasive fungal infections, particularly aspergillosis, compared to the prevention and treatment of cytomegalovirus infection and graft-versus-host disease in bone marrow transplant (BMT) recipients. Allogeneic BMT recipients who develop graft-versus-host disease and remain immunosuppressed for long periods are at major risk for development of these infections. Prevention of environmental exposure, antifungal chemoprophylaxis, and attempts at early diagnosis are essential for the reduction of mortality from invasive fungal infections. Chest computerized axial tomography is extremely useful in diagnosing pulmonary aspergillosis. However, microbiologic or histologic identification of infection remains essential. Unfortunately, the response to therapy in BMT recipients remains suboptimal. With the development of the lipid formulations of amphotericin B, the newer azoles, and the echinocandins, safer and more efficacious options have become available. The optimal use of antifungal agents or their combinations remains to be determined. PMID:12901327

  4. [The effect of nutrition on bone marrow transplantation].

    PubMed

    Olóriz, M R; del Campo, M; Sierra, D; Tamayo, B; Fuente, E

    1991-01-01

    Malnutrition alone may provoke considerable immune alterations, mainly in the immunocellular function, and in particular in the T lymphocyte and macrophage-monocytic function. This gives rise to an increase in proneness to infections, which in patients subjected to bone marrow transplants, will be increased by the intense neutropenia suffered by them. This study shows the greater incidence of infection among badly nourished patients compared to nourished patients. It was also observed that short bouts of high temperature mainly occurred in a subgroup of patients with an acceptable nutritional level, which in our opinion was the cause for none of them developing the infectious illness. Finally, one of the germs most often found in these patients is Staphylococcus epidermis, and the most common method of entry is through the catheters used in the administration of medicines and artificial nutrition. Emphasis is placed on the role played by nursing in preventing this type of infection. PMID:1760483

  5. Heart and kidney transplantation using total lymphoid irradiation and donor bone marrow in mongrel dogs

    SciTech Connect

    Kahn, D.R.; Dufek, J.H.; Hong, R.; Caldwell, W.L.; Thomas, F.J.; Kolenda, D.R.; Swanson, D.K.; Struble, R.A.

    1980-07-01

    Heart and kidney allografts showed markedly prolonged survival in unrelated mongrel dogs following total lymphoid irradiation (TLI) and donor bone marrow without any other immunosuppression. In every animal the heart survived longer than the kidney. Placing the kidney allograft in the abdomen with the bone marrow given intraperitoneally doubled kidney survival over placement in the neck, but heart survival was equally prolonged in the abdomen or neck. Splenectomy before TLI or after TLI, but just before transplantation, almost completely eliminated the prolonged survival of both heart and kidney allografts. Thus there is suggestive evidence that TLI plus bone marrow from the donor may be valuable for transplantation in man, particularly heart transplantation.

  6. Enhancing mental health services to bone marrow transplant recipients through a mindfulness-based therapeutic intervention.

    PubMed

    Horton-Deutsch, Sara; O'Haver Day, Pamela; Haight, Regina; Babin-Nelson, Michele

    2007-05-01

    Complementary and alternative therapies are gaining recognition in the treatment of many disease states. The importance of treating psychological and emotional problems associated with bone marrow transplant has been substantiated by research evidence. This feasibility study tested a mindfulness-based therapeutic intervention to treat such problems in this context. Pretests and post-tests were administered to patients (n=24) undergoing bone marrow transplant. Results indicate that the mindfulness-based therapeutic intervention has the potential to be an effective therapy for bone marrow transplant recipients.

  7. Enhancing mental health services to bone marrow transplant recipients through a mindfulness-based therapeutic intervention.

    PubMed

    Horton-Deutsch, Sara; O'Haver Day, Pamela; Haight, Regina; Babin-Nelson, Michele

    2007-05-01

    Complementary and alternative therapies are gaining recognition in the treatment of many disease states. The importance of treating psychological and emotional problems associated with bone marrow transplant has been substantiated by research evidence. This feasibility study tested a mindfulness-based therapeutic intervention to treat such problems in this context. Pretests and post-tests were administered to patients (n=24) undergoing bone marrow transplant. Results indicate that the mindfulness-based therapeutic intervention has the potential to be an effective therapy for bone marrow transplant recipients. PMID:17400146

  8. CXCR2 modulates bone marrow vascular repair and haematopoietic recovery post-transplant.

    PubMed

    Hale, Sarah J M; Hale, Ashley B H; Zhang, Youyi; Sweeney, Dominic; Fisher, Nita; van der Garde, Mark; Grabowska, Rita; Pepperell, Emma; Channon, Keith; Martin-Rendon, Enca; Watt, Suzanne M

    2015-05-01

    Murine models of bone marrow transplantation show that pre-conditioning regimens affect the integrity of the bone marrow endothelium and that the repair of this vascular niche is an essential pre-requisite for successful haematopoietic stem and progenitor cell engraftment. Little is known about the angiogenic pathways that play a role in the repair of the human bone marrow vascular niche. We therefore established an in vitro humanized model, composed of bone marrow stromal and endothelial cells and have identified several pro-angiogenic factors, VEGFA, ANGPT1, CXCL8 and CXCL16, produced by the stromal component of this niche. We demonstrate for the first time that addition of CXCL8 or inhibition of its receptor, CXCR2, modulates blood vessel formation in our bone marrow endothelial niche model. Compared to wild type, Cxcr2(-/-) mice displayed a reduction in bone marrow cellularity and delayed platelet and leucocyte recovery following myeloablation and bone marrow transplantation. The delay in bone marrow recovery correlated with impaired bone marrow vascular repair. Taken together, our data demonstrate that CXCR2 regulates bone marrow blood vessel repair/regeneration and haematopoietic recovery, and clinically may be a therapeutic target for improving bone marrow transplantation.

  9. Chromothriptic cure of WHIM syndrome: Implications for bone marrow transplantation.

    PubMed

    McDermott, David H; Gao, Ji-Liang; Murphy, Philip M

    2015-01-01

    We recently reported a 59 year old female, designated WHIM-09, who was born with the rare immunodeficiency disease WHIM syndrome but underwent spontaneous phenotypic reversion as an adult. The causative WHIM mutation CXCR4 (R334X) was absent in her myeloid and erythroid lineage, but present in her lymphoid lineage and in epithelial cells, defining her as a somatic genetic mosaic. Genomic and hematologic analysis revealed chromothripsis (chromosome shattering) on one copy of chromosome 2, which deleted 164 genes including CXCR4 (R334X) in a single haematopoietic stem cell (HSC) (Fig. 1). Experiments in mice indicated that deleting one copy of Cxcr4 is sufficient to confer a selective advantage for engraftment of transplanted HSCs, suggesting a mechanism for clinical cure in WHIM-09. Genome editing may allow autologous transplantation of HSCs lacking one copy of CXCR4 without bone marrow conditioning as a general cure strategy in WHIM syndrome, safely recapitulating the outcome in patient WHIM-09. Figure 1.Chromothripsis (chromosomal shattering) resulted in clinical cure of a patient with a rare immunodeficiency (WHIM syndrome) by deleting the mutant copy of CXCR4. PMID:26459672

  10. Applications of Next Generation Sequencing to Blood and Marrow Transplantation

    PubMed Central

    Chapman, Michael; Warren, Edus H.; Wu, Catherine J.

    2011-01-01

    Since the advent of next-generation sequencing (NGS) in 2005, there has been an explosion of published studies employing the technology to tackle previously intractable questions in many disparate biological fields. This has been coupled with technology development that has occurred at a remarkable pace. This review discusses the potential impact of this new technology on the field of blood and marrow stem cell transplantation. Hematologic malignancies have been among the forefront of those cancers whose genomes have been the subject of NGS. Hence, these studies have opened novel areas of biology that can be exploited for prognostic, diagnostic, and therapeutic means. Because of the unprecedented depth, resolution and accuracy achievable by NGS, this technology is well-suited for providing detailed information on the diversity of receptors that govern antigen recognition; this approach has the potential to contribute important insights into understanding the biologic effects of transplantation. Finally, the ability to perform comprehensive tumor sequencing provides a systematic approach to the discovery of genetic alterations that can encode peptides with restricted tumor expression, and hence serve as potential target antigens of GvL responses. Altogether, this increasingly affordable technology will undoubtedly impact the future practice and care of patients with hematologic malignancies. PMID:22226099

  11. In vivo cell kinetics of the bone marrow transplantation using dual colored transgenic rat system

    NASA Astrophysics Data System (ADS)

    Kai, Kotaro; Teraoka, Satoshi; Adachi, Yasushi; Ikehara, Susumu; Murakami, Takashi; Kobayashi, Eiji

    2008-02-01

    Because bone marrow is an adequate site for bone marrow stem cells, intra-bone marrow - bone marrow transplantation (IBM-BMT) is an efficient strategy for bone marrow transplantation (BMT). However, the fate of the transplanted cells remains unclear. Herein, we established a dual-colored transgenic rat system utilizing green fluorescent protein (GFP) and a luciferase (luc) marker. We then utilized this system to investigate the in vivo kinetics of transplanted bone marrow cells (BMCs) after authentic intravenous (IV)-BMT or IBM-BMT. The in vivo fate of the transplanted cells was tracked using an in vivo luminescent imaging technique; alterations in peripheral blood chimerism were also followed using flow cytometry. IBM-BMT and IV-BMT were performed using syngeneic and allogeneic rat combinations. While no difference in the proliferation pattern was observed between the two treatment groups at 7 days after BMT, different distribution patterns were clearly observed during the early phase. In the IBM-BMT-treated rats, the transplanted BMCs were engrafted immediately at the site of the injected bone marrow and expanded more rapidly than in the IV-BMT-treated rats during this phase. Graft-versus-host disease was also visualized. Our bio-imaging system using dual-colored transgenic rats is a powerful tool for performing quantitative and morphological assessments in vivo.

  12. Survival of free and encapsulated human and rat islet xenografts transplanted into the mouse bone marrow.

    PubMed

    Meier, Raphael P H; Seebach, Jörg D; Morel, Philippe; Mahou, Redouan; Borot, Sophie; Giovannoni, Laurianne; Parnaud, Geraldine; Montanari, Elisa; Bosco, Domenico; Wandrey, Christine; Berney, Thierry; Bühler, Leo H; Muller, Yannick D

    2014-01-01

    Bone marrow was recently proposed as an alternative and potentially immune-privileged site for pancreatic islet transplantation. The aim of the present study was to assess the survival and rejection mechanisms of free and encapsulated xenogeneic islets transplanted into the medullary cavity of the femur, or under the kidney capsule of streptozotocin-induced diabetic C57BL/6 mice. The median survival of free rat islets transplanted into the bone marrow or under the kidney capsule was 9 and 14 days, respectively, whereas that of free human islets was shorter, 7 days (bone marrow) and 10 days (kidney capsule). Infiltrating CD8+ T cells and redistributed CD4+ T cells, and macrophages were detected around the transplanted islets in bone sections. Recipient mouse splenocytes proliferated in response to donor rat stimulator cells. One month after transplantation under both kidney capsule or into bone marrow, encapsulated rat islets had induced a similar degree of fibrotic reaction and still contained insulin positive cells. In conclusion, we successfully established a small animal model for xenogeneic islet transplantation into the bone marrow. The rejection of xenogeneic islets was associated with local and systemic T cell responses and macrophage recruitment. Although there was no evidence for immune-privilege, the bone marrow may represent a feasible site for encapsulated xenogeneic islet transplantation.

  13. Propofol promotes spinal cord injury repair by bone marrow mesenchymal stem cell transplantation

    PubMed Central

    Zhou, Ya-jing; Liu, Jian-min; Wei, Shu-ming; Zhang, Yun-hao; Qu, Zhen-hua; Chen, Shu-bo

    2015-01-01

    Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats. PMID:26487860

  14. Allogeneic bone marrow transplantation for postpolycythemic myeloid metaplasia with myelofibrosis: a case report.

    PubMed

    de Revel, T; Giraudier, S; Nedellec, G; Joussemet, M; Bourin, P; Schill, H; Gaillard, J F; Auzanneau, G

    1995-07-01

    Myeloid metaplasia with myelofibrosis develops in about 10% of patients with polycythemia vera. We report a case of a 48-year-old female with postpolycythemic myelofibrosis successfully treated with allogeneic HLA-matched bone marrow transplantation.

  15. Blockage of caspase-1 activation ameliorates bone marrow inflammation in mice after hematopoietic stem cell transplantation.

    PubMed

    Qiao, Jianlin; Wu, Jinyan; Li, Yuanyuan; Xia, Yuan; Chu, Peipei; Qi, Kunming; Yan, Zhiling; Yao, Haina; Liu, Yun; Xu, Kailin; Zeng, Lingyu

    2016-01-01

    Conditioning regimens before hematopoietic stem cell transplantation (HSCT), cause damage to bone marrow and inflammation. Whether inflammasomes are involved in bone marrow inflammation remains unclear. The study aims to evaluate the role of inflammasomes in bone marrow inflammation after HSCT. On days 7, 14, 21 and 28 after HSCT, mice were sacrificed for analysis of bone marrow inflammation, pro-inflammatory cytokines secretion, inflammasomes expression and caspase-1 activation. Bone marrow inflammation with neutrophils and macrophages infiltration was observed after HSCT. Secretion of IL-1β, IL-18, TNF-α and IL-6 were elevated, with increased caspase-1 activation and inflammasomes expression. Caspase-1 inhibitor administration after HSCT significantly reduced infiltration of neutrophils and macrophages into bone marrow and increased the numbers of megakaryocytes and platelets. In conclusion, inflammasomes activation is involved in bone marrow inflammation after HSCT and caspase-1 inhibition attenuates bone marrow inflammation and promoted hematopoietic reconstitution, suggesting targeting caspase-1 might be beneficial for improving HSCT outcomes.

  16. Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

    PubMed

    Teh, A; Bosco, J J; Leong, K W; Saw, M H; Menaka, N; Devashanti, P

    1997-03-01

    Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

  17. Use of spleen organ cultures to monitor hemopoietic progenitor cell regeneration following irradiation and marrow transplantation

    SciTech Connect

    von Melchner, H.; Metcalf, D.; Mandel, T.E.

    1980-11-01

    After lethal irradiation of C57BL mice followed by the injection of 10/sup 7/ marrow cells, total cellularity and progenitor cell levels exceeded pretreatment levels within 12 days in the spleen, but regeneration remained incomplete in the marrow. The exceptional regenerative capacity of progenitor populations in the spleen was observed in organ cultures of spleen slices prepared 24 h after irradiation and transplantation, excluding continuous repopulation from the marrow as a significant factor in splenic regeneration.

  18. HLA-haploidentical blood or marrow transplantation with high-dose, post-transplantation cyclophosphamide.

    PubMed

    Fuchs, E J

    2015-06-01

    In the past, partially HLA-mismatched related donor, or HLA-haploidentical, blood or marrow transplantation (haploBMT), for hematologic malignancies has been complicated by unacceptably high incidences of graft rejection or GvHD resulting from intense bi-directional alloreactivity. Administration of high doses of cyclophosphamide early after haploBMT selectively kills proliferating, alloreactive T cells while sparing non-alloreactive T cells responsible for immune reconstitution and resistance to infection. In the clinic, haploBMT with high-dose, post-transplantation cyclophosphamide is associated with acceptably low incidences of fatal graft rejection, GvHD and non-relapse mortality, and provides an acceptable treatment option for hematologic malignancies patients lacking suitably HLA-matched donors. HaploBMT with PTCy is now being investigated as a treatment of hemoglobinopathy and as a method for inducing tolerance to solid organs transplanted from the same donor. Ongoing and future clinical trials will establish the hierarchy of donor preference for hematologic malignancy patients lacking an HLA-matched sibling.

  19. Thyroid dysfunction among long-term survivors of bone marrow transplantation

    SciTech Connect

    Sklar, C.A.; Kim, T.H.; Ramsay, N.K.

    1982-11-01

    Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.

  20. Perfusion Method for Intra-bone Marrow Collection and Stem Cell Transplantation: A Critical Review.

    PubMed

    Korrapati, Narasimhulu; Nanganuru, Harikrishna Yadav

    2014-03-19

    A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Bone marrow is the soft, fatty tissue inside our bones. Bone marrow transplantation (BMT) is a powerful strategy for the treatment of leukemia, aplastic anemia, congenital immunodeficiency and autoimmune diseases. In humans, bone marrow cells (BMCs) have usually been collected by multiple bone marrow aspirations from the iliac crest. We have established a new "perfusion" method for collecting BMCs with minimal contamination with the peripheral blood using the long bones of cynomolgus monkeys. This method has proven to be a simple and safe method for harvesting BMCs and reduces the risk of acute graft versus host disease in allogeneic BMT. Intra-bone marrow-BMT (IBM-BMT) provides distinct advantages because it recruits donor-derived hematopoietic stem cells and mesenchymal stem cells. IBM-BMT has been shown to currently be the best strategy for allogeneic BMT. Here we review the perfusion method (for harvesting BMCs) and IBM-BMT (for their transplantation) and show that this combination will become a powerful new clinical strategy for allogeneic BMT.

  1. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    PubMed

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  2. Regression of Adjuvant-Induced Arthritis in Rats Following Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    van Bekkum, Dirk W.; Bohre, Els P. M.; Houben, Paul F. J.; Knaan-Shanzer, Shoshan

    1989-12-01

    Total body irradiation followed by bone marrow transplantation was found to be an effective treatment for adjuvant arthritis induced in rats. This treatment is most effective when applied shortly after the clinical manifestation of arthritis--i.e., 4-7 weeks after administration of Mycobacterium tuberculosis. Transplantation of bone marrow at a later stage results in a limited recovery, in that the inflammatory reaction regresses but the newly formed excessive bone is not eliminated. Local irradiation of the affected joints had no effect on the disease. It could also be excluded that the recovery of arthritis following marrow transplantation is due to lack of available antigen. Transplantation of syngeneic bone marrow is as effective as that of allogeneic bone marrow from a rat strain that is not susceptible to induction of adjuvant arthritis. The beneficial effect of this treatment cannot be ascribed to the immunosuppressive effect of total body irradiation, since treatment with the highly immunosuppressive drug Cyclosporin A resulted in a regression of the joint swelling but relapse occurred shortly after discontinuation of the treatment.

  3. Implant placement and restoration following bone marrow transplantation for chronic leukemia: a case report.

    PubMed

    Curtis, J W

    1996-01-01

    Bone marrow transplantation is used with increasing frequency to treat various hematologic diseases, particularly the leukemias. A case involving dental implant therapy in a woman who had undergone successful allogeneic bone marrow transplantation for treatment of chronic myelogenous leukemia is presented to illustrate specific considerations in treatment planning, surgical management, and overall prosthetic rehabilitation. Five mandibular endosseous implants were placed in November 1991 and subsequently restored with a fixed detachable prosthesis. The patient experienced no complications related to the implants or prosthesis during the 3 years after restoration.

  4. Mesenchymal Bone Marrow-derived Stem Cells Transplantation in Patients with HCV Related Liver Cirrhosis

    PubMed Central

    Lukashyk, Sviatlana P.; Tsyrkunov, Vladimir M.; Isaykina, Yanina I.; Romanova, Oksana N.; Shymanskiy, Artur T.; Aleynikova, Olga V.; Kravchuk, Rimma I.

    2014-01-01

    Background and Aims To evaluate the effect of intraparenchymal transplantation of mesenchymal bone marrow-derived stem cells (BMSCs) in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). Methods Mononuclear cells were isolated from patient bone marrow and were passaged several times in vitro in order to reach the required volume. Attributes of the BMSCs were evaluated by the presence of the surface markers CD105+, CD90+, and CD73+. Cells from each passage were evaluated for sterility, and they were transplanted intraparenchymally into liver tissue. Clinical and laboratory data were evaluated and morphological studies of liver biopsy were performed prior to and 6 months after transplantation. Results On clinical evaluation, the general state of these patients was improved at 1 month following transplantation of BMSCs. At 1 and 6 months post-transplantation, jaundice was absent in four (67%) patients. After 6 months, functional hepatic indices were improved, i.e. decrease of ALT and AST activity and bilirubin level. However, these decreases were not statistically different (P>0.05). Expression of CD34 and α-SMA in liver biopsy samples were decreased at 6 months after transplantation, consistent with structural improvements in mitochondria and nuclear compartments. Conclusions Intraparenchymal transplantation of autologous BMSCs improved the functional condition of the liver, stimulated reparative processes in hepatocytes, and decreased extracellular matrix protein (EMP) count in hepatic tissues of patients with LC. It was well tolerated and was not associated with any complications both during and after BMSC transplantation. PMID:26356872

  5. Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation.

    PubMed

    Bozkurt, Mehmet; Klimczak, Aleksandra; Nasir, Serdar; Zor, Fatih; Krokowicz, Lukasz; Siemionow, Maria

    2013-01-01

    Cellular and vascularized bone marrow cells have been used to induce donor-specific chimerism in various models of composite tissue allotransplantation. Although thymus transplantation has been reported in the literature, the effect of thymus transplantation on chimerism levels in vascularized bone containing composite tissue allotransplantation has not been reported. In this study, a new method for composite vascularized sternal bone marrow transplant model is descried that can be applied to augment chimerism after transplantation. A total of seven composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin transplantations were performed in two groups. The first group (n = 5) was designed as an allotransplantation group and the second group (n = 2) was designed as an isotransplantation group. Composite osseomusculocutaneous sternum, ribs, thymus, and pectoralis muscles allografts were harvested on the common carotid artery and external jugular vein and a heterotopic transplantation was performed to the inguinal region of the recipient rat. Cyclosporine A monotherapy was administered in order to prevent acute and chronic allograft rejection. Animals sacrificed when any sign of rejection occurred. The longest survival was 156 day post-transplant. Assessment of bone marrow cells within sternum bone component and flow cytometry analysis of donor-specific chimerism in the peripheral blood of recipients were evaluated. Our results showed that this composite allograft carried 7.5 × 10(6) of viable hematopoietic cells within the sternum component. At day 7 post-transplant chimerism was developed in T-cell population and mean level was assessed at 2.65% for RT1(n) /CD4 and at 1.0% for RT1(n) /CD8. In this study, a new osseomusculocutaneous sternum, ribs, thymus, pectoralis muscle, and skin allotransplantation model is reported which can be used to augment hematopoietic activity for chimerism induction after transplantation.

  6. Cure of murine thalassemia by bone marrow transplantation without eradication of endogenous stem cells

    SciTech Connect

    Wagemaker, G.; Visser, T.P.; van Bekkum, D.W.

    1986-09-01

    alpha-Thalassemic heterozygous (Hbath/+) mice were used to investigate the possible selective advantage of transplanted normal (+/+) hemopoietic cells. Without conditioning by total-body irradiation (TBI), infusion of large numbers of normal bone marrow cells failed to correct the thalassemic peripheral blood phenotype. Since the recipients' stem cells are normal with respect to number and differentiation capacity, it was thought that the transplanted stem cells were not able to lodge, or that they were not stimulated to proliferate. Therefore, a nonlethal dose of TBI was given to temporarily reduce endogenous stem cell numbers and hemopoiesis. TBI doses of 2 or 3 Gy followed by infusion of normal bone marrow cells proved to be effective in replacing the thalassemic red cells by normal red cells, whereas a dose of 1 Gy was ineffective. It is concluded that cure of thalassemia by bone marrow transplantation does not necessarily require eradication of thalassemic stem cells. Consequently, the objectives of conditioning regimens for bone marrow transplantation of thalassemic patients (and possibly other nonmalignant hemopoietic disorders) should be reconsidered.

  7. The Human Figure Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

    ERIC Educational Resources Information Center

    Packman, Wendy L.; Beck, Vanessa L.; VanZutphen, Kelly H.; Long, Janet K.; Spengler, Gisele

    2003-01-01

    There is little research on the psychological impact of bone marrow transplantation (BMT) on family members. This study uses the Human Figure Drawing (HFD) to measure siblings' emotional distress toward BMT. Among the siblings, feelings of isolation, anger, depression, anxiety, and low self-esteem emerged as major themes. Findings indicate the…

  8. The Kinetic Family Drawing with Donor and Nondonor Siblings of Pediatric Bone Marrow Transplant Patients.

    ERIC Educational Resources Information Center

    Packman, Wendy L.; Crittenden, Mary R.; Fischer, Jodie B. Rieger; Cowan, Morton J.; Long, Janet K.; Gruenert, Carol; Schaeffer, Evonne; Bongar, Bruce

    1998-01-01

    Utilizes the Kinetic Family Drawings-Revised (KFD-R) to measure siblings' (N=44) feelings and attitudes toward bone marrow transplants. Data from drawings and discussions with siblings underscore that not all children are affected by stress in the same way. How a particular child responds depends on factors such as life history, personality,…

  9. [Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation].

    PubMed

    Echeverri-Toro, Lina; Arango, Andrés; Ospina, Sigifredo; Agudelo, Carlos

    2015-01-01

    We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia. PMID:26849691

  10. Cirrhosis due to chronic hepatitis E infection in a child post-bone marrow transplant.

    PubMed

    Halac, Ugur; Béland, Kathie; Lapierre, Pascal; Patey, Natacha; Ward, Pierre; Brassard, Julie; Houde, Alain; Alvarez, Fernando

    2012-05-01

    Chronic hepatitis E virus (HEV) infection occurs in immunosuppressed adults. We detected HEV ribonucleic acid in serum of an adolescent patient who had undergone bone marrow transplantation and subsequently presented with persistently increased aminotransferases and histologic chronic hepatitis, and eventually developed cirrhosis. Phylogenetic analysis revealed these HEV strains were similar to swine genotype 3a, suggesting a possible zoonosis. PMID:22341950

  11. [Bordetella bronchiseptica recurrent bacteraemia in a patient with bone marrow transplantation].

    PubMed

    Echeverri-Toro, Lina; Arango, Andrés; Ospina, Sigifredo; Agudelo, Carlos

    2015-01-01

    We report a case of recurrent bacteraemia caused by Bordetella bronchiseptica in an immunocompromised patient with a history of allogenic bone marrow transplantation for myelodysplastic syndrome, who was admitted to hospital with febrile syndrome. Bordetella bronchiseptica is an uncommon human pathogen which mainly affects immunocompromised patients, being a rare cause of bacteraemia.

  12. T Cell Repertoire Development in XSCID Dogs Following Non-conditioned Allogeneic Bone Marrow Transplantation

    PubMed Central

    Vernau, William; Hartnett, Brian J.; Kennedy, Douglas R.; Moore, Peter F.; Henthorn, Paula S.; Weinberg, Kenneth I.; Felsburg, Peter J.

    2007-01-01

    Dogs with X-linked severe combined immunodeficiency (XSCID) can be successfully treated by bone marrow transplants (BMT) resulting in full immunologic reconstitution and engraftment of both donor B and T cells without the need for pre-transplant conditioning. In this study, we evaluated the T cell diversity in XSCID dogs 4 months to 10 1/2 years following BMT. At 4 months post transplantation, when the number of CD45RA+ (naïve) T cells had peaked and plateaued, the T cells in the transplanted dogs showed the same complex, diverse repertoire as those of normal young adult dogs. A decline in T cell diversity became evident approximately 3 1/2 years post transplant, but the proportion of Vβ families showing a polyclonal Gaussian spectratype still predominated up to 7 1/2 years post transplant. In two dogs evaluated at 7 1/2 and 10 1/2 years post transplant, >75% of the Vβ families consisted of a skewed or oligoclonal spectratype that was associated with a CD4/CD8 ratio of <0.5. The decline in the complexity of T cell diversity in the transplanted XSCID dogs is similar to that reported for XSCID patients following BMT. However, in contrast to transplanted XSCID boys who show a significant decline in their T cell diversity by 10 to 12 years following BMT, transplanted XSCID dogs maintain a polyclonal, diverse T cell repertoire through mid-life. PMID:17697962

  13. Marrow transplantation from tolerant donors to treat and prevent autoimmune diseases in BXSB mice

    SciTech Connect

    Himeno, K.; Good, R.A.

    1988-04-01

    Autoimmune-prone BXSB male mice were supralethally irradiated and transplanted with CBA/H bone marrow cells. A complete and long-term chimerism was established when donor mice had been induced to develop tolerance of BXSB male antigens by combined treatment with BXSB male spleen cells and cyclophosphamide. Such chimeras did not express autoimmune phenomena or develop lethal autoimmune manifestations. Nor did the recipient mice develop the wasting syndrome or evidence of persistent immunodeficiencies that have been seen in other strains of autoimmune-resistant mice that had been transplanted with bone marrow cells across major histocompatibility complex barriers following an initial purging of the bone marrow of Thy-1+ cells using anti-Thy-1+C.

  14. Prognostic factors in bone marrow transplantation for beta thalassemia major: experiences from Iran.

    PubMed

    Ghavamzadeh, A; Nasseri, P; Eshraghian, M R; Jahani, M; Baybordi, I; Nateghi, J; Khodabandeh, A; Sadjadi, A R; Mohyeddin, M; Khademi, Y

    1998-12-01

    This study concerns the effects of several pre-transplant features on outcome for patients with beta thalassemia major who underwent bone marrow transplantation (BMT). Seventy patients with beta thalassemia major underwent bone marrow transplantation during the period 1991-1997 in Shariati Hospital in Tehran, Iran. The survival and rejection curves levelled off at 8 and 18 months after transplantation at 82.6% and 11.4%, respectively. Pre-transplant clinical features (age, serum ferritin, portal fibrosis, hepatomegaly and quality of chelation therapy) were examined for their effects on survival and recurrence of thalassemia in this group of patients who were less than 16 years old. Increasing age, presence of portal fibrosis and increasing serum ferritin were significantly associated with reduced probability of survival (P = 0.0047, P = 0.016 and P = 0.024, respectively). Hepatomegaly and inadequate pre-transplant chelation therapy which were documented as poor prognostic factors in previous studies, were not evaluable in this study. We also showed the benefits of transplanting more than 5.5 x 10(8)/kg cells in this group of patients with no increase in complications.

  15. Effects of Microtus fortis lymphocytes on Schistosoma japonicum in a bone marrow transplantation model.

    PubMed

    Hu, Yuan; Xu, Yuxin; Lu, Weiyuan; Quan, Hong; Shen, Yujuan; Yuan, Zhongying; Zhang, Jing; Zang, Wei; He, Yongkang; Cao, Jianping

    2014-07-01

    Microtus fortis is a non-permissive host for Schistosoma japonicum. While M. fortis lymphocytes are known to provide natural resistance against S. japonicum, the specific mechanism remains unclear. A bone marrow transplantation (BMT) model was established using immunodeficient mice, either nude (experiment 1) or V(D)J recombination activation gene deficient mice (RAG-1(-/-)) (experiment 2) as recipients and M. fortis or C57BL/6 mice as donors. The growth and development of S. japonicum were evaluated in each group to assess the role of M. fortis lymphocytes in the response to infection. Lymphocyte ratios and S. japonicum-specific antibody production in transplanted groups increased significantly compared to those in non-transplanted group. Spleen indices and density of splenic lymphocytes in transplanted RAG-1(-/-) mice were higher than those in non-transplanted RAG-1(-/-) mice. No difference in the worm burden was observed among group A (transplants derived from M. fortis), B (transplants derived from C57BL/6 mouse) and C (non-transplanted mice), although worms in group A were shorter than those in other groups, except non-transplanted RAG-1(-/-) mice. Reproductive systems of worms in mice (nude or RAG-1(-/-)) transplanted from M. fortis were not as mature as those in mice (nude or RAG-1(-/-)) transplanted from C57BL/6 mouse and non-transplanted nude mice, but they were more mature than worms in non-transplanted RAG-1(-/-) mice. Therefore, the transplantation model using nude and RAG-1(-/-) mice was successfully established. The M. fortis lymphocytes did not appear to affect the S. japonicum worm burden, but they led to schistosome shortening and a significant reduction in parasite spawning. Thus, M. fortis cellular and humoral immunity provides a defense against schistosomes by negatively impacting the parasite growth and reproductive development.

  16. Nutritional issues in adolescents after bone marrow transplant: a literature review.

    PubMed

    Rodgers, Cheryl; Walsh, Teresa

    2008-01-01

    Bone marrow transplantation and related complications can cause gastrointestinal (GI) side effects that can lead to poor nutrition, which has been associated with several morbidity and mortality issues. Adolescents require adequate nutrition not only to maintain health but to advance with normal growth and development. This article synthesizes the bone marrow transplant (BMT) literature regarding adolescents' nutritional needs, etiologies of altered oral intake, GI symptoms, nutritional assessments, nutritional interventions, and quality of life associated with poor nutrition. In addition, gaps in knowledge in the literature are identified. To provide effective and thorough care to patients during their BMT recovery, the knowledge base of nutritional and eating issues after transplant needs to become more comprehensive. Nurses play an important role in gathering and reporting clinical information. By anticipating potential risk factors, assessing and identifying symptoms, and initiating appropriate interventions promptly, patients can experience a more positive BMT experience.

  17. Videophone support for an eight-year-old boy undergoing paediatric bone marrow transplantation.

    PubMed

    Bensink, Mark; Shergold, Jill; Lockwood, Liane; Little, Margaret; Irving, Helen; Russell, Trevor; Wootton, Richard

    2006-01-01

    We report the use of an Internet-based videophone to support a child undergoing bone marrow transplantation (BMT). Over the Christmas period, an eight-year-old boy with an underlying diagnosis of attention-deficit/hyperactivity disorder (ADHD) and a history of absconding and aggressive non-compliant behaviour was treated by BMT. We installed an Internet-based videophone in the patient's hospital room two days post-transplant. A second videophone was installed in the patient's home and used the existing home telephone line. In all, 14 videophone calls were made over a nine-day period. The videophone improved interfamily social and emotional support, and appeared to reduce some of the inherent anxiety and distress resulting from paediatric bone marrow transplantation.

  18. The role of bone marrow-derived cells during the bone healing process in the GFP mouse bone marrow transplantation model.

    PubMed

    Tsujigiwa, Hidetsugu; Hirata, Yasuhisa; Katase, Naoki; Buery, Rosario Rivera; Tamamura, Ryo; Ito, Satoshi; Takagi, Shin; Iida, Seiji; Nagatsuka, Hitoshi

    2013-03-01

    Bone healing is a complex and multistep process in which the origin of the cells participating in bone repair is still unknown. The involvement of bone marrow-derived cells in tissue repair has been the subject of recent studies. In the present study, bone marrow-derived cells in bone healing were traced using the GFP bone marrow transplantation model. Bone marrow cells from C57BL/6-Tg (CAG-EGFP) were transplanted into C57BL/6 J wild mice. After transplantation, bone injury was created using a 1.0-mm drill. Bone healing was histologically assessed at 3, 7, 14, and 28 postoperative days. Immunohistochemistry for GFP; double-fluorescent immunohistochemistry for GFP-F4/80, GFP-CD34, and GFP-osteocalcin; and double-staining for GFP and tartrate-resistant acid phosphatase were performed. Bone marrow transplantation successfully replaced the hematopoietic cells into GFP-positive donor cells. Immunohistochemical analyses revealed that osteoblasts or osteocytes in the repair stage were GFP-negative, whereas osteoclasts in the repair and remodeling stages and hematopoietic cells were GFP-positive. The results indicated that bone marrow-derived cells might not differentiate into osteoblasts. The role of bone marrow-derived cells might be limited to adjustment of the microenvironment by differentiating into inflammatory cells, osteoclasts, or endothelial cells in immature blood vessels.

  19. A Role For Photodynamic Therapy In Autologous Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    Sieber, Fritz

    1988-02-01

    Simultaneous exposure to the amphipathic fluorescent dye merocyanine 540 (MC 540) and light of a suitable wavelength rapidly kills leukemia, lymphoma, and neuroblastoma cells but spares normal pluripotent hematopoietic stem cells. Tests in several preclinical models and early results of a phase I clinical trial suggest that MC 540-mediated photosensitization may be useful for the extracorporeal purging of autologous remission bone marrow grafts.

  20. What Is a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... procedure allows the recipient to get new stem cells that work properly. Stem cells are found in bone marrow, ... the body doesn't make enough red blood cells or they don't work properly. Certain immune-deficiency diseases that prevent the ...

  1. Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation.

    PubMed

    Storek, J; Joseph, A; Espino, G; Dawson, M A; Douek, D C; Sullivan, K M; Flowers, M E; Martin, P; Mathioudakis, G; Nash, R A; Storb, R; Appelbaum, F R; Maloney, D G

    2001-12-15

    The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G(2) (IgG(2)) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed more than [corrected] 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC(+) CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC(+) CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG(2) and specific IgG against Haemophilus influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo-generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible. PMID:11739150

  2. Rh antibodies against the pretransplant red cells following Rh-incompatible bone marrow transplantation.

    PubMed

    Heim, M U; Schleuning, M; Eckstein, R; Huhn, D; Siegert, W; Clemm, C; Ledderose, G; Kolb, H J; Wilmanns, W; Mempel, W

    1988-01-01

    A 22-year-old, blood group O, Rh-positive (R2r) man received bone marrow from his blood group A, Rh-negative (rr), HLA-identical sister for treatment of acute lymphocytic leukemia. The patient's pretransplantation serum contained anti-A in a low concentration; therefore, plasmapheresis was not done prior to transfusion of bone marrow. To prevent graft-versus-host disease, bone marrow was incubated with absorbed rabbit antithymocyte globulin prior to infusion, and the patient was treated with methotrexate in the posttransplantation period. After transplantation, the patient received 6 units of group O, Rh-negative (rr) packed red cells from random donors and 6 units of platelets from the marrow donor. Three months after transplantation, 0.5 percent of his red cells were still of the host's type (group O, Rh-positive), as detected by immunofluorescence technique in blood smears. Four months after transplantation, three different Rh antibodies--anti-D, -E, and -G--were detected. Since the patient received only Rh-negative red cell transfusions, it is concluded that he was immunized to his original red cells.

  3. Origin of cell populations after bone marrow transplantation. Analysis using DNA sequence polymorphisms.

    PubMed Central

    Ginsburg, D; Antin, J H; Smith, B R; Orkin, S H; Rappeport, J M

    1985-01-01

    After successful bone marrow transplantation, patient hematopoietic and lymphoid cells are replaced by cells derived from the donor marrow. To document and characterize successful engraftment, host and donor cells must be distinguished from each other. We have used DNA sequence polymorphism analysis to determine reliably the host or donor origin of posttransplant cell populations. Using a selected panel of six cloned DNA probes and associated sequence polymorphisms, at least one marker capable of distinguishing between a patient and his sibling donor can be detected in over 95% of cases. Posttransplant patient peripheral leukocytes were examined by DNA restriction enzyme digestion and blot hybridization analysis. We have studied 18 patients at times varying from 13 to 1,365 d after marrow transplantation. Mixed lymphohematopoietic chimerism was detected in 3 patients, with full engraftment documented in 15. One patient with severe combined immunodeficiency syndrome was demonstrated to have T cells of purely donor origin, with granulocytes and B cells remaining of host origin. Posttransplant leukemic relapse was studied in one patient and shown to be of host origin. DNA analysis was of particular clinical value in three cases where failure of engraftment or graft loss was suspected. In two of the three cases, full engraftment was demonstrated and in the third mixed lymphohematopoietic chimerism was detected. DNA sequence polymorphism analysis provides a powerful tool for the documentation of engraftment after bone marrow transplantation, for the evaluation of posttransplant lymphoma or leukemic relapse, and for the comprehensive study of mixed hematopoietic and lymphoid chimeric states. Images PMID:3882761

  4. Rh antibodies against the pretransplant red cells following Rh-incompatible bone marrow transplantation.

    PubMed

    Heim, M U; Schleuning, M; Eckstein, R; Huhn, D; Siegert, W; Clemm, C; Ledderose, G; Kolb, H J; Wilmanns, W; Mempel, W

    1988-01-01

    A 22-year-old, blood group O, Rh-positive (R2r) man received bone marrow from his blood group A, Rh-negative (rr), HLA-identical sister for treatment of acute lymphocytic leukemia. The patient's pretransplantation serum contained anti-A in a low concentration; therefore, plasmapheresis was not done prior to transfusion of bone marrow. To prevent graft-versus-host disease, bone marrow was incubated with absorbed rabbit antithymocyte globulin prior to infusion, and the patient was treated with methotrexate in the posttransplantation period. After transplantation, the patient received 6 units of group O, Rh-negative (rr) packed red cells from random donors and 6 units of platelets from the marrow donor. Three months after transplantation, 0.5 percent of his red cells were still of the host's type (group O, Rh-positive), as detected by immunofluorescence technique in blood smears. Four months after transplantation, three different Rh antibodies--anti-D, -E, and -G--were detected. Since the patient received only Rh-negative red cell transfusions, it is concluded that he was immunized to his original red cells. PMID:3130695

  5. Bone marrow-derived progenitor cells in de novo liver regeneration in liver transplant.

    PubMed

    Lee, Sung-Gyu; Moon, Sung-Hwan; Kim, Hee-Je; Lee, Ji Yoon; Park, Soon-Jung; Chung, Hyung-Min; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Hojong; Kwon, Tae-Won; Cho, Yong-Pil

    2015-09-01

    The study was designed (1) to examine the hypothesis that circulating progenitor cells play a role in the process of de novo regeneration in human liver transplants and that these cells arise from a cell population originating in, or associated with, the bone marrow and (2) to investigate whether the transplanted liver volume has an effect on the circulating recipient-derived progenitor cells that generate hepatocytes during this process. Clinical data and liver tissue characteristics were analyzed in male individuals who underwent sex-mismatched adult-to-adult living donor liver transplantation using dual left lobe grafts. Dual left lobe grafts were examined at the time of transplantation and 19 to 27 days after transplantation. All recipients showed recovery of normal liver function and a significant increase in the volume of the engrafted left lobes after transplantation. Double staining for a Y-chromosome probe and the CD31 antigen showed the presence of hybrid vessels composed of recipient-derived cells and donor cells within the transplanted liver tissues. Furthermore, CD34-expressing cells were observed commingling with Y-chromosome+ cells. The ratio of recipient-derived vessels and the number of Y+ CD34+ cells tended to be higher when smaller graft volumes underwent transplantation. These findings suggest that the recruitment of circulating bone marrow-derived progenitor cells could contribute to vessel formation and de novo regeneration in human liver transplants. Moreover, graft volume may be an important determinant for the active mobilization of circulating recipient-derived progenitor cells and their contribution to liver regeneration.

  6. Effects of sublethal irradiation on patterns of engraftment after murine bone marrow transplantation.

    PubMed

    Andrade, Jacob; Ge, Shundi; Symbatyan, Goar; Rosol, Michael S; Olch, Arthur J; Crooks, Gay M

    2011-05-01

    Attempts to reduce the toxicity of hematopoietic stem cell transplantation have led to the use of various immunosuppressive, yet nonmyeloablative preparative regimens that often include low-dose irradiation. To determine the effects of low-dose irradiation on the dynamics of donor cell engraftment after bone marrow transplantation (BMT), we coupled standard endpoint flow cytometric analysis with in vivo longitudinal bioluminescence imaging performed throughout the early (<10 days) and late (days 10-90) post-BMT periods. To exclude the contribution of irradiation on reducing immunologic rejection, severely immune-deficient mice were chosen as recipients of allogeneic bone marrow. Flow cytometric analysis showed that sublethal doses of total body irradiation (TBI) significantly increased long-term (14 weeks) donor chimerism in the bone marrow compared with nonirradiated recipients (P < .05). Bioluminescence imaging demonstrated that the effect of TBI (P < .001) on chimerism occurred only after the first 7 days post-BMT. Flow cytometric analysis on day 3 showed no increase in the number of donor cells in irradiated bone marrow, confirming that sublethal irradiation does not enhance marrow chimerism early after transplantation. Local irradiation also significantly increased late (but not early) donor chimerism in the irradiated limb. Intrafemoral injection of donor cells provided efficient early chimerism in the injected limb, but long-term systemic donor chimerism was highest with i.v. administration (P < .05). Overall, the combination of TBI and i.v. administration of donor cells provided the highest levels of long-term donor chimerism in the marrow space. These findings suggest that the major effect of sublethal irradiation is to enhance long-term donor chimerism by inducing proliferative signals after the initial phase of homing.

  7. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation

    PubMed Central

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4’,6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons. PMID:26309595

  8. Spinal cord injury in rats treated using bone marrow mesenchymal stem-cell transplantation.

    PubMed

    Chen, Yu-Bing; Jia, Quan-Zhang; Li, Dong-Jun; Sun, Jing-Hai; Xi, Shuang; Liu, Li-Ping; Gao, De-Xuan; Jiang, Da-Wei

    2015-01-01

    The aim of this study was to observe the effects of bone marrow mesenchymal stem-cell transplantation (BMSCs) in repairing acute spinal cord damage in rats and to examine the potential beneficial effects. 192 Wistar rats were randomized into 8 groups. Spinal cord injury was created. Behavior and limb functions were scored. Repairing effects of BMSCs transplantation was evaluated and compared. In vitro 4',6-diamidino-2-phenylindole (DAPI)-tagged BMSCs were observed, and whether they migrated to the area of spinal cord injury after intravenous tail injection was investigated. The expression of neuron-specific protein (NSE) on BMSCs was examined. Fifteen days after transplantation, the BMSCs-treated groups scored significantly higher in limb function tests than the untreated group. Pathological sections of the bone marrow after operation showed significant recovery in treated groups in comparison to the control group. After transplantation, small amounts of fluorescent-tagged BMSCs can be found in the blood vessels in the area of spinal cord injury, and fluorescent-tagged BMSCs were diffused in extravascular tissues, whereas the DAPI-tagged BMSCs could not be detected,and BrdU/NSE double-labeled cells were found in the injured marrow. BMSCs improve behavioral responses and can repair spinal cord injuries by migrating to the injured area, where they can differentiate into neurons.

  9. Tolerance induction using nanoparticles bearing HY peptides in bone marrow transplantation.

    PubMed

    Hlavaty, Kelan A; McCarthy, Derrick P; Saito, Eiji; Yap, Woon Teck; Miller, Stephen D; Shea, Lonnie D

    2016-01-01

    Allogeneic cell therapies have either proven effective or have great potential in numerous applications, though the required systemic, life-long immunosuppression presents significant health risks. Inducing tolerance to allogeneic cells offers the potential to reduce or eliminate chronic immunosuppression. Herein, we investigated antigen-loaded nanoparticles for their ability to promote transplant tolerance in the minor histocompatibility antigen sex-mismatched C57BL/6 model of bone marrow transplantation. In this model, the peptide antigens Dby and Uty mediate rejection of male bone marrow transplants by female CD4+ and CD8+ T cells, respectively, and we investigated the action of nanoparticles on these T cell subsets. Antigens were coupled to or encapsulated within poly(lactide-co-glycolide) (PLG) nanoparticles with an approximate diameter of 500 nm. Delivery of the CD4-encoded Dby epitope either coupled to or encapsulated within PLG particles prevented transplant rejection, promoted donor-host chimerism, and suppressed proliferative and IFN-γ responses in tolerized recipients. Nanoparticles modified with the Uty peptide did not induce tolerance. The dosing regimen was investigated with Dby coupled particles, and a single dose delivered the day after bone marrow transplant was sufficient for tolerance induction. The engraftment of cells was significantly affected by PD-1/PDL-1 costimluation, as blockade of PD-1 reduced engraftment by ∼50%. In contrast, blockade of regulatory T cells did not impact the level of chimerism. The delivery of antigen on PLG nanoparticles promoted long-term engraftment of bone marrow in a model with a minor antigen mismatch in the absence of immunosuppression, and this represents a promising platform for developing a translatable, donor-specific tolerance strategy.

  10. Bone marrow transplantation for CVID-like humoral immune deficiency associated with red cell aplasia.

    PubMed

    Sayour, Elias J; Mousallem, Talal; Van Mater, David; Wang, Endi; Martin, Paul; Buckley, Rebecca H; Barfield, Raymond C

    2016-10-01

    Patients with common variable immunodeficiency (CVID) have a higher incidence of autoimmune disease, which may mark the disease onset; however, anemia secondary to pure red cell aplasia is an uncommon presenting feature. Here, we describe a case of CVID-like humoral immune deficiency in a child who initially presented with red cell aplasia and ultimately developed progressive bone marrow failure. Although bone marrow transplantation (BMT) has been associated with high mortality in CVID, our patient was successfully treated with a matched sibling BMT and engrafted with >98% donor chimerism and the development of normal antibody titers to diphtheria and tetanus toxoids. PMID:27273469

  11. [Bone marrow transplantation in aplastic anemia. Experience at a Mexican institution. Bone marrow transplantation group of the Salvador Zubirán National Institute of Nutrition].

    PubMed

    León-Rodríguez, E; Sosa Sánchez, R; Gómez, E; Ochoa Sosa, C

    1993-01-01

    During the period of May 1986 through February 1991, nine allogeneic bone marrow transplants (BMT) on eight severe aplastic anemia (SAA) patients were performed at the Instituto Nacional de la Nutrición Salvador Zubirán in Mexico City. Mean age at BMT was 18 years (age interval 12-30); seven were men; all patients had a clinical history of multiple blood transfusions; six individuals were infected at the time of the transplant. The conditioning regimens were: cyclophosphamide (Cy) in three patients; Cy+ total nodal radiation in five; and total nodal radiation only in the second transplant of one patient. Graft versus host disease (GVHD) prophylaxis was attempted with methotrexate plus cyclosporin A (CsA) in six patients, methylprednisolone plus CsA in two, and prednisone + CsA in the patient retransplanted. All procedures were carried out under single reverse isolation without gut decontamination. Seven of the nine procedures grafted (two cases died on days +8 and +25 due to infection). In the surviving, the median time for reaching > 1.0 white blood cells x 10(9)/L was 22 days (time interval 11-31); > 0.5 neutrophils x 10(9)/L in 27 days (time interval 15-42) and the same lapse to reach > 50 platelets x 10(9)/L. Length of hospital stay was 42 days (time interval 15-61). Acute GVHD was seen in one of the seven patients surviving the period of bone marrow aplasia (14%). Of six long term survivors (including one patient with a second transplant) chronic GVHD was present in four (67%): chronic GVHD was fatal in one individual but was well controlled in three.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Organization and Development of Bone Marrow Donation and Transplantation in Poland.

    PubMed

    Filipiak, Jagoda; Dudkiewicz, Małgorzata; Czerwiński, Jarosław; Kosmala, Karolina; Łęczycka, Anna; Malanowski, Piotr; Żalikowska-Hołoweńko, Jolanta; Małkowski, Piotr; Danielewicz, Roman

    2015-10-01

    This paper describes bone marrow donation and transplantation in Poland in terms of its history, current state, and information on the quality control system. Based on data gathered from the informatics systems of the Polish Central Unrelated Potential Bone Marrow Donor and Cord Blood Registry and the Polish transplant registries, as well as World Marrow Donor Association statistics, we performed an overview study to collect and compare numbers on hematopoietic stem cells donations and transplantations in Poland in the years 2010-2014. In the last 5 years, the number of registered potential hematopoietic stem cells donors in Poland increased by more than 4 times, from about 146,000 to over 750,000. During the same period, the number of patients qualified to hematopoietic stem cells transplantation from unrelated donor increased from 557 in 2010 to 817 in 2014. We observed a striking change in the percentage of transplantations performed in Polish centers using material collected from national donors--from 24% to 60%. This shift was also evident in the number of search procedures closed with acceptation of Polish donors--from 27% in 2010 to 58% in 2014. Another consequence of Polish registry growth is the increasing number of donations from Polish donors for international patients. Between 2010 and 2014, the percent of donation for non-national patient increased from 33% to 76%, placing Poland in 6th place in the ranking of the HSC "exporters" worldwide. Growth of transplantation rates involves standardization process, which is a natural way of development for national organizations in the field of HSCT because of its international character.

  13. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  14. Efficient conditional gene expression following transplantation of retrovirally transduced bone marrow stem cells.

    PubMed

    Chung, Jie-Yu; Mackay, Fabienne; Alderuccio, Frank

    2015-01-01

    Retroviral gene therapy combined with bone marrow stem cell transplantation can be used to generate mice with ectopic gene expression in the bone marrow compartment in a quick and cost effective manner when compared to generating and maintaining transgenic mouse lines. However a limitation of this procedure is the lack of cell specificity in gene expression that is associated with the use of endogenous retroviral promoters. Restricting gene expression to specific cell subsets utilising tissue-specific promoter driven retroviral vectors is a challenge. Here we describe the generation of conditional expression of retrovirally encoded genes in specific bone marrow derived cell lineages utilising a Cre-dependent retroviral vector. By utilising Lck and CD19 restricted Cre transgenic bone marrow stem cells, we generate chimeric animals with T or B lymphocyte restricted gene expression respectively. The design of the Cre-dependent retroviral vector enables expression of encoded MOG and GFP genes only in association with Cre mediated DNA inversion. Importantly this strategy does not significantly increase the size of the retroviral vector; as such we are able to generate bone marrow chimeric animals with significantly higher chimerism levels than previous studies utilising Cre-dependent retroviral vectors and Cre transgenic bone marrow stem cells. This demonstrates that the use of Cre-dependent retroviral vectors is able to yield high chimerism levels for experimental use and represent a viable alternative to generating transgenic animals.

  15. Autologous bone marrow transplantation following chemotherapy and irradiation in dogs with spontaneous lymphomas. [. gamma. rays

    SciTech Connect

    Bowles, C.A.; Bull, M.; McCormick, K.; Kadin, M.; Lucas, D.

    1980-09-01

    Thirty dogs with spontaneous lymphomas were administered two to six cycles of chemotherapy and were randomized into 3 groups to receive 800 rads of total body irradiation and autologous bone marrow transplantation. Of 10 dogs irradiated after chemotherapy-induced remission and infused with remission marrow (group 1), 8 (80%) had successful grafts and experienced remissions lasting 62 to 1024 days. Of 9 dogs irradiated during remission and infused with remission marrow mixed with autologous tumor cells (group 2), 6 (66%) had remission lasting 15 to 45 days. Eleven dogs with progressive tumor growth (relapse) following chemotherapy were irradiated and infused with remission marrow (group 3). Tumor remission lasting 39 to 350 days was observed in 5 dogs (45%) in this group, and 6 dogs died in less than 30 days. Dogs in groups 1 to 3 had median survival times of 216, 60, and 45 days, respectively. The prolonged survival times for dogs in group 1 compared to dogs in groups 2 and 3 suggest that protocols involving irradiation and autologous marrow grafting in this model would be most effective when these protocols are applied to animals having a minimum tumor burden at the time of irradiation and when the grafting is done with tumor-free autologous marrow.

  16. Professional attitudes toward patient safety culture in a bone marrow transplant unit.

    PubMed

    Fermo, Vivian Costa; Radünz, Vera; Rosa, Luciana Martins da; Marinho, Monique Mendes

    2016-03-01

    Objective To identify the attitude of health professionals toward the patient safety culture at a bone marrow transplant unit. Methods Quantitative research approach, cross-sectional survey conducted at a bone marrow transplant unit in Santa Catarina, Brazil. Data were collected using a Safety Attitudes Questionnaire with 33 health professionals in August and September of 2013. A total of 37 attitudes were assessed according to six safety dimensions of patient safety culture. Data were analysed by applying descriptive and inferential statistics, ANOVA and the Kruskal-Wallis test with a p value equal to or under 0.05. Results Attitudes regarding the dimension "job satisfaction" were positive for the patient safety culture, and there was a significant difference between the professionals in this dimension (p-value 0.05). The other dimensions were not assessed positively. Conclusion The attitudes of health professionals toward patient safety must be strengthened. PMID:26934614

  17. Bacteriological findings in patients with bone marrow transplantation (Karl Marx University Leipzig, 1985-1987).

    PubMed

    Wonitzki, C; Hoffmann, F A

    1989-01-01

    The results of the bacteriological surveillance cultures for 26 patients with bone marrow transplantation (Karl Marx University Leipzig, G.D.R., 1985-1987) are presented. 5.9% of all surveillance cultures contained facultatively pathogenic germs (with Pseudomonas aeruginosa as the most frequent representative, which was the reason of a sepsis in two patients). Coagulasenegative Staphylococci and other germs with an obscure pathogenicity were isolated upon a large scale, especially from the mucous membrane regions. There are hints, that above all special strains of coagulasenegative Staphylococci "colonize" the patient's body (also for longer periods) and turn into the blood too. During the total decontamination intestinal anaerobic flora is absent. After closing of total decontamination Clostridium perfringens is the first detectable anaerobic species. During the selective decontamination systemic applications of antibiotics are able to obliterate anaerobic findings for certain periods. Recommendations for an effective arrangement of the surveillance cultures of bone marrow transplantation patients are given.

  18. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    NASA Astrophysics Data System (ADS)

    Rőszer, Tamás; Pintye, Éva; Benkő, Ilona

    2008-12-01

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  19. Bone Marrow Transplantation in Mice as a Tool to Generate Genetically Modified Animals

    SciTech Connect

    Roszer, Tamas; Pintye, Eva; Benko', Ilona

    2008-12-08

    Transgenic mice can be used either as models of known inherited human diseases or can be applied to perform phenotypic tests of genes with unknown function. In some special applications of gene modification we have to create a tissue specific mutation of a given gene. In some cases however the gene modification can be lethal in the intrauterine life, therefore we should engraft the mutated cells in the postnatal life period. After total body irradiation transplantation of bone marrow cells can be a solution to introduce mutant hematopoietic stem cells into a mature animal. Bone marrow transplantation is a useful and novel tool to study the role of hematopoietic cells in the pathogenesis of inflammation, autoimmune syndromes and many metabolic alterations coupled recently to leukocyte functions.

  20. The Blood and Marrow Transplant Clinical Trials Network: An Effective Infrastructure for Addressing Important Issues in Hematopoietic Cell Transplantation.

    PubMed

    2016-10-01

    Hematopoietic cell transplantation (HCT) is a rapidly evolving field with active preclinical and clinical development of new strategies for patient assessment, graft selection and manipulation, and pre- and post-transplantation drug and cell therapy. New strategies require evaluation in definitive clinical trials; however, HCT trials face unique challenges, including the relatively small number of transplantations performed at any single center, the diverse indications for HCT requiring dissimilar approaches, the complex nature of the intervention itself, the risk of multiple complications in the immediate post-transplantation period, and the risk of important, though infrequent, late effects. The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) was established by the US National Heart Lung and Blood Institute and the National Cancer Institute to meet these challenges. In its 15 years as a network, the BMT CTN has proven to be a successful infrastructure for planning, implementing, and completing such trials and for providing definitive answers to questions leading to improvements in the understanding and practice of HCT. It has opened 37 trials, about one-half phase 2 and one-half phase 3, enrolled more than 8000 patients, and published 57 papers addressing important issues in the treatment of patients with life-threatening malignant and nonmalignant blood disorders. This review describes the network's accomplishments, key components of its success, lessons learned over the past 15 years, and challenges for the future.

  1. Morganella morganii pericarditis 3 years after allogenic bone marrow transplantation for mantle cell lymphoma.

    PubMed

    Yang, Zhi-Tao; Lecuit, Marc; Suarez, Felipe; Carbonnelle, Etienne; Viard, Jean-Paul; Dupont, Bertrand; Buzyn, Agnès; Lortholary, Olivier

    2006-11-01

    We report herein a case of Morganella morganii-associated acute purulent pericarditis that developed 3 years after allogenic bone marrow transplantation. The patient was successfully treated with surgical drainage and cefotaxime for 6 weeks. Splenectomy and immunosuppression for chronic GVH-D are likely to have favored the development of this rare infectious complication after BMT. M. morganii should be added to the list of bacteria causing purulent pericarditis, especially in immunocompromised hosts.

  2. Evaluation of Vickers-Trexler isolator in children undergoing bone marrow transplantation.

    PubMed Central

    Watson, J G; Rogers, T R; Selwyn, S; Smith, R G

    1977-01-01

    Four children, 5 months to 15 years of age, underwent bone marrow transplantation in Vickers-Trexler isolator tents. Two grafts were elective. During 170 days of isolation no clinical infections due to exogenous micro-organisms developed despite severe immunodeficiency. The decontamination regimen and sterile procedures used, as well as the microbiological results, are described. This form of isolation in paediatric practice was found to be highly acceptable to both patients and staff. Images Fig. 1 Fig. 2 Fig. 3 PMID:327945

  3. Marrow transplantation in the treatment of a murine heritable hemolytic anemia

    SciTech Connect

    Barker, J.E.; McFarland-Starr, E.C.

    1989-05-15

    Mice with hemolytic anemia, sphha/sphha, have extremely fragile RBCs with a lifespan of approximately one day. Neither splenectomy nor simple transplantation of normal marrow after lethal irradiation cures the anemia but instead causes rapid deterioration and death of the mutant unless additional prophylactic procedures are used. In this report, we show that normal marrow transplantation preceded by sublethal irradiation increases but does not normalize RBC count. The mutant RBCs but not all the WBCs are replaced by donor cells. Splenectomy of the improved recipient causes a dramatic decrease in RBC count, indicating that the mutant spleen is a site of donor-origin erythropoiesis as well as of RBC destruction. Injections of iron dextran did not improve RBC counts. Transplantation of primary recipient marrow cells into a secondary host with a heritable stem cell deficiency (W/Wv) corrects the defect caused by residence of the normal cells in the sphha/sphha host. The original +/+ donor cells replace the RBCs of the secondary host, and the RBC count is normalized. Results indicate that the environment in the sphha/sphha host is detrimental to normal (as well as mutant) erythroid cells but the restriction is not transmitted.

  4. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation

    PubMed Central

    Becker, Amy M.; Callahan, Derrick J.; Richner, Justin M.; Choi, Jaebok; DiPersio, John F.; Diamond, Michael S.; Bhattacharya, Deepta

    2015-01-01

    Specific G protein coupled receptors (GPRs) regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation. PMID:26197390

  5. GPR18 Controls Reconstitution of Mouse Small Intestine Intraepithelial Lymphocytes following Bone Marrow Transplantation.

    PubMed

    Becker, Amy M; Callahan, Derrick J; Richner, Justin M; Choi, Jaebok; DiPersio, John F; Diamond, Michael S; Bhattacharya, Deepta

    2015-01-01

    Specific G protein coupled receptors (GPRs) regulate the proper positioning, function, and development of immune lineage subsets. Here, we demonstrate that GPR18 regulates the reconstitution of intraepithelial lymphocytes (IELs) of the small intestine following bone marrow transplantation. Through analysis of transcriptional microarray data, we find that GPR18 is highly expressed in IELs, lymphoid progenitors, and mature follicular B cells. To establish the physiological role of this largely uncharacterized GPR, we generated Gpr18-/- mice. Despite high levels of GPR18 expression in specific hematopoietic progenitors, Gpr18-/- mice have no defects in lymphopoiesis or myelopoiesis. Moreover, antibody responses following immunization with hapten-protein conjugates or infection with West Nile virus are normal in Gpr18-/- mice. Steady-state numbers of IELs are also normal in Gpr18-/- mice. However, competitive bone marrow reconstitution experiments demonstrate that GPR18 is cell-intrinsically required for the optimal restoration of small intestine TCRγδ+ and TCRαβ+ CD8αα+ IELs. In contrast, GPR18 is dispensable for the reconstitution of large intestine IELs. Moreover, Gpr18-/- bone marrow reconstitutes small intestine IELs similarly to controls in athymic recipients. Gpr18-/- chimeras show no changes in susceptibility to intestinal insults such as Citrobacter rodentium infections or graft versus host disease. These data reveal highly specific requirements for GPR18 in the development and reconstitution of thymus-derived intestinal IEL subsets in the steady-state and after bone marrow transplantation. PMID:26197390

  6. Evaluation of stem cell reserve using serial bone marrow transplantation and competitive repopulation in a murine model of chronic hemolytic anemia

    SciTech Connect

    Maggio-Price, L.; Wolf, N.S.; Priestley, G.V.; Pietrzyk, M.E.; Bernstein, S.E.

    1988-09-01

    Serial transplantation and competitive repopulation were used to evaluate any loss of self-replicative capacity of bone marrow stem cells in a mouse model with increased and persistent hemopoietic demands. Congenic marrows from old control and from young and old mice with hereditary spherocytic anemia (sphha/sphha) were serially transplanted at 35-day intervals into normal irradiated recipients. Old anemic marrow failed or reverted to recipient karyotype at a mean of 3.5 transplants, and young anemic marrow reverted at a mean of 4.0 transplants, whereas controls did so at a mean of 5.0 transplants. In a competitive assay in which a mixture of anemic and control marrow was transplanted, the anemic marrow persisted to 10 months following transplantation; anemic marrow repopulation was greater if anemic marrow sex matched with the host. It is possible that lifelong stress of severe anemia decreases stem cell reserve in the anemic sphha/sphha mouse marrow. However, marginal differences in serial transplantation number and the maintenance of anemic marrow in a competition assay would suggest that marrow stem cells, under prolonged stress, are capable of exhibiting good repopulating and self-replicating abilities.

  7. Abnormal humoral immune responses in peripheral blood lymphocyte cultures of bone marrow transplant recipients.

    PubMed Central

    Pahwa, S G; Pahwa, R N; Friedrich, W; O'Reilly, R J; Good, R A

    1982-01-01

    The present study was aimed at investigating recovery of humoral immunity in vitro after bone marrow transplantation in patients with acute leukemia and severe aplastic anemia. Hemolytic plaque assays were utilized to quantitate pokeweed mitogen-stimulated polyclonal immunoglobulin production and sheep erythrocyte antigen-specific antibody responses in cultures of peripheral blood mononuclear cells of 39 patients beginning at 1 month, for variable periods up to a maximum of 4 years after marrow transplantation. Three phases were identified: an early period of primary B cell dysfunction with concomitant immunoregulatory T cell abnormalities--i.e., decreased helper and increased suppressor activities; an intermediate phase in which B cell dysfunction could be attributed in large measure to immunoregulatory T cell abnormalities; and a late phase of normal B and T lymphocyte functions. Patients with graft-versus-host disease differed from those without it in that they often did not manifest increased T cell suppressor activity in the early period, and they were noted to have prolonged and profound B and T cell abnormalities in the chronic phase of their disease. In selected patients, simultaneous assessment of ratios of Leu-2 to Leu-3 antigens on T cells by monoclonal antibodies and of immunoregulatory T cell functions revealed a correlation between the two only late in the post-transplant period. These studies provide an insight into the ontogeny of B cell function in the post-transplant period and indicate that in certain situations phenotypic alterations in T cell subsets cannot reliably be used to predict abnormalities in their function in recipients of marrow transplantation. Images PMID:6211673

  8. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    SciTech Connect

    Orozco, Johnnie J.; Back, Tom; Kenoyer, Aimee L.; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani; Hylarides, Mark; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.; Pagel, John M.

    2013-05-15

    Anti-CD45 Radioimmunotherapy using an Alpha-Emitting Radionuclide 211At Combined with Bone Marrow Transplantation Prolongs Survival in a Disseminated Murine Leukemia Model ABSTRACT Despite aggressive chemotherapy combined with hematopoietic cell transplant (HCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using antibodies (Ab) labeled primarily with beta-emitting radionuclides has been explored to reduce relapse.

  9. Multiple cotton wool spots following bone marrow transplantation for treatment of acute lymphatic leukaemia.

    PubMed Central

    Gloor, B; Gratwohl, A; Hahn, H; Kretzschmar, S; Robert, Y; Speck, B; Daicker, B

    1985-01-01

    Three patients with acute lymphatic leukaemia developed visual impairment due to occlusion of small retinal vessels with multiple cotton wool spots after treatment which included whole body and skull irradiation followed by bone marrow transplantation and cyclosporin A. Withdrawal of cyclosporin A and treatment with corticosteroids was followed by recovery of visual acuity. This retinopathy and the retinal changes seen in the immunodeficiency syndrome are thought to be closely related. The possible role of cyclosporin A is discussed, though cotton wool spots and retinal haemorrhages have never been described in renal transplant patients during treatment with this drug. Withdrawal of cyclosporin A, which is highly effective in preventing graft-versus-host disease, can be fatal. Irradiation of the skull prior to bone marrow transplantation and intrathecal administration of methotrexate may be the most important factors causing the retinal ischaemic signs described here. The inclusion of an ophthalmologist in the team monitoring transplant patients would lead to increased documentation and a better understanding of this disease. Images PMID:3888252

  10. Bone marrow-derived hematopoietic stem and progenitor cells infiltrate allogeneic and syngeneic transplants.

    PubMed

    Fan, Z; Enjoji, K; Tigges, J C; Toxavidis, V; Tchipashivili, V; Gong, W; Strom, T B; Koulmanda, M

    2014-12-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineage(negative) Sca-1(+) cKit(+) ("LSK") cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic "LSK" HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, "LSK" HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intramedullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs.

  11. Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants)

    MedlinePlus

    ... donor cells may be harvested (removed) in an operating room, and then processed in the lab right ... called bone marrow harvest . It’s done in an operating room, while the donor is under general anesthesia ( ...

  12. Transplantation tolerance in primates after total lymphoid irradiation and allogeneic bone marrow injection

    SciTech Connect

    Smit, J.A.; Hill, R.R.H.; Myburgh, J.A.; Browde, S.

    1980-08-01

    After total lymphoid irradiation (TLI), allogeneic bone marrow (BM) injection, and organ transplantation in baboons, there is a prolonged period of reduced lymphocyte proliferative responsiveness to polyclonal mitogens and allogeneic lymphocytes. The effect observed is greater with the use of fractionated TLI than after single doses of irradiation. Suppressor cell activity can be demonstrated in vitro in most animals by inhibition of mixed lymphocyte reactivity (MLR) by mitomycin-treated recipient lymphocytes harvested after TLI, with or without allogeneic BM injection, and organ transplantation. Preliminary data suggest the presence of both donor-specific and nondonor-specific suppression, although other interpretations are possible, and suppressor phenomena may not be responsible for the transplantation tolerance observed.

  13. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    PubMed

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  14. IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation.

    PubMed

    Caselli, Anna; Olson, Timothy S; Otsuru, Satoru; Chen, Xiaohua; Hofmann, Ted J; Nah, Hyun-Duck; Grisendi, Giulia; Paolucci, Paolo; Dominici, Massimo; Horwitz, Edwin M

    2013-10-01

    The efficiency of hematopoietic stem cell (HSC) engraftment after bone marrow (BM) transplantation depends largely on the capacity of the marrow microenvironment to accept the transplanted cells. While radioablation of BM damages osteoblastic stem cell niches, little is known about their restoration and mechanisms governing their receptivity to engraft transplanted HSCs. We previously reported rapid restoration and profound expansion of the marrow endosteal microenvironment in response to marrow radioablation. Here, we show that this reorganization represents proliferation of mature endosteal osteoblasts which seem to arise from a small subset of high-proliferative, relatively radio-resistant endosteal cells. Multiple layers of osteoblasts form along the endosteal surface within 48 hours after total body irradiation, concomitant with a peak in marrow cytokine expression. This niche reorganization fosters homing of the transplanted hematopoietic cells to the host marrow space and engraftment of long-term-HSC. Inhibition of insulin-like growth factor (IGF)-1-receptor tyrosine kinase signaling abrogates endosteal osteoblast proliferation and donor HSC engraftment, suggesting that the cytokine IGF-1 is a crucial mediator of endosteal niche reorganization and consequently donor HSC engraftment. Further understanding of this novel mechanism of IGF-1-dependent osteoblastic niche expansion and HSC engraftment may yield clinical applications for improving engraftment efficiency after clinical HSC transplantation.

  15. Normalization of red cell enolase level following allogeneic bone marrow transplantation in a child with Diamond-Blackfan anemia.

    PubMed

    Park, Jeong A; Lim, Yeon Jung; Park, Hyeon Jin; Kong, Sun Young; Park, Byung Kiu; Ghim, Thad T

    2010-04-01

    We describe a girl with Diamond-Blackfan anemia with accompanying red cell enolase deficiency. At the age of 9 yr old, the patient received allogeneic bone marrow transplantation from her HLA-identical sister who had normal red cell enolase activity. While the post transplant DNA analysis with short tandem repeat has continuously demonstrated a stable mixed chimerism on follow-up, the patient remains transfusion independent and continues to show a steady increase in red cell enolase activity for over two and a half years following bone marrow transplantation.

  16. Early establishment of hematopoietic chimerism following allogeneic peripheral blood stem cell transplantation in comparison with allogeneic bone marrow transplantation.

    PubMed

    Nakao, S; Zeng, W; Yamazaki, H; Wang, H; Takami, A; Sugimori, N; Miura, Y; Shiobara, S; Matsuda, T; Shinagawa, Y; Harada, M

    1999-04-01

    To characterize the process of the establishment of complete chimerism after allogeneic peripheral blood stem cell transplantation (allo-PBSCT), we determined the origin of leukocytes in peripheral blood (PB) obtained from 23 patients in the very early period after allo-PBSCT using amplification of mini- or microsatellite regions of genomic DNA. Donor-specific alleles were amplified from the PB obtained at day 8 post-transplant for 19 allo-PBSCT patients. Among the 19 patients, 12 showed only donor-specific alleles (complete chimerism) while 7 did both donor and host-specific alleles (mixed chimerism). Although donor specific alleles were amplified in 10 of 12 patients who received allogeneic bone marrow transplantation (allo-BMT) similarly to allo-PBSCT, all of these ten showed mixed chimerism. When the chimeric state was examined in PB samples obtained serially at 2-3-day intervals post-transplant, host-specific alleles in allo-PBSCT patients were not detectable in the PB much earlier than those in allo-BMT patients. These findings indicate that the appearance of donor-derived cells associated with the disappearance of host-derived cells in the circulation occurs earlier after allo-PBSCT as compared with allo-BMT, leading to the rapid establishment of complete chimerism.

  17. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    PubMed

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-02-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600-1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2), an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 10(6) bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm(2) for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage.

  18. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment

    PubMed Central

    Li, Xianchao; Hou, Wensheng; Wu, Xiaoying; Jiang, Wei; Chen, Haiyan; Xiao, Nong; Zhou, Ping

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation is an effective treatment for neonatal hypoxic-ischemic brain damage. However, the in vivo transplantation effects are poor and their survival, colonization and differentiation efficiencies are relatively low. Red or near-infrared light from 600–1,000 nm promotes cellular migration and prevents apoptosis. Thus, we hypothesized that the combination of red light with bone marrow mesenchymal stem cell transplantation would be effective for the treatment of hypoxic-ischemic brain damage. In this study, the migration and colonization of cultured bone marrow mesenchymal stem cells on primary neurons after oxygen-glucose deprivation were detected using Transwell assay. The results showed that, after a 40-hour irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2, an increasing number of green fluorescence-labeled bone marrow mesenchymal stem cells migrated towards hypoxic-ischemic damaged primary neurons. Meanwhile, neonatal rats with hypoxic-ischemic brain damage were given an intraperitoneal injection of 1 × 106 bone marrow mesenchymal stem cells, followed by irradiation under red light-emitting diodes at 660 nm and 60 mW/cm2 for 7 successive days. Shuttle box test results showed that, after phototherapy and bone marrow mesenchymal stem cell transplantation, the active avoidance response rate of hypoxic-ischemic brain damage rats was significantly increased, which was higher than that after bone marrow mesenchymal stem cell transplantation alone. Experimental findings indicate that 660 nm red light emitting diode irradiation promotes the migration of bone marrow mesenchymal stem cells, thereby enhancing the contribution of cell transplantation in the treatment of hypoxic-ischemic brain damage. PMID:25206807

  19. Content of stromal precursor cells in heterotopic transplants of bone marrow in CBA mice of various ages.

    PubMed

    Gorskaya, Yu F; Kuralesova, A I; Shuklina, E Yu; Nesterenko, V G

    2002-02-01

    Efficiency of colony formation of stromal precursor cells in cultured bone marrow transplants from old (24 month) CBA mice implanted to young (2-month-old) mice almost 3-fold surpassed that in cultured transplants implanted to old recipients. The content of nucleated cells in bone marrow transplants from senescence accelerated mice SAMP increased more than 2-fold, if SAMR mice with normal aging rate were used as the recipients instead of SAMP mice. Bone marrow taken from old and young CBA mice endured the same number of transplantations if the recipient mice were of the same age (5 month). It was concluded that stromal tissue considerably changes with age and is under strict control of the body. PMID:12432868

  20. Successful liver allografts in mice by combination with allogeneic bone marrow transplantation

    SciTech Connect

    Nakamura, T.; Good, R.A.; Yasumizu, R.; Inoue, S.; Oo, M.M.; Hamashima, Y.; Ikehara, S.

    1986-06-01

    Successful liver allografts were established by combination with allogeneic bone marrow transplantation. When liver tissue of BALB/c (H-2d) or C57BL/6J (H-2b) mice was minced and grafted under the kidney capsules of C3H/HeN (H-2k) mice, it was rejected. However, when C3H/HeN mice were irradiated and reconstituted with T-cell-depleted BALB/c or BALB/c nu/nu bone marrow cells, or with fetal liver cells of BALB/c mice, they accepted both donor (stem-cell)-type (BALB/c) and host (thymus)-type (C3H/HeN) liver tissue. Assays for both mixed-lymphocyte reaction and induction of cytotoxic T lymphocytes revealed that the newly developed T cells were tolerant of both donor (stem-cell)-type and host (thymus)-type major histocompatibility complex determinants. We propose that liver allografts combined with bone marrow transplantation should be considered as a viable therapy for patients with liver disease such as liver cirrhosis and hepatoma.

  1. Mean platelet volume as an indicator of platelet rejuvenation following bone-marrow transplantation. Master's thesis

    SciTech Connect

    Seanger, D.G.

    1986-07-01

    Thrombocytopenia of unpredictable duration and severity is an expected outcome of the radiation/chemotherapy protocols performed prior to bone-marrow transplantation. Serial evaluation of the platelet count and mean platelet volume of patients diagnosed with acute leukemia demonstrated the mean platelet volume to increase into reference limits 24 to 40 hours prior to a rise in the platelet count in those patients whose bone-marrow successfully responded to induction chemotherapy. Serial platelet counts and measurements of mean platelet volume were performed on 31 patients following bone marrow transplantation. Numerous platelet transfusions, together with sustained thrombocytopenia, inhibited accurate assessment of 29 of 31 patients. Two patients, however, demonstrated a rise in the mean platelet volume prior to an increase in the platelet count. Both of these patients received no platelet transfusions during the period preceding or following the rise in the platelet count. It was proposed that the serial evaluation of the mean platelet volume may assist practitioners in the decision-making process of deciding whether platlet transfusions are required, or an increase in the number of circulating platelets is imminent. A decision not to transfuse would have the direct benefit of decreasing patient costs, in conjunction with eliminating a potential source for the development of an antibody against platelets.

  2. Osteoblast-specific gene expression after transplantation of marrow cells: Implications for skeletal gene therapy

    PubMed Central

    Hou, Zhen; Nguyen, Que; Frenkel, Baruch; Nilsson, Susan K.; Milne, Moira; van Wijnen, André J.; Stein, Janet L.; Quesenberry, Peter; Lian, Jane B.; Stein, Gary S.

    1999-01-01

    Somatic gene therapies require targeted transfer of the therapeutic gene(s) into stem cells that proliferate and then differentiate and express the gene in a tissue-restricted manner. We have developed an approach for gene therapy using marrow cells that takes advantage of the osteoblast specificity of the osteocalcin promoter to confine expression of chimeric genes to bone. Adherent marrow cells, carrying a reporter gene [chloramphenicol acetyltransferase (CAT)] under the control of a 1.7-kilobase rat osteocalcin gene promoter, were expanded ex vivo. After transplantation by intravenous infusion, engrafted donor cells in recipient mice were detected by the presence of the transgene in a broad spectrum of tissues. However, expression of the transgene was restricted to osteoblasts and osteocytes, as established by biochemical analysis of CAT activity and immunohistochemical analysis of CAT expression at the single cell level. Our data indicate that donor cells achieved long-term engraftment in various tissues of the recipients and that the CAT gene under control of the osteocalcin promoter is expressed specifically in bone. Thus, transplantation of multipotential marrow cells containing the osteocalcin promoter-controlled transgene provides an efficacious approach to deliver therapeutic gene expression to osteoblasts for treatment of bone disorders or tumor metastasis to the skeleton. PMID:10377408

  3. Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

    PubMed Central

    Tao, Hao; Lin, Yazhou; Zhang, Guoqing; Gu, Rui; Chen, Bohua

    2016-01-01

    Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks. PMID:27588177

  4. In vivo imaging of transplanted hematopoietic stem and progenitor cells in mouse calvarium bone marrow

    PubMed Central

    Lo Celso, Cristina; Lin, Charles P; Scadden, David T

    2011-01-01

    In vivo imaging of transplanted hematopoietic stem and progenitor cells (HSPCs) was developed to investigate the relationship between HSPCs and components of their microenvironment in the bone marrow. In particular, it allows a direct observation of the behavior of hematopoietic cells during the first few days after transplantation, when the critical events in homing and early engraftment are occurring. By directly imaging these events in living animals, this method permits a detailed assessment of functions previously evaluated by crude assessments of cell counts (homing) or after prolonged periods (engraftment). This protocol offers a new means of investigating the role of cell-intrinsic and cell-extrinsic molecular regulators of hematopoiesis during the early stages of transplantation, and it is the first to allow the study of cell-cell interactions within the bone marrow in three dimensions and in real time. In this paper, we describe how to isolate, label and inject HSPCs, as well as how to perform calvarium intravital microscopy and analyze the resulting images. A typical experiment can be performed and analyzed in ~1 week. PMID:21212779

  5. Evaluation of epithelial chimerism after bone marrow mesenchymal stromal cell infusion in intestinal transplant patients.

    PubMed

    Kilinc, S; Gurkan, U A; Guven, S; Koyuncu, G; Tan, S; Karaca, C; Ozdogan, O; Dogan, M; Tugmen, C; Pala, E E; Bayol, U; Baran, M; Kurtulmus, Y; Pirim, I; Kebapci, E; Demirci, U

    2014-01-01

    Intestinal transplantation is the most effective treatment for patients with short bowel syndrome and small bowel insufficiencies. We evaluated epithelial chimerism after infusion of autologous bone marrow mesenchymal stromal cells (BMSCs) in patients undergoing cadaveric donor isolated intestinal transplantation (I-ITx). BMSCs were isolated from patients' bone marrow via iliac puncture and expanded in vitro prior to infusion. Two out of the 3 patients were infused with autologous BMSCs, and small intestine tissue biopsies collected post-operatively were analyzed for epithelial chimerism using XY fluorescent in situ hybridization and short tandem repeat polymerase chain reaction. We observed epithelial chimeric effect in conditions both with and without BMSC infusion. Although our results suggest a higher epithelial chimerism effect with autologous BMSC infusion in I-ITx, the measurements in multiple biopsies at different time points that demonstrate the reproducibility of this finding and its stability or changes in the level over time would be beneficial. These approaches may have potential implications for improved graft survival, lower immunosuppressant doses, superior engraftment of the transplanted tissue, and higher success rates in I-ITx.

  6. Cytomegalovirus pneumonitis and bone marrow transplantation: identification of a specific high risk group.

    PubMed Central

    Foot, A B; Caul, E O; Roome, A P; Darville, J M; Oakhill, A

    1993-01-01

    AIMS--To study the association between cytomegalovirus (CMV) excretion and interstitial pneumonitis in allogeneic bone marrow transplant (BMT) recipients, with reference to donor and recipient CMV antibody response. METHODS--The incidence of CMV excretion was prospectively studied in 62 allogeneic bone marrow transplantations performed on adults and children. All recipients received CMV seronegative blood products. Prophylaxis with high dose acyclovir and CMV immune globulin was given to high risk patients (donor or recipient, or both, CMV seropositive). RESULTS--CMV excretion was detected in eight of 26 (31%) high risk patients but in only one of 36 low risk patients (donor and recipient both CMV seronegative). Five of the eight (63%) excretors in the high risk category developed CMV, of whom four (80%) belonged to the seropositive recipient/seronegative donor group, and included the three CMV seropositive recipients whose CMV complement fixation antibody titres were 64 or greater before transplantation. CONCLUSIONS--These findings suggest that there is a subgroup of patients at especially high risk of developing CMV. PMID:8391547

  7. Bone Marrow Transplantation Transfers Age-Related Susceptibility to Neovascular Remodeling in Murine Laser-Induced Choroidal Neovascularization

    PubMed Central

    Espinosa-Heidmann, Diego G.; Malek, Goldis; Mettu, Priyatham S.; Caicedo, Alejandro; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K.; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W.

    2013-01-01

    Purpose. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow–derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Methods. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Results. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Conclusions. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization. PMID:24135751

  8. Disturbances in dental development after total body irradiation in bone marrow transplant recipients

    SciTech Connect

    Dahlloef, G.B.; Barr, M.; Bolme, P.; Modeer, T.; Loennqvist, B.R.; Ringden, O.; Heimdahl, A.

    1988-01-01

    The dental status of 16 children who had been treated with bone marrow transplantation (BMT) for serious bone marrow diseases was followed for up to 6 years. Several types of disturbances in dental development were observed in children who had been conditioned with total body irradiation (TBI) at 10 Gy before BMT. Thus, impaired root development that caused short V-shaped roots was found in all patients, a complete failure of root development and premature apical closure were found in five patients, enamel hypoplasia was observed in four patients, and microdontia was observed in three patients conditioned with TBI. Patients younger than 6 years of age at BMT exhibited the most severe and extensive dental aberrations. The TBI at 10 Gy appeared to be the major cause of the disturbances found.

  9. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Szyska, Martin; Na, Il-Kang

    2016-01-01

    The bone marrow is the origin of all hematopoietic lineages and an important homing site for memory cells of the adaptive immune system. It has recently emerged as a graft-versus-host disease (GvHD) target organ after allogeneic stem cell transplantation (alloHSCT), marked by depletion of both hematopoietic progenitors and niche-forming cells. Serious effects on the restoration of hematopoietic function and immunological memory are common, especially in patients after myeloablative conditioning therapy. Cytopenia and durable immunodeficiency caused by the depletion of hematopoietic progenitors and destruction of bone marrow niches negatively influence the outcome of alloHSCT. The complex balance between immunosuppressive and cell-depleting treatments, GvHD and immune reconstitution, as well as the desirable graft-versus-tumor (GvT) effect remains a great challenge for clinicians. PMID:27066008

  10. Outcomes of pediatric bone marrow transplantation for leukemia and myelodysplasia using matched sibling, mismatched related, or matched unrelated donors.

    PubMed

    Shaw, Peter J; Kan, Fangyu; Woo Ahn, Kwang; Spellman, Stephen R; Aljurf, Mahmoud; Ayas, Mouhab; Burke, Michael; Cairo, Mitchell S; Chen, Allen R; Davies, Stella M; Frangoul, Haydar; Gajewski, James; Gale, Robert Peter; Godder, Kamar; Hale, Gregory A; Heemskerk, Martin B A; Horan, John; Kamani, Naynesh; Kasow, Kimberly A; Chan, Ka Wah; Lee, Stephanie J; Leung, Wing H; Lewis, Victor A; Miklos, David; Oudshoorn, Machteld; Petersdorf, Effie W; Ringdén, Olle; Sanders, Jean; Schultz, Kirk R; Seber, Adriana; Setterholm, Michelle; Wall, Donna A; Yu, Lolie; Pulsipher, Michael A

    2010-11-11

    Although some trials have allowed matched or single human leukocyte antigen (HLA)-mismatched related donors (mmRDs) along with HLA-matched sibling donors (MSDs) for pediatric bone marrow transplantation in early-stage hematologic malignancies, whether mmRD grafts lead to similar outcomes is not known. We compared patients < 18 years old reported to the Center for International Blood and Marrow Transplant Research with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and myelodysplastic syndrome undergoing allogeneic T-replete, myeloablative bone marrow transplantation between 1993 and 2006. In total, patients receiving bone marrow from 1208 MSDs, 266 8/8 allelic-matched unrelated donors (URDs), and 151 0-1 HLA-antigen mmRDs were studied. Multivariate analysis showed that recipients of MSD transplants had less transplantation-related mortality, acute graft-versus-host disease (GVHD), and chronic GVHD, along with better disease-free and overall survival than the URD and mmRD groups. No differences were observed in transplant-related mortality, acute and chronic GVHD, relapse, disease-free survival, or overall survival between the mmRD and URD groups. These data show that mmRD and 8/8 URD outcomes are similar, whereas MSD outcomes are superior to the other 2 sources. Whether allele level typing could identify mmRD recipients with better outcomes will not be known unless centers alter practice and type mmRD at the allele level.

  11. Rationale for bone marrow transplantation in the treatment of autoimmune diseases.

    PubMed Central

    Ikehara, S; Good, R A; Nakamura, T; Sekita, K; Inoue, S; Oo, M M; Muso, E; Ogawa, K; Hamashima, Y

    1985-01-01

    Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (less than 1.5 mo) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (greater than 2 mo) or male BXSB (H-2b) mice (9 mo) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (less than 2 mo), the recipients survived for more than 3 mo after the bone marrow transplantation and showed no graft-versus-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnormal T-cell functions were restored to normal. The newly developed T cells were found to be tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/1 or BXSB) major histocompatibility complex (MHC) determinants. Therefore, T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. However, normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considerable involution, as in the case of BXSB or MRL/1 mice in the present studies. These findings suggest that marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead be attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice. Images PMID:3887403

  12. Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients.

    PubMed Central

    Krüger, H U; Schuler, U; Proksch, B; Göbel, M; Ehninger, G

    1990-01-01

    The effect of the 4-quinolone antimicrobial agent ciprofloxacin on the concentration in plasma and the pharmacokinetics of the immunosuppressive agent cyclosporine was studied in 10 bone marrow transplant recipients. There were no statistically or clinically significant changes in cyclosporine trough concentrations or areas under the concentration-time curve following oral doses of 500 mg of ciprofloxacin every 12 h for 4 days. The data suggest a lack of relevant pharmacokinetic interaction of ciprofloxacin with cyclosporine. There was no indication of an enhanced nephrotoxicity for this drug combination. PMID:2203301

  13. A random effects model for multistate survival analysis with application to bone marrow transplants.

    PubMed

    Bhattacharyya, Mouchumi; Klein, John P

    2005-03-01

    We present an extension of the non-homogeneous Markov model for a bone marrow transplant recovery process which allows for possible associations between the transition intensities. The associations between intensities are modeled by a correlated gamma frailty model. Based on a parametric model for the conditional transition intensities, we obtain estimates of the model parameters. We use these estimates to make predictions of patient's eventual prognosis given the current medical history of the patient. Estimates of the uncertainty in our predictions are obtained by a modified bootstrap technique. PMID:15836863

  14. Idiopathic interstitial pneumonia following bone marrow transplantation: the relationship with total body irradiation

    SciTech Connect

    Keane, T.J.; Van Dyk, J.; Rider, W.D.

    1981-10-01

    Interstitial pneumonia is a frequent and often fatal complication of allogenic bone marrow transplantation. Thirty to 40 percent of such cases are of unknown etiology and have been labelled as cases of idiopathic interstitial pneumonia. Idiopathic cases are more commonly associated with the use of total body irradiation; their occurrence appears to be independent of immunosupression or graft versus host disease. Evidence is presented from the literature suggesting that the development of idiopathic interstitial pneumonia is related to the absolute absorbed dose of radiation to lung. The similarity of idiopathic pneumonia to radiation pneumonitis seen in a different clinical setting is described.

  15. Allogeneic bone marrow transplantation in hematologic disorders of childhood: new trends and controversies.

    PubMed

    Barth, E; Malorgio, C; Tamaro, P

    2000-11-01

    Bone marrow transplantation (BMT) represents an important therapeutic choice for several kinds of disorders: hematologic, metabolic and neoplastic pathologies can be treated with this strategy. The aim of this article is to describe the main indications for allogeneic BMT in haematologic disorders of childhood and possible problems related to this procedure. We consider only hematologic aspects, paying particular attention to unusual disorders of infancy as myelodysplastic syndromes and aplastic anemia. We also consider quality of life after a BMT in patients with sickle cell anemia and thalassemia major and compare this with quality of life of patients receiving chronic periodic blood transfusions.

  16. Suppressor cells in transplantation tolerance. II. maturation of suppressor cells in the bone marrow chimera

    SciTech Connect

    Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

    1981-10-01

    Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods.

  17. Suppressor cells in transplantation tolerance II. Maturation of suppressor cells in the bone marrow chimera

    SciTech Connect

    Tutschka, P.J.; Ki, P.F.; Beschorner, W.E.; Hess, A.D.; Santos, G.W.

    1981-10-01

    Histoincompatible bone marrow allografts were established in lethally irradiated rats. At various times after transplantation, the spleen cells were harvested, subjected to mixed lymphocyte cultures, and assayed for suppressor cells in vitro and in vivo by adoptive transfer studies. Alloantigen-nonspecific suppressor cells appeared in the chimera at 40 days after grafting, coinciding with the resolution of graft-versus-host disease (GVHD). At 250 days the nonspecific suppressor cells were replaced by suppressor cells specifically suppressing donor-versus-host alloantigen responses. At 720 days suppressor cells could no longer be identified by in vitro methods but were identified by in vivo adoptive transfer of transplantation tolerance. After injection of host-type antigen into chimeras, the suppressor cells could be again demonstrated by in vitro methods.

  18. Phase I/II study of Holmium-166-DOTMP for bone marrow ablation in multiple myeloma prior to bone marrow transplantation (BMT)

    SciTech Connect

    Podoloff, D.A.; Bhadkamkar, V.H.; Kasi, L.P.

    1994-05-01

    We evaluated a bone seeking radionuclide, Ho-166 DOTMP (which has both beta and gamma energies) as an agent for bone marrow ablation prior to bone marrow transplant. Six men and 1 woman in the age range 42-59 yrs. who had previously failed conventional chemotherapy using VAD (Vincristine, Adriamycin, Dexamethasone) were treated. Each patient received a diagnostic dose (Dx) of 30 mCi of Ho-166 DOTMP and underwent serial total body images using photopeak and scatter windows. Transmission images were obtained on day O. Transmission, scatter and photopeak images were used to calculate marrow dose and skeletal uptake. Therapy dose (Tx) was established to deliver a prescribed absorbed dose to the marrow. Bone marrow biopsy samples from lilac crest were obtained to determine activity concentration and to calculate marrow dose. The Dx was followed by a Tx of 25 Gy (3 pts.), 40 Gy (3 pts.) and 50 Gy (1 pt.). Additional total body imaging was accomplished prior to each Tx and SPECT after the final Tx. Bone retention varied from 26-33%. The calculated red marrow dose varied from 11 to 48 Gy. Toxicity was minimal and included: myalgia (1), nausea (2), increased BUN (1), sore throat (1), fever (1x1 day). Bone marrow ablation was achieved in 3/7 pts. The last pt. treated at the highest dose level had greater than 75% reduction in myeloma protein. We conclude that at doses as high as 31.8 mCi/Kg no significant toxicity has been observed. Diagnostic pretherapy imaging and derived dosimetry is helpful in prescribing a red marrow dose prior to radionuclide therapy. The MTD has not yet been reached. However, thus far Ho-166 DOTMP has safely ablated bone marrow prior to BMT.

  19. CMV infections in bone marrow transplanted patients--evaluation of prophylaxis with Cytotect (CMV hyperimmuneglobulin).

    PubMed

    Zintl, F; Färber, I; Hermann, J; Fuchs, D; Prager, J; Wutzler, P

    1989-01-01

    Cytomegalovirus (CMV) infection is a frequent and clinically important infection following bone marrow transplantation. Candidates for this study were patients admitted for transplantation: 22 patients received bone marrow from a HLA-identical, MCR-nonreactive sibling, in 9 patients an autologous BMT was performed. The anti-CMV IgG (Cytotect) was administered at a dosage of 1 ml/kg on days -7, 13, 33, 53, 73 and 93 after BMT. 5 patients in the very beginning of our BMT program did not receive Cytotect. Patients were given random blood products from the bloodbank not tested for CMV positivity. Active CMV infection or seroconversion in our patients was defined as a rise in IgG titer against the late antigen of fourfold or more or an IgM increase. In the allogeneic BMT group the pretransplant serological status was in 6 cases negative in recipients and donor, in 7 patients positive in recipients and negative in donors, and in 4 patients positive in recipients and donors. Of the 6 patients seronegative in recipients and donors, 3 developed active infection and of the 7 patients pretransplant positive with seronegative donors 3 developed active infection and 4 latent infections during the period from 2 to 100 days following grafting. 1 patient out of the group transplanted in third partial remission of AML developed interstitial pneumonia and died on day +30.4 of the 4 cases with seropositivity of recipients and donors developed active CMV infection. Of 9 patients with autologous transplantation 6 patients were pretransplant seropositive. 3 of these 6 developed active infection and 2 latent infection 30 to 180 days after grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Bone marrow transplantation following total lymphoid irradiation. I. Correlation with field size and suppressor cell induction

    SciTech Connect

    Lowry, R.P.; Carpenter, C.B.; Gurley, K.E.; Merrill, J.P.

    1983-07-01

    Total lymphoid irradiation (TLI) induces a unique state of immunosuppression. Although permanent bone marrow chimerism has been obtained in rodents prepared by TLI, uniform marrow engraftment has been more difficult to obtain in larger mammals. Accordingly, studies were performed to assess the immunologic perturbations induced by TLI in inbred LEW rats, and to explore the effect of altering field size of irradiation on the induction of suppressor cells and the success of allogeneic bone marrow transplantation. Additional abdominal shielding to protect a single kidney (right) from irradiation during TLI presented successful of bone marrow engraftment (WF leads to LEW, N . 5) but chimerism was uniformly obtained (N . 3) using the full irradiation field (P less than .05) Lymphopenia and a relative monocytosis were noted in all rats subjected to TLI. Although TLI using the full irradiation field eliminated alloreactivity of nylon-wool-purified spleen cells, significant, if reduced, alloreactivity was noted in rats subjected to TLI using smaller irradiation fields. Irradiated (1500 rads) nylon-wool-purified splenic T cells of rats subjected to TLI using the full field effected significantly greater suppression (P less than .001) of a normal mixed lymphocyte culture than did cells from rats subjected to TLI with right kidney shields in place (relative response reduced to 15.2 +/- 5.7% versus 64.3 +/- 11.7%). Success of bone marrow engraftment in rats prepared by TLI was correlated, therefore, with the induction of a profound lymphopenia, elimination of alloreactivity, and the development of a potent splenic suppressor system.

  1. The Cooperative Care model: an innovative approach to deliver blood and marrow stem cell transplant care.

    PubMed

    Schmit-Pokorny, Kim; Franco, Theresa; Frappier, Bettina; Vyhlidal, Ruth Caddy

    2003-01-01

    Competition among healthcare institutions, the need to improve outcomes, and the desire to decrease costs have motivated blood and marrow stem cell transplant centers to develop innovative care models. In an effort to meet these challenges, a major midwestern medical center adapted the transplant process to the outpatient setting. This transition created greater educational and care demands for patients and families. To address these demands and provide improved accommodations and amenities for patients and families, the center adopted an innovative model of care, Cooperative Care, for transplant recipients. Cooperative Care embraces patients and families as key members of the healthcare team. A family member serves as a primary caregiver for the patient during the acute inpatient phase of the transplant. Care becomes more personal and individualized, cost is reduced, the rate of rehospitalization potentially is decreased, and patients ultimately become more confident and competent in caring for themselves. The healthcare team shifted its care philosophy to incorporate a care partner, increase patient control and independence, and create greater emphasis on education. Outcomes, including patient satisfaction, have demonstrated success and motivated expansion of this model to other patient populations.

  2. Transplantation of bone marrow derived cells promotes pancreatic islet repair in diabetic mice

    SciTech Connect

    Gao Xiaodong; Song Lujun; Shen Kuntang; Wang Hongshan; Niu Weixin Qin Xinyu

    2008-06-20

    The transplantation of bone marrow (BM) derived cells to initiate pancreatic regeneration is an attractive but as-yet unrealized strategy. Presently, BM derived cells from green fluorescent protein transgenic mice were transplanted into diabetic mice. Repair of diabetic islets was evidenced by reduction of hyperglycemia, increase in number of islets, and altered pancreatic histology. Cells in the pancreata of recipient mice co-expressed BrdU and insulin. Double staining revealed {beta} cells were in the process of proliferation. BrdU{sup +} insulin{sup -} PDX-1{sup +} cells, Ngn3{sup +} cells and insulin{sup +} glucagon{sup +} cells, which showed stem cells, were also found during {beta}-cell regeneration. The majority of transplanted cells were mobilized to the islet and ductal regions. In recipient pancreas, transplanted cells simultaneously expressed CD34 but did not express insulin, PDX-1, Ngn3, Nkx2.2, Nkx6.1, Pax4, Pax6, and CD45. It is concluded that BM derived cells especially CD34{sup +} cells can promote repair of pancreatic islets. Moreover, both proliferation of {beta} cells and differentiation of pancreatic stem cells contribute to the regeneration of {beta} cells.

  3. [Effect of bone marrow cells transplantation on the decidua formation in pseudopregnant rats].

    PubMed

    Domnina, A P; Mikhaĭlov, V M; Nikol'skiĭ, N N

    2014-01-01

    One of the most common causes of the current pregnancy loss is the failure of the decidual reaction of endometrial cells. It is assumed that a partial source of decidual cells in endometrial tissue is bone marrow cells (BMCs). In the present work, we have studied possible effect of BMCs transplantation on the process of decidualization using the model of pseudopregnancy in rats. BMCs were flushed from the rat femurs and tibias. The obtained suspension of single BMCs was injected into one of rat uterine horns on the 5th day of pseudopregnancy. PBS without cells was injected into the contralateral horn served as the control. Rats were sacrificed on the 11th day of pseudopregnancy. Decidua formed in the experimental uterine horn showed an increase in the meso-antimezometral direction of their diameter of about 1.5-2 times as compared with a control horn. The weight of decidual tissue in the experimental horn exceeded 3 times the weight of the control one. The presence of transplanted BMCs in decidual tissue was documented by preliminary double staining of BMCs with membrane dye PKH 26 Red and nuclear dye Hoechst 33342. Histological analysis of decidua sections after transplantation revealed any alterations neither in cell differentiation nor in tissue structure. We conclude that BMCs transplantation stimulates decidualization in animals.

  4. Expression of T cell antigen receptor genes in the thymus of irradiated mice after bone marrow transplantation

    SciTech Connect

    Matsuzaki, G.; Yoshikai, Y.; Kishihara, K.; Nomoto, K.

    1988-01-15

    Sequential appearance of the expression of T cell antigen receptor genes was investigated in the thymus of irradiated mice at the early stage after transplantation of Thy-1 congeneic H-2 compatible allogeneic bone marrow cells. The first cells to repopulate the thymus on day 7 after bone marrow transplantation were intrathymic radioresistant T cell precursors, which expanded mainly to CD4+CD8+ host-type thymocytes by day 14. A high level of gamma gene expression but a much reduced level of alpha and beta gene expression were detected in the host-type thymocytes on day 7. During regeneration of these cells, gamma-chain messages fell to low level and alpha and beta mRNA levels increased. The thymus of the recipients began to be repopulated by donor-derived T cells about 2 wk after bone marrow transplantation and was almost completely replaced by the third week. An ordered expression of gamma then beta and alpha-chain gene transcript was also observed in the donor-type thymocytes at the early stage after bone marrow transplantation. The use of thymocytes at early stage in whole-body irradiated bone marrow chimera provides a pertinent source for investigating the molecular mechanism of T cell differentiation in adult thymus.

  5. A Comparison of Outcomes for Cord Blood Transplantation and Unrelated Bone Marrow Transplantation in Adult Aplastic Anemia.

    PubMed

    Kuwatsuka, Yachiyo; Kanda, Junya; Yamazaki, Hirohito; Mori, Takehiko; Miyamura, Koichi; Kako, Shinichi; Uchida, Naoyuki; Ohashi, Kazuteru; Ozawa, Yukiyasu; Takahashi, Yoshiyuki; Kato, Chiaki; Iwato, Koji; Ishiyama, Ken; Kobayashi, Hikaru; Eto, Tetsuya; Kahata, Kaoru; Kato, Jun; Miyamoto, Toshihiro; Kato, Koji; Mori, Shinicihro; Atsuta, Yoshiko; Kimura, Fumihiko; Kanda, Yoshinobu

    2016-10-01

    Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. PMID:27401034

  6. Increased serum IgE concentrations during infection and graft versus host disease after bone marrow transplantation.

    PubMed Central

    Walker, S A; Rogers, T R; Perry, D; Hobbs, J R; Riches, P G

    1984-01-01

    Serum IgE concentrations estimated in 25 bone marrow transplant recipients during episodes of infection or graft versus host disease, or both, were raised not only in some patients with acute graft versus host disease but also in many patients with infection. Raised values were not seen in chronic graft versus host disease. The routine estimation of serum IgE in bone marrow transplant recipients had minimal value because of the lack of specificity of the IgE response. PMID:6368605

  7. Infections after Transplantation of Bone Marrow or Peripheral Blood Stem Cells from Unrelated Donors.

    PubMed

    Young, Jo-Anne H; Logan, Brent R; Wu, Juan; Wingard, John R; Weisdorf, Daniel J; Mudrick, Cathryn; Knust, Kristin; Horowitz, Mary M; Confer, Dennis L; Dubberke, Erik R; Pergam, Steven A; Marty, Francisco M; Strasfeld, Lynne M; Brown, Janice Wes M; Langston, Amelia A; Schuster, Mindy G; Kaul, Daniel R; Martin, Stanley I; Anasetti, Claudio

    2016-02-01

    Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections

  8. Phase 1 Trial of Autologous Bone Marrow Stem Cell Transplantation in Patients with Spinal Cord Injury

    PubMed Central

    Kakabadze, Zurab; Mardaleishvili, Konstantine; Chutkerashvili, Gocha; Chelishvili, Irakli; Harders, Albrecht; Loladze, George; Shatirishvili, Gocha; Kipshidze, Nodar; Chakhunashvili, David; Chutkerashvili, Konstantine

    2016-01-01

    Introduction. A total of 18 patients, with complete motor deficits and paraplegia caused by thoracic and lumbar spine trauma without muscle atrophy or psychiatric problems, were included into this study. Materials and Methods. The bone marrow was aspirated from the anterior iliac crest under local anesthesia and the mononuclear fraction was isolated by density gradient method. At least 750 million mononuclear-enriched cells, suspended in 2 mL of saline, were infused intrathecally. Results and Discussion. The study reports demonstrated improvement of motor and sensory functions of various degrees observed in 9 of the 18 (50%) cases after bone marrow stem cell transplantation. Measured by the American Spinal Injury Association (ASIA) scale, 7 (78%) out of the 9 patients observed an improvement by one grade, while two cases (22%) saw an improvement by two grades. However, there were no cases in which the condition was improved by three grades. Conclusions. Analysis of subsequent treatment results indicated that the transplantation of mononuclear-enriched autologous BMSCs is a feasible and safe technique. However, successful application of the BMSCs in the clinical practice is associated with the necessity of executing more detailed examinations to evaluate the effect of BMSCs on the patients with spinal cord injury. PMID:27433165

  9. Mucositis and salivary antioxidants in patients undergoing bone marrow transplantation (BMT)

    PubMed Central

    Mazzeo, Marcelo A.; López, María M.; Linares, Jorge A.; Jarchum, Gustavo; Wietz, Fernando M.; Finkelberg, Ana B.

    2014-01-01

    Objectives: High doses of chemotherapy generate DNA damage in patients undergoing bone marrow transplantation (BMT), due to the production of reactive oxygen species (ROS). In order to evaluate the local defensive effectiveness of the patient undergoing BMT, the concentrations of the antioxidants superoxide dismutase (SOD) and uric acid (UA) were measured in saliva. Study Design: Basal saliva samples were collected from 20 patients undergoing BMT at the Oncology Department, Sanatorio Allende (Córdoba), in the stages: initial, prior to conditioning therapy (I); middle: 7 to 10 days after BMT (M) and final stage, 30 days after discharge from isolation (F). SOD levels were determined using a RANDOX kit (RANSOD superoxide dismutase manual), and for uric acid enzymatic UOD / PAP spectrophotometric method, ( Trinder Color Kit , Wiener Lab) was used. Results: 85% of the patients developed oral mucositis. SOD concentration in the M stage was significantly higher (p<0.01) compared with stage I, and it reversed in stage F. UA concentration was significantly lower (p<0.001) in stage M compared with stage I, and in stage F it recovered the initial values. Conclusions: SOD increase in stage M coincided with the appearance of mucositis, which could be interpreted as a defensive mechanism of saliva against oxidative stress produced by chemotherapy. UA decrease in stage M would favour the development of higher degrees of mucositis. Key words:Bone marrow transplantation, mucositis, superoxide dismutase, uric acid. PMID:24608218

  10. Histological Study of Bone Marrow and Umbilical Cord Stromal Cell Transplantation in Regenerating Rat Peripheral Nerve

    PubMed Central

    Zarbakhsh, Sam; Goudarzi, Nasim; Shirmohammadi, Maryam; Safari, Manouchehr

    2016-01-01

    Objective Bone marrow and umbilical cord stromal cells are multipotential stem cells that have the ability to produce growth factors that play an important role in survival and generation of axons. The goal of this study was to evaluate the effects of the two different mesenchymal stem cells on peripheral nerve regeneration. Materials and Methods In this experimental study, a 10 mm segment of the left sciatic nerve of male Wistar rats (250-300 g) was removed with a silicone tube interposed into this nerve gap. Bone marrow stromal cells (BMSCs) and human umbilical cord stromal cells (HUCSCs) were respectively obtained from rat and human. The cells were sepa- rately cultured and transplanted into the nerve gap. The sciatic nerve regeneration was evaluated by immunohistochemistry, and light and electron microscopy. Moreover, histo- morphology of the gastrocnemius muscle was observed. Results The nerve regeneration in the BMSCs and HUCSCs groups that had received the stem cells was significantly more favorable than the control group. In addition, the BM- SCs group was significantly more favorable than the HUCSCs group (P<0.05). Conclusion The results of this study suggest that both homograft BMSCs and het- erograft HUCSCs may have the potential to regenerate peripheral nerve injury and transplantation of BMSCs may be more effective than HUCSCs in rat. PMID:26862526

  11. Use of CT densitometry to predict lung toxicity in bone marrow transplant patients

    SciTech Connect

    el-Khatib, E.E.; Freeman, C.R.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.

    1989-01-01

    Total body irradiation (TBI) is considered an integral part of the preparation of patients with hematological malignancies for marrow transplantation. One of the major causes of death following bone marrow transplantation is interstitial pneumonia. Its pathogenesis is complex but radiation may play a major role in its development. Computed tomography (CT) has been used in animal and human studies as a sensitive non-invasive method for detecting changes in the lung following radiotherapy. In the present study CT scans are studied before and up to 1 year after TBI. Average lung densities measured before TBI showed large variations among the individual patients. On follow-up scans, lung density decreases were measured for patients who did not develop lung complications. Significant lung density increases were measured in patients who subsequently had lung complications. These lung density increases were observed prior to the onset of respiratory complications and could be correlated with the clinical course of the patients, suggesting the possibility for the usage of CT lung densitometry to predict lung complications before the onset of clinical symptoms.

  12. Percutaneous Bone Marrow Transplantation Using Fractional Ablative Erbium:YAG Laser

    PubMed Central

    Rodriguez-Menocal, Luis; Salgado, Marcela; Davis, Stephen; Waibel, Jill; Shabbir, Arsalan; Cox, Audrey; Badiavas, Evangelos V.

    2014-01-01

    Topical application of therapeutic agents has been a mainstay in Dermatology for the treatment of skin disorders but is not commonly used for systemic delivery. For a topically applied agent to reach distant body sites it must first overcome the barrier function of the skin and then penetrate into deeper structures before reaching the systemic circulation. This has limited the use of topically applied agents to those having specific charge, solubility and size restrictions. Pretreatment of the skin with ablative fractional laser appears to enhance the uptake of some topically applied drugs but the ability to effectively deliver agents to distant sites is largely unproven. In this report we used a fractional ablative Erb:YAG (Erbium/Yttrium Aluminum Garnet) laser to facilitate the transfer of bone marrow stem cells through the skin in a murine bone marrow transplant model. Chimerism could be detected in the peripheral blood of recipient C57BL/6 mice that were pretreated with ablative fractional laser and had topically applied enhanced green fluorescent protein (GFP) labeled bone marrow cells from syngeneic donor transgenic mice. This study indicates that fractional laser can be used to deliver stem cells through the skin and remain functionally intact. PMID:24667438

  13. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies.

    PubMed

    King, Allison A; Kamani, Naynesh; Bunin, Nancy; Sahdev, Indira; Brochstein, Joel; Hayashi, Robert J; Grimley, Michael; Abraham, Allistair; Dioguardi, Jacqueline; Chan, Ka Wah; Douglas, Dorothea; Adams, Roberta; Andreansky, Martin; Anderson, Eric; Gilman, Andrew; Chaudhury, Sonali; Yu, Lolie; Dalal, Jignesh; Hale, Gregory; Cuvelier, Geoff; Jain, Akshat; Krajewski, Jennifer; Gillio, Alfred; Kasow, Kimberly A; Delgado, David; Hanson, Eric; Murray, Lisa; Shenoy, Shalini

    2015-12-01

    Fifty-two children with symptomatic sickle cell disease sickle cell disease (SCD) (N = 43) or transfusion-dependent thalassemia (N = 9) received matched sibling donor marrow (46), marrow and cord product (5), or cord blood (1) allografts following reduced intensity conditioning (RIC) with alemtuzumab, fludarabine, and melphalan between March 2003 and May 2014*. The Kaplan-Meier probabilities of overall and event-free survival at a median of 3.42 (range, 0.75-11.83) years were 94.2% and 92.3% for the group, 93% and 90.7% for SCD, and 100% and 100% for thalassemia, respectively. Treatment-related mortality (all related to graft versus host disease, GVHD) was noted in three (5.7%) recipients, all 17-18 years of age. Acute and chronic GVHD was noted in 23% and 13%, respectively, with 81% of recipients off immunosuppression by 1 year. Graft rejection was limited to the single umbilical cord blood recipient who had prompt autologous hematopoietic recovery. Fourteen (27%) had mixed chimerism at 1 year and beyond; all had discontinued immunosuppression between 4 and 12 months from transplant with no subsequent consequence on GVHD or rejection. Infectious complications included predominantly bacteremia (48% were staphylococcus) and CMV reactivation (43%) necessitating preemptive therapy. Lymphocyte recovery beyond 6 months was associated with subsidence of infectious complications. All patients who engrafted were transfusion independent; no strokes or pulmonary complications of SCD were noted, and pain symptoms subsided within 6 months posttransplant. These findings support using RIC for patients with hemoglobinopathy undergoing matched sibling marrow transplantation (*www.Clinical Trials.gov: NCT00920972, NCT01050855, NCT02435901). PMID:26348869

  14. Long-term outcome of Hurler syndrome following bone marrow transplantation.

    PubMed

    Whitley, C B; Belani, K G; Chang, P N; Summers, C G; Blazar, B R; Tsai, M Y; Latchaw, R E; Ramsay, N K; Kersey, J H

    1993-04-15

    Previous reports suggested a therapeutic response of lysosomal storage diseases such as Hurler syndrome following bone marrow transplantation. However, a clearer understanding of outcome has awaited long-term follow-up. We evaluated prospectively 11 consecutive patients with Hurler syndrome receiving marrow from an HLA-identical sib donor between September 1983-October 1988. Follow-up evaluations included assessment of donor engraftment by restriction fragment polymorphism analysis, determination of leukocyte alpha-L-iduronidase level, measurement of lumbar cerebrospinal fluid (CSF) pressure, computerized tomography (CT) of the brain, and psychometric testing. In this series there was a survival rate of 9/11 (82%) with all survivors showing complete (7 patients) or partial (2 patients) donor engraftment. Prospective longitudinal evaluation of the 9 surviving children, now 3.8-8.9 years posttransplantation (median 5.5) demonstrated persistence of previously deficient leukocyte alpha-L-iduronidase at levels reflecting the donor genotype and degree of donor engraftment. Urinary glycosaminoglycan excretion declined to near-normal within 5 months of donor engraftment. Prior to treatment, 7 of 8 children studied were found to have occult intracranial hypertension (lumbar CSF pressure > 20 cm CSF); however, all surviving children attained normal or near-normal pressure within 18 months of donor engraftment. Longterm follow-up CT imaging of the brain did not show progressive volume loss (cerebral atrophy) after donor engraftment. Of 9 survivors, 4 children having a developmental quotient (DQ, Mental Development Index on Bayley Scales of Infant Development) above 80 prior to transplantation subsequently maintained IQ scores above this level. However, 5 patients with lower pretransplant DQ scores now have significant cognitive deficits and attention deficit hyperactivity disorder. Progressive brain damage resulting from communicating hydrocephalus may be prevented by

  15. Liver Transplantation After Bone Marrow Transplantation for End Stage Liver Disease with Severe Hepatopulmonary Syndrome in Dyskeratosis Congenita: A Literature First.

    PubMed

    Mahansaria, Shyam Sunder; Kumar, Senthil; Bharathy, Kishore G S; Kumar, Sachin; Pamecha, Viniyendra

    2015-12-01

    Dyskeratosis congenita is a multisystem genetic disorder. Although hepatic involvement is reported in about 7% of patients with dyskeratosis congenita, it is not well characterized and often attributed to hemochromatosis from frequent blood transfusions. A few case reports describe cirrhosis and hepatic cell necrosis in affected individuals in autosomal dominant pedigrees. Bone marrow failure and malignancies are the principal causes of death in dyskeratosis congenita. We describe the first case of living donor liver transplantation, in dyskeratosis congenita for decompensated cirrhosis with portal hypertension. The patient also had associated severe hepatopulmonary syndrome, interstitial lung disease, bilateral hip replacement for avascular necrosis of the head of femur, and a past history of bone marrow transplantation for bone marrow failure. PMID:26900277

  16. Inhibition of Autoimmune Chagas-Like Heart Disease by Bone Marrow Transplantation

    PubMed Central

    Guimaro, Maria C.; Alves, Rozeneide M.; Rose, Ester; Sousa, Alessandro O.; de Cássia Rosa, Ana; Hecht, Mariana M.; Sousa, Marcelo V.; Andrade, Rafael R.; Vital, Tamires; Plachy, Jiří; Nitz, Nadjar; Hejnar, Jiří; Gomes, Clever C.; L. Teixeira, Antonio R.

    2014-01-01

    Background Infection with the protozoan Trypanosoma cruzi manifests in mammals as Chagas heart disease. The treatment available for chagasic cardiomyopathy is unsatisfactory. Methods/Principal Findings To study the disease pathology and its inhibition, we employed a syngeneic chicken model refractory to T. cruzi in which chickens hatched from T. cruzi inoculated eggs retained parasite kDNA (1.4 kb) minicircles. Southern blotting with EcoRI genomic DNA digests revealed main 18 and 20 kb bands by hybridization with a radiolabeled minicircle sequence. Breeding these chickens generated kDNA-mutated F1, F2, and F3 progeny. A targeted-primer TAIL-PCR (tpTAIL-PCR) technique was employed to detect the kDNA integrations. Histocompatible reporter heart grafts were used to detect ongoing inflammatory cardiomyopathy in kDNA-mutated chickens. Fluorochromes were used to label bone marrow CD3+, CD28+, and CD45+ precursors of the thymus-dependent CD8α+ and CD8β+ effector cells that expressed TCRγδ, vβ1 and vβ2 receptors, which infiltrated the adult hearts and the reporter heart grafts. Conclusions/Significance Genome modifications in kDNA-mutated chickens can be associated with disruption of immune tolerance to compatible heart grafts and with rejection of the adult host's heart and reporter graft, as well as tissue destruction by effector lymphocytes. Autoimmune heart rejection was largely observed in chickens with kDNA mutations in retrotransposons and in coding genes with roles in cell structure, metabolism, growth, and differentiation. Moreover, killing the sick kDNA-mutated bone marrow cells with cytostatic and anti-folate drugs and transplanting healthy marrow cells inhibited heart rejection. We report here for the first time that healthy bone marrow cells inhibited heart pathology in kDNA+ chickens and thus prevented the genetically driven clinical manifestations of the disease. PMID:25521296

  17. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  18. Second allogeneic stem cell transplant for aplastic anaemia: a retrospective study by the Severe Aplastic Anaemia Working Party of the European Society for Blood and Marrow Transplantation.

    PubMed

    Cesaro, Simone; Peffault de Latour, Regis; Tridello, Gloria; Pillon, Marta; Carlson, Kristina; Fagioli, Franca; Jouet, Jean-Pierre; Koh, Mickey B C; Panizzolo, Irene Sara; Kyrcz-Krzemien, Slawomira; Maertens, Johan; Rambaldi, Alessandro; Strahm, Brigitte; Blaise, Didier; Maschan, Alexei; Marsh, Judith; Dufour, Carlo

    2015-11-01

    We analysed the outcome of a second allogeneic haematopoietic stem cell transplant (alloHSCT) in 162 patients reported to the European Society for Blood and Marrow Transplantation between 1998 and 2009. Donor origin was a sibling in 110 and an unrelated donor in 52 transplants, respectively. The stem cell source was bone marrow in 31% and peripheral blood in 69% of transplants. The same donor as for the first alloHSCT was used in 81% of transplants whereas a change in the choice of stem cell source was reported in 56% of patients, mainly from bone marrow to peripheral blood. Neutrophil and platelet engraftment occurred in 85% and 72% of patients, after a median time of 15 and 17 days, respectively. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 21% and 37% of patients, respectively. Graft failure (GF) occurred in 42 patients (26%). After a median follow-up of 3·5 years, the 5-year overall survival (OS) was 60·7%. In multivariate analysis, the only factor significantly associated with a better outcome was a Karnofsky/Lansky score ≥80 (higher OS). We conclude that a second alloHSCT is feasible rescue option for GF in SAA, with a successful outcome in 60% of cases.

  19. Molecular Mechanisms Mediating Retinal Reactive Gliosis Following Bone Marrow Mesenchymal Stem Cell Transplantation

    PubMed Central

    Tassoni, Alessia; Gutteridge, Alex; Barber, Amanda C.; Osborne, Andrew

    2015-01-01

    abstract A variety of diseases lead to degeneration of retinal ganglion cells (RGCs) and their axons within the optic nerve resulting in loss of visual function. Although current therapies may delay RGC loss, they do not restore visual function or completely halt disease progression. Regenerative medicine has recently focused on stem cell therapy for both neuroprotective and regenerative purposes. However, significant problems remain to be addressed, such as the long‐term impact of reactive gliosis occurring in the host retina in response to transplanted stem cells. The aim of this work was to investigate retinal glial responses to intravitreally transplanted bone marrow mesenchymal stem cells (BM‐MSCs) to help identify factors able to modulate graft‐induced reactive gliosis. We found in vivo that intravitreal BM‐MSC transplantation is associated with gliosis‐mediated retinal folding, upregulation of intermediate filaments, and recruitment of macrophages. These responses were accompanied by significant JAK/STAT3 and MAPK (ERK1/2 and JNK) cascade activation in retinal Muller glia. Lipocalin‐2 (Lcn‐2) was identified as a potential new indicator of graft‐induced reactive gliosis. Pharmacological inhibition of STAT3 in BM‐MSC cocultured retinal explants successfully reduced glial fibrillary acidic protein expression in retinal Muller glia and increased BM‐MSC retinal engraftment. Inhibition of stem cell‐induced reactive gliosis is critical for successful transplantation‐based strategies for neuroprotection, replacement, and regeneration of the optic nerve. Stem Cells 2015;33:3006–3016 PMID:26175331

  20. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection.

    PubMed

    Avery, R K; Bolwell, B J; Yen-Lieberman, B; Lurain, N; Waldman, W J; Longworth, D L; Taege, A J; Mossad, S B; Kohn, D; Long, J R; Curtis, J; Kalaycio, M; Pohlman, B; Williams, J W

    2004-12-01

    Ganciclovir-resistant cytomegalovirus (CMV) infection is an emerging problem in transplant recipients. Foscarnet resistance and cidofovir resistance have also been described, but no previous reports have suggested treatment regimens for patients with CMV refractory to all three of these drugs. Leflunomide, an immunosuppressive drug used in rheumatoid arthritis and in rejection in solid-organ transplantation, has been reported to have novel anti-CMV activity. However, its clinical utility in CMV treatment has not been described previously. We report an allogeneic bone marrow transplant recipient who developed CMV infection refractory to sequential therapy with ganciclovir, foscarnet, and cidofovir. The patient was ultimately treated with a combination of leflunomide and foscarnet. Both phenotypic and genotypic virologic analysis was performed on sequential CMV isolates. The patient's high CMV-DNA viral load became undetectable on leflunomide and foscarnet, but the patient, who had severe graft-versus-host disease (GVHD) of the liver, expired with progressive liver failure and other complications. We concluded that leflunomide is a new immunosuppressive agent with anti-CMV activity, which may be useful in the treatment of multiresistant CMV. However, the toxicity profile of leflunomide in patients with underlying GVHD remains to be defined. PMID:15489872

  1. Sexual functioning in patients undergoing bone marrow transplantation: a longitudinal study.

    PubMed

    Humphreys, C T; Tallman, B; Altmaier, E M; Barnette, V

    2007-04-01

    Patients undergoing bone marrow transplantation (BMT) reported numerous sexual difficulties pretransplantation and at 1- and 3-years post transplantation. The most commonly reported problems pretransplant were a lack of sexual interest for men and self-perceived unattractiveness for women. At year 1, men reported more concern about physical attractiveness and increased problems with erection, ejaculation and orgasm. Women reported more sexual problems across all categories. At year 3, difficulties for men remained relatively consistent or decreased compared to year 1 with the exception of an increased concern about physical appearance. At year 3, women reported increased sexual interest; concerns about body appearance, vaginal dryness, painful intercourse and orgasm remained higher than at baseline, although all had decreased from year 1. Half of patients at all time points reported no discussion of sexuality with their health care provider. Baseline level of depression was significantly and positively related to sexual functioning at year 3 post transplant. These results suggest that sexual problems are significant for BMT survivors and that treatment of depression and health-care-provider education are possible interventional targets for improving sexual function and quality of life following BMT. PMID:17322932

  2. Outcome of allogeneic bone marrow transplantation for children with advanced acute myeloid leukemia

    PubMed Central

    Nemecek, ER; Gooley, TA; Woolfrey, AE; Carpenter, PA; Matthews, DC; Sanders, JE

    2010-01-01

    Summary Allogeneic bone marrow transplantation (BMT) may offer the only chance of cure for children with acute myeloid leukemia (AML) in second complete remission (CR2) or with relapsed disease, but the outcome of these patients has not been clearly defined. We conducted a retrospective study of 58 children, median age 7.4 years (range 0.8–17.3), who received matched related or unrelated BMT at our institution for AML in CR2 (n = 12), in untreated first relapse (n = 11) or with refractory disease (n = 35), to identify risk factors associated with disease-free survival (DFS). Life threatening to fatal regimen-related toxicity was observed in 22% of patients. Estimates of DFS at 5 years (95% confidence interval) for patients in CR2, with untreated first relapse and refractory disease were 58% (27–80%), 36% (11–63%) and 9% (2–21%), respectively. Non-relapse mortality estimates were 0%, 27% (0–54%) and 17% (5–30%), and relapse estimates were 42% (14–70%), 36% (8–65%) and 74% (60–89%), respectively. Advanced disease phase and cytogenetic abnormalities at the time of transplantation were each associated with decreased DFS and increased relapse in multivariable regression models. Survival for children transplanted in CR2 or untreated first relapse is higher than that previously reported, but relapse remains the major cause of treatment failure regardless of disease stage. PMID:15361903

  3. Autologous Bone Marrow Mononuclear Cell Transplantation Delays Progression of Carotid Atherosclerosis in Rabbits.

    PubMed

    Cui, Kefei; Ma, Xiao; Yu, Lie; Jiang, Chao; Fu, Chao; Fu, Xiaojie; Yu, Xiaofang; Huang, Yuanjing; Hou, Suyun; Si, Caifeng; Chen, Zhengguang; Yu, Jing; Wan, Jieru; Wang, Jian

    2016-09-01

    Bone marrow mononuclear cells (BMMNCs) can counteract oxidative stress and inhibit the inflammatory response in focal ischemic stroke models. However, the effect of BMMNC transplantation on carotid atherosclerosis needs to be determined. The carotid atherosclerotic plaque model was established in New Zealand White rabbits by balloon injury and 8 weeks of high-fat diet. Rabbits were randomized to receive an intravenous injection of autologous bromodeoxyuridine (BrdU)-labeled BMMNCs or an equal volume of phosphate-buffered saline. Plaques were evaluated for expression of proinflammatory and anti-inflammatory cytokines, anti-oxidant proteins, and markers of cell death. BMMNCs migrated into atherosclerotic plaque on the first day after cell transplantation. BMMNC-treated rabbits had smaller plaques and more collagen deposition than did the vehicle-treated controls on day 28 (p < 0.05). BMMNC treatment significantly increased endothelial nitric oxide synthase and the anti-oxidant enzymes glutathione peroxidase and superoxide dismutase in plaques compared to vehicle treatment on day 7. BMMNC-treated rabbits also had lower levels of cleaved caspase-3 expression; lower levels of proinflammatory cytokines interleukin-1β, tumor necrosis factor alpha, and matrix metalloproteinase 9; and higher levels of insulin-like growth factor-1 and its receptor (p < 0.05). Autologous BMMNC transplantation can suppress the process of atherosclerotic plaque formation and is associated with enhanced anti-oxidative effect, reduced levels of inflammatory cytokines and cleaved caspase-3, and increased expression of insulin-like growth factor-1 and its receptor. BMMNC transplantation represents a novel approach for the treatment of carotid atherosclerosis. PMID:26232064

  4. Bone Marrow Mononuclear Cell Transplantation Restores Inflammatory Balance of Cytokines after ST Segment Elevation Myocardial Infarction

    PubMed Central

    Alestalo, Kirsi; Miettinen, Johanna A.; Vuolteenaho, Olli; Huikuri, Heikki; Lehenkari, Petri

    2015-01-01

    Background Acute myocardial infarction (AMI) launches an inflammatory response and a repair process to compensate cardiac function. During this process, the balance between proinflammatory and anti-inflammatory cytokines is important for optimal cardiac repair. Stem cell transplantation after AMI improves tissue repair and increases the ventricular ejection fraction. Here, we studied in detail the acute effect of bone marrow mononuclear cell (BMMNC) transplantation on proinflammatory and anti-inflammatory cytokines in patients with ST segment elevation myocardial infarction (STEMI). Methods Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) were randomly assigned to receive either BMMNC or saline as an intracoronary injection. Cardiac function was evaluated by left ventricle angiogram during the PCI and again after 6 months. The concentrations of 27 cytokines were measured from plasma samples up to 4 days after the PCI and the intracoronary injection. Results Twenty-six patients (control group, n = 12; BMMNC group, n = 14) from the previously reported FINCELL study (n = 80) were included to this study. At day 2, the change in the proinflammatory cytokines correlated with the change in the anti-inflammatory cytokines in both groups (Kendall’s tau, control 0.6; BMMNC 0.7). At day 4, the correlation had completely disappeared in the control group but was preserved in the BMMNC group (Kendall’s tau, control 0.3; BMMNC 0.7). Conclusions BMMNC transplantation is associated with preserved balance between pro- and anti-inflammatory cytokines after STEMI in PCI-treated patients. This may partly explain the favorable effect of stem cell transplantation after AMI. PMID:26690350

  5. Total lymphoid irradiation and cyclophosphamide conditioning prior to bone marrow transplantation for patients with severe aplastic anemia

    SciTech Connect

    Ramsay, N.K.; Kim, T.H.; McGlave, P.; Goldman, A.; Nesbit, M.E. Jr.; Krivit, W.; Woods, W.G.; Kersey, J.H.

    1983-09-01

    A preparative regimen, consisting of total lymphoid irradiation and cyclophosphamide, was utilized in 40 patients with severe aplastic anemia undergoing allogeneic marrow transplantation. This regimen was successful in decreasing rejection in these previously transfused patients, as only one patient rejected the marrow graft. Twenty-nine of the 40 transplanted patients are surviving from 1.5 to 59 mo, with a median follow-up of 24 mo. The actuarial survival rate for these heavily transfused patients with aplastic anemia is 72% at 2 yr. This preparative regimen is extremely effective in decreasing rejection following transplantation for severe aplastic anemia. Future efforts in this area must be aimed at the elimination of graft-versus-host disease and control of fatal infections.

  6. Transplant Outcomes for Children with T Cell Acute Lymphoblastic Leukemia in Second Remission: A Report from the Center for International Blood and Marrow Transplant Research.

    PubMed

    Burke, Michael J; Verneris, Michael R; Le Rademacher, Jennifer; He, Wensheng; Abdel-Azim, Hisham; Abraham, Allistair A; Auletta, Jeffery J; Ayas, Mouhab; Brown, Valerie I; Cairo, Mitchell S; Chan, Ka Wah; Diaz Perez, Miguel A; Dvorak, Christopher C; Egeler, R Maarten; Eldjerou, Lamis; Frangoul, Haydar; Guilcher, Gregory M T; Hayashi, Robert J; Ibrahim, Ahmed; Kasow, Kimberly A; Leung, Wing H; Olsson, Richard F; Pulsipher, Michael A; Shah, Niketa; Shah, Nirali N; Thiel, Elizabeth; Talano, Julie-An; Kitko, Carrie L

    2015-12-01

    Survival for children with relapsed T cell acute lymphoblastic leukemia (T-ALL) is poor when treated with chemotherapy alone, and outcomes after allogeneic hematopoietic cell transplantation (HCT) is not well described. Two hundred twenty-nine children with T-ALL in second complete remission (CR2) received an HCT after myeloablative conditioning between 2000 and 2011 and were reported to the Center for International Blood and Marrow Transplant Research. Median age was 10 years (range, 2 to 18). Donor source was umbilical cord blood (26%), matched sibling bone marrow (38%), or unrelated bone marrow/peripheral blood (36%). Acute (grades II to IV) and chronic graft-versus-host disease occurred in, respectively, 35% (95% confidence interval [CI], 27% to 45%) and 26% (95% CI, 20% to 33%) of patients. Transplant-related mortality at day 100 and 3-year relapse rates were 13% (95% CI, 9% to 18%) and 30% (95% CI, 24% to 37%), respectively. Three-year overall survival and disease-free survival rates were 48% (95% CI, 41% to 55%) and 46% (95% CI, 39% to 52%), respectively. In multivariate analysis, patients with bone marrow relapse, with or without concurrent extramedullary relapse before HCT, were most likely to relapse (hazard ratio, 3.94; P = .005) as compared with isolated extramedullary disease. In conclusion, HCT for pediatric T-ALL in CR2 demonstrates reasonable and durable outcomes, and consideration for HCT is warranted. PMID:26327632

  7. Irradiated or aseptically prepared frozen dairy desserts: acceptability to bone marrow transplant recipients.

    PubMed

    Dong, F M; Hashisaka, A E; Rasco, B A; Einstein, M A; Mar, D R; Aker, S N

    1992-06-01

    Sterile ice cream and frozen yogurt were offered to immunosuppressed patients recovering from bone marrow transplantation. To obtain sterile products, two of the dairy desserts (prepackaged ice cream and frozen yogurt bars) were exposed to 40 kGy of cobalt 60 irradiation. Four different flavors of ice cream were aseptically prepared under a laminar airflow hood using commercially sterilized ingredients. A commercially sterile, frozen milk-based drink on the low-microbial menu served as the control. Ratings of the seven products by 17 patients indicated that a frozen vanilla milk-based drink and aseptically prepared chocolate ice cream were highly acceptable to recovery immunosuppressed patients who have difficulty eating most foods. However, the seven desserts received higher ratings from a sensory panel of healthy individuals than from the patient panel, confirming that new foods for the low-microbial diet should be "market-tested" by the targeted patient population before inclusion in the menu.

  8. Bone marrow transplantation in a Holstein heifer with bovine leucocyte adhesion deficiency.

    PubMed

    Nagahata, H; Matsuki, S; Higuchi, H; Inanami, O; Kuwabara, M; Kobayashi, K

    1998-07-01

    Bone marrow transplantation (BMT) was performed in a 9-month-old heifer with bovine leucocyte adhesion deficiency (BLAD). Clinical and haematological findings, selected neutrophil function and CD18 expression of neutrophils in a B2 integrin-deficient heifer were examined. Twelve months after BMT, a small fluorescent region in the CD18-positive area of a flow cytometric profile was demonstrated and estimated to represent 0.3-0.5% of the CD18-positive neutrophils as measured by flow cytometric analysis following immunomagnetic separation. The animal's clinical condition appeared to improve and stabilize over our observation period of 28 months following BMT. Newly expressed CD18 seemed to play an important role in ameliorating the clinical signs of BLAD in this heifer. PMID:9691847

  9. [Estimating the grade of patient satisfaction at the bone marrow transplantation department in Florence hospitals].

    PubMed

    Marsullo, M; Tozzi, S; Biagini, S; Rinaldi, L

    2000-01-01

    The satisfaction of the patients admitted to the bone marrow transplant unit of Careggi Hospital was evaluated by the nursing team. The aim of the evaluation was to measure the level of satisfaction for the nursing care and services and the areas of improvement. The questionnaire, with 23 questions referring to 5 areas (hotel care, Nurses' reliability, Ability to reassure, to answer to patients' needs and Empathy) derived from the conceptual model of Servqual. Ninety patients were given (or mailed) the questionnaire during a follow-up visit. Patients were asked to answer the questions evaluating each aspect on a scale from 1 (falls short of expectation) to 10 (exceeds all expectations). The answers show a very high satisfaction (> 8) for all the areas except for the food that reported a medium score of 5.2. Further analysis will allow a better understanding of the causes of dissatisfaction. PMID:11107367

  10. Divergent Quasispecies Evolution in de novo Hepatitis C Virus Infection Associated with Bone Marrow Transplantation

    PubMed Central

    Wang, Weihua; Lin, Jianguo; Tan, De; Xu, Yanjuan; Brunt, Elizabeth M.; Fan, Xiaofeng; Di Bisceglie, Adrian M.

    2011-01-01

    Quasispecies is a remarkable characteristic of hepatitis C virus (HCV) and has profound roles in HCV biology and clinical practice. The understanding of HCV quasispecies behavior, in particular in acute HCV infection, is valuable for vaccine development and therapeutic interference. However, acute HCV infection is seldom encountered in clinic practice due to its silent onset. In the present study, we reported a unique case of de novo HCV infection associated with the transplantation of bone marrow from a HCV-positive donor. HCV quasispecies diversity was determined in both the donor and the recipient over a 4-year follow-up, accompanied with simultaneous measurement of HCV neutralizing antibody. Detailed genetic and phylogenetic analyses revealed a divergent quasispecies evolution, which was not related to dynamic changes of HCV neutralizing antibody. Instead, our data suggested an essential role of the fitness adaptation of founder viral population in driving such an evolutionary pattern. PMID:21945614

  11. Bone Marrow Transplantation Alters the Tremor Phenotype in the Murine Model of Globoid-Cell Leukodystrophy

    PubMed Central

    Reddy, Adarsh S.; Wozniak, David F.; Farber, Nuri B.; Dearborn, Joshua T.; Fowler, Stephen C.; Sands, Mark S.

    2012-01-01

    Tremor is a prominent phenotype of the twitcher mouse, an authentic genetic model of Globoid-Cell Leukodystrophy (GLD, Krabbe’s disease). In the current study, the tremor was quantified using a force-plate actometer designed to accommodate low-weight mice. The actometer records the force oscillations caused by a mouse’s movements, and the rhythmic structure of the force variations can be revealed. Results showed that twitcher mice had significantly increased power across a broad band of higher frequencies compared to wildtype mice. Bone marrow transplantation (BMT), the only available therapy for GLD, worsened the tremor in the twitcher mice and induced a measureable alteration of movement phenotype in the wildtype mice. These data highlight the damaging effects of conditioning radiation and BMT in the neonatal period. The behavioral methodology used herein provides a quantitative approach for assessing the efficacy of potential therapeutic interventions for Krabbe’s disease. PMID:24013457

  12. [Estimating the grade of patient satisfaction at the bone marrow transplantation department in Florence hospitals].

    PubMed

    Marsullo, M; Tozzi, S; Biagini, S; Rinaldi, L

    2000-01-01

    The satisfaction of the patients admitted to the bone marrow transplant unit of Careggi Hospital was evaluated by the nursing team. The aim of the evaluation was to measure the level of satisfaction for the nursing care and services and the areas of improvement. The questionnaire, with 23 questions referring to 5 areas (hotel care, Nurses' reliability, Ability to reassure, to answer to patients' needs and Empathy) derived from the conceptual model of Servqual. Ninety patients were given (or mailed) the questionnaire during a follow-up visit. Patients were asked to answer the questions evaluating each aspect on a scale from 1 (falls short of expectation) to 10 (exceeds all expectations). The answers show a very high satisfaction (> 8) for all the areas except for the food that reported a medium score of 5.2. Further analysis will allow a better understanding of the causes of dissatisfaction.

  13. Bone marrow transplantation as a strategy for the treatment of autoimmune hearing loss in MRL/Mp-lpr/lpr mice.

    PubMed

    Iwai, Hiroshi; Lee, Shinryu; Inaba, Muneo; Baba, Susumu; Yamashita, Toshio; Ikehara, Susumu

    2005-11-01

    Sensorineural hearing loss (SNHL) has been reported to develop as a main part of or in combination with systemic and organ-specific autoimmune diseases. The aim of the current study is to treat autoimmune SNHL in MRL/Mp-lpr/lpr (MRL/lpr) mice, a murine model of systemic autoimmune disease, using allogeneic bone marrow transplantation (BMT), which replaces recipient bone marrow cells with bone marrow cells from a non-autoimmune-prone donor. The results indicate that BMT can be used to treat SNHL; cochlear pathology, serum autoantibodies and lupus nephritis are ameliorated. Therefore, it is conceivable that the autoimmune SNHL in the MRL/lpr mice results not from defects in the cochlea, including the stria vascularis, but from defects in the bone marrow, and BMT would therefore provide a curative effect on inner ear autoimmune dysfunction associated with systemic autoimmune diseases.

  14. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children.

    PubMed

    Legrand, F; Berrebi, D; Houhou, N; Freymuth, F; Faye, A; Duval, M; Mougenot, J F; Peuchmaur, M; Vilmer, E

    2001-03-01

    Adenovirus infection remains an important cause of mortality after bone marrow transplantation (BMT). Currently no efficient antiviral treatment is known. Thus, testing new modalities of early diagnosis and treatment is a crucial objective. Adenovirus infection is defined by the combination of symptoms and the isolation of virus from the source of clinical symptoms. The involvement of two or more organs and the presence of virus in blood cultures define disseminated disease. Seven children with a median age of 7 years received bone marrow transplantation for leukemia. All received an unrelated graft without T cell depletion. Adenovirus was sought in blood, urine and biopsy specimens using PCR and culture. Analysis of biopsy specimens included systematic immunohistochemistry. Cidofovir treatment was initiated as soon as biopsy revealed the histopathological signs of adenovirus. Cidofovir was given at 5 mg/kg once weekly for 3 weeks then every 2 weeks. Six patients had diarrhoea and one patient had cystitis. Adenovirus infection and disseminated disease were diagnosed in four cases and three cases, respectively. In six cases, serotype A31 was isolated from gastrointestinal biopsy and in two cases serotypes B2 and C6 were detected in blood and urine. Cidofovir treatment was associated with clinical improvement of diarrhoea, cystitis and fever in five patients, in whom the virus became undetectable in cultures and PCR analyses despite the persistence of immunodeficiency. The median follow-up was 360 days after BMT (240-570). One child died of invasive aspergillosis and another of disseminated adenovirus after interruption of cidofovir therapy. Further studies in immunocompromised patients will be needed to extend these promising results concerning the role of cidofovir in adenovirus infection.

  15. A simplified method for purification, concentration and freezing of bone marrow cells for autologous transplantation.

    PubMed

    Wendel, S; Dayawansa, T; Das, P C; Smit Sibinga, C T

    1990-04-01

    Autologous bone marrow (BM) transplantation is being increasingly applied in hematological and oncological patients. However, because of the need to purify and preserve BM requiring high technology, such treatments are virtually concentrated in the "developed" countries. This paper examines methods of BM purification and freezing that could make the technique potentially applicable in developing countries. Hemapheresis is routinely applied for BM purification in our Dutch Centre, where the buffy coats obtained from routine blood donations were utilised in experimental settings. Using DMSO as cryoprotectant, semi-purified white cells were frozen in liquid N2 (LN2), by mechanical freezer or snap-frozen at -55 degrees C. Different types of containers were compared including plastic tubes and ordinary blood bags. After thawing the results show that snap-freezing had a deleterious effect but the cell yields and viability were similar in LN2 or the mechanical freezer where the tubes and the bag were equally effective as containers (86% cell recovery with 90% viability). In the purification/concentration stage, reduction of the volume of the material by extra centrifugation, thus requiring less DMSO, produced better results--96% cell yield and 90% viability after thawing. This simplified method was applied in a general hospital in Sao Paulo where four oncology patients underwent BM collection. BM was purified and concentrated within a blood bank facility. Hydroxyethyl starch sedimentation and centrifugation of the material in plastic blood bags gave 80% BM cell harvest. After thawing from the mechanical freezer 1 x 10(8) BM cells/kg were available for reinfusion to patients. There was no immediate untoward reaction. Three of the patients showed signs of bone marrow regeneration by three weeks, but one patient died 16 days after transplantation, of septicemia. We conclude that certain high-technology procedures for ABMT can be adapted for existing facilities in developing

  16. Detection of Invasive Aspergillosis in Bone Marrow Transplant Recipients Using Real-Time PCR

    PubMed Central

    Nabili, Mojtaba; Shokohi, Tahereh; Janbabaie, Ghasem; Hashemi-Soteh, Mohammad Bagher; Ali-Moghaddam, Kamran; Aghili, Seyed Reza

    2013-01-01

    Objective: The invasive aspergillosis (IA) is a serious opportunistic infection caused by various species of Aspergillus in immunocompromised individuals. Basically, rapid and early diagnosis prevents IA progression. In this study we performed a Real Time PCR/ Fluorescence Resonance Energy Transfer (FRET) for diagnosis of IA in hematologic malignancies and bone marrow transplant recipients. Materials and Methods: Sixty two patients with hematologic malignancies and marrow transplant recipients were evaluated for IA in Sari and Tehran from 2009 to 2010. The primer and hybridization probe were designed to amplify the specific sequence of 18S rRNA genes using Light Cycler system and FRET. Galactomannan (GM) assay was performed on serums which obtained from selected patients using the Platelia Aspergillus kit. Results: According to the criteria defined by the European Organization for Research and Treatment of Cancer and Mycoses Study Group (EORTC/MSG) for IA, 18 (29%) patients out of 62 patients were stratified into probable and possible groups. The female-to-male ratio was 1:2; the mean age of the patients was 36 years. The most common malignancies in these patients were acute lymphoblastic leukemia (38.9%). The minimum detection limit was 10 conidia (101 CFU/ml) equivalents (100 fg) per PCR reaction. GM assay was positive in 20.9% and real-time PCR probe set assay were positive in 17.7% patients who had clinical signs and host factor according to the mentioned criteria. Conclusion: Using the Real-Time PCR/FRET assay in whole blood specimens seems to be a promising method for diagnosis of IA, especially when used in combination with the GM detection test. PMID:23853434

  17. Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease.

    PubMed

    Kanamaru, Takuya; Kamimura, Naomi; Yokota, Takashi; Nishimaki, Kiyomi; Iuchi, Katsuya; Lee, Hyunjin; Takami, Shinya; Akashiba, Hiroki; Shitaka, Yoshitsugu; Ueda, Masayuki; Katsura, Ken-Ichiro; Kimura, Kazumi; Ohta, Shigeo

    2015-04-24

    Stem cell transplantation therapy is currently in clinical trials for the treatment of ischemic stroke, and several beneficial aspects have been reported. Similarly, in Alzheimer's disease (AD), stem cell therapy is expected to provide an efficient therapeutic approach. Indeed, the intracerebral transplantation of stem cells reduced amyloid-β (Aβ) deposition and rescued memory deficits in AD model mice. Here, we show that intravenous transplantation of bone marrow-derived mononuclear cells (BMMCs) improves cognitive function in two different AD mouse models, DAL and APP mice, and prevents neurodegeneration. GFP-positive BMMCs were isolated from tibiae and femurs of 4-week-old mice and then transplanted intravenously into DAL and APP mice. Transplantation of BMMCs suppressed neuronal loss and restored memory impairment of DAL mice to almost the same level as in wild-type mice. Transplantation of BMMCs to APP mice reduced Aβ deposition in the brain. APP mice treated with BMMCs performed significantly better on behavioral tests than vehicle-injected mice. Moreover, the effects were observed even with transplantation after the onset of cognitive impairment in DAL mice. Together, our results indicate that intravenous transplantation of BMMCs has preventive effects against the cognitive decline in AD model mice and suggest a potential therapeutic effect of BMMC transplantation therapy.

  18. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions. PMID:27695456

  19. Immunological Basis of Bone Marrow Failure after Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Masouridi-Levrat, Stavroula; Simonetta, Federico; Chalandon, Yves

    2016-01-01

    Bone marrow failure (BMF) syndromes are severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this paper, we distinguish two different entities, the graft failure (GF) and the poor graft function (PGF), and we review the current understanding of the interactions between the immune and hematopoietic compartments in these conditions. We first discuss how GF occurs as the result of classical alloreactive immune responses mediated by residual host cellular and humoral immunity persisting after conditioning and prevented by host and donor regulatory T cells. We next summarize the current knowledge about the contribution of inflammatory mediators to the development of PGF. In situations of chronic inflammation complicating allo-HSCT, such as graft-versus-host disease or infections, PGF seems to be essentially the result of a sustained impairment of hematopoietic stem cells (HSC) self-renewal and proliferation caused by inflammatory mediators, such as interferon-γ (IFN-γ) and tumor necrosis factor-α, and of induction of apoptosis through the Fas/Fas ligand pathway. Interestingly, the production of inflammatory molecules leads to a non-MHC restricted, bystander inhibition of hematopoiesis, therefore, representing a promising target for immunological interventions. Finally, we discuss immune-mediated impairment of bone marrow microenvironment as a potential mechanism hampering hematopoietic recovery. Better understanding of immunological mechanisms responsible for BMF syndromes after allo-HSCT may lead to the development of more efficient immunotherapeutic interventions.

  20. Bone Marrow Transplantation Improves Endothelial Function in Hypertensive Dahl Salt-Sensitive Rats

    PubMed Central

    Yu, Hong; Shao, Hongwei; Yan, Jing; Tsoukias, Nikolaos M.; Zhou, Ming-Sheng

    2012-01-01

    Bone marrow-derived endothelial progenitor cells (EPCs) constitute an important endogenous system in the maintenance of endothelial integrity and vascular homeostasis. Cardiovascular risk factors are associated with a reduced number and functional capacity of EPCs. Here we investigated the effect of transplantation of bone marrow-derived cells from Dahl salt-resistant rat into age-matched Dahl salt-sensitive (DS) rat on blood pressure, endothelial function, and circulating EPC number. The recipient DS rats were fed a normal (0.5% NaCl, NS) or high salt (4% NaCl, HS) diet for 6 weeks after BMT. DS rats on a NS or a HS diet without BMT were used as controls. Hypertensive DS (HS-DS) rat (systolic blood pressure: 213 ± 4 mmHg vs. 152 ± 4 mmHg in NS, p<0.05) manifested impaired endothelium-dependent relaxation to acetylcholine (EDR), increased gene expression of vascular oxidative stress and proinflamamtory cytokines, and decreased eNOS expression. BMT on HS-DS rat significantly improved EDR and eNOS expression, reduced oxidative stress without reduction in SBP (206 ± 6 mmHg). Flow cytometry analysis showed that there was no difference in the number of circulating EPCs, demonstrated by expression of EPC markers CD34, cKit, and vascular endothelial growth factor, between hypertensive and normotensive rats. Surprisingly, BMT resulted in a 5–10 fold increase in the above-mentioned EPC markers in hypertensive, but not normotensive rat. These results suggest that DS rat has an impaired ability to increase bone marrow-derived EPCs in response to HS diet challenge, which may contribute to endothelial dysfunction. PMID:22995801

  1. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010.

    PubMed

    Baronciani, D; Angelucci, E; Potschger, U; Gaziev, J; Yesilipek, A; Zecca, M; Orofino, M G; Giardini, C; Al-Ahmari, A; Marktel, S; de la Fuente, J; Ghavamzadeh, A; Hussein, A A; Targhetta, C; Pilo, F; Locatelli, F; Dini, G; Bader, P; Peters, C

    2016-04-01

    Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients <18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88 ± 1% and 81 ± 1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91 ± 1% and 83 ± 1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90-96% and an EFS of 83-93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results. PMID:26752139

  2. Transplantation of islet cells across major histocompatibility barriers after total lymphoid irradiation and infusion of allogeneic bone marrow cells

    SciTech Connect

    Britt, L.D.; Scharp, D.W.; Lacy, P.E.; Slavin, S.

    1982-08-01

    Diabetic Lewis rats (AgB1/L) were evaluated as recipients of allogeneic Wistar-Furth (AgB2/2) isolated adult islets without the use of standard recipient immunosuppression. One group was treated with fractionated total lymphoid irradiation (TLI) and Wistar-Furth bone marrow cell reconstitution to proven chimerism prior to islet transplantation. This group returned to a prediabetic state following Wistar-Furth islet transplantation without any evidence of rejection for 100 days posttransplant. A second group of Lewis rats received only TLI without bone marrow treatment. They gave a varying result following islet transplantation with one recipient showing evidence of prolonged islet survival. A third chimeric control group did not receive isolated islets and did not alter their diabetic state. A fourth group was not given TLI nor donor bone marrow cells and uniformly rejected their allogeneic islets by 7 days. Thus, allogeneic adult islets will survive across major rat histocompatibility barriers using TLI and donor bone marrow chimerism as the only form of immunosuppression.

  3. Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I.

    PubMed

    Pievani, Alice; Azario, Isabella; Antolini, Laura; Shimada, Tsutomu; Patel, Pravin; Remoli, Cristina; Rambaldi, Benedetta; Valsecchi, Maria Grazia; Riminucci, Mara; Biondi, Andrea; Tomatsu, Shunji; Serafini, Marta

    2015-03-01

    Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear.

  4. Motor and cognitive testing of bone marrow transplant patients after chemoradiotherapy

    NASA Technical Reports Server (NTRS)

    Parth, P.; Dunlap, W. P.; Kennedy, R. S.; Ordy, J. M.; Lane, N. E.

    1989-01-01

    Assessment of cognitive and motor performance of bone marrow transplant patients prior to, during, and following intensive toxic chemoradiotherapy may provide an important adjunct to measures of physiological and medical status. The present study is an attempt to assess whether, as side-effects, these aggressive treatments result in cognitive performance deficits, and if so, whether such changes recover posttreatment. Measurement of cognitive ability in this situation presents special problems not encountered with one-time tests intended for healthy adults. Such tests must be sensitive to changes within a single individual, which emphasizes the crucial importance of high reliability, stability across repeated-measures, and resistance to confounding factors such as motivation and fatigue. The present research makes use of a microbased portable test battery developed to have reliable and sensitive tests which were adapted to study the special requirements of transplant patients who may suffer cognitive deficits as a result of treatment. The results showed slight but significant changes in neuropsychological capacity when compared to baseline levels and controls, particularly near the beginning of treatment. The sensitivity of the battery in detecting such subtle temporary changes is discussed in terms of past research showing effects of other stressors, such as stimulated high altitude and ingestion of alcohol, on these measures.

  5. Effect of body mass in children with hematologic malignancies undergoing allogeneic bone marrow transplantation

    PubMed Central

    Aplenc, Richard; Zhang, Mei-Jie; Sung, Lillian; Zhu, Xiaochun; Ho, Vincent T.; Cooke, Kenneth; Dvorak, Christopher; Hale, Gregory; Isola, Luis M.; Lazarus, Hillard M.; McCarthy, Philip L.; Olsson, Richard; Pulsipher, Michael; Bunin, Nancy

    2014-01-01

    The rising incidence of pediatric obesity may significantly affect bone marrow transplantation (BMT) outcomes. We analyzed outcomes in 3687 children worldwide who received cyclophosphamide-based BMT regimens for leukemias between 1990 and 2007. Recipients were classified according to age-adjusted body mass index (BMI) percentiles as underweight (UW), at risk of UW (RUW), normal, overweight (OW), or obese (OB). Median age and race were similar in all groups. Sixty-one percent of OB children were from the United States/Canada. Three-year relapse-free and overall survival ranged from 48% to 52% (P = .54) and 55% to 58% (P = .81) across BMI groups. Three-year leukemia relapses were 33%, 33%, 29%, 25%, and 21% in the UW, RUW, normal, OW, and OB groups, respectively (P < .001). Corresponding cumulative incidences for transplant-related mortality (TRM) were 18%, 19%, 21%, 22%, and 28% (P < .01). Multivariate analysis demonstrated a decreased risk of relapse compared with normal BMI (relative risk [RR] = 0.73; P < .01) and a trend toward higher TRM (RR = 1.28; P = .014). BMI in children is not significantly associated with different survival after BMT for hematologic malignancies. Obese children experience less relapse posttransplant compared with children with normal BMI; however, this benefit is offset by excess in TRM. PMID:24711663

  6. Acute GVHD after allogeneic hematopoietic transplantation affects early marrow reconstitution and speed of engraftment.

    PubMed

    Milone, Giuseppe; Camuglia, Maria Grazia; Avola, Giuseppe; Di Marco, Annalia; Leotta, Salvatore; Cupri, Alessandra; Spina, Paolo; Romano, Alessandra; Spina, Eleonora; Azzaro, Maria Pia; Berritta, Deja; Parisi, Marina; Tripepi, Giovanni

    2015-06-01

    Our aim was to study the influence of acute graft-versus-host disease (a-GVHD) on primary engraftment times after allogeneic transplantation. Primary engraftment and frequency of marrow granulocyte-macrophage colony-forming units and erythroid burst-forming units, at day +18, were studied in 126 allogeneic transplants. Patients were grouped according to the time when a-GVHD treatment with corticosteroids was started. The no-a-GVHD group are those who, during the first 3 months, had no need for a-GVHD treatment; the early-a-GVHD group are those who needed a-GVHD treatment within 19 days; and the postengraftment-a-GVHD group are those who were not on corticosteroid treatment at the time of engraftment but needed it after day +19. The no-a-GVHD group reached a neutrophil count (N) > 0.5 × 10(9)/L in a median of 17.8 days. The postengraftment-a-GVHD group reached N > 0.5 × 10(9)/L in a median of 21.4 days (p = 0.0003). The early-a-GVHD group had N > 0.5 × 10(9)/L in a median of +17.0 days (p = 0.23). When factors important for engraftment were studied in a multivariate analysis, postengraftment a-GVHD was a significant factor in delayed neutrophil and platelet engraftment. Both the early-a-GVHD and postengraftment-a-GVHD groups showed a significant reduction in frequency of granulocyte-macrophage colony-forming units and erythroid burst-forming units found in marrow at day +18. In conclusion, a-GVHD may influence early marrow reconstitution and is a relevant factor for primary myeloid and platelet engraftment. PMID:25704053

  7. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease

    PubMed Central

    Fuchs, Ephraim J.; Luznik, Leo; Lanzkron, Sophie M.; Gamper, Christopher J.; Jones, Richard J.; Brodsky, Robert A.

    2012-01-01

    Allogeneic marrow transplantation can cure sickle cell disease; however, HLA-matched donors are difficult to find, and the toxicities of myeloablative conditioning are prohibitive for most adults with this disease. We developed a nonmyeloablative bone marrow transplantation platform using related, including HLA-haploidentical, donors for patients with sickle cell disease. The regimen consisted of antithymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation, and graft-versus-host disease prophylaxis with posttransplantation high-dose cyclophosphamide, mycophenolate mofetil, and tacrolimus or sirolimus. After screening 19 patients, we transplanted 17, 14 from HLA-haploidentical and 3 from HLA-matched related donors. Eleven patients engrafted durably. With a median follow-up of 711 days (minimal follow up 224 days), 10 patients are asymptomatic, and 6 patients are off immunosupression. Only 1 patient developed skin-only acute graft-versus-host disease that resolved without any therapy; no mortality was seen. Nonmyeloablative conditioning with posttransplantation high-dose cyclophosphamide expands the donor pool, making marrow transplantation feasible for most patients with sickle cell disease, and is associated with a low risk of complications, even with haploidentical related donors. Graft failure, 43% in haploidentical pairs, remains a major obstacle but may be acceptable in a fraction of patients if the majority can be cured without serious toxicities. PMID:22955919

  8. Increased serum concentrations of tumour necrosis factor in beta thalassaemia: effect of bone marrow transplantation.

    PubMed Central

    Meliconi, R; Uguccioni, M; Lalli, E; Nesci, S; Delfini, C; Paradisi, O; Lucarelli, G; Gasbarrini, G; Facchini, A

    1992-01-01

    AIMS: Serum concentrations of tumour necrosis factor-alpha (TNF) were determined in beta thalassemic patients before and after bone marrow transplantation (BMT) to evaluate whether changes in TNF concentrations after BMT were related to immune mediated complications. METHODS: Serum TNF concentrations were determined by enzyme linked immunoassay (EIA) in paired samples from 71 patients with beta thalassemia before and after BMT. Serial samples from 13 patients were also studied for up to six months after BMT. Forty one normal healthy children matched for sex and age were studied as controls. RESULTS: beta thalassemic patients had high serum TNF concentrations before transplantation compared with controls. These were not related to sex, age, duration of disease, number of blood transfusions, transferrin concentrations or splenectomy. DQw1 positive patients showed significantly lower TNF concentrations than non-DQw1 cases. Patients with severe liver fibrosis had significantly higher TNF concentrations. No correlation was found between TNF values and BMT outcome before transplantation but TNF alpha values fell significantly after BMT. The decrease persisted only in patients with successful engraftment. In serial samples studied for up to six months after BMT, TNF values decreased but in four out of five patients with graft rejection and in all five with acute graft versus host disease (GVHD) sharp increases occurred at the time of clinical symptoms. No correlation was found between the degree of GVHD and serum TNF-alpha concentrations nor between TNF-alpha concentrations after BMT and the presence of bacterial, viral, and fungal infections. CONCLUSIONS: About 50% of beta thalassemic patients have increased serum TNF, and the changes after BMT are related to the occurrence of immune mediate complications. The persistence of low TNF concentrations after successful engraftment may be due to the preparative regimen and the lack of adverse immune reactions. PMID:1740519

  9. Chimerism of bone marrow mesenchymal stem/stromal cells in allogeneic hematopoietic cell transplantation: is it clinically relevant?

    PubMed

    Miura, Yasuo; Yoshioka, Satoshi; Yao, Hisayuki; Takaori-Kondo, Akifumi; Maekawa, Taira; Ichinohe, Tatsuo

    2013-01-01

    Multipotent mesenchymal stem/stromal cells (MSCs) have been extensively used as a transplantable cell source for regenerative medicine and immunomodulatory therapy. Specifically in allogeneic hematopoietic stem cell transplantation (HSCT), co-transplantation or post-transplant infusion of MSCs derived from bone marrow (BM) of non-self donors has been implicated in accelerating hematopoietic recovery, ameliorating graft-vs.-host disease, and promoting tissue regeneration. However, irrespective of the use of MSC co-administration, post-transplant chimerism of BM-derived MSCs after allogeneic HSCT has been reported to remain of host origin, suggesting that the infused donor MSCs are immunologically rejected or not capable of long-term engraftment in the host microenvironment. Also, hematopoietic cell allografts currently used for HSCT do not seem to contain sufficient amount of MSCs or their precursors to reconstitute host BM microenvironment. Since the toxic conditioning employed in allo-HSCT may impair the function of host MSCs to maintain hematopoietic/regenerative stem cell niches and to provide a local immunomodulatory milieu, we propose that new directions for enhancing immunohematopoietic reconstitution and tissue repair after allogeneic HSCT include the development of strategies to support functional replenishment of residual host MSCs or to support more efficient engraftment of infused donor MSCs. Future areas of research should include in vivo tracking of infused MSCs and detection of their microchimeric presence in extra-marrow sites as well as in BM.

  10. Pathology of the thymus after allogeneic bone marrow transplantation in man. A histologic immunohistochemical study of 36 patients.

    PubMed Central

    Müller-Hermelink, H. K.; Sale, G. E.; Borisch, B.; Storb, R.

    1987-01-01

    A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:3314529

  11. Deficient Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplantation

    PubMed Central

    Glenn, Jared W.; Cody, Mark J.; McManus, Meghann P.; Pulsipher, Michael A.; Schiffman, Joshua D.; Yost, Christian Con

    2016-01-01

    Overwhelming infection causes significant morbidity and mortality among patients treated with bone marrow transplantation (BMT) for primary immune deficiencies, syndromes of bone marrow failure, or cancer. The polymorphonuclear leukocyte (PMN; neutrophil) is the first responder to microbial invasion and acts within the innate immune system to contain and clear infections. PMNs contain, and possibly clear, infections in part by forming neutrophil extracellular traps (NETs). NETs are extensive lattices of extracellular DNA and decondensed chromatin decorated with antimicrobial proteins and degradative enzymes, such as histones, myeloperoxidase, and neutrophil elastase. They trap and contain microbes, including bacteria and fungi, and may directly affect extracellular microbial killing. Whether or not deficient NET formation contributes to the increased risk for overwhelming infection in patients undergoing BMT remains incompletely characterized, especially in the pediatric population. We examined NET formation in vitro in PMNs isolated from 24 patients who had undergone BMT for 13 different clinical indications. For these 24 study participants, the median age was 7 years. For 6 of the 24 patients, we examined NET formation by PMNs isolated from serial, peripheral blood samples drawn at three different clinical time points: pre-BMT, pre-engraftment, and post-engraftment. We found decreased NET formation by PMNs isolated from patients prior to BMT and during the pre-engraftment and post-engraftment phases, with decreased NET formation compared with healthy control PMNs detected even out to 199 days after their BMT. This decrease in NET formation after BMT did not result from neutrophil developmental immaturity as we demonstrated that >80% of the PMNs tested using flow cytometry expressed both CD10 and CD16 as markers of terminal differentiation along the neutrophilic lineage. These pilot study results mandate further exploration regarding the mechanisms or factors

  12. Deficient Neutrophil Extracellular Trap Formation in Patients Undergoing Bone Marrow Transplantation.

    PubMed

    Glenn, Jared W; Cody, Mark J; McManus, Meghann P; Pulsipher, Michael A; Schiffman, Joshua D; Yost, Christian Con

    2016-01-01

    Overwhelming infection causes significant morbidity and mortality among patients treated with bone marrow transplantation (BMT) for primary immune deficiencies, syndromes of bone marrow failure, or cancer. The polymorphonuclear leukocyte (PMN; neutrophil) is the first responder to microbial invasion and acts within the innate immune system to contain and clear infections. PMNs contain, and possibly clear, infections in part by forming neutrophil extracellular traps (NETs). NETs are extensive lattices of extracellular DNA and decondensed chromatin decorated with antimicrobial proteins and degradative enzymes, such as histones, myeloperoxidase, and neutrophil elastase. They trap and contain microbes, including bacteria and fungi, and may directly affect extracellular microbial killing. Whether or not deficient NET formation contributes to the increased risk for overwhelming infection in patients undergoing BMT remains incompletely characterized, especially in the pediatric population. We examined NET formation in vitro in PMNs isolated from 24 patients who had undergone BMT for 13 different clinical indications. For these 24 study participants, the median age was 7 years. For 6 of the 24 patients, we examined NET formation by PMNs isolated from serial, peripheral blood samples drawn at three different clinical time points: pre-BMT, pre-engraftment, and post-engraftment. We found decreased NET formation by PMNs isolated from patients prior to BMT and during the pre-engraftment and post-engraftment phases, with decreased NET formation compared with healthy control PMNs detected even out to 199 days after their BMT. This decrease in NET formation after BMT did not result from neutrophil developmental immaturity as we demonstrated that >80% of the PMNs tested using flow cytometry expressed both CD10 and CD16 as markers of terminal differentiation along the neutrophilic lineage. These pilot study results mandate further exploration regarding the mechanisms or factors

  13. Extramedullary Relapse Following Total Marrow and Lymphoid Irradiation in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Kim, Ji Hyun; Stein, Anthony; Schultheiss, Timothy E.; Palmer, Joycelynne; Liu, An; Rosenthal, Joseph; Forman, Stephen J.

    2014-05-01

    Purpose: Approximately 5% to 20% of patients who undergo total body irradiation (TBI) in preparation for hematopoietic cell transplantation (HCT) can develop extramedullary (EM) relapse. Whereas total marrow and lymphoid irradiation (TMLI) provides a more conformally targeted radiation therapy for patients, organ sparing has the potential to place the patient at a higher risk for EM relapse than TBI. This study evaluated EM relapse in patients treated with TMLI at our institution. Methods and Materials: Patients eligible for analysis had been enrolled in 1 of 3 prospective TMLI trials between 2006 and 2012. The TMLI targeted bones, major lymph node chains, liver, spleen, testes, and brain, using image-guided tomotherapy with total dose ranging from 12 to 15 Gy. Results: A total of 101 patients with a median age of 47 years were studied. The median follow-up was 12.8 months. Incidence of EM relapse and bone marrow (BM) relapse were 12.9% and 25.7%, respectively. Of the 13 patients who had EM relapse, 4 also had BM relapse, and 7 had EM disease prior to HCT. There were a total of 19 EM relapse sites as the site of initial recurrence: 11 soft tissue, 6 lymph node, 2 skin. Nine of these sites were within the target region and received ≥12 Gy. Ten initial EM relapse sites were outside of the target region: 5 sites received 10.1 to 11.4 Gy while 5 sites received <10 Gy. Pretransplantation EM was the only significant predictor of subsequent EM relapse. The cumulative incidence of EM relapse was 4% at 1 year and 11.4% at 2 years. Conclusions: EM relapse incidence was as frequent in regions receiving ≥10 Gy as those receiving <10 Gy. EM relapse rates following TMLI that included HCT regimens were comparable to published results with regimens including TBI and suggest that TMLI is not associated with an increased EM relapse risk.

  14. Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation.

    PubMed

    Yokoyama, Yuichiro; Terai, Shuji; Ishikawa, Tsuyoshi; Aoyama, Koji; Urata, Yohei; Marumoto, Yoshio; Nishina, Hiroshi; Nakamura, Kazuyuki; Okita, Kiwamu; Sakaida, Isao

    2006-04-01

    We previously found that transplantation with bone marrow cells (BMCs) improves liver function and liver fibrosis in cirrhotic mice. In the presence of liver damage induced by carbon tetrachloride (CCl4), transplanted BMC migrated into the peri-portal region and trans-differentiated into hepatocytes that produce albumin. Thus under these conditions, BMC transplantation induces liver regeneration. Detecting serum marker proteins is important to monitor the recovery of liver function of cirrhotic mice after BMC transplantation. We therefore initially resolved proteins extracted from serum samples at 48 h after BMC transplantation by 2-DE and compared spot intensity between control and BMC groups of mice. Six protein spots increased in the BMC group compared with the control group. MS revealed that these spots comprised apolipoprotein A1 (apoA1), apolipoprotein C3 (apoC3), vitamin D-binding protein, alpha-1-antitrypsin and proteasome subunit alpha type 1. We subsequently confirmed the levels of apoA1 in serum and liver samples by immunoblotting. ApoA1 increased at early stage (48 h and 1 wk) after BMC transplantation in this mouse model of liver cirrhosis. The early elevation of apoA1 might be useful to predict liver regeneration in cirrhotic mice after BMC transplantation.

  15. Transplantation of goat bone marrow stromal cells to the degenerating intervertebral disc in a goat disc-injury model

    PubMed Central

    Zhang, Yejia; Drapeau, Susan; An, Howard S.; Thonar, Eugene J-M.A.; Anderson, D. Greg

    2010-01-01

    Study Design In vivo randomized controlled study in the goat intervertebral disc (IVD) injury model. Objective To define the effects of allogeneic bone marrow-derived stromal cell injected into the degenerating goat IVDs. Summary of Background Data Transplantation of bone marrow stromal cells to the degenerating disc has been suggested as a means to correct the biologic incompetence of the disc. However, large animal models with IVDs similar in shape and size to those of humans are needed to define the efficacy and safety of this approach. Methods Goat IVD degeneration was induced by stabbing with a #15 blade. One month after disc injury, the injured discs were randomly selected to receive goat bone marrow-derived stromal cell (suspended in hydrogel), saline (control), or hydrogel (control) injections. Three and 6 months after stem cell transplantation, goats were euthanized and the IVD were examined for biochemical content and tissue morphology. MR images at 3- and 6-month time points were also examined. Results The goat large animal model shows early degenerative changes following disc injury. Degenerating IVDs injected with bone marrow stromal cells showed significantly increased proteoglycan (PG) accumulation within their nucleus pulposus (NP) region. However, collagen content, MRI grade and histology did not show statistically significant differences between the cell-treated and control IVDs. Conclusions Following transplantation of bone marrow stromal cells, NP tissue contained more PG than control discs. Although this result was promising, the rate and severity of degeneration in this goat disc injury were modest, suggesting that a more severe injury and a larger sample size is indicated for future studies to better define the utility of cell therapies in this model. PMID:20890267

  16. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia

    PubMed Central

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-01-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16–72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15–2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  17. Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia.

    PubMed

    Arai, Yasuyuki; Kondo, Tadakazu; Yamazaki, Hirohito; Takenaka, Katsuto; Sugita, Junichi; Kobayashi, Takeshi; Ozawa, Yukiyasu; Uchida, Naoyuki; Iwato, Koji; Kobayashi, Naoki; Takahashi, Yoshiyuki; Ishiyama, Ken; Fukuda, Takahiro; Ichinohe, Tatsuo; Atsuta, Yoshiko; Mori, Takehiko; Teshima, Takanori

    2016-05-01

    Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human-leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16-72 years) with aplastic anemia who underwent bone marrow transplantation from younger (≤39 years, n=281) or older (≥40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15-2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft-versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID:26858357

  18. Dose response and factors related to interstitial pneumonitis after bone marrow transplant

    SciTech Connect

    Sampath, Sagus; Schultheiss, Timothy E. . E-mail: schultheiss@coh.org; Wong, Jeffrey

    2005-11-01

    Purpose: Total body irradiation (TBI) and chemotherapy are common components of conditioning regimens for bone marrow transplantation. Interstitial pneumonitis (IP) is a known regimen-related complication. Using published data of IP in a multivariate logistic regression, this study sought to identify the parameters in the bone marrow transplantation conditioning regimen that were significantly associated with IP and to establish a radiation dose-response function. Methods and Materials: A retrospective review was conducted of articles that reported IP incidence along with lung dose, fractionation, dose rate, and chemotherapy regimen. In the final analysis, 20 articles (n = 1090 patients), consisting of 26 distinct TBI/chemotherapy regimens, were included in the analysis. Multivariate logistic regression was performed to determine dosimetric and chemotherapeutic factors that influenced the incidence of IP. Results: A logistic model was generated from patients receiving daily fractions of radiation. In this model, lung dose, cyclophosphamide dose, and the addition of busulfan were significantly associated with IP. An incidence of 3%-4% with chemotherapy-only conditioning regimens is estimated from the models. The {alpha}/{beta} value of the linear-quadratic model was estimated to be 2.8 Gy. The dose eliciting a 50% incidence, D {sub 50}, for IP after 120 mg/kg of cyclophosphamide was 8.8 Gy; in the absence of chemotherapy, the estimated D {sub 50} is 10.6 Gy. No dose rate effect was observed. The use of busulfan as a substitute for radiation is equivalent to treating with 14.8 Gy in 4 fractions with 50% transmission blocks shielding the lung. The logistic regression failed to find a model that adequately fit the multiple-fraction-per-day data. Conclusions: Dose responses for both lung radiation dose and cyclophosphamide dose were identified. A conditioning regimen of 12 Gy TBI in 6 daily fractions induces an IP incidence of about 11% in the absence of lung shielding

  19. Interleukin 2 immunotherapy in children with neuroblastoma after high-dose chemotherapy and autologous bone marrow transplantation.

    PubMed

    Favrot, M C; Michon, J; Floret, D; Cochat, C; Negrier, S; Mathiot, C; Coze, C; Zucker, J M; Franks, C R; Bouffet, E

    1990-01-01

    Four children with persistent neuroblastoma after marrow ablative chemoradiotherapy and autologous bone marrow transplantation received continuous infusion of recombinant interleukin 2, 75 to 120 days after the graft. Recombinant interleukin 2 therapy did not induce any major or nonreversible toxicity, hematological toxicity in particular. One patient entered complete remission for 9 months and a second patient had a long-lasting normalization of urinary catecholamine metabolites with more than 50% regression of bone marrow metastases (8 months). In three children, recombinant interleukin 2 and a second patient entered complete remission for 9 months therapy was followed by major increase and activation of circulating natural killer cells which amounted to 80% of the circulating mononuclear cells.

  20. Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

    PubMed

    Hartmann, O; Benhamou, E; Beaujean, F; Kalifa, C; Lejars, O; Patte, C; Behard, C; Flamant, F; Thyss, A; Deville, A

    1987-08-01

    Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy. PMID:3305792

  1. Hematopoietic microenvironment. Origin, lineage, and transplantability of the stromal cells in long-term bone marrow cultures from chimeric mice

    SciTech Connect

    Perkins, S.; Fleischman, R.A.

    1988-04-01

    Studies of bone marrow transplant patients have suggested that the stromal cells of the in vitro hematopoietic microenvironment are transplantable into conditioned recipients. Moreover, in patients with myeloproliferative disorders, all of the stromal cells, which include presumptive endothelial cells, appear to be derived from hematopoietic precursors. To confirm these findings, we have constructed two chimeric mouse models: (a) traditional radiation chimeras, and (b) fetal chimeras, produced by placental injection of bone marrow into genetically anemic Wx/Wv fetuses, a technique that essentially precludes engraftment of nonhematopoietic cells. Using two-color indirect immunofluorescence, the stromal cells in long-term bone marrow culture derived from these chimeras were analyzed for donor or host origin by strain-specific H-2 antigens, and for cell lineage by a variety of other specific markers. 75-95% of the stromal cells were shown to be hematopoietic cells of the monocyte-macrophage lineage, based upon donor origin, phagocytosis, and expression of specific hematopoietic surface antigens. The remaining 5-25% of the stromal cells were exclusively host in origin. Apart from occasional fat cells, these cells uniformly expressed collagen type IV, laminin, and a surface antigen associated with endothelial cells. Since these endothelial-like cells are not transplantable into radiation or fetal chimeras, they are not derived from hematopoietic stem cells. The contrast between our findings and human studies suggests either unexpected species differences in the origin of stromal lineages or limitations in the previous methodology used to detect nonhematopoietic stromal cells.

  2. The peripheral chimerism of bone marrow-derived stem cells after transplantation: regeneration of gastrointestinal tissues in lethally irradiated mice.

    PubMed

    Filip, Stanislav; Mokrý, Jaroslav; Vávrová, Jiřina; Sinkorová, Zuzana; Mičuda, Stanislav; Sponer, Pavel; Filipová, Alžběta; Hrebíková, Hana; Dayanithi, Govindan

    2014-05-01

    Bone marrow-derived cells represent a heterogeneous cell population containing haematopoietic stem and progenitor cells. These cells have been identified as potential candidates for use in cell therapy for the regeneration of damaged tissues caused by trauma, degenerative diseases, ischaemia and inflammation or cancer treatment. In our study, we examined a model using whole-body irradiation and the transplantation of bone marrow (BM) or haematopoietic stem cells (HSCs) to study the repair of haematopoiesis, extramedullary haematopoiesis and the migration of green fluorescent protein (GFP(+)) transplanted cells into non-haematopoietic tissues. We investigated the repair of damage to the BM, peripheral blood, spleen and thymus and assessed the ability of this treatment to induce the entry of BM cells or GFP(+) lin(-) Sca-1(+) cells into non-haematopoietic tissues. The transplantation of BM cells or GFP(+) lin(-) Sca-1(+) cells from GFP transgenic mice successfully repopulated haematopoiesis and the haematopoietic niche in haematopoietic tissues, specifically the BM, spleen and thymus. The transplanted GFP(+) cells also entered the gastrointestinal tract (GIT) following whole-body irradiation. Our results demonstrate that whole-body irradiation does not significantly alter the integrity of tissues such as those in the small intestine and liver. Whole-body irradiation also induced myeloablation and chimerism in tissues, and induced the entry of transplanted cells into the small intestine and liver. This result demonstrates that grafted BM cells or GFP(+) lin(-) Sca-1(+) cells are not transient in the GIT. Thus, these transplanted cells could be used for the long-term treatment of various pathologies or as a one-time treatment option if myeloablation-induced chimerism alone is not sufficient to induce the entry of transplanted cells into non-haematopoietic tissues.

  3. Allogeneic bone marrow transplantation in mice after total lymphoid irradiation: influence of breeding conditions and strain of recipient mice

    SciTech Connect

    Waer, M.; Ang, K.K.; van der Schueren, E.; Vandeputte, M.

    1984-02-01

    Different groups of C57BL/ka or BALB/c mice received a dose of 34 Gy or 42 Gy of fractionated total lymphoid irradiation (TLI) before bone marrow transplantation with 30 x 10/sup 6/ BALB/c or C57BL nucleated bone marrow cells, respectively. BALB/c mice that were not bred in specific pathogen-free conditions before TLI showed a high morbidity and mortality rate after 34 Gy of TLI and allogeneic bone marrow transplantation as compared with BALB/c or C57BL that were bred in pathogen-free conditions before irradiation. Many of the conventionally bred BALB/c mice had clinical and histologic signs of graft-vs-host disease after TLI and allogeneic bone marrow infusion. Although leucocytosis and lymphocytosis and the immunologic competence as measured with in vitro tests were equally depressed after 34 Gy TLI in BALB/c and C57BL mice, chimerism was nevertheless significantly easier to obtain in BALB/c mice. The incidence of chimerism after TLI could be enhanced in C57BL mice by increasing the total radiation dose from 34 to 42 Gy. This augmentation of chimerism was paralleled by the induction of more suppressor cells after 42 Gy of TLI in C57BL mice.

  4. Effect of Ex Vivo Culture of CD34+ Bone Marrow Cells on Immune Reconstitution of XSCID Dogs Following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Kennedy, Douglas R.; McLellan, Kyle; Moore, Peter F.; Henthorn, Paula S.; Felsburg, Peter J.

    2009-01-01

    Successful genetic treatment of most primary immunodeficiencies or hematological disorders will require the transduction of pluripotent, self-renewing hematopoietic stem cells (HSC) rather than their progeny in order to achieve enduring production of genetically corrected cells and durable immune reconstitution. Current ex vivo transduction protocols require manipulation of HSC by culture in cytokines for various lengths of time depending upon the retroviral vector that may force HSC to enter pathways of proliferation, and possibly differentiation, that could limit their engraftment potential, pluripotentiality and long-term repopulating capacity. We have compared the ability of normal CD34+ cells cultured in a standard cytokine cocktail for 18 hours or 4.5 days to reconstitute XSCID dogs following bone marrow transplantation in the absence of any pre-transplant conditioning with that of freshly isolated CD34+ cells. CD34+ cells cultured under standard γ-retroviral transduction conditions (4.5 days) showed decreased engraftment potential and ability to sustain long-term thymopoiesis. In contrast, XSCID dogs transplanted with CD34+ cells cultured for 18 hours showed a robust T cell immune reconstitution similar to dogs transplanted with freshly isolated CD34+ cells, however, the ability to sustain long-term thymopoiesis was impaired. These results emphasize the need to determine ex vivo culture conditions that maintain both the engraftment potential and “stem cell” potential of the cultured cells. PMID:19450750

  5. Screening for religious/spiritual struggle in blood and marrow transplant patients

    PubMed Central

    Fitchett, George; Berry, Donna L.

    2016-01-01

    Purpose A growing body of research documents the harmful effects of religious/spiritual (R/S) struggle (e.g., feeling abandoned or punished by God) among patients with a wide variety of diagnoses. Documented effects include poorer quality of life, greater emotional distress, poorer recovery, and increased disability. This study reports the use of a screening protocol that identified patients who may have been experiencing R/S struggle. We also examined the prevalence and correlates of possible R/S struggle, its association with quality of life, pain, and depressive symptoms and compared the results from the screening protocol with social workers’ assessments. Methods One hundred seventy-eight blood and marrow transplant patients completed the Electronic Self-Report Assessment—Cancer (ESRA-C) which included the Rush Religious Struggle Screening Protocol and other measures of quality of life, pain, and depressive symptoms prior to transplant therapy. All participants were assessed by a social worker, 90 % within 2 weeks of the ESRA-C assessment. Results Using the Rush Protocol, 18 % of the patients were identified as potentially experiencing R/S struggle. R/S struggle was not reported in any social work assessments. In a multivariable model, potential R/S struggle was more likely in patients who were more recently diagnosed, male, and Asian/Pacific Islanders. There were no significant associations between potential R/S struggle and quality of life, pain, or depressive symptoms. Conclusions Early identification of patients with R/S struggle will facilitate their referral for further assessment and appropriate intervention. Further research is needed to identify the best methods of screening patients for R/S struggle. PMID:23052922

  6. Air-leak Syndrome by Pleuroparenchymal Fibroelastosis after Bone Marrow Transplantation.

    PubMed

    Ishii, Tomoya; Bandoh, Shuji; Kanaji, Nobuhiro; Tadokoro, Akira; Watanabe, Naoki; Imataki, Osamu; Dobashi, Hiroaki; Kushida, Yoshio; Haba, Reiji; Yokomise, Hiroyasu

    2016-01-01

    Objective Air-leak syndrome (ALS) is a life-threatening pulmonary complication following allogeneic bone marrow transplantation (allo-BMT) which is thought to be associated with graft-versus-host disease (GVHD). Recently, it has been reported that pleuroparenchymal fibroelastosis (PPFE) also occurs after allo-BMT and often causes ALS. We sought to extract common features of ALS caused by PPFE after allo-BMT. Methods The clinical data of patients who developed ALS caused by PPFE after undergoing allo-BMT (ALS-PPFE) between April 1996 and December 2007 at our institution were collected and reviewed retrospectively. The clinical findings, radiological and pathological features and treatment outcomes of ALS-PPFE were assessed. Results Five patients who developed ALS had histologically proven PPFE (four men, one woman: median age, 37 years). The age of onset of ALS-PPFE was 13 to 109 months (median, 68.8 months) after BMT. Alkylating agents were used as conditioning chemotherapy for BMT in all patients. Only one patient developed chronic GVHD (limited type). The common radiological findings were subpleural thickening and traction bronchiectasis predominantly in the bilateral upper lung fields. The histological pulmonary specimens showed no findings of bronchiolitis obliterans or GVHD. Immunosuppressive therapy was not effective in any of the cases, and all patients died of respiratory failure with or without lung transplantation. Conclusion ALS-PPFE is an extremely late-onset noninfectious pulmonary complication of allo-BMT. This complication is progressive, resistant to immunosuppressive treatment and has a poor prognosis. No association was found between PPFE and GVHD. PMID:26781007

  7. Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation.

    PubMed

    Gerritsen, E J; Van Tol, M J; Van 't Veer, M B; Wels, J M; Khouw, I M; Touw, C R; Jol-Van Der Zijde, C M; Hermans, J; Rümke, H C; Radl, J

    1994-12-15

    After bone marrow transplantation (BMT), a prolonged dysregulation of humoral immunity can be observed. In the present study, we investigated whether this is reflected in an abnormal production of specific antibodies (Ab) to the T-cell-dependent recall antigen tetanus-toxoid (TT). The study group consisted of children receiving transplants of an unmodified allogeneic graft and of adults receiving either a T-cell-depleted allogeneic or an unmodified autologous BM graft. Findings were compared with those in healthy controls. In pediatric graft recipients, who were routinely revaccinated early after BMT, the Ab response was quantitatively superior to that in adult graft recipients who did not receive early revaccination. In the majority of graft recipients, the time period after vaccination required to reach the peak level of antibodies was prolonged and the number of responding TT-specific B-cell clones was markedly decreased in comparison with controls. In controls, a low frequency of dominant B-cell clones may produce low quantities of homogeneous Ab components (H-Ab) against a heterogeneous background. However, in BM graft recipients, "overshooting" of Ab production by separate B-cell clones was observed, resulting in the development of H-Ab at a relatively high concentration. These abnormalities were present up to 10 years after BMT, irrespective of either the age of the recipient, the modulation of the graft, or the vaccination schedule used. It is hypothesized that the dysregulated Ab production is the consequence of activation of a restricted number of resting memory B cells, present in germinal centers, repopulating gradually after BMT. Our data show that routine revaccination early after BMT improves the humoral immune response. However, because of a clonally dysregulated Ab production, long-lasting qualitative defects may be present even after normalization of Ab titers.

  8. Perceptions of stress, burnout, and support systems in pediatric bone marrow transplantation nursing.

    PubMed

    Gallagher, Regan; Gormley, Denise K

    2009-12-01

    Bone marrow transplantation (BMT) is used to treat various conditions, ranging from immune disorders to many types of cancer. The critical complexity of patients and the environment in which BMT nurses work can lead to stress, burnout, and, ultimately, poor retention. This study aimed to investigate nurses' perceptions of work-related stress and burnout as well as current support systems for nurses. The study included 30 BMT staff nurses from a large pediatric medical center in the midwestern United States. Critical illness or acuity of patients was reported as the most stressful factor; long work hours was the least stressful factor. Most nurses perceived moderate to high levels of emotional exhaustion, and 33% reported moderate levels of depersonalization. Fifty percent perceived high levels of personal accomplishment, despite the critical illness or acuity of their patients, demanding patient families, rotating shifts, short staffing, and caring for dying patients. Most nurses felt that support systems were in place and that staff was accessible, but most respondents were undecided about the helpfulness of the support systems. Results suggest that support systems may significantly affect work satisfaction and feelings of accomplishment for BMT nurses.

  9. Green Tea and Bone Marrow Transplantation: From Antioxidant Activity to Enzymatic and Multidrug-resistance Modulation.

    PubMed

    Peluso, Ilaria; Palmery, Maura; Vitalone, Annabella

    2016-10-25

    Epigallocatechin-3-gallate (EGCG), the main flavonoid of green tea (GT), could play an active role in the prevention of oxidative-stress-related diseases, such as hematologic malignancies. Some effects of EGCG are not imputable to antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma non-enzymatic antioxidant capacity (NEAC). However, hyperuricemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, both before and after bone marrow transplantation (BMT). Besides this, food-drug interactions could be associated with GT consumption and could have clinical implications. The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways were discussed, with particular reference to the potential role of GT and EGCG in BMT. Moreover, on reviewing data on NEAC, isoprostanes, uric acid, and various enzymes from human studies on GT, its extract, or EGCG, an increase in NEAC, without effect on isoprostanes, and contrasting results on UA and enzymes were observed. Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems.

  10. The 'euthyroid sick syndrome': incidence, risk factors and prognostic value soon after allogeneic bone marrow transplantation.

    PubMed

    Vexiau, P; Perez-Castiglioni, P; Socié, G; Devergie, A; Toubert, M E; Aractingi, S; Gluckman, E

    1993-12-01

    We studied the incidence of thyroid function abnormalities observed soon after allogeneic bone marrow transplantations (BMT) and their predictive value on the overall prognosis. Free serum thyroxine, free serum triiodothyronine, total serum reverse triiodothyronine and serum thyrotropin levels were systematically measured in 78 patients before and 3 months after BMT. 41 (52%) had normal hormone levels and 37 (48%) had abnormal ones, among whom four (5%) had peripheral compensated hypothyroidism and 33 (43%) were described as having 'euthyroid sick syndrome' (low thyroxine state, or low T3 syndrome). Two factors strongly influenced the appearance of thyroid abnormalities: steroid dose at the time of thyroid function testing, and age (< or = 16 years/ > 16 years). Among the younger patients, 21 had no thyroid abnormalities, while five did. Among the older patients, 20 had no thyroid abnormalities, while 32 did (P < 0.001). The occurrence of thyroid abnormalities seemed to influence survival strongly, since the 30-month projected survival time was 83% for patients without abnormalities whereas it was 49% for patients with an abnormal profile (P < 0.001). In conclusion, evidence obtained among our population reveals that euthyroid sick syndrome indicates a poor prognosis and that it is very important to monitor thyroid hormone levels (particularly free hormones) soon after allogeneic BMT and regularly thereafter. PMID:7918043

  11. [Cognition, needs, satisfaction, and emotional responses for home care in bone marrow transplantation patients].

    PubMed

    Sheu, L C; Chen, T C; Hwang, S L

    1997-12-01

    Bone marrow transplantation (BMT) is an aggressive treatment which can induce considerable physical and psychological stresses. Patients face various problems in self care and psychological adjustment after discharge from the hospital. The purpose of this study was to explore the cognition, needs, satisfaction, and emotional responses toward home care in BMT patients and the factors influencing them. Forth BMT patients were enrolled from the outpatient clinic of BMT in a medical center. A descriptive research design was adopted. Cognition, needs, satisfaction, anxiety and depression for home care in these patients were collected by questionaires. The results showed that BMT patients had inadequate knowledge about how to care for themselves at home. High need and low satisfaction on disease adjustment and home care were found in these patients. All patients experienced anxiety and depression. Occupation, education, and socioeconomic status were found to affect patient's cognition. Religious belief influenced needs and satisfaction for home care in these patients. Sex and social-economic status emotional reaction of patients. This study will help health personnel understand the cognition, needs and satisfaction for home care in BMT patients. It can be used as a reference for organizing discharge plan and extending the continuity of care for BMT patients.

  12. Kinetics of lymphocyte reconstitution after allogeneic bone marrow transplantation: markers of graft-versus-host disease.

    PubMed

    Zinöcker, Severin; Sviland, Lisbet; Dressel, Ralf; Rolstad, Bent

    2011-07-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2-6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L(+) T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4(+)CD25(hi)FoxP3(+) T(reg), which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT.

  13. Functional analysis of CD8 lymphocytes in long-term surviving patients after bone marrow transplantation.

    PubMed

    Divine, M; Lecouedic, J P; Gourdin, M F; Oudhriri, N; Zohair, M; Henni, T; Beaujan, F; Vernant, J P; Reyes, F; Farcet, J P

    1988-03-01

    The recovery of T-cell populations after bone marrow transplantation (BMT) is characterized by a persistent expansion of CD8 lymphocytes. Previously, we have shown that beyond 1 year posttransplantation the CD8 lymphocytes consist, to a large extent, of CD8+ HNK1+ cells that suppress, like normal CD8 lymphocytes, immunoglobulin production in vitro. We have further investigated the functional capabilities of CD8 lymphocytes, mostly HNK1+ (from 50 to 77%), in seven long-term BMT patients. As normal, patient CD8 lymphocytes do not suppress (1) phytohemagglutinin (PHA)-induced interleukin 2 (IL2) receptor expression and IL2 responsiveness by normal T cells or (2) the mixed lymphocyte reaction of donor cells. Also as normal, patient CD8 lymphocytes can be activated into potent cytotoxic effectors. Therefore, under the present experimental conditions, the increase in the absolute number of CD8 lymphocytes in the long-term BMT patients is characterized by an expansion of the CD8+ HNK1+-cell subpopulation and a normal suppressor/cytotoxic potential on a per-CD8+ cell basis. PMID:2967308

  14. Effectiveness of oral chlorhexidine for reducing stomatitis in a pediatric bone marrow transplant population.

    PubMed

    Raether, D; Walker, P O; Bostrum, B; Weisdorf, D

    1989-03-01

    Disruption of the oral mucosal lining and the lack of normal defense mechanisms predispose bone marrow transplant (BMT) patients to life-threatening infections, often caused by oral flora. Chlorhexidine, used as an oral antiseptic, appears promising in limiting oral bacteria and fungi, and therefore, may decrease oral complications associated with BMT. The purpose of this study was to determine in pediatric BMT recipients if a 0.12% chlorhexidine mouthrinse, used as an adjunct to normal in-hospital oral care regimens, would decrease the severity of oral mucositis as measured by oral ulcerations, bacteremia, and length of hospital stay. Forty-seven pediatric BMT subjects were included in this double-blind study. Subjects were instructed to use 15 ml of a mouthrinse 3 times daily to be swished and gargled for 30 sec. Each subject had 7 oral sites scored for the percentage of ulcerated mucosa twice weekly until day +35 or hospital discharge or death. Blood was cultured daily during neutropenia. Additionally, the number of days from onset of cytoreduction to hospital discharge or death was recorded for each subject. Alpha was set at .05. There was no significant difference in the severity of oral ulceration between the chlorhexidine and placebo groups (P = .18). Chlorhexidine did not reduce the development of bacteremia (P greater than .5), nor did it significantly decrease the length of hospital stay (P = .68).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

    SciTech Connect

    Cheng, Jonathan C.; Schultheiss, Timothy E. Wong, Jeffrey Y.C.

    2008-08-01

    Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age {>=}18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.

  16. Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

    PubMed Central

    Lv, Wen; Li, Wen-yu; Xu, Xiao-yan; Jiang, Hong; Bang, Oh Yong

    2015-01-01

    This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke. PMID:26487854

  17. Bone marrow cell transplantation is associated with fibrogenic cells apoptosis during hepatic regeneration in cholestatic rats.

    PubMed

    Nunes de Carvalho, Simone; da Cunha Lira, Dalvaci; Costa Cortez, Erika Afonso; de Andrade, Daniela Caldas; Thole, Alessandra Alves; Stumbo, Ana Carolina; de Carvalho, Lais

    2013-04-01

    Liver fibrosis is accompanied by hepatocyte death and proliferation of α-SMA(+) fibrogenic cells (activated hepatic stellate cells and myofibroblasts), which synthesize extracellular matrix components that contribute to disorganization of the hepatic parenchyma and loss of liver function. Therefore, apoptosis of these fibrogenic cells is important to hepatic regeneration. This study aimed to analyze the effect of cell therapy using bone marrow mononuclear cell (BMMNC) transplantation on α-SMA expression and on apoptosis of hepatic cells during liver fibrosis induced by bile duct ligation (BDL). Livers were collected from normal rats, fibrotic rats after 14 and 21 days of BDL, and rats that received BMMNC at 14 days of BDL and were analyzed after 7 days. Apoptosis in fibrogenic cells was analyzed by immunoperoxidase, confocal microscopy, and Western blotting, and liver regeneration was assessed by proliferating cell nuclear antigen staining. Results showed that caspase-3 and proliferating cell nuclear antigen expression were significantly increased in the BMMNC-treated group. Additionally, confocal microscopy analysis showed cells coexpressing α-SMA and caspase-3 in these animals, suggesting fibrogenic cell death. These results suggest a novel role for BMMNC in liver regeneration during fibrotic disease by stimulating fibrogenic cells apoptosis and hepatocyte proliferation, probably through secretion of specific cytokines that modulate the hepatic microenvironment toward an antifibrogenic balance.

  18. Characterization of plasma cell populations at autopsy after human allogeneic bone marrow transplantation.

    PubMed Central

    Cousineau, S.; Belanger, R.; Perreault, C.

    1986-01-01

    Postmortem fixed tissue sections of the lymphoid and digestive systems of eight consecutive leukemic patients dying of various diseases after bone marrow transplantation (BMT) were analyzed for the presence of the heavy chains gamma, alpha, mu, delta, and epsilon and light chains kappa and lambda, with the use of a standard immunoperoxidase method. Two distinct types of plasma cell populations were found. The first type was a widely distributed polyclonal plasma cell population, lacking IgD-positive plasma cells and germinal centers. The second type of plasma cell population, found in 6 of 8 patients, was a group of monoclonal plasma cell populations positive for the heavy chains gamma, alpha, mu, or delta. Recent immunohistologic observations of the human lymph node suggest that the first type of polyclonal plasma cell population could arise from a nonspecific expansion of sIgM+, sIgD- B lymphocytes. The lack of germinal centers, a structure closely involved in specific-antibody production, may correlate with the poor specific-antibody response documented in patients after BMT. The monoclonal plasma cell populations, found with an unexpectedly high frequency, are probably related to a functional T-cell defect. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3089020

  19. Acute renal failure in patients following bone marrow transplantation: prevalence, risk factors and outcome.

    PubMed

    Gruss, E; Bernis, C; Tomas, J F; Garcia-Canton, C; Figuera, A; Motellón, J L; Paraiso, V; Traver, J A; Fernandez-Rañada, J M

    1995-01-01

    To assess the prevalence, risk factors, clinical causes and outcome of acute renal failure (ARF) following bone marrow transplantation (BMT), a retrospective analysis of 275 patients was undertaken. ARF was diagnosed in 72 patients (26%) and occurred in 81.9% within the first month. The three main clinical causes were multifactorial (36%), nephrotoxic (29%), and veno-occlusive disease of the liver (VOD) 15%. The prevalence was higher in allogeneic BMT (36%) than in autologous BMT (6.5%). Risk factors related to the development of ARF wee preexisting VOD and age older than 25 years. Logistic regression in allogeneic BMT confirmed this association (VOD, odds ratio 3.8; age offer than 25, odds ratio 1.9). Underlying disease, graft-versus-host disease, sepsis, conditioning therapy, and sex were not associated with ARF. Seventeen cases of ARF required hemodialysis (24%) mainly in association with VOD (70.5%). The overall morality from ARF was 45.8%, the dialyzed group having the highest mortality (88%). Survival in the ARF group was continuously worse up to 3 months and the actuarial survival at 10 years was 29.7 versus 53.2%. We conclude that ARF is a common complication mainly in allogeneic BMT and carries a grave prognosis. VOD and age were risk factors for ARF.

  20. Green Tea and Bone Marrow Transplantation: From Antioxidant Activity to Enzymatic and Multidrug-resistance Modulation.

    PubMed

    Peluso, Ilaria; Palmery, Maura; Vitalone, Annabella

    2016-10-25

    Epigallocatechin-3-gallate (EGCG), the main flavonoid of green tea (GT), could play an active role in the prevention of oxidative-stress-related diseases, such as hematologic malignancies. Some effects of EGCG are not imputable to antioxidant activity, but involve modulation of antioxidant enzymes and uric acid (UA) levels. The latter is the major factor responsible of the plasma non-enzymatic antioxidant capacity (NEAC). However, hyperuricemia is a frequent clinical feature caused by tumor lysis syndrome or cyclosporine side effects, both before and after bone marrow transplantation (BMT). Besides this, food-drug interactions could be associated with GT consumption and could have clinical implications. The molecular mechanisms involved in the redox and drug metabolizing/transporting pathways were discussed, with particular reference to the potential role of GT and EGCG in BMT. Moreover, on reviewing data on NEAC, isoprostanes, uric acid, and various enzymes from human studies on GT, its extract, or EGCG, an increase in NEAC, without effect on isoprostanes, and contrasting results on UA and enzymes were observed. Currently, few and contrasting available evidences suggest caution for GT consumption in BMT patients and more studies are needed to better understand the potential impact of EGCG on oxidative stress and metabolizing/transporting systems. PMID:26047551

  1. Catheter-related candidemia caused by Candida lipolytica in a patient receiving allogeneic bone marrow transplantation.

    PubMed

    D'Antonio, Domenico; Romano, Ferdinando; Pontieri, Eugenio; Fioritoni, Giuseppe; Caracciolo, Claudia; Bianchini, Stefano; Olioso, Paola; Staniscia, Tommaso; Sferra, Roberta; Boccia, Stefania; Vetuschi, Antonella; Federico, Giovanni; Gaudio, Eugenio; Carruba, Giuseppe

    2002-04-01

    Candida lipolytica was recovered from the blood and the central venous catheter in a patient receiving allogeneic bone marrow transplantation. Two C. lipolytica strains from different geographical areas and the ATCC 9773 strain of C. lipolytica were used as controls. C. lipolytica was identified by standard methods. MICs indicated antifungal susceptibilities to amphotericin B, fluconazole, and itraconazole for all strains. In vitro testing and scanning electron microscopy showed that C. lipolytica was capable of producing large amounts of viscid slime material in glucose-containing solution, likely responsible for the ability of the yeast to adhere to catheter surfaces. Restriction fragment length polymorphisms revealed an identical profile for all clinical isolates, unrelated to those observed for the control strains. This finding suggested the absence of microevolutionary changes in the population of the infecting strain, despite the length of the sepsis and the potential selective pressure of amphotericin B, which had been administered to the patient for about 20 days. The genomic differences that emerged between the isolates and the control strains were indicative of a certain degree of genetic diversity between C. lipolytica isolates from different geographical areas. PMID:11923360

  2. [Transplantation of bone marrow from unrelated donors in Italy: activity and results].

    PubMed

    Dini, G; Miano, M; Morreale, G; Lanino, E

    1999-01-01

    Unrelated donor (UD) bone marrow transplantation (BMT) represents an attractive option for patients with haematological, oncological or genetic diseases lacking a compatible familiar donor. Between September 1988 and December 1997 the search of a donor has been activated for 1724 patients in Italy. Until May 1998, 413 BMT from UD have been performed in 28 different authorized italian centres. Forty out of these patients were affected by genetic diseases apart from SCID (severe combined immunodeficiency). Sixty-month disease free survival (DFS) of this group was 62%. Seventy-four out of 215 children with acute lymphoblastic leukemia (ALL) for whom a donor search was started underwent a BMT. Six year DFS was 25%. Fifty-nine out of 379 patients with chronic myeloid leukemia (CML) for whom a donor search was activated underwent BMT. Forty-eight month DFS was 41.5%. Inborn errors curable with BMT, relapsed ALL and CML represent an absolute indication for UD BMT. In these cases donor search should be activated yearly.

  3. Patient satisfaction with nursing staff in bone marrow transplantation and hematology units.

    PubMed

    Piras, A; Poddigue, M; Angelucci, E

    2010-01-01

    Several validated questionnaires for assessment of hospitalized patient satisfaction have been reported in the literature. Many have been designed specifically for patients with cancer. User satisfaction is one indicator of service quality and benefits. Thus, we conducted a small qualitative survey managed by nursing staff in our Bone Marrow Transplantation Unit and Acute Leukemia Unit, with the objectives of assessing patient satisfaction, determining critical existing problems, and developing required interventions. The sample was not probabilistic. A questionnaire was developed using the Delphi method in a pilot study with 30 patients. Analysis of the data suggested a good level of patient satisfaction with medical and nursing staffs (100%), but poor satisfaction with food (48%), services (38%), and amenities (31%). Limitations of the study were that the questionnaire was unvalidated and the sample was small. However, for the first time, patient satisfaction was directly measured at our hospital. Another qualitative study will be conducted after correction of the critical points that emerged during this initial study, in a larger sample of patients. PMID:20692459

  4. [Bronchiolitis obliterans with severe obstructive ventilation disorder after a bone marrow transplant. Study of 7 cases].

    PubMed

    Philit, F; Wiesendanger, T; Guyotat, D; Troncy, J; Fière, D; Cordier, J F

    1991-01-01

    In 40 to 60% of bone marrow grafts there are pulmonary complications of which the most frequent is the occurrence of an interstitial pneumonia. We report 7 cases here of a more rare complication, that of bronchiolitis obliterans (BO). Between December 1979 and November 1989, 7 patients (3.4% of our cases of GMO) have developed over several months a chronic obstructive respiratory failure (a mean VEMS of 43% of the theoretical value) in the year following the transplantation (mean delay 190 days). 6 patients presented with cutaneous, digestive or hepatic signs of chronic graft v host illness (GVH) whereas the prevalence of this complication in the population studied was 17%. Treatment combining bronchodilators and immunosuppressants was only successful in 2 cases and the outcome was fatal in the 5 other cases as a result of respiratory failure (mean delay 208 days between the appearance of respiratory symptoms and death). The pathogenesis of BO after GMO remains poorly understood. It may rest on an immune process during the course of which the BO would be the result of a chronic pulmonary GVH. Another hypothesis is that the state of the immunosuppression in these patients would favour the appearance of a bronchiolitis of an infectious origin, particularly viral. The prognosis of BO after GMO is very poor and in the absence of specific effective treatment the therapeutic strategy remains essentially that of prevention by the early detection of respiratory anomalies.

  5. [Treatment of severe aplastic anemia with bone marrow transplants or with antithymocyte globulin. Evaluation of 27 patients].

    PubMed

    Arranz, R; Steegmann, J L; Fernández-Garesse, D; Figuera, A; Vázquez, L; Fernández-Rañada, J M

    1989-02-01

    The therapeutic results obtained in 27 patients with severe aplastic anemia (SAA) have been studied retrospectively. Ten patients underwent allogenic bone marrow transplantation (BMT) and 17 received antithymocyte globulin (ATG). Five of the ten patients transplanted (50%) are living and show normal hemopoiesis. Although prophylaxis was used, the incidence of host-versus-graft disease (grade II-IV) was 40% and concomitant pneumonitis was the main cause of death. Twenty courses of ATG were given to the 17 patients. 12 responses were achieved (60%), of which two were complete and the remaining were partial. Two patients who did not respond initially and one who recurred responded to a second course. Eleven patients survived (64.7%) of which 10 were disease-free (58.8%). One of them had remission controlled with cyclosporine. The probability of long-term survival is 48% in the group transplanted and 61.6% in the group treated with ATG, showing no statistical differences.

  6. Survival of irradiated recipient mice after transplantation of bone marrow from young, old and “early aging” mice

    PubMed Central

    Guest, Ian; Ilic, Zoran; Sell, Stewart

    2015-01-01

    Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16–18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best. PMID:26796640

  7. Survival of irradiated recipient mice after transplantation of bone marrow from young, old and "early aging" mice.

    PubMed

    Guest, Ian; Ilic, Zoran; Scrable, Heidi; Sell, Stewart

    2015-12-01

    Bone marrow transplantation is used to examine survival, hematopoietic stem cell function and pathology in recipients of young and old wild type bone marrow derived stem cells (BMDSCs) as well as cells from p53-based models of premature aging. There is no difference in the long term survival of recipients of 8 week-old p53+/m donor cells compared to recipients of 8 week-old wild-type (WT) donor cells (70 weeks) or of recipients of 16-18 weeks-old donor cells from either p53+/m or WT mice. There is shorter survival in recipients of older versus younger WT donor bone marrow, but the difference is only significant when comparing 8 and 18 week-old donors. In the p44-based model, short term survival/engraftment is significantly reduced in recipients of 11 month-old p44 donor cells compared to 4 week-old p44 or wild type donor cells of either age; mid-life survival at 40 weeks is also significantly less in recipients of p44 cells. BMDSCs are readily detectable within recipient bone marrow, lymph node, intestinal villi and liver sinusoids, but not in epithelial derived cells. These results indicate that recipients of young BMDSCs may survive longer than recipients of old bone marrow, but the difference is marginal at best.

  8. Allogeneic cell transplant expands bone marrow distribution by colonizing previously abandoned areas: an FDG PET/CT analysis.

    PubMed

    Fiz, Francesco; Marini, Cecilia; Campi, Cristina; Massone, Anna Maria; Podestà, Marina; Bottoni, Gianluca; Piva, Roberta; Bongioanni, Francesca; Bacigalupo, Andrea; Piana, Michele; Sambuceti, Gianmario; Frassoni, Francesco

    2015-06-25

    Mechanisms of hematopoietic reconstitution after bone marrow (BM) transplantation remain largely unknown. We applied a computational quantification software application to hybrid 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) images to assess activity and distribution of the hematopoietic system throughout the whole skeleton of recently transplanted patients. Thirty-four patients underwent PET/CT 30 days after either adult stem cell transplantation (allogeneic cell transplantation [ACT]; n = 18) or cord blood transplantation (CBT; n = 16). Our software automatically recognized compact bone volume and trabecular bone volume (IBV) in CT slices. Within IBV, coregistered PET data were extracted to identify the active BM (ABM) from the inactive tissue. Patients were compared with 34 matched controls chosen among a published normalcy database. Whole body ABM increased in ACT and CBT when compared with controls (12.4 ± 3 and 12.8 ± 6.8 vs 8.1 ± 2.6 mL/kg of ideal body weight [IBW], P < .001). In long bones, ABM increased three- and sixfold in CBT and ACT, respectively, compared with controls (0.9 ± 0.9 and 1.7 ± 2.5 vs 0.3 ± 0.3 mL/kg IBW, P < .01). These data document an unexpected distribution of transplanted BM into previously abandoned BM sites.

  9. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects. PMID:27651781

  10. Acellular allogeneic nerve grafting combined with bone marrow mesenchymal stem cell transplantation for the repair of long-segment sciatic nerve defects: biomechanics and validation of mathematical models

    PubMed Central

    Li, Ya-jun; Zhao, Bao-lin; Lv, Hao-ze; Qin, Zhi-gang; Luo, Min

    2016-01-01

    We hypothesized that a chemically extracted acellular allogeneic nerve graft used in combination with bone marrow mesenchymal stem cell transplantation would be an effective treatment for long-segment sciatic nerve defects. To test this, we established rabbit models of 30 mm sciatic nerve defects, and treated them using either an autograft or a chemically decellularized allogeneic nerve graft with or without simultaneous transplantation of bone marrow mesenchymal stem cells. We compared the tensile properties, electrophysiological function and morphology of the damaged nerve in each group. Sciatic nerves repaired by the allogeneic nerve graft combined with stem cell transplantation showed better recovery than those repaired by the acellular allogeneic nerve graft alone, and produced similar results to those observed with the autograft. These findings confirm that a chemically extracted acellular allogeneic nerve graft combined with transplantation of bone marrow mesenchymal stem cells is an effective method of repairing long-segment sciatic nerve defects.

  11. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

    PubMed

    Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

    2016-06-01

    Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation. PMID:26901703

  12. Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey.

    PubMed

    Niederwieser, D; Baldomero, H; Szer, J; Gratwohl, M; Aljurf, M; Atsuta, Y; Bouzas, L F; Confer, D; Greinix, H; Horowitz, M; Iida, M; Lipton, J; Mohty, M; Novitzky, N; Nunez, J; Passweg, J; Pasquini, M C; Kodera, Y; Apperley, J; Seber, A; Gratwohl, A

    2016-06-01

    Data on 68 146 hematopoietic stem cell transplants (HSCTs) (53% autologous and 47% allogeneic) gathered by 1566 teams from 77 countries and reported through their regional transplant organizations were analyzed by main indication, donor type and stem cell source for the year 2012. With transplant rates ranging from 0.1 to 1001 per 10 million inhabitants, more HSCTs were registered from unrelated 16 433 donors than related 15 493 donors. Grafts were collected from peripheral blood (66%), bone marrow (24%; mainly non-malignant disorders) and cord blood (10%). Compared with 2006, an increase of 46% total (57% allogeneic and 38% autologous) was observed. Growth was due to an increase in reporting teams (18%) and median transplant activity/team (from 38 to 48 HSCTs/team). An increase of 167% was noted in mismatched/haploidentical family HSCT. A Strengths, Weaknesses, Opportunities, Threats (SWOT) analysis revealed the global perspective of WBMT to be its major strength and identified potential to be the key professional body for patients and authorities. The limited data collection remains its major weakness and threat. In conclusion, global HSCT grows over the years without plateauing (allogeneic>autologous) and at different rates in the four World Health Organization regions. Major increases were observed in allogeneic, haploidentical HSCT and, to a lesser extent, in cord blood transplantation.

  13. Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum.

    PubMed

    Barba, Pere; Burns, Linda J; Litzow, Mark R; Juckett, Mark B; Komanduri, Krishna V; Lee, Stephanie J; Devlin, Sean M; Costa, Luciano J; Khan, Shakila; King, Andrea; Klein, Andreas; Krishnan, Amrita; Malone, Adriana; Mir, Muhammad A; Moravec, Carina; Selby, George; Roy, Vivek; Cochran, Melissa; Stricherz, Melisa K; Westmoreland, Michael D; Perales, Miguel-Angel; Wood, William A

    2016-03-01

    The American Society for Blood and Marrow Transplantation (ASBMT) Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data of cases posted in the CCF from January 29, 2014 to March 18, 2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) were autologous HCT, and in 16 (12%), the type of transplantation (autologous versus allogeneic) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (n = 23, 17%), and multiple myeloma (MM; n = 20, 15%). When compared with the US transplantation activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were over-represented in the CCF, whereas MM was under-represented (P < .001). A total of 259 topics were addressed in the CCF with a median of 2 topics/case (range, 1 to 6). Particularly common topics included whether transplantation was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives.

  14. Success of an International Learning Health Care System in Hematopoietic Cell Transplantation: The American Society of Blood and Marrow Transplantation Clinical Case Forum.

    PubMed

    Barba, Pere; Burns, Linda J; Litzow, Mark R; Juckett, Mark B; Komanduri, Krishna V; Lee, Stephanie J; Devlin, Sean M; Costa, Luciano J; Khan, Shakila; King, Andrea; Klein, Andreas; Krishnan, Amrita; Malone, Adriana; Mir, Muhammad A; Moravec, Carina; Selby, George; Roy, Vivek; Cochran, Melissa; Stricherz, Melisa K; Westmoreland, Michael D; Perales, Miguel-Angel; Wood, William A

    2016-03-01

    The American Society for Blood and Marrow Transplantation (ASBMT) Clinical Case Forum (CCF) was launched in 2014 as an online secure tool to enhance interaction and communication among hematopoietic cell transplantation (HCT) professionals worldwide through the discussion of challenging clinical care issues. After 14 months, we reviewed clinical and demographical data of cases posted in the CCF from January 29, 2014 to March 18, 2015. A total of 137 cases were posted during the study period. Ninety-two cases (67%) were allogeneic HCT, 29 (21%) were autologous HCT, and in 16 (12%), the type of transplantation (autologous versus allogeneic) was still under consideration. The diseases most frequently discussed included non-Hodgkin lymphoma (NHL; n = 30, 22%), acute myeloid leukemia (n = 23, 17%), and multiple myeloma (MM; n = 20, 15%). When compared with the US transplantation activity reported by the US Department of Health and Human Services, NHL and acute lymphoblastic leukemia cases were over-represented in the CCF, whereas MM was under-represented (P < .001). A total of 259 topics were addressed in the CCF with a median of 2 topics/case (range, 1 to 6). Particularly common topics included whether transplantation was indicated (n = 57, 41%), conditioning regimen choice (n = 44, 32%), and post-HCT complications after day 100 (n = 43, 31%). The ASBMT CCF is a successful tool for collaborative discussion of complex cases in the HCT community worldwide and may allow identification of areas of controversy or unmet need from clinical, educational and research perspectives. PMID:26718665

  15. Concise review: bone marrow mononuclear cells for the treatment of ischemic syndromes: medicinal product or cell transplantation?

    PubMed

    Cuende, Natividad; Rico, Laura; Herrera, Concha

    2012-05-01

    In November of 2011, the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA) published two scientific recommendations regarding the classification of autologous bone marrow-derived mononuclear cells (BM-MNCs) and autologous bone marrow-derived CD133+ cells as advanced therapy medicinal products (ATMPs), specifically tissue-engineered products, when intended for regeneration in ischemic heart tissue on the basis that they are not used for the same essential function (hematological restoration) that they fulfill in the donor. In vitro and in vivo evidence demonstrates that bone marrow cells are physiologically involved in adult neovascularization and tissue repair, making their therapeutic use for these purposes a simple exploitation of their own essential functions. Therefore, from a scientific/legal point of view, nonsubstantially manipulated BM-MNCs and CD133+ cells are not an ATMP, because they have a physiological role in the processes of postnatal neovascularization and, when used therapeutically for vascular restoration in ischemic tissues, they are carrying out one of their essential physiological functions (the legal definition recognizes that cells can have several essential functions). The consequences of classifying BM-MNCs and CD133+ cells as medicinal products instead of cellular transplantation, like bone marrow transplantation, in terms of costs and time for these products to be introduced into clinical practice, make this an issue of crucial importance. Therefore, the recommendations of EMA/CAT could be reviewed in collaboration with scientific societies, in light of organizational and economic consequences as well as scientific knowledge recently acquired about the mechanisms of postnatal neovascularization and the function of bone marrow in the regeneration of remote tissues.

  16. Kinetics of versican-expressing macrophages in bone marrow after cord blood stem cell transplantation for treatment of acute myelogenous leukaemia

    PubMed Central

    Senda, Miho; Fukuyama, Ryuichi; Nagasaka, Tetsuro

    2016-01-01

    Aims To determine versican-producing cells in normocellular bone marrow and to evaluate chronological alteration in the number of versican-producing macrophages in bone marrow of patients with acute myelogenous leukaemia (AML) after cord blood stem cell transplantation (CBSCT) to gain insight in the significance of versican in recovery of haematopoiesis. Methods We enrolled seven age-matched unrelated patients with normocellular bone marrow for determining versican-producing cells in bone marrow, CBSCT-treated patients with AML, 18 with fine and other four with poor engraftment, for determining chronological alteration of versican-expressing and CD68-expressing cells in transplanted bone marrow in reference to the total cells. Clot samples of patients with AML were collected from the +16 to +55 day after transplantation and separated into four groups. We included an AML case whose specimen was obtained on the +9 day. Cells positive in immunohistochemistry using antibodies to versican and CD68 were counted to obtain the mean±SD in a unit area of the bone marrow, plotted chronologically and compared with the numbers from the age-matched normocellular group. Results We determined by a double immunohistochemistry that the versican-expressing cells in bone marrow are macrophages. The time-course curve demonstrated an inverse relationship between the versican-positive macrophages and the total cells in the transplanted bone marrow for over 55 days. In bone marrow of poor engraftment cases, versican-positive macrophages appeared to be decreased in comparison with age-matched and sampling day-matched patients. Conclusions These results suggest that versican and/or versican-expressing macrophages positively contribute to bone marrow regeneration of patients with AML after CBSCT. PMID:26951084

  17. Neuroprotective effects of intravenous transplantation of bone marrow mononuclear cells from 5-fluorouracil pre-treated rats on ischemic stroke.

    PubMed

    Li, Y; Mao, W W; Zhang, C G; Wan, L; Jing, C H; Hua, X M; Li, S T; Cheng, J

    2016-03-15

    Our previous findings showed bone marrow mononuclear cells (BMMNCs) from 5- fluorouracil (5-FU) pre-treated rats (named BMRMNCs) had a better therapeutic efficacy in ischemia/reperfusion rats as compared to BMMNCs from untreated rats. This study was undertaken to explore the potential mechanisms underlying the neuroprotective effects of BMRMNCs in middle cerebral artery occlusion (MCAO) rat model. Rats were intravenously pre-treated with 5-FU and BMRMNCs were collected at different time points. The contents of growth factors in the supernatant and CXCR4 expression were detected by ELISA and flow cytometry, respectively. MCAO was introduced to rats, and BMMNCs and BMRMNCs collected at 7 days after 5-FU pre-treatment were independently transplanted via the tail vein 24h later. The neurological function was evaluated before cell transplantation and at 24h, 7d and 14d after cell transplantation. Rats were sacrificed at 14d after cell transplantation, the brains were collected for TTC staining, infarct volume detection, NISSL staining, counting of viable cells in the CA1 region, and observation of transplanted cells. BMRMNCs had elevated expressions of growth factors as well as CXCR4 expression. Our results confirmed the better therapeutic effects of BMRMNCs in MCAO rats, demonstrated by reduction in infarct volume, improvement of neurological function and more viable cells in the hippocampus. In addition, more transplanted cells were found after BMRMNCs transplantation at 7 days and 14 days although there was no marked difference at 14 days. These findings indicate that BMRMNCs transplantation may protect ischemic stroke, at least partially, via increasing the secretion of growth factors and migration to the injured site.

  18. Development of a single probe for documentation of chimerism following bone marrow transplantation.

    PubMed Central

    Yam, P; Petz, L D; Ali, S; Stock, A D; Wallace, R B

    1987-01-01

    Although numerous genetic markers are available for studying chimerism after bone marrow transplantation (BMT), there remains a need for a practical and highly informative method that is applicable in the early posttransplantation period. Using DNA restriction-fragment-length polymorphisms (RFLPs), we have evaluated the feasibility of developing a single synthetic oligonucleotide probe to study post-BMT chimerism. We have thus tested three candidate probes, termed O-3315-32, O-3315-80, and O-AY-29, that are homologous to tandemly repetitive sequences. Our results demonstrated donor-specific and recipient-specific fragments in 11 of 11 HLA-matched sibling pairs tested using probes O-3315-32 and O-3315-80. When probe O-AY-29 was used, 14 of 17 sibling pairs showed both donor and recipient markers, one had only a recipient marker, and two were identical. We showed that each of the three synthetic probes was effective in documenting donor marrow engraftment, mixed hematopoietic chimerism, the patient's pre-BMT phenotype (by using cultured skin fibroblasts obtained after BMT), and the origin of the malignant hematopoietic cells (i.e., of donor or recipient origin) in patients who developed recurrent hematologic malignancy following BMT. Compared with the use of cloned genomic probes, there are several important advantages to the use of synthetic oligonucleotide probes in studying post-BMT chimerism. Synthetic probes have absolute hybridization specificity and can be designed to suit the purposes of an individual study, since they have adjustable specificity that can be altered by changes in the length of the probe and by changes in the hybridization temperature. A single synthetic probe analogous to several highly polymorphic loci can have a polymorphism information content sufficiently high so that all but a small percentage of BMT patients could be followed easily; for example, if a probe were complementary to three highly polymorphic unlinked loci, it would

  19. Cyclosporin A and methotrexate in canine marrow transplantation: engraftment, graft-versus-host disease, and induction of intolerance

    SciTech Connect

    Deeg, H.J.; Storb, R.; Weiden, P.L.; Raff, R.F.; Sale, G.E.; Atkinson, K.; Graham, T.C.; Thomas, E.D.

    1982-07-01

    We examined the effect of methotrexate (MTX) and cyclosporin A (Cy A) on engraftment, graft-versus-host disease (GVHD), and the induction of tolerance in dogs prepared for marrow transplantation by 9 Gy of total body irradiation and grafted with bone marrow and buffy coat cells. Nineteen dogs were given grafts from DLA-identical littermates followed by immunosuppression with Cy A for 25 or 100 days. All had sustained engraftment, and 12 became healthy long-term chimeras. Sixty dogs were given grafts from DLA-nonidentical unrelated donors. Among nine given MTX only postgrafting, one rejected the graft nd eight died with GVHD. Among 18 dogs given Cy A only postgrafting, eight failed to achieve engraftment, seven died of various causes, and three died with GVHD. Thirty-four dogs were given both MTX and Cy A in various regimens postgrafting. The only long-term survivors were 4 of 10 dogs given MTX on days 1, 3, 6, and 11 and Cy A from days 0 through 100. Two have chronic GVHD. We conclude that Cy A can induce graft-host tolerance across minor, but not major, histocompatibility differences. The combination of MTX early after transplantation with Cy A prevents failure of engraftment of histoincompatible marrow and some recipients become long-term survivors.

  20. Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

    PubMed

    Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

    2016-01-01

    We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more

  1. Bone marrow transplantation improves autoinflammation and inflammatory bone loss in SH3BP2 knock-in cherubism mice.

    PubMed

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2015-02-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2(KI/KI)) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2(KI/KI) mice. Bone marrow (BM) cells from wild-type (Sh3bp2(+/+)) mice were transplanted to 6-week-old Sh3bp2(KI/KI) mice with developing inflammation and to 10-week-old Sh3bp2(KI/KI) mice with established inflammation. Six-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10weeks after BMT compared to Sh3bp2(KI/KI) mice transplanted with Sh3bp2(KI/KI) BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20weeks in 6-week-old Sh3bp2(KI/KI) mice transplanted with Sh3bp2(+/+) BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2(KI/KI) mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients.

  2. Bone Marrow Transplantation Improves Autoinflammation and Inflammatory Bone Loss in SH3BP2 Knock-In Cherubism Mice

    PubMed Central

    Yoshitaka, Teruhito; Kittaka, Mizuho; Ishida, Shu; Mizuno, Noriyoshi; Mukai, Tomoyuki; Ueki, Yasuyoshi

    2014-01-01

    Cherubism (OMIM#118400) is a genetic disorder in children characterized by excessive jawbone destruction with proliferation of fibro-osseous lesions containing a large number of osteoclasts. Mutations in the SH3-domain binding protein 2 (SH3BP2) are responsible for cherubism. Analysis of the knock-in (KI) mouse model of cherubism showed that homozygous cherubism mice (Sh3bp2KI/KI) spontaneously develop systemic autoinflammation and inflammatory bone loss and that cherubism is a TNF-α-dependent hematopoietic disorder. In this study, we investigated whether bone marrow transplantation (BMT) is effective for the treatment of inflammation and bone loss in Sh3bp2KI/KI mice. Bone marrow (BM) cells from wild-type (Sh3bp2+/+) mice were transplanted to 6-week-old Sh3bp2KI/KI mice with developing inflammation and to 10-week-old Sh3bp2KI/KI mice with established inflammation. Six-week-old Sh3bp2KI/KI mice transplanted with Sh3bp2+/+ BM cells exhibited improved body weight loss, facial swelling, and survival rate. Inflammatory lesions in the liver and lung as well as bone loss in calvaria and mandibula were ameliorated at 10 weeks after BMT compared to Sh3bp2KI/KI mice transplanted with Sh3bp2KI/KI BM cells. Elevation of serum TNF-α levels was not detected after BMT. BMT was effective for up to 20 weeks in 6-week-old Sh3bp2KI/KI mice transplanted with Sh3bp2+/+ BM cells. BMT also ameliorated the inflammation and bone loss in 10-week-old Sh3bp2KI/KI mice. Thus our study demonstrates that BMT improves the inflammation and bone loss in cherubism mice. BMT may be effective for the treatment of cherubism patients. PMID:25445458

  3. Evidence for Kidney Rejection after Combined Bone Marrow and Renal Transplantation Despite Ongoing Whole-blood Chimerism in Rhesus Macaques

    PubMed Central

    Ramakrishnan, Swetha K; Page, Andrew; Farris, Alton B.; Singh, Karnail; Leopardi, Frank; Hamby, Kelly; Sen, Sharon; Polnett, Aneesah; Deane, Taylor; Song, Mingqing; Stempora, Linda; Strobert, Elizabeth; Kirk, Allan D.; Larsen, Christian P.; Kean, Leslie S.

    2012-01-01

    Although there is evidence linking hematopoietic chimerism-induction and solid organ transplant tolerance, the mechanistic requirements for chimerism-induced tolerance are not clearly elucidated. To address this, we used an MHC-defined primate model to determine the impact of impermanent, T cell-poor, mixed-chimerism on renal allograft survival. We compared two cohorts: one receiving a bone marrow + renal transplant (“BMT/renal”) and one receiving only a renal transplant. Both cohorts received maintenance immunosuppression with CD28/CD40-directed costimulation blockade and sirolimus. As previously demonstrated, this transplant strategy consistently induced compartmentalized donor chimerism, (significant whole-blood chimerism, lacking T cell chimerism). This chimerism was not sufficient to prolong renal allograft acceptance: the BMT/renal mean survival time (MST, 76 days) was not significantly different than the renal transplant alone MST (85 days, p= 0. 46), with histopathology documenting T-cell mediated rejection. Flow cytometric analysis revealed significant enrichment for CD28-/CD95+ CD4+ and CD8+ Tem cells in the rejected kidney, suggesting a link between CD28-negative Tem and costimulation blockade-resistant rejection. These results suggest that in some settings, transient T cell-poor chimerism is not sufficient to induce tolerance to a concurrently placed renal allograft and that the presence of this chimerism per se is not an independent biomarker to identify tolerance. PMID:22642491

  4. Early vancomycin-resistant enterococcus (VRE) bacteremia after allogeneic bone marrow transplantation is associated with a rapidly deteriorating clinical course.

    PubMed

    Avery, R; Kalaycio, M; Pohlman, B; Sobecks, R; Kuczkowski, E; Andresen, S; Mossad, S; Shamp, J; Curtis, J; Kosar, J; Sands, K; Serafin, M; Bolwell, B

    2005-03-01

    Vancomycin-resistant enterococcal (VRE) infection is a growing threat. We studied the incidence, risk factors, and clinical course of early-onset VRE bacteremia in allogeneic hematopoietic stem cell transplant recipients. We carried out a chart review of 281 allogeneic hematopoietic stem cell transplant recipients from 1997-2003, including preparative regimen, diagnosis, status of disease, graft-versus-host disease prophylaxis, antimicrobial therapy, and survival. VRE bacteremia developed in 12/281 (4.3%) recipients; 10 (3.6%) were within 21 days of transplant. Diagnoses were acute leukemia (7), NHL (2), and MDS (1). In all, 70% had refractory/relapsed disease; 30% were in remission. In total, 50% had circulating blasts. Nine of 10 had matched unrelated donors (7/9 with CD8+ T-cell depletion). The average time to positive VRE cultures was 15 days; average WBC was 0.05, and 80% had concomitant infections. Despite treatment, all patients died within 73 days of VRE bacteremia. Intra-abdominal complications were common. Causes of death included bacterial or fungal infection, multiorgan failure, VOD, ARDS, and relapse. A total of 60% of patients engrafted neutrophils, but none engrafted platelets. Early VRE bacteremia after allogeneic bone marrow transplant is associated with a rapidly deteriorating clinical course, although not always directly due to VRE. Early VRE may be a marker for the critical condition of these high-risk patients at the time of transplant. PMID:15640812

  5. Transplantation of bone marrow mesenchymal stem cells for the treatment of type 2 diabetes in a macaque model.

    PubMed

    Pan, Xing-hua; Song, Qiao-qiao; Dai, Jie-jie; Yao, Xiang; Wang, Jin-xiang; Pang, Rong-qing; He, Jie; Li, Zi-an; Sun, Xiao-mei; Ruan, Guang-ping

    2013-01-01

    Bone marrow mesenchymal stem cells (BMSCs) are self-renewing, multipotent cells that can migrate to pathological sites and thereby provide a new treatment in diabetic animals. Superparamagnetic iron oxide/4',6-diamidino-2-phenylindole (DAPI) double-labeled BMSCs were transplanted into the pancreatic artery of macaques to treat type 2 diabetes mellitus (T2DM). The treatment efficiency of BMSCs was also evaluated. After successful induction of the T2DM model, the treatment group received double-labeled BMSCs via the pancreatic artery. Six weeks after BMSC transplantation, the fasting blood glucose and blood lipid levels measured in the treatment group were significantly lower (p < 0.05) than in the model group, although they were not reduced to normal levels (p < 0.05). Additionally, the serum C-peptide levels were significantly increased (p < 0.05). An intravenous glucose tolerance test and C-peptide release test had significant changes to the area under the curve. Within 14 days of the transplantation of labeled cells, the pancreatic and kidney tissue of the treatment group emitted a negative signal that was visible on magnetic resonance imaging (MRI). Six weeks after transplantation, DAPI signals appeared in the pancreatic and kidney tissue, which indicates that the BMSCs were mainly distributed in damaged tissue. Labeled stem cells can be used to track migration and distribution in vivo by MRI. In conclusion, the transplantation of BMSCs for the treatment of T2DM is safe and effective.

  6. Interleukin-1 genotype and outcome of unrelated donor bone marrow transplantation.

    PubMed

    MacMillan, Margaret L; Radloff, Gretchen A; DeFor, Todd E; Weisdorf, Daniel J; Davies, Stella M

    2003-05-01

    The interleukin 1 (IL-1) gene family includes three members (IL-1-alpha, IL-1-beta and IL-1Ra) that mediate immune and inflammatory responses through two specific cell surface receptors. Cytosine to thymine transitions at codons -889 and -511 in the IL-1-alpha and IL-1-beta genes, respectively, and an 86-base pair repeat in the IL-1Ra are believed to influence gene transcription. We have genotyped these three polymorphisms in 90 donor/recipient pairs undergoing unrelated donor bone marrow transplantation (BMT) at the University of Minnesota. We found no association between the occurrence of acute GVHD and donor and/or recipient polymorphisms of any of the three IL-1 genes. The presence of at least one IL-1alpha- 889 T allele in the donor was associated with significantly improved survival in univariate analysis (survival at 1 year 40% C/C donor, 68% T/C donor, 75% T/T donor, P < 0.01). Multiple regression analysis showed that if the donor and recipient each possessed the IL-1alpha T allele there was significantly improved survival [relative risk (RR) 0.2, P < 0.01] and decreased treatment-related mortality (TRM; RR 0.2, P = 0.01). The presence of the IL-1beta T allele in donor and recipient was also associated with improved survival (RR 0.2, P < 0.01) and decreased TRM (RR 0.1, P < 0.01). These data suggest that donor polymorphism in IL-1alpha and IL-1beta might influence survival after unrelated donor BMT, but does not alter risk of GVHD.

  7. Anti-tetanus toxoid antibody production after mismatched T cell-depleted bone marrow transplantation.

    PubMed

    Benkerrou, M; Wara, D W; Elder, M; Dror, Y; Merino, A; Colombe, B W; Garovoy, M; Cowan, M J

    1994-03-01

    We explored B-cell function after tetanus toxoid (TT) immunization in 12 children with severe combined immunodeficiency disease or leukemia who were long-term survivors of an HLA-matched sibling or haplocompatible T cell-depleted parental bone marrow transplant (BMT), 10 of their healthy donors, and 13 normal controls. Specific in vivo and in vitro anti-TT antibody (Ab) production were measured by ELISA. We studied donors' and recipients' peripheral blood mononuclear cells (PBMC) and mixed E- (non-T cells) and E+ cells (T cells) spontaneously and after stimulation by TT in the absence or presence of interleukin-2 (IL-2), IL-4, and IL-6. Five of the 12 patients and all donors and controls responded with in vivo anti-TT Ab. In vitro anti-TT Ab production correlated with the in vivo response. All seven of the nonresponders were either fully engrafted or mixed chimeras (donor T cells but autologous B cells and monocytes). We could not identify a T-cell defect in four of the five nonresponders who were tested. In contrast, E- cells from three of three responders cooperated with fresh donor E+ cells even when they shared only one HLA haplotype. In three of seven nonresponders, in vitro anti-TT Ab production was restored after the addition of IL-4 or IL-6 but not IL-2. Our results suggest that the humoral immunodeficiency that exists post mismatched T cell-depleted BMT is either a B-cell, a monocyte, or a B-cell/T-cell cooperation defect which, in some patients, may be correctible with the addition of a cytokine. Also, it is not necessary to engraft donor B cells to achieve normal antibody responses and the ability to respond does not appear to correlate with pretransplant chemotherapy.

  8. Needs of lay caregivers of bone marrow transplant patients in Turkey: a multicenter study.

    PubMed

    Aslan, O; Kav, S; Meral, C; Tekin, F; Yesil, H; Ozturk, U; Bulut, Z; Anaboifo, A; Dover, M; Yazar, B

    2006-01-01

    The purpose of this research was to identify the needs of lay caregivers of bone marrow transplant (BMT) patients throughout the BMT trajectory. The sample consisted of 58 lay caregivers of BMT patients (5 of which were inpatients) from the 4 BMT units in Ankara, Turkey. Data were collected through a demographic data form and the Psychological and Social Needs Scale. Data analysis was performed using SPSS 10.0 for Windows. Among the descriptive statistics, frequencies and percentages were used to define the characteristics of lay caregivers and responses related to information. Mean values, standard deviations, and the Pearson correlation coefficients were also calculated for the results of the subscales. Most of the lay caregivers were spouses. The rest were other family members: brother/sister, mother, son/daughter, or father. Only one lay caregiver was a friend. The most common type of BMT was autologous. Most of the surveys were completed by the lay caregivers whose patients had been out of the hospital for 100+ days after BMT. The lay caregivers were educated on the BMT process by various sources, and 67.24% of them expressed satisfaction with the information that they were given. A majority of them preferred face-to-face communication with a healthcare professional. The categories of the information provided were diagnosis and treatment, homecare after discharge, follow-ups and laboratory tests, and nutrition. They indicated a need for more information, particularly regarding homecare after discharge and diagnosis. Fear was the highest scoring psychological needs/problems of lay caregivers, whereas leisure activity deficit was highest among the social needs/problems. The information gathered from this study led us to reevaluate our healthcare services for both patients and lay caregivers to improve physical, psychological, and social aspects of the nursing care as a whole.

  9. Immunosuppressive Effects of Multipotent Mesenchymal Stromal Cells on Graft-Versus-Host Disease in Rats Following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Nevruz, Oral; Avcu, Ferit; Ural, A. Uğur; Pekel, Aysel; Dirican, Bahar; Safalı, Mükerrem; Akdağ, Elvin; Beyzadeoğlu, Murat; İde, Tayfun; Sengül, Ali

    2013-01-01

    Objective: Graft-versus-host disease (GVHD) is a major obstacle to successful allogeneic bone marrow transplantation (allo-BMT). While multipotent mesenchymal stromal cells (MSCs) demonstrate alloresponse in vitro and in vivo, they also have clinical applications toward prevention or treatment of GVHD. The aim of this study was to investigate the ability of MSCs to prevent or treat GVHD in a rat BMT model. Materials and Methods: The GVHD model was established by transplantation of Sprague Dawley rats’ bone marrow and spleen cells into lethally irradiated (950 cGy) SDxWistar rat recipients. A total of 49 rats were randomly assigned to 4 study and 3 control groups administered different GVHD prophylactic regimens including MSCs. After transplantation, clinical GVHD scores and survival status were monitored. Results: All irradiated and untreated control mice with GVHD died. MSCs inhibited lethal GVHD as efficiently as the standard GVHD prophylactic regimen. The gross and histopathological findings of GVHD and the ratio of CD4/CD8 expression decreased. The subgroup given MSCs displayed higher in vivo proportions of CD25+ T cells and plasma interleukin-2 levels as compared to conventional GVHD treatment after allo-BMT. Conclusion: Our results suggest that clinical use of MSCs in both prophylaxis against and treatment of established GVHD is effective. This study supports the use of MSCs in the prophylaxis and treatment of GVHD after allo-BMT; however, large scale studies are needed. Conflict of interest:None declared. PMID:24385804

  10. The Co-Transplantation of Bone Marrow Derived Mesenchymal Stem Cells Reduced Inflammation in Intramuscular Islet Transplantation

    PubMed Central

    Yoshimatsu, Gumpei; Sakata, Naoaki; Tsuchiya, Haruyuki; Minowa, Takashi; Takemura, Taro; Morita, Hiromi; Hata, Tatsuo; Fukase, Masahiko; Aoki, Takeshi; Ishida, Masaharu; Motoi, Fuyuhiko; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2015-01-01

    Aims/Hypothesis Although the muscle is one of the preferable transplant sites in islet transplantation, its transplant efficacy is poor. Here we attempted to determine whether an intramuscular co-transplantation of mesenchymal stem cells (MSCs) could improve the outcome. Methods We co-cultured murine islets with MSCs and then analyzed the morphological changes, viability, insulin-releasing function (represented by the stimulation index), and gene expression of the islets. We also transplanted 500 islets intramuscularly with or without 5 × 105 MSCs to diabetic mice and measured their blood glucose level, the glucose changes in an intraperitoneal glucose tolerance test, and the plasma IL-6 level. Inflammation, apoptosis, and neovascularization in the transplantation site were evaluated histologically. Results The destruction of islets tended to be prevented by co-culture with MSCs. The stimulation index was significantly higher in islets co-cultured with MSCs (1.78 ± 0.59 vs. 7.08 ± 2.53; p = 0.0025). In terms of gene expression, Sult1c2, Gstm1, and Rab37 were significantly upregulated in islets co-cultured with MSCs. Although MSCs were effective in the in vitro assays, they were only partially effective in facilitating intramuscular islet transplantation. Co-transplanted MSCs prevented an early inflammatory reaction from the islets (plasma IL-6; p = 0.0002, neutrophil infiltration; p = 0.016 inflammatory area; p = 0.021), but could not promote neovascularization in the muscle, resulting in the failure of many intramuscular transplanted islets to engraft. Conclusions In conclusion, co-culturing and co-transplanting MSCs is potentially useful in islet transplantation, especially in terms of anti-inflammation, but further augmentation for an anti-apoptosis effect and neovascularization is necessary. PMID:25679812

  11. Neuroprotective Effects of Bone Marrow Stromal Cell Transplantation in Combination With Treadmill Exercise Following Traumatic Brain Injury

    PubMed Central

    2016-01-01

    Purpose: Traumatic brain injury (TBI) causes cognitive impairments, motor deficits, and neuropsychiatric/behavioral deficits problems. Transplantation of bone marrow stromal cells (BMSCs) facilitates functional recovery from brain insults. Treadmill exercise increases neurogenesis and inhibits apoptosis. In this study, we investigated the effects of BMSC transplantation in combination with treadmill exercise on memory function, by evaluating its effect on neurogenesis and apoptosis in the hippocampus following TBI. Methods: TBI was induced using an electromagnetic-controlled cortical impact device. BMSCs were transplanted into both sides of traumatic scar region 1 week after TBI induction. One week after transplantation of BMSCs, the rats in the exercise groups were trained to run on a treadmill for 30 minutes once daily for 28 days. Step-down avoidance task and radial 8-arm maze test were conducted. Levels of 5-bromo-2ʹ-deoxyuridine and caspase-3 were evaluated using immunohistochemistry. Western blot was used to evaluate the expression of brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), total-extracellular signal-regulated kinase 1 and 2 (t-ERK1/2), phosphorylated-ERK1/2 (p-ERK1/2), Bcl-2, and Bax. Results: TBI deteriorated memory function, suppressed neurogenesis, and accelerated apoptosis in the hippocampus. Treadmill exercise and BMSC transplantation independently improved memory function by increasing neurogenesis with suppression of apoptosis through the BDNF-ERK pathway in the TBI-induced rats. Combination of BMSC transplantation with treadmill exercise showed additional enhancement of neurogenesis and suppression of apoptosis in the hippocampus. Conclusions: The present study shows that treadmill exercise may aid the therapeutic effect of BMSC transplantation on TBI in rats. PMID:27230460

  12. Indications for Autologous and Allogeneic Hematopoietic Cell Transplantation: Guidelines from the American Society for Blood and Marrow Transplantation.

    PubMed

    Majhail, Navneet S; Farnia, Stephanie H; Carpenter, Paul A; Champlin, Richard E; Crawford, Stephen; Marks, David I; Omel, James L; Orchard, Paul J; Palmer, Jeanne; Saber, Wael; Savani, Bipin N; Veys, Paul A; Bredeson, Christopher N; Giralt, Sergio A; LeMaistre, Charles F

    2015-11-01

    Approximately 20,000 hematopoietic cell transplantation (HCT) procedures are performed in the United States annually. With advances in transplantation technology and supportive care practices, HCT has become safer, and patient survival continues to improve over time. Indications for HCT continue to evolve as research refines the role for HCT in established indications and identifies emerging indications where HCT may be beneficial. The American Society for Blood and Marrow Transplantation (ASBMT) established a multiple-stakeholder task force consisting of transplant experts, payer representatives, and a patient advocate to provide guidance on "routine" indications for HCT. This white paper presents the recommendations from the task force. Indications for HCT were categorized as follows: (1) Standard of care, where indication for HCT is well defined and supported by evidence; (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but HCT has been shown to be effective therapy; (3) Standard of care, rare indication, for rare diseases where HCT has demonstrated effectiveness but large clinical trials and observational studies are not feasible; (4) Developmental, for diseases where preclinical and/or early phase clinical studies show HCT to be a promising treatment option; and (5) Not generally recommended, where available evidence does not support the routine use of HCT. The ASBMT will periodically review these guidelines and will update them as new evidence becomes available.

  13. Migration and Differentiation of GFP-transplanted Bone Marrow-derived Cells into Experimentally Induced Periodontal Polyp in Mice

    PubMed Central

    Matsuda, Saeka; Shoumura, Masahito; Osuga, Naoto; Tsujigiwa, Hidetsugu; Nakano, Keisuke; Okafuji, Norimasa; Ochiai, Takanaga; Hasegawa, Hiromasa; Kawakami, Toshiyuki

    2016-01-01

    Perforation of floor of the dental pulp is often encountered during root canal treatment in routine clinical practice of dental caries. If perforation were large, granulation tissue would grow to form periodontal polyp. Granulation tissue consists of proliferating cells however their origin is not clear. It was shown that the cells in granulation tissue are mainly from migration of undifferentiated mesenchymal cells of the bone marrow. Hence, this study utilized GFP bone marrow transplantation mouse model. The floor of the pulp chamber in maxillary first molar was perforated using ½ dental round bur. Morphological assessment was carried out by micro CT and microscopy and GFP cell mechanism was further assessed by immunohistochemistry using double fluorescent staining with GFP-S100A4; GFP-Runx2 and GFP-CD31. Results of micro CT revealed alveolar bone resorption and widening of periodontal ligament. Histopathological examination showed proliferation of fibroblasts with some round cells and blood vessels in the granulation tissue. At 2 weeks, the outermost layer of the granulation tissue was lined by squamous cells with distinct intercellular bridges. At 4 weeks, the granulation tissue became larger than the perforation and the outermost layer was lined by relatively typical stratified squamous epithelium. Double immunofluorescent staining of GFP and Runx2 revealed that both proteins were expressed in spindle-shaped cells. Double immunofluorescent staining of GFP and CD31 revealed that both proteins were expressed in vascular endothelial cells in morphologically distinct vessels. The results suggest that fibroblasts, periodontal ligament fibroblasts and blood vessels in granulation tissue were derived from transplanted-bone marrow cells. Thus, essential growth of granulation tissue in periodontal polyp was caused by the migration of undifferentiated mesenchymal cells derived from bone marrow, which differentiated into fibroblasts and later on differentiated into

  14. Mouse bone marrow-derived mesenchymal stem cells inhibit leukemia/lymphoma cell proliferation in vitro and in a mouse model of allogeneic bone marrow transplant

    PubMed Central

    SONG, NINGXIA; GAO, LEI; QIU, HUIYING; HUANG, CHONGMEI; CHENG, HUI; ZHOU, HONG; LV, SHUQING; CHEN, LI; WANG, JIANMIN

    2015-01-01

    The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft-versus-host disease (aGVHD). However, the role of MSCs in graft-versus-leukemia remains to be determined. In the present study, we co-cultured C57BL/6 mouse bone marrow (BM)-derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit-8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)-10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies. PMID:25901937

  15. Interrupted development of dentition in children receiving bone marrow transplantation for acute lymphocytic Leukemia: a case series.

    PubMed

    Rowland, Chris; Kaste, Sue; Owens, Amber

    2013-01-01

    This case series depicts dental anomalies that may develop in children who have undergone bone marrow transplantation (BMT) for acute lymphoblastic leukemia (ALL). The most common finding in these patients was root stunting; other abnormalities included microdontia, hypodontia, taurodontia, caries, enamel pearls, and pulpal calcification. Recognition of these adverse effects of BMT on odontogenesis, as demonstrated on panoramic radiograph images, will allow healthcare providers to explain to parents and patients the possible dental outcomes associated with BMT and to optimize their dental health regimen.

  16. Occurrence of Donor Cell-derived Lymphoid Blast Crisis 24 Years Following Related Bone Marrow Transplantation for Chronic Myeloid Leukemia.

    PubMed

    Kurosawa, Shuhei; Doki, Noriko; Hino, Yutaro; Sakaguchi, Masahiro; Fukushima, Kazuaki; Shingai, Naoki; Hattori, Keiichiro; Watanabe, Ken; Hagino, Takeshi; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2016-01-01

    We herein report a unique case of donor cell leukemia (DCL), as donor cell-derived lymphoid blast crisis of chronic myeloid leukemia (CML) was observed 24 years after related bone marrow transplantation for CML in the chronic phase. Short tandem repeat testing of the leukemic blast sample revealed full donor chimerism, strongly indicative of DCL. The original donor is healthy with a normal complete blood cell count for the past 24 years. This rare case may provide a precious opportunity to consider not only the underlying mechanism of DCL, but also the pathogenesis of CML.

  17. Stop waiting and start creating: service learning with an outpatient bone marrow transplant unit art cart program.

    PubMed

    Fletcher, Tina; Bayer, Christina; Beyer, Emily; Gonzales, Jessica; Ralston, Ashley; Yount, Phyllis

    2013-01-01

    This paper examines how master of occupational therapy students, their occupational therapy instructor, and a community-based licensed clinical social worker collaborated in a service learning art cart program on an outpatient bone marrow transplant unit. As they progressed through the phases of Kolb's model of service learning, occupational therapy students, their occupational therapy instructor, and the licensed clinical social worker were all able to meet mutual goals of serving a unique patient population, increasing knowledge of best practices, and building and fostering university/community relationships.

  18. What Happens During a Bone Marrow Transplant? | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of white blood cells. Without these cells, a person can develop life-threatening infections. A transplant provides stem cells to replace the missing white blood cells. Types of Transplants The two ...

  19. Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography versus bone marrow biopsy.

    PubMed

    Gheysens, Olivier; Thielemans, Sanne; Morscio, Julie; Boeckx, Nancy; Goffin, Karolien E; Deroose, Christophe M; Sagaert, Xavier; Wlodarska, Iwona; Verhoef, Gregor; Dierickx, Daan; Tousseyn, Thomas

    2016-10-01

    Detecting bone marrow involvement (BMI) in lymphoma is important as it adversely affects stage. Bone marrow biopsy (BMB) remains the standard to detect BMI but is prone to sampling error. We retrospectively investigated whether (18)F-fluorodeoxyglucose positron emission tomography with computed tomography ((18)F-FDG-PET/CT) could identify BMI in patients with post-transplant lymphoproliferative disorder (PTLD) with sufficient accuracy in comparison with staging BMB. Twenty-five patients diagnosed with PTLD who underwent (18)F-FDG-PET/CT and BMB within one month were evaluated. Based on our criteria, six patients (24%) were considered positive for BMI on (18)F-FDG-PET/CT compared to one by BMB. Although we cannot completely exclude false positive results on (18)F-FDG-PET/CT, our data indicate a significantly higher sensitivity of (18)F-FDG-PET/CT compared to BMB (100% vs 17%) but similar specificity. These data confirm the high diagnostic performance of (18)F-FDG-PET/CT for detecting BMI, but prospective studies are needed to determine whether (18)F-FDG-PET/CT could indeed replace staging BMB in PTLD.

  20. Myeloablative therapy and bone marrow rescue in advanced neuroblastoma. Report from the Italian Bone Marrow Transplant Registry. Italian Association of Pediatric Hematology-Oncology, BMT Group.

    PubMed

    Garaventa, A; Rondelli, R; Lanino, E; Dallorso, S; Dini, G; Bonetti, F; Arrighini, A; Santoro, N; Rossetti, F; Miniero, R; Andolina, M; Amici, A; Indolfi, P; Lo Curto, M; Favre, C; Paolucci, P; Pession, A; De Bernardi, B

    1996-07-01

    This study reports a large cooperative experience in myeloablative therapy and bone marrow rescue undertaken to define better the outcome of children with disseminated neuroblastoma after megatherapy. Between 1984 and 1993, 135 children underwent myeloablative therapy with bone marrow transplantation (BMT) in nine Italian Centres. One hundred and seventeen children received unpurged autologous BMT, five allogeneic BMT and 13 peripheral blood progenitor cells as rescue. Of these 135 children, 57 were in 1st CR, 11 in 2nd or subsequent CR, 42 in 1st PR, and 25 had more advanced disease. Twelve children (9%) died of toxicity, 86 relapsed or progressed at 1-68 months (median 7 months) and 80 of these subsequently died of progressive disease. Forty-three children are still alive with 37 in continuous remission at a median of 65 months (30-123 months) after BMT. Overall and disease-free survival at 8 years are 28.5% (s.e. 4.3) and 26% (s.e. 4), respectively. Disease-free survival is 34.6% (s.e. 6.7) for the patients grafted in 1st complete remission, 23.6% (s.e. 6.6) for patients grafted in 1st partial remission, 36.4% (s.e. 14.5) for patients grafted in 2nd or subsequent CR, and 8% (5.4) for patients with advanced disease. We conclude these data confirm that early toxicity of myeloablative therapy is manageable and that myeloablative therapy with bone marrow rescue may contribute to an improved long-term survival of children with disseminated neuroblastoma but the objective of cure of all patients remains distant.

  1. Titration of IgG antibodies against varicella zoster virus before bone marrow transplantation is not predictive of future zoster.

    PubMed

    Webster, A; Grint, P; Brenner, M K; Prentice, H G; Griffiths, P D

    1989-02-01

    Serum antibodies to varicella zoster virus (VZV) were measured in 77 patients about to undergo allogeneic bone marrow transplantation, and in 65 of their donors. Ten patients developed zoster within the first 6 months following transplant. There was no significant difference in the mean pretransplant antibody titre between those patients who did or did not subsequently develop zoster. Likewise, the level of antibody to VZV amongst donors had no effect on the subsequent development of zoster. We conclude that the pretransplant level of antibody to VZV is not predictive of subsequent zoster infection, and would not be helpful in identifying patients for trials of antiviral prophylaxis. These results contrast with those previously found for another herpesvirus, herpes simplex (HSV), where antibody level pretransplant is predictive of future HSV recurrence.

  2. Local transplantation of ex vivo expanded bone marrow-derived CD34-positive cells accelerates fracture healing.

    PubMed

    Kawakami, Yohei; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Matsumoto, Tomoyuki; Kuroda, Ryosuke; Shoji, Taro; Fukui, Tomoaki; Masuda, Haruchika; Akimaru, Hiroshi; Mifune, Yutaka; Kuroda, Tomoya; Horii, Miki; Yokoyama, Ayumi; Kurosaka, Masahiro; Asahara, Takayuki

    2012-01-01

    Transplantation of bone marrow (BM) CD34(+) cells, an endothelial/hematopoietic progenitor-enriched cell population, has shown therapeutic efficiency in the treatment of ischemic diseases enhancing neovascularization. However, the number of CD34(+) cells obtained from bone marrow is not sufficient for routine clinical application. To overcome this issue, we developed a more efficient and clinically applicable CD34(+) cell expansion method. Seven-day ex vivo expansion culture of BM CD34(+) cells with a cocktail of five growth factors containing VEGF, SCF, IL-6, Flt-3 ligand, and TPO resulted in reproducible more than 20-fold increase in cell number. The favorable effect of the local transplantation of culture expanded (cEx)-BM CD34(+) cells on rat unhealing fractures was equivalent or higher than that of nonexpanded (fresh) BM CD34(+) cells exhibiting sufficient therapeutic outcome with frequent vasculogenic/osteogenic differentiation of transplanted cEx-BM CD34(+) cells and fresh BM CD34(+) cells as well as intrinsic enhancement of angiogenesis/osteogenesis at the treated fracture sites. Specifically, cEx-BM CD34(+) cell treatment demonstrated the best blood flow recovery at fracture sites compared with the nonexpanded BM CD34(+) cells. In vitro, cEx-BM CD34(+) cells showed higher colony/tube-forming capacity than nonexpanded BM CD34(+) cells. Both cells demonstrated differentiation potential into osteoblasts. Since fresh BM CD34(+) cells can be easily collected from fracture sites at the time of primary operation and stored for future use, autologous cEx-BM CD34(+) cell transplantation would be not only a simple but also a promising therapeutic strategy for unhealing fractures in the field of orthopedic trauma surgery.

  3. Fate of bone marrow mesenchymal stem cells following the allogeneic transplantation of cartilaginous aggregates into osteochondral defects of rabbits.

    PubMed

    Yoshioka, Tomokazu; Mishima, Hajime; Kaul, Zeenia; Ohyabu, Yoshimi; Sakai, Shinsuke; Ochiai, Naoyuki; Kaul, Sunil C; Wadhwa, Renu; Uemura, Toshimasa

    2011-06-01

    The purpose of this study was to track mesenchymal stem cells (MSCs) labelled with internalizing quantum dots (i-QDs) in the reparative tissues, following the allogeneic transplantation of three-dimensional (3D) cartilaginous aggregates into the osteochondral defects of rabbits. QDs were conjugated with a unique internalizing antibody against a heat shock protein-70 (hsp70) family stress chaperone, mortalin, which is upregulated and expressed on the surface of dividing cells. The i-QDs were added to the culture medium for 24 h. Scaffold-free cartilaginous aggregates formed from i-QD-labelled MSCs (i-MSCs), using a 3D culture system with chondrogenic supplements for 1 week, were transplanted into osteochondral defects of rabbits. At 4, 8 and 26 weeks after the transplantation, the reparative tissues were evaluated macroscopically, histologically and fluoroscopically. At as early as 4 weeks, the defects were covered with a white tissue resembling articular cartilage. In histological appearance, the reparative tissues resembled hyaline cartilage on safranin-O staining throughout the 26 weeks. In the deeper portion, subchondral bone and bone marrow were well remodelled. On fluoroscopic evaluation, QDs were tracked mainly in bone marrow stromata, with some signals detected in cartilage and the subchondral bone layer. We showed that the labelling of rabbit MSCs with anti-mortalin antibody-conjugated i-QDs is a tolerable procedure and provides a stable fluorescence signal during the cartilage repair process for up to 26 weeks after transplantation. The results suggest that i-MSCs did not inhibit, and indeed contributed to, the regeneration of osteochondral defects.

  4. Effect of the bone marrow cell transplantation on elevated plus-maze performance in hippocampal-injured mice.

    PubMed

    da Cruz e Alves-de-Moraes, Luís Bruno; Ribeiro-Paes, João Tadeu; Longo, Beatriz Monteiro; Ferrazoli, Enéas Galdini; de Andrade, Telma Gonçalves Carneiro Spera

    2013-07-01

    Several reports have shown that the hippocampus plays an important role in different aspects of the emotional control. There is evidence that lesions in this structure cause behavioral disinhibition, with reduction of reactions expressing fear and anxiety. Thus, to portray the aptitude of cell therapy to abrogate injuries of hippocampal tissue, we examined the behavioral effects of bone marrow mononuclear cells (BMMCs) transplantation on C57BL/6 mice that had the hippocampus damaged by electrolytic lesion. For this purpose, mice received, seven days after bilateral electrolytic lesion in the dorsal hippocampus, culture medium or BMMCs expressing the enhanced green fluorescent protein (EGFP) transgene. One week after transplantation, animals were tested in the elevated plus-maze (EPM). On the whole, three assessment sessions in the EPM were carried out, with seven days separating each trial. Thirty-five days after the induction of injury, mice were sacrificed and their brains removed for immunohistochemistry. The behavioral evaluation showed that the hippocampal lesion caused disinhibition, an effect which was slightly lessened, from the second EPM test, in transplanted subjects. On the other hand, immunohistochemical data revealed an insignificant presence of EGFP(+) cells inside the brains of injured mice. In view of such scenario, we hypothesized that the subtle rehabilitation of the altered behavior might be a result from a paracrine effect from the transplanted cells. This might have been caused by the release of bioactive factors capable of boosting endogenous recuperative mechanisms for a partial regaining of the hippocampal functions.

  5. Decision-making in adult thalassemia patients undergoing unrelated bone marrow transplantation: quality of life, communication and ethical issues.

    PubMed

    Caocci, G; Pisu, S; Argiolu, F; Giardini, C; Locatelli, F; Vacca, A; Orofino, M G; Piras, E; De Stefano, P; Addari, M C; Ledda, A; La Nasa, G

    2006-01-01

    Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed. PMID:16299541

  6. Severe Papillomavirus Infection Progressing to Metastatic Squamous Cell Carcinoma in Bone Marrow-Transplanted X-Linked SCID Dogs

    PubMed Central

    Goldschmidt, Michael H.; Kennedy, Jeffrey S.; Kennedy, Douglas R.; Yuan, Hang; Holt, David E.; Casal, Margret L.; Traas, Anne M.; Mauldin, Elizabeth A.; Moore, Peter F.; Henthorn, Paula S.; Hartnett, Brian J.; Weinberg, Kenneth I.; Schlegel, Richard; Felsburg, Peter J.

    2006-01-01

    Canine X-linked severe combined immunodeficiency (XSCID) is due to mutations in the common gamma chain (γc) gene and is identical clinically and immunologically to human XSCID, making it a true homologue of the human disease. Bone marrow-transplanted (BMT) XSCID dogs not only engraft donor T cells and reconstitute normal T-cell function but, in contrast to the majority of transplanted human XSCID patients, also engraft donor B cells and reconstitute normal humoral immune function. Shortly after our initial report of successful BMT of XSCID dogs, it soon became evident that transplanted XSCID dogs developed late-onset severe chronic cutaneous infections containing a newly described canine papillomavirus. This is analogous to the late-onset cutaneous papillomavirus infection recently described for human XSCID patients following BMT. Of 24 transplanted XSCID dogs followed for at least 1 year post-BMT, 71% developed chronic canine papillomavirus infection. Six of the transplanted dogs that developed cutaneous papillomas were maintained for >3 1/2 years post-BMT for use as breeders. Four of these six dogs (67%) developed invasive squamous cell carcinoma (SCC), with three of the dogs (75%) eventually developing metastatic SCC, an extremely rare consequence of SCC in the dog. This finding raises the question of whether SCC will develop in transplanted human XSCID patients later in life. Canine XSCID therefore provides an ideal animal model with which to study the role of the γc-dependent signaling pathway in the response to papillomavirus infections and the progression of these viral infections to metastatic SCC. PMID:16775349

  7. Haploidentical transplantation. Importance of histocompatibility testing and chimerism studies in allogeneic bone marrow/stem cell transplantation.

    PubMed

    Rebellato, L M; Dobbs, L J

    2001-01-01

    The transplantation of hematopoietic stem cells is sometimes the only treatment option for certain types of malignancies and hematological disorders. The best way to ensure a positive outcome from this type of procedure is to secure an identical human lymphocyte antigen-matched donor or use an autologous graft. This article reviews the indications for transplantation, the recipient and donor selection process, and posttransplant follow-up. The advantages of using haploidentical donors and the typing process also will be discussed.

  8. Fate of Transplanted Bone Marrow Derived Mesenchymal Stem Cells Following Spinal Cord Injury in Rats by Transplantation Routes

    PubMed Central

    Kang, Eun-Sun; Ha, Kee-Yong

    2012-01-01

    This research was performed to investigate the differences of the transplanted cells' survival and differentiation, and its efficacy according to the delivery routes following spinal cord injury. Allogenic mesenchymal stem cells (MSCs) were transplanted intravenously (IV group) or intralesionally (IL group) at post-injury 1 day in rats. Behavioral improvement, engraftment and differentiation of the transplanted cells and the expression of neurotrophic factors of the transplanted groups were analyzed and compared with those of the control group. At 6 weeks post-injury, the mean BBB motor scales in the control, IV and IL groups were 6.5 ± 1.8, 11.1 ± 2.1, and 8.5 ± 2.8, respectively. Regardless of the delivery route, the MSCs transplantation following spinal cord injuries presented better behavioral improvement. The differentiations of the engrafted cells were different according to the delivery routes. The engrafted cells predominantly differentiated into astrocytes in the IV group and on the other hand, engrafted cells of the IL group demonstrated relatively even neural and glial differentiation. The expressions of neuronal growth factor were significantly higher in the IL group (mean relative optical density, 2.4 ± 0.15) than those in the control (2.16 ± 0.04) or IV group (1.7 ± 0.23). Transplantation of MSCs in the early stage of spinal cord injury gives a significant clinical improvement. However, the fate of the transplanted MSCs and expression of neuronal growth factors are different along the transplantation route. PMID:22690088

  9. Canine bone marrow-derived mesenchymal stromal cells suppress alloreactive lymphocyte proliferation in vitro but fail to enhance engraftment in canine bone marrow transplantation.

    PubMed

    Lee, Won Sik; Suzuki, Yasuhiro; Graves, Scott S; Iwata, Mineo; Venkataraman, G M; Mielcarek, Marco; Peterson, Laura J; Ikehara, Susumu; Torok-Storb, Beverly; Storb, Rainer

    2011-04-01

    Stable mixed hematopoietic chimerism has been consistently established in dogs who were mildly immunosuppressed by 200 cGy of total body irradiation (TBI) before undergoing dog leukocyte antigen (DLA)-identical bone marrow (BM) transplantation and who received a brief course of immunosuppression with mycophenolate mofetil (28 days) and cyclosporine (35 days) after transplantation. However, when TBI was reduced from 200 to 100 cGy, grafts were nearly uniformly rejected within 3-12 weeks. Here, we asked whether stable engraftment could be accomplished after a suboptimal dose of 100 cGy TBI with host immunosuppression enhanced by donor-derived mesenchymal stromal cells (MSCs) given after transplantation. MSCs were cultured from BM cells and evaluated in vitro for antigen expression. They showed profound immunosuppressive properties in mixed lymphocyte reactions (MLRs) in a cell dose-dependent manner not restricted by DLA. MSC and lymphocyte contact was not required, indicating that immunosuppression was mediated by soluble factors. Prostaglandin E2 was increased in culture supernatant when MSCs were cocultured in MLRs. The addition of indomethacin restored lymphocyte proliferation in cultures containing MSCs. MSCs expressed CD10, CD13, CD29, CD44, CD73/SH-3, CD90/Thy-1, and CD106/VCAM-1. For in vivo studies, MSCs were injected on the day of BM grafting and on day 35, the day of discontinuation of posttransplantation cyclosporine. MSCs derived from the respective BM donors failed to avert BM graft rejection in 4 dogs who received DLA-identical grafts after nonmyeloablative conditioning with 100 cGy TBI in a time course not significantly different from that of control dogs not given MSCs. Although the MSCs displayed in vitro characteristics similar to those reported for MSCs from other species, their immunosuppressive qualities failed to sustain stable BM engraftment in vivo in this canine model. PMID:20457265

  10. An informative constitutional cytogenetic marker found in a patient post bone marrow transplantation

    SciTech Connect

    Zaslav, A.L.; Graziano, J.; Ebert, R.

    1994-09-01

    It is cytogenetically difficult to distinguish between host and donor cells in allogeneic bone marrow transplantation (BMT) individuals of the same sex. Here we describe a patient with a cytogenetic marker found after BMT. A 7-month-old male presented with leukemia which was CD7+, CD33+, HLADR+, and CD4-, CD8-, indicating a diagnosis of acute stem cell leukemia (ASCL). Cytogenetic analysis revealed an abnormal clone in all of the cells analyzed: 46,XY,t(2;8)(p11.2;q24),inv(9)(p13p24). This translocation is associated with B-cell acute lymphoblastic leukemia (ALL); thus, it was possible for this patient to develop B-cell ALL. The abnormal clone persisted along with normal 46,XY cells, and evolved in several of seven additional analyses. The patient was treated with two courses of chemotherapy and failed to attain cytogenetic remission. While in relapse, the patient received a BMT from his 3-year-old brother. Two weeks later, a different translocation was seen in all cells: 46,XY,t(3;12)(p21;q21). This result could be interpreted in two ways: (1) the structural abnormality was indicative of a newly evolved clone related to the patient`s disease; or (2) the donor was a balanced translocation carrier. Cytogenetic analysis of peripheral blood from the donor revealed the same translocation seen in the patient. Parental blood chromosomes were normal indicating that the donor carried a de novo balanced translocation. Subsequent chromosome analysis of both peripheral blood and BM from the patient revealed the presence of the translocation in all cells. De novo balanced translocations are rare and occur with a frequency of 1/2,000 live borns. The family received genetic counseling and was informed of the possible reproductive risks to translocation carriers. This unusual finding will serve as a useful cytogenetic marker to assist in monitoring the patient`s clinical course, i.e., chimerism and remission status.

  11. Intravenous Autologous Bone Marrow Mononuclear Cell Transplantation for Stroke: Phase1/2a Clinical Trial in a Homogeneous Group of Stroke Patients.

    PubMed

    Taguchi, Akihiko; Sakai, Chiaki; Soma, Toshihiro; Kasahara, Yukiko; Stern, David M; Kajimoto, Katsufumi; Ihara, Masafumi; Daimon, Takashi; Yamahara, Kenichi; Doi, Kaori; Kohara, Nobuo; Nishimura, Hiroyuki; Matsuyama, Tomohiro; Naritomi, Hiroaki; Sakai, Nobuyuki; Nagatsuka, Kazuyuki

    2015-10-01

    The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20-75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤ 5 points during the first 7 days after stroke, and NIHSS score of ≥ 10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7-10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 10(8) and 3.4 × 10(8) cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach.

  12. Ex Vivo Expanded Allogeneic Mesenchymal Stem Cells With Bone Marrow Transplantation Improved Osteogenesis in Infants With Severe Hypophosphatasia.

    PubMed

    Taketani, Takeshi; Oyama, Chigusa; Mihara, Aya; Tanabe, Yuka; Abe, Mariko; Hirade, Tomohiro; Yamamoto, Satoshi; Bo, Ryosuke; Kanai, Rie; Tadenuma, Taku; Michibata, Yuko; Yamamoto, Soichiro; Hattori, Miho; Katsube, Yoshihiro; Ohnishi, Hiroe; Sasao, Mari; Oda, Yasuaki; Hattori, Koji; Yuba, Shunsuke; Ohgushi, Hajime; Yamaguchi, Seiji

    2015-01-01

    Patients with severe hypophosphatasia (HPP) develop osteogenic impairment with extremely low alkaline phosphatase (ALP) activity, resulting in a fatal course during infancy. Mesenchymal stem cells (MSCs) differentiate into various mesenchymal lineages, including bone and cartilage. The efficacy of allogeneic hematopoietic stem cell transplantation for congenital skeletal and storage disorders is limited, and therefore we focused on MSCs for the treatment of HPP. To determine the effect of MSCs on osteogenesis, we performed multiple infusions of ex vivo expanded allogeneic MSCs for two patients with severe HPP who had undergone bone marrow transplantation (BMT) from asymptomatic relatives harboring the heterozygous mutation. There were improvements in not only bone mineralization but also muscle mass, respiratory function, and mental development, resulting in the patients being alive at the age of 3. After the infusion of MSCs, chimerism analysis of the mesenchymal cell fraction isolated from bone marrow in the patients demonstrated that donor-derived DNA sequences existed. Adverse events of BMT were tolerated, whereas those of MSC infusion did not occur. However, restoration of ALP activity was limited, and normal bony architecture could not be achieved. Our data suggest that multiple MSC infusions, following BMT, were effective and brought about clinical benefits for patients with lethal HPP. Allogeneic MSC-based therapy would be useful for patients with other congenital bone diseases and tissue disorders if the curative strategy to restore clinically normal features, including bony architecture, can be established.

  13. [Intracardial transplantation of mononuclear cells of the autologous bone marrow in complex treatment of patients with valvular heart diseases].

    PubMed

    Davydenko, V V; Gretsenko, V V; Afanas'ev, B V; Pizin, V M; Mochalov, O Iu; Degtereva, O A; Matiukov, A A

    2007-01-01

    The authors present the first clinical experience with intramyocardial transplantation of the mononuclear fraction of cells of the autologous bone marrow in complex surgical treatment of 10 patients with valvular heart disease. The cellular transplantation was fulfilled intraoperatively when making a prosthetic mitral (5 patients) and aortal (5 patients) valves on the open heart under conditions of extracorporeal circulation. Simultaneously direct revascularization of the myocardium (aorto-coronary and mammary-coronary shunts) was performed in 4 patients (1--with a mitral and 3--with aortal heart diseases). An investigation of the results of the examination including ECG, EchoCG and investigation of the myocardium perfusion using one-photon emission computed tomography fulfilled in the early postoperative period and within 6-12 months after operation has shown that the cell cardiomyoplasty with mononuclear fraction of cells of the autologous bone marrow improves the myocardium perfusion, however, in the early postoperative period the appearance of transitory impairments of the heart rate is possible. PMID:18050635

  14. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

    PubMed

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R; He, Wensheng; Couriel, Daniel R; Urbano-Ispizua, Alvaro; Cutler, Corey S; Bacigalupo, Andrea A; Battiwalla, Minoo; Flowers, Mary E; Juckett, Mark B; Lee, Stephanie J; Loren, Alison W; Klumpp, Thomas R; Prockup, Susan E; Ringdén, Olle T H; Savani, Bipin N; Socié, Gérard; Schultz, Kirk R; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N; Jacobsohn, David A; Hayashi, Robert J; Drobyski, William R; Frangoul, Haydar A; Akpek, Görgün; Ho, Vincent T; Lewis, Victor A; Gale, Robert Peter; Koreth, John; Chao, Nelson J; Aljurf, Mahmoud D; Cooper, Brenda W; Laughlin, Mary J; Hsu, Jack W; Hematti, Peiman; Verdonck, Leo F; Solh, Melhelm M; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D; McCarthy, Philip L; Pérez-Simón, José A; Khera, Nandita; Lewis, Ian D; Atsuta, Yoshiko; Olsson, Richard F; Saber, Wael; Waller, Edmund K; Blaise, Didier; Pidala, Joseph A; Martin, Paul J; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J; Horowitz, Mary M; Pavletic, Steven Z

    2015-02-01

    Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

  15. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research.

    PubMed

    Arai, Sally; Arora, Mukta; Wang, Tao; Spellman, Stephen R; He, Wensheng; Couriel, Daniel R; Urbano-Ispizua, Alvaro; Cutler, Corey S; Bacigalupo, Andrea A; Battiwalla, Minoo; Flowers, Mary E; Juckett, Mark B; Lee, Stephanie J; Loren, Alison W; Klumpp, Thomas R; Prockup, Susan E; Ringdén, Olle T H; Savani, Bipin N; Socié, Gérard; Schultz, Kirk R; Spitzer, Thomas; Teshima, Takanori; Bredeson, Christopher N; Jacobsohn, David A; Hayashi, Robert J; Drobyski, William R; Frangoul, Haydar A; Akpek, Görgün; Ho, Vincent T; Lewis, Victor A; Gale, Robert Peter; Koreth, John; Chao, Nelson J; Aljurf, Mahmoud D; Cooper, Brenda W; Laughlin, Mary J; Hsu, Jack W; Hematti, Peiman; Verdonck, Leo F; Solh, Melhelm M; Norkin, Maxim; Reddy, Vijay; Martino, Rodrigo; Gadalla, Shahinaz; Goldberg, Jenna D; McCarthy, Philip L; Pérez-Simón, José A; Khera, Nandita; Lewis, Ian D; Atsuta, Yoshiko; Olsson, Richard F; Saber, Wael; Waller, Edmund K; Blaise, Didier; Pidala, Joseph A; Martin, Paul J; Satwani, Prakash; Bornhäuser, Martin; Inamoto, Yoshihiro; Weisdorf, Daniel J; Horowitz, Mary M; Pavletic, Steven Z

    2015-02-01

    Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. PMID:25445023

  16. Studies of allogeneic bone marrow and spleen cell transplantation in a murine model using ultraviolet-B light

    SciTech Connect

    Pamphilon, D.H.; Alnaqdy, A.A.; Godwin, V.; Preece, A.W.; Wallington, T.B. )

    1991-05-01

    Ultraviolet irradiation inhibits alloreactive and mitogen-induced responses and might reduce both graft-versus-host and host-versus-graft reactions after bone marrow transplantation (BMT). We have studied proliferative responses to mitogens and reactivity in mixed lymphocyte culture after irradiation with ultraviolet (UV)-B light using splenocytes from Balb/c (H-2d) and CBA (H-2k) mice. Response to mitogens and in MLC was strongly inhibited by 20 J/m{sup 2} and abolished at 50 J/m{sup 2}. Clonogenic cell recovery (CFU-GM; CFU-S) after UV-B irradiation was also reduced. When bone marrow and spleen cells were transplanted from parent (Balb/c) animals into F1 hybrid (Balb/c X CBA) recipients, all animals died with features indicative of graft-versus-host disease (GVHD) in 34 days. If the grafts were first irradiated with 100 J/m{sup 2} of UV-B at a mean wavelength of 310 nm, then 76% survived to day 80 when they were killed and shown to have normal marrow cellularity. The remainder died in marrow aplasia or of GVHD. H-2 typing in a group of surviving recipients showed either donor hematopoiesis only (8 of 15), mixed allogeneic chimerism (5 of 15), or recipient type hematopoiesis (2 of 15). Higher doses (200 to 300 J/m{sup 2}) were detrimental to survival with 88% of recipients dying in marrow aplasia. Syngeneic BMT in Balb/c mice showed slower hematopoietic reconstitution when the grafts were first irradiated with 100 J/m{sup 2}. After BMT from Balb/c to CBA mice all recipients of unirradiated grafts died within 54 days. By contrast, after graft irradiation with 100 J/m{sup 2} survival of recipient animals to day 80 was 59%. If these grafts were treated with 50 J/m{sup 2} survival was only 26% with an increase in deaths due to GVHD. Hematopoiesis at day 80 in a group of survivors studied by Ig heavy chain allotyping indicated donor type hematopoiesis in 6 of 10 (50 J/m{sup 2}) and 2 of 9 (100 J/m{sup 2}).

  17. Efficacy and Safety of Bone Marrow Cell Transplantation for Chronic Ischemic Heart Disease: A Meta-Analysis

    PubMed Central

    Xiao, Chun; Zhou, Shijie; Liu, Yueqiang; Hu, Huozhen

    2014-01-01

    Background Although bone marrow-derived cells (BMCs) have shown great therapeutic potential in patients with chronic ischemic heart disease (CIHD), the exact efficacy and safety of BMCs therapy is still not completely defined. Material/Methods We searched PubMed, OVID, EMBASE, the Cochrane Library, and ClinicalTrials.gov and finally identified 20 qualified trials in this meta-analysis. Assessment of efficacy was based on left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and left ventricular end-diastolic volume (LVEDV) improvement, by weighted mean difference (WMD) with 95% confidence intervals (CIs). Results of all-cause death, ventricular arrhythmia, recurrent myocardial infarction, and cerebrovascular accident were pooled to assess safety. Subgroup analysis was performed by stratifying RCTs into 2 subgroups of those with revascularization and without revascularization. Results BMC transplantation significantly improved LVEF in patients with revascularization (3.35%, 95% CI 0.72% to 5.97%, p=0.01; I2=85%) and without revascularization (3.05%, 95% CI 0.65% to 5.45%, p=0.01; I2=86%). In patients without revascularization, BMC transplantation was associated with significantly decreased LVESV (−11.75 ml, 95% CI −17.81 ml to −5.69 ml, p=0.0001; I2=81%), and LVEDV (−7.80 ml, 95% CI −15.31 ml to −0.29 ml, p=0.04; I2=39%). Subgroup analysis showed that the route of transplantation, baseline LVEF, and type of cells delivered could influence the efficacy of BMC transplantation. Conclusions Autologous transplantation of BMCs was safe and effective for patients who were candidates for revascularization with CABG/PCI and those who were not. However, large clinical trials and long-term follow-up are required to confirm these benefits. PMID:25270584

  18. Graft versus neuroblastoma reaction is efficiently elicited by allogeneic bone marrow transplantation through cytolytic activity in the absence of GVHD.

    PubMed

    Ash, Shifra; Gigi, Vered; Askenasy, Nadir; Fabian, Ina; Stein, Jerry; Yaniv, Isaac

    2009-12-01

    Continuous efforts are dedicated to develop immunotherapeutic approaches to neuroblastoma (NB), a tumor that relapses at high rates following high-dose conventional cytotoxic therapy and autologous bone marrow cell (BMC) reconstitution. This study presents a series of transplant experiments aiming to evaluate the efficacy of allogeneic BMC transplantation. Neuro-2a cells were found to express low levels of class I major histocompatibility complex (MHC) antigens. While radiation and syngeneic bone marrow transplantation (BMT) reduced tumor growth (P < 0.001), allogeneic BMT further impaired subcutaneous development of Neuro-2a cells (P < 0.001). Allogeneic donor-derived T cells displayed direct cytotoxic activity against Neuro-2a in vitro, a mechanism of immune-mediated suppression of tumor growth. The proliferation of lymphocytes from congenic mice bearing subcutaneous tumors was inhibited by tumor lysate, suggesting that a soluble factor suppresses cytotoxic activity of syngeneic lymphocytes. However, the growth of Neuro-2a cells was impaired when implanted into chimeric mice at various times after syngeneic and allogeneic BMT. F1 (donor-host) splenocytes were infused attempting to foster immune reconstitution, however they engrafted transiently and had no effect on tumor growth. Taken together, these data indicate: (1) Neuro-2a cells express MHC antigens and immunogenic tumor associated antigens. (2) Allogeneic BMT is a significantly better platform to develop graft versus tumor (GVT) immunotherapy to NB as compared to syngeneic (autologous) immuno-hematopoietic reconstitution. (3) An effective GVT reaction in tumor bearing mice is primed by MHC disparity and targets tumor associated antigens.

  19. Intra-bone marrow-bone marrow transplantation slows disease progression and prolongs survival in G93A mutant SOD1 transgenic mice, an animal model mouse for amyotrophic lateral sclerosis.

    PubMed

    Ohnishi, Shizuo; Ito, Hidefumi; Suzuki, Yasuhiro; Adachi, Yasushi; Wate, Reika; Zhang, Jianhua; Nakano, Satoshi; Kusaka, Hirofumi; Ikehara, Susumu

    2009-11-01

    It has been reported that bone marrow transplantation (BMT) has clinical effects on not only hematopoietic diseases and autoimmune diseases but also solid malignant tumors and metabolic diseases. We have found that intra-bone marrow-bone marrow transplantation (IBM-BMT) is superior to conventional intravenous BMT, since IBM-BMT enables rapid recovery of donor hematopoiesis and reduces the extent of graft-versus-host disease (GVHD). In this experiment, we examined the effects of IBM-BMT on symptomatic G93A mutant SOD1 transgenic mice (mSOD1 Tg mice), a model mouse line for amyotrophic lateral sclerosis (ALS). Symptomatic mSOD1 Tg mice (12 weeks old) were irradiated with 6Gyx2 at a 4-hour interval, one day before IBM-BMT. The mice were transplanted with bone marrow cells (BMCs) from 12-wk-old eGFP-transgenic C57BL/6 mice (eGFP Tg mice) or BMCs from 12-wk-old mSOD1 Tg mice. The ALS model mice transplanted with BMCs from eGFP Tg mice showed longer survival and slower disease progression than those transplanted with BMCs from mSOD1 Tg mice or untreated mSOD1 Tg mice. There was a significantly high number of eGFP(+) cells in the anterior horn of the spinal cord of the mSOD1 Tg mice transplanted with BMCs of eGFP Tg mice, some of which expressed Iba-1, a marker of microglia, although they did not differentiate into neural cells. These results suggest that the replacement with normal hematopoietic cells improved the neural cell environment, thereby slowing the progression of the disease.

  20. Total lymphoid irradiation, high-dose chemotherapy and autologous bone marrow transplantation for chemotherapy-resistant Hodgkin's disease.

    PubMed

    Yahalom, J; Gulati, S; Shank, B; Clarkson, B; Fuks, Z

    1989-11-01

    Seventeen patients with advanced stage Hodgkin's disease who relapsed or failed to respond to multiple regimens of combination chemotherapy (mostly Mechlorethamine, Vincristine, Procarbarzine, Prednisone and Adriamycin, Bleomycin, Vinblastine, Dacarbazine) were treated with accelerated hyperfractionated total lymphoid irradiation (TLI) and high-dose chemotherapy followed by autologous bone marrow transplantation (AuBMT). Candidates for the protocol did not have prior radiation therapy and had no evidence of bone marrow involvement. Their bone marrow was initially harvested and cryopreserved. The treatment protocol consisted of reinduction with conventional doses of combination chemotherapy followed by boost local field irradiation to areas of residual disease (1500 cGy within 5 days) and total lymphoid irradiation (2004 cGy given in 12 fractions of 167 cGy each t.i.d. delivered within 4 days). The patients were treated with Etoposide (250 mg/m2/day I.V. X 3 days) and high-dose Cyclophosphamide (60 mg/kg/day I.V. X 2 days). Cryopreserved (unpurged) autologous bone marrow was infused 48 hr after completion of chemotherapy. Of the 17 patients treated, four were in relapse and 13 refractory to multiple regimens of combination chemotherapy. Four patients died during the immediate peritransplant period (2--septicemia, 2--pulmonary complications). Of the 13 surviving patients, 12 entered a complete remission and one had a partial remission and died of disease 6 months later. One patient relapsed 5 months after treatment and is currently alive with disease. Eleven patients (65%) are alive with no evidence of disease 4-35 months (median 20 months) following completion of therapy. Treatment with this protocol results in a high rate of complete remission and a potential for long-term disease-free survival in previously unirradiated patients with advanced stage refractory or relapsed Hodgkin's disease who have exhausted conventional modes of chemotherapy. PMID:2478511

  1. Does location matter? Rural vs urban outcomes after blood and marrow transplantation in a population-based Canadian cohort.

    PubMed

    Paulson, K; Lambert, P; Bredeson, C; Demers, A; Nowatzki, J; Richardson, E; Rubinger, M; Szwajcer, D; Seftel, M D

    2010-07-01

    Specialized health services, such as blood and marrow transplantation (BMT), are usually based in large urban centers. Previous research has suggested that rural patients undergoing BMT have a higher risk of death. We performed a cohort study using data from both the Manitoba BMT Program and the provincial Cancer Registry to determine whether patients from the rural areas would have inferior survival after BMT and whether rural patients have reduced access to BMT. A total of 463 adult Manitobans, who underwent BMT between January 1990 and December 2006, were assessed. We analyzed area of residence (rural vs urban), disease and BMT characteristics, and calculated the OS. Patients undergoing autologous and allogeneic transplants were analyzed separately. When adjusted for gender, age at BMT and year of BMT, area of residence was not a significant predictor of mortality. A relative survival analysis was also conducted, and area of residence was again not a significant predictor of mortality. To measure access to BMT in urban vs rural patients, we evaluated all patients with newly diagnosed Hodgkin's Lymphoma (HL) during this same period. Of 432 Manitobans diagnosed with HL, 182 (42%) were rural and 250 (58%) were urban. In contrast, 69% of patients undergoing transplant for HL were urban. In conclusion, using population-based data from a Canadian province, we were unable to show a survival disadvantage for rural patients after controlling for other variables. BMT utilization in rural populations deserves further study.

  2. Total body irradiation as preparation for bone marrow transplantation in treatment of acute leukemia and aplastic anemia

    SciTech Connect

    Serota, F.T.; Burkey, E.D.; August, C.S.; D'Angio, G.J.

    1983-12-01

    In an attempt to improve survival while minimizing toxicity, many bone marrow transplant centers are now studying the use of cytoreduction regimens with an increased amount of radiation in single-dose or fractionated-exposure schedules for patients with leukemia and aplastic anemia. In order to review the current results, the literature prior to September, 1982 was surveyed and data were tabulated for each transplant center regarding the number of patients receiving transplants, diagnoses, cytoreduction regimen, clinical status, remission duration, relapse rate, causes of death and incidence of interstitial pneumonia. The incidence and severity of cataracts, growth failure, hypothyroidism and second malignant neoplasms were noted, and the data obtained from the literature search were updated and expanded by telephone questionnaire when possible. Marked variation in the technique of tranplantation was found among the participating institutions, making it difficult to determine the contribution of the various TBI doses, dose rates and fractionation schedules to the efficacy and toxicity of the combined regimen. In order to define the risk-benefit ratio of the various TBI regimens more clearly, prospective controlled, randomized studies will be required.

  3. Bone marrow engraftment and associated dermatologic sequelae in a three-yr-old after liver transplantation.

    PubMed

    Sheu, Johanna; Saavedra, Arturo P; Degar, Barbara A; Duncan, Christine N; Fawaz, Rima; Tan, Jennifer K; Schmidt, Birgitta A; Kim, Heung B; Huang, Jennifer T

    2015-03-01

    We present a case of a three-yr-old child with a history of multisystem Langerhans cell histiocytosis treated with systemic chemotherapy, who developed progressive liver failure and received an orthotopic split liver transplant while continuing on chemotherapy. One month following transplant, he developed acute graft-vs.-host disease of the skin and gastrointestinal tract. Peripheral blood chimerism studies post-transplant demonstrated an increasing predominance of donor lymphocytes and granulocytes. Shortly after, the patient developed vitiligo, and two yr after transplantation, the patient developed skin manifestations of psoriasis. We discuss and review the current literature, which demonstrates that chimerism following liver transplantation is rare and in our patient may be related to his profound immunosuppression around the time of liver transplant as well the development of acute graft-versus-host disease. While autoimmune disease can occur after solid organ and stem cell transplant, our patient developed skin manifestations of autoimmunity after liver transplantation, which is also rarely described. PMID:25516432

  4. A paediatric case of successful non-myeloablative bone marrow transplantation after azacitidine therapy for non-Down syndrome acute megakaryoblastic leukaemia with monosomy 7.

    PubMed

    Koga, Yuhki; Oba, Utako; Kato, Wakako; Ono, Hiroaki; Nakashima, Kentaro; Takada, Hidetoshi

    2016-09-01

    We report a patient with non-Down syndrome AML, also known as AMKL, with monosomy 7, who was also obese and had a hearing impairment and mental retardation. Non-myeloablative bone marrow transplantation was performed successfully after the patient received less aggressive azacitidine treatment, without the usual intensive induction chemotherapy regimen for AML. PMID:27384975

  5. Propofol injection combined with bone marrow mesenchymal stem cell transplantation better improves electrophysiological function in the hindlimb of rats with spinal cord injury than monotherapy.

    PubMed

    Wang, Yue-Xin; Sun, Jing-Jing; Zhang, Mei; Hou, Xiao-Hua; Hong, Jun; Zhou, Ya-Jing; Zhang, Zhi-Yong

    2015-04-01

    The repair effects of bone marrow mesenchymal stem cell transplantation on nervous system damage are not satisfactory. Propofol has been shown to protect against spinal cord injury. Therefore, this study sought to explore the therapeutic effects of their combination on spinal cord injury. Rat models of spinal cord injury were established using the weight drop method. Rats were subjected to bone marrow mesenchymal stem cell transplantation via tail vein injection and/or propofol injection via tail vein using an infusion pump. Four weeks after cell transplantation and/or propofol treatment, the cavity within the spinal cord was reduced. The numbers of PKH-26-positive cells and horseradish peroxidase-positive nerve fibers apparently increased in the spinal cord. Latencies of somatosensory evoked potentials and motor evoked potentials in the hindlimb were noticeably shortened, amplitude was increased and hindlimb motor function was obviously improved. Moreover, the combined effects were better than cell transplantation or propofol injection alone. The above data suggest that the combination of propofol injection and bone marrow mesenchymal stem cell transplantation can effectively improve hindlimb electrophysiological function, promote the recovery of motor funtion, and play a neuroprotective role in spinal cord injury in rats.

  6. What to Expect during a Blood and Marrow Stem Cell Transplant

    MedlinePlus

    ... transplant, and recovery in the hospital. Preparation You'll check into the hospital a few days before ... easily get an infection. As a result, you'll stay in a hospital room that has special ...

  7. Clinical variability of cyclosporine pharmacokinetics in adult and pediatric patients after renal, cardiac, hepatic, and bone-marrow transplants.

    PubMed

    Clardy, C W; Schroeder, T J; Myre, S A; Wadhwa, N K; Pesce, A J; First, M R; McEnery, P T; Balistreri, W F; Harris, R E; Melvin, D B

    1988-10-01

    The most important limitation associated with the clinical use of cyclosporine is the narrow therapeutic range between its efficacy and toxicity. Effective treatment is further complicated by significant variation in intrapatient and interpatient pharmacokinetics of the drug. We describe a practical approach to pharmacokinetic analysis that does not interfere with the cyclosporine dosage regimen or with clinical management of the patient. To optimize therapy, we individualized patient management by using noncompartmental pharmacokinetic analysis. Mean residence time (MRT) and volume of distribution at steady-state were calculated from data on concentration vs time after dose. We applied this approach to 24 kidney, 12 heart, 8 bone-marrow, 7 liver, and 5 pancreas transplants. Individualized requirements for cyclosporine dose and dosage interval can be predicted from these parameters. MRT is the most useful pharmacokinetic parameter, because it allows prediction of the optimal dosage interval. PMID:3048779

  8. Allogeneic bone marrow transplantation in a 7-year-old girl with congenital erythropoietic porphyria: a treatment dilemma.

    PubMed

    Taibjee, S M; Stevenson, O E; Abdullah, A; Tan, C Y; Darbyshire, P; Moss, C; Goodyear, H; Heagerty, A; Whatley, S; Badminton, M N

    2007-03-01

    Congenital erythropoietic porphyria (CEP, Günther's disease) has a very variable phenotype. In the more severely affected, bone marrow transplantation (BMT) is potentially curative, but is not without risks. We describe a 7-year-old girl with CEP characterized by severe photosensitivity but only mild anaemia, in whom the difficult decision to proceed with allogeneic BMT was made after discussion in a multidisciplinary team. She has shown successful engraftment, accompanied by biochemical and clinical resolution of her metabolic disease. She remains well 3 years later, the oldest patient with CEP receiving BMT to survive beyond 12 months. However, she has experienced significant morbidity including florid cutaneous graft-versus-host disease with postinflammatory hypopigmentation. Her case is important in highlighting the delay in diagnosis not uncommon in this condition and the complex decision-making process involved in proceeding with BMT.

  9. Social support, optimism, and self-efficacy predict physical and emotional well-being after bone marrow transplantation.

    PubMed

    Hochhausen, Nicole; Altmaier, Elizabeth M; McQuellon, Richard; Davies, Stella M; Papadopolous, Esperanza; Carter, Shelly; Henslee-Downey, Jean

    2007-01-01

    This study examined whether three psychosocial variables (social support, self-efficacy, and optimism) assessed prior to bone marrow transplantation (BMT) predicted physical and emotional wellbeing one year post-BMT. Data were gathered on 87 participants enrolled in a multicenter, randomized trial examining the impact of ex-vivo T-cell depletion on disease-free survival in leukemia patients receiving allogeneic BMT. Social support, optimism, and self-efficacy significantly predicted emotional and physical well-being one year post-BMT, controlling for age, gender, maximum grade of acute GVHD, and treatment arm. Attention to psychosocial factors prior to BMT and during recovery appears critical for physical and mental well-being, especially considering the influence of psychosocial variables independent of medical risk factors.

  10. Systemic interleukin-2 therapy in children with progressive neuroblastoma after high dose chemotherapy and bone marrow transplantation.

    PubMed

    Favrot, M C; Floret, D; Negrier, S; Cochat, P; Bouffet, E; Zhou, D C; Franks, C R; Bijman, T; Brunat-Mentigny, M; Philip, I

    1989-09-01

    Two children with active metastatic neuroblastoma after high dose chemotherapy and bone marrow transplantation (BMT) received a high dose continuous infusion of interleukin-2 (IL2) 120 days after an autologous BMT for patient 1 and 90 days after an allogeneic non T cell-depleted BMT for patient 2. Usual side effects of IL2 therapy were observed without life-threatening complications or any major hematological toxicity. The reactivation of graft-versus-host disease during IL2 infusion in patient 2 was the major BM-related complication but it improved with IL2 interruption and corticosteroids. IL2 induced a complete remission (9+ months) in patient 1 with the disappearance of bone metastases and local tumor but patient 2 progressed after cessation of therapy. Patient 1 presented with a large excess of circulating NK cells in the period after autologous BMT and IL2 induced a preferential outgrowth of this lymphocyte subset.

  11. [Relapsed acute myeloid leukemia with Down syndrome showing long disease-free survival after bone marrow transplantation].

    PubMed

    Daifu, Tomoo; Kato, Itaru; Matubara, Hiroshi; Abe, Daisuke; Uryu, Kumiko; Tokumasu, Mayu; Umeda, Katsutsugu; Watanabe, Kenichiro; Izawa, Kazusi; Asai, Kouichi; Nakahata, Tatsutoshi; Adachi, Souichi

    2009-02-01

    We report a sixteen-year-old boy with Down syndrome and relapse of AML (M7), who has been in complete remission (CR) more than 12 months after bone marrow transplantation (BMT) from an HLA-matched sibling donor. Because monosomy 7 was detected at onset of AML and he experienced relapse after the treatment of AML 99 Down protocol, his prognosis was considered very poor. However, he achieved CR following chemotherapy that included high-dose AraC and BMT from an HLA-matched sibling donor without severe complication. He has remained in CR for more than 12 months after BMT. In this case, GATA1 mutation was not detected at either onset or relapse of AML and it is suggested that this case is in a different risk group than the usual Down syndrome patient with AML showing GATA1 mutation.

  12. Second allogeneic hematopoietic cell transplantation for Patients with Fanconi anemia and Bone Marrow Failure

    PubMed Central

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P.; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K.; Bonfim, Carmem; Camitta, Bruce M.; Fasth, Anders L.; Gale, Robert Peter; Lee, Michelle A.; Lund, Troy C.; Myers, Kasiani C.; Olsson, Richard F.; Page, Kristin M.; Prestidge, Tim D.; Radhi, Mohamed; Shah, Ami J.; Schultz, Kirk R.; Wirk, Baldeep; Wagner, John E.; Deeg, H. Joachim

    2015-01-01

    Second allogeneic hematopoietic cell transplantation (HCT) is the only salvage option for those for develop graft failure after their first HCT. Data on outcomes after second HCT in Fanconi anemia (FA) are scarce. We report outcomes after second allogeneic HCT for FA (n=81). The indication for second HCT was graft failure after the first HCT. Transplants occurred between 1990 and 2012. The timing of second transplantation predicted subsequent graft failure and survival. Graft failure was high when the second transplant occurred less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between first and second transplant was less than 3 months compared to 23% when the interval was longer (p<0.001). Consequently, survival rates were substantially lower when the interval between first and second transplant was less than 3 months, 23% at 1-year compared to 58%, when the interval was longer (p=0.001). The corresponding 5-year probabilities of survival were 16% and 45%, respectively (p=0.006). Taken together, these data suggest that fewer than half of FA patients undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to lower graft failure after first HCT. PMID:26116087

  13. Comparison of haematopoietic stem cell engraftment through the retro-orbital venous sinus and the lateral vein: alternative routes for bone marrow transplantation in mice.

    PubMed

    Leon-Rico, D; Fernández-García, M; Aldea, M; Sánchez, R; Peces-Barba, M; Martinez-Palacio, J; Yáñez, R M; Almarza, E

    2015-04-01

    Bone marrow transplantation in mice is performed by intravenous administration of haematopoietic repopulating cells, usually via the lateral tail vein. This technique can be technically challenging to carry out and may cause distress to the mice. The retro-orbital sinus is a large area where there is a confluence of several vessels that provides an alternative route for intravenous access. Retro-orbital injection, although aesthetically unpleasant, can be performed rapidly without requiring mechanical restriction or heat-induced vasodilation. In addition, this technique can be easily learned by novice manipulators. This route of administration has been reported for use in bone marrow transplantation but there is no comparison of retro-orbital and tail vein injections reported for this specific purpose, although both routes have been compared for many other applications. Here, we provide for the first time a comprehensive comparison between tail vein and retro-orbital injections for two different bone marrow transplant scenarios in P3B and B6D2F1 mice. In both cases, no significant differences regarding donor engraftment were observed between mice transplanted using each of the techniques. Haematological counts and leukocyte subpopulation distribution were practically identical between both animal groups. Moreover, donor engraftment levels were less homogenous when cells were transplanted by tail vein injection, probably due to a higher risk of failure associated with this technique. All these data suggest that retro-orbital injection is a compelling alternative to conventional tail vein injection for bone marrow transplant in mice, providing similar and more homogenous haematopoietic reconstitution.

  14. Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors.

    PubMed

    Molloy, K; Goulden, N; Lawler, M; Cornish, J; Oakhill, A; Pamphilon, D; Potter, M; Steward, C; Langlands, K; Humphries, P; McCann, S R

    1996-04-01

    Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.

  15. A donor thrombomodulin gene variation predicts graft-versus-host disease development and mortality after bone marrow transplantation.

    PubMed

    Nomoto, Haruka; Takami, Akiyoshi; Espinoza, J Luis; Matsuo, Keitaro; Mizuno, Shohei; Onizuka, Makoto; Kashiwase, Koichi; Morishima, Yasuo; Fukuda, Takahiro; Kodera, Yoshihisa; Doki, Noriko; Miyamura, Koichi; Mori, Takehiko; Nakao, Shinji; Ohtake, Shigeki; Morishita, Eriko

    2015-10-01

    Thrombomodulin, encoded by the THBD gene, is a critical regulator of coagulation and innate immunity. Its gene variant (rs3176123, 2729A>C) in the 3' untranslated region has been reported to be associated with vasculopathies. The present study analyzed the impact of THBD variation on transplant outcomes in a cohort of 317 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. The donor A/C or C/C genotype vs. the donor A/A genotype resulted in a lower incidence of grades II-IV acute graft-versus-host disease [GVHD; hazard ratio (HR) 0.66; 95 % confidence interval (CI) 0.44-0.99; P = 0.05] according to a multivariate analysis. In patients with grades II-IV acute GVHD, the donor A/C or C/C genotype vs. the donor A/A genotype was associated with significantly better overall survival rates (HR 0.45; 95 % CI 0.21-0.99, P = 0.05), while this effect was absent in other patients. A functional analysis using lymphocytes obtained from healthy individuals revealed that the 2729C allele has a higher level of THBD mRNA than the 2729A allele. These findings suggest the functional relevance of the rs3176123 variation and indicate that higher thrombomodulin expression by individuals with the 2729C allele likely accounts for their decreased risk for acute GVHD development and subsequent mortality. PMID:26246110

  16. Late effects in survivors of Hodgkin and non-Hodgkin lymphoma treated with autologous hematopoietic cell transplantation: a report from the bone marrow transplant survivor study.

    PubMed

    Majhail, Navneet S; Ness, Kirsten K; Burns, Linda J; Sun, Can-Lan; Carter, Andrea; Francisco, Liton; Forman, Stephen J; Bhatia, Smita; Baker, K Scott

    2007-10-01

    We determined the prevalence of self-reported late-effects in survivors of autologous hematopoietic cell transplantation (HCT) for Hodgkin lymphoma (HL, n = 92) and non-Hodgkin lymphoma (NHL, n = 184) using a 255-item questionnaire and compared them to 319 sibling controls in the Bone Marrow Transplant Survivor Study. Median age at HCT was 39 years (range: 13-69) and median posttransplant follow-up was 6 years (range: 2-17). Median age at survey was 46 years (range: 21-73) for survivors and 44 years (range: 19-79) for siblings. Compared to siblings, HCT survivors reported a significantly higher frequency of cataracts, dry mouth, hypothyroidism, bone impairments (osteoporosis and avascular necrosis), congestive heart failure, exercise-induced shortness of breath, neurosensory impairments, inability to attend work or school, and poor overall health. Compared to those receiving no total-body irradiation (TBI), patients treated with TBI-based conditioning had higher risks of cataracts (odds-ratio [OR] 4.9, 95% confidence interval [CI] 1.5-15.5) and dry mouth (OR 3.4, 95% CI 1.1-10.4). Females had a greater likelihood of reporting osteoporosis (OR 8.7, 95% CI: 1.8-41.7), congestive heart failure (OR 4.3, 95% CI 1.1-17.2), and abnormal balance, tremor, or weakness (OR 2.4, 95% CI 1.0-5.5). HL and NHL survivors of autologous HCT have a high prevalence of long-term health-related complications and require continued monitoring for late effects of transplantation. PMID:17889351

  17. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies

    PubMed Central

    Davies, Jeff K.; Gribben, John G.; Brennan, Lisa L.; Yuk, Dongin; Nadler, Lee M.

    2008-01-01

    We report the outcomes of 24 patients with high-risk hematologic malignancies or bone marrow failure (BMF) who received haploidentical bone marrow transplantation (BMT) after ex vivo induction of alloantigen-specific anergy in donor T cells by allostimulation in the presence of costimulatory blockade. Ninety-five percent of evaluable patients engrafted and achieved full donor chimerism. Despite receiving a median T-cell dose of 29 ×106/kg, only 5 of 21 evaluable patients developed grade C (n = 4) or D (n = 1) acute graft-versus-host disease (GVHD), with only one attributable death. Twelve patients died from treatment-related mortality (TRM). Patients reconstituted T-cell subsets and immunoglobulin levels rapidly with evidence of in vivo expansion of pathogen-specific T cells in the early posttransplantation period. Five patients reactivated cytomegalovirus (CMV), only one of whom required extended antiviral treatment. No deaths were attributable to CMV or other viral infections. Only 1 of 12 evaluable patients developed chronic GVHD. Eight patients survive disease-free with normal performance scores (median follow-up, 7 years). Thus, despite significant early TRM, ex vivo alloanergization can support administration of large numbers of haploidentical donor T cells, resulting in rapid immune reconstitution with very few viral infections. Surviving patients have excellent performance status and a low rate of chronic GVHD. PMID:18617635

  18. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    SciTech Connect

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-02-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection.

  19. Cellular Origins of Regenerating Nodules and Malignancy in the FAH Model of Liver Injury after Bone Marrow Cell Transplantation

    PubMed Central

    Wang, Pei-Rong; Li, Yi

    2016-01-01

    In previous reports, we and other groups have shown that proliferating hepatocytes are formed by the fusion of donor hematopoietic cells with host hepatocytes in the Fah−/− model. Thus, it would be interesting to determine whether cell fusion occurs during malignancy. However, it is difficult to demonstrate such processes using this model. Therefore, we established a new strain to study the processes of regenerating nodules and malignancy and their origins. The FAH−/− mouse model was crossed with the ROSAnZ strain and their offspring was genotyped for FAH−/− and ROSAnZ mutations to create a new strain (Fah−/−-ROSAnZ). Using this strain as recipients, we performed bone marrow transplantation experiments. As a result, we could not demonstrate the presence of any epithelial cells except hepatocytes that were of donor origin in regenerating tissue, and no evidence of cell fusion was found in tumors. The hepatic malignancy was of host origin in these mice. There was higher expression of extracellular matrix proteins and more inflammatory cells in liver tumor nodules than in regenerating normal liver nodules. Hepatocytes generated by fusion with bone marrow cells did not form malignant tumors. Extracellular matrix and inflammatory cells had significantly accumulated in liver tumors. PMID:26962307

  20. Granulocyte-macrophage colony-stimulating factor dependent monocyte-mediated cytotoxicity post-autologous bone marrow transplantation.

    PubMed

    Nagler, A; Shur, I; Barak, V; Fabian, I

    1996-08-01

    We investigated the in vitro antitumor activity of monocytes derived from autologous bone marrow transplanted (ABMT) patients treated in vivo with granulocyte-macrophage colony-stimulating factor (GM-CSF). Thirty-four patients (17 female, 17 male), median age 42 (range 3-57) years, were enrolled in the study. Fourteen patients were diagnosed with non-Hodgkin's lymphoma (NHL), eight with Hodgkin's disease (HD), nine with breast cancer and three with neuroblastoma. Six patients who did not receive GM-CSF post-ABMT served as controls. We assessed cytotoxicity, antibody-dependent cellular cytotoxicity (ADCC), expression of the activation antigen CD16, and cytokine production by an enriched population of monocytes (> 90% CD+14) pre-, during and post-GM-CSF administration. Within the group of patients receiving treatment, ADCC was significantly higher during in vivo GM-CSF administration than post-therapy (P < 0.05) and in 50% of these patients, ADCC increased during in vivo GM-CSF administration over pretreatment values. In addition, in vivo GM-CSF administration caused the monocytes to secrete elevated levels of tumor necrosis factor-alpha (TNF-alpha) and GM-CSF (P < 0.05). We conclude that GM-CSF augments monocyte-mediated cytotoxicity post-ABMT, and therefore may have a role in controlling minimal residual disease post-transplant.

  1. Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection.

    PubMed

    Nino, Nanako; Kozaki, Aiko; Hasegawa, Daiichiro; Ueda, Go; Takahashi, Hironobu; Miyata, Kenji; Ochi, Satoshi; Yamashita, Tatsuya; Takafuji, Satoru; Uemura, Suguru; Yokoi, Takehito; Saito, Atsuro; Ishida, Toshiaki; Kawasaki, Keiichiro; Nakamura, Kazuhiro; Kobayashi, Masao; Kosaka, Yoshiyuki

    2016-06-01

    We herein describe a 2-year-old boy with severe congenital neutropenia (SCN) who was successfully treated with reduced-intensity bone marrow transplantation (HSCT). He had suffered recurrent episodes of bacterial pneumonia from 12 months of age, and was found to have severe neutropenia with white blood cell counts below 100/μl. The patient harbored a heterozygous missense mutation in ELANE exon 4 (p.Gln134Pro, NM_001972.2: c.401A>C). This was a novel mutation. Due to intractable pneumonia and severe persistent neutropenia, reduced-intensity HSCT was performed from an HLA-matched sibling donor. The preparative regimen consisted of melphalan, fludarabine, and 4 Gy of total body irradiation. Hematopoietic engraftment was rapidly obtained, i.e., by day +14, and complete donor chimerism was subsequently achieved. The lung complications observed pre-transplantation markedly improved after neutrophil recovery, i.e., by day +60. We concluded that HSCT is a useful treatment for SCN patients, especially for those at high risk of leukemic transformation. Fludarabine-based reduced-intensity HSCT may represent a safe and effective therapeutic option for patients with SCN who need HSCT even if they have intractable infectious complications. PMID:27384854

  2. Autologous bone marrow transplantation as consolidation therapy in newly diagnosed non-Hodgkin's lymphoma: long-term outcome.

    PubMed

    Montuoro, A; Lalle, M; Ingletto, D

    2000-10-01

    Autologous bone marrow transplantation (ABMT) often produces durable remission in patients with intermediate-high grade non-Hodgkin's lymphoma (NHL). We present a retrospective review of 32 eligible newly diagnosed patients with NHL treated with conventional induction chemotherapy followed by ABMT consolidation therapy. These patients were treated in our department between 1984-1994 and followed up for 5-172 months with a median time of 82 months. In our patients the status of disease at transplant was 30 complete remissions and 2 partial remissions. All patients received a CBV-like high-dose preparative regimen. At 136 months the probability of disease-free survival (DFS) and overall (OS) is 66% and 70% respectively. Seven patients died from the disease. There was one case of toxicity related death. Our aim was to achieve a status of minimal disease and then consolidate it with high-dose polychemotherapy regimen. This study confirms that a significant number of patients with aggressive responding NHL can achieve prolonged RFS and OS after ABMT. Our data document the importance of long-term follow-up in interpreting the results of ABMT in NHL. PMID:10995890

  3. The potential utility of bone marrow or umbilical cord blood transplantation for the treatment of type I diabetes mellitus.

    PubMed

    Mabed, Mohamed

    2011-04-01

    The pathology of type 1 diabetes mellitus (T1D) involves the autoimmune destruction or malfunction of pancreatic β cells, leading to a lack of insulin. The absence of insulin is life-threatening, necessitating daily hormone injections from an exogenous source. Insulin injections do not adequately mimic the precise regulation of β cells on glucose homeostasis, however, eventually leading to complications in diabetic patients. There currently is no definitive cure for T1D. Pancreas transplantation, although quite successful, is an invasive intervention that is restricted to patients with advanced complications, requires constant immunosuppression, and is severely limited by donor availability. Recent progress in human islet cell isolation and immunosuppressive protocols has restored euglycemia in patients who received islet cells from 2 or 3 pancreas donors. However, because of the scarcity of cadaver pancreata and the low yield of islet cells obtained by the procedure, not all patients have access to this surgical intervention. Thus, other therapeutic approaches are needed to arrest immune aggression, preserve β cell mass, and provide efficient replacement. In this sense, bone marrow and umbilical cord blood transplantation are promising possibilities that merit exploration. In this review, we summarize multiple strategies that have been proposed and tested for potential therapeutic benefit in patients with T1D.

  4. Autologous haematopoietic stem cell transplants for autoimmune disease--feasibility and transplant-related mortality. Autoimmune Disease and Lymphoma Working Parties of the European Group for Blood and Marrow Transplantation, the European League Against Rheumatism and the International Stem Cell Project for Autoimmune Disease.

    PubMed

    Tyndall, A; Fassas, A; Passweg, J; Ruiz de Elvira, C; Attal, M; Brooks, P; Black, C; Durez, P; Finke, J; Forman, S; Fouillard, L; Furst, D; Holmes, J; Joske, D; Jouet, J; Kötter, I; Locatelli, F; Prentice, H; Marmont, A M; McSweeney, P; Musso, M; Peter, H H; Snowden, J A; Sullivan, K; Gratwohl, A

    1999-10-01

    This ongoing multicentre prospective phase I/II trial enrolled 74 consecutive patients from 22 centres worldwide with severe autoimmune disease, 35 with rheumatological disorders, 31 with neurological, five with haematological and three with vasculitides. They were treated with autologous peripheral blood or bone marrow transplants according to predetermined criteria. Two patients died after mobilisation before transplant. Seventy-two patients were given 73 transplants, seven bone marrow, and 66 mobilised peripheral blood stem cell transplants. The graft was manipulated to remove T and/or B cells in 43 cases. All 73 transplants engrafted. Five patients died of transplant-related complications: two from bleeding, three from infections. Two patients died of progressive disease. The transplant-related mortality at 1 year of 9% (1-17%; 95% CI) is comparable to the transplant-related mortality of 6% (3-9%; 95% CI) in patients transplanted during the same period in Europe for non-Hodgkin's lymphoma in sensitive relapse (P = 0.39). Sixty patients are evaluable for response, 40 patients (65%) showed some improvement in their disease. Haematopoietic stem cell transplants are feasible for patients with severe refractory autoimmune disease. Transplant-related mortality is comparable to results in patients with non-Hodgkin's lymphoma in responsive relapse. Two-thirds of the patients show at least some response. These preliminary data are promising. Although associated with considerable risk, randomised trials comparing autologous stem cell transplants to conventional therapy are warranted.

  5. Haploidentical, G-CSF-primed, unmanipulated bone marrow transplantation for patients with high-risk hematological malignancies: an update.

    PubMed

    Arcese, W; Picardi, A; Santarone, S; De Angelis, G; Cerretti, R; Cudillo, L; Pennese, E; Bavaro, P; Olioso, P; Dentamaro, T; Cupelli, L; Chierichini, A; Ferrari, A; Mengarelli, A; Tirindelli, M C; Testi, M; Di Piazza, F; Di Bartolomeo, P

    2015-06-01

    Ninety-seven patients affected by high-risk hematological malignancies underwent G-CSF primed, unmanipulated bone marrow (BM) transplantation from a related, haploidentical donor. All patients were prepared with an identical conditioning regimen including Thiotepa, Busilvex, Fludarabine (TBF) and antithymocyte globulin given at myeloablative (MAC = 68) or reduced (reduced intensity conditioning (RIC) = 29) dose intensity and received the same GvHD prophylaxis consisting of the combination of methotrexate, cyclosporine, mycofenolate-mofetil and basiliximab. Patients were transplanted in 1st or 2nd CR (early phase: n = 60) or in > 2nd CR or active disease (advanced phase: n = 37). With a median time of 21 days (range 12-38 days), the cumulative incidence (CI) of neutrophil engraftment was 94 ± 3%. The 100-day CI of III-IV grade acute GvHD and the 2-year CI of extensive chronic GvHD were 9 ± 3% and 12 ± 4%, respectively. Overall, at a median follow-up of 2.2 years (range 0.3-5.6), 44 out of 97 (45%) patients are alive in CR. The 5-year probability of overall survival (OS) and disease-free survival (DFS) for patients in early and advanced phase was 53 ± 7 vs 24 ± 8% (P = 0.006) and 48 ± 7 vs 22 ± 8% (P = 0.01), respectively. By comparing MAC with RIC patient groups, the transplant-related mortality was equivalent (36 ± 6 vs 28 ± 9%) while the relapse risk was lower for the MAC patients (22 ± 6 vs 45 ± 11%), who showed higher OS (48 ± 7 vs 29 ± 10%) and DFS (43 ± 7 vs 26 ± 10%). However, all these differences did not reach a statistical significance. In multivariate analysis, diagnosis and recipient age were significant factors for OS and DFS. In conclusion, this analysis confirms, on a longer follow-up and higher number of patients, our previous encouraging results obtained by using MAC and RIC TBF regimen as conditioning for G-CSF primed, unmanipulated BM transplantation from related, haploidentical donor in patients with high-risk hematological

  6. The study of indicators of bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous injection of gold nanorods

    NASA Astrophysics Data System (ADS)

    Dikht, Nataliya I.; Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Matveeva, Olga V.; Navolokin, Nikita A.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.

    2015-03-01

    In study the evaluation of the influence of gold nanorods on morphological indicators of red bone marrow and peripheral blood of rats with diabetes and transplanted liver tumor after intravenous administration of gold nanorods was conducted. We used gold nanorods with length 41 ± 8 nm and diameter of 10.2±2 nm, synthesized in the laboratory of nanobiotechnology IBPPM RAS (Saratov). After intravenous administration of gold nanorods the decrease of leukocytes, platelets and lymphocytes was observed in animals of control group in blood. It was marked the decrease of the number of mature cellular elements of the leukocyte germ in bone marrow - stab neutrophils and segmented leukocytes, and the increase of immature elements- metamyelocytes, indicating the activation of leukocyte germ after nanoparticle administration. The decrease of leukocyte amount was noted in blood and the increase of cellular elements of the leukocyte germ was revealed in bone marrow, indicating the activation of leukocyte germ in rats with alloxan diabetes and transplanted tumors. The changes of morphological indicators of blood and bone marrow testify about stimulation of myelocytic sprouts of hemopoiesis in bone marrow as a result of reduction of mature cells in peripheral blood after gold nanoparticle administration.

  7. Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery.

    PubMed

    Tiberghien, P; Laithier, V; Mabed, M; Racadot, E; Reynolds, C W; Angonin, R; Loumi, R; Pavy, J J; Cahn, J Y; Noir, A

    1993-04-01

    Administration of interleukin-1 beta (IL-1 beta) before a lethal irradiation with or without allogeneic bone marrow transplantation (BMT) protects greater than 90% of the irradiated mice. To approach the mechanisms responsible for the radioprotective effect of IL-1, we examined the effects of IL-1 pretreatment on engraftment and kinetics of peripheral blood, spleen, and marrow cell reconstitution after irradiation and BMT. Although the BMT was not necessary for the survival of the IL-1-pretreated lethally irradiated mice, allogeneic marrow did engraft in these mice as evaluated in the spleen and marrow 2 months after BMT. IL-1 pretreatment significantly accelerated hematopoietic recovery versus transplanted saline-treated controls with a pronounced enhancement of peripheral leukocyte, platelet, and erythrocyte recovery. Leukocyte recovery in IL-1-pretreated mice was unique in that IL-1 first induced an early transient (maximum at day 7) increase of peripheral granulocytes before accelerating leukocyte recovery after day 11. IL-1 pretreatment also significantly enhanced marrow cell recovery after allogeneic BMT with an eightfold increase in marrow cellularity from day 4 to 11 versus control transplanted mice. When lethal irradiation was not followed by allogeneic BMT. IL-1 pretreatment also affected the peripheral reconstitution of leukocytes, platelets, and erythrocytes. Interestingly, in the absence of BMT, IL-1 also induced an early circulation of peripheral granulocytes. Overall, our data demonstrate that a single administration of IL-1 before lethal irradiation and allogeneic BMT can induce an early transient increase of circulating granulocytes, followed by an accelerated multilineage recovery and long-term allogeneic engraftment. PMID:8461477

  8. Early high dose chemotherapy intensification with autologous bone marrow transplantation in lymphoma associated with retention of fertility and normal pregnancies in females. Scotland and Newcastle Lymphoma Group, UK.

    PubMed

    Jackson, G H; Wood, A; Taylor, P R; Lennard, A L; Lucraft, H; Heppleston, A; Robinson, P; Moore, J; Proctor, S J

    1997-12-01

    As more centres consider autologous bone marrow and peripheral blood stem cell transplantation for patients with high risk Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) the long term sequelae of such treatments have to be considered. One of the most important side effects of such intensive treatment is loss of fertility. Sperm banking before treatment commences is available for males but unfortunately cryopreservation of ova/ovarian tissue is not yet possible for females. We have transplanted 30 women, 23 were under 40 years and report ten females who have had successful pregnancies (including two twin pregnancies and one triplet pregnancy), leading to live births following autologous bone marrow transplantation (ABMT) for poor prognosis HD and NHL in first or second complete remission. None of these children have shown evidence of birth defects (median follow up of two years). Of the twenty one pregnancies reported to the European Bone Marrow Transplantation Registry (EBMTR) following ABMT for lymphoma, eight of the seventeen unassisted cases came from our centres. The Newcastle/SNLG autotransplant differs from the approach in many EBMTR centres in that it uses melphalan or melphalan/etoposide alone instead of the more common four drug containing regimens and yet sustained complete remission rates indicate that the non-ablative approach is equally effective as more aggressive regimens on the disease with the huge advantage of preserved fertility in females. This approach to conditioning for ABMT should be considered when treating women in the reproductive age group.

  9. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. I. Orthoptic liver allographs

    SciTech Connect

    Myburgh, J.A.; Smit, J.A.; Browde, S.; Hill, R.R.H.

    1980-05-01

    Fractionated total lymphoid irradiation (TLI) and allogeneic bone marrow (BM) injection have been reported to produce stable chimerism without graft-versus-host disease (GVHD) in inbred mice and rats and mongrel dogs, and transplantation tolerance for skin and heart grafts in rodents. This concept has been studied in outbred chacma baboons receiving orthotopic liver allografts with the use of five different irradiation protocols. Eight fractions of 200 rad to the whole torso, followed immediately by allogeneic BM injections, and liver grafts from the BM donors 3 to 4 weeks later resulted in markedly prolonged survivals of 63 to 106 days in four baboons (median survival of untreated controls 19 days). Only one of the four animals died directly from the effects of rejection. BM chimerism was demonstrated in two baboons. There were no clinical or histological signs of GVHD in any of the animals. Two fractions of TLI, totaling 800 rad, 23 hr apart and followed immediately by BM injection and liver grafting resulted in profound thrombocytopenia and death form intraperitoneal hemorrhage in four of five baboons. In one animal BM injection and liver transplantation were delayed for 75 days. The baboon is still alive more than 6 months later. Three groups received single doses of 300, 400, and 500 rad to the whole torso, followed by allogeneic BM injections 1 and 2 weeks later, and liver transplants from their BM donors after an additional 3 to 4 weeks. The four baboons receiving 300 rad survived for 42, 86, 123, and >180 days. Two of the four baboons receiving 400 rad died of septic intraabdominal complications with minimal or no evidence of rejection. Fourh of the five baboons receiving 500 rad died from rejection.

  10. Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study.

    PubMed

    Bhatia, Smita; Robison, Leslie L; Francisco, Liton; Carter, Andrea; Liu, Yan; Grant, Marcia; Baker, K Scott; Fung, Henry; Gurney, James G; McGlave, Philip B; Nademanee, Auayporn; Ramsay, Norma K C; Stein, Anthony; Weisdorf, Daniel J; Forman, Stephen J

    2005-06-01

    We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.

  11. Nonmyeloablative Conditioning with Busulfan before Matched Littermate Bone Marrow Transplantation Results in Reversal of the Disease Phenotype in Canine Leukocyte Adhesion Deficiency

    PubMed Central

    Sokolic, Robert A.; Bauer, Thomas R.; Gu, Yu-Chen; Hai, Mehreen; Tuschong, Laura M.; Burkholder, Tanya; Colenda, Lyn; Bacher, John; Starost, Matthew F.; Hickstein, Dennis D.

    2005-01-01

    Leukocyte adhesion deficiency (LAD)–1, a primary immunodeficiency disease caused by molecular defects in the leukocyte integrin CD18 molecule, is characterized by recurrent, life-threatening bacterial infections. Myeloablative hematopoietic stem cell transplantation is the only curative treatment for LAD-1. Recently, canine LAD (CLAD) has been shown to be a valuable animal model for the preclinical testing of nonmyeloablative transplantation regimens for the treatment of children with LAD-1. To develop new allogeneic transplantation approaches for LAD-1, we assessed a nonmyeloablative conditioning regimen consisting of busulfan as a single agent before matched littermate allogeneic bone marrow transplantation in CLAD. Three CLAD dogs received busulfan 10 mg/kg intravenously before infusion of matched littermate bone marrow, and all dogs received posttransplantation immunosuppression with cyclosporin A and mycophenolate mofetil. Initially, all 3 dogs became mixed chimeras, and levels of donor chimerism sufficient to reverse the CLAD phenotype persisted in 2 animals. The third dog maintained donor microchimerism with an attenuated CLAD phenotype. These 3 dogs have all been followed up for at least 1 year after transplantation. These results indicate that a nonmyeloablative conditioning regimen with chemotherapy alone is capable of generating stable mixed chimerism and reversal of the disease phenotype in CLAD. PMID:16182176

  12. Diabetes, hypertension, and cardiovascular events in survivors of hematopoietic cell transplantation: a report from the bone marrow transplantation survivor study

    PubMed Central

    Scott Baker, K.; Ness, Kirsten K.; Steinberger, Julia; Carter, Andrea; Francisco, Liton; Burns, Linda J.; Sklar, Charles; Forman, Stephen; Weisdorf, Daniel; Gurney, James G.; Bhatia, Smita

    2007-01-01

    We ascertained the prevalence of self-reported late occurrence of diabetes, hypertension, and cardiovascular (CV) disease in 1089 hematopoietic cell transplantation (HCT) survivors who underwent HCT between 1974 and 1998, survived at least 2 years, and were not currently taking immunosuppressant agents and compared them with 383 sibling controls. All subjects completed a 255-item health questionnaire. The mean age at survey completion was 39.3 years for survivors and 38.6 years for siblings; mean follow-up was 8.6 years. Adjusting for age, sex, race, and body mass index (BMI), survivors of allogeneic HCT were 3.65 times (95% confidence interval [CI], 1.82-7.32) more likely to report diabetes than siblings and 2.06 times (95% CI, 1.39-3.04) more likely to report hypertension compared with siblings but did not report other CV outcomes with any greater frequency. Recipients of autologous HCTs were no more likely than siblings to report any of the outcomes studied. Allogeneic HCT survivors were also more likely to develop hypertension (odds ratio [OR] = 2.31; 95% CI, 1.45-3.67) than autologous recipients. Total body irradiation (TBI) exposure was associated with an increased risk of diabetes (OR = 3.42; 95% CI, 1.55-7.52). Thus, HCT survivors have a higher age- and BMI-adjusted risk of diabetes and hypertension, potentially leading to a higher than expected risk of CV events with age. PMID:17047152

  13. [Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

    PubMed

    Ostendorf, P; Ehninger, G; Dopfer, R; Schmidt, H; Haen, M; Link, H; Schüch, K; Müller, C A; Wernet, P; Klingebiel, T

    1986-05-15

    Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti

  14. Exposure of early pediatric trainees to blood and marrow transplantation leads to higher recruitment to the field.

    PubMed

    Shereck, Evan; Shenoy, Shalini; Pulsipher, Michael; Burns, Linda; Bracey, Arthur; Chell, Jeffrey; Snyder, Edward; Nemecek, Eneida

    2013-09-01

    The National Marrow Donor Program (NMDP) projects the need for allogeneic unrelated blood and marrow transplantation (BMT) in the United States as 10,000 per year. Although the NMDP is preparing to facilitate that number by the year 2015, there are several barriers to meeting this goal, including the need to recruit more health care personnel, including BMT physicians. To learn how best to recruit BMT physicians, we examined why practicing BMT physicians chose to enter the field and why others did not. We conducted a Web-based survey among pediatric hematology/oncology (PHO) and BMT physician providers and trainees to identify the factors influencing their decision to choose or not choose a career in BMT. Out of 259 respondents (48% male, 74% of Caucasian origin), 94 self-identified as BMT physicians, 112 as PHO physicians, and 53 as PHO trainees. The PHO and BMT providers spent an average of 53% of their time in clinical activities. More than two-thirds of PHO providers reported providing BMT services at their institutions, most commonly for inpatient coverage (73%). The proportion of providers exposed to BMT early in training was significantly higher among BMT providers compared with PHO providers (51% versus 18% in medical school [P < .0001]; 70% versus 50% during residency [P < .005]). Exposure during fellowship (94%) did not differ between the 2 groups. The decision to pursue a career in BMT was made before fellowship (medical school or residency) by 50% of the respondents. A lower proportion of BMT providers than PHO providers reported current involvement in the education of medical students and residents (76% versus 98%; P < .0001). Of the 53 trainees who responded, 64% reported not contemplating a career in BMT. Of these, 68% identified inadequate exposure to BMT before PHO fellowship as the reason behind this decision. Only 26% reported receiving exposure to the BMT field while in medical school, and 43% reported exposure during residency. The 2 most

  15. Concentration of bone marrow mononuclear cells for in vitro treatment and AB0-incompatible transplantation: a rapid and reproducible procedure using the haemonetics V50 cell separator.

    PubMed

    Wiesneth, M; Hertenstein, B; Koerner, K; Heimpel, H; Heit, W

    1988-01-01

    Forty-nine allogeneic and 14 autologous bone marrow grafts were processed with the Haemonetics V50 cell separator (Haemonetics Corp., Braintree, USA) for in vitro treatment with antibodies and cryopreservation respectively. The concentration of hemopoietic progenitor cells was performed without any sedimentation or density gradient agents. The recovery is given in percent (mean +/- sd) of the original marrow values: mononuclear cells (MNC) 74 +/- 10%, polymorphonuclear cells (PMC) 48 +/- 17%, red blood cells (RBC) 12 +/- 5%, granulocyte/monocyte progenitors (CFU-GM) 83 +/- 36%, and erythroid progenitors (BFU-E) 78 +/- 38%. The recovery of nucleated cells (NC) was 90 +/- 13% and the viability 82 +/- 11% after cryopreservation. The technique described provides a simple, rapid and efficient preparation of large bone marrow volumes for in vitro treatment and AB0-incompatible transplantation.

  16. Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

    PubMed Central

    Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D’aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; de Latour, Regis Peffault

    2016-01-01

    Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia. PMID:27056924

  17. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  18. Treated of type 1 diabetes mellitus in non-obese diabetic mice by transplantation of allogeneic bone marrow and pancreatic tissue

    SciTech Connect

    Yasumizu, R.; Sugiura, K.; Iwai, H.; Inaba, M.; Makino, S.; Ida, T.; Imura, H.; Hamashima, Y.; Good, R.A.; Ikehara, S.

    1987-09-01

    Non-obese diabetic (NOD) mice provide a model for type 1 diabetes mellitus. We previously showed that allogeneic bone marrow transplantation (ABMT) can prevent and treat insulitis and overt diabetes in NOD mice. However, ABMT alone could not be used to treat overt diabetes in NOD mice whose islets had been completely destroyed. To provide insulin-producing cells, pancreatic tissue from newborn mice was grafted under the renal capsules in combination with ABMT. The aims of concomitant ABMT are as follows. (i) It induces immunological tolerance to the donor-type major histocompatibility complex determinants and permits the host to accept subsequent pancreatic allografts from the bone marrow donor. (ii) ABMT replaces abnormal stem cells with normal stem cells. After transplantation of bone marrow plus newborn pancreas, NOD mice showed reduction of the glycosuria and a normal response in the glucose-tolerance test. Immunohistological study revealed the presence of clustered insulin-containing beta cells in the grafted pancreatic transplants. ABMT may become a viable treatment of established type 1 diabetes mellitus in humans.

  19. Long-term clinical results of autologous bone marrow CD 133+ cell transplantation in patients with ST-elevation myocardial infarction

    NASA Astrophysics Data System (ADS)

    Kirgizova, M. A.; Suslova, T. E.; Markov, V. A.; Karpov, R. S.; Ryabov, V. V.

    2015-11-01

    The aim of the study was investigate the long-term results of autologous bone marrow CD 133+ cell transplantation in patients with primary ST-Elevation Myocardial Infarction (STEMI). Methods and results: From 2006 to 2007, 26 patients with primary STEMI were included in an open randomized study. Patients were randomized to two groups: 1st - included patients underwent PCI and transplantation of autologous bone marrow CD 133+ cell (n = 10); 2nd - patients with only PCI (n = 16). Follow-up study was performed 7.70±0.42 years after STEMI and consisted in physical examination, 6-min walking test, Echo exam. Total and cardiovascular mortality in group 1 was lower (20% (n = 2) vs. 44% (n = 7), p = 0.1 and 22% (n = 2) vs. 25% (n = 4), (p=0.53), respectively). Analysis of cardiac volumetric parameters shows significant differences between groups: EDV of 100.7 ± 50.2 mL vs. 144.40±42.7 mL, ESV of 56.3 ± 37.8 mL vs. 89.7 ± 38.7 mL in 1st and 2nd groups, respectively. Data of the study showed positive effects of autologous bone marrow CD 133+ cell transplantation on the long-term survival of patients and structural status of the heart.

  20. MC1288, a vitamin D analog, prevents acute graft-versus-host disease in rat bone marrow transplantation.

    PubMed

    Pakkala, I; Taskinen, E; Pakkala, S; Räisänen-Sokolowski, A

    2001-04-01

    The major obstacle to successful bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Vitamin D analogs have shown their efficacy in solid organ transplantation. The purpose of this study was to investigate the suitability of a novel vitamin D analog, MC1288, in the prevention of acute GVHD in a rat BMT model. Allogeneic BMT were performed from Lewis to BN rats (n = 18). The animals were divided into four groups: an untreated control group, MC1288, cyclosporin A (CsA), and MC1288 + CsA-treated groups. Rats were harvested for histology and immunohistochemistry on day 20 after BMT. Histological changes for GVHD in liver, skin, and spleen were scored. Positivity in immunostaining was quantified as the number of positive cells/high power field. Treatment with MC1288 decreased clinical signs of GVHD compared with untreated or CsA-treated rats. Histological manifestations of GVHD, expressed as mean total increment, were significantly lower (1.4 +/- 0.5) in MC1288 than in untreated (5.0 +/- 1.6) or CsA (3.5 +/- 1.0) groups. Combining MC1288 and CsA further improved histology (1.1 +/- 0.6). The expression of CD4, CD8, MHC class II, interleukin-2 receptor, nitric oxide 2, and NKR-P1A (NK cells) positivity was significantly decreased in the liver and skin of BMT rats by MC1288. MC1288 was effective in preventing clinical and histological signs and symptoms of GVHD. This novel vitamin D analog could be used as an immunomodulating agent in BMT.

  1. T cell lymphoproliferative disorder following bone marrow transplantation for severe aplastic anemia.

    PubMed

    Wang, L C; Lu, M Y; Yu, J; Jou, S T; Chiang, I P; Lin, K H; Lin, D T

    2000-10-01

    Post-transplant lymphoproliferative disorder (PTLD) is uncommonly of T cell origin, especially following BMT. We describe a 13-year-old boy with severe aplastic anemia (SAA) and no evidence of Fanconi's anemia who underwent BMT at 11 years of age using CY 10 mg/kg once daily i.v. on days -5, -4, antilymphocyte globulin (ALG) 30 mg/kg once daily i.v. on days -5 approximately -3 and CsA from day -1 as conditioning. The BMT failed and he received a further peripheral blood stem cell transplant (PBSCT) 240 days after BMT. Conditioning was with CY 50 mg/kg once daily i.v. on days -5 approximately -2, and ALG 15 mg/kg once daily i.v. on days -4 approximately -2. GVHD prophylaxis included CsA and MTX. Engraftment was later confirmed by cytogenetic studies. Desquamation and ulcers of the oral mucosa and mouth angle developed in the 13th month post PBSCT. A buccal mucosa biopsy on day +524 revealed only plasmacytosis. Immunosuppressants were discontinued at that point. Generalized lymphadenopathy, prolonged fever (waxing and waning) and facial swelling developed in the 18th month post PBSCT. A neck lymph node biopsy on day +601 showed T cell lymphoma of diffuse large cell type with monoclonal TCR gamma-chain gene rearrangement. A FISH study showed that the malignant T cells were of recipient origin. EBV in situ hybridization was negative. He did not receive further treatment apart from discontinuation of immunosuppressants. He was followed up in our out-patient clinic and showed good performance 1170 days post PBSCT. We speculate that a different mechanism was operating in the pathogenesis of T cell lymphoma in this case. Risk factors include SAA and two transplants, conditioned with CY and ALG, long term use of CsA and treatment with azathioprine. PMID:11081391

  2. Comparison of Characteristics and Outcomes of Trial Participants and Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 Trial.

    PubMed

    Khera, Nandita; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Aljurf, Mahmoud D; Akpek, Görgün; Atsuta, Yoshiko; Beattie, Sara; Bredeson, Christopher N; Burns, Linda J; Dalal, Jignesh D; Freytes, César O; Gupta, Vikas; Inamoto, Yoshihiro; Lazarus, Hillard M; LeMaistre, Charles F; Steinberg, Amir; Szwajcer, David; Wingard, John R; Wirk, Baldeep; Wood, William A; Joffe, Steven; Hahn, Theresa E; Loberiza, Fausto R; Anasetti, Claudio; Horowitz, Mary M; Lee, Stephanie J

    2015-10-01

    Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and nonparticipants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients.

  3. Comparison of Characteristics and Outcomes of Trial Participants and Nonparticipants: Example of Blood and Marrow Transplant Clinical Trials Network 0201 Trial.

    PubMed

    Khera, Nandita; Majhail, Navneet S; Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Aljurf, Mahmoud D; Akpek, Görgün; Atsuta, Yoshiko; Beattie, Sara; Bredeson, Christopher N; Burns, Linda J; Dalal, Jignesh D; Freytes, César O; Gupta, Vikas; Inamoto, Yoshihiro; Lazarus, Hillard M; LeMaistre, Charles F; Steinberg, Amir; Szwajcer, David; Wingard, John R; Wirk, Baldeep; Wood, William A; Joffe, Steven; Hahn, Theresa E; Loberiza, Fausto R; Anasetti, Claudio; Horowitz, Mary M; Lee, Stephanie J

    2015-10-01

    Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multicenter study comparing peripheral blood (PB) with bone marrow transplantation from unrelated donors, conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). We compared characteristics and outcomes of study participants (n = 494) and nonparticipants (n = 1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the 2 groups using Cox proportional hazards regression models. No significant differences in age, sex, disease distribution, race/ethnicity, HLA matching, comorbidities, and interval from diagnosis to hematopoietic cell transplantation were seen between the participants and nonparticipants. Nonparticipants were more likely to have lower performance status, lower risk disease, and older donors, and to receive myeloablative conditioning and antithymocyte globulin. Nonparticipants were also more likely to receive PB grafts, the intervention tested in the trial (66% versus 50%, P < .001). Overall survival, transplantation-related mortality, and incidences of acute or chronic graft-versus-host disease were comparable between the 2 groups though relapse was higher (hazard ratio, 1.22; 95% confidence interval, 1.02 to 1.46; P = .028) in nonparticipants. Despite differences in certain baseline characteristics, survival was comparable between study participants and nonparticipants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. PMID:26071866

  4. Suppression of lentivirus-mediated transgenic dendritic cells in graft-versus-host disease after allogeneic bone marrow transplantation in mice.

    PubMed

    Xu, Y J; Chen, W R; Li, D P; Song, L X; Wu, J Q; Zhang, P; Li, Z Y; Huang, Y H

    2015-01-01

    We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase. PMID:26436385

  5. Current use and outcome of blood and marrow transplantation in childhood according to the Italian Registry.

    PubMed

    Pession, A; Locatelli, F; Rondelli, R; Prete, A; Paolucci, G

    1998-12-01

    Since 1985 data concerning patients affected by malignant and non-malignant diseases, aged <17 years, grafted in 16 centers nationwide, have been collected and stored in a central data base organized at the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) Operation Office within the AIEOP BMT Registry. The information, collected and structurally integrated with other specific disease-oriented national data bases, permitted the elaboration and the following publication of several analyses on survival, relapse probability and transplant-related mortality for the different diseases.

  6. Hemopoietic stem cell transplantation using mouse bone marrow and spleen cells fractionated by lectins.

    PubMed Central

    Reisner, Y; Itzicovitch, L; Meshorer, A; Sharon, N

    1978-01-01

    Mouse bone marrow and spleen cells were fractionated with the aid of soybean agglutinin and peanut agglutinin. A test for spleen colony-forming units in the isolated fractions showed that the hemopoietic stem cells are agglutinated by both of these lectins. The capacity of the agglutinated fractions to reconstitute lethally irradiated allogeneic mice was investigated. A sequential fractionation of splenocytes from SWR donors by soybean agglutinin and peanut agglutinin, or a single fractionation by soybean agglutinin of splenocytes from BALB/c donors, afforded a cell fraction that successfully reconstituted lethally irradiated (BALB/c X C57BL/6)F1 mice, without complications due to graft-versus-host reaction. Images PMID:26916

  7. Dietary dehydroepiandrosterone inhibits bone marrow and leukemia cell transplants: role of food restriction.

    PubMed

    Catalina, Fernando; Milewich, Leon; Kumar, Vinay; Bennett, Michael

    2003-12-01

    Dietary dehydroepiandrosterone (DHEA) inhibits the proliferation of syngeneic bone marrow cells (BMC) infused into lethally irradiated mice. Potential mechanisms for suppression of hematopoiesis were evaluated and the findings were as follows: (i) depletion of NK, T, B or macrophage cells failed to reverse suppression by DHEA; (ii) stem cell stimulation by erythropoietin, growth hormone, interleukin-2, Friend leukemia virus, or cyclophosphamide failed to reverse suppression; (iii) supplementation of fatty acids, mevalonate, or deoxyribonucleotides, which are dependent upon glucose-6-phosphate dehydrogenase function, did not enhance BMC growth in mice fed DHEA; (iv) DHEA downstream metabolites 4-androstenedione and 17beta-estradiol, as well as the synthetic steroid, 16alpha-chloroepiandrosterone (but not testosterone or 5-androstene-3beta,17beta-diol), also inhibited BMC growth. Tamoxifen antagonized the effects of 17beta-estradiol but not DHEA; (v) dietary DHEA causes hypothermia, but housing of DHEA-fed mice at 34 degrees C to maintain normal body temperature did not reverse suppression; (vi) DHEA leads to a decrease in food intake in rodents. Pair-feeding control diet to mice fed DHEA mimicked the effects of dietary DHEA; (vii) adrenalectomy and orchiectomy decrease the levels of stress and sex hormones, respectively. Neither procedure affected the ability of food restriction or DHEA feeding to inhibit hematopoiesis; (viii) growth of GR-3 NM pre-B leukemia cells in unirradiated mice was also suppressed by DHEA or food restriction. We conclude that DHEA, by reducing food intake in mice, inhibits bone marrow and leukemia cell growth. The precise mechanism(s) by which reduced food intake per se inhibits hematopoiesis is not known, but may involve an increased rate of cellular apoptosis.

  8. Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.

    PubMed

    Selvaggi, K J; Wilson, J W; Mills, L E; Cornwell, G G; Hurd, D; Dodge, W; Gingrich, R; Martin, S E; McMillan, R; Miller, W

    1994-03-15

    We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.

  9. Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.

    PubMed

    Selvaggi, K J; Wilson, J W; Mills, L E; Cornwell, G G; Hurd, D; Dodge, W; Gingrich, R; Martin, S E; McMillan, R; Miller, W

    1994-03-15

    We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM. PMID:8123862

  10. Second Allogeneic Hematopoietic Cell Transplantation for Patients with Fanconi Anemia and Bone Marrow Failure.

    PubMed

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K; Bonfim, Carmem; Camitta, Bruce M; Fasth, Anders L; Gale, Robert Peter; Lee, Michelle A; Lund, Troy C; Myers, Kasiani C; Olsson, Richard F; Page, Kristin M; Prestidge, Tim D; Radhi, Mohamed; Shah, Ami J; Schultz, Kirk R; Wirk, Baldeep; Wagner, John E; Deeg, H Joachim

    2015-10-01

    A second allogeneic hematopoietic cell transplantation (HCT) is the sole salvage option for individuals who develop graft failure after their first HCT. Data on outcomes after second HCT in patients with Fanconi anemia (FA) are scarce. Here we report outcomes after second allogeneic HCT for FA (n = 81). The indication for second HCT was graft failure after the first HCT. Transplantations were performed between 1990 and 2012. The timing of the second HCT predicted subsequent graft failure and survival. Graft failure was high when the second HCT was performed less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between the first HCT and second HCT was less than 3 months, compared with 23% when the interval was longer (P < .001). Consequently, the 1-year survival rate was substantially lower when the interval between the first and second HCTs was less than 3 months compared with longer (23% vs 58%; P = .001). The corresponding 5-year probability of survival was 16% and 45%, respectively (P = .006). Taken together, these data suggest that fewer than one-half of patients with FA undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to reduce the rate of graft failure after first HCT. PMID:26116087

  11. Transplanted Human Bone Marrow Mesenchymal Stem Cells Seeded onto Peptide Hydrogel Decrease Alveolar Bone Loss

    PubMed Central

    Karlström, Erik; Cedervall, Jessica; Wendel, Mikael

    2012-01-01

    Abstract Alveolar bone loss can be caused by periodontitis or periodontal trauma. We have evaluated the effects of transplanted undifferentiated human mesenchymal stem cells (hMSCs) on alveolar bone reaction and periodontal ligament healing in an experimental periodontal wound model. The hMSCs seeded onto a self-assembling peptide hydrogel in combination with collagen sponge were implanted into the right mandible of 12 rats and followed for 1 (n=6) or 4 weeks (n=6) postoperatively. The other 12 sham-treated rats were used as controls. Histological and histomorphometrical methods were used to assess the periodontal tissue reaction. The alveolar bone volume density was significantly higher at 1 week after surgery, and the osteoclast number was significantly lower at both 1 week and 4 weeks postoperatively in the mandibles treated with hMSCs. The implanted cells were detected only at 1 week after surgery. In conclusion, transplanted hMSCs can contribute to alveolar bone preservation after a periodontal surgical trauma at least by decreasing local osteoclast number. PMID:23514848

  12. Biochemical and molecular analysis in a patient with the severe form of Hunter syndrome after bone marrow transplantation

    SciTech Connect

    Li, P.; Huffman, P.; Thompson, J.N.

    1996-09-06

    Hunter syndrome (mucopolysaccharidosis type II, or MPS II) results from a deficiency of iduronate-2-sulfatase (IDS) activity due to a primary genetic defect in the X-chromosomal iduronate-2-sulfatase gene. We have studied a 10-year-old male, diagnosed with Hunter syndrome at age 2 years, who underwent bone marrow transplantation (BMT) at age 5 years. To evaluate the metabolic effect of BMT, biochemical and enzymatic studies, were performed. Urinary glycosaminoglycans (GAGs) were quantitated, and iduronate-2-sulfatase activity was measured in serum, leukocytes, and liver homogenates. Decreased urinary glycosaminoglyan excretion and increased iduronate-2-sulfatase activity in serum and leukocytes were observed. Furthermore, molecular analysis was performed using reverse transcriptional polymerase chain reaction (RT-PCR) sequencing and restriction enzyme assay. The patient was found to have a novel nonsense mutation, L279X (TTA to TGA) in exon 6 of the IDS gene, inherited from his mother. A comparison of the DNA contents of cultured skin fibroblasts prior to BMT with leukocyte DNA after BMT showed coexisting host mutant and donor normal alleles in post-BMT leukocyte DNA. We postulate that the L279X mutation is a severe disease-causing mutation for Hunter syndrome. 20 refs., 3 figs., 2 tabs.

  13. [Detection of mixed lymphoid chimerism after allogeneic bone marrow transplantation: demonstration by interphase cytogenetics in paraffin-embedded tissue].

    PubMed

    Friedrich, T; Ott, G; Kalla, J; Helbig, W; Schwenke, H; Kubel, M; Pönisch, W; Feyer, P; Friedrich, A

    1994-01-01

    In bone marrow transplantation (BMT) the detection of residual host lymphoid or haematopoietic cells surviving conditioning therapy is because of its association to graft-versus-host disease, graft-versus-leukemia reaction, and relapse of leukemia a matter of great interest. We studied the occurrence of this mixed lymphoid chimerism (MC) in the formol-fixed lymphatic tissue of lymph nodes and spleen from 21 autopsies after allogeneic sex-mismatched BMT (5 females, 16 males, survival 5 to 1140 days after BMT). In situ hybridisation with biotinylated centromer-specific anti-X- and anti-Y-chromosome probes was performed on pepsin-digested paraffin sections. The number of double X-, single X-, and Y-chromosome bearing cells was analysed microscopically. Because of artefacts only 14 cases remained for valid investigation. MC was detected in 6 cases (5 out of 11 males 5 days to 840 days and 1 out of 3 females 76 days after BMT). MC occurred after whole body irradiation with 10 Gy (n = 5) and 7 Gy (n = 1). In 1 autopsy relapse of leukemia caused host cell infiltration. Cases with MC did not express histological signs of acute or chronic graft-versus-host disease, but 5 out of 8 with complete lymphoid chimerism did. The sensitivity of interphase cytogenetics on paraffin embedded tissue is low.

  14. Multiple extramedullary relapses without bone marrow involvement after second allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    PubMed

    Yoo, Sang Woo; Chung, Eun Jin; Kim, Sun Young; Ko, Jeong Hee; Baek, Hey Sung; Lee, Hyun Ju; Oh, Sung Hee; Jeon, Seok Cheol; Lee, Woong Soo; Park, Chan Kum; Lee, Chul Hoon

    2012-06-01

    EMR without BM involvement after allogeneic HSCT is extremely rare, especially in children; only a few cases have been reported. A two-yr-old boy was diagnosed with AML (M4) and underwent allogeneic HSCT in first complete remission with BM from HLA-matched unrelated donor without GVHD. Four yr later, he had a BM relapse and after induction and consolidation chemotherapy, he received a second HSCT from an unrelated donor using peripheral blood stem cells. His second post-transplant course was complicated by extensive chronic GVHD involving the skin, oral cavity, and lungs, which was treated with tacrolimus and corticosteroid. Two yr later, he noticed a mild swelling in the right cheek area. The BM showed a complete remission marrow and a soft tissue biopsy was compatible with granulocytic sarcoma. PET-CT showed multifocal bone involvements. He received chemotherapy, and the chloromas decreased in size. We report a case of diffuse EMR of AML without BM involvement after a second allogeneic HSCT. PMID:21923886

  15. Recovery of immune functions in dogs after total body irradiation and transplantation of autologous blood or bone marrow cells

    SciTech Connect

    Pruemmer, O.R.; Raghavachar, A.; Fliedner, T.M.

    1985-10-01

    The restoration of immune functions was followed in dogs for 101 days after fractionated total body irradiation and autologous transfusion of peripheral blood leukocytes (PBL) or bone marrow (BM) cells. Median numbers of 0.9 X 10(5) granulocyte-macrophage progenitor cells per kilogram of body weight were transferred in either group of recipients. The following parameters recovered more rapidly in PBL recipients as opposed to BM recipients: total blood lymphocyte, T- and B-cell counts, serum levels of immunoglobulins IgM and IgA, in vitro blastogenic responses after stimulation with concanavalin A and pokeweed mitogen, and in vitro plasma cell formation after polyclonal B-cell activation with pokeweed mitogen with or without lipopolysaccharide. No major differences were noted for the restoration of serum IgG levels. Circulating lymphocyte and T-cell numbers remained subnormal for more than three months in both groups, whereas B-cell numbers and serum levels of IgA continued to be depressed in BM recipients only. Thus, autologous PBL restored immune functions more rapidly than did BM. Transplantation of PBL, alone or in addition to autologous BM, might also shorten the period of immunodeficiency after cytoreduction in a variety of malignancies in man.

  16. Anti-CD45 radioimmunotherapy using (211)At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model.

    PubMed

    Orozco, Johnnie J; Bäck, Tom; Kenoyer, Aimee; Balkin, Ethan R; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Frayo, Shani L; Hylarides, Mark D; Green, Damian J; Gopal, Ajay K; Press, Oliver W; Pagel, John M

    2013-05-01

    Despite aggressive chemotherapy combined with hematopoietic stem cell transplantation (HSCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using monoclonal antibodies labeled with β-emitting radionuclides has been explored to reduce relapse. β emitters are limited by lower energies and nonspecific cytotoxicity from longer path lengths compared with α emitters such as (211)At, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using (211)At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of (211)At-anti-murine CD45 mAb (30F11) to marrow and spleen within 24 hours (18% and 79% injected dose per gram of tissue [ID/g], respectively), with lower kidney and lung uptake (8.4% and 14% ID/g, respectively). In syngeneic HSCT studies, (211)At-B10-30F11 RIT improved the median survival of leukemic mice in a dose-dependent fashion (123, 101, 61, and 37 days given 24, 20, 12, and 0 µCi, respectively). This approach had minimal toxicity with nadir white blood cell counts >2.7 K/µL 2 weeks after HSCT and recovery by 4 weeks. These data suggest that (211)At-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML. PMID:23471305

  17. Monitoring of chimerism using fluorescence in situ hybridization in a child with severe combined immune deficiency following bone marrow transplant

    SciTech Connect

    Wenger, S.L.; Chen, X.O.; Katz, A.J. |

    1994-09-01

    A boy with severe combined immunodeficiency received a bone marrow transplant from his sister when he was approximately 3 years of age. His peripheral blood karyotype at age 3 and 4 years was 46,XX (20 cells analyzed). Because of a decline in antibody production at 19 years of age, the patient`s peripheral blood was analyzed again for suspected chimerism. His karyotype in phytohemagglutinin (PHA)-stimulated culture was 46,XX in 49 cells and 46,XY in one cell. Both metaphase and interphase cells were examined for sex chromosome constitution using X and Y dual-color alpha-satellite probes for fluorescence in situ hybridization (FISH). FISH results for metaphase cells showed 1/50 XY cells, but 38% of interphase cells showed the presence of both X and Y centromere. Pokeweed mitogen (PWM)-stimulated cultures grew poorly and were therefore analyzed using FISH only: 81% of interphase cells were 46,XX. The discrepancy between metaphase and interphase in the PHA-stimulated cultures most likely represents a failure of this boy`s own XY T-cells to be stimulated.

  18. Early Results of Clinical Application of Autologous Whole Bone Marrow Stem Cell Transplantation for Critical Limb Ischemia with Buerger's Disease.

    PubMed

    Heo, Seon-Hee; Park, Yoong-Seok; Kang, Eun-Suk; Park, Kwang-Bo; Do, Young-Soo; Kang, Kyung-Sun; Kim, Dong-Ik

    2016-01-01

    Our goal was to evaluate early results of the clinical application of autologous whole bone marrow stem cell transplantation (AWBMSCT) for critical limb ischemia (CLI) in patients with Buerger's disease. We retrospectively analyzed the data of 58 limbs of 37 patients (mean age, 43.0 years; range, 28-63 years; male, 91.9%) with Buerger's disease with CLI who were treated with AWBMSCT from March 2013 to December 2014. We analyzed Rutherford category, pain score, pain-free walking time (PFWT), total walking time (TWT), ankle brachial pressure index (ABPI), and toe brachial pressure index (TBPI), and investigated wound healing and occurrence of unplanned amputations. The mean follow-up duration was 11.9 ± 7.2 months (range, 0.9-23.9 months) and 100%, 72.4%, and 74.1% of patients were available to follow-up 1, 3 and 6 months after AWBMST, respectively. At 6 months, patients demonstrated significant improvements in Rutherford category (P < 0.0001), pain score (P < 0.0001), PFWT (P < 0.0001) and TBPI (P < 0.0001). ABPI was increased compared to baseline, but the difference was not significant. A total of 76.5% ischemic wounds achieved complete or improved healing. AWBMSCT is a safe and effective alternative or adjunctive treatment modality to achieve clinical improvement in patients with CLI. PMID:26791280

  19. Anti-CD45 radioimmunotherapy using 211At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model

    PubMed Central

    Orozco, Johnnie J.; Bäck, Tom; Kenoyer, Aimee; Balkin, Ethan R.; Hamlin, Donald K.; Wilbur, D. Scott; Fisher, Darrell R.; Frayo, Shani L.; Hylarides, Mark D.; Green, Damian J.; Gopal, Ajay K.; Press, Oliver W.

    2013-01-01

    Despite aggressive chemotherapy combined with hematopoietic stem cell transplantation (HSCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using monoclonal antibodies labeled with β-emitting radionuclides has been explored to reduce relapse. β emitters are limited by lower energies and nonspecific cytotoxicity from longer path lengths compared with α emitters such as 211At, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using 211At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of 211At-anti-murine CD45 mAb (30F11) to marrow and spleen within 24 hours (18% and 79% injected dose per gram of tissue [ID/g], respectively), with lower kidney and lung uptake (8.4% and 14% ID/g, respectively). In syngeneic HSCT studies, 211At-B10-30F11 RIT improved the median survival of leukemic mice in a dose-dependent fashion (123, 101, 61, and 37 days given 24, 20, 12, and 0 µCi, respectively). This approach had minimal toxicity with nadir white blood cell counts >2.7 K/µL 2 weeks after HSCT and recovery by 4 weeks. These data suggest that 211At-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML. PMID:23471305

  20. Anti-CD45 radioimmunotherapy using (211)At with bone marrow transplantation prolongs survival in a disseminated murine leukemia model.

    PubMed

    Orozco, Johnnie J; Bäck, Tom; Kenoyer, Aimee; Balkin, Ethan R; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Frayo, Shani L; Hylarides, Mark D; Green, Damian J; Gopal, Ajay K; Press, Oliver W; Pagel, John M

    2013-05-01

    Despite aggressive chemotherapy combined with hematopoietic stem cell transplantation (HSCT), many patients with acute myeloid leukemia (AML) relapse. Radioimmunotherapy (RIT) using monoclonal antibodies labeled with β-emitting radionuclides has been explored to reduce relapse. β emitters are limited by lower energies and nonspecific cytotoxicity from longer path lengths compared with α emitters such as (211)At, which has a higher energy profile and shorter path length. We evaluated the efficacy and toxicity of anti-CD45 RIT using (211)At in a disseminated murine AML model. Biodistribution studies in leukemic SJL/J mice showed excellent localization of (211)At-anti-murine CD45 mAb (30F11) to marrow and spleen within 24 hours (18% and 79% injected dose per gram of tissue [ID/g], respectively), with lower kidney and lung uptake (8.4% and 14% ID/g, respectively). In syngeneic HSCT studies, (211)At-B10-30F11 RIT improved the median survival of leukemic mice in a dose-dependent fashion (123, 101, 61, and 37 days given 24, 20, 12, and 0 µCi, respectively). This approach had minimal toxicity with nadir white blood cell counts >2.7 K/µL 2 weeks after HSCT and recovery by 4 weeks. These data suggest that (211)At-anti-CD45 RIT in conjunction with HSCT may be a promising therapeutic option for AML.

  1. Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet-Rich Plasma Accelerate Distraction Osteogenesis in A Canine Model

    PubMed Central

    Dehghan, Mohammad Mehdi; Baghaban Eslaminejad, Mohamadreza; Motallebizadeh, Nader; Ashrafi Halan, Javad; Tagiyar, Leila; Soroori, Sarang; Nikmahzar, Agbibi; Pedram, Mirsepehr; Shahverdi, Abdolhossein; Kazemi Mehrjerdi, Hossein; Izadi, Sadra

    2015-01-01

    Objective Distraction osteogenesis (DO) is a surgical procedure used to generate large volumes of new bone for limb lengthening. Materials and Methods In this animal experimental study, a 30% lengthening of the left tibia (mean distraction distance: 60.8 mm) was performed in ten adult male dogs by callus distraction after osteotomy and application of an Ilizarov fixator. Distraction was started on postoperative day seven with a distraction rate of 0.5 mm twice per day and carried out at a rate of 1.5 mm per day until the end of the study. Autologous bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich plasma (PRP) as the treatment group (n=5) or PRP alone (control group, n=5) were injected into the distracted callus at the middle and end of the distraction period. At the end of the consolidation period, the dogs were sacrificed after which computerized tomography (CT) and histomorphometric evaluations were performed. Results Radiographic evaluationsrevealed that the amount and quality of callus formations were significantly higher in the treatment group (P<0.05). As measured by CT scan, the healing parametersin dogs of the treatment group were significantly greater (P<0.05). New bone formation in the treatment group was significantly higher (P<0.05). Conclusion The present study showed that the transplantation of BM-MSCs positively affects early bony consolidation in DO. The use of MSCs might allow a shortened period of consolidation and therefore permit earlier device removal. PMID:26199903

  2. Transplantation of NGF-gene-modified bone marrow stromal cells into a rat model of Alzheimer' disease.

    PubMed

    Li, Li-Yan; Li, Jin-Tao; Wu, Qing-Ying; Li, Jin; Feng, Zhong-Tang; Liu, Su; Wang, Ting-Hua

    2008-02-01

    It is well known that bone marrow stromal cells (BMSC) grafted into the hippocampus of the rat model of Alzheimer's disease (AD) could survive and differentiate into cholinergic neurons as well as contribute towards functional restoration. The present study evaluated the effects of BMSC as a seed cell modified by nerve growth factor (NGF) gene into the hippocampus of AD rats. The beta-amyloid protein was injected bilaterally into the rat hippocampus to reproduce the AD model. After the human total RNA was extracted, the NGF gene was amplified by reverse transcription-polymerase chain reaction, then cloned into the pcDNA3. BMSC derived from a green fluorescence protein transgenic mouse were isolated, cultured, identified, and transfected by the NGF recombinant. The NGF-gene-modified BMSC were then transplanted into the hippocampus of AD rats. The results showed that implanted BMSC survived, migrated and expressed NGF as well as differentiated into ChAT-positive neurons. A significant improvement in learning and memory in AD rats was also seen in NGF-gene-modified BMSC group, when compared with the BMSC group. The present findings suggested that BMSC provided an effective carrier for delivery of NGF into AD rats, and the administration of NGF-gene-modified BMSC may be considered as a potential strategy for the development of effective therapies for the treatment of AD.

  3. Manhattan transfer: lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942-1961.

    PubMed

    Kraft, Alison

    2009-01-01

    This study investigates how, in the late 1940s and 1950s, fears of nuclear accidents and nuclear warfare shaped postwar radiobiology. The new and intense forms of radiation generated by nuclear reactor technology, and which would be released in the event of a nuclear war, created concerns about a public-health hazard unprecedented in form and scale. Fears of inadvertent exposure to acute and potentially lethal radiation launched a search for anti-radiation therapies, out of which emerged the new technique of bone marrow transplantation (BMT). This study analyzes the use of BMT first as a research tool to explore the biological effects of ionizing radiation, and then as an adjunct to radiotherapy for the treatment of cancer. In highlighting how BMT became the province of different research and clinical constituencies, this study develops an understanding of the forces and contingencies that shaped its development. Exploring the emergence of BMT and the uses to which it was put, it reveals that BMT remained a technique in the making -- unstable and far from standardized, even as it became both a widely used research tool and rapidly made its way into the clinic. More broadly, it casts new light on one route through which the Manhattan Project influenced postwar radiobiology; it also affords new insights into one means by which radiobiology came to serve the interests of the Cold War state. In its focus on BMT this paper provides a new perspective on the evolving relationship between radiobiology and biomedicine in the postwar period.

  4. Human tonsil-derived mesenchymal stromal cells enhanced myelopoiesis in a mouse model of allogeneic bone marrow transplantation

    PubMed Central

    Ryu, Jung-Hwa; Park, Minhwa; Kim, Bo-Kyung; Kim, Yu-Hee; Woo, So-Youn; Ryu, Kyung-Ha

    2016-01-01

    Mesenchymal stromal cells (MSCs) have therapeutic potential for repairing tissue damage and are involved in immune regulation. MSCs are predominantly isolated from bone marrow (BM), adipose tissue or placental tissue. Further to these well-known sources, the isolation of MSCs from human tonsils was previously reported. The aim of the present study was to investigate a potential role for tonsil-derived MSCs (T-MSCs) in BM reconstitution and application towards supplementing hematopoiesis in a mouse model of BM transplantation (BMT). Eight-week-old BALB/c female mice received 80 mg/kg busulfan (Bu)/200 mg/kg cyclophosphamide (Cy) conditioning chemotherapy for BM ablation. Subsequently, human T-MSCs were injected into the Bu/Cy-treated mice with or without BM cells (BMCs) obtained from allogeneic C57BL/6 male mice. After 3 weeks, peripheral blood and BM was collected for analysis. The red blood cell count in the group that received BMCs had almost returned to normal, whereas mononuclear cell counts and BM cellularity were most improved in the T-MSCs + BMCs group. These results indicate that the T-MSCs enhanced myelopoiesis in the allogeneic BMT mouse model, as evidenced by the restoration of BM with hematopoietic cells, as well as increased myeloid colony formation in vitro. Therefore, T-MSCs may provide a source of MSCs to facilitate myelopoiesis and megakaryocytosis following BMT. PMID:27511380

  5. Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis.

    PubMed

    Truong, Nhung Hai; Nguyen, Nam Hai; Le, Trinh Van; Vu, Ngoc Bich; Huynh, Nghia; Nguyen, Thanh Van; Le, Huy Minh; Phan, Ngoc Kim; Pham, Phuc Van

    2016-01-01

    Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment. PMID:26839564

  6. Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis

    PubMed Central

    Truong, Nhung Hai; Nguyen, Nam Hai; Le, Trinh Van; Vu, Ngoc Bich; Huynh, Nghia; Nguyen, Thanh Van; Le, Huy Minh; Phan, Ngoc Kim

    2016-01-01

    Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment. PMID:26839564

  7. Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis.

    PubMed

    Truong, Nhung Hai; Nguyen, Nam Hai; Le, Trinh Van; Vu, Ngoc Bich; Huynh, Nghia; Nguyen, Thanh Van; Le, Huy Minh; Phan, Ngoc Kim; Pham, Phuc Van

    2016-01-01

    Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-α1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment.

  8. Combined procedure of vascularized bone marrow transplantation and mesenchymal stem cells graft - an effective solution for rapid hematopoietic reconstitution and prevention of graft-versus-host disease.

    PubMed

    Coliţă, Andrei; Coliţă, Anca; Zamfirescu, Dragos; Lupu, Anca Roxana

    2012-09-01

    Hematopoietic stem cell transplantation (HSCT) is a a standard therapeutic option for several diseases. The success of the procedure depends on quality and quantity of transplanted cells and on stromal capacity to create an optimal microenvironment, that supports survival and development of the hematopoietic elements. Conditions associated with stromal dysfunction lead to slower/insufficient engraftment and/or immune reconstitution. A possible solution to this problem is to realize a combined graft of hematopoietic stem cells along with the medular stroma in the form of vascularized bone marrow transplant (VBMT). Another major drawback of HSCT is the risk of graft versus host disease (GVHD). Recently, mesenchymal stromal cells (MSC) have demonstrated the capacity to down-regulate alloreactive T-cell and to enhance the engraftment. Cotransplantation of MSC could be a therapeutic option for a better engraftment and GVHD prevention. PMID:22677297

  9. Autologous bone marrow stem cell transplantation for the treatment of postoperative hand infection with a skin defect in diabetes mellitus: A case report.

    PubMed

    Liu, Yihong; Liu, Yuchen; Wang, Pujie; Tian, Haoming; Ai, Jianzhong; Liu, Yangbo; Zhou, Yi; Liu, Zhongwen; Guo, Wenjun; Yang, Shenke

    2014-06-01

    Among stem cells, autologous mesenchymal stem cells (MSCs) are ideal for transplantation by virtue of limited rejection reactions and marked proliferative ability. This study presents a novel method by which MSCs were harvested from the bone marrow of a patient who presented with severe post-traumatic infection and a non-healing skin defect in the hand, secondary to uncontrolled diabetes mellitus (DM). An autologous MSC suspension was injected into the persistent skin defect after stabilizing the blood glucose level and appropriate infection control. During the course of a regular 18-month postoperative follow-up, the patient exhibited immediate recovery with no transplant-associated complications, as well as no evidence of tumorigenicity. Thus, transplantation of autologous MSCs may play a role in the clinical application of stem cells, particularly for treatment of skin defects following surgery in cases of DM and for those caused by various other traumas.

  10. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function.

    PubMed

    Kong, Y; Wang, Y-T; Hu, Y; Han, W; Chang, Y-J; Zhang, X-H; Jiang, Z-F; Huang, X-J

    2016-02-01

    Poor graft function (PGF), including early and late PGF, is a serious complication following allotransplant. We recently reported that bone marrow microenvironment abnormalities may occur in cases of late PGF. Whether these abnormalities occur in early PGF remains unknown. To answer this question, we performed a nested case-control study comparing cellular elements of the bone marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and endothelial cells were analyzed by flow cytometry and by hematoxylin-eosin and immunohistochemical staining in situ. Subjects with early and late PGF had similar abnormalities in these cell types compared with transplant recipients without PGF. However, none of the aforementioned elements of the bone marrow microenvironment were significantly different between early and late PGF patients. Our data suggest that similar abnormalities in the bone marrow microenvironment may occur in early and late PGF post allotransplant. Cellular approaches, such as the administration of mesenchymal stem cells, promise to be beneficial therapeutic strategies in patients with early or late PGF.

  11. Systemic aspects of conjugal resilience in couples with a child facing cancer and marrow transplantation

    PubMed Central

    Martin, Julie; Péloquin, Katherine; Vachon, Marie-France; Duval, Michel; Sultan, Serge

    2016-01-01

    Introduction The negative impact of paediatric cancer on parents is well known and is even greater when intensive treatments are used. This study aimed to describe how couples whose child has received a transplant for the treatment of leukaemia view conjugal resilience and to evaluate the role of we-ness as a precursor of conjugal adjustment. Methods Four parental couples were interviewed. Interviews were analysed in two ways: inductive thematic analysis and rating of verbal content with the We-ness Coding Scale. Results Participants report that conjugal resilience involves the identification of the couple as a team and cohesion in the couple. Being a team generates certain collaborative interactions that lead to conjugal resilience. A sense of we-ness in parents is associated with fluctuation in the frequency of themes. Discussion Participants’ vision of conjugal resilience introduced novel themes. The sense of we-ness facilitates cohesion and the process of conjugal resilience. PMID:27687510

  12. Determination of Eligibility in Related Pediatric Hematopoietic Cell Donors: Ethical and Clinical Considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association.

    PubMed

    Bitan, Menachem; van Walraven, Suzanna M; Worel, Nina; Ball, Lynne M; Styczynski, Jan; Torrabadella, Marta; Witt, Volker; Shaw, Bronwen E; Seber, Adriana; Yabe, Hiromasa; Greinix, Hildegard T; Peters, Christina; Gluckman, Eliane; Rocha, Vanderson; Halter, Joerg; Pulsipher, Michael A

    2016-01-01

    Related donors for hematopoietic cell (HC) transplantation are a growing population in recent years because of expanding indications for allogeneic transplantation. The safety and welfare of the donor are major concerns for the transplantation community, especially for related sibling donors of young recipients who are children and, thus, not able to fully consent. Because donation of HC does not improve the donor's own physical health and carries a risk of side effects, careful assessment of medical risks specific to the individual donor, as well as consideration of ethical and legal aspects associated with donation from a child, must be considered. In addition, donor centers must balance the needs of both the donor and the recipient, understanding the inherent conflict parents may have as they can be overly focused on the very sick child receiving a transplant, rather than on the relatively less significant health or emotional problems that a sibling donor may have, which could impact risk with donation. Likewise, consideration must be made regarding the nature of the relationship of the sibling donor to the recipient and also aspects of performing research on pediatric HC donors. In this article, as members of the Donor Issues Committee of the Worldwide Network for Blood and Marrow Transplantation, we review key ethical concerns associated with pediatric donation and then give recommendations for screening potential child donors with underlying health conditions. These recommendations are aimed at protecting the physical and emotional well-being of childhood donors and arise out of the Third International Conference on Health and Safety of Donors sponsored by the Worldwide Network for Blood and Marrow Transplantation. PMID:26307344

  13. Plasmid-based genetic modification of human bone marrow-derived stromal cells: analysis of cell survival and transgene expression after transplantation in rat spinal cord

    PubMed Central

    Ronsyn, Mark W; Daans, Jasmijn; Spaepen, Gie; Chatterjee, Shyama; Vermeulen, Katrien; D'Haese, Patrick; Van Tendeloo, Viggo FI; Van Marck, Eric; Ysebaert, Dirk; Berneman, Zwi N; Jorens, Philippe G; Ponsaerts, Peter

    2007-01-01

    Background Bone marrow-derived stromal cells (MSC) are attractive targets for ex vivo cell and gene therapy. In this context, we investigated the feasibility of a plasmid-based strategy for genetic modification of human (h)MSC with enhanced green fluorescent protein (EGFP) and neurotrophin (NT)3. Three genetically modified hMSC lines (EGFP, NT3, NT3-EGFP) were established and used to study cell survival and transgene expression following transplantation in rat spinal cord. Results First, we demonstrate long-term survival of transplanted hMSC-EGFP cells in rat spinal cord under, but not without, appropriate immune suppression. Next, we examined the stability of EGFP or NT3 transgene expression following transplantation of hMSC-EGFP, hMSC-NT3 and hMSC-NT3-EGFP in rat spinal cord. While in vivo EGFP mRNA and protein expression by transplanted hMSC-EGFP cells was readily detectable at different time points post-transplantation, in vivo NT3 mRNA expression by hMSC-NT3 cells and in vivo EGFP protein expression by hMSC-NT3-EGFP cells was, respectively, undetectable or declined rapidly between day 1 and 7 post-transplantation. Further investigation revealed that the observed in vivo decline of EGFP protein expression by hMSC-NT3-EGFP cells: (i) was associated with a decrease in transgenic NT3-EGFP mRNA expression as suggested following laser capture micro-dissection analysis of hMSC-NT3-EGFP cell transplants at day 1 and day 7 post-transplantation, (ii) did not occur when hMSC-NT3-EGFP cells were transplanted subcutaneously, and (iii) was reversed upon re-establishment of hMSC-NT3-EGFP cell cultures at 2 weeks post-transplantation. Finally, because we observed a slowly progressing tumour growth following transplantation of all our hMSC cell transplants, we here demonstrate that omitting immune suppressive therapy is sufficient to prevent further tumour growth and to eradicate malignant xenogeneic cell transplants. Conclusion In this study, we demonstrate that genetically

  14. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    SciTech Connect

    Belkacemi, Yazid . E-mail: y-belkacemi@o-lambret.fr; Labopin, Myriam; Hennequin, Christophe; Hoffstetter, Sylvette; Mungai, Raffaello; Wygoda, Marc; Lundell, Marie; Finke, Jurgen; Aktinson, Chris; Lorchel, Frederic; Durdux, Catherine; Basara, Nadezda

    2007-02-01

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population

  15. Macrophage function in murine allogeneic bone marrow radiation chimeras in the early phase after transplantation

    SciTech Connect

    Roesler, J.; Baccarini, M.; Vogt, B.; Lohmann-Matthes, M.L. )

    1989-08-01

    We tested several of the functions of macrophages (M phi) in the early phase after allogeneic bone marrow transfer to get information about this important aspect of the nonspecific immune system in the T-cell-deficient recipient. On days 3-5 after transfer, the number of M phi was reduced in the spleen, liver, lungs, and peritoneal cavity (Pe). The phagocytosis of sheep red blood cells (SRBC) by these M phi was normal or even enhanced, as in the case of Pe-M phi. Already on days 8-12 after transfer, the number of M phi in spleen and liver exceeded that of controls, whereas the number was still reduced in lungs and Pe. We examined their ability to kill P815 tumor cells, to produce tumor necrosis factor-alpha (TNF alpha), to phagocytose SRBC, to produce reactive oxygen intermediates (ROI) in vitro and to kill Listeria monocytogenes in vivo. Most functions were normal and often even enhanced, depending on the organ origin, but the ability of Pe-M phi to produce ROI was reduced. Proliferative response to macrophage colony-stimulating factor (M-CSF) and killing of YAC-1 tumor cells revealed a high frequency of macrophage precursor cells in the spleen and liver and a high natural killer (NK) activity in the liver. Altogether, enhanced nonspecific immune function, especially preactivated M phi, may enable chimeras to survive attacks by opportunistic pathogens.

  16. Donor MHC class II antigen is essential for induction of transplantation tolerance by bone marrow cells.

    PubMed

    Umemura, A; Monaco, A P; Maki, T

    2000-05-01

    Posttransplant infusion of donor bone marrow cells (BMC) induces tolerance to allografts in adult mice, dogs, nonhuman primates, and probably humans. Here we used a mouse skin allograft model and an allogeneic radiation chimera model to examine the role of MHC Ags in tolerance induction. Infusion of MHC class II Ag-deficient (CIID) BMC failed to prolong C57BL/6 (B6) skin grafts in ALS- and rapamycin-treated B10.A mice, whereas wild-type B6 or MHC class I Ag-deficient BMC induced prolongation. Removal of class II Ag-bearing cells from donor BMC markedly reduced the tolerogenic effect compared with untreated BMC, although graft survival was significantly longer in mice given depleted BMC than that in control mice given no BMC. Infusion of CIID BMC into irradiated syngeneic B6 or allogeneic B10.A mice produced normal lymphoid cell reconstitution including CD4+ T cells except for the absence of class II Ag-positive cells. However, irradiated B10.A mice reconstituted with CIID BMC rejected all B6 and a majority of CIID skin grafts despite continued maintenance of high degree chimerism. B10.A mice reconstituted with B6 BMC maintained chimerism and accepted both B6 and CIID skin grafts. Thus, expression of MHC class II Ag on BMC is essential for allograft tolerance induction and peripheral chimerism with cells deficient in class II Ag does not guarantee allograft acceptance. PMID:10779744

  17. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

    PubMed Central

    Farge, Dominique; Labopin, Myriam; Tyndall, Alan; Fassas, Athanasios; Mancardi, Gian Luigi; Van Laar, Jaap; Ouyang, Jian; Kozak, Tomas; Moore, John; Kötter, Ina; Chesnel, Virginie; Marmont, Alberto; Gratwohl, Alois; Saccardi, Riccardo

    2010-01-01

    Background Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. Design and Methods In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996–2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. Results Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers’ experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. Conclusions This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with

  18. Comparison of Characteristics and Outcomes of Trial Participants and Non-participants: Example of Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial

    PubMed Central

    Khera, Nandita; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Aljurf, Mahmoud D.; Akpek, Görgün; Atsuta, Yoshiko; Beattie, Sara; Bredeson, Christopher N.; Burns, Linda J.; Dalal, Jignesh D.; Freytes, César O.; Gupta, Vikas; Inamoto, Yoshihiro; Lazarus, Hillard M.; LeMaistre, Charles F.; Steinberg, Amir; Szwajcer, David; Wingard, John R.; Wirk, Baldeep; Wood, William A.; Joffe, Steven; Hahn, Theresa E.; Loberiza, Fausto R.; Anasetti, Claudio; Horowitz, Mary M.; Lee, Stephanie J.

    2015-01-01

    BACKGROUND Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) transplantation from unrelated donors (URD), conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). METHODS AND FINDINGS We compared characteristics and outcomes of study participants (n=494) and non-participants (n=1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time-period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the two groups using Cox proportional hazards regression models. No significant differences in age, sex and disease distribution, race/ ethnicity, HLA matching, comorbidities and interval from diagnosis to HCT were seen between the participants and non-participants. Non-participants were more likely to have lower performance status, lower-risk disease, and older donors, and to receive myeloablative conditioning and anti-thymocyte globulin. Non-participants were also more likely to receive PB grafts, the intervention tested in the trial (66% vs. 50% p<0.001). Overall survival, transplant-related mortality, and incidences of acute or chronic GVHD were comparable between the two groups though relapse was higher (HR 1.22, 95% CI 1.02–1.46, p=0.028) in non-participants. CONCLUSION Despite differences in certain baseline characteristics, survival was comparable between study participants and non-participants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. PMID:26071866

  19. Ongoing graft-versus-host disease is a risk factor for azoospermia after allogeneic hematopoietic stem cell transplantation: a survey of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Rovó, Alicia; Aljurf, Mahmoud; Chiodi, Sandra; Spinelli, Simonetta; Salooja, Nina; Sucak, Gülsan; Hunter, Ann; Kim, Tan Swee; Socié, Gérard; van Lint, Maria Teresa; Passweg, Jakob R.; Arat, Mutlu; Badoglio, Manuela; Tichelli, André

    2013-01-01

    The aim of this study was to assess the degree of spermatogenesis defects in sperm analysis in long-term male survivors after allogeneic hematopoietic stem cell transplantation in order to identify the risk factors related to potential infertility after hematopoietic stem cell transplantation and to provide data on longitudinal sperm recovery after hematopoietic stem cell transplantation. Here, the Late Effects Working Party of the European Group for Blood and Marrow Transplantation reports data of sperm analysis from 224 males who underwent hematopoietic stem cell transplantation. Median time between transplantation and sperm analysis was 63 months (8–275 months). At last sperm analysis, presence of any degree of spermatozoa was reported in 70 (31%) and complete azoospermia in 154 (69%) patients. In multivariate analysis, being conditioned with total body irradiation (RR 7.1; 95% CI: 3.4–14.8) and age over 25 years at transplantation (RR 2.4; 95% CI: 1.09–5.2) were significantly associated with higher risk for azoospermia. In patients not conditioned with total body irradiation, ongoing chronic graft-versus-host disease is the main adverse factor for sperm recovery (RR of 3.11; 95% CI: 1.02–9.47; P=0.045). Already established risk factors, such as total body irradiation and age older than 25 years at hematopoietic stem cell transplantation, were seen to be the most relevant adverse risk factor for sperm production after hematopoietic stem cell transplantation. Furthermore, for the first time, ongoing graft-versus-host disease has been shown to be the most relevant adverse factor for sperm recovery, particularly in patients conditioned without total body irradiation. We also introduce a useful scoring system to predict the probability of male long-term survivors’ azoospermia. PMID:22929982

  20. Very late nonfatal consequences of fractionated TBI in children undergoing bone marrow transplant

    SciTech Connect

    Faraci, Maura; Cohen, Amnon; Lanino, Edoardo; Sacco, Oliviero; Cabria, Manlio; De Marco, Riccardo; Stella, Gilberto; Dallorso, Sandro; Vitale, Vito; Dini, Giorgio

    2005-12-01

    Purpose: To describe long-term late consequences in children who received total body irradiation (TBI) for hematopoietic stem cell transplantation 10 years earlier. Methods and Materials: A cohort of 42 children treated with TBI between 1985 and 1993, still alive at least 10 years after fractionated TBI (FTBI), was evaluated. Twenty-five patients received FTBI at 330 cGy/day for 3 days (total dose 990 cGy), whereas 17 children were administered fractions of 200 cGy twice daily for 3 days (total dose 1200 cGy). Twenty-seven patients received autologous and 16 allogeneic hematopoietic stem cell transplantation. Median age at TBI was 6.3 years, and 18.4 years at most recent follow-up. Results: Cataract was diagnosed in 78% of patients after a median of 5.7 years. Hypothyroidism was detected in 12%, whereas thyroid nodules were observed in 60% of our population after a median interval of 10.2 years. Patients treated with 990 cGy developed thyroid nodules more frequently than those treated with 1200 cGy (p = 0.0002). Thyroid carcinoma was diagnosed in 14% of the total population. Females who received FTBI after menarche more frequently developed temporary ovarian dysfunction than those treated before menarche, but cases of persistent ovarian dysfunction did not differ between the two groups. Indirect signs of germinal testicular dysfunction were detected in 87% of males. Restrictive pulmonary disease was observed in 74% of patients. Osteochondroma was found in 29% of patients after a median interval of 9.2 years. This latter complication appeared more frequently in patients irradiated before the age of 3 years (p < 0.001). Conclusions: This study shows that late effects that are likely permanent, although not fatal, are frequent in survivors 10 years after TBI. However, some of the side effects observed shortly after TBI either disappeared or remained unchanged without signs of evolution. Monitoring is recommended to pursue secondary prevention strategies and counseling

  1. Cyclophosphamide decreases O6-alkylguanine-DNA alkyltransferase activity in peripheral lymphocytes of patients undergoing bone marrow transplantation.

    PubMed Central

    Lee, S. M.; Crowther, D.; Scarffe, J. H.; Dougal, M.; Elder, R. H.; Rafferty, J. A.; Margison, G. P.

    1992-01-01

    O6-alkylguanine-DNA-alkyltransferase (ATase) levels were measured in extracts of peripheral blood lymphocytes taken at various times during chemotherapy from 19 patients with various haematological malignancies. Seven patients with advanced Hodgkin's disease received preparative treatment consisting of cyclophosphamide (1.5 g m-2, daily) administered on days 1 to 4 and BCNU (600 mg m-2) on day 5 prior to autologous bone marrow rescue (ABMR) delivered on day 7. Treatment in the remaining 12 patients consisted of cyclophosphamide (1.8 g m-2, daily) given on days 1 and 2 followed at day 4 with total body irradiation (TBI) administered in six fractions over the subsequent 3 days to a total dose of 1200 cGy prior to bone marrow transplantation. In the Hodgkin's group, significant decreases in ATase activity were seen during the cyclophosphamide treatment, and the median ATase nadir was 32% (range 0% to 57%) of pretreatment levels following 4 days of cyclophosphamide. In one patient, no ATase activity was detectable following the 4th cyclophosphamide treatment. ATase activities decreased further after BCNU administration to a median of 19% (range 0% to 32%) of pretreatment levels. Extensive cyclophosphamide-induced reduction of lymphocyte ATase levels was also seen in the other group of 12 patients treated with cyclophosphamide/TBI: postcyclophosphamide median ATase nadir was 35% (range 12% to 78%) of the pretreatment levels. No ATase depletion was seen when cyclophosphamide (up to 10 mM) was incubated for 2 h with pure recombinant human ATase in vitro whereas ATase activity was reduced by 90% on preincubation with 100 microns acrolein or with greater than 1 mM phosphoramide mustard. This suggests that a cyclophosphamide-induced decrease in ATase levels in human peripheral lymphocytes in vivo may be due to depletion mediated by the production of intracellular acrolein. Since ATase appears to be a principal mechanism in cellular resistance to the cytotoxic effects of BCNU

  2. Protothecal peritonitis in child after bone marrow transplantation: case report and literature review of paediatric cases.

    PubMed

    Sykora, T; Horakova, J; Buzzasyova, D; Sladekova, M; Poczova, M; Sufliarska, S

    2014-11-01

    The case presented here illustrates a protothecal infection caused by Prototheca wickerhamii in a paediatric haematopoietic stem cell recipient followed by a review of the literature of all 13 paediatric cases published since 1980. Protothecosis is a rare disease caused by algae, not described in this setting before. Infection was proven additionally post-mortem from peritoneal dialysis fluid. Even though no death of a paediatric patient due to this infection has been reported and the mortality rate associated with protothecosis is low, our patient died from multiorgan failure as a result of numerous post-transplant complications and a strain of cultivated alga that was highly resistant to antifungal agents. Prototheca spp. show various susceptibility profiles, and there is no direct correlation between in vitro activity and clinical response. There are different treatment regimens described but there are no clear published guidelines of specific therapy of protothecosis. Paediatric cases were successfully treated mostly with amphotericin B and azoles. As the number of immunocompromised patients increases, it is necessary to think more about unusual pathogens such as Prototheca. PMID:25566393

  3. Protothecal peritonitis in child after bone marrow transplantation: case report and literature review of paediatric cases

    PubMed Central

    Sykora, T; Horakova, J; Buzzasyova, D; Sladekova, M; Poczova, M; Sufliarska, S

    2014-01-01

    The case presented here illustrates a protothecal infection caused by Prototheca wickerhamii in a paediatric haematopoietic stem cell recipient followed by a review of the literature of all 13 paediatric cases published since 1980. Protothecosis is a rare disease caused by algae, not described in this setting before. Infection was proven additionally post-mortem from peritoneal dialysis fluid. Even though no death of a paediatric patient due to this infection has been reported and the mortality rate associated with protothecosis is low, our patient died from multiorgan failure as a result of numerous post-transplant complications and a strain of cultivated alga that was highly resistant to antifungal agents. Prototheca spp. show various susceptibility profiles, and there is no direct correlation between in vitro activity and clinical response. There are different treatment regimens described but there are no clear published guidelines of specific therapy of protothecosis. Paediatric cases were successfully treated mostly with amphotericin B and azoles. As the number of immunocompromised patients increases, it is necessary to think more about unusual pathogens such as Prototheca. PMID:25566393

  4. Sequence similarity matching: proposal of a structure-based rating system for bone marrow transplantation.

    PubMed

    Elsner, H-A; Blasczyk, R

    2002-06-01

    Recent advances in DNA-based typing have led to the detection of a continuously growing number of HLA alleles. For this reason, HLA matching in transplantation of hematopoietic stem cells from unrelated donors has become increasingly complicated. When there is no genotypically identical sibling and there are several alternative potential donors that all have a mismatch at a relevant HLA locus, until now no rating system has existed indicating different levels of allogenicity. In order to find a theoretical approach to this problem we propose a rating system ('dissimilarity index') based on structural data of HLA class I molecules, and on published data about frequencies of naturally occurring amino acid exchanges. For demonstration we employ our rating system for the comparison of the HLA-A*23 and A*24 groups, both of which allelic products are subdivisions of the serological HLA-A9 family. Remarkable differences between the subtypes were revealed, which were superior to a simple sequence comparison. More surprisingly, it was uncovered that some alleles of the A*24 group showed fewer differences to A*2301 than to alleles within their own subtype group. Sequence similarity matching may serve as a starting point for the clinical evaluation of acceptable mismatches within the HLA-A9 family and serve as a model for other HLA class I groups. PMID:12047359

  5. Aspergillus Flavus Endocarditis of the Native Mitral Valve in a Bone Marrow Transplant Patient

    PubMed Central

    Demir, Tolga; Ergenoglu, Mehmet Umit; Ekinci, Abdurrahman; Tanrikulu, Nursen; Sahin, Mazlum; Demirsoy, Ergun

    2015-01-01

    Patient: Male, 36 Final Diagnosis: Aspergillus flavus endocarditis Symptoms: Malaise • fatigue and dyspnea Medication: — Clinical Procedure: Mitral vale replacemnet Specialty: Cardiology Objective: Rare disease Background: Infective endocarditis due to Aspergillus species is an uncommon infection with a high mortality rate. It mostly occurs after the implantation of prosthetic heart valves. Parenteral nutrition, immunosuppression, broad-spectrum antibiotic regimens, and illegal intravenous drug use are the risk factors for developing infection. Case Report: We report a case of Aspergillus flavus native mitral valve endocarditis in a patient who had allogeneic stem cell transplantation in the past due to myelodysplastic syndrome. Conclusions: Although it is rare and there is limited experience available with the diagnosis and treatment, early recognition and therapeutic intervention with systemic antifungal therapy and aggressive surgical intervention are critical to prevent further complications that may eventually lead to death. In addition, better novel diagnostic tools are needed to facilitate more accurate identification of patients with invasive Aspergillus and to permit earlier initiation of antifungal treatment. PMID:25603977

  6. Therapeutic angiogenesis for peripheral artery diseases by autologous bone marrow cell transplantation.

    PubMed

    Matoba, Satoaki; Matsubara, Hiroaki

    2009-01-01

    Critical limb ischemia (CLI) is a terminal stage of peripheral artery disease (PAD). The number of patients with CLI is increasing, and the disease has a major impact on patients' quality of life. In spite of the marked advances in surgery and interventional angioplasty, a large number of patients require revascularization. To treat these patients, cell based angiogenesis is attracting a great deal of attention as a new strategy. "Therapeutic angiogenesis" is a term that has become widely used in the last decade. Despite negative results in several clinical trials of cytokine-based angiogenesis, cell based therapy produced effective angiogenesis. This cell-based angiogenesis originates from persistent basic research. The first clinical randomized pilot study was reported in 2002. Up to now, more than 30 clinical studies on the use of mononuclear cells or progenitor cells for the treatment have been published. As the prognosis of the patients with CLI is poor, it has been discussed with respect to their safety and feasibility. With the increasing number of treated patients, the accumulated outcomes from these clinical studies are demonstrating this therapy to be reliable. They reveal indications of the stage of the patients with PAD and the timing of treatments. However, clinical data concerning long time prognosis and a standardized protocol have not been discussed sufficiently. This review summarises data from recent clinical outcomes from 17 studies (11 involving BMMNC that included >10 patients, 6 involving PBMNC that included >10 patients) that are treating patients with PAD by autologous cell transplantation.

  7. A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer

    PubMed Central

    Duvall, Eric; Spoelstra, Nicole; Klump, Vincent; Sznol, Mario; Cooper, Dennis; Spritz, Richard A.; Chang, Joseph T.; Pawelek, John M.

    2013-01-01

    Background Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically. Methods We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes. Results All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event. Conclusions Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome. PMID:23840523

  8. A Depleting Anti-CD45 Monoclonal Antibody as Isolated Conditioning for Bone Marrow Transplantation in the Rat

    PubMed Central

    Jäger, Mark D.; Vondran, Florian W. R.; Ramackers, Wolf; Röseler, Tilmann; Schlitt, Hans J.; Bektas, Hüseyin; Klempnauer, Jürgen; Timrott, Kai

    2016-01-01

    Objective A monoclonal antibody (mAb) against the leukocyte common antigen CD45 (RT7 in rats) could facilitate bone marrow transplantation (BMT). This study in rats evaluates a depletive rat anti-RT7a mAb as isolated tool for BMT conditioning without using irradiation or any chemotherapeutic / immunosuppressive agent. Methods The model used a CD45 di-allelic polymorphism (RT7a/RT7b). The anti-RT7a mAb was intravenously administered to LEW.1W rats (RT1uRT7a) at 5, 10 and 15 mg/kg. 1x108 BM cells of MHC syngeneic (RT1u), MHC disparate (RT1l) or MHC haploidentical (RT1u/l) donors were transplanted. All BM donor strains carried the RT7b allele so that their CD45+ cells were not affected by the anti-RT7a mAb. Recipients were monitored for reconstitution and donor-chimerism in blood leukocytes. Results mAb dosages of 5 or 10 mg/kg were myelosuppressive, whereas 15 mg/kg was myeloablative. Multi-lineage donor-chimerism at day 100 indicated engraftment of MHC syngeneic BM after any used mAb dosage (5 mg/kg: 46+/-7%; 10 mg/kg: 62+/-5%; 15 mg/kg: 80+/-4%). MHC disparate BM resulted in autologous reconstitution after conditioning by 10 mg/kg of the mAb and caused transient chimerism ending up in death associated with aplasia after conditioning by 15 mg/kg of the mAb. MHC haploidentical BM (F1 to parental) engrafted only after conditioning by 15 mg/kg (chimerism at day 100: 78+/-7%). Abandonment of α/β TCR+ cell depletion from BM grafts impaired the engraftment process after conditioning using 15 mg/kg of the mAb in the MHC syngeneic setting (2 of 6 recipients failed to engraft) and the MHC haploidentical setting (3 of 6 recipients failed). Conclusion This depletive anti-RT7a mAb is myelosuppressive and conditions for engraftment of MHC syngeneic BM. The mAb also facilitates engraftment of MHC haploidentical BM, if a myeloablative dose is used. RT7b expressing, BM-seeded α/β TCR+ cells seem to impair the engraftment process after myeloablative mAb conditioning. PMID

  9. Mixed bone marrow or mixed stem cell transplantation for prevention or treatment of lupus-like diseases in mice.

    PubMed

    Good, Robert A; Wang, Bing-Yan; El-Badri, Nagwa S; Steele, Ann; Verjee, Tazim

    2002-01-01

    Scientific analyses fortified by interpretations of immunodeficiency diseases as 'experiments of nature' have revealed the specific immune systems to be comprised of T cells subserving cell-mediated immunities plus B cells and plasma cells which produce and secrete antibodies. These two separate cellular systems regularly interact with each other to produce a coordinated defense which permits mammals to live within a sea of microorganisms that threaten the integrity and the survival of individuals. We have shown that bone marrow transplantation (BMT) can be used as a form of cellular engineering to construct or reconstruct the immune systems and cure otherwise fatal severe combined immunodeficiency. When severe aplastic anemia complicated the first BMT which was performed to cure a fatal severe combined immunodeficiency, a second BMT cured for the first time a complicating severe aplastic anemia. Subsequently, BMT has been used effectively to treat some 75 otherwise fatal diseases such as resistant leukemias, lymphomas, inborn errors of metabolism, and genetic anomalies of the hematopoietic development such as sickle cell anemia, thalassemia, congenital neutropenias, and many other diseases. More recently, we have employed BMT in mice both to cure and cause autoimmunities, and, together, these experiments showed that autoimmunities actually reside in the hematopoietic stem cells. We have also found that mixed BMT or mixed hematopoietic stem cell transplantation (HSCT) can be used to prevent and cure the most complex autoimmunities such as those occurring in BXSB mice and in (NZW x BXSB)F1 W/BF1 mice. Untreated, the former develop fulminating lethal glomerulonephritis plus numerous humoral autoimmunities. Mice of the (W/B)F1 strain develop autoimmune thrombocytopenic purpura, coronary vascular disease with myocardial infarction, glomerulonephritis, and numerous autoantibodies. All of these abnormalities are prevented or cured by mixed syngeneic (autoimmune) plus

  10. Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers

    ClinicalTrials.gov

    2016-08-23

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Alkylating Agent-Related Acute Myeloid Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Post-Transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Richter Syndrome; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  11. Concurrent activation of granulocytes and osteoclasts in busulfan-suppressed bone marrow in response to transplantation of a mammary carcinoma in mice.

    PubMed

    McCracken, C H; Lottsfeldt, J L; Lee, M Y

    1988-05-01

    Transplantation of CE mammary adenocarcinoma (CE maca) into normal mice produces both neutrophilia and hypercalcemia due to osteoclastic bone resorption. In order to explore the physiology of osteoclast formation in vivo, the time course of neutrophilia and osteoclast development was examined in mice that had been pretreated with busulfan prior to the CE maca implantation. Busulfan-treated tumor-bearing mice (BUTUM), busulfan-treated control mice (BUCON), tumor-bearing mice with no busulfan (TUM), and normal controls (CON) were sacrificed on days 4, 7, 11, 14, and 17 after tumor implantation. Leukocyte counts, serum calcium levels, marrow cellularity, and marrow colony-forming units (CFU) were determined. Osteoclasts were quantified histologically by the osteoclast: endosteum ratio (OER). BUCON bone marrow was hypoplastic with CFU remaining significantly lower than that of controls over the course of the experiment. In contrast, BUTUM marrow CFU increased dramatically with the growth of the tumor. The most predominant increase was observed in neutrophilic CFU. Development of hypercalcemia closely paralleled neutrophilia in both TUM and BUTUM mice, although these changes were significantly delayed in the BUTUM group. The neutrophil count and serum calcium levels remained within normal control levels for BUCON mice. The OER correlated with serum calcium, and it closely paralleled the neutrophil count in TUM and BUTUM mice. These results clearly indicated the stimulation of bone marrow neutrophilic granulocyte progenitors and osteoclasts by the CE maca, indicating that the bone marrow is the primary target of this tumor. There may be a closely related mechanism in osteoclast and granulocyte stimulation by one or more CE maca factors. PMID:3360066

  12. Hyperfractionation versus single dose irradiation in human acute lymphocytic leukemia cells: application to TBI for marrow transplantation.

    PubMed

    Shank, B

    1993-04-01

    A major purpose of total body irradiation (TBI) for bone marrow transplantation in leukemia patients is to help eradicate all leukemia cells; the ideal regimen has not yet been determined. To answer basic questions regarding leukemic cell survival kinetics, a human acute lymphoblastic leukemia (ALL) cell line (Reh), with the common ALL antigen (CALLA-positive), has been used to assess in vitro the efficacy of one widely used hyperfractionated TBI (HTBI) regimen versus single dose TBI (SDTBI). The regimen studied in this model was 1.2-1.25 Gy/fraction, 3 fractions/day, 5 h apart each day, for 5 days (11-12 fractions) for a total dose of 13.2-15.0 Gy. It was found that: (i) cell survival was consistent with the linear-quadratic model for early responding tissues (alpha/beta = 7.0 Gy). (ii) The change in shape of the 'effective' cell survival curve for three fractions/day was consistent with the hypothesis that there was complete repair between fractions. (iii) Cell regrowth between fractions was minimal (< or = 5%). (iv) Division delay between fractions (2.9 h/Gy) could explain the small contribution to the survival curve of regrowth between fractions. (v) For a full HTBI course to 15 Gy, cell survival was predicted to be approximately 5 x 10(-5), compared with approximately 10(-3) for a low dose rate (0.04-0.07 Gy/min) SDTBI to 10 Gy; the latter projected from the initial slope of the high dose rate, single dose survival curve. PMID:8327730

  13. Numerical impairment of nestin(+) bone marrow niches in acute GvHD after allogeneic hematopoietic stem cell transplantation for AML.

    PubMed

    Medinger, M; Krenger, W; Jakab, A; Halter, J; Buser, A; Bucher, C; Passweg, J; Tzankov, A

    2015-11-01

    The nestin(+) perivascular bone marrow (BM) stem cell niche (N(+)SCN) may be involved in GvHD. To investigate whether acute GvHD (aGvHD) reduces the number of N(+)SCN, we examined patients with AML who had undergone allogeneic hematopoietic stem cell transplantation. In the test cohort (n=8), the number of N(+)SCN per mm(2) in BM biopsies was significantly reduced in aGvHD patients at the time of aGvHD compared with patients who did not have aGvHD (1.2±0.78 versus 2.6±0.93, P=0.04). In the validation cohort (n=40), the number of N(+)SCN was reduced (1.9±0.99 versus 2.6±0.90 N(+)SCN/mm(2), P=0.05) in aGvHD patients. Receiver operating curves suggested that the cutoff score that best discriminated between patients with and without aGvHD was 2.29 N(+)SCN/mm(2). Applying this cutoff score, 9/11 patients with clinically relevant aGvHD (⩾grade 2) and 13/20 with any type of GvHD had decreased N(+)SCN numbers compared with only 10/29 patients without clinically relevant aGvHD (P=0.007) and 6/20 patients without any type of GvHD (P=0.028). In patients tracked over time, N(+)SCN density returned to normal after aGvHD resolved or remained stable in patients who did not have aGvHD. Our results show a decrease in the number of N(+)SCN in aGvHD.

  14. Bone marrow transplantation in the rat. III. Structure of the liver inflammatory lesion in acute graft-versus-host disease

    SciTech Connect

    Leszczynski, D.; Renkonen, R.; Haeyry, P.

    1985-08-01

    The liver is a major parenchymal target organ of acute graft-versus-host disease (aGVHD) after bone marrow transplantation in the rat. The authors have analyzed the nature of cellular infiltrates in the liver using monoclonal antibodies against white cell subsets and investigated the anatomic distribution of the inflammatory cell subsets inside the liver parenchyma. Several types of white cells are present in a normal control liver: In the portal area the T-helper (Th) cells predominate, (surface) immunoglobulin-expressing B cells are present in ample numbers, and most of the phagocytes are Ia-positive. In the central vein area the T-suppressor/killer cells (Tsk) dominate, no B cells are present, and most of the phagocytes are Ia-negative. During aGVHD the number of T cells increases rapidly in the portal area; and after an initial strong increase, the Th/Tsk ratio decreases but remains still above 1. In the central vein area there is also an increase in the number of T cells, compared with that in the syngeneic recipient, but the Th/Tsk ratio rapidly decreases and remains uniformly below 1. During aGVHD the B cells entirely disappear from the portal area, whereas a small but distinct number of mature plasma cells with intracellular immunoglobulin appear in the central vein area. Following irradiation the Ia-positive phagocytic cells entirely disappear from the portal area and decrease distinctly in number in the central vein area. During aGVHD the number of Ia-positive phagocytes increases again in both locations. In the central vein area the positive phagocytes are seen over the background level, and, concomitantly, the Ia-negative phagocytes disappear.

  15. Prostaglandin E2 Production and T Cell Function in Mouse Adenovirus Type 1 Infection following Allogeneic Bone Marrow Transplantation

    PubMed Central

    McCarthy, Mary K.; Procario, Megan C.; Wilke, Carol A.; Moore, Bethany B.; Weinberg, Jason B.

    2015-01-01

    Adenovirus infections are important complications of bone marrow transplantation (BMT). We demonstrate delayed clearance of mouse adenovirus type 1 (MAV-1) from lungs of mice following allogeneic BMT. Virus-induced prostaglandin E2 (PGE2) production was greater in BMT mice than in untransplanted controls, but BMT using PGE2-deficient donors or recipients failed to improve viral clearance, and treatment of untransplanted mice with the PGE2 analog misoprostol did not affect virus clearance. Lymphocyte recruitment to the lungs was not significantly affected by BMT. Intracellular cytokine staining of lung lymphocytes demonstrated impaired production of INF-γ and granzyme B by cells from BMT mice, and production of IFN-γ, IL-2, IL-4, and IL-17 following ex vivo stimulation was impaired in lymphocytes obtained from lungs of BMT mice. Viral clearance was not delayed in untransplanted INF-γ-deficient mice, suggesting that delayed viral clearance in BMT mice was not a direct consequence of impaired IFN-γ production. However, lung viral loads were higher in untransplanted CD8-deficient mice than in controls, suggesting that delayed MAV-1 clearance in BMT mice is due to defective CD8 T cell function. We did not detect significant induction of IFN-β expression in lungs of BMT mice or untransplanted controls, and viral clearance was not delayed in untransplanted type I IFN-unresponsive mice. We conclude that PGE2 overproduction in BMT mice is not directly responsible for delayed viral clearance. PGE2-independent effects on CD8 T cell function likely contribute to the inability of BMT mice to clear MAV-1 from the lungs. PMID:26407316

  16. Antimycotic therapy with liposomal amphotericin-B for patients undergoing bone marrow or peripheral blood stem cell transplantation.

    PubMed

    Krüger, W; Stockschläder, M; Sobottka, I; Betker, R; De Wit, M; Kröger, N; Grimm, J; Arland, M; Fiedler, W; Erttmann, R; Zander, A R

    1997-02-01

    Suspected deep or systemic mycosis in patients undergoing high-dose therapy and autologous or allogeneic bone marrow transplantation (BMT) requires an immediate systemic antimycotic therapy. Intravenous therapy with the standard drug conventional amphotericin-B is associated with severe adverse effects like nephrotoxicity and chills. Furthermore, BMT patients often receive other potential nephrotoxic drugs such as CsA or virustatics. In this study, we report 74 BMT-patients treated with liposomal amphotericin-B for culture-documented aspergillosis (n = 5) or candidiasis (n = 6), or for serologically (n = 35) or clinically suspected mycosis or as prophylaxis (n = 2). Therapy was initiated with a median dose of 2.8 (0.64-5.09) mg/kg body-weight and continued for 13 (1-55) days. The drug was excellently tolerated and only in one was therapy stopped due to severe chills and fever. Severe organ impairment was not observed under therapy with liposomal amphotericin-B. Creatinine decreased in five patients after an increase under preceding therapy with the conventional formulation. Influence of liposomal amphotericin-B on bilirubin and transaminases was difficult to evaluate due to therapy-related toxicity, veno-occlusive disease (VOD), and graft-versus-host disease (GvHD). 10/11 culture-positive patients died from aspergillosis (5/5) or candidiasis (5/6), but in 9/11 of these subjects the immunity was additionally compromised by GvHD, steroid therapy, and VOD. Liposomal amphotericin-B was effective in preventing relapse of systemic mycosis in 10/12 patients with a history of aspergillosis (n = 11) or candidiasis (n = 1). We conclude, that favourable toxicity of liposomal amphotericin-B should encourage dose escalation studies of liposomal amphotericin-B randomised against the conventional formulation and that the comparison of patients undergoing BMT with patients under standard chemotherapy might be difficult because of additional risk factors of the BMT-patients. PMID

  17. Manhattan transfer: lethal radiation, bone marrow transplantation, and the birth of stem cell biology, ca. 1942-1961.

    PubMed

    Kraft, Alison

    2009-01-01

    This study investigates how, in the late 1940s and 1950s, fears of nuclear accidents and nuclear warfare shaped postwar radiobiology. The new and intense forms of radiation generated by nuclear reactor technology, and which would be released in the event of a nuclear war, created concerns about a public-health hazard unprecedented in form and scale. Fears of inadvertent exposure to acute and potentially lethal radiation launched a search for anti-radiation therapies, out of which emerged the new technique of bone marrow transplantation (BMT). This study analyzes the use of BMT first as a research tool to explore the biological effects of ionizing radiation, and then as an adjunct to radiotherapy for the treatment of cancer. In highlighting how BMT became the province of different research and clinical constituencies, this study develops an understanding of the forces and contingencies that shaped its development. Exploring the emergence of BMT and the uses to which it was put, it reveals that BMT remained a technique in the making -- unstable and far from standardized, even as it became both a widely used research tool and rapidly made its way into the clinic. More broadly, it casts new light on one route through which the Manhattan Project influenced postwar radiobiology; it also affords new insights into one means by which radiobiology came to serve the interests of the Cold War state. In its focus on BMT this paper provides a new perspective on the evolving relationship between radiobiology and biomedicine in the postwar period. PMID:20073126

  18. Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

    PubMed Central

    Hollenbach, Jill A.; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J.; Maiers, Martin

    2015-01-01

    We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals. PMID:26287376

  19. Race, Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics.

    PubMed

    Hollenbach, Jill A; Saperstein, Aliya; Albrecht, Mark; Vierra-Green, Cynthia; Parham, Peter; Norman, Paul J; Maiers, Martin

    2015-01-01

    We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents' information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.

  20. Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection.

    PubMed

    Zhou, X; Loomis-King, H; Gurczynski, S J; Wilke, C A; Konopka, K E; Ptaschinski, C; Coomes, S M; Iwakura, Y; van Dyk, L F; Lukacs, N W; Moore, B B

    2016-05-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  1. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; Van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different perameters involved in the transplantation.

  2. Cross-species bone marrow transplantation: Evidence for tolerance induction, stem cell engraftment, and maturation of T lymphocytes in a xenogeneic stromal environment (rat----mouse)

    SciTech Connect

    Ildstad, S.T.; Wren, S.M.; Boggs, S.S.; Hronakes, M.L.; Vecchini, F.; Van den Brink, M.R. )

    1991-08-01

    Transplantation of untreated F344 rat bone marrow into irradiated B10 mouse recipients (non-TCD F344----B10) to produce fully xenogeneic chimeras resulted in stable xenogeneic lymphoid chimerism, ranging from 82% to 97% rat. Survival of animals was excellent, without evidence for GVH disease. The specificity of tolerance which resulted was highly donor-specific; MHC disparate third party mouse and rat skin grafts were promptly rejected while donor-specific F344 grafts were significantly prolonged (MST greater than 130 days). Multi-lineage rat stem cell-derived progeny including lymphoid cells (T- and B-lymphocytes), myeloid cells, erythrocytes, platelets, and natural killer (NK) cells were present in the fully xenogenic chimeras up to 7 months after bone marrow transplantation. Immature rat T-lymphocytes matured and acquired the {alpha}/{beta} T-cell receptor in the thymus of chimeras in a pattern similar to normal rat controls, suggesting that immature T-lymphocytes of rat origin could interact with the murine xenogeneic thymic stroma to undergo normal maturation and differentiation. This model may be useful to study the mechanisms responsible for the induction and maintenance of donor-specific transplantation tolerance across a species barrier.

  3. Influence of overall treatment time in a fractionated total lymphoid irradiation as an immunosuppressive therapy in allogeneic bone marrow transplantation in mice

    SciTech Connect

    Waer, M.; Ang, K.K.; Vandeputte, M.; van der Schueren, E.

    1982-11-01

    Three groups of C/sub 57//BL/Ka mice received total lymphoid irradiation (TLI) in a total dose of 34 Gy in three different fractionation schedules. In the first group daily fractions of 2 Gy were given during 3 1/2 weeks. In the second group 4 to 5 fractions with 3 1/2 hr interval were given each day, thus delivering 17 fractions in 4 days. In the third group three fractions were given daily for two consecutive days and was repeated two times after 8 or 9 days interval, resulting in a total treatment time of 3 1/2 weeks. The tolerance of all different schedules was excellent. No difference in the peripheral white blood cell and lymphocyte counts nor the degree of immunosuppression as measured by phytohaemaglutinin or concanavalin A induced blastogenesis and mixed lymphocyte reaction were observed at the end of the treatment and up to 200 days. When bone marrow transplantation was performed one day after the end of each schedule, chimerism without signs of graft versus host disease was induced in all the groups. However, from the results in a limited number of animals it seems that concentrated schedules were less effective for chimerism induction. It has been demonstrated that it is possible to reduce drastically the overall treatment time for TLI before bone marrow transplantation. Further investigations are necessary in order to determine the optimal time-dose-fractionation factors and the different parameters involved in the transplantation.

  4. Improved survival of poor prognosis diffuse histiocytic (large cell) lymphoma managed with sequential induction chemotherapy, "boost" radiation therapy, and autologous bone marrow transplantation.

    PubMed

    Chadha, M; Shank, B; Fuks, Z; Clarkson, B D; Bonfiglio, P; Gnecco, C; Gulati, S

    1988-03-01

    From 1981 to 1985, 33 patients with the diagnosis of diffuse histiocytic (large cell) lymphoma (DHL) with a poor prognosis received induction multi-drug chemotherapy followed by autologous marrow cryopreservation. Thirty patients who had residual disease after chemotherapy were given "boost" irradiation to these sites, followed immediately by hyperfractionated total body irradiation, 1320 to 1375 cGy in 11 fractions over 4 days, then cyclophosphamide (60 mg/kg/d) for 2 days. All patients received an autologous bone marrow transplant (ABMT), with 15 patients receiving marrow purged with 4-hydroperoxycyclophosphamide. Patients were transplanted either as part of a planned induction-transplant approach (Group I), or as salvage after relapse on the same induction regimen (Group II), or other conventional chemotherapy regimens (Group III). In the entire group, 16 of 33 patients (48%) are alive free of lymphoma with a median follow-up of 32 months (11 to 53 mo). Actuarial (Kaplan-Meier) survival is 51% at 2 years and 46% at 3 years, with only 1 patient dying after 2 years out of 11 at risk. Eight patients (24%) succumbed to early treatment related complications. Nine patients (27%) died from relapse. Patients receiving ABMT as planned sequential therapy post-induction (Group I) did significantly better than patients given ABMT as salvage therapy after relapse on prior chemotherapy (Groups II and III) and better than the historical group of patients treated with chemotherapy alone. At 2 years, the survival in Group I is 79% versus 0% for Group II versus 48% for Group III. Historically, this group of high risk patients had a 2-year disease-free survival of 20% or less with chemotherapy alone. PMID:3277931

  5. Selective T-cell Ablation with Bismuth-213 Labeled Anti-TCR Alpha Beta as Nonmyeloablative Conditionaing for Allogeneic Canine Marrow Transplantion

    SciTech Connect

    Bethge, W. A.; Wilbur, D. Scott; Storb, R.; Hamlin, Donald K.; Santos, E. B.; Brechbiel, M. W.; Fisher, Darrell R.; Sandmaier, B. M.

    2003-06-15

    Two major immunological barriers, the host versus graft (HVG) and the graft versus host (GVH) reaction, must be overcome for successful allogeneic hematopoietic stem cell transplantation. T-cells are involved in these barriers in the major histocompatibility complex-identical settings. We hypothesized that selective ablation of T-cells using radioimmunotherapy, together with postgrafting immunosuppression, would ensure stable allogeneic engraftment. We developed a canine model of nonmyeloablative marrow transplantation in which host immune reactions are impaired by a single dose of 2 Gy total body irradiation (TBI), and where both GVH and residual HVG reactions are controlled by postgrafting immunosuppression with mycophenolate mofetil (MMF) and cyclosporine (CSP). We substituted the alpha-emitter bismuth-213 linked to a monoclonal antibody against TCR(alpha,beta)using the metal-binding chelate CHX-A”-DTPA, for 2 Gy TBI. Biodistribution studies using a gamma-emitting indium-111-labeled anti-TCR mAb showed uptake primarily in blood, marrow, lymph nodes, spleen and liver. In a dosimetry study, 4 dogs were treated with 0.13-0.46 mg/kg TCR mAb labeled with 3.7-5.6 mCi/kg (137-207 MBq/kg) Bi-213. The treatment was administered in 6 injections on days -3 and -2 followed by transplantion of dog leukocyte antigen-identical marrow on day 0 and postgrafting immunosuppression with MMF and CSP. Therapy was well tolerated except for elevations of transaminases, which were transient in all but one dog. No other organ toxicities or signs of graft-versus-host-disease were noted. The dogs had prompt allogeneic hematopoietic engraftment and achieved stable mixed donor-host hematopoietic chimerism with donor contributions ranging from 5-55 % with >30 weeks follow up.

  6. Multi-Institutional Study of Post-Transplantation Cyclophosphamide As Single-Agent Graft-Versus-Host Disease Prophylaxis After Allogeneic Bone Marrow Transplantation Using Myeloablative Busulfan and Fludarabine Conditioning

    PubMed Central

    Kanakry, Christopher G.; O'Donnell, Paul V.; Furlong, Terry; de Lima, Marcos J.; Wei, Wei; Medeot, Marta; Mielcarek, Marco; Champlin, Richard E.; Jones, Richard J.; Thall, Peter F.; Andersson, Borje S.; Luznik, Leo

    2014-01-01

    Purpose The clinical safety and efficacy of intravenous busulfan and fludarabine (IV Bu/Flu) myeloablative conditioning as well as graft-versus-host disease (GVHD) prophylaxis with high-dose, post-transplantation cyclophosphamide (PTCy) have been demonstrated independently in several single-institutional studies. We hypothesized that combining these two promising approaches in a multi-institutional study of human leukocyte antigen (HLA) -matched bone marrow transplantation would provide low rates of severe acute and chronic GVHD, low toxicity, and effective disease control. Patients and Methods Ninety-two adult patients (median age, 49 years; range, 21 to 65 years) with high-risk hematologic malignancies were enrolled at three centers (clinical trial No. NCT00809276). Forty-five patients received related allografts, and 47 received unrelated allografts. GVHD prophylaxis was solely with PTCy at 50 mg/kg/day on post-transplantation days +3 and +4. Results The cumulative incidences of grades 2 to 4 acute, grades 3 to 4 acute, and chronic GVHD were 51%, 15%, and 14%, respectively. Nonrelapse mortality (NRM) at 100 days and 1 year were 9% and 16%, respectively. With a median follow-up period of 2.2 years, the 2-year disease-free survival (DFS) and overall survival (OS) rates were 62% and 67%, respectively. Donor relatedness did not affect NRM, DFS, or OS. Patients in complete remission (CR) without evidence of minimal residual disease (MRD) had markedly better DFS (80%) and OS (80%) than patients in CR with MRD or with active disease at the time of transplantation (DFS, P = .0005; OS, P = .019). Conclusion This multi-institutional study demonstrates that PTCy can be safely and effectively combined with IV Bu/Flu myeloablative conditioning and confirms PTCy's efficacy as single-agent, short-course GVHD prophylaxis for both acute and chronic GVHD after bone marrow transplantation from HLA-matched donors. PMID:25267759

  7. Fecal microbiota transplantation and bacterial consortium transplantation have comparable effects on the re-establishment of mucosal barrier function in mice with intestinal dysbiosis

    PubMed Central

    Li, Ming; Liang, Pin; Li, Zhenzhen; Wang, Ying; Zhang, Guobin; Gao, Hongwei; Wen, Shu; Tang, Li

    2015-01-01

    Fecal microbiota transplantation (FMT) is a promising therapy, despite some reports of adverse side effects. Bacterial consortia transplantation (BCT) for targeted restoration of the intestinal ecosystem is considered a relatively safe and simple procedure. However, no systematic research has assessed the effects of FMT and BCT on immune responses of intestinal mucosal barrier in patients. We conducted complementary studies in animal models on the effects of FMT and BCT, and provide recommendations for improving the clinical outcomes of these treatments. To establish the dysbiosis model, male BALB/c mice were treated with ceftriaxone intra-gastrically for 7 days. After that, FMT and BCT were performed on ceftriaxone-treated mice for 3 consecutive days to rebuild the intestinal ecosystem. Post-FMT and post-BCT changes of the intestinal microbial community and mucosal barrier functions were investigated and compared. Disruption of intestinal microbial homeostasis impacted the integrity of mucosal epithelial layer, resulting in increased intestinal permeability. These outcomes were accompanied by overexpression of Muc2, significant decrease of SIgA secretion, and overproduction of defensins and inflammatory cytokines. After FMT and BCT, the intestinal microbiota recovered quickly, this was associated with better reconstruction of mucosal barriers and re-establishment of immune networks compared with spontaneous recovery (SR). Although based on a short-term study, our results suggest that FMT and BCT promote the re-establishment of intestinal microbial communities in mice with antibiotic-induced dysbiosis, and contribute to the temporal and spatial interactions between microbiota and mucosal barriers. The effects of BCT are comparable to that of FMT, especially in normalizing the intestinal levels of Muc2, SIgA, and defensins. PMID:26217323

  8. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives—a position statement from the European Society for Blood and Marrow Transplantation (EBMT)

    PubMed Central

    Mohty, M; Malard, F; Abecassis, M; Aerts, E; Alaskar, A S; Aljurf, M; Arat, M; Bader, P; Baron, F; Bazarbachi, A; Blaise, D; Ciceri, F; Corbacioglu, S; Dalle, J-H; Duarte, R F; Fukuda, T; Huynh, A; Masszi, T; Michallet, M; Nagler, A; NiChonghaile, M; Pagluica, T; Peters, C; Petersen, F B; Richardson, P G; Ruutu, T; Savani, B N; Wallhult, E; Yakoub-Agha, I; Carreras, E

    2015-01-01

    Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children. PMID:25798682

  9. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation.

    PubMed

    Mohty, M; Malard, F; Abecassis, M; Aerts, E; Alaskar, A S; Aljurf, M; Arat, M; Bader, P; Baron, F; Bazarbachi, A; Blaise, D; Ciceri, F; Corbacioglu, S; Dalle, J-H; Dignan, F; Fukuda, T; Huynh, A; Masszi, T; Michallet, M; Nagler, A; NiChonghaile, M; Okamoto, S; Pagliuca, A; Peters, C; Petersen, F B; Richardson, P G; Ruutu, T; Savani, B N; Wallhult, E; Yakoub-Agha, I; Duarte, R F; Carreras, E

    2016-07-01

    Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation. PMID:27183098

  10. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation

    PubMed Central

    Mohty, M; Malard, F; Abecassis, M; Aerts, E; Alaskar, A S; Aljurf, M; Arat, M; Bader, P; Baron, F; Bazarbachi, A; Blaise, D; Ciceri, F; Corbacioglu, S; Dalle, J-H; Dignan, F; Fukuda, T; Huynh, A; Masszi, T; Michallet, M; Nagler, A; NiChonghaile, M; Okamoto, S; Pagliuca, A; Peters, C; Petersen, F B; Richardson, P G; Ruutu, T; Savani, B N; Wallhult, E; Yakoub-Agha, I; Duarte, R F; Carreras, E

    2016-01-01

    Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation. PMID:27183098

  11. The human leucocyte antigen-G 14-basepair polymorphism correlates with graft-versus-host disease in unrelated bone marrow transplantation for thalassaemia.

    PubMed

    La Nasa, Giorgio; Littera, Roberto; Locatelli, Franco; Lai, Sara; Alba, Francesco; Caocci, Giovanni; Lisini, Daniela; Nesci, Sonia; Vacca, Adriana; Piras, Eugenia; Bernardo, Maria Ester; Di Cesare-Merlone, Alessandra; Orrù, Sandro; Carcassi, Carlo

    2007-10-01

    The presence of the 14-bp insertion polymorphism of the human leucocyte antigen (HLA)-G gene (HLA-G) promotes immune tolerance through increased synthesis of HLA-G molecules. We investigated this polymorphism in a large cohort of 53 thalassaemia patients transplanted from an unrelated donor. Sixteen patients (30.2%) homozygous for the 14-bp deletion had a higher risk of developing acute graft-versus-host disease (aGvHD) than patients homozygous for the 14-bp insertion (-14-bp/-14-bp vs +14-bp/+14-bp: Relative Risk = 15.0; 95% confidence interval 1.59-141.24; P = 0.008). Therefore, the 14-bp polymorphism could be an important predictive factor for aGvHD following bone marrow transplantation. PMID:17897304

  12. Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice

    PubMed Central

    Gibson, Brian W; Boles, Nathan C; Souroullas, George P; Herron, Alan J; Fraley, Joe K; Schwiebert, Rebecca S; Sharp, John J; Goodell, Margaret A

    2015-01-01

    Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with γ irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a 137Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal-dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a 137Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the 137Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the 137Cs source was associated with lower overall morbidity due to opportunistic infection. PMID:26141441

  13. Comparison of Cesium-137 and X-ray Irradiators by Using Bone Marrow Transplant Reconstitution in C57BL/6J Mice.

    PubMed

    Gibson, Brian W; Boles, Nathan C; Souroullas, George P; Herron, Alan J; Fraley, Joe K; Schwiebert, Rebecca S; Sharp, John J; Goodell, Margaret A

    2015-06-01

    Mice are used extensively in transplantation studies involving bone marrow ablation. Due to the increasing security issues and expenses involved with γ irradiators, self-contained X-ray irradiators have been increasing in popularity. We hypothesized that bone marrow ablation by irradiation of mice with a (137)Cs irradiator would be comparable to that from an X-ray source irradiator. A lethal-dose curve was obtained by irradiating C57BL/6J mice with 500, 700, 900, and 1100 cGy from either source. These data were used to determine the lethal radiation exposure range for a noncompetitive bone marrow engraftment curve for each source. At 90 d after reconstitution, the bone marrow engraftment curves revealed significant differences between the 2 sources in the establishment of B cell, myeloid, and T cell lineages. Murine B cell reconstitution after exposure to a (137)Cs source was greater than that after X-ray exposure at each dose level, whereas the converse was true for myeloid cell reconstitution. At the 1050- and 1100-cGy doses, mice irradiated by using the X-ray source demonstrated higher levels of T cell reconstitution but decreased survival compared with mice irradiated with the (137)Cs source. We concluded that although both sources ablated endogenous bone marrow sufficiently to enable stem cell engraftment, there are distinct physiologic responses that should be considered when choosing the optimal source for use in a study and that irradiation from the (137)Cs source was associated with lower overall morbidity due to opportunistic infection. PMID:26141441

  14. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection.

    PubMed

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

  15. The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

    PubMed Central

    Buzoianu-Anguiano, Vinnitsa; Orozco-Suárez, Sandra; García-Vences, Elisa; Caballero-Chacón, Sara; Guizar-Sahagún, Gabriel; Chavez-Sanchez, Luis; Grijalva, Israel

    2015-01-01

    Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model. PMID:26634157

  16. Subclinical pulmonary function defects following autologous and allogeneic bone marrow transplantation: relationship to total body irradiation and graft-versus-host disease

    SciTech Connect

    Tait, R.C.; Burnett, A.K.; Robertson, A.G.; McNee, S.; Riyami, B.M.; Carter, R.; Stevenson, R.D. )

    1991-06-01

    Pulmonary function results pre- and post-transplant, to a maximum of 4 years, were analyzed in 98 patients with haematological disorders undergoing allogeneic (N = 53) or autologous bone marrow transplantation (N = 45) between 1982 and 1988. All received similar total body irradiation based regimens ranging from 9.5 Gy as a single fraction to 14.4 Gy fractionated. FEV1/FVC as a measure of airway obstruction showed little deterioration except in patients experiencing graft-versus-host disease in whom statistically significant obstructive ventilatory defects were evident by 6 months post-transplant (p less than 0.01). These defects appeared to be permanent. Restrictive ventilatory defects, as measured by reduction in TLC, and defects in diffusing capacity (DLCO and KCO) were also maximal at 6 months post-transplant (p less than 0.01). Both were related, at least in part, to the presence of GVHD (p less than 0.01) or use of single fraction TBI with absorbed lung dose of 8.0 Gy (p less than 0.05). Fractionated TBI resulted in less marked restricted ventilation and impaired gas exchange, which reverted to normal by 2 years, even when the lung dose was increased from 11.0 Gy to between 12.0 and 13.5 Gy. After exclusion of patients with GVHD (30% allografts) there was no significant difference in pulmonary function abnormalities between autograft and allograft recipients.

  17. Ultrasound imaging as the basis of a clinical diagnosis of systemic bartonellosis in a patient after bone marrow transplantation. A case report

    PubMed Central

    Goździk, Jolanta; Woźniak, Magdalena; Czogała, Wojciech

    2016-01-01

    Infections in immunocompromised patients after hematopoietic stem cell transplantation can have a severe and atypical course. Some opportunistic pathogens are difficult to detect in microbiological tests, and that is why treatment success depends on an accurate clinical diagnosis. This article presents a case of a 7-year-old girl with severe aplastic anemia treated with bone marrow transplantation with post-transplantation period complicated by persistent, hectic fever, with peak episodes of 39–40°C, lasting several weeks. Repeated microbiological tests failed to reveal the etiological agent, and empirical anti-infective treatment was ineffective. In the fourth week of fever, imaging showed multiple foci resembling abscesses in the patient's internal organs and, subsequently, in soft tissues. The characteristics of these changes and data concerning environmental exposure led to the clinical diagnosis of cat scratch disease (bartonellosis) with multi-organ involvement and enabled the targeted treatment to be implemented. Fever subsided and organ lesions regressed. In this case, repeated ultrasound imaging was the basic diagnostic tool that helped arrive at a correct diagnosis and implement effective treatment of this life-threatening complication after hematopoietic stem cell transplantation. PMID:27446604

  18. Long-term effects of allogeneic bone marrow transplantation (BMT) on pituitary, gonad, thyroid and adrenal function in adults.

    PubMed

    Kauppila, M; Koskinen, P; Irjala, K; Remes, K; Viikari, J

    1998-08-01

    To evaluate the late-effects of allogeneic bone marrow transplantation (BMT) on endocrine function 20 adults (10 females, 10 males) with hematological malignancies were studied after a mean of 3.2 years (range 1.0-10.0) following BMT. The mean age of patients at the time of BMT was 39 years. Dynamic tests of the hypothalamic-pituitary axis included growth hormone releasing hormone (GHRH), gonadotropin releasing hormone (GnRH) and thyrotropin releasing hormone (TRH) stimulations with measurements of serum growth hormone (GH), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyrotropin (TSH) and prolactin (PRL) responses. Adrenal function was assessed with the adrenocorticotropin (ACTH) test. Five patients (25%) had a subnormal GH response to GHRH stimulation, but all had a normal serum insulin-like growth factor I (IGF-I) value. There was an inverse nonlinear relationship between the body mass index (BMI; kg/m2) and GH response but no relation between the GH response and total body irradiation (TBI), intrathecal treatment or occurrence of graft-versus-host disease. In females, serum FSH and LH basal levels and responses to GnRH, in spite of oestrogen substitution therapy in 9/10 patients, indicated ovarian failure and early menopause. Most responses to GnRH were delayed. All males had elevated serum basal FSH levels indicating damage in seminiferous tubulus and infertility. Serum basal LH was elevated only in four males but testosterone values were all within normal limits. However, the mean free androgen index (FAI) was in the low normal range, and two subjects had abnormally low FAI. Serum free thyroxine (fT4) levels were normal in all but one, but an exaggerated TSH response to TRH occurred in seven patients (35%). Four of them had received TBI and one total nodal irradiation suggesting radiation-induced damage to the thyroid gland. In 19 of the 20 patients, adrenal function judged with ACTH test was normal. We conclude that functional impairments

  19. Bone marrow transplantation across major histocompatibility barriers in mice: II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    SciTech Connect

    Vallera, D.A.; Soderling, C.C.B.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatability barriers.Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then given to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 100-rad TLI. In TLI plus CY-conditioned recipients, it was also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for these findings are discussed. (JMT)

  20. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.

    PubMed

    Imahashi, Nobuhiko; Ohashi, Haruhiko; Terakura, Seitaro; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Sawa, Masashi; Yokohata, Emi; Kurahashi, Shingo; Ozawa, Yukiyasu; Nishida, Tetsuya; Kiyoi, Hitoshi; Watamoto, Koichi; Kohno, Akio; Kasai, Masanobu; Kato, Chiaki; Iida, Hiroatsu; Naoe, Tomoki; Miyamura, Koichi; Murata, Makoto

    2015-07-01

    Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen. PMID:25680895

  1. Chimerism status after unrelated donor bone marrow transplantation with fludarabine-melphalan conditioning is affected by the melphalan dose and is predictive of relapse.

    PubMed

    Imahashi, Nobuhiko; Ohashi, Haruhiko; Terakura, Seitaro; Miyao, Kotaro; Sakemura, Reona; Kato, Tomonori; Sawa, Masashi; Yokohata, Emi; Kurahashi, Shingo; Ozawa, Yukiyasu; Nishida, Tetsuya; Kiyoi, Hitoshi; Watamoto, Koichi; Kohno, Akio; Kasai, Masanobu; Kato, Chiaki; Iida, Hiroatsu; Naoe, Tomoki; Miyamura, Koichi; Murata, Makoto

    2015-07-01

    Little is known regarding the chimerism status after reduced-intensity conditioning transplantation when bone marrow is used as a stem cell source. We prospectively analyzed lineage-specific chimerism and retrospectively evaluated clinical outcomes in 80 adult patients who underwent unrelated donor bone marrow transplantation (URBMT) with fludarabine plus melphalan (FM) as the conditioning regimen. Mixed donor chimerism (MDC) was seen in 43 and 10 % of patients at days 14 and 28, respectively. Melphalan at ≤130 mg/m(2) was associated with an increased incidence of MDC at day 28 (P = 0.03). Patients with MDC at day 14 showed a marginally increased risk of primary graft failure and a marginally decreased risk of graft-versus-host disease. In multivariate analysis, MDC at day 14 was associated with higher overall mortality (hazard ratio (HR) = 2.1; 95 % confidence interval (CI), 1.1-4.2; P = 0.04) and relapse rate (HR = 3.0; 95 % CI, 1.2-7.5; P = 0.02), but not with non-relapse mortality (HR = 1.8; 95 % CI, 0.70-4.6; P = 0.23). Thus, the FM regimen yields prompt complete donor chimerism after URBMT, but the melphalan dose significantly impacts the kinetics of chimerism. Chimerism status evaluation at day 14 may be instrumental in predicting relapse after URBMT with the FM regimen.

  2. Effect of donor chimerism to reduce the level of glycosaminoglycans following bone marrow transplantation in a murine model of mucopolysaccharidosis type II.

    PubMed

    Yokoi, Kentaro; Akiyama, Kazumasa; Kaneshiro, Eiko; Higuchi, Takashi; Shimada, Yohta; Kobayashi, Hiroshi; Akiyama, Masaharu; Otsu, Makoto; Nakauchi, Hiromitsu; Ohashi, Toya; Ida, Hiroyuki

    2015-03-01

    Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficient activity of the iduronate-2-sulfatase. This leads to accumulation of glycosaminoglycans (GAGs) in the lysosomes of various cells. Although it has been proposed that bone marrow transplantation (BMT) may have a beneficial effect for patients with MPS II, the requirement for donor-cell chimerism to reduce GAG levels is unknown. To address this issue, we transplanted various ratios of normal and MPS II bone marrow cells in a mouse model of MPS II and analyzed GAG accumulation in various tissues. Chimerism of whole leukocytes and each lineage of BMT recipients' peripheral blood was similar to infusion ratios. GAGs were significantly reduced in the liver, spleen, and heart of recipients. The level of GAG reduction in these tissues depends on the percentage of normal-cell chimerism. In contrast to these tissues, a reduction in GAGs was not observed in the kidney and brain, even if 100 % donor chimerism was achieved. These observations suggest that a high degree of chimerism is necessary to achieve the maximum effect of BMT, and donor lymphocyte infusion or enzyme replacement therapy might be considered options in cases of low-level chimerism in MPS II patients.

  3. Function of von Willebrand factor after crossed bone marrow transplantation between normal and von Willebrand disease pigs: effect on arterial thrombosis in chimeras.

    PubMed Central

    Nichols, T C; Samama, C M; Bellinger, D A; Roussi, J; Reddick, R L; Bonneau, M; Read, M S; Bailliart, O; Koch, G G; Vaiman, M

    1995-01-01

    von Willebrand factor (vWF) is essential for the induction of occlusive thrombosis in stenosed and injured pig arteries and for normal hemostasis. To separate the relative contribution of plasma and platelet vWF to arterial thrombosis, we produced chimeric normal and von Willebrand disease pigs by crossed bone marrow transplantation; von Willebrand disease (vWD) pigs were engrafted with normal pig bone marrow and normal pigs were engrafted with vWD bone marrow. Thrombosis developed in the chimeric normal pigs that showed normal levels of plasma vWF and an absence of platelet vWF; but no thrombosis occurred in the chimeric vWD pigs that demonstrated normal platelet vWF and an absence of plasma vWF. The ear bleeding times of the chimeric pigs were partially corrected by endogenous plasma vWF but not by platelet vWF. Our animal model demonstrated that vWF in the plasma compartment is essential for the development of arterial thrombosis and that it also contributes to the maintenance of bleeding time and hemostasis. Images Fig. 2 Fig. 3 PMID:7708664

  4. Persistence of T8+/HNK-1+ suppressor lymphocytes in the blood of long-term surviving patients after allogeneic bone marrow transplantation.

    PubMed

    Leroy, E; Calvo, C F; Divine, M; Gourdin, M F; Baujean, F; Ben Aribia, M H; Mishal, Z; Vernant, J P; Farcet, J P; Senik, A

    1986-10-01

    Fifteen patients and their respective bone marrow donors were entered in this study 1 to 5 yr after allogeneic bone marrow transplantation. Peripheral blood E rosetting (T) cells were analyzed for their phenotypic characteristics as well as for their ability to regulate Ig synthesis in the in vitro PWM system. A close relationship was found between a high proportion of T8+/HNK-1+ cells and/or T8+/HLA-DR+ cells and a strong (greater than or equal to 50%) inhibition of the antibody response. It was noteworthy that even the patients without suppressor activity had high proportions of such cells when compared with normal marrow donors. Moreover, the suppression occurred irrespective of the presence or absence of chronic GVHD. Through negative selection experiments (with MAb and complement) and through immunofluorescence cell sorting, it was shown that the suppressor cells expressed the T8+, HNK-1+, HLA-DR- phenotype. They did not carry the Leu-11, NKH1A, or NKH2 determinants, which are expressed on mature functional NK cells. When examined by electron microscopy, they exhibited a morphology of resting agranular lymphocytes. The significant increase of these suppressor cells among the BMT patients was not correlated with clinical syndromes such as chronic GVHD or opportunistic viral infections, which argues against the notion of in vivo profound immunodeficiency coexisting with these cells. PMID:2944951

  5. A study of thiotepa, etoposide and fractionated total body irradiation as a preparative regimen prior to bone marrow transplantation for poor prognosis patients with neuroblastoma.

    PubMed

    Kamani, N; August, C S; Bunin, N; Leahey, A; Bayever, E; Goldwein, J; Zusman, J; Evans, A E; Angio, G D

    1996-06-01

    We report the toxicity and efficacy of a new conditioning regimen for bone marrow transplantation (BMT) in children with poor prognosis neuroblastoma (NBL). Twenty-seven patients with poor prognosis NBL were treated with teniposide (360 mg/m2) or etoposide (500 mg/m2), thiotepa (600-900 mg/m2), and 1200 cGy fractionated total body irradiation (fTBI) followed by autologous marrow rescue (n = 19) or allogeneic BMT from HLA-identical siblings (n = 8). The two patients who received teniposide, 600 mg/m2 thiotepa and fTBI had minimal toxicity but relapsed 4 and 12 months post-auto BMT. The next two patients received 750 mg/m2 thiotepa, 500 mg/m2 etoposide and TBI. They tolerated the conditioning regimen well and are alive and in remission 77 and 75 months post-BMT. At the next thiotepa dose level (900 mg/m2), the first two allograft recipients both experienced fatal regimen-related toxicity. All subsequent allograft recipients received 750 mg/m2 thiotepa and autograft recipients received 900 mg/m2 thiotepa. As of 1 April 1995, eight of the 19 patients who received autologous marrow are surviving disease-free 21 to 77 months post-BMT. Nine autograft recipients relapsed at 2 to 37 months following transplantation. One patient died of hepatic veno-occlusive disease 2 months after auto BMT, and one of pneumonia 6 months post-transplantation. Three allograft recipients have relapsed at 6, 10 and 39 months post-transplant and three are alive and in remission 75, 53 and 27 months post-BMT. Overall, 11/27 patients (41%) are alive and in remission 21-77 months (median 47 months) following BMT. A conditioning regimen consisting of 500 mg/m2 etoposide, thiotepa (750 mg/m2 for allograft recipients and 900 mg/m2 for autograft recipients) and 1200 cGy fTBI has acceptable toxicity and is at least as effective as melphalan-containing regimens in the treatment of high-risk NBL.

  6. Bone marrow transplantation across major histocompatibility barriers in mice. II. T cell requirement for engraftment in total lymphoid irradiation-conditioned recipients

    SciTech Connect

    Vallera, D.A.; Soderling, C.C.; Carlson, G.J.; Kersey, J.H.

    1982-03-01

    Studies were undertaken to examine the role of T lymphocytes in engraftment of bone marrow (BM) in animals conditioned with total lymphoid irradiation (TLI) prior to transplantation across major histocompatibility barriers. Donor BM (added as a source of lymphohematopoietic stem cells) and spleen cells (added as a source of graft-versus-host disease (GVHD)-causing cells) were pretreated in vitro with monoclonal anti-Thy-1.2 plus complement (C). T cell-depleted grafts were then give to allogeneic mice conditioned with 900 rad of single dose TLI plus cyclophosphamide (CY). These mice did not engraft. Even in the absence of added spleen cells, elimination of the small T cell population from donor BM grafts prevented engraftment compared with animals that received the same conditioning regimen and untreated donor cells. These control animals demonstrated uniform evidence of engraftment about 1 month after transplantation. Similar findings were reported when recipients were conditioned with fractionated 17 x 200-rad TLI. In TLI plus CY-conditional recipients, we have also observed that increasing the donation of treated bone marrow cells still did not result in significant engraftment. Furthermore, graft failure in mice receiving normal dosages of anti-Thy-1.2 plus C-treated donor cells was not a strain-restricted phenomenon. Moreover, removal of bone marrow T cells with monoclonal anti-Lyt-1 plus complement also resulted in graft failure in TLI-conditioned recipients. In contrast to TLI conditioning, when Thy-1.2 plus C-treated donor cells were given to recipients conditioned with total body irradiation (TBI), a high percentage of engraftment was demonstrated by an H-2 microcytotoxicity assay. Plausible mechanisms for there findings are discussed.

  7. Bone marrow transplantation across major histocompatability barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants

    SciTech Connect

    Vellera, D.A.; Soderling, C.C.B.; Kersey, J.H.

    1982-02-01

    We studied the effect of eliminating T cells from donor grafts of mice in a system in which bone marrow was transplanted across major histocompatibility barriers. BALB/c bone marrow (added as a source of hematopoietic stem cells) combined with equal volumes of spleen cells (added as a source of GVHD-promoting cells) was pretreated in vitro with monoclonal anti-Lyt-1.2 or Lyt-2.2 plus absorbed rabbit complement before injection into C57BL/6 total-body-irradiated recipients. Functional activity of anti-Lyt monoclonal antibodies was determined in CML assay. Treatment with anti Lyt-1.2 plus C did not have any anti-stem cell activity, as measured by CFU-S assay, and protected recipients from the onset of lethal GVHD. Treatment with Lyt-2.2 plus C also did not reduce CFU-S; however, mice receiving treated marrow did develop GVHD and were all dead by 2 mo, as were untreated control mice. Surviving ''anti-Lyt-1.2 + C chimeras'' demonstrated a high percentage of donor mononuclear cells in their peripheral blood. Similar results were obtained when C3H/HeN donor BMS was treated with monoclonal anti-Lyt-1.1 plus C and injected into C57BL/6 recipients. These findings show that monoclonal antibodies directed against determinants unrelated to Thy-1 can eliminate T cells in the presence of C and successfully protect transplanted mice from lethal GVHD. They also suggest that these anti-lyt antibodies may be useful tools in determining subpopulations of T cells that contribute to the development of GVHD.

  8. CD154 blockade and donor-specific transfusions in DLA-identical marrow transplantation in dogs conditioned with 1-Gy total body irradiation.

    PubMed

    Jochum, Christoph; Beste, Mechthild; Zellmer, Eustacia; Graves, Scott S; Storb, Rainer

    2007-02-01

    Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose (2 Gy) of total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from dog leukocyte antigen (DLA)-identical littermates (hematopoietic cell transplantation [HCT]). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we investigated whether stable engraftment after 1-Gy TBI could be accomplished by reducing host-versus-donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMCs). We found that the anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked alloimmune responses in vitro. Based on pharmacokinetic studies, 6 dogs received a single intravenous injection of 5 mg/kg anti-CD154 antibody (on day -5), followed 1 day later by donor PBMCs. On day 0, the dogs were given 1 Gy of TBI and underwent DLA-identical marrow grafts. Postgraft immunosuppression consisted of MMF and CSP. All 6 dogs demonstrated initial engraftment; 3 dogs sustained the engraftment for >26 weeks, whereas 3 dogs rejected their grafts, after 9, 22, and 24 weeks, and survived with autologous recovery. Graft survival was significantly improved over that in 11 historical controls conditioned with 1-Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = .03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1-Gy TBI. PMID:17241922

  9. Co- transplantation of Bone Marrow Stromal Cells with Schwann Cells Evokes Mechanical Allodynia in the Contusion Model of Spinal Cord Injury in Rats

    PubMed Central

    Pourheydar, Bagher; Joghataei, Mohammad Taghi; Bakhtiari, Mehrdad; Mehdizadeh, Mehdi; Yekta, Zahra; Najafzadeh, Norooz

    2012-01-01

    Objective: Several studies have shown that, although transplantation of neural stem cells into the contusion model of spinal cord injury (SCI) promotes locomotor function and improves functional recovery, it induces a painful response, Allodynia. Different studies indicate that bone marrow stromal cells (BMSCs) and Schwann cells (SCs) can improve locomotor recovery when transplanted into the injured rat spinal cord. Since these cells are commonly used in cell therapy, we investigated whether co-transplantation of these cells leads to the development of Allodynia. Materials and Methods: In this experimental research, the contusion model of SCI was induced by laminectomy at the T8-T9 level of the spinal cord in adult female wistar rats (n=40) weighting (250-300g) using the New York University Device. BMSCs and SCs were cultured and prelabeled with 5-bromo-2-deoxyuridine (BrdU) and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) respectively. The rats were divided into five groups of 8 including: a control group (laminectomy only), three experimental groups (BMSC, SC and Co-transplant) and a sham group. The experimental groups received BMSCs, SCs, and BMSCs and SCs respectively by intraspinal injection 7 days after injury and the sham group received serum only. Locomotion was assessed using Basso, Beattie and Bresnahan (BBB) test and Allodynia by the withdrawal threshold test using Von Frey Filaments at 1, 7, 14, 21, 28, 35, 42, 49 and 56 days after SCI. The statistical comparisons between groups were carried out by using repeated measures analysis of variances (ANOVA). Results: Significant differences were observed in BBB scores in the Co- transplant group compared to the BMSC and SC groups (p< 0.05). There were also significant differences in the withdrawal threshold means between animals in the sham group and the BMSC, SC and the Co-transplant groups (p<0.05).BBB scores and withdrawal threshold means showed that co-transplation improved

  10. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    PubMed

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis. PMID:26763584

  11. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    PubMed

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

  12. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    PubMed

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT. PMID:26910296

  13. Autologous bone marrow stromal cell transplantation as a treatment for acute radiation enteritis induced by a moderate dose of radiation in dogs.

    PubMed

    Xu, Wenda; Chen, Jiang; Liu, Xu; Li, Hongyu; Qi, Xingshun; Guo, Xiaozhong

    2016-05-01

    Radiation enteritis is one of the most common complications of cancer radiotherapy, and the development of new and effective measures for its prevention and treatment is of great importance. Adult bone marrow stromal stem cells (ABMSCs) are capable of self-renewal and exhibit low immunogenicity. In this study, we investigated ABMSC transplantation as a treatment for acute radiation enteritis. We developed a dog model of acute radiation enteritis using abdominal intensity-modulated radiation therapy in a single X-ray dose of 14 Gy. ABMSCs were cultured in vitro, identified via immunofluorescence and flow cytometry, and double labeled with CM-Dil and superparamagnetic iron oxide (SPIO) before transplantation, which took place 48 hours after abdominal irradiation in a single fraction. The dog model of acute radiation enteritis was transplanted with cultured ABMSCs labeled with CM-Dil and SPIO into the mesenteric artery through the femoral artery. Compared with untreated control groups, dogs treated with ABMSCs exhibited substantially longer survival time and improved relief of clinical symptoms. ABMSC transplantation induced the regeneration of the intestinal epithelium and the recovery of intestinal function. Furthermore, ABMSC transplantation resulted in elevated serum levels of the anti-inflammatory cytokine interleukin-11 (IL10) and intestinal radioprotective factors, such as keratinocyte growth factor, basic fibroblast growth factor-2, and platelet-derived growth factor-B while reducing the serum level of the inflammatory cytokine IL17. ABMSCs induced the regeneration of the intestinal epithelium and regulated the secretion of serum cytokines and the expression of radioprotective proteins and thus could be beneficial in the development of novel and effective mitigators of and protectors against acute radiation enteritis.

  14. Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions.

    PubMed

    Kumar, Rajat; Kimura, Fumihiko; Ahn, Kwang Woo; Hu, Zhen-Huan; Kuwatsuka, Yachiyo; Klein, John P; Pasquini, Marcelo; Miyamura, Koichi; Kato, Koji; Yoshimi, Ayami; Inamoto, Yoshihiro; Ichinohe, Tatsuo; Wood, William Allen; Wirk, Baldeep; Seftel, Matthew; Rowlings, Philip; Marks, David I; Schultz, Kirk R; Gupta, Vikas; Dedeken, Laurence; George, Biju; Cahn, Jean-Yves; Szer, Jeff; Lee, Jong Wook; Ho, Aloysius Y L; Fasth, Anders; Hahn, Theresa; Khera, Nandita; Dalal, Jignesh; Bonfim, Carmem; Aljurf, Mahmoud; Atsuta, Yoshiko; Saber, Wael

    2016-05-01

    Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States-Canada (n = 486) and other HIC (n = 1264); upper middle income (UMIC) (n = 482); and combined lower-middle, low-income countries (LM-LIC) (n = 142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC (P < .001). There was no significant difference in OS between BM and PBSCs in UMIC (P = .32) or LM-LIC (P = .23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P = .002). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications. PMID:26797402

  15. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  16. Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: Evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery

    SciTech Connect

    Tiberghien, P.; Longo, D.L.; Wine, J.W.; Alvord, W.G.; Reynolds, C.W. )

    1990-10-01

    Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery.

  17. European Group for Blood and Marrow Transplantation Centers with FACT-JACIE Accreditation Have Significantly Better Compliance with Related Donor Care Standards.

    PubMed

    Anthias, Chloe; O'Donnell, Paul V; Kiefer, Deidre M; Yared, Jean; Norkin, Maxim; Anderlini, Paolo; Savani, Bipin N; Diaz, Miguel A; Bitan, Menachem; Halter, Joerg P; Logan, Brent R; Switzer, Galen E; Pulsipher, Michael A; Confer, Dennis L; Shaw, Bronwen E

    2016-03-01

    Previous studies have identified healthcare practices that may place undue pressure on related donors (RDs) of hematopoietic cell products and an increase in serious adverse events associated with morbidities in this population. As a result, specific requirements to safeguard RD health have been introduced to Foundation for the Accreditation of Cellular Therapy/The Joint Accreditation Committee ISCT and EBMT (FACT-JACIE) Standards, but the impact of accreditation on RD care has not previously been evaluated. A survey of transplant program directors of European Group for Blood and Marrow Transplantation member centers was conducted by the Donor Health and Safety Working Committee of the Center for International Blood and Marrow Transplant Research to test the hypothesis that RD care in FACT-JACIE accredited centers is more closely aligned with international consensus donor care recommendations than RD care delivered in centers without accreditation. Responses were received from 39% of 304 centers. Our results show that practice in accredited centers was much closer to recommended standards as compared with nonaccredited centers. Specifically, a higher percentage of accredited centers use eligibility criteria to assess RDs (93% versus 78%; P = .02), and a lower percentage have a single physician simultaneously responsible for an RD and their recipient (14% versus 35%; P = .008). In contrast, where regulatory standards do not exist, both accredited and nonaccredited centers fell short of accepted best practice. These results raise concerns that despite improvements in care, current practice can place undue pressure on donors and may increase the risk of donation-associated adverse events. We recommend measures to address these issues through enhancement of regulatory standards as well as national initiatives to standardize RD care.

  18. Extended Follow-Up of Autologous Bone Marrow Transplantation with 4-Hydroperoxycyclophosphamide (4-HC) Purging for Indolent or Transformed Non-Hodgkin's Lymphomas

    PubMed Central

    Kasamon, Yvette L.; Jones, Richard J.; Gocke, Christopher D.; Blackford, Amanda L.; Seifter, Eric J.; Davis-Sproul, Janice M.; Gore, Steven D.; Ambinder, Richard F.

    2010-01-01

    Autologous blood or marrow transplantation (ABMT) for low-grade lymphomas can prolong event-free survival but requires long-term follow-up. We report one of the longest follow-ups to a prospective transplantation study in such diseases. On a phase II study, 80 patients with low-grade, transformed, or mantle cell lymphoma received ABMT with 4-hydroperoxycyclophosphamide (4-HC) purging as part of initial or salvage therapy. Diagnoses included nontransformed follicular lymphoma in 63% and transformed lymphoma in 15%. With 16.6 year median follow-up for survival, actuarial 10-year event-free and overall survivals were 34% (95% confidence interval, 25 – 46%) and 45% (35 – 57%). Median event-free and overall survivals were 3.0 and 8.0 years. Early non-relapse mortality incidence was 8%; myelodysplasia or leukemia incidence was 4%. Most relapses occurred within 3 years, with a median time to diagnosis of relapse of 1.8 years (range, 0.1 – 15.6 years). On multivariate analysis, age > 50, ≥ 3 prior chemotherapy regimens, and ABMT after relapse were associated with significantly inferior survival. Fifteen patients (19%) were event-free > 15 years after transplantation, raising the possibility of a plateau in the progression-free survival curve. Thus, 4-HC-purged ABMT can produce extended remissions in a subgroup of patients with indolent lymphomas. PMID:20655387

  19. Autologous Bone-Marrow-Derived-Mononuclear-Cells-Enriched Fat Transplantation in Breast Augmentation: Evaluation of Clinical Outcomes and Aesthetic Results in a 30-Year-Old Female

    PubMed Central

    Vrabic, Erik; Hodzic, Enes

    2013-01-01

    Autologous fat transfer (lipofilling) is becoming an invaluable tool for breast augmentation as well as for breast reconstruction. Autologous lipofilling has several advantages, including biocompatibility, versatility, natural appearance, and low donor site morbidity. The main limitation is unpredictable fat graft resorption, which ranges from 25% to 80%, probably as a result of ischaemia and lack of neoangiogenesis. To obviate these disadvantages, several studies have searched for new ways of increasing the viability of the transplanted fat tissue. One promising approach is to enrich the fat graft with autologous bone-marrow-derived mononuclear cells (BMMNCs) before transplantation. BMMNCs produce many angiogenic and antiapoptotic growth factors, and their secretion is significantly enhanced by hypoxia. All of these mechanisms of actions could be beneficial for the stimulation of angiogenesis in ischemic tissues by BMMNCs administration. In our aesthetic surgery practice, we use fat transplantation enriched with BMMNCs, which caused a significant improvement in survival of fat grafts, compared with that of traditional lipofilling. Our experience with freshly isolated autologous fat enriched with BMMNCs for breast augmentation procedures is presented. The concept of this surgical and tissue handling technique is based on ability of BMMNCs to stimulate blood vessel growth. PMID:24024064

  20. Specially modified stromal and immune microenvironment in injected bone marrow following intrabone transplantation facilitates allogeneic hematopoietic stem cell engraftment.

    PubMed

    Chen, Chen; Su, Yingjun; Chen, Jianwu; Song, Yajuan; Zhuang, Ran; Xiao, Bo; Guo, Shuzhong

    2016-07-01

    For allogeneic hematopoietic stem cell transplantation (HSCT), the first key step is the engraftment of hematopoietic stem cells (HSCs) across the major histocompatibility complex (MHC) barrier. Intrabone bone marrow transplantation (IBBMT) could replace more recipient stromal cells with donor cells and facilitate allogeneic organ transplantation compared with the conventional intravenous approach. However, it remains unknown whether and how IBBMT reconstructs the immune microenvironment for allogeneic HSCs. We explored where the BM microenvironment changes by determining BM stromal cell chimerism and measuring the change in CXCL-12 expression and regulatory T cells in recipient BM. We found that most stromal cells were replaced by allogeneic cells in the injected BM, with higher expression of immune regulatory cytokines (interleukin-10) compared with the contralateral BM and the intravenous group BM. This difference was independent of injury caused by intrabone injection. Consistent with the microenvironment modification, the allogeneic the engraftment rate and reconstitution capacity of HSCs were enhanced in the injected BM compared with the contralateral BM and intravenous group BM. Surgical removal of the injected bone at 7 days rather than 21 days reduced the levels of allogeneic granulocytes and HSCs in the peripheral blood. In conclusion, IBBMT specially modifies stromal cells in the injected BM which provide immune protective cues that improve the engraftment of allogeneic HSCs in an early period. PMID:27090963

  1. Intracerebral transplantation of bone marrow-derived mesenchymal stem cells reduces amyloid-beta deposition and rescues memory deficits in Alzheimer's disease mice by modulation of immune responses.

    PubMed

    Lee, Jong Kil; Jin, Hee Kyung; Endo, Shogo; Schuchman, Edward H; Carter, Janet E; Bae, Jae-Sung

    2010-02-01

    Alzheimer's disease (AD) is characterized by the deposition of amyloid-beta peptide (Abeta) and the formation of neurofibrillary tangles. Transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) has been suggested as a potential therapeutic approach to prevent various neurodegenerative disorders, including AD. However, the actual therapeutic impact of BM-MSCs and their mechanism of action in AD have not yet been ascertained. The aim of this study was therefore to evaluate the therapeutic effect of BM-MSC transplantation on the neuropathology and memory deficits in amyloid precursor protein (APP) and presenilin one (PS1) double-transgenic mice. Here we show that intracerebral transplantation of BM-MSCs into APP/PS1 mice significantly reduced amyloid beta-peptide (Abeta) deposition. Interestingly, these effects were associated with restoration of defective microglial function, as evidenced by increased Abeta-degrading factors, decreased inflammatory responses, and elevation of alternatively activated microglial markers. Furthermore, APP/PS1 mice treated with BM-MSCs had decreased tau hyperphosphorylation and improved cognitive function. In conclusion, BM-MSCs can modulate immune/inflammatory responses in AD mice, ameliorate their pathophysiology, and improve the cognitive decline associated with Abeta deposits. These results demonstrate that BM-MSCs are a potential new therapeutic agent for AD.

  2. Transplantation.

    PubMed

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  3. Adult thymus transplantation with allogeneic intra-bone marrow–bone marrow transplantation from same donor induces high thymopoiesis, mild graft-versus-host reaction and strong graft-versus-tumour effects

    PubMed Central

    Miyake, Takashi; Hosaka, Naoki; Cui, Wenhao; Nishida, Teruhisa; Takaki, Takashi; Inaba, Muneo; Kamiyama, Yasuo; Ikehara, Susumu

    2009-01-01

    Although allogeneic bone marrow transplantation (BMT) plus donor lymphocyte infusion (DLI) is performed for solid tumours to enhance graft-versus-tumour (GVT) effects, a graft-versus-host reaction (GVHR) is also elicited. We carried out intra-bone marrow–bone marrow transplantation (IBM-BMT) plus adult thymus transplantation (ATT) from the same donor to supply alloreactive T cells continually. Normal mice treated with IBM-BMT + ATT survived for a long time with high donor-derived thymopoiesis and mild GVHR. The percentage of CD4+ FoxP3+ regulatory T cells in the spleen of the mice treated with IBM-BMT + ATT was lower than in normal B6 mice or mice treated with IBM-BMT alone, but higher than in mice treated with IBM-BMT + DLI; the mice treated with IBM-BMT + DLI showed severe GVHR. In tumour-bearing mice, tumour growth was more strongly inhibited by IBM-BMT + ATT than by IBM-BMT alone. Mice treated with IBM-BMT + a high dose of DLI also showed tumour regression comparable to that of mice treated with IBM-BMT + ATT but died early of GVHD. By contrast, mice treated with IBM-BMT + a low dose of DLI showed longer survival but less tumour regression than the mice treated with IBM-BMT + ATT. Histologically, significant numbers of CD8+ T cells were found to have infiltrated the tumour in the mice treated with IBM-BMT + ATT. The number of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL)-positive apoptotic tumour cells also significantly increased in the mice treated with IBM-BMT + ATT. Allogeneic IBM-BMT + ATT thus can induce high thymopoiesis, preserving strong GVT effects without severe GVHR. PMID:18778285

  4. Regeneration of red bone marrow in rat lower jaw after transplantation of mesenchymal stem cells into the site of injury.

    PubMed

    Maiborodin, I V; Matveeva, V A; Kolesnikov, I S; Drovosekov, M N; Toder, M S; Shevela, A I

    2012-02-01

    Regeneration processes in rat mandibular bone after transplantation of a suspension of autologous BM MSC in culture medium were studied by methods of light microscopy and X-ray densitometry. It was found that the structures of red BM in the callus after transplantation of autologous BM MSC formed earlier than in natural reparation. The formation of cavities containing BM determines lower tissue density at the site of injury after transplantation of autologous BM MSC on weeks 4 and 5 of observation than during spontaneous healing. These changes progressed throughout the observation period and attested to accelerated bone tissue reparation.

  5. Factors influencing outcome in de novo myelodysplastic syndromes treated by allogeneic bone marrow transplantation: a long-term study of 71 patients Société Française de Greffe de Moelle.

    PubMed

    Sutton, L; Chastang, C; Ribaud, P; Jouet, J P; Kuentz, M; Attal, M; Reiffers, J; Tigaud, J M; Rio, B; Dauriac, C; Legros, M; Dreyfus, F; Lioure, B; Troussard, X; Milpied, N; Witz, F; Oriol, P; Cahn, J Y; Michallet, M; Gluckman, E; Ifrah, N; Pico, J L; Vilmer, E; Leblond, V

    1996-07-01

    We report on 71 consecutive patients with de novo myelodysplastic syndromes referred to physicians belonging to the Société française de greffe de moelle from 1982 through 1991 and transplanted with marrow from HLA-identical siblings. There were 16 cases of refractory anemia, 27 of refractory anemia with excess of blast cells, and 28 of refractory anemia with excess of blast cells in transformation. Seventeen patients had received cytoreductive chemotherapy before the graft. The disease progressed in 17 patients between diagnosis and grafting. Twenty-three patients are alive with a median follow-up of 6 years, whereas 24 died from relapse and 24 from transplant-related complications. Kaplan-Meier estimates of event-free survival, relapse and transplant-related mortality at 7 years were 32%, 48%, and 39%, respectively. The log-rank test and Cox's model revealed better outcome among young patients, patients in an early stage of the French-American-British (FAB) classification or with a low percentage of marrow blasts before transplantation, patients who did not undergo cytoreductive chemotherapy before transplantation, and patients conditioned with total body irradiation and cyclophosphamide. The high rate of relapse in advanced FAB stages has led us to graft patients earlier in the course of the disease, and we are currently conducting a multicenter, randomized study to determine the value of intensive chemotherapy before grafting in patients with an excess of marrow blasts.

  6. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    PubMed

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity.

  7. Autologous stem cell transplantation for patients aged 60 years or older with refractory or relapsed classical Hodgkin's lymphoma: a retrospective analysis from the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC).

    PubMed

    Stamatoullas, A; Brice, P; Gueye, M S; Mareschal, S; Chevallier, P; Bouabdallah, R; Nguyenquoc, S; Francois, S; Turlure, P; Ceballos, P; Monjanel, H; Bourhis, J-H; Guillerm, G; Mohty, M; Biron, P; Cornillon, J; Belhadj, K; Bonmati, C; Dilhuydy, M-S; Huynh, A; Bernard, M; Chrétien, M-L; Peffault de Latour, R; Tilly, H

    2016-07-01

    This report retrospectively analyzed the outcome of 91 patients aged 60 years or older with refractory/relapsed (R/R) classical Hodgkin's lymphoma (cHL) who underwent autologous stem cell transplantation (ASCT) between 1992 and 2013 and were reported to the French Society of Bone Marrow Transplantation and Cell Therapies registry. The median age at transplant was 63 years. The majority of patients exhibited disease chemosensitivity to salvage treatment (57 complete responses, 30 partial responses, 1 progressive disease and 3 unknown). The most frequent conditioning regimen consisted of BCNU, cytarabine, etoposide, melphalan (BEAM) chemotherapy (93%). With a median follow-up of 54 months, 5-year estimates of overall survival (OS) and progression free survival (PFS) for the entire group were 67 and 54%, respectively. Despite the missing data, in univariate analysis, the number of salvage chemotherapy lines (1-2 versus ⩾3) significantly influenced the OS, unlike the other prognostic factors (stage III-IV at relapse, disease status before ASCT and negative positron emission tomography (PET) scan) encountered in younger patients. In spite of its limitations, this retrospective study with a long-term follow-up suggests that ASCT is a valid treatment option for chemosensitive R/R cHL in selected elderly patients, with an acceptable rate of toxicity. PMID:27042842

  8. In vivo infusion of anti-LFA-1 and anti-CD2 antibodies prevents graft failure after HLA partially incompatible bone marrow transplantation in children with high risk acute lymphoblastic leukaemia.

    PubMed

    Cavazzana-Calvo, M; Jabado, N; Bordigoni, P; Michel, G; Haddad, E; Mechinaud, F; Landman-Parker, J; Leblanc, T; Plouvier, E; Baruchel, A; Stephan, J L; Souillet, G; Vilmer, E; Wijdenes, J; Le Deist, F; Fischer, A

    1997-12-01

    Bone marrow transplantation (BMT) from matched sibling donors is the therapy of choice for children with high-risk acute lymphoblastic leukaemia in children. It is however not available to more than two-thirds of patients who lack a matched donor. Here, we review the outcome of 28 patients with high-risk ALL who were transplanted in France with alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives. For these patients, we tested the possibility to prevent T-depleted marrow graft rejection by infusing in vivo two monoclonal antibodies directed against adhesion receptors i.e., LFA-1 and CD2. Two previous multicenter trials in children transplanted with partially incompatible bone marrow for inborn errors of metabolism showed their efficacy in this setting. Twenty eight patients were enrolled in this study and followed for a median of 4.4 years. Bone marrow engraftment occurred in 81% of the evaluable patients. Post-transplantation leukaemic relapse was the most frequent cause of death in this group of patients, and occurred in 39% of patients. The second most frequent complication was infectious disease, while an EBV-induced B-lymphocyte proliferative disorder occurred in four patients. In conclusion, T-cell-depletion combined with infusion of anti-LFA-1 and anti-CD2 antibodies is efficient in preventing graft failure and GVHD in this group of children with high-risk leukaemia undergoing partially incompatible BMT. The overall DFS is not improved in contrast to what has been previously observed in patients with immunodeficiencies transplanted with a similar rejection prophylaxis. Other approaches are therefore needed aiming either at preserving donor T-cell mediated immunity or accelerating immune reconstitution.

  9. Oncofertility Consortium

    MedlinePlus

    ... September 15, 2016 National Physicians Cooperative Brigid Martz Smith July 21, 2016 Postdoctoral Position in Pediatric Fertility ... 2016 Oncofertility Consortium Clinic/Center Map Brigid Martz Smith June 30, 2016 Zika Virus Concerns Grow as ...

  10. Overcoming psychosocial and developmental barriers to blood and marrow transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with chronic myelogenous leukemia.

    PubMed

    Khazal, Sajad; Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M

    2014-11-01

    Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

  11. Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells.

    PubMed

    Capitelli, Caroline Santos; Lopes, Carolina Salomão; Alves, Angélica Cristina; Barbiero, Janaína; Oliveira, Lucas Felipe; da Silva, Valdo José Dias; Vital, Maria Aparecida Barbato Frazão

    2014-01-01

    The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic

  12. Multi-institutional Feasibility Study of a Fast Patient Localization Method in Total Marrow Irradiation With Helical Tomotherapy: A Global Health Initiative by the International Consortium of Total Marrow Irradiation

    SciTech Connect

    Takahashi, Yutaka; Vagge, Stefano; Agostinelli, Stefano; Han, Eunyoung; Matulewicz, Lukasz; Schubert, Kai; Chityala, Ravishankar; Ratanatharathorn, Vaneerat; Tournel, Koen; Penagaricano, Jose A.; Florian, Sterzing; Mahe, Marc-Andre; Verneris, Michael R.; Weisdorf, Daniel J.; and others

    2015-01-01

    Purpose: To develop, characterize, and implement a fast patient localization method for total marrow irradiation. Methods and Materials: Topographic images were acquired using megavoltage computed tomography (MVCT) detector data by delivering static orthogonal beams while the couch traversed through the gantry. Geometric and detector response corrections were performed to generate a megavoltage topogram (MVtopo). We also generated kilovoltage topograms (kVtopo) from the projection data of 3-dimensional CT images to reproduce the same geometry as helical tomotherapy. The MVtopo imaging dose and the optimal image acquisition parameters were investigated. A multi-institutional phantom study was performed to verify the image registration uncertainty. Forty-five MVtopo images were acquired and analyzed with in-house image registration software. Results: The smallest jaw size (front and backup jaws of 0) provided the best image contrast and longitudinal resolution. Couch velocity did not affect the image quality or geometric accuracy. The MVtopo dose was less than the MVCT dose. The image registration uncertainty from the multi-institutional study was within 2.8 mm. In patient localization, the differences in calculated couch shift between the registration with MVtopo-kVtopo and MVCT-kVCT images in lateral, cranial–caudal, and vertical directions were 2.2 ± 1.7 mm, 2.6 ± 1.4 mm, and 2.7 ± 1.1 mm, respectively. The imaging time in MVtopo acquisition at the couch speed of 3 cm/s was <1 minute, compared with ≥15 minutes in MVCT for all patients. Conclusion: Whole-body MVtopo imaging could be an effective alternative to time-consuming MVCT for total marrow irradiation patient localization.

  13. Patient and healthcare perspectives on the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic: a qualitative study

    PubMed Central

    Sinclair, Shane; McConnell, Shelagh; Raffin Bouchal, Shelley; Ager, Naree; Booker, Reanne; Enns, Bert; Fung, Tak

    2015-01-01

    Objectives The purpose of this study was to use a qualitative approach to better understand the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic from the perspectives of patients and healthcare providers. Setting Participants were recruited from the bone marrow transplant clinic of a large urban outpatient cancer care centre in western Canada. Participants: Focus groups were conducted with patients (n=7) and healthcare providers (n=9) to explore the importance of addressing spiritual issues across the treatment trajectory and to identify factors associated with effectively addressing these needs. Results Data were analysed using the qualitative approach of latent content analysis. Addressing spiritual issues was understood by patients and healthcare providers, as a core, yet under addressed, component of comprehensive care. Both sets of participants felt that addressing basic spiritual issues was the responsibility of all members of the interdisciplinary team, while recognising the need for specialised and embedded support from a spiritual care professional. While healthcare providers felt that the impact of the illness and treatment had a negative effect on patients’ spiritual well-being, patients felt the opposite. Skills, challenges, key time points and clinical indicators associated with addressing spiritual issues were identified. Conclusions Despite a number of conceptual and clinical challenges associated with addressing spiritual issues patients and their healthcare providers emphasised the importance of an integrated approach whereby basic spiritual issues are addressed by members of the interdisciplinary team and by an embedded spiritual care professional, who in addition also provides specialised support. The identification of clinical issues associated with addressing spiritual needs provides healthcare providers with clinical guidance on how to better integrate this aspect of care into

  14. Effects of a cloned cell line with NK activity on bone marrow transplants, tumour development and metastasis in vivo

    NASA Astrophysics Data System (ADS)

    Warner, John F.; Dennert, Gunther

    1982-11-01

    Natural killer (NK) cells cloned in vitro have been transferred into NK-deficient hosts. These cells have been shown to have a role in the rejection of allogeneic bone marrow grafts, resistance to both radiation-induced thymic leukaemia and challenge with melanoma tumour cells. It appears that NK cells have an important role in immune surveillance.

  15. Serial transplantation and long-term engraftment of intra-arterially delivered clonally derived mesenchymal stem cells to injured bone marrow.

    PubMed

    Lin, Paul; Correa, Diego; Kean, Thomas J; Awadallah, Amad; Dennis, James E; Caplan, Arnold I

    2014-01-01

    It has been hypothesized that mesenchymal stem cells (MSCs) home to sites of injury. Nevertheless, efficient delivery of MSCs to target organs and description of their ultimate fate remain major challenges. We provide evidence that intra-arterially (IA) injected MSCs selectively engraft from the circulation as perivascular cells in the bone marrow (BM) after a localized radiation injury. Luciferase-expressing MSCs, derived from a conditionally immortalized clone (BMC-9) representing a pure population of cells, were arterially delivered into mice irradiated in one leg. Cell distribution was measured by bioluminescent imaging and final destination assessed by luciferase immunolocalization. IA injections resulted in engraftment only in the irradiated leg where cells localize and proliferate abluminal to the BM vasculature, a phenomenon not replicated with intravenous injections or with IA injections of kidney cells harvested from the same donor used for MSCs. Furthermore, MSCs harvested from the engrafted marrow and serially transplanted retain the ability to selectively engraft at sites of injury. This study demonstrates that MSCs can serially engraft at sites of injury from the circulation, that they reside in the perivascular space, and that arterial delivery is more efficient than venous delivery for cell engraftment. PMID:24067545

  16. APOE3, but not APOE4, bone marrow transplantation mitigates behavioral and pathological changes in a mouse model of Alzheimer disease.

    PubMed

    Yang, Yue; Cudaback, Eiron; Jorstad, Nikolas L; Hemingway, Jake F; Hagan, Catherine E; Melief, Erica J; Li, Xianwu; Yoo, Tom; Khademi, Shawn B; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-09-01

    Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein-expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT-recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT-recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.

  17. Nutritional support of bone marrow transplant recipients: a prospective, randomized clinical trial comparing total parental nutrition to an enteral feeding program

    SciTech Connect

    Szeluga, D.J.

    1985-01-01

    Allogeneic and autologous bone marrow transplantation (BMT) have been associated with nutritionally-depleting side effects. Total parental nutrition (TPN) has become the standard, but it has not been demonstrated that TPN is the appropriate method of nutritional support. Therefore, in a prospective, randomized clinical trial TPN and enteral feeding were compared for their effectiveness in maintaining the nutritional status of patients through the first 29 post-transplant days. Nutritional assessment included measurement of serum proteins, body weight, anthropometry and isotope dilution analysis of body composition. Total body water (TBW) and extracellular fluid (ECF) were quantified by standard radioisotope dilution techniques using tritiated water and /sup 169/ytterbium-diethylenetriaminepentaacetate, respectively as the tracers. Consenting patients 10-58 years of age were stratified by type of BMT (autologous or allogeneic) and randomized to either TPN plus ad libitum oral feeding or the individualized enteral feeding program (EFP), which included one-on-one counseling, meal-by-meal menu selection, special snacks and tube feeding. There were no differences in the rate of hematologic recovery, incidence of graft-versus-host disease, organ toxicity, length of hospitalization or survival. Therefore, the observed changes in body composition were not clinically significant. Even allowing for increased dietary service, the EFP was only half as expensive as TPN. It was concluded that TPN is not superior to the EFP and therefore, TPN should be reserved for patients who demonstrate intolerance to enteral feeding.

  18. Remission of Collagen-Induced Arthritis through Combination Therapy of Microfracture and Transplantation of Thermogel-Encapsulated Bone Marrow Mesenchymal Stem Cells

    PubMed Central

    Liu, He; Ding, Jianxun; Wang, Jincheng; Wang, Yinan; Yang, Modi; Zhang, Yanbo; Chang, Fei; Chen, Xuesi

    2015-01-01

    The persistent inflammation of rheumatoid arthritis (RA) always leads to partial synovial hyperplasia and the destruction of articular cartilage. Bone marrow mesenchymal stem cells (BMMSCs) have been proven to possess immunosuppressive effects, and widely explored in the treatment of autoimmune diseases. However, poor inhibitory effect on local inflammatory state and limited capacity of preventing destruction of articular cartilage by systemic BMMSCs transplantation were observed. Herein, toward the classical type II collagen-induced arthritis in rats, the combination treatment of microfracture and in situ transplantation of thermogel-encapsulated BMMSCs was verified to obviously down-regulate the ratio of CD4+ to CD8+ T lymphocytes in peripheral blood. In addition, it resulted in the decreased levels of inflammatory cytokines, such as interleukin-1β, tumor necrosis factor-α and anti-collagen type II antibody, in the serum. Simultaneously, the combination therapy also could inhibit the proliferation of antigen specific lymphocytes and local joint inflammatory condition, and prevent the articular cartilage damage. The results indicated that the treatment programs could effectively stimulate the endogenous and exogenous BMMSCs to exhibit the immunosuppression and cartilage protection capability. This study provided a new therapeutic strategy for autoimmune inflammatory diseases, such as RA. PMID:25774788

  19. Suitability Criteria for Adult Related Donors: A Consensus Statement from the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues.

    PubMed

    Worel, Nina; Buser, Andreas; Greinix, Hildegard T; Hägglund, Hans; Navarro, Willis; Pulsipher, Michael A; Nicoloso de Faveri, Grazia; Bengtsson, Mats; Billen, Annelies; Espino, German; Fechter, Mirjam; Giudice, Valeria; Hölig, Kristina; Kanamori, Heiwa; Kodera, Yoshihisa; Leitner, Gerda; Netelenbos, Tanja; Niederwieser, Dietger; van Walraven, Suzanna M; Rocha, Vanderson; Torosian, Tigran; Vergueiro, Carmen; Weisdorf, Daniel; Yabe, Hiromasa; Halter, Jörg P

    2015-12-01

    The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care, and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pretransplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published, allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues, we intended to develop a consensus document with recommendations for donor workup and final clearance of family donors who would not be able to serve as unrelated donors because of their age or pre-existing diseases. This article covers different topics intending to support decision-making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases.

  20. Songwriting and digital video production interventions for pediatric patients undergoing bone marrow transplantation, part II: an analysis of patient-generated songs and patient perceptions regarding intervention efficacy.

    PubMed

    Robb, Sheri L; Ebberts, Allison G

    2003-01-01

    Part I of this exploratory case study examined patient anxiety levels and depressive symptoms according to phase of bone marrow transplantation (BMT). The second part of this study examines more qualitative outcomes of the music therapy intervention. Purposes of this part of the study included: (1) to examine the lyrical content of patient-generated songs and (2) to compare patient perceptions regarding the effectiveness of a 6-week music condition with a no-music contact condition. Six pediatric BMT patients participated in the study. Three participants experienced the music condition and three participants experienced the no-music contact condition. Both conditions consisted of six, 1-hour sessions that occurred over a 3-week period. Content analysis of patient-generated songs revealed expression of issues related to the following themes: hope, positive coping, appreciation, mental status, control, time, bewilderment, treatment, and diagnosis. Examination of patient-generated songs provided insight into each patient's experience with transplantation and the coping strategies used during treatment. Outcomes from a poststudy questionnaire are summarized.

  1. Adverse Fat Depots and Marrow Adiposity Are Associated With Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation.

    PubMed

    Mostoufi-Moab, Sogol; Magland, Jeremy; Isaacoff, Elizabeth J; Sun, Wenli; Rajapakse, Chamith S; Zemel, Babette; Wehrli, Felix; Shekdar, Karuna; Baker, Joshua; Long, Jin; Leonard, Mary B

    2015-09-01

    Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12 to 25 years) a median of 9.7 (4.3 to 19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p < 0.001) and greater VAT (p < 0.01), MAT (p < 0.001), and fat infiltration of muscle (p = 0.04) independent of WB-FM, versus matched controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure versus controls (all p = 0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT, and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p < 0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p < 0.01), and positively correlated with WB-FM and VAT (both p < 0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors

  2. Adverse Fat Depots and Marrow Adiposity Are Associated with Skeletal Deficits and Insulin Resistance in Long-Term Survivors of Pediatric Hematopoietic Stem Cell Transplantation

    PubMed Central

    Mostoufi-Moab, Sogol; Magland, Jeremy; Isaacoff, Elizabeth J.; Sun, Wenli; Rajapakse, Chamith S.; Zemel, Babette; Wehrli, Felix; Shekdar, Karuna; Baker, Joshua; Long, Jin; Leonard, Mary B.

    2015-01-01

    Allogeneic hematopoietic stem-cell transplantation (alloHSCT) survivors treated with total body irradiation (TBI) exhibit bone deficits and excess adiposity, potentially related to altered mesenchymal stem cell differentiation into osteoblasts or adipocytes. We examined associations among fat distribution, bone microarchitecture, and insulin resistance in alloHSCT survivors after TBI. This was a cross-sectional observational study of 25 alloHSCT survivors (aged 12–25 years) a median of 9.7 (4.3–19.3) years after alloHSCT compared to 25 age-, race-, and sex-matched healthy controls. Vertebral MR spectroscopic imaging and tibia micro-MRI were used to quantify marrow adipose tissue (MAT) and trabecular microarchitecture. Additional measures included DXA whole-body fat mass (WB-FM), leg lean mass (Leg-LM), trunk visceral adipose tissue (VAT), and CT calf muscle density. Insulin resistance in alloHSCT survivors was estimated by HOMA-IR. AlloHSCT survivors had lower Leg-LM (p<0.001), and greater VAT (p<0.01), MAT (p<0.001) and fat infiltration of muscle (p=0.04) independent of WB-FM, vs. matched-controls; BMI did not differ. Survivors had lower bone volume fraction and abnormal microarchitecture including greater erosion and more rod-like structure vs. controls (all p=0.04); 14 had vertebral deformities and two had compression fractures. Greater WB-FM, VAT, MAT and muscle fat infiltration were associated with abnormal trabecular microarchitecture (p<0.04 for all). AlloHSCT HOMA-IR was elevated, associated with younger age at transplantation (p<0.01), and positively correlated with WB-FM and VAT (both p<0.01). In conclusion, the markedly increased marrow adiposity, abnormal bone microarchitecture, and abnormal fat distribution highlight the risks of long-term treatment-related morbidity and mortality in alloHSCT recipients after TBI. Trabecular deterioration was associated with marrow and visceral adiposity. Furthermore, long-term survivors demonstrated sarcopenic

  3. Suppressor cell activity following total lymphoid irradiation (TLI), bone marrow (BM) injection, and kidney transplantation in baboons

    SciTech Connect

    Smit, J.A.; Myburgh, J.A.; Hill, R.R.H.; Browde, S.

    1981-03-01

    Induction of specific tissue transplantation tolerance by fractionated TLI was first described in adult mice, rats, and dogs. The method was equally effective in inducing unresponsiveness in outbred baboons, and irradiation given in fractions was confirmed to be more efficient than single dose. This study investigated the cumulative effect of 600 to 2400 rad TLI on the immune response of baboons treated according to a schedule applicable to patients awaiting renal transplantation. The possible mechanisms involved in tolerogenesis include the following: broad nonspecific nonreactivity, clonal deletion, suppressor cell activity, and enhancement.

  4. Derivation of male germ cells from ram bone marrow mesenchymal stem cells by three different methods and evaluation of their fate after transplantation into the testis.

    PubMed

    Ghasemzadeh-Hasankolaei, Mohammad; Eslaminejad, Mohammadreza Baghaban; Sedighi-Gilani, Mohammadali

    2016-01-01

    Mesenchymal stem cells (MSCs) have the capacity to differentiate into germ cells (GCs). This research, for the first time