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Sample records for marrow transplant consortium

  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; ...

  2. 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 ...

  3. 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 - ...

  4. 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 ...

  5. Bone Marrow Transplantation

    MedlinePlus

    Bone marrow is the spongy tissue inside some of your bones, such as your hip and thigh bones. It contains immature cells, called stem cells. The ... platelets, which help the blood to clot. A bone marrow transplant is a procedure that replaces a ...

  6. 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 ...

  7. 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 ...

  8. Bone-marrow transplant - series (image)

    MedlinePlus

    Bone-marrow transplants are performed for: deficiencies in red blood cells (aplastic anemia) and white blood cells (leukemia or ... Bone-marrow transplants prolong the life of patients who might otherwise die. As with all major organ transplants, however, ...

  9. Bone Marrow Transplants: "Another Possibility at Life"

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Bone Marrow Transplants “Another Possibility at Life” Past Issues / Summer ... year, and, for 16,000 of them, a bone marrow transplant is the best treatment option, notes Susan ...

  10. 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 ...

  11. Bone marrow transplant - discharge

    MedlinePlus

    ... sugar-free popsicles or sugar-free hard candies. Take care of your dentures, braces, or other dental products. ... Take care not to get infections for up to 1 year or more after your transplant. Practice safe ...

  12. Osteosarcoma after bone marrow transplantation.

    PubMed

    Ueki, Hideaki; Maeda, Naoko; Sekimizu, Masahiro; Tsukushi, Satoshi; Nishida, Yoshihiro; Horibe, Keizo

    2013-03-01

    Three children treated with bone marrow transplantation for acute lymphoblastic leukemia, Diamond-Blackfan anemia, and congenital amegakaryocytic thrombocytopenia developed secondary osteosarcoma in the left tibia at the age of 13, 13, and 9 years, respectively, at 51, 117, and 106 months after transplantation, respectively. Through treatment with chemotherapy and surgery, all 3 patients are alive without disease. We surveyed the literature and reviewed 10 cases of osteosarcoma after hematopoietic stem cell transplantation (SCT), including our 3 cases. Eight of the patients had received myeloablative total body irradiation before SCT. The mean interval from SCT to the onset of osteosarcoma was 6 years and 4 months, and the mean age at the onset of osteosarcoma was 14 years and 5 months. The primary site of the post-SCT osteosarcoma was the tibia in 6 of 10 cases, in contrast to de novo osteosarcoma, in which the most common site is the femur. At least 7 of the 10 patients are alive without disease. Osteosarcoma should be one of the items for surveillance in the follow-up of patients who undergo SCT. PMID:22995925

  13. 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 ...

  14. Liver disease after bone marrow transplantation.

    PubMed Central

    Farthing, M J; Clark, M L; Sloane, J P; Powles, R L; McElwain, T J

    1982-01-01

    Liver dysfunction occurs after bone marrow transplantation but the relative importance of graft versus host disease and other factors, such as infection, radiation, and drugs, has not been clearly established. We have studied liver status before and after bone marrow transplantation in 43 consecutive patients and have related this to survival and factors that are recognised to cause liver injury. Minor abnormalities of liver tests occurred in 21% of patients before grafting but this did not influence survival or the development of liver disease after transplantation. During the first 50 days after grafting, 83% of patients had abnormal liver tests which were more severe in patients who subsequently died. Alanine transaminase was significantly higher in non-survivors and appeared to predict survival early after transplantation. Only non-survivors developed clinical signs of liver disease. Severe liver disease was always associated with graft versus host disease and atypia of the small bile ducts was the most useful histological marker of hepatic involvement with this disease. Two of the patients with hepatic graft versus host disease also has hepatic veno-occlusive disease and three fatalities had opportunistic infection of the liver, although, in the latter, death was not due primarily to liver dysfunction. Previous hepatitis and androgen therapy could not be implicated as important causes of hepatic damage but chemotherapy for acute leukaemia and conditioning regimens for bone marrow transplantation appear to be the most important factors in the development of hepatic veno-occlusive disease. Images Fig. 3 Fig. 4 PMID:7042484

  15. Post-bone marrow transplant patient management.

    PubMed Central

    Poliquin, C. M.

    1990-01-01

    Increasingly, bone marrow transplant (BMT) is the treatment of choice for certain hematologic diseases. BMT is, however, a risky procedure with many potentially serious complications. Some complications are the result of the conditioning regimen, a stage of transplantation that includes large doses of chemotherapy and/or radiation therapy. Conditioning-induced neutropenia and thrombocytopenia often result in infection, bleeding, and mucositis. Veno-occlusive disease (VOD), a chemotherapy-induced hepatotoxicity, can cause a mild to severe form of liver disease. Other complications are directly attributable to the engrafted new marrow. Graft-versus-host disease, a rejection process initiated by immunocompetent donor T lymphocytes, is a complication frequently observed in allogeneic BMT. Approximately 14-28 days after the day of transplant, signs of engraftment begin to appear. When specific discharge criteria are met, the BMT patient is discharged from the hospital. Specific follow-up medical care is ongoing for about one year after BMT. PMID:2293508

  16. [Allogenic bone marrow transplantation complications. Part II].

    PubMed

    Saloua, L; Tarek, B O; Abderrahman, A; Abdeladhim, B A

    2000-03-01

    Bone marrow transplantation increase the chances of cure of many hematology and also neoplasms cancers. The procedure is however a cause of expected mortality and morbidity. The complications are represented by mucocutaneous, toxicity graft versus host disease, veno-occlusive disease and most importantly injections consequences all this complications needs to be prevented and treated considering the risk associated to the moderling immunosuppression. PMID:11026816

  17. National Cancer Institute-National Heart, Lung and Blood Institute/pediatric Blood and Marrow Transplant Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: long-term organ damage and dysfunction.

    PubMed

    Nieder, Michael L; McDonald, George B; Kida, Aiko; Hingorani, Sangeeta; Armenian, Saro H; Cooke, Kenneth R; Pulsipher, Michael A; Baker, K Scott

    2011-11-01

    Long-term complications after hematopoietic cell transplantation (HCT) have been studied in detail. Although virtually every organ system can be adversely affected after HCT, the underlying pathophysiology of these late effects remain incompletely understood. This article describes our current understanding of the pathophysiology of late effects involving the gastrointestinal, renal, cardiac, and pulmonary systems, and discusses post-HCT metabolic syndrome studies. Underlying diseases, pretransplantation exposures, transplantation conditioning regimens, graft-versus-host disease, and other treatments contribute to these problems. Because organ systems are interdependent, long-term complications with similar pathophysiologic mechanisms often involve multiple organ systems. Current data suggest that post-HCT organ complications result from cellular damage that leads to a cascade of complex events. The interplay between inflammatory processes and dysregulated cellular repair likely contributes to end-organ fibrosis and dysfunction. Although many long-term problems cannot be prevented, appropriate monitoring can enable detection and organ-preserving medical management at earlier stages. Current management strategies are aimed at minimizing symptoms and optimizing function. There remain significant gaps in our knowledge of the pathophysiology of therapy-related organ toxicities disease after HCT. These gaps can be addressed by closely examining disease biology and identifying those patients at greatest risk for adverse outcomes. In addition, strategies are needed for targeted disease prevention and health promotion efforts for individuals deemed at high risk because of their genetic makeup or specific exposure profile. PMID:21963877

  18. Who Needs a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... to find out whether you have any medical problems that could cause complications after the transplant. (See "What To Expect Before a Blood and Marrow Stem Cell Transplant" for more information.) Rate This Content: NEXT >> ...

  19. Transplantation immunology: Solid Organ and bone marrow

    PubMed Central

    Chinen, Javier; Buckley, Rebecca H.

    2010-01-01

    Development of the field of organ and tissue transplantation has accelerated remarkably since the human major histocompatibility complex (MHC) was discovered in 1967. Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. The roles of the different components of the immune system involved in the tolerance or rejection of grafts and in graft-versus-host disease have been clarified. These components include: antibodies, antigen presenting cells, helper and cytotoxic T cell subsets, immune cell surface molecules, signaling mechanisms and cytokines that they release. The development of pharmacologic and biological agents that interfere with the alloimmune response and graft rejection has had a crucial role in the success of organ transplantation. Combinations of these agents work synergistically, leading to lower doses of immunosuppressive drugs and reduced toxicity. Reports of significant numbers of successful solid organ transplants include those of the kidneys, liver, heart and lung. The use of bone marrow transplantation for hematological diseases, particularly hematological malignancies and primary immunodeficiencies, has become the treatment of choice in many of these conditions. Other sources of hematopoietic stem cells are also being used, and diverse immunosuppressive drug regimens of reduced intensity are being proposed to circumvent the mortality associated with the toxicity of these drugs. Gene therapy to correct inherited diseases by infusion of gene-modified autologous hematopoietic stem cells has shown efficacy in two forms of severe combined immunodeficiency, providing an alternative to allogeneic tissue transplantation. PMID:20176267

  20. Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial.

    PubMed

    Morris, Joan; Rudebeck, Mattias; Neudorf, Steven; Moore, Theodore; Duerst, Reggie; Shah, Ami J; Graham, Michael; Aquino, Victor; Morris, Christopher; Olsson, Birgitta

    2016-07-01

    Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen. PMID:26968792

  1. [Current problems in pediatric bone marrow transplantation].

    PubMed

    Kato, S

    1993-05-01

    Bone marrow transplantation (BMT) has been increasingly applied to a variety of potentially fatal diseases in childhood. However, trends of indication of BMT are changing because chemotherapy in leukemia and immunosuppressive therapy with/without colony stimulating factor in aplastic anemia are improving. Several progresses have been noted in matched unrelated BMT and peripheral blood stem cell transplantation as well as in sibling BMT or autologous BMT. Many efforts are being made to decrease rejection rate or leukemia relapse and to improve quality of life by new conditioning regimens. Attempts to induce GVL effects or syngeneic GVHD are currently under progress. The quality of life in long term surviving children are generally good and acceptable, although delay in growth, infertility, cataract and obstructive lung disease are seen in a few patients. PMID:8315825

  2. Publication bias in blood and marrow transplantation.

    PubMed

    Saeed, Mahwash; Paulson, Kristjan; Lambert, P; Szwajcer, David; Seftel, Matthew

    2011-06-01

    Only a small proportion of abstracts lead to full publication. Abstracts with "positive" results are more likely to be published than other abstracts, leading to publication bias. To date, this issue has not been examined in the blood and marrow transplantation (BMT) literature. We hypothesized that because BMT centers are often based at academic centers, the proportion of abstracts leading to publication will be high. All abstracts presented at the Canadian Blood and Marrow Transplant Group biannual meetings in 2002, 2004, and 2006 were reviewed and categorized by study type, funding source, single-center or multicenter study, form of presentation, and positive or negative results, using the authors' definitions. To determine publication, each reference was searched on multiple databases (MEDLINE, EMBASE, Web of Science, and CINAHL) by first, second, and final author names. Two authors performed abstract categorization and searching, and disagreements were resolved by consensus. Of the 141 abstracts reviewed, only 43 were published (30.4%). Twenty-one studies were published from 2002 (36.8%), compared with 12 from 2004 (24.0%) and 10 from 2006 (29.4%) (P = .35). Neither positive results nor the number of involved centers were associated with the likelihood of publication. Clinical studies (retrospective or prospective) were more likely to be published than nonclinical studies (P = .014). Funded studies and oral presentations were more likely to be published (P = .009 and .004, respectively). A low rate of publication is seen in the field of BMT. Studies with clinical outcomes, externally funded studies, and studies presented orally were more likely to be published. However, there was no publication bias in favor of studies with positive results. Publication bias should be evaluated further at larger BMT meetings, and efforts should be made to encourage full publication of scientific abstracts. PMID:21130176

  3. Probabilistic Prediction of the Outcome of Bone-Marrow Transplantation

    PubMed Central

    Suermondt, H. Jacques; Amylon, Michael D.

    1989-01-01

    Bone-marrow transplantation is considered the treatment of choice for pediatric patients with recurring acute lymphoblastic leukemia, provided that a suitable donor is available. Many prognostic factors are known that help to predict the likely outcome of transplantation. We have implemented a system that applies probabilistic reasoning to the available data about individual patients to help determine the risk of recurrence and morbidity after transplantation, and to predict life expectancy. The resulting predictions can be used to decide whether marrow transplantation is the most desirable treatment modality for the patient.

  4. 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.

  5. [Renal transplantation without maintenance immunosuppression. Identical twins and kidney transplantation following a successful bone marrow graft].

    PubMed

    Hadi, Riad Abdel; Thomé, Gustavo Gomes; Ribeiro, Adriana Reginato; Manfro, Roberto Ceratti

    2015-01-01

    Renal transplantation without maintenance immunosuppression has been sporadically reported in the literature. The cases include non-adherent patients who discontinued their immunosuppressive medications, transplantation between identical twins, kidney transplantation after a successful bone marrow graft from the same donor and simultaneous bone marrow and kidney transplantation for the treatment of multiple myeloma with associated renal failure. There are also ongoing clinical trials designed to induce donor specific transplant tolerance with infusion of hematopoietic cells from the same kidney donor. Here we describe two cases of renal transplantation without immunosuppression as examples of situations described above. PMID:26154652

  6. Post-bone marrow transplant thrombotic microangiopathy.

    PubMed

    Obut, F; Kasinath, V; Abdi, R

    2016-07-01

    Thrombotic microangiopathy (TMA) is a systemic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ failure. Post-bone marrow transplant TMA (post-BMT TMA) is a life-threatening condition that has been reported to afflict between 0.5 and 63.6% of BMT patients. The incidence of post-BMT TMA is affected by evolving therapies such as conditioning regimens. The etiology of post-BMT TMA is thought to be multifactorial, including the effects of immunosuppressive agents, viral infections, TBI and GvHD. A growing body of evidence highlights the importance of complement system activation and endothelial damage in post-BMT TMA. Although plasmapheresis has commonly been used, its therapeutic rationale for the majority of post-BMT TMA cases is unclear in the absence of circulatory inhibitors. It has become possible to target complement activation with eculizumab, a drug that blocks the terminal complement pathway. Early studies have highlighted the importance of anti-complement therapies in treating post-BMT TMA. Moreover, finding complement gene mutations may identify patients at risk, but whether such patients benefit from prophylactic anti-complement therapies before BMT remains to be studied. This review focuses on diagnostic criteria, pathophysiology, treatment and renal outcomes of post-BMT TMA. PMID:26974272

  7. 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

  8. 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. PMID:23652881

  9. 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 ...

  10. 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

  11. 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.

  12. Total lymphatic irradiation and bone marrow in human heart transplantation

    SciTech Connect

    Kahn, D.R.; Hong, R.; Greenberg, A.J.; Gilbert, E.F.; Dacumos, G.C.; Dufek, J.H.

    1984-08-01

    Six patients, aged 36 to 59 years, had heart transplants for terminal myocardial disease using total lymphatic irradiation (TLI) and donor bone marrow in addition to conventional therapy. All patients were poor candidates for transplantation because of marked pulmonary hypertension, unacceptable tissue matching, or age. Two patients are living and well more than four years after the transplants. Two patients died of infection at six and seven weeks with normal hearts. One patient, whose preoperative pulmonary hypertension was too great for an orthotopic heart transplant, died at 10 days after such a procedure. The other patient died of chronic rejection seven months postoperatively. Donor-specific tolerance developed in 2 patients. TLI and donor bone marrow can produce specific tolerance to donor antigens and allow easy control of rejection, but infection is still a major problem. We describe a new technique of administering TLI with early reduction of prednisone that may help this problem.

  13. Total body irradiation in bone marrow transplantation: the influence of fractionation and delay of marrow infusion

    SciTech Connect

    Lichter, A.S.; Tracy, D.; Lam, W.C.; Order, S.E.

    1980-03-01

    Bone marrow transplantation (BMT) after total body irradiation (TBI) and cyclophosphamide is being employed increasingly in the therapy of end stage leukemia. Interstitial pneumonitis (IP) represents a major acute toxicity after allogeneic transplantation. A more rapid reconstitution of lymphoid organs and bone marrow post transplant may result in increased immune competence and hence fewer opportunistic pulmonary infections and IP. By delaying the infusion of marrow to 72 hr after TBI (1250 rad at 7.5 rad/min) instead of the customary 24 hr, we can demonstrate an increase in initial repopulation of thymus, spleen and bone marrow, with syngeneic transplants in Lewis rats. Interstitial pneumonitis may also be caused, in part, by the pulmonary toxicity of large single exposures of TBI. Clinical and laboratory data suggest that fractionated TBI may be less toxic to the lung. When fractionated TBI (625 rad x 2, 7.5 rad/min) is compared to single dose TBI (1250 rad, 7.5 rad/min), and increased initial repopulation of lymphoid organs is observed when fractionated therapy is employed. Delay in marrow infusion and fractionation of TBI exposure may have clinical advantages in patients who receive BMT.

  14. Late renal dysfunction in adult survivors of bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E. )

    1991-06-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction.

  15. 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. PMID:22434694

  16. Regulatory Immunotherapy in Bone Marrow Transplantation

    PubMed Central

    Morales-Tirado, Vanessa; Luszczek, Wioleta; van der Merwe, Marié; Pillai, Asha

    2011-01-01

    Every year individuals receive hematopoietic stem cell transplantation (HSCT) to eradicate malignant and nonmalignant disease. The immunobiology of allotransplantation is an area of ongoing discovery, from the recipient's conditioning treatment prior to the transplant to the donor cell populations responsible for engraftment, graft-versus-host disease, and graft-versus-tumor effect. In this review, we focus on donor-type immunoregulatory T cells, namely, natural killer T cells (NKT) and regulatory T cells (Treg), and their current and potential roles in tolerance induction after allogeneic HSCT. PMID:22262950

  17. Bone marrow transplantation after the Chernobyl nuclear accident

    SciTech Connect

    Baranov, A.; Gale, R.P.; Guskova, A.; Piatkin, E.; Selidovkin, G.; Muravyova, L.; Champlin, R.E.; Danilova, N.; Yevseeva, L.; Petrosyan, L. )

    1989-07-27

    On April 26, 1986, an accident at the Chernobyl nuclear power station in the Soviet Union exposed about 200 people to large doses of total-body radiation. Thirteen persons exposed to estimated total-body doses of 5.6 to 13.4 Gy received bone marrow transplants. Two transplant recipients, who received estimated doses of radiation of 5.6 and 8.7 Gy, are alive more than three years after the accident. The others died of various causes, including burns (the cause of death in five), interstitial pneumonitis (three), graft-versus-host disease (two), and acute renal failure and adult respiratory distress syndrome (one). There was hematopoietic (granulocytic) recovery in nine transplant recipients who could be evaluated, six of whom had transient partial engraftment before the recovery of their own marrow. Graft-versus-host disease was diagnosed clinically in four persons and suspected in two others. Although the recovery of endogenous hematopoiesis may occur after exposure to radiation doses of 5.6 to 13.4 Gy, we do not know whether it is more likely after the transient engraftment of transplanted stem cells. Because large doses of radiation affect multiple systems, bone marrow recovery does not necessarily ensure survival. Furthermore, the risk of graft-versus-host disease must be considered when the benefits of this treatment are being weighed.

  18. Cell survival kinetics in peripheral blood and bone marrow during total body irradiation for marrow transplantation

    SciTech Connect

    Shank, B.; Andreeff, M.; Li, D.

    1983-11-01

    Cell survival kinetics in both peripheral blood and in bone marrow have been studied over the time course of hyperfractionated total body irradiation (TBI) for bone marrow transplantation. Our unique TBI regimen allows the study of the in vivo radiation effect uncomplicated by prior cyclophosphamide, since this agent is given after TBI in our cytoreduction scheme. Peripheral blood cell concentrations were monitored with conventional laboratory cell counts and differentials. Absolute bone marrow cell concentrations were monitored by measuring cell concentrations in an aspirate sample and correcting for dilution with blood by a cell cycle kinetic method using cytofluorometry. For lymphocytes in peripheral blood in patients in remission, the effective D/sub 0/ ranged from 373 rad in 10 children less than or equal to 10 y old, to 536 rad in the four patients between 11 to 17 y old, while n = 1.0 in all groups. There was no trend observed according to age. Granulocytes had a much higher effective D/sub 0/, approximately 1000 rad in vivo. Absolute nucleated cell concentration in marrow dropped slowly initially, due to an increased lymphocyte concentration in marrow during a concurrent drop in lymphocyte concentration in peripheral blood, but eventually fell on the last day of TBI ranging from 7 to 44% of the initial marrow nucleated cell concentration. Marrow myeloid elements, however, dropped continuously throughout the course of TBI.

  19. 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.

  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. From evidence to clinical practice in blood and marrow transplantation.

    PubMed

    Khera, Nandita

    2015-11-01

    Clinical practice in the field of blood and marrow transplantation (BMT) has evolved over time, as a result of thousands of basic and clinical research studies. While it appears that scientific discovery and adaptive clinical research may be well integrated in case of BMT, there is lack of sufficient literature to definitively understand the process of translation of evidence to practice and if it may be selective . In this review, examples from BMT and other areas of medicine are used to highlight the state of and potential barriers to evidence uptake. Strategies to help improve knowledge transfer are discussed and the role of existing framework provided by the Center for International Blood and Marrow Transplant Registry (CIBMTR) to monitor uptake and BMT Clinical Trials Network (BMT CTN) to enhance translation of evidence into practice is highlighted. PMID:25934009

  3. 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

  4. Effect of nephrotoxic drugs on the development of radiation nephropathy after bone marrow transplantation

    SciTech Connect

    Lawton, C.A.; Fish, B.L.; Moulder, J.E. )

    1994-03-01

    Chronic renal failure is a significant cause of late morbidity in bone marrow transplant patients whose conditioning regimen includes total body irradiation (TBI). Radiation is a major cause of this syndrome (bone marrow transplant nephropathy), but it may not be the only cause. These studies use a rat syngeneic bone marrow transplant model to determine whether nephrotoxic agents used in conjunction with bone marrow transplantation (BMT) could be enhancing or accelerating the development of radiation nephropathy. Rats received 11-17 Gy TBI in six fractions over 3 days followed by syngeneic bone marrow transplant. In conjunction with the bone marrow transplants, animals received either no drugs, cyclosporine, amphotericin, gentamicin, or busulfan. Drugs were given in schedules analogous to their use in clinical bone marrow transplantation. Drug doses were chosen so that the drug regimen alone caused detectable acute nephrotoxicity. Animals were followed for 6 months with periodic renal function tests. Gentamicin had no apparent interactions with TBI. Amphotericin increased the incidence of engraftment failure, but did not enhance radiation nephropathy. Cyclosporin with TBI caused late morbidity that appeared to be due to neurological problems, but did not enhance radiation nephropathy. Busulfan resulted in a significant enhancement of radiation nephropathy. Of the nephrotoxins used in conjunction with bone marrow transplantation only radiation and busulfan were found to be risk factors for bone marrow transplant nephropathy. 34 refs., 4 figs., 2 tabs.

  5. Interstitial pneumonitis after bone marrow transplantation. Assessment of risk factors

    SciTech Connect

    Weiner, R.S.; Bortin, M.M.; Gale, R.P.; Gluckman, E.; Kay, H.E.; Kolb, H.J.; Hartz, A.J.; Rimm, A.A.

    1986-02-01

    Data from 932 patients with leukemia who received bone marrow transplants were analyzed to determine factors associated with an increased risk of developing interstitial pneumonitis. Interstitial pneumonitis developed in 268 patients for a 2-year actuarial incidence of 35 +/- 4% (SD) and with a mortality rate of 24%. Six factors were associated with an increased risk: use of methotrexate rather than cyclosporine after transplantation (relative risk, 2.3; p less than 0.0002); older age (relative risk, 2.1; p less than 0.0001); presence of severe graft-versus-host disease (relative risk, 1.9; p less than 0.003); long interval from diagnosis to transplantation (relative risk, 1.6; p less than 0.002); performance ratings before transplantation of less than 100% (relative risk, 2.1; p less than 0.0001); and high dose-rates of irradiation in patients given methotrexate after transplantation (relative risk, 3.2; p less than 0.03). The risk of developing interstitial pneumonitis ranged from 8% in patients with none of these adverse risk factors to 94% in patients with all six. These findings may help to identify patients at high risk for this complication.

  6. 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

  7. 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

  8. 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

  9. Bone marrow transplantation in subjects with mental disorders.

    PubMed

    Akaho, Rie; Sasaki, Tsukasa; Yoshino, Miyo; Hagiya, Katsuko; Akiyama, Hideki; Sakamaki, Hisashi

    2003-06-01

    Bone marrow transplantation (BMT) is a critical treatment of malignant illnesses including leukemia and others. Successful achievement of BMT requires the patients to tolerate isolation for several weeks to avoid infections. They are also required to follow several regulations and instructions to survive the treatment because the patients' physical condition is complicated due to the malignant illness, preparatory treatment and transplant of bone marrow from other subjects. These could be a significant challenge for patients with mental disorders. Here the cases are reported of seven leukemia patients who were referred to the Metropolitan Komagome Hospital for BMT from April 1996 through May 2000, who had been suffering from mental disorders, including schizophrenia, bipolar I mood disorder, panic disorder, dysthymic disorder, autistic disorder, and borderline personality disorder, prior to the treatment. The BMT was achieved in six out of the seven subjects; the exception was a subject with borderline personality disorder. Psychiatric treatments, including medication, to improve and maintain mental status appeared to be critical for the achievement of BMT in several patients. Understanding of the status of the malignant disease and the role of BMT was another significant issue. Test admission seemed to be helpful to reduce concerns and anxiety both in the patients and hospital staff. PMID:12753572

  10. 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

  11. [The role of blood banks in bone marrow transplantation].

    PubMed

    Höcker, P; Wagner, A; Sklenar, G

    1991-01-01

    The transfusion service (TS) plays an important role in bone marrow transplantation (BMT). Many of the techniques and methods employed are also used in the daily work of a TS like tissue typing, apheresis techniques, handling of blood and its components under sterile conditions. In the pretransplantation phase the TS is responsible for the typing of recipient and presumptive donors, harvesting of autologous blood and selection of appropriate blood components. During BMT the TS can perform bone marrow harvesting, depletion of red cells in case of ABO-incompatibility and bone marrow manipulation when T-cell depletion or purging procedures are considered. Peripheral stem cell harvest by apheresis is also best performed by the TS experienced in such techniques. Storage of hematopoietic cells in liquid nitrogen and thawing are also techniques already used in most of the transfusion services. Post BMT, the support with blood components, irradiated and almost free of white cells to avoid TA-GVH and CMV-infection, is a major job of the TS. These facts demonstrate that a well organized transfusion service is a 'conditio sine qua non' for successful BMT. PMID:1725636

  12. Unmanipulated haploidentical blood and marrow transplantation: where we are.

    PubMed

    Wu, T; Lu, D P

    2009-06-01

    Human leukocyte antigen (HLA)-mismatched/haploidentical blood and marrow transplants (haplo-BMT) from family donors have been intensively studied because of the decreasing family size in mainland China, and also because the Chinese Marrow Donor Program is still not big enough. The protocol for unmanipulated haplo-BMT has been designated as 'GIAC' by Dr DP Lu--'G' represents granulocyte colony-stimulating factor mobilisation; 'I' stands for immunosuppression during pre-conditioning being prolonged and intensified; 'A' stands for the use of antithymocyte globulin; 'C' means combined use of bone marrow and peripheral blood as the graft. Haplo-BMT with GIAC regimen has been shown to be feasible for many applications as reported in 2004. Under this protocol, haplo-BMT has achieved comparable outcomes in terms of severe acute graft-versus-host disease (GVHD), chronic GVHD, relapse, treatment-related mortality (TRM), disease-free survival (DFS), and overall survival with HLA-identical sibling transplantation. The probabilities of DFS at 2 years in haplo-BMT setting were 70.7%, 49.6%, 22.2% in standard-risk, high-risk, advanced disease groups, respectively. As the third party cells, cord blood co-infusion could significantly reduce the incidence and severity of acute GVHD, and also 100-day TRM. The majority of refractory cytomegalovirus, Epstein-Barr virus and aspergillus infections can be controlled by adoptive cellular therapy. Many patients who early relapsed after BMT and failed, or are ineligible for standard therapy, have been salvaged with dendritic cell-primed cytokine-induced killer cells. With these new strategies, the lower TRM and improved DFS have been attained. Therefore, it is better to consider haplo-BMT for the patients with otherwise incurable haematological malignancies at earlier stage, when matched sibling or unrelated donors are not available. PMID:19494393

  13. Preemptive Bone Marrow Transplantation for FANCD1/BRCA2.

    PubMed

    Khan, Nicholas E; Rosenberg, Philip S; Lehmann, Harold P; Alter, Blanche P

    2015-10-01

    Children with biallelic mutations in FANCD1/BRCA2 are at uniquely high risks of leukemia and solid tumors. Preemptive bone marrow transplantation (PE-BMT) has been proposed to avoid the development of leukemia, but empirical study of PE-BMT is unlikely because of the rarity of these children and the unknown benefit of PE-BMT. We used survival analysis to estimate the risks of leukemia and the expected survival if leukemia could be eliminated by curative PE-BMT. We used the results in a decision analysis model to explore the plausibility of PE-BMT for children with variable ages at diagnosis and risks of transplantation-related mortality. For example, PE-BMT at 1 year of age with a 10% risk of transplantation-related mortality increased the mean survival by 1.7 years. The greatest benefit was for patients diagnosed between 1 and 3 years of age, after which the benefit of PE-BMT decreased with age at diagnosis, and the risk of death from solid tumors constituted a relatively greater burden of mortality. Our methods may be used to model survival for other hematologic disorders with limited empirical data and a pressing need for clinical guidance. PMID:26183081

  14. Cytomegalovirus infection in the bone marrow transplant patient

    PubMed Central

    Bhat, Vivek; Joshi, Amit; Sarode, Rahul; Chavan, Preeti

    2015-01-01

    Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear. PMID:26722656

  15. UNRELATED DONOR BONE MARROW TRANSPLANTATION FOR MYELODYSPLASTIC SYNDROME IN CHILDREN

    PubMed Central

    Woodard, Paul; Carpenter, Paul A.; Davies, Stella M.; Gross, Thomas G.; He, Wensheng; Zhang, Mei-Jie; Horn, Biljana N.; Margolis, David A.; Perentesis, John P.; Sanders, Jean E.; Schultz, Kirk R.; Seber, Adriana; Woods, William G.; Eapen, Mary

    2010-01-01

    We describe long-term disease-free survival after unrelated donor bone marrow transplantation (BMT) for myelodysplastic syndrome (MDS) in 118 patients aged ≤18 years. Forty-six patients had refractory cytopenia (RC), 55, refractory anemia with excess blasts (RAEB) and 17, refractory anemia with excess blasts in transformation (RAEB-t). Transplant-related mortality was higher after mismatched BMT (relative risk [RR] 3.29, p=0.002). Disease recurrence was more likely with advanced stages of MDS at the time of BMT: RAEB (RR 6.50, p=0.01) or RAEB-t (RR 11.00, p=0.004). Treatment failure (recurrent disease or death from any cause; inverse of disease-free survival [DFS]) occurred in 68 patients. Treatment failure was higher after mismatched BMT (RR 2.79, p=0.001) and in those with RAEB-t (RR 2.38, p=0.02). Secondary MDS or chemotherapy prior to BMT was not associated with recurrence or treatment failure. Similarly, cytogenetic abnormalities were not associated with transplant outcomes. Eight-year DFS for patients with RC after matched and mismatched unrelated donor BMT was 65% and 40%, respectively. Corresponding DFS for patients with RAEB and RAEB-t was 48% and 28%, respectively. When a matched adult unrelated donor is available, BMT should be offered as first-line therapy and children with RC can be expected to have the best outcome. PMID:20813197

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

    PubMed

    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

  17. 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

  18. 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

  19. A systematic review of psychosocial factors affecting survival after bone marrow transplantation.

    PubMed

    Hoodin, Flora; Weber, Shauncie

    2003-01-01

    An electronic database search identified 15 studies of psychosocial factors affecting survival after bone marrow transplantation. The studies were assessed for methodological quality by two reviewers using the procedures of Bland and colleagues. Although some studies found that psychological variables affect survival after bone marrow transplantation, the reviewers' analysis of the methodologically sound studies suggested that survival after bone marrow transplantation is not substantively affected by depressed mood or other psychopathology in adults or by social support in adults or children. Longer survival may be related to lower "anxious preoccupation," higher "fighting spirit," and better quality of life ratings before and soon after transplant in adults. Overall, however, the literature is insufficiently developed to provide definitive evidence for a relationship between psychological variables and survival after bone marrow transplantation. Future primary studies in this area should be designed to maximize replicability and generalizability. PMID:12724499

  20. 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

  1. The single-staff model for bone marrow transplantation.

    PubMed

    Giles, K; Winslow, M N; Vaughan, W P

    1994-11-01

    This paper will demonstrate the advantages of pursuing an integrated model of care that utilizes one staff of caregivers in one facility for all phases of patient care from the time of patient evaluation through the time the patient returns to the care of his or her primary physician. We took the opportunity afforded by the development of a new program at the University of Alabama at Birmingham, the Bone Marrow Transplantation (BMT) Program, to reconsider as many variables as possible in an attempt to develop a model of care that would represent the best of all worlds, i.e., high levels of quality of care, quality of life, staff job enrichment, patient convenience, operational efficiency, and cost reduction. PMID:10140894

  2. Extrathymic development of murine T cells after bone marrow transplantation

    PubMed Central

    Holland, Amanda M.; Zakrzewski, Johannes L.; Tsai, Jennifer J.; Hanash, Alan M.; Dudakov, Jarrod A.; Smith, Odette M.; West, Mallory L.; Singer, Natalie V.; Brill, Jessie; Sun, Joseph C.; van den Brink, Marcel R.M.

    2012-01-01

    Restoring T cell competence is a significant clinical challenge in patients whose thymic function is severely compromised due to age or cytoreductive conditioning. Here, we demonstrate in mice that mesenteric LNs (MLNs) support extrathymic T cell development in euthymic and athymic recipients of bone marrow transplantation (BMT). Furthermore, in aged murine BMT recipients, the contribution of the MLNs to the generation of T cells was maintained, while the contribution of the thymus was significantly impaired. Thymic impairment resulted in a proportional increase in extrathymic-derived T cell progenitors. Extrathymic development in athymic recipients generated conventional naive TCRαβ T cells with a broad Vβ repertoire and intact functional and proliferative potential. Moreover, in the absence of a functional thymus, immunity against known pathogens could be augmented using engineered precursor T cells with viral specificity. These findings demonstrate the potential of extrathymic T cell development for T cell reconstitution in patients with limited thymic function. PMID:23160195

  3. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls. PMID:124758

  4. Modern approaches to HLA-haploidentical blood or marrow transplantation

    PubMed Central

    Kanakry, Christopher G.; Fuchs, Ephraim J.; Luznik, Leo

    2015-01-01

    Allogeneic blood or bone-marrow transplantation (alloBMT) is a potentially curative treatment for a variety of haematological malignancies and nonmalignant diseases. Historically, human leukocyte antigen (HLA)-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with alloBMT using other donors. Although only approximately one-third of patients have an HLA-matched sibling, nearly all patients have HLA-haploidentical related donors. Early studies using HLA-haploidentical alloBMT resulted in unacceptably high rates of graft rejection and graft-versus-host disease (GVHD), leading to high nonrelapse mortality and consequently poor survival. Several novel approaches to HLA-haploidentical alloBMT have yielded encouraging results with high rates of successful engraftment, effective GVHD control and favourable outcomes. In fact, outcomes of several retrospective comparative studies seem similar to those seen using other allograft sources, including those of HLA-matched-sibling alloBMT. In this Review, we provide an overview of the three most-developed approaches to HLA-haploidentical alloBMT: T-cell depletion with ‘megadose’ CD34+ cells; granulocyte colony-stimulating factor-primed allografts combined with intensive pharmacological immunosuppression, including antithymocyte globulin; and high-dose, post-transplantation cyclophosphamide. We review the preclinical and biological data supporting each approach, results from major clinical studies, and completed or ongoing clinical studies comparing these approaches with other alloBMT platforms. PMID:26305035

  5. 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

  6. Value of surveillance cultures in a bone marrow transplantation unit.

    PubMed

    Czirók, E; Prinz, G Y; Dénes, R; Reményi, P; Herendi, A

    1997-09-01

    Because of the increased risk of infection with the associated diagnostic and therapeutic problems in bone marrow transplantation (BMT) patients, the usefulness of surveillance cultures (SC) at the BMT department of the National Institute of Haematology, Blood Transfusion, Transplantation and Immunology, Budapest, was reviewed. Between January 1992 and May 1995, 26 BMT operations were performed; 13 patients had 23 febrile espisodes. In 12 of these episodes infection was clinically documented; however, SC of these patients yielded bacteria identical with those in the blood culture in only two episodes (1 and 6 days before their blood cultures became positive, respectively). Out of a total of 1187 samples from these patients, potentially pathogenic bacteria were isolated from 145 SC and 43 blood cultures (drawn on 31 different days). Suppression of the gastrointestinal flora could be achieved by the department's decontamination regimen; however, overgrowth by gram-positive organisms (mainly coagulase-negative staphylococci) occurred in the intestine and at other body sites. On the basis of these results, SC are of limited value in predicting infection or identifying the causative organisms of fever. On the other hand, SC are useful in confirming the efficiency of suppression of the body flora by antimicrobial agents. Specific treatment was based on suitably sampled materials, and close contact between physicians, infectious disease specialists and microbiologists was essential. PMID:9291891

  7. 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.

  8. Remodeling of the thoracic aorta after bone marrow cell transplantation

    PubMed Central

    Felix, Alyne; Monteiro, Nemesis; Rocha, Vinícius Novaes; Oliveira, Genilza; Moraes, Alan Cesar; Andrade, Cherley; Nascimento, Ana Lucia; de Carvalho, Laís; Thole, Alessandra; Carvalho, Jorge

    2014-01-01

    Stem cells are characterized by their ability to differentiate into multiple cell lineages and display the paracrine effect. The aim of this work was to evaluate the effect of therapy with bone marrow cells (BMCs) on blood glucose, lipid metabolism and aortic wall remodeling in mice through the administration of a high fat diet and subsequent BMCs transplantation. C57BL/6 mice were fed a control diet (CO group) or an atherogenic diet (AT group). After 16 weeks, the AT group was divided into four groups: an AT 14 days group and AT 21 days group, that were given an injection of vehicle and sacrificed at 14 and 21 days after, respectively; AT-BMC 14 days group and AT-BMC 21 days group that was given an injection of BMCs and sacrificed at 14 and 21 days after. The CO group was sacrificed along with other groups. The BMCs transplant had reduced blood glucose, triglycerides and total cholesterol. The Qa (1/mm2) was quantitatively reduced in AT 14 days group, AT 21 days group and was high in AT-BMC 21 days group. The AT 21 days group exhibited increased tunica media and elastic system fibers. The immunolabeling for α-SMA and VEGF showed less immunolabeling in transplanted groups with BMCs. The immunostaining for PCNA seems to be more expressive in the group AT-BMC 21 days group. To conclude, our results support the concept that in mice, the injection of BMCs improve glucose levels, lipid metabolism and remodeling of the aortic wall in animals using atherogenic diet. PMID:25337194

  9. Pain Management for Children during Bone Marrow and Stem Cell Transplantation

    PubMed Central

    Vasquenza, Kelly; Ruble, Kathy; Chen, Allen; Billett, Carol; Kozlowski, Lori; Atwater, Sara; Kost-Byerly, Sabine

    2014-01-01

    Pain management for children during bone marrow and stem cell transplantation is a significant clinical challenge for the health care team. Pain management strategies vary by institution. This paper reports on the use of a pediatric pain management service and patient-and caregiver-controlled analgesia for children undergoing transplant. This 2-year retrospective chart review examined the pain management practices and outcomes of children undergoing bone marrow and stem cell transplants in a large urban teaching hospital during 2008 and 2009. We concluded that patient- and caregiver-controlled analgesia is a well-tolerated modality for pain control during hospitalization for transplantation at this institution. PMID:25267531

  10. What Are the Risks of a Blood and Marrow Stem Cell Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. What Are the Risks of a Blood and Marrow Stem Cell Transplant? ... are more likely to have graft failure. Other Risks The chemotherapy and/or radiation you receive during ...

  11. Development and characterization of a lung-protective method of bone marrow transplantation in the mouse.

    PubMed

    Janssen, William J; Muldrow, Alaina; Kearns, Mark T; Barthel, Lea; Henson, Peter M

    2010-05-31

    Allogeneic bone marrow transplantation is a common method used to study the contribution of myeloid and lymphoid cell populations in murine models of disease. The method requires lethal doses of radiation to ablate the bone marrow. Unintended consequences of radiation include organ injury and inflammatory cell activation. The goal of our study was to determine the degree to which bone marrow transplantation alters lungs and to develop a system to protect the lungs during radiation. C57BL/6 mice were subjected to total body irradiation with 900cGy and then transplanted with bone marrow from green fluorescent protein (GFP) expressing mice. Resultant chimeras exhibited a significant decline in alveolar macrophage numbers within 72h, modest influx of neutrophils in the lungs at 14days, and repopulation of the lungs by alveolar macrophages of bone marrow origin by 28days. Neutrophil influx and alveolar macrophage turnover were prevented when 1cm thick lead shields were used to protect the lungs during radiation, such that 8weeks after transplantation less than 30% of alveolar macrophages were of donor origin. Lung-shielded mice achieved a high level of bone marrow engraftment with greater than 95% of circulating leukocytes expressing GFP. In addition, their response to intratracheal lipopolysaccharide was similar to non-transplanted mice. We describe a model whereby lead shields protect resident cell populations in the lungs from radiation during bone marrow transplantation but permit full bone marrow engraftment. This system may be applicable to other organ systems in which protection from radiation during bone marrow transplantation is desired. PMID:20347833

  12. Aortic stenosis in a patient with Hurler's syndrome after bone marrow transplantation.

    PubMed

    Watanabe, Naruhito; Anagnostopoulos, Petros V; Azakie, Anthony

    2011-06-01

    We describe a case of severe aortic stenosis in a 16-year-old male with Hurler's syndrome who had prior bone marrow transplantation. The excised aortic valve leaflets showed characteristic pathologic findings of Hurler's syndrome. This is the first case report of aortic valve replacement in a patient with Hurler's syndrome treated with bone marrow transplantation that demonstrates progression of the aortic valve disease despite treatment. PMID:21262073

  13. Herpes simplex virus (HSV) colitis in a bone marrow transplant recipient.

    PubMed

    Naik, H R; Chandrasekar, P H

    1996-02-01

    Herpes simplex virus (HSV) infections are common in bone marrow transplantation patients. Unusual sites may be involved, however colonic disease with HSV is rare. We report a successfully treated case of colitis due to HSV, cytomegalovirus, Clostridium difficile and graft-versus-host disease in an allogeneic marrow recipient. PMID:8640181

  14. 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.

  15. Body Composition After Bone Marrow Transplantation in Childhood

    PubMed Central

    Ruble, Kathy; Hayat, Matthew; Stewart, Kerry J.; Chen, Allen

    2014-01-01

    Purpose/Objectives To describe the body composition and fat distribution of childhood bone marrow transplantation (BMT) survivors at least one year post-transplantation and examine the ability of the Centers for Disease Control and Prevention criteria to identify survivors with elevated body fat percentage. Design Cross-sectional, descriptive. Setting Pediatric oncology program at a National Cancer Institute–designated comprehensive cancer center. Sample 48 childhood BMT survivors (27 males and 21 females). Methods Measurements included dual-energy x-ray absorptiometry scan, height, weight, and physical activity. Descriptive statistics were reported and mixed-model linear regression models were used to describe findings and associations. Main Research Variables Total body fat percentage and central obesity (defined as a ratio of central to peripheral fat of 1 or greater). Findings Fifty-four percent of survivors had body fat percentages that exceeded recommendations for healthy body composition and 31% qualified as having central obesity. Previous treatment with total body irradiation was associated with higher body fat percentage and central obesity, and graft-versus-host disease was associated with lower body fat percentage. The body mass index (BMI) criteria did not correctly identify the BMT survivors who had elevated body fat percentage. Conclusions Survivors of childhood BMT are at risk for obesity and central obesity that is not readily identified with standard BMI criteria. Implications for Nursing Nurses caring for BMT survivors should include evaluation of general and central obesity in their assessments. Patient education materials and resources for healthy weight and muscle building should be made available to survivors. Research is needed to develop appropriate interventions. PMID:22374492

  16. Current Opinion of Bone Marrow Stromal Cell Transplantation for Ischemic Stroke

    PubMed Central

    KURODA, Satoshi

    2016-01-01

    This article reviews recent advancement and perspective of bone marrow stromal cell (BMSC) transplantation for ischemic stroke, based on current information of basic and translational research. The author would like to emphasize that scientific approach would enable us to apply BMSC transplantation into clinical situation in near future. PMID:26984453

  17. Establishment of a bone marrow transplant satellite pharmacy.

    PubMed

    Woloschuk, D M; Nazeravich, D R; Gray, L J; Larter, J M

    1993-02-01

    The planning, establishment and operation of a bone marrow transplant (B.M.T.) satellite pharmacy in a 1100-bed teaching hospital are described. The B.M.T. satellite pharmacy was established because of the specialized pharmaceutical care needs of this patient population with a high risk for drug-related problems. The satellite pharmacy, which is located within a 19-bed Oncology Unit, provides integrated clinical-distributive services (unit-dose, IV-admixture system) to all B.M.T. patients. The satellite is open 10.5 hours per day, seven days per week. Staff consists of three full-time equivalent (F.T.E.) staff pharmacists, a 0.5 F.T.E. technician, and one F.T.E. clinical pharmacist. Staff pharmacists rotate between provision of B.M.T. pharmacy services, and provision of pharmacy services for the provincial Home Parenteral Nutrition program. The pharmacists are responsible for all aspects of drug distribution and clinical services for B.M.T. patients. Additional drug distribution and clinical services are provided to other Oncology Unit patients. The establishment of a satellite pharmacy has provided unique opportunities for pharmaceutical care of the B.M.T. patient. PMID:10124614

  18. Assessment of psychological distress in prospective bone marrow transplant patients.

    PubMed

    Trask, P C; Paterson, A; Riba, M; Brines, B; Griffith, K; Parker, P; Weick, J; Steele, P; Kyro, K; Ferrara, J

    2002-06-01

    Patient psychological distress is associated with many aspects of the bone marrow transplantation (BMT) process and has been linked with poor treatment outcomes. We assessed psychological distress in potential BMT candidates, and compared patient and nurse coordinator ratings of emotional distress at the time of initial BMT consultation. Fifty patients self-reported psychological distress using both the NCCN Distress Thermometer (DT) and the Hospital Anxiety and Depression Scale (HADS). Coordinators rated patient emotional distress using the DT and Coordinator Rating Scales that measure anxiety and depression. Fifty and 51% of patients self-reported clinically significant levels of emotional distress and anxiety, respectively, but only 20% self-reported clinically significant levels of depression. There was good correlation between ratings using the brief DT and the more comprehensive HADS. There was significant but only moderate agreement between patient and coordinator ratings of emotional distress and anxiety, with coordinators underestimating the number of patients with high levels of emotional distress. In addition, coordinator ratings of patient emotional distress primarily reflected anxiety, whereas anxiety and depression together only minimally accounted for patient self-reports of psychological distress. These findings suggest that: (1) the DT can be a useful screening device; (2) approximately half of patients at the time of initial consultation for BMT already experience significant levels of psychological distress; and (3) coordinators observe emotional distress primarily as anxiety, but patients experience psychological distress as something more than anxiety and depression. PMID:12080358

  19. Reconstitution of the CD45RO(+) and CD20(+) lymphoid marrow population following allogeneic bone marrow transplantation for Ph(+) CML.

    PubMed

    Thiele, J; Kvasnicka, H M; Beelen, D W; Welter, A; Schneider, S; Leder, L D; Schaefer, U W

    2001-02-01

    Following bone marrow transplantation (BMT) investigations on the recovery of the B and T lymphocyte populations have focused on the peripheral blood and only marginally regard the bone marrow. An immunohistochemical and morphometric study was performed on 352 trephine biopsies derived from 123 patients with chronic myelogenous leukemia (CML) at standardized endpoints before and after allogeneic BMT and compared to a control group. The purpose of this investigation was to quantify the B-CD20(+) and T-CD45RO(+) lymphocyte subsets and to determine possible relationships with the occurrence of acute and chronic GVHD. Moreover, we studied the dynamics of lymphocyte repopulation in the post-transplant period, correlations with the total peripheral lymphocyte count and differences associated with sibling vs alternate HLA-compatible (unmanipulated) marrow grafts. Morphometric analysis revealed a very fast regeneration of CD45RO(+) and CD20(+) marrow lymphocytes in the first 2 weeks following BMT. In less than 2 months, in most patients, the post-transplant quantity of lymphocytes was comparable to that of the normal bone marrow. This finding was opposed to the profound depression of the absolute lymphocyte count in the peripheral blood. No relevant relationships could be calculated between engraftment status and the lymphocyte repopulation in the bone marrow. On the other hand, significant correlations were calculable between the development of (chronic and acute) GVHD including severity with the number of CD45RO(+) lymphocytes. In non-related graft constellations a more frequent evolution of acute grade III + IV GVHD was detectable. This complication was accompanied by an increased quantity of CD45RO(+) lymphocytes in the marrow. PMID:11313672

  20. Demonstration of clonable alloreactive host T cells in a primate model for bone marrow transplantation

    SciTech Connect

    Reisner, Y.; Ben-Bassat, I.; Douer, D.; Kaploon, A.; Schwartz, E.; Ramot, B.

    1986-06-01

    The phenomenon of marrow rejection following supralethal radiochemotherapy was explained in the past mainly by non-T-cell mechanisms known to be resistant to high-dose irradiation. In the present study a low but significant number of radiochemoresistant-clonable T cells was found in the peripheral blood and spleen of Rhesus monkeys following the cytoreductive protocol used for treatment of leukemia patients prior to bone marrow transplantation. More than 95% of the clonable cells are concentrated in the spleen 5 days after transplant. The cells possess immune memory as demonstrated by the generation of alloreactive-specific cytotoxicity. The present findings suggest that host-versus-graft activity may be mediated by alloreactive T cells. It is hoped that elimination of such cells prior to bone marrow transplantation will increase the engraftment rate of HLA-nonidentical marrow in leukemia patients.

  1. 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.

  2. Immunoglobulin levels in dogs after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Vriesendorp, H.M.; Halliwell, R.E.; Johnson, P.M.; Fey, T.A.; McDonough, C.M.

    1985-06-01

    The influence of total-body irradiation (TBI) and autologous or allogeneic bone marrow transplantation on serum immunoglobulin subclasses was determined in a dog model. Only IgG1 levels decreased after low-dose (+/- 4.5 Gy) TBI, but levels of all immunoglobulin classes fell after high-dose TBI (8.5 GyX1 or 2X6.0 Gy). After autologous bone marrow transplantation IgM levels were the first and IgE levels were the last to return to normal. After successful allogeneic bone marrow transplantation prolonged low IgM and IgE levels were found but IgA levels increased rapidly to over 150% of pretreatment values. A comparison of dogs with or without clinical signs or graft-versus-host disease (GVHD), revealed no differences in IgM levels. Dogs with GVHD had higher IgA but lower IgE levels. Dogs that rejected their allogeneic bone marrow cells showed significant early rises in IgE and IgA levels in comparison with dogs with GVHD. These results differ from the observations made on Ig levels in human bone marrow transplant patients. No significant differences in phytohemagglutinin stimulation tests were found between dogs with or without GVHD or dogs receiving an autologous transplant for the first four months after TBI and transplantation. An early primary or secondary involvement of humoral immunity in GVHD and graft rejection in dogs is postulated.

  3. Bone marrow transplantation for acute myelogenous leukemia: factors associated with early mortality

    SciTech Connect

    Bortin, M.M.; Gale, R.P.; Kay, H.E.; Rimm, A.A.

    1983-03-04

    Comprehensive data were reported to the International Bone Marrow Transplant Registry, Milwaukee, regarding 156 patients with acute myelogenous leukemia who were treated with allogeneic bone marrow transplantation between 1978 and 1980. The minimum observation period was 15 months after transplant and most deaths occurred within the first six months. Prognostic factors were evaluated for associations with early mortality or life-threatening complications. Most early deaths were due to infections, interstitial pneumonitis, and graft-v-host disease (GVHD). Multivariate analyses disclosed five factors with significant associations with early death or a major cause of early death: (1) disease status; (2) dose-rate of irradiation; (3) drug used to prevent GVHD; (4) severity of GVHD; and (5) dose of marrow cells.It is emphasized that several of the important prognostic factors are within the control of the referring physician or the transplant team.

  4. Intravenous transplantation of bone marrow mesenchymal stem cells promotes neural regeneration after traumatic brain injury

    PubMed Central

    Anbari, Fatemeh; Khalili, Mohammad Ali; Bahrami, Ahmad Reza; Khoradmehr, Arezoo; Sadeghian, Fatemeh; Fesahat, Farzaneh; Nabi, Ali

    2014-01-01

    To investigate the supplement of lost nerve cells in rats with traumatic brain injury by intravenous administration of allogenic bone marrow mesenchymal stem cells, this study established a Wistar rat model of traumatic brain injury by weight drop impact acceleration method and administered 3 × 106 rat bone marrow mesenchymal stem cells via the lateral tail vein. At 14 days after cell transplantation, bone marrow mesenchymal stem cells differentiated into neurons and astrocytes in injured rat cerebral cortex and rat neurological function was improved significantly. These findings suggest that intravenously administered bone marrow mesenchymal stem cells can promote nerve cell regeneration in injured cerebral cortex, which supplement the lost nerve cells. PMID:25206912

  5. Long Term Clinical Outcome of Patients with Severe Combined Immunodeficiency who Received Related Donor Bone Marrow Transplants without Pre-transplant Chemotherapy or Post-transplant GVHD Prophylaxis

    PubMed Central

    Railey, Mary Dell; Lokhnygina, Yuliya; Buckley, Rebecca H.

    2009-01-01

    Objective To determine long term health benefits of non-ablative bone marrow transplantation for severe combined immunodeficiency (SCID), we investigated our cohort of 161 related donor bone marrow transplanted SCID patients. Only 16 (10%) had HLA-identical donors. Study design All 124 survivors were sent questionnaires about their current clinical statuses. Details from clinic visits were also compiled. One hundred eleven patients (90%) were reached. We compared outcomes of patients transplanted before and after 3.5 months of life and by molecular defect. Results The overall survival rate is 77%, but the rate for the 48 infants transplanted in the first 3.5 months of life is 94%, compared with 70% for the 113 transplanted after 3.5 months (p=0.002). Twenty-eight (76%) of the 37 deceased patients died from viral infections present at diagnosis. One or more clinical problems were reported to have been present in the past two years in 71 (64%) of the survivors, although 95 (86%) are considered healthy by their families. Conclusions Most patients with SCID transplanted with related donor marrow without pre-transplant chemotherapy have done well long-term, but those transplanted at <3.5 months of age had a superior survival rate, a lower rate of clinical problems, less need for booster transplants and better nutritional status. PMID:19818451

  6. Molecular relapse in chronic myelogenous leukemia patients after bone marrow transplantation detected by polymerase chain reaction

    SciTech Connect

    Sawyers, C.L.; Timson, L.; Clark, S.S.; Witte, O.N.; Champlin, R. ); Kawasaki, E.S. )

    1990-01-01

    Relapse of chronic myelogenous leukemia after bone marrow transplantation can be detected by using clinical, cytogenetic, or molecular tools. A modification of the polymerase chain reaction can be used in patients to detect low levels of the BCR-ABL-encoded mRNA transcript, a specific marker for chronic myelogenous leukemia. Early detection of relapse after bone marrow transplantation could potentially alter treatment decisions. The authors prospectively evaluated 19 patients for evidence of molecular relapse, cytogenetic relapse, and clinical relapse after bone marrow transplantation. They used the polymerase chain reaction to detect residual BCR-ABL mRNA in patients followed up to 45 months after treatment and found 4 patients with BCR-ABL mRNA expression following bone marrow transplantation. Fifteen patients did not express detectable BCR-ABL mRNA. All 19 patients remain in clinical remission. In this prospective study of chronic myelogenous leukemia patients treated with bone marrow transplantation, molecular relapse preceded cytogenetic relapse in those patients who persistently express BCR-ABL mRNA. They recommend using standard clinical and cytogenetic testing to make patient care decisions until further follow-up determines the clinical outcome of those patients with residual BCR-ABL mRNA transcripts detected by polymerase chain reaction.

  7. Acute myocardial infarction after bone marrow transplantation: an unsuspected late complication.

    PubMed

    Gatt, M E; Liebster, D; Leibowitz, D; Matzner, Y

    2003-02-01

    Acute myocardial infarction is a common disease rarely seen as a complication of bone marrow transplantation in young patients. We report on a 25-year-old patient 3.5 years after bone marrow transplantation who suffered an acute anterior wall myocardial infarction complicated by cardiogenic shock. The patient was treated with thrombolysis and emergent coronary angioplasty but died a few hours following admission. We suggest that the combination of low-dose chest irradiation and prolonged immunosuppression with graft-versus-host disease contributed to the development of the coronary artery disease in this patient. Though rarely encountered, physicians caring for young patients after bone marrow transplantation should be aware of potential ischemic complications. PMID:12601497

  8. Bone marrow transplantation in Basel: single center experience from 1973 to 1989.

    PubMed

    Speck, B; Nissen, C; Tichelli, A; Roth, J; Dazzi, H; Stebler, C H; Wernli, M; Signer, E; Gratwohl, A

    1989-01-01

    Bone marrow transplantation with a small to medium-sized single hospital team is feasible. It leads to results similar to those observed at large centers and with the same major risk factors: age, stage of the disease at the time of transplant, degree of histocompatibility, graft-versus-host disease prevention method, and selection. A single small to medium-sized center cannot conduct prospective randomized studies but it can pioneer new concepts. Bone marrow transplantation today offers a good choice for patients suffering from otherwise lethal bone marrow diseases. These include severe aplastic anemia, acute leukemias, chronic myeloid and chronic lymphoid leukemia, myelodysplastic syndrome, and congenital disorders. Changes in outcome are due to innovative steps, such as the introduction of CsA for GvHD prevention. In addition they are certainly influenced by unrecognized changes in the patient selection process. PMID:2487556

  9. 5-Azacytidine as Salvage Treatment in Relapsed Myeloid Tumors after Allogeneic Bone Marrow Transplantation

    PubMed Central

    Bolaños-Meade, Javier; Smith, B. Douglas; Gore, Steven D.; McDevitt, Michael A.; Luznik, Leo; Fuchs, Ephraim J.; Jones, Richard J.

    2011-01-01

    Relapse after allogeneic blood or marrow transplantation carries a very poor prognosis. Current strategies for management that include donor lymphocyte infusions (DLIs) and salvage chemotherapies are usually toxic and ineffective. Here we report the outcome of 10 patients with myeloid malignancies that received 5-azacytidine after a failed allogeneic bone marrow transplant. Of the 10 patients, 6 achieved a complete remission, 1 had stable disease, and 3 progressed after a median of 6 cycles administered. Only 1 patient has died (of disease progression), and no flares of graft-versus-host disease (GVHD) were observed with 5-azacytidine. As of latest follow-up, the median overall survival (OS) for the group was 422.5 days (127–1411). These results further suggest that 5-azacytidine is an active agent after failing an allogeneic bone marrow transplant, and prospective studies are warranted. PMID:20951817

  10. Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for lymphoid malignancies.

    PubMed

    Vose, J M; Kennedy, B C; Bierman, P J; Kessinger, A; Armitage, J O

    1992-02-01

    The study was made to evaluate the long-term physical and psychosocial changes after high-dose therapy and autologous bone marrow or peripheral stem transplantation for recurrent lymphoid malignancies. Patients who had undergone high dose therapy and autologous bone marrow or peripheral stem cell transplantation for recurrent lymphoid malignancies at least 1 year previously were contacted by phone interview regarding their status after the transplant. The patients' comments were confirmed by checking medical records when possible. Fifty patients who had undergone transplantation at the University of Nebraska Medical Center at least 1 year before the interview were available for interview and willing to answer questions. After transplant, many patients noticed temporary changes in their appearance, which usually returned to normal within 1 year. Few patients reported remarkable cardiovascular, gastrointestinal, or pulmonary changes after transplantation. However, up to one-third of the patients reported changes in sexual function or desire. The most common infectious problem after transplant was Herpes zoster, which occurred in 25% of the patients. Overall, the patients had a positive outlook after high-dose therapy and transplantation, with most being able to return to work and enjoy a normal life style. Ninety-six percent of the patients stated that they would be willing to undergo high-dose therapy and transplantation again under the same circumstances. PMID:1730128

  11. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma

    PubMed Central

    Giralt, Sergio; Garderet, Laurent; Durie, Brian; Cook, Gordon; Gahrton, Gosta; Bruno, Benedetto; Hari, Paremesweran; Lokhorst, Henk; McCarthy, Phillip; Krishnan, Amrita; Sonneveld, Pieter; Goldschmidt, Harmut; Jagannath, Sundar; Barlogie, Bart; Mateos, Maria; Gimsing, Peter; Sezer, Orhan; Mikhael, Joseph; Lu, Jin; Dimopoulos, Meletios; Mazumder, Amitabha; Palumbo, Antonio; Abonour, Rafat; Anderson, Kenneth; Attal, Michel; Blade, Joan; Bird, Jenny; Cavo, Michele; Comenzo, Raymond; de la Rubia, Javier; Einsele, Hermann; Garcia-Sanz, Ramon; Hillengass, Jens; Holstein, Sarah; Johnsen, Hans Erik; Joshua, Douglas; Koehne, Guenther; Kumar, Shaji; Kyle, Robert; Leleu, Xavier; Lonial, Sagar; Ludwig, Heinz; Nahi, Hareth; Nooka, Anil; Orlowski, Robert; Rajkumar, Vincent; Reiman, Anthony; Richardson, Paul; Riva, Eloisa; Miguel, Jesus San; Turreson, Ingemar; Usmani, Saad; Vesole, David; Bensinger, William; Qazilbash, Muzaffer; Efebera, Yvonne; Mohty, Mohamed; Gasparreto, Christina; Gajewski, James; LeMaistre, Charles F.; Bredeson, Chris; Moreau, Phillipe; Pasquini, Marcelo; Kroeger, Nicolaus; Stadtmauer, Edward

    2016-01-01

    In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short

  12. American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma.

    PubMed

    Giralt, Sergio; Garderet, Laurent; Durie, Brian; Cook, Gordon; Gahrton, Gosta; Bruno, Benedetto; Hari, Paremesweran; Lokhorst, Henk; McCarthy, Phillip; Krishnan, Amrita; Sonneveld, Pieter; Goldschmidt, Harmut; Jagannath, Sundar; Barlogie, Bart; Mateos, Maria; Gimsing, Peter; Sezer, Orhan; Mikhael, Joseph; Lu, Jin; Dimopoulos, Meletios; Mazumder, Amitabha; Palumbo, Antonio; Abonour, Rafat; Anderson, Kenneth; Attal, Michel; Blade, Joan; Bird, Jenny; Cavo, Michele; Comenzo, Raymond; de la Rubia, Javier; Einsele, Hermann; Garcia-Sanz, Ramon; Hillengass, Jens; Holstein, Sarah; Johnsen, Hans Erik; Joshua, Douglas; Koehne, Guenther; Kumar, Shaji; Kyle, Robert; Leleu, Xavier; Lonial, Sagar; Ludwig, Heinz; Nahi, Hareth; Nooka, Anil; Orlowski, Robert; Rajkumar, Vincent; Reiman, Anthony; Richardson, Paul; Riva, Eloisa; San Miguel, Jesus; Turreson, Ingemar; Usmani, Saad; Vesole, David; Bensinger, William; Qazilbash, Muzaffer; Efebera, Yvonne; Mohty, Mohamed; Gasparreto, Christina; Gajewski, James; LeMaistre, Charles F; Bredeson, Chris; Moreau, Phillipe; Pasquini, Marcelo; Kroeger, Nicolaus; Stadtmauer, Edward

    2015-12-01

    In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward. After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short

  13. Peripheral blood stem cell versus bone marrow transplantation: A perspective from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

    PubMed

    Byrne, Michael; Savani, Bipin N; Mohty, Mohamad; Nagler, Arnon

    2016-07-01

    Over the past decade, transplantation of peripheral blood hematopoietic cells has increased and is now the predominant graft source for related or unrelated adult allogeneic hematopoietic stem cell transplantation. At the same time, increasing numbers of patients are receiving reduced-intensity conditioning (RIC) prior to hematopoietic stem cell infusion. In prior work using smaller patient numbers and limited data, RIC peripheral blood stem cell (PBSC) transplantation was shown to be noninferior to RIC bone marrow (BM) transplantation for acute leukemia. A recent, large registry analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation showed that peripheral blood grafts result in superior outcomes compared with BM after RIC regimens for acute leukemia. The T-cell-replete PBSC allografts are associated with significant graft-versus-leukemia (GVL) benefits that are important drivers of improved leukemia-free survival and overall survival. However, an increased risk of chronic graft-versus-host disease (cGVHD) after peripheral blood grafts is concerning and long-term follow-up comparing peripheral versus BM grafts after RIC regimens is needed. Further assessment of the long-standing risks should be undertaken in an effort to better understand whether the risk of cGVHD among peripheral blood graft recipients translates into continued GVL effects and long-term remissions and cures or if it results in late morbidity and mortality. PMID:27106798

  14. 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.

  15. [Remembering the first successful bone marrow transplantation performed in 1977 in Novi Sad].

    PubMed

    Popović, K

    1998-01-01

    The author describes circumstances under which a young man with a severe idiopathic aplastic anemia, pancytopenia and hemorrhagic syndrome had undergone the first successful bone marrow transplantation performed at the Department of Haematology of the Internal Clinic in Novi Sad in 1977. As the patient did not react to the androgenic therapy and he had a healthy twin-brother with the same blood group and HLA system and MCL, differing only in Rh genotype, bone marrow transplantation was suggested. Attempted transplantation without immunosuppression and with a small number of bone marrow cells was performed in 1976 at the Military Medical Academy (MMA) in Belgrade, but it was unsuccessful. The patient suffered from a serious pancytopenia and hemorrhagic syndrome, and survived due to blood transfusions. There were 56 blood transfusions with more than 20 liters of blood. At that time bone marrow transplantations were not performed in Yugoslavia, only MMA started this method. The patient could not be transported, so the author with his associates decided to perform a new transplantation with immunosuppressive therapy with cyclophosphamide and with sufficient number of bone marrow cells, believing that it was the only chance their patient had to get better. Without special equipment, improvising a sterile room, the author performed a new transplantation. Two weeks later first signs of improvement of pancytopenia occurred, whereas after reticulocytic crisis, 45 days later, the number of blood cells reached normal values. On the occasion of examining Rh genotype of our patient it was established that, instead of previous Rh genotype inherited from his father, after retransplantation he had a new Rh phenotype acquired from his brother who inherited it from their mother. It was a proof that the transplantation was a complete success. On the occasion of 20th anniversary of that event in 1977, the whole team, which had performed the retransplantation, met their ex

  16. [Studies of immunological status, following autologous bone marrow transplantation in man (author's transl)].

    PubMed

    Gorin, N C; Muller, J Y; Salmon, C; Fine, J M; Rouger, P; Fortier, B; Petit, J C; Girard, O; Leblanc, G; David, R; Stachowiak, J; Parlier, Y; Najman, A; Duhamel, G

    1980-05-10

    Following transplant, circulating immunoglobulin levels fell moderately and remained depressed less than 2 months for IgG, and for variable and longer periods of time for IgM and IgA. Repeated quantitative determinations of antibodies against multiple antigens did not show any decrease in the pretransplant levels. Indeed some patients developed herpes and cytomegalovirus infections to which they responded by a sharp increase in antibody titers. In 2 cases, a primary immunization was demonstrated (against CMV and BK virus) with increasing levels of IgM and IgG antibodies. Lymphocyte counts in peripheral blood returned to 500 mm# between day 10 and 29 (median day 18) and to pretransplant values within 6 weeks. Non specific stimulation of lymphocytes by mitogens in the immediate post-transplant period showed a decreased response to PHA and Con A, whereas the responses to pokeweek mitogens and alloantigens were only slightly diminished. The degree of the responses was related to the dose of cryopreserved marrow infused. We conclude that:--although the minimum dose for autologous bone marrow transplantation in man is around 0,5 10(8) nucleated bone marrow cells/Kg, much higher doses should be used to ensure faster and better restoration of immune reactivity.--The similarity of the immunological dysfunction following autologous and allogeneous bone marrow transplantation suggest that, in the immediate post-transplant period, the role of GVHD in cellular immunity depression may be minimal. PMID:7008023

  17. Diagnosis and clinical associations of zinc depletion following bone marrow transplantation.

    PubMed Central

    Papadopoulou, A; Nathavitharana, K; Williams, M D; Darbyshire, P J; Booth, I W

    1996-01-01

    Following the emergence of biochemical zinc deficiency after bone marrow transplantation, the clinical value of plasma alkaline phosphatase activity as an early indicator of biochemical zinc depletion was investigated in this group of patients. Serial measurements of plasma zinc and alkaline phosphatase activities in 28 consecutive children (median age 8.7 years; 16 males) undergoing bone marrow transplantation were carried out and clinical associations recorded. A significant fall in plasma zinc occurred after the bone marrow transplant, and 19 children developed biochemical zinc deficiency (Zn < 11 mumol/l) at a median of 7 days following the transplant. Zinc depletion was more common in younger patients and in children with diarrhoea. A positive correlation was found between plasma zinc and alkaline phosphatase activities. Zinc depleted patients had more febrile episodes of longer duration and were more likely to have a positive blood culture. Haemopoetic recovery was not affected by zinc deficiency. Following zinc supplementation, alkaline phosphatase showed a significant increase. The sensitivity of a low alkaline phosphatase as a screening test for biochemical zinc deficiency was 83%, with a specificity of 86%. Low alkaline phosphatase activity following bone marrow transplant is an indication for zinc supplements. PMID:8669934

  18. Optimal graft source for allogeneic hematopoietic stem cell transplant: bone marrow or peripheral blood?

    PubMed

    Adhikari, Janak; Sharma, Priyadarshani; Bhatt, Vijaya Raj

    2016-08-01

    Peripheral blood (PB), compared with bone marrow graft, has higher stem cell content, leads to faster engraftment and is more convenient for collection. Consequently, the use of PB graft has significantly increased in recent years. Although the use of PB graft is acceptable or even preferred to bone marrow graft in matched related donor allogeneic transplant due to a possibility of improved survival, PB graft increases the risk of chronic graft-versus-host disease and associated long-term toxicities in the setting of matched unrelated donor allogeneic transplant. In haploidentical transplant, mitigation of graft-versus-host disease with the use of post-transplant cyclophosphamide is a hypothesis-generating possibility; however, available studies have significant limitations to draw any definite conclusion. PMID:27168462

  19. Treatment of non-Hodgkin's lymphoma with marrow transplantation in identical twins

    SciTech Connect

    Appelbaum, F.R.; Fefer, A.; Cheever, M.A.; Buckner, C.D.; Greenberg, P.D.; Kaplan, H.G.; Storb, R.; Thomas, E.D.

    1981-09-01

    Eight patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemotherapy, a supralethal dose of total-body irradiation, and a bone marrow transplant from a normal identical twin. Seven patients experienced complete remission. Four of the seven patients (two with diffuse poorly differentiated lymphocytic lymphoma, one with composite lymphoma, and one with diffuse moderately well differentiated lymphocytic lymphoma) remain in complete unmaintained remission 12-126 mo from transplantation. One patient relapsed after 10 mo but was retreated and is alive in unmaintained complete remission 73 mo from transplantation. One patient died of Pseudomonas pneumonia while in complete remission and one patient relapsed and died of progressive lymphoma. These results demonstrate that intensive chemoradiotherapy and twin marrow transplantation can induce frequent and enduring remissions in patients with disseminated non-Hodgkin's lymphoma who have failed conventional therapy.

  20. Interleukin-2 and syngeneic bone marrow transplantation in a murine fibrosarcoma model.

    PubMed

    Ho, S P; Stebler, B; Ershler, W B

    1991-04-01

    Mice received interleukin-2 (IL-2) either before and after, or just after intravenous inoculation of syngeneic fibrosarcoma cells. Fewer pulmonary tumor colonies were observed in those animals treated with IL-2, and the best results were observed when IL-2 was administered prior to tumor inoculation. When mice were lethally irradiated and reconstituted with tumor-contaminated bone marrow, IL-2 treatment was also associated with fewer tumor lung colonies. IL-2 may prove to be a useful adjuvant therapy, particularly in the setting of autologous bone marrow transplantation when the infused marrow is contaminated with tumor cells. PMID:1873353

  1. Hyperfractionated total body irradiation for bone marrow transplantation. Results in seventy leukemia patients with allogeneic transplants

    SciTech Connect

    Shank, B.; Chu, F.C.H.; Dinsmore, R.; Kapoor, N.; Kirkpatrick, D.; Teitelbaum, H.; Reid, A.; Bonfiglio, P.; Simpson, L.; O'Reilly, R.J.

    1983-11-01

    From May, 1979 to March, 1981, 76 leukemia patients were prepared for bone marrow transplantation (BMT) with a new hyperfractionated total body irradiation (TBI) regimen (1320 cGy in 11 fractions, 3x/day), followed by cyclophosphamide, 60 mg/kg, for two days. Partial lung shielding was done on each treatment, with supplemental electron beam treatments of the chest wall to compensate, and of the testes, a sanctuary site. This regimen was initiated to potentially reduce fatal interstitial pneumonitis as well as decrease leukemic relapse. Overall actuarial survival at 1 year for acute non-lymphocytic leukemia (ANLL) patients is 63%, while relapse-free survival at 1 year is 53%. On the other hand, for acute lymphocytic leukemia (ALL) patients, there is no significant difference between relapse or remission patients with regard to overall survival or relapse-free survival, when relapse is defined as > 5% blasts in the marrow at the time of cytoreduction. Overall actuarial survival at 1 year for ALL is 61% and relapse-free survival is 45% at 1 year. Fatal interstitial pneumonitis has dropped to 18% compared with 50% in our previous single-dose TBI regimen (1000 cGy), in which the same doses of cyclophosphamide were given prior to TBI. In conclusion, not only has fatal interstitial pneumonitis been reduced by hyperfractionation and partial lung blocking, but there may be a survival advantage in ALL patients in relapse, who have a survival equal to that of remission patients. This may indicate a greater cell kill with the higher dose (1320 cGy) attained with this regimen, in these patients with a higher leukemic cell burden.

  2. Cytogenetic conversion following allogeneic bone marrow transplantation for advanced chronic myelogenous leukemia

    SciTech Connect

    McGlave, P.B.; Miller, W.J.; Hurd, D.D.; Arthur, D.C.; Kim, T.

    1981-11-01

    We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allogeneic bone marrow transplantation after preparation with busulfan, vincristine, cyclophosphamide, and fractionated total body irradiation. Engraftment and conversion to normal chromosome patterns after transplantation occurred in all five patients. None of the patients reverted to an abnormal chromosome pattern or demonstrated clinical or hematologic evidence of recurrent disease during the course of this study; however, longest survival from transplant was 248 days. Allogeneic bone marrow transplantation can eradicate the abnormal clone even in far advanced chronic myelogenous leukemia and can provide normal hematopoiesis. We suggest that clinical complications of chemotherapeutic toxicity and infection were responsible for the short survival in this group of patients, and that these complications could be decreased by performing transplantation in the chronic phase or early accelerated phase of the disease.

  3. Autologous adult bone marrow stem cell transplantation in an animal model of huntington's disease: behavioral and morphological outcomes.

    PubMed

    Lescaudron, Laurent; Unni, Divya; Dunbar, Gary L

    2003-07-01

    We investigated the effects of autologous bone marrow stem cell transplantation in a rat model of Huntington's Disease. Thirteen days after bilateral quinolinic lesions (QA), bone marrow was implanted into the damaged striatum. The ability of the transplants to reverse QA-induced cognitive deficits in the radial-arm water maze (RAWM) was examined. The transplants significantly reduced working memory deficits. Most of the transplanted cells appeared quite primitive. Because only a few cells expressed neural phenotypes, we suggest that the release of growth factors by the transplants allowed surviving cells within the caudate to function more efficiently and to facilitate other compensatory responses. PMID:12881187

  4. Apoptosis of ileal crypt epithelia after allogeneic bone marrow transplantation without graft-versus-host disease

    PubMed Central

    Kreft, Andreas; Russo, Alexandra; Lux, Steffi; Waiz, Lioudmila; Seidmann, Larissa; Faber, Jörg; Kirkpatrick, Charles J

    2015-01-01

    Key Clinical Message Intestinal crypt cell apoptosis may occur after allogeneic bone marrow transplantation without clinically overt graft-versus-host disease. We describe this phenomenon in a case of a 12-year-old girl who had segments of the ileum resected because of a relapse of acute lymphoblastic leukemia. The diagnostic difficulties are discussed. PMID:25984309

  5. 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…

  6. 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,…

  7. Human bone marrow mesenchymal stem cell transplantation attenuates axonal injury in stroke rats

    PubMed Central

    Xu, Yi; Du, Shiwei; Yu, Xinguang; Han, Xiao; Hou, Jincai; Guo, Hao

    2014-01-01

    Previous studies have shown that transplantation of human bone marrow mesenchymal stem cells promotes neural functional recovery after stroke, but the neurorestorative mechanisms remain largely unknown. We hypothesized that functional recovery of myelinated axons may be one of underlying mechanisms. In this study, an ischemia/reperfusion rat model was established using the middle cerebral artery occlusion method. Rats were used to test the hypothesis that intravenous transplantation of human bone marrow mesenchymal stem cells through the femoral vein could exert neuroprotective effects against cerebral ischemia via a mechanism associated with the ability to attenuate axonal injury. The results of behavioral tests, infarction volume analysis and immunohistochemistry showed that cerebral ischemia caused severe damage to the myelin sheath and axons. After rats were intravenously transplanted with human bone marrow mesenchymal stem cells, the levels of axon and myelin sheath-related proteins, including microtubule-associated protein 2, myelin basic protein, and growth-associated protein 43, were elevated, infarct volume was decreased and neural function was improved in cerebral ischemic rats. These findings suggest that intravenously transplanted human bone marrow mesenchymal stem cells promote neural function. Possible mechanisms underlying these beneficial effects include resistance to demyelination after cerebral ischemia, prevention of axonal degeneration, and promotion of axonal regeneration. PMID:25657721

  8. 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.

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

    PubMed

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

    2015-09-01

    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. Route of delivery influences biodistribution of human bone marrow-derived mesenchymal stromal cells following experimental bone marrow transplantation

    PubMed Central

    Wang, Fangjing; Eid, Saada; Dennis, James E; Cooke, Kenneth R; Auletta, Jeffery J; Lee, Zhenghong

    2015-01-01

    Mesenchymal stromal cells (MSCs) have shown promise as treatment for graft-versus-host disease (GvHD) following allogeneic bone marrow transplantation (alloBMT). Mechanisms mediating in vivo effects of MSCs remain largely unknown, including their biodistribution following infusion. To this end, human bone-marrow derived MSCs (hMSCs) were injected via carotid artery (IA) or tail vein (TV) into allogeneic and syngeneic BMT recipient mice. Following xenogeneic transplantation, MSC biodistribution was measured by bioluminescence imaging (BLI) using hMSCs transduced with a reporter gene system containing luciferase and by scintigraphic imaging using hMSCs labeled with [99mTc]-HMPAO. Although hMSCs initially accumulated in the lungs in both transplant groups, more cells migrated to organs in alloBMT recipient as measured by in vivo BLI and scintigraphy and confirmed by ex vivo BLI imaging, immunohistochemistry and quantitative RT-PCR. IA injection resulted in persistent whole–body hMSC distribution in alloBMT recipients, while hMSCs were rapidly cleared in the syngeneic animals within one week. In contrast, TV-injected hMSCs were mainly seen in the lungs with fewer cells traveling to other organs. Summarily, these results demonstrate the potential use of IA injection to alter hMSC biodistribution in order to more effectively deliver hMSCs to targeted tissues and microenvironments. PMID:27330253

  11. 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. PMID:26639193

  12. Nonspecific suppressor T cells cause decreased mixed lymphocyte culture reactivity in bone marrow transplant patients

    SciTech Connect

    Harada, M.; Ueda, M.; Nakao, S.; Kondo, K.; Odaka, K.; Shiobara, S.; Matsue, K.; Mori, T.; Matsuda, T.

    1986-07-15

    Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period.

  13. [Pregnancy outcome in five women after autologous bone marrow transplantation for acute lymphoblastic leukaemia].

    PubMed

    Hołowiecka, Aleksandra; Zielińska, Monika; Rozmus, Wioletta; Krzemień, Sławomira; Hołowiecki, Jerzy

    2005-10-01

    There are reports of successful pregnancies in women with haematological malignancies after either autologous or allogeneic bone marrow transplantation (BMT). We report six cases of uncomplicated pregnancies in five women treated with high-dose chemotherapy, radiotherapy and autologous bone marrow transplantation (ABMT) for acute lymphoblastic leukaemia. One patient was diagnosed as having leukaemia during pregnancy. The pregnancy ended with medical termination. Each woman received conditioning regimens without total body irradiation (TBI). Of five women, who received AMBT, all resumed spontaneous cyclical menstruation post transplantation. All of them conceived naturally between 15-52 months following ABMT. We noted one miscarriage in our 29-year-old patient. Six pregnancies went to term and each resulted in the successful delivery of a full-term baby. We did not notice any case of relapse of leukaemia in pregnancy. PMID:16417095

  14. Toxic Epidermal Necrolysis in Recessive Dystrophic Epidermolysis Bullosa following Bone Marrow Transplantation.

    PubMed

    Boull, Christina L; Hylwa, Sara A; Sajic, Dusan; Wagner, John E; Tolar, Jakub; Hook, Kristen P

    2016-06-01

    A 3-year-old child with recessive dystrophic epidermolysis bullosa treated with bone marrow transplantation subsequently developed body-wide epidermal detachment distinct from his epidermolysis bullosa. Toxic epidermal necrolysis was diagnosed by examination and skin biopsy. Although graft-vs-host disease was considered, he had no features of this diagnosis by laboratory studies or skin biopsy, and he improved without addition of further immune suppressants. Throughout the episode, the patient was maintained on cyclosporine A, a component of his transplant regimen, and also a reported therapy for toxic epidermal necrolysis. He had full recovery. Re-epithelialization occurred in a unique folliculocentric pattern, which we postulate was related to the patient's mesenchymal stem cell infusion, received as an adjunct to his marrow transplantation. PMID:26976809

  15. Avascular necrosis of bone after allogeneic bone marrow transplantation: clinical findings, incidence and risk factors.

    PubMed

    Socié, G; Sélimi, F; Sedel, L; Frija, J; Devergie, A; Esperou Bourdeau, H; Ribaud, P; Gluckman, E

    1994-03-01

    In the present study we describe the incidence, clinical course, and management of avascular necrosis of bone following allogeneic bone marrow transplantation, and identify risk factors related to its development. All patients developing avascular necrosis of bone after allogeneic bone marrow transplantation between January 1974 and September 1992 were included in the analysis and were studied using the Hôpital Saint Louis Bone Marrow Transplant Database and hospital records. 27/727 allogeneic transplant recipients developed avascular necrosis leading to an 8.1% incidence at 5 years, by product limit estimate, ranging from 5% to 11.2%. Symptoms developed 119-1747 d (median 398 d) after transplantation. In these 27 patients a total of 52 joints were affected (mean 1.92 per patient, range 1-7). The hip joint was most often affected (69% of patients). All patients had joint pain that led to diagnosis by means of standard radiographs with or without the help of technetium-99 scans and/or magnetic resonance imaging. All but three patients received steroid therapy for acute graft-versus-host disease. Among 10 factors tested, three were shown to be significantly linked to an increased risk for developing avascular necrosis by multivariate analysis: male gender (relative risk (RR) 4.72, P = 0.002), age older than 16 (RR = 3.87, P = 0.004), and acute graft-versus-host disease requiring steroid therapy (RR = 6.30, P = 0.0002). 10 patients (37%) required joint replacement within 19 months (range 2-42) following diagnosis of avascular necrosis. In conclusion, avascular necrosis of bone is a frequent late complication of allogeneic bone marrow transplantation causing significant morbidity and requiring replacement surgery in one-third of affected patients. In this 18-year single-centre survey, older age, male gender and steroid therapy given for acute graft-versus-host disease were shown to independently increase the risk of avascular necrosis of bone. PMID:8043445

  16. 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 ...

  17. Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa.

    PubMed

    Kwon, Jang-Woo; Jo, Hyo Gyeong; Park, Sang Man; Ku, Cheol Hyo; Park, Dong-Joon

    2016-09-01

    To develop a new therapeutic method to treat olfactory deficits, we investigated the engraftment and regenerative effects of transplanted bone marrow stromal cells (BMSCs) on damaged rat olfactory mucosa. To induce olfactory nerve degeneration, one side of the olfactory mucosa of Sprague-Dawley rats was damaged via Triton X-100 irrigation. Phosphate-buffered saline containing syngeneic BMSCs was injected into the olfactory mucosa for transplantation. PKH fluorescent cell dye labeling of BMSCs was used to monitor the transplanted cells. After transplantation of BMSCs, the thickness and regeneration of olfactory mucosa were analyzed using hematoxylin-eosin (H&E) staining. S100 immunohistochemical staining was used to measure nerve sheath regeneration. The increase in NGF (nerve growth factor) level in the olfactory mucosa was measured by Western blot analysis. Transplanted bone marrow stromal cells were engrafted to the lamia propria of damaged mucosa. The mean time for normalization of thickness and morphological recovery of the olfactory mucosa was 4 weeks in the therapeutic group and 9 weeks in the control group. S100 immunoreactivity was higher on the BMSC-treated side than on the control side. During regeneration, the expression of NGF increased in the olfactory mucosa of the experimental group. Based on these results, BMSC transplantation accelerated regeneration of olfactory mucosa damaged by Triton X-100, and NGF may be essential to this regenerative process. PMID:26940801

  18. Bone marrow (stem cell) donation

    MedlinePlus

    Stem cell transplant; Allogeneic-donation ... There are two types of bone marrow donation: Autologous bone marrow transplant is when people donate their own bone marrow. "Auto" means self. Allogenic bone marrow transplant is when another person ...

  19. 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

  20. Graft failure in children receiving HLA-mismatched marrow transplants with busulfan-containing regimens.

    PubMed

    Schultz, K R; Ratanatharathorn, V; Abella, E; Eisenbrey, A B; Karanes, C; Lum, L G; de Planque, M M; Uberti, J P; Ravindranath, Y; Sensenbrenner, L L

    1994-06-01

    Identifying risk factors that lead to graft failure may reduce morbidity and mortality after bone marrow transplantation (BMT) for hematologic malignancies. We evaluated engraftment of all patients with acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML) and myelodysplastic syndrome (MDS) receiving an unmanipulated marrow allogeneic BMT at the Detroit Medical Center from 1987 to 1992 using a busulfan, cyclophosphamide +/- cytarabine preparative regimen. Three of 118 patients had graft failure (2.5%; (95% confidence interval (CI) 0.7%, 6.4%). Graft failure was high in patients < or = 15 years with 3 of 12 patients with failure (25.0%) compared with 0 of 106 patients > 15 years (p = 0.002). Failure to engraft was not seen in HLA-identical (related or unrelated) donor transplants (0 of 103) whereas 3 of 15 HLA-mismatched donors failed (p = 0.003). Patient diagnosis, locus of HLA-mismatch, cytarabine in the preparative regimen, marrow cell dose and the relative reactive index (RRI) were not significant factors. Altered busulfan kinetics secondary to young age was probably not a major factor since 8 of 8 HLA-identical donor transplants engrafted in children. These findings demonstrate that patients receiving an unmanipulated marrow graft using busulfan-containing regimens were at a high risk for graft failure only if they were < or = 15 years of age and had an HLA-mismatched donor. More immunosuppressive preparative regimens, possibly including total body irradiation, should be considered to prevent potential graft failure in children. PMID:7920320

  1. Pregnancy after autologous bone marrow transplantation for malignant lymphomas.

    PubMed

    Brice, P; Pautier, P; Marolleau, J P; Castaigne, S; Gisselbrecht, C

    1994-10-01

    In the present paper, we report two cases of normal pregnancy after high dose chemotherapy and autologous stem cell transplantation (ASCT) in two of the 72 women belonging to a group of 188 patients transplanted in our unit for advanced malignant lymphoma. These pregnancies occurred 19 and 33 months after high dose therapy in two women aged 27 and 28, neither of whom had received previous total body irradiation or pelvic radiotherapy. There are several reasons for the relatively low frequency of pregnancies after ASCT. In particular, the median age of the patients is 35 years, most of these women are transplanted in relapse and have received previous pretreatment with alkylating agents and the disease free survival rate does not exceed 40%. The preservation of long term fertility should be taken into account when deciding therapeutic options for young women with curable disease. PMID:7892134

  2. Informational Theory of Aging: The Life Extension Method Based on the Bone Marrow Transplantation

    PubMed Central

    Karnaukhov, Alexey V.; Karnaukhova, Elena V.; Sergievich, Larisa A.; Karnaukhova, Natalia A.; Bogdanenko, Elena V.; Manokhina, Irina A.; Karnaukhov, Valery N.

    2015-01-01

    The method of lifespan extension that is a practical application of the informational theory of aging is proposed. In this theory, the degradation (error accumulation) of the genetic information in cells is considered a main cause of aging. According to it, our method is based on the transplantation of genetically identical (or similar) stem cells with the lower number of genomic errors to the old recipients. For humans and large mammals, this method can be realized by cryopreservation of their own stem cells, taken in a young age, for the later autologous transplantation in old age. To test this method experimentally, we chose laboratory animals of relatively short lifespan (mouse). Because it is difficult to isolate the required amount of the stem cells (e.g., bone marrow) without significant damage for animals, we used the bone marrow transplantation from sacrificed inbred young donors. It is shown that the lifespan extension of recipients depends on level of their genetic similarity (syngeneity) with donors. We have achieved the lifespan increase of the experimental mice by 34% when the transplantation of the bone marrow with high level of genetic similarity was used. PMID:26491435

  3. Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation.

    PubMed Central

    Speck, B; Gratwohl, A; Nissen, C; Leibundgut, U; Ruggero, D; Osterwalder, B; Burri, H P; Cornu, P; Jeannet, M

    1981-01-01

    Fifty-three patients with severe aplastic anaemia were admitted to this hospital between January 1976 and June 1980, of whom three arrived in terminal condition and died before treatment for their basic disease could be given. Thus 50 patients were treated and evaluated in a prospective study according to one protocol. Eighteen patients with an HLA-identical sibling underwent bone-marrow transplantation with the aim of achieving haematopoietic chimerism. Thirty-two patients without an HLA-identical sibling were given antilymphocyte globulin with or without an infusion of HLA-haplotype-identical marrow. All these 32 patients received low-dose androgens after the procedure. In the first group eight patients (44%) survived. In the two other groups, 22 patients survived (69%), of whom 20 were completely self-sustaining (63%). Engraftment and graft-versus-host disease did not occur in the group who received antilymphocyte globulin and haploidentical marrow, and the haematopoietic reconstitutions in these patients were all autologous. These results confirm the efficacy of antilymphocyte globulin in the treatment of severe aplastic anaemia and show that such treatment is at least as good as bone-marrow transplantation. Its mechanism of action remains unknown, but most patients with aplastic anaemia have a pool of haematopoietic stem cells able to repopulate the marrow after this type of treatment. PMID:6783204

  4. Visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

    PubMed Central

    Zhang, Rui-ping; Xu, Cheng; Liu, Yin; Li, Jian-ding; Xie, Jun

    2015-01-01

    An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7-8. Superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesenchymal stem cells reached the lesion site in these rats than in those without magnetic guidance or superparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan (BBB) locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guidance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury. PMID:25878588

  5. A CLINICAL TRIAL COMBINING DONOR BONE MARROW INFUSION AND HEART TRANSPLANTATION: INTERMEDIATE-TERM RESULTS

    PubMed Central

    Pham, Si M.; Rao, Abdul S.; Zeevi, Adriana; Kormos, Robert L.; McCurry, Kenneth R.; Hattler, Brack G.; Fung, John J.; Starzl, Thomas E.; Griffith, Bartley P.

    2010-01-01

    Background Donor chimerism (the presence of donor cells of bone marrow origin) is present for years after transplantation in recipients of solid organs. In lung recipients, chimerism is associated with a lower incidence of chronic rejection. To augment donor chimerism with the aim to enhance graft acceptance and to reduce immunosuppression, we initiated a trial combining infusion of donor bone marrow with heart transplantation. Reported herein are the intermediate-term results of this ongoing trial. Methods Between September 1993 and August 1998, 28 patients received concurrent heart transplantation and infusion of donor bone marrow at 3.0 × 108 cells/kg (study group). Twenty-four contemporaneous heart recipients who did not receive bone marrow served as controls. All patients received an immunosuppressive regimen consisting of tacrolimus and steroids. Results Patient survival was similar between the study and control groups (86% and 87% at 3 years, respectively). However, the proportion of patients free from grade 3A rejection was higher in the study group (64% at 6 months) than in the control group (40%; P = .03). The prevalence of coronary artery disease was similar between the two groups (freedom from disease at 3 years was 78% in study patients and 69% in controls). Similar proportions of study (18%) and control (15%) patients exhibited in vitro evidence of donor-specific hyporesponsiveness. Conclusions The infusion of donor bone marrow reduces the rate of acute rejection in heart recipients. Donor bone marrow may play an important role in strategies aiming to enhance the graft acceptance. PMID:10733755

  6. Genetic polymorphisms predicting the outcome of bone marrow transplants.

    PubMed

    Dickinson, Anne M; Middleton, Peter G; Rocha, Vanderson; Gluckman, Eliane; Holler, Ernst

    2004-12-01

    Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor alpha, interleukin-10, interferon gamma and interleukin (IL)-6, associate with more severe acute graft-versus-host disease (aGvHD). Donor genotype for IL-1 receptor antagonist (IL-1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL-1Ra, IL-6 and donor IL-1 alpha) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FC gamma receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and other post-transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA-matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non-HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT. PMID:15566351

  7. Establishing a Bone Marrow Stromal Cell Transplant Program at the National Institutes of Health Clinical Center

    PubMed Central

    Sabatino, Marianna; Ren, Jiaqiang; England, Lee; Kuznetsov, Sergei A.; Klein, Harvey G.; Robey, Pamela G.

    2014-01-01

    A repository of cryopreserved bone marrow stromal cell (BMSC) products prepared from marrow aspirates of healthy subjects has been created and is being used to treat patients with inflammatory bowel disease, cardiovascular disease, and acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. New methods of manufacturing BMSCs are being investigated including the use of an automated bioreactor for BMSC expansion and the replacement of fetal bovine serum with human platelet lysate as a media supplement. Efforts are also being made to identify markers that can be used to assess the potency of BMSCs. PMID:24368014

  8. Correction of enzyme deficiency in mice by allogeneic bone marrow transplantation with total lymphoid irradiation

    SciTech Connect

    Slavin, S.; Yatziv, S.

    1980-12-05

    Enzyme deficiency was corrected in mice after allogeneic bone marrow transplantation with occurrence of graft versus host disease. Beta-Glucuronidase-deficient C3H/HeJ mice were treated with total lymphoid irradiation. Normal bone marrow cells (30 x 10(6)) from BALB/o to C3H/HeJ chimeras (> 90 percent circulating donor-type cells) without graft versus host disease. Beta-Glucuronidase activity increases to normal levels in all chimeras as measured in the liver and in the plasma. Activity was maintained throughout an observation period of 7 months.

  9. 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

  10. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia.

    PubMed

    Weisdorf, D J; Billett, A L; Hannan, P; Ritz, J; Sallan, S E; Steinbuch, M; Ramsay, N K

    1997-10-15

    Bone marrow transplantation (BMT) can cure patients with high-risk or recurrent acute lymphoblastic leukemia (ALL). Those lacking a related donor can receive either autologous or histocompatible unrelated donor (URD) marrow. Autotransplantation may result in higher risk of relapse, whereas URD allografts, although associated with serious posttransplant toxicities, may reduce relapse risk. Six years (1987 to 1993) of consecutive autologous BMT (University of Minnesota, Dana Farber Cancer Institute; n = 214) were compared with URD transplants (National Marrow Donor Program; n = 337). Most transplants (70% autologous, 48% URD) were in early remission (first or second complete remission [CR1 or CR2]); 376 patients (75% autologous, 64% URD) were less than 18 years old. Autologous BMT led to significantly lower transplant-related mortality (TRM; relative risk [RR] 0.35; P = .001). URD transplantation offered greater protection against relapse (autologous RR 3.1; P = .001). Patients greater than 18 years old, women, and BMT recipients beyond CR2 had higher TRM, whereas adults, BMT recipients in CR2+, or BMT recipients during 1991 through 1993 had significantly more relapse. After 25 months median follow-up, 100 URD and 56 autologous recipients survive leukemia free. URD BMT in CR2 resulted in superior disease-free survival (DFS), especially for adult patients. Multivariate analysis showed superior DFS for children, men, and BMT during CR1 or 2. Autologous and URD BMT can extend survival for a minority of patients unlikely to be cured by chemotherapy, and the results with either technique are comparable. Greater toxicity and TRM after URD BMT are counterbalanced by better protection against relapse. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for patients with ALL. PMID:9376576

  11. 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

    2015-01-01

    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. PMID:26423563

  12. Standardization and cross validation of alloreactive IFNγ ELISPOT assays within the clinical trials in organ transplantation consortium.

    PubMed

    Ashoor, I; Najafian, N; Korin, Y; Reed, E F; Mohanakumar, T; Ikle, D; Heeger, P S; Lin, M

    2013-07-01

    Emerging evidence indicates memory donor-reactive T cells are detrimental to transplant outcome and that quantifying the frequency of IFNγ-producing, donor-reactive PBMCs by ELISPOT has potential utility as an immune monitoring tool. Nonetheless, differences in assay performance among laboratories limit the ability to compare results. In an effort to standardize assays, we prepared a panel of common cellular reagent standards, developed and cross validated a standard operating procedure (SOP) for alloreactive IFNγ ELISPOT assays in several research laboratories supported by the NIH-funded Clinical Trials in Organ Transplantation (CTOT) Consortium. We demonstrate that strict adherence to the SOP and centralized data analysis results in high reproducibility with a coefficient of variance (CV) of ≈ 30%. This standardization of IFNγ ELISPOT assay will facilitate interpretation of data from multicenter transplantation research studies and provide the foundation for developing clinical laboratory testing strategies to guide therapeutic decision-making in transplant patients. PMID:23710568

  13. Blood and marrow transplantation for sickle cell disease: Is less more?

    PubMed Central

    Bolaños-Meade, Javier; Brodsky, Robert A.

    2015-01-01

    Blood and marrow transplantation is a curative therapy for patients with sickle cell disease yet this is option seldom used. Clinical studies have shown however that children transplanted for this condition can achieve excellent results. In children with sickle cell disease transplanted following conditioning with busulfan, cyclophosphamide, and anti-thymocyte globulin, cure rates in excess of 80% can be obtained when an HLA-matched sibling is used as the donor. However, the large majority of patients with sickle cell disease will not have such a donor, or will not be able to tolerate high dose conditioning regimens. Therefore novel approaches such as non-myeloablative regimes, and alternative donors such as haploidentical, unrelated, or cord blood grafts are currently being explored in clinical trials. Recent reports on non-myeloablative conditioning (HLA-matched or haploidentical donors) highlight the safety and efficacy of these approaches with low mortality and high efficacy suggesting that in the near future non-myeloablation could be the preferred type of conditioning and donor availability will not be a barrier anymore to proceed to transplant. This review will focus on the results obtained when bone marrow transplants are used to treat sickle cell disease and will discuss the results obtained with these novel approaches. PMID:25217413

  14. Late juvenile metachromatic leukodystrophy treated with bone marrow transplantation; a 4-year follow-up study.

    PubMed

    Navarro, C; Fernández, J M; Domínguez, C; Fachal, C; Alvarez, M

    1996-01-01

    We treated a 28-year-old woman who had metachromatic leukodystrophy with bone marrow transplantation. Leukocyte arylsulfatase A levels increased to the donor's range after successful graft. Motor and sensory nerve conduction values did not change significantly in the 4 years after the transplant, and subcortical white matter lesions, as shown on MRI, remained stable during that period of time. The results, after 4 years of follow-up, indicate that the disease has not progressed and signs and symptoms are stabilized. PMID:8559389

  15. Borderline personality disorder and bone marrow transplantation: ethical considerations and review.

    PubMed

    Weitzner, M A; Lehninger, F; Sullivan, D; Fields, K K

    1999-01-01

    Bone marrow transplantation (BMT) is rapidly becoming a part of conventional cancer treatment. However, it remains a 'last-ditch' treatment option for patients who have exhausted other treatment modalities. Patients experience a significant amount of emotional distress during all stages of the BMT process. Patients with personality disorders experience even more emotional distress than average and their behavior is often detrimental to effective patient-staff interactions. A case of a borderline patient is presented with a discussion of the ethical issues involved in the evaluation of these patients and the determination of their appropriateness for transplant. PMID:10202782

  16. 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.

  17. Unrelated Donor Bone Marrow Transplantation for Children With Acute Myeloid Leukemia Beyond First Remission or Refractory to Chemotherapy

    PubMed Central

    Bunin, Nancy J.; Davies, Stella M.; Aplenc, Richard; Camitta, Bruce M.; DeSantes, Kenneth B.; Goyal, Rakesh K.; Kapoor, Neena; Kernan, Nancy A.; Rosenthal, Joseph; Smith, Franklin O.; Eapen, Mary

    2008-01-01

    Purpose Identify prognostic factors that influence outcome after unrelated donor bone marrow transplantation in children with acute myeloid leukemia (AML). Patients and Methods Included are 268 patients (age ≤ 18 years) with AML in second complete remission (n = 142), relapse (n = 90), or primary induction failure (n = 36) at transplantation. All patients received bone marrow grafts from an unrelated donor and a myeloablative conditioning regimen. Cox regression models were constructed to identify risk factors that influence outcome after transplantation. Results In this analysis, the only risk factor that predicted leukemia recurrence and overall and leukemia-free survival was disease status at transplantation. The 5-year probabilities of leukemia-free survival were 45%, 20%, and 12% for patients who underwent transplantation at second complete remission, relapse, and primary induction failure, respectively. As expected, risk of acute but not chronic graft-versus-host disease (GVHD) was lower with T-cell–depleted bone marrow grafts; T-cell–depleted grafts were not associated with higher risks of leukemia recurrence. We observed similar risks of leukemia relapse in patients with and without acute and chronic GVHD. Conclusion Children who underwent transplantation in remission had a superior outcome compared with children who underwent transplantation during relapse or persistent disease. Nevertheless, 20% of children who underwent transplantation in relapse are long-term survivors, suggesting that unrelated donor bone marrow transplantation is an effective therapy in a significant proportion of children with recurrent or primary refractory AML. PMID:18779619

  18. 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. PMID:25445328

  19. 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.

  20. 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

  1. 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.

  2. Bone marrow and stem cell transplantation at King Hussein cancer center.

    PubMed

    Abdel-Rahman, F; Hussein, Aa; Rihani, R; Hlalah, Oa; El Taani, H; Sharma, S; Nserat, T; Sarhan, Mm

    2008-08-01

    Bone marrow and stem cell transplantation in Jordan has been performed since the 1990s, but the first comprehensive program was established at King Hussein Cancer Center (KHCC) in March 2003. The program, in addition to other health care institutions in Amman, serves approximately 5.6 million Jordanians. Also, we treat several patients per year from neighboring Arab countries. The program at KHCC performs an average of 80 transplants per year. During the past 4 years 320 patients received transplants at KHCC; 26% of them received an autologous graft and 74% allogeneic grafts. Of the allogeneic grafts 91% were taken from matched family members, 6.7% were haploidentical from one of the parents, and 2.3% were from an unrelated donor or umbilical cord blood. The actuarial overall survival among all patients has been around 65%. The most common indication for transplantation at KHCC was leukemia/MDS followed by benign nonmalignant hematological/immune deficiency/metabolic disorders, with thalassemia major being the most common among this group. The cost of SCT is variable and depends on many factors including the type of transplant and the attending post-transplant complications. The average charge for autologous transplant (both adults and pediatrics) is 24,695 JD (one JD equals 1.42 USD), and the average charge for allogeneic transplant (both adults and pediatrics) excluding haploidentical transplant is 46,787 JD. We have not noticed any peculiar patterns of complications following BMT; however, we have seen a high incidence of chronic GVHD following minitransplant with fludarabine and single-dose TBI (Seattle protocol). At the inception of the program, invasive fungal infection mainly related to building construction, and central line complications were significant. Measures implemented to control such complications were successful to a large extent. We report our results to the EBMT group and we are accredited as an unrelated transplantation center. Although from a

  3. Playing musical chairs with bone marrow transplantation to eliminate leukemia stem cells

    PubMed Central

    Boyd, Allison L; Bhatia, Mickie

    2015-01-01

    Increasing attention has been focused on the interactions between leukemia cells and their bone marrow (BM) microenvironment. We have recently shown that leukemic stem cells (LSCs) share common BM “niches” with their healthy counterparts. As a result of these shared niche requirements, human LSCs can be mobilized using existing pharmacological agents that facilitate competitive healthy reconstitution, leading to eradication of leukemia during BM transplantation. PMID:27308468

  4. Disseminated Fusarium solani infection with cutaneous nodules in a bone marrow transplant patient.

    PubMed

    Mowbray, D N; Paller, A S; Nelson, P E; Kaplan, R L

    1988-12-01

    Fusarium is a ubiquitous fungus that commonly colonizes ulcerated, burned, or traumatized skin and may cause keratitis and onychomycosis in healthy hosts. Serious disseminated infection due to Fusarium has been reported with increasing frequency in immunocompromised patients. We describe a bone marrow transplant patient who developed fungal septicemia and disseminated skin nodules due to Fusarium solani. Fusarium should be recognized as a potential cause of deep fungal infection in immunocompromised patients. PMID:3069758

  5. [Phases in the rehabilitation of male and female bone marrow transplant patients].

    PubMed

    Arnold, R; Bergerhoff, P; Denzinger, R; Hertenstein, B; Kächele, H; Novak, P; Schwilk, C; Simons, C

    1992-06-01

    Teamwork is essential when investigating the long-term adoption of such medical intervention that are highly demanding on patients, physicians and nursing staff. Bone marrow transplantation represent such an intervention for a series of well defined hematological diseases. The contribution demonstrates the multiple perspective approach of the Ulm team. A case report illustrates the multiplicity of clinical issues. The state of research allows the sketching of a process model on rehabilitation. PMID:1494634

  6. Follow-up of nine patients with Hurler syndrome after bone marrow transplantation.

    PubMed

    Guffon, N; Souillet, G; Maire, I; Straczek, J; Guibaud, P

    1998-07-01

    We report our experience in nine patients with Hurler syndrome (six with a severe and three with an intermediate phenotype) who successfully engrafted after bone marrow transplantation. The donor was a human leukocyte antigen-identical sibling in six cases, the human leukocyte antigen-identical father in one case, and an unrelated donor in two cases. One patient with Hurler syndrome and an intermediate phenotype received two successive grafts from the same donor. There was a beneficial effect of bone marrow transplantation on visceral features (hepatosplenomegaly, obstruction of the upper airway, and coarse facies); however, dysostosis multiplex worsened. All patients but one required surgery for carpal tunnel syndrome. Visual acuity was low because of corneal clouding, and two patients had glaucoma several years after the graft. Five patients had normal hearing before the graft that remained normal, and four had hearing impairment that improved. All patients had learning difficulties, but none had severe mental retardation (IQ ranging from 75 to 103). The follow-up of patients with severe Hurler syndrome engrafted for more than 10 years emphasizes the limits and benefits of bone marrow transplantation. PMID:9672523

  7. 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.

  8. Ethical issues of informed consent: mothers' experiences enrolling their children in bone marrow transplantation research.

    PubMed

    Stevens, Patricia E; Pletsch, Pamela K

    2002-04-01

    Twelve mothers whose children had undergone bone marrow transplantation were interviewed about their experiences giving informed consent. They were asked to describe how they were introduced to bone marrow transplantation as a course of action to treat their gravely ill children, what their understanding of the protocol was, and the process by which they gave their consent. Their stories reveal complex ethical issues that may surface in the course of informed consent for research involving children. Findings suggest that mothers perceive life-and-death circumstances when a child is offered bone marrow transplantation, altering the voluntary nature of the research enterprise. The emotional trauma of the diagnosis decreases a mother's ability to absorb and understand vital information, and the emergent nature of the children's condition and the urgency to begin treatment further compromise informed consent by constricting the time and resources mothers may need to make a decision. Once a protocol is underway, mothers often experience regrets and self-recriminations about their decision to consent. Recommendations are offered that expand upon the current cognitive/rational approach to informed consent and take into account emotional experiences and the importance of building relationships to ensure informed consent over the life of a clinical trial. PMID:11984094

  9. 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

  10. 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

  11. Secondary neuroendocrine tumor after allogeneic bone marrow transplantation.

    PubMed

    Tamura, Shinichi; Ishida, Hiroyuki; Naito, Takeshi; Kondo, Osamu; Inoue, Masami; Kawa, Keisei; Kawabata, Kenji; Hojo, Hiroshi; Ouchi, Kazutaka; Imamura, Toshihiko

    2015-12-01

    Here we report a case of aggressive neuroendocrine tumor (NET), which is an extremely rare secondary solid tumor that occurs after allogeneic hematopoietic cell transplantation (allo-HSCT). A patient with chronic active Epstein-Barr virus infection received allo-HSCT from an HLA-DR two allele-mismatched unrelated donor. Four years later, he developed NET with multiple metastases. He received thoraco-abdominal irradiation as a conditioning regimen, and developed repeated episodes of intestinal graft-versus-host disease, for which he received long-term immunosuppressive therapy. Although these factors may be potential contributing factors to the development of secondary NET, the exact pathogenesis remains unclear. PMID:26711919

  12. 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.

  13. 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.

  14. Imiquimod and Photodynamic Therapy Are Useful in the Treatment of Porokeratosis in Children with Bone Marrow Transplantation.

    PubMed

    Gracia-Cazaña, Tamara; Vera-Álvarez, Jesús; García-Patos, Vicente; Gilaberte, Yolanda

    2015-01-01

    Porokeratosis is an uncommon disorder that affects keratinization. Immunosuppression may favor the development of porokeratotic lesions. Patients who receive allogenic transplants represent a therapeutic challenge to dermatologists. We report two cases of porokeratosis in children with bone marrow transplant and their excellent response to imiquimod and photodynamic therapy. PMID:26223374

  15. 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

  16. Donor origin of circulating endothelial progenitors after allogeneic bone marrow transplantation.

    PubMed

    Ikpeazu, C; Davidson, M K; Halteman, D; Browning, P J; Brandt, S J

    2000-01-01

    Endothelial cell precursors circulate in blood and express antigens found on hematopoietic stem cells, suggesting that such precursors might be subject to transplantation. To investigate, we obtained adherence-depleted peripheral blood mononuclear cells from 3 individuals who had received a sex-mismatched allogeneic bone marrow transplant (BMT) and cultured the cells on fibronectin-coated plates with endothelial growth factors. The phenotype of the spindle-shaped cells that emerged in culture was characterized by immunofluorescent staining, and the origin of the cells was determined using a polymerase chain reaction (PCR)-based assay for polymorphic short tandem repeats (STRs). The cells manifested a number of endothelial characteristics-such as von Wlllebrand factor, CD31, and Flk-1/KDR expression; Bandeiraea simplicifolia lectin 1 binding; and acetylated low-density lipoprotein uptake-but lacked expression of certain markers of activation or differentiation, including intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and the epitope for the anti-endothelial cell antibody P1H12. For each patient and at all time points studied (ranging from 5 to 52 months after transplantation), STR-PCR analysis showed that cultured cells and nucleated blood cells came exclusively from the bone marrow donor. These results demonstrate that circulating endothelial progenitors are both transplantable and capable of long-term repopulation of human allogeneic BMT recipients. PMID:10905767

  17. Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia.

    PubMed

    Bacigalupo, Andrea; Giammarco, Sabrina; Sica, Simona

    2016-08-01

    Standard front-line treatment for acquired aplastic anemia (AA) for patients is either immunosuppressive therapy (IST) or bone marrow transplantation (BMT), usually from an HLA identical sibling. Whereas long-term survival is comparable with either treatment, important differences remain: IST patients may have incomplete or no recovery, are exposed to late clonal disorders and relapse of the original disease. Transplantation is a curative treatment, but patients are exposed to transplant-related complications both acute and chronic, such as chronic graft versus host disease (cGvHD). In the year 2000, a study by the European Group for Blood and Marrow Transplantation (EBMT), looked at failure free survival (FFS), in patients receiving first-line BMT from an HLA identical sibling, or the first-line IST. Young patients with low neutrophil counts benefited of the first-line BMT; the opposite was true for older patients with higher neutrophil counts; and a third intermediate group of patients had comparable survival irrespective of the first-line therapy. We have now studied a more recent cohort of patients to assess whether things have changed over the years. We have found similar results, although overall survival has improved, as a consequence of changes in the IST and BMT protocols. PMID:27278666

  18. 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.

  19. 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 ( ...

  20. Clinical application of intrauterine bone marrow transplantation for treatment of genetic diseases--feasibility studies.

    PubMed

    Slavin, S; Naparstek, E; Ziegler, M; Lewin, A

    1992-01-01

    Intrauterine bone marrow transplantation (BMT) may represent a new approach for correction of a large variety of genetic disorders in utero. The procedure may become feasible for more genetic disorders in the future, since a large majority of potentially correctible diseases can be diagnosed at an early stage of gestation in utero using molecular probes that permit analysis of small biologic samples and even few cells that may be obtained by chorionic villi biopsy and/or amniocentesis. Haploidentical paternal marrow (2 cases) and sibling bone marrow cells from a disease-free family members, were infused into the fetus. GVHD was avoided following in vitro T-lymphocyte depletion using monoclonal antilymphocyte (CDW52) antibodies (Campath-1) without affecting stem cell viability, similarly to the procedures in routine use in clinical BMT programs in man. Three women underwent intrauterine BMT at 34, 23 and 25 weeks of gestation for metachromatic leucodystrophy (Arylsulfatase A deficiency, 2 cases) and beta thalassemia major (1 case), respectively. A total of 33 x 10(8), 30 x 10(8) and 30 x 10(8) bone marrow cells were infused intraperitoneally (1 case), intraportally plus intraperitoneally (2 cases) with no fetal distress. Although the procedure was uneventful and no clinical evidence of GVHD was observed following delivery, correction of the basic disorders was not accomplished because of anticipated rejection of marrow allografts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1504665

  1. Intra-Bone Marrow Transplantation Confers Superior Multilineage Engraftment of Murine Aorta-Gonad Mesonephros Cells Over Intravenous Transplantation.

    PubMed

    Sanjuan-Pla, Alejandra; Romero-Moya, Damia; Prieto, Cristina; Bueno, Clara; Bigas, Anna; Menendez, Pablo

    2016-02-01

    Hematopoietic stem cell (HSC) engraftment has been achieved using single-cell transplantation of prospectively highly purified adult HSC populations. However, bulk transplants are still performed when assessing the HSC potential of early embryonic hematopoietic tissues such as the aorta-gonad mesonephros (AGM) due to very low HSC activity content early in development. Intra-bone marrow transplantation (IBMT) has emerged as a superior administration route over intravenous (IV) transplantation for assessing the reconstituting ability of human HSCs in the xenotransplant setting since it bypasses the requirement for homing to the BM. In this study, we compared the ability of IBMT and IV administration of embryonic day 11.5 AGM-derived cells to reconstitute the hematopoietic system of myeloablated recipients. IBMT resulted in higher levels of AGM HSC long-term multilineage engraftment in the peripheral blood, BM, spleen, and thymus of primary and secondary recipients, and in limiting dilution experiments. The administration route did not skew the multilineage contribution pattern, but IBMT conferred higher Lineage(-)Sca-1(+)c-kit(+) long-term engraftment, in line with the superior IBMT reconstitution. Therefore, IBMT represents a superior administration route to detect HSC activity from developmentally early sources with limited HSC activity content, such as the AGM. PMID:26603126

  2. 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

  3. 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

  4. Ultrastructural study of the cornea in a bone marrow-transplanted Hurler syndrome patient.

    PubMed

    Huang, Y; Bron, A J; Meek, K M; Vellodi, A; McDonald, B

    1996-04-01

    This case report describes a 14-year-old girl with Hurler syndrome, who had received a successful bone marrow-transplant at the age of two. Corneal clouding was present at the time of transplant and has only partially cleared. A right penetrating keratoplasty was performed and the corneal specimen was examined by light microscopy, transmission electron microscopy with Cuprolinic blue staining for proteoglycans, and low-angle X-ray diffraction. The results show the corneal stroma to be disrupted by vacuolated stromal cells. There is abnormal accumulation of proteoglycans in the vacuolated stromal cells and nearby stroma. These proteoglycans mainly contain chondroitin/dermatan sulphate glycosaminoglycans since they are susceptible to chondroitinase ABC. There are a large range of fibril diameters (12.5-50.1 nm) and there is an abnormal distribution of the fibril diameters measured from micrographs. Both are confirmed by X-ray diffraction results (the mean collagen fibril diameters are in a range between 29.7 and > 51.1 nm). X-ray diffraction also shows that the mean centre-to-centre distance of the fibrils slightly increases. These findings suggest that proteoglycans play a role in modelling the stromal structure and can also explain the corneal clouding. Many long-spacing collagen structures with a mean periodicity of 91.8 nm are observed in the corneal stroma. The finding that the long-spacing collagen consists of fine collagen fibrils and that very few proteoglycans filaments bind to them suggests that some change in the interaction of proteoglycans and collagen is responsible for the formation of long-spacing collagen. To our knowledge, this is the first ultrastructural study of the cornea from a bone marrow-transplant patient with Hurler syndrome. The structural features documented here relate to a cornea incompletely corrected by bone marrow transplantation. PMID:8795456

  5. High Incidence of Xenogenic Bone Marrow Engraftment in Pig-to-Baboon Intra-Bone Bone Marrow Transplantation

    PubMed Central

    Tasaki, M.; Wamala, I.; Tena, A.; Villani, V.; Sekijima, M.; Pathiraja, V.; Wilkinson, R. A.; Pratts, S.; Cormack, T.; Clayman, E.; Arn, J. S.; Shimizu, A.; Fishman, J. A.; Sachs, D. H.; Yamada, K.

    2015-01-01

    Previous attempts of α-1,3-galactocyltransferase knockout (GalTKO) pig bone marrow (BM) transplantation (Tx) into baboons have demonstrated a loss of macro-chimerism within 24 h in most cases. In order to achieve improved engraftment with persistence of peripheral chimerism, we have developed a new strategy of intra-bone BM (IBBM) Tx. Six baboons received GalTKO BM cells, with one-half of the cells transplanted into the bilateral tibiae directly and the remaining cells injected intravenously (IBBM/BM-Tx) with a conditioning immunosuppressive regimen. In order to assess immune responses induced by the combined IBBM/BM-Tx, three recipients received donor SLA-matched GalTKO kidneys in the peri-operative period of IBBM/BM-Tx (Group 1), and the others received kidneys 2 months after IBBM/BM-Tx (Group 2). Peripheral macro-chimerism was continuously detectable for up to 13 days (mean 7.7 days; range 3–13) post-IBBM/BM-Tx and in three animals, macro-chimerism reappeared at days 10, 14 and 21. Pig CFUs, indicating porcine progenitor cell engraftment, were detected in the host BM in four of six recipients on days 14, 15, 19 and 28. In addition, anti-pig unresponsiveness was observed by in vitro assays. GalTKO/pCMV-kidneys survived for extended periods (47 and 60 days). This strategy may provide a potent adjunct for inducing xenogeneic tolerance through BM-Tx. PMID:25676635

  6. 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.

  7. Revascularization of ischemic limbs after transplantation of human bone marrow cells with high aldehyde dehydrogenase activity

    PubMed Central

    Capoccia, Benjamin J.; Robson, Debra L.; Levac, Krysta D.; Maxwell, Dustin J.; Hohm, Sarah A.; Neelamkavil, Marian J.; Bell, Gillian I.; Xenocostas, Anargyros; Link, Daniel C.; Piwnica-Worms, David; Nolta, Jan A.

    2009-01-01

    The development of cell therapies to treat peripheral vascular disease has proven difficult because of the contribution of multiple cell types that coordinate revascularization. We characterized the vascular regenerative potential of transplanted human bone marrow (BM) cells purified by high aldehyde dehydrogenase (ALDHhi) activity, a progenitor cell function conserved between several lineages. BM ALDHhi cells were enriched for myelo-erythroid progenitors that produced multipotent hematopoietic reconstitution after transplantation and contained nonhematopoietic precursors that established colonies in mesenchymal-stromal and endothelial culture conditions. The regenerative capacity of human ALDHhi cells was assessed by intravenous transplantation into immune-deficient mice with limb ischemia induced by femoral artery ligation/transection. Compared with recipients injected with unpurified nucleated cells containing the equivalent of 2- to 4-fold more ALDHhi cells, mice transplanted with purified ALDHhi cells showed augmented recovery of perfusion and increased blood vessel density in ischemic limbs. ALDHhi cells transiently recruited to ischemic regions but did not significantly integrate into ischemic tissue, suggesting that transient ALDHhi cell engraftment stimulated endogenous revascularization. Thus, human BM ALDHhi cells represent a progenitor-enriched population of several cell lineages that improves perfusion in ischemic limbs after transplantation. These clinically relevant cells may prove useful in the treatment of critical ischemia in humans. PMID:19324906

  8. 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

  9. Immunological recovery in 48 patients following syngeneic marrow transplantation for hematological malignancy. [/sup 60/Co

    SciTech Connect

    Whiterspoon R.P.; Kopecky, K.; Storb, R.F.

    1982-02-01

    Immunological function of 48 syngeneic transplant patients prepared with 120 mg of cyclophosphamide per kg and 9.2 to 12.0 Gy (920 to 1000 rad) total body irradiation was compared with that of 153 allogeneic recipients. Lymphocyte counts and T cell numbers in syngeneic recipients were low during the first post-transplant month but higher than those of allogeneic recipients. Serum immunoglobulin levels in syngeneic recipients were normal by completion of the first post-transplantation month and were higher than allogeneic recipients at that time. Total hemolytic complement (CH/sub 50/) and third (C3) and fourth (C4) components were normal throughout the post-transplantation course in both groups of patients. Antibody production to primary injection of bacteriophage THETAX174 (Phage) was low in both syngeneic and allogeneic recipients during the first post-transplantation month and rose gradually thereafter. Some syngeneic recipients failed to produce normal amounts of IgG in their secondary response to phage. Antibody production after primary and secondary injection of keyhole limpet hemocyanin or pneumococcal polysaccharide was lower than normal early after grafting and rose later, comparable to that seen in allogeneic recipients. We conclude that immunological recovery in syngeneic recipients is very similar to recovery in allogeneic recipients except in the first month postgrafting where twins are slightly better than allogeneic recipients for lymphocyte and immunoglobulin levels. Other mechanisms than those listed here must play an important role in protecting the syngeneic marrow graft recipient from opportunistic infection. (JMT)

  10. Transient increase of serum IgD levels after allogeneic bone-marrow transplantation.

    PubMed Central

    Korver, K; Radl, J; Schellekens, P T; Vossen, J M

    1988-01-01

    Serum IgD levels were followed longitudinally twice a week for up to 100 days in 60 children undergoing allogeneic bone-marrow transplantation (n = 52) or immunosuppression (n = 8) for the treatment of leukaemia, severe aplastic anaemia or severe combined immunodeficiency. In 40 out of the 49 post-transplantation periods analysed (82%), a transient sharp increase of serum IgD was detected, irrespective of initial disease. A similar peak was found in one out of five children after immunosuppressive treatment. A second IgD peak was only recorded in grafted patients (14/49 post-transfusion periods). Peak levels of IgD ranged from 1.3 to 185.7 IU/ml (median 12.2 IU/ml), which represents a 2.6 to 22.4-fold increase over 'baseline' levels. In the transplanted leukaemia and aplastic anaemia patients, the rise of serum IgD occurred at the same time (geometric mean 16 days after transplantation) and was shown to represent heterogeneous polyclonal IgD in six of them. The onset of the serum IgD peak was significantly delayed in children suffering from severe combined immunodeficiency (P less than 0.05) and was demonstrated in one patient to consist of homogeneous IgD. No relation was found between either the occurrence of clinical acute graft-versus-host disease or infections after treatment, and the time of onset of IgD elevations. To detect transient serum IgD peaks as described here, frequent sampling of sera is necessary. The origin of the early IgD peaks seems to reside within the recipient's cells by an unknown mechanism. The late IgD peaks are most probably an expression of gradual reconstitution of the immune system following bone-marrow transplantation. PMID:3044651

  11. Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation.

    PubMed Central

    Lortan, J E; Vellodi, A; Jurges, E S; Hugh-Jones, K

    1992-01-01

    Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period. PMID:1606736

  12. 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. PMID:25131122

  13. 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

  14. Long-term enzyme replacement therapy in beta-glucuronidase--deficient mice by allogeneic bone marrow transplantation

    SciTech Connect

    Yatziv, S.; Weiss, L.; Morecki, S.; Fuks, Z.; Slavin, S.

    1982-06-01

    Enzyme replacement therapy was successfully accomplished in beta-Glu-deficient C3H/HeJ mice after transplantation of BM cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI. Enzyme activity increased from 20.5 +/- 7.0 nmol/mg of protein per hour to 180 +/- 30.2 in the liver (p less than 0.001) and from 8.2 +/- 2.0 to 17.5 +/- 5.0 nmol/ml/hr in the plasma (p less than 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immunologic rejection of the marrow allograft and GVHD were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. The data suggest that allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.

  15. Exercise and stress management training prior to hematopoietic cell transplantation: Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0902.

    PubMed

    Jacobsen, Paul B; Le-Rademacher, Jennifer; Jim, Heather; Syrjala, Karen; Wingard, John R; Logan, Brent; Wu, Juan; Majhail, Navneet S; Wood, William; Rizzo, J Douglas; Geller, Nancy L; Kitko, Carrie; Faber, Edward; Abidi, Muneer H; Slater, Susan; Horowitz, Mary M; Lee, Stephanie J

    2014-10-01

    Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during HCT. The study randomized 711 patients at 21 centers to receive 1 of 4 training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both, or neither. Participants completed self-reported assessments at enrollment and up to 180 days after HCT. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the Physical Component Summary and Mental Component Summary scales of the Medical Outcomes Study Short Form 36 at day +100 among the groups, based on an intention-to-treat analysis. There also were no differences in overall survival, days of hospitalization through day +100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patients randomized to training in stress management reported more use of those techniques, but patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial. PMID:24910380

  16. 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

  17. Bone Marrow GvHD after Allogeneic Hematopoietic Stem Cell Transplantation.

    PubMed

    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

  18. 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.

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

    PubMed Central

    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.

    2010-01-01

    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. PMID:20671124

  20. Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: incidence and risk factors. European Group or Blood and Marrow Transplantation (EBMT) Working Party on Late Effects.

    PubMed

    Tichelli, A; Duell, T; Weiss, M; Socié, G; Ljungman, P; Cohen, A; van Lint, M; Gratwohl, A; Kolb, H J

    1996-06-01

    The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 +/- 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 +/- 6% for patients with and 10 +/- 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratoconjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset kerato- conjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjögren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity. PMID:8807122

  1. 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

  2. Four successful pregnancies in a patient with mucopolysaccharidosis type I treated by allogeneic bone marrow transplantation.

    PubMed

    Remérand, G; Merlin, E; Froissart, R; Brugnon, F; Kanold, J; Janny, L; Deméocq, F

    2009-12-01

    To date, little is known about the fertility of women suffering from mucopolysaccharidosis type I (MPS I). We report on a female patient with MPS I treated by allogeneic bone marrow transplantation (BMT) at the age of 4 years (after a conditioning regimen containing busulfan 16 mg/kg and cyclophosphamide 100 mg/kg) who had four successful pregnancies without any reproductive assistance. Clinical and biological examinations of the children were normal. On the basis of this case, we discuss the fertility counselling of female MPS I patients at the time of BMT. PMID:19280364

  3. Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

    PubMed

    Sica, S; Di Mario, A; Pagano, L; Etuk, B; Salutari, P; Leone, G

    1992-01-01

    Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT. PMID:1519431

  4. 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.

  5. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes.

    PubMed

    Dalle, Jean-Hugues; Peffault de Latour, Régis

    2016-04-01

    Inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of rare hematological disorders characterized by the impairment of hematopoiesis, which harbor specific clinical presentations and pathogenic mechanisms. Some of these syndromes may progress through clonal evolution, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Most prominent are failures of DNA repair such as Fanconi Anemia and much rarer failure of ribosomal apparatus, e.g., Diamond Blackfan Anemia or of telomere elongation such as dyskeratosis congenita. In these congenital disorders, hematopoietic stem cell transplantation (HSCT) is often a consideration. However, HSCT will not correct the underlying disease and possible co-existing extra-medullary (multi)-organ defects, but will improve BMF. Indications as well as transplantation characteristics are most of the time controversial in this setting because of the rarity of reported cases. The present paper proposes a short overview of current practices. PMID:26872907

  6. Successful Bone Marrow Transplantation in a Child with X-Linked Hyper-IgM Syndrome.

    PubMed

    Isam, Haddadin; Al-Wahadneh, A

    2004-01-01

    A 13-year-old boy was diagnosed at the age of three years as having hyper IgM Immunodeficiency syndrome (HIgM). It is a rare congenital disease characterized by recurrent infections and very low level of serum immunoglobulin (IgG, IgA) and elevated IgM. Conservative treatment with antibiotics and regular intravenous immunoglobulin (IVIG) was not satisfactory. At the age of five, the patient developed Hodgkin's lymphoma, which was treated successfully with chemotherapy. Experience with Bone Marrow Transplantation (BMT) in such cases is limited as a definitive treatment for this kind of syndromes. He was transplanted from his HLA-matched sister, and three years post BMT follow-up he showed good clinical recovery and immunoreconstitution. PMID:17642786

  7. Bone marrow transplantation in the prevention of intellectual disability due to inherited metabolic disease: ethical issues.

    PubMed

    Louhiala, P

    2009-07-01

    Many inherited metabolic diseases may lead to varying degrees of brain damage and thus also to intellectual disability. Bone marrow transplantation (BMT) has been used for over two decades as a form of secondary prevention to stop or reverse the progress of the disease process in some of these conditions. At the population level the impact of BMT on the prevalence of intellectual disability is minute, but at the individual level its impact on the prognosis of the disease and the well-being of the patient can be substantial. The dark side of BMT use is the burden of side effects, complications and transplantation-related mortality in less successful cases. The ethical issues involved in this therapy are discussed in this review. PMID:19567689

  8. Listeriosis in bone marrow transplant recipients: incidence, clinical features, and treatment.

    PubMed

    Chang, J; Powles, R; Mehta, J; Paton, N; Treleaven, J; Jameson, B

    1995-11-01

    Cultures of blood and/or cerebrospinal fluid from four of 1,013 bone marrow transplant recipients treated at our center between January 1972 and April 1994 were positive for Listeria monocytogenes. The overall occurrence of listeriosis was 0.39 case per 100 transplantations. Allograft recipients had received prior treatment with parenteral methylprednisolone, thus supporting an association between listeriosis and corticosteroids. Treatment with parenteral ampicillin (200 mg/[kg.d]) and gentamicin is recommended for a minimum of 3 weeks before oral therapy. Two patients with penicillin allergies in this study failed to respond to chloramphenicol-based therapeutic regimens. Recurrent meningitis occurred in two patients, and the therapeutic use of intrathecal gentamicin/vancomycin did not confer a survival advantage (i.e., the patients did not survive). PMID:8589157

  9. HIGH-DOSE CHEMOTHERAPY WITH BLOOD OR BONE MARROW TRANSPLANTS FOR RHABDOMYOSARCOMA

    PubMed Central

    Stiff, Patrick J.; Agovi, Manza-A.; Antman, Karen H.; Blaise, Didier; Camitta, Bruce M.; Cairo, Mitchell S.; Childs, Richard W.; Edwards, John R; Gale, Robert Peter; Hale, Gregory A.; Lazarus, Hillard M.; Arora, Mukta

    2009-01-01

    Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children, is cured with conventional therapy in 70%. However, 5 year survival for those who relapse is about 30% and drops to about 15% for those with unfavorable histologies (alveolar/undifferentiated subtypes). We describe outcomes of 62 subjects receiving autologous blood/bone marrow transplants for RMS between 1989 and 2003 and reported to CIBMTR. Histological subtype was confirmed by reviewing pathology reports. Transplant-related mortality (TRM), progression-free survival (PFS) and survival were evaluated. Overall 73% of subjects were < 20 years; 39% had cancer bulk >5cm, 63% had metastasis at diagnosis, 55% had unfavorable histologies, 92% had cancer responsive to chemotherapy pretransplant and 67% were in 1st remission. The 1-year TRM was 5% (95% CI, 1–12%) and the 5 year PFS and survival were 29% (95% CI, 18–41%) and 32% (95% CI, 21–44%) respectively. There was only a 4% relapse rate after the first year. There were no differences in 5 year PFS or survival based on histological subtype, transplant in 1st remission vs. relapse (36% vs. 29%; p=0.5), or transplantation for poor-risk histologies in 1st remission vs. relapse (34% vs. 33%; p=0.9). Our data indicate that autotransplants for RMS disease are typically done in patients with disease responsive to chemotherapy pretransplant, with approximately one-third long-term survivors. Despite high risk factors, we also found a low TRM, perhaps reflecting the migration from marrow to blood stem cells as the graft source. Even when performed after relapse for alveolar/undifferentiated histologies, long-term survivals were seen seemingly better than results with conventional therapies. PMID:19961947

  10. Post-transplant bendamustine reduces GvHD while preserving GvL in experimental haploidentical bone marrow transplantation.

    PubMed

    Stokes, Jessica; Hoffman, Emely A; Zeng, Yi; Larmonier, Nicolas; Katsanis, Emmanuel

    2016-07-01

    Advances in haploidentical bone marrow transplantation (h-BMT) have drastically broadened the treatment options for patients requiring BMT. The possibility of significantly reducing the complications resulting from graft-versus-host disease (GvHD) with the administration of post-transplant cyclophosphamide (PT-CY) has substantially improved the efficacy and applicability of T cell-replete h-BMT. However, higher frequency of disease recurrence remains a major challenge in h-BMT with PT-CY. There is a critical need to identify novel strategies to prevent GvHD while sparing the graft-versus-leukaemia (GvL) effect in h-BMT. To this end, we evaluated the impact of bendamustine (BEN), given post-transplant, on GvHD and GvL using clinically relevant murine h-BMT models. We provide results indicating that post-transplant bendamustine (PT-BEN) alleviates GvHD, significantly improving survival, while preserving engraftment and GvL effects. We further document that PT-BEN can mitigate GvHD even in the absence of Treg. Our results also indicate that PT-BEN is less myelosuppressive than PT-CY, significantly increasing the number and proportion of CD11b(+) Gr-1(hi) cells, while decreasing lymphoid cells. In vitro we observed that BEN enhances the suppressive function of myeloid-derived suppressor cells (MDSCs) while impairing the proliferation of T- and B-cells. These results advocate for the consideration of PT-BEN as a new therapeutic platform for clinical implementation in h-BMT. PMID:27030315

  11. Living related liver transplantation in an adult patient with hepatocellular adenoma and carcinoma 13 years after bone marrow transplantation for Fanconi anemia: a case report

    PubMed Central

    Colle, Isabelle; Laureys, Geneviève; Raevens, Sarah; Libbrecht, Louis; Reyntjens, Koen; Geerts, Anja; Rogiers, Xavier; Troisi, Roberto; Hoehn, Holger; Schindler, Detlev; Hanenberg, Helmut; De Wilde, Vincent; Van Vlierberghe, Hans

    2013-01-01

    Fanconi anemia is an inherited bone marrow failure syndrome, characterised by failing DNA repair. Hematopoetic stem cell transplantation, known to be curative for the bone marrow failure, does neither prevent or cure other manifestations such as the development of malignancies. We describe a 26-year-old male patient with known Fanconi anemia and Marfan syndrome who in 1994 underwent a successful bone marrow transplantation of stem cells from his HLA-identical sister. In 2006, three hepatocellular carcinoma (HCC) lesions in the liver were detected and promptly resected. The resection specimen contained 3 lesions, all showing activation of the beta-catenin pathway: a well differentiated steatotic HCC with remnants of the underlying adenoma from which it arose, an adenoma with small foci of well differentiated HCC and a cholestatic adenoma. Known risk factors for developing HCC include Fanconi anemia itself and the use of androgens (oxymetholone) for a period of 3 years preceeding transplantation. Because of the increased risk of developing additional HCC’s, liver transplantation was proposed, taking into account that immunosuppression increases the risk of other malignancies. By using part of the liver of the HLA-identical sister, already acting as bone marrow donor 13 years before, immunosuppression could be avoided. A left lobe liver transplantation was performed without immediate complications for donor and acceptor on July 2, 2007. Nine months after liver transplantation the recipient developed an anastomotic biliary stricture that had to be dilated by percutaneous transhepatic cholangiography. Two months later however, the stenosis recurred, necessitating a surgical reanastomosis (hepaticojejunostomy). Five years after liver transplantation the patient is still doing well. This case report is twofold special being the first case reporting Fanconi anemia linked to Marfan syndrome and being the first reported case of Fanconi anemia who was treated for

  12. 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.

  13. 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.

  14. Biological significance of HLA locus matching in unrelated donor bone marrow transplantation

    PubMed Central

    Kashiwase, Koichi; Matsuo, Keitaro; Azuma, Fumihiro; Morishima, Satoko; Onizuka, Makoto; Yabe, Toshio; Murata, Makoto; Doki, Noriko; Eto, Tetsuya; Mori, Takehiko; Miyamura, Koichi; Sao, Hiroshi; Ichinohe, Tatsuo; Saji, Hiroo; Kato, Shunichi; Atsuta, Yoshiko; Kawa, Keisei; Kodera, Yoshihisa; Sasazuki, Takehiko

    2015-01-01

    We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell–replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection. PMID:25519752

  15. Principles of Bone Marrow Transplantation (BMT): Providing Optimal Veterinary and Husbandry Care to Irradiated Mice in BMT Studies

    PubMed Central

    Duran-Struuck, Raimon; Dysko, Robert C

    2009-01-01

    Bone marrow transplantation (BMT) is the treatment of choice for many leukemias, solid tumors, and metabolic diseases. The field of bone marrow research is highly dependent on in vivo experimentation, because in vitro techniques do not mimic these complicated in vivo systems. Therefore, understanding the medical and husbandry care needs of these transiently immunodeficient bone marrow recipient animals is crucial for researchers, veterinary and animal care personnel. Here we discuss the principles of bone marrow transplantation, mouse pathogens that can interfere with transplantation research, and important husbandry and veterinary practices for mice that may help to minimize unnecessary infections during the transplantation process. Whole-body irradiation is one of the most common tools for myeloablation of the recipient's bone marrow. We discuss the crucial role of the irradiator for BMT research and the importance of aseptic husbandry practices to lessen the possibility of the irradiator for being a source for disease transmission. Finally, we discuss some important guidelines for Institutional Animal Use and Care Committees reviewing irradiation and BMT protocols. PMID:19245745

  16. 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.

  17. 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

  18. Haploidentical Bone Marrow Transplantation With Clofarabine and Busulfan Conditioning for a Child With Multiple Recurrent Acute Lymphoblastic Leukemia.

    PubMed

    Aoki, Yuki; Miyawaki, Reiji; Imai, Kohsuke; Takagi, Masatoshi; Kajiwara, Michiko; Ishiwata, Yasuyoshi; Yasuhara, Masato; Morio, Tomohiro; Mizutani, Shuki; Tomizawa, Daisuke

    2016-01-01

    Outcome of children with acute lymphoblastic leukemia (ALL) has improved over the years, but not for those with multiple recurrences because of high therapy resistance and heavily pretreated history that potentially cause physical damages. We describe the case of an 11-year-old boy with a third relapse of ALL and a history of 2 allogeneic bone marrow transplantations. He was successfully treated with clofarabine combination chemotherapy and achieved a fourth remission at 16 months following haploidentical bone marrow transplantation with conditioning regimen of clofarabine and busulfan. Clofarabine/busulfan conditioning might be a preferable option for children with multiple recurrent ALL, and warrants further investigation. PMID:26523380

  19. 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

  20. The outcome of children requiring admission to an intensive care unit following bone marrow transplantation.

    PubMed

    Hayes, C; Lush, R J; Cornish, J M; Foot, A M; Henderson, J; Jenkins, I; Murphy, P; Oakhill, A; Pamphilon, D H; Steward, C G; Weir, P; Wolf, A; Marks, D I

    1998-08-01

    We report the results of a retrospective study of the role of intensive care unit (ICU) admission in the management of 367 children who underwent bone marrow transplantation (BMT) at a tertiary referral institution. 39 patients (11%) required 44 ICU admissions for a median of 6 d. 70% received marrow from unrelated donors, half of which were mismatched; 80% had leukaemia and two-thirds were considered high-risk transplants. Respiratory failure was the major reason for admission to ICU. 75% of admissions required mechanical ventilation (for a median of 5 d) and 20 patients had lung injury as defined by the criteria of the Seattle group. None of 11 patients with proven viral pneumonitis survived (P = 0.06) and only one of 20 patients with lung injury survived (P < 0.01). Six of seven patients with a primary neurological problem survived (P < 0.001); these appear to represent a good outcome group. Age, the presence of graft-versus-host disease, the use of inotropes, isolated renal or hepatic impairment, and paediatric risk of mortality (PRISM) score were not predictive of outcome. In total, 12 patients (27% of admissions) survived and were discharged from hospital 30d or more after admission and eight (18%) survived >6 months. ICU admission can be beneficial to selected children post-BMT but it may be less useful in proven viral pneumonitis. Where mechanical ventilation is required, the duration of this support should be limited unless there is rapid improvement. PMID:9722291

  1. 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

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

    PubMed

    Kakabadze, Zurab; Kipshidze, Nickolas; 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

  3. 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

  4. Spread of Pseudomonas fluorescens due to contaminated drinking water in a bone marrow transplant unit.

    PubMed

    Wong, Vanessa; Levi, Katrina; Baddal, Buket; Turton, Jane; Boswell, Tim C

    2011-06-01

    Pseudomonas infections are an important cause of morbidity and mortality in immunocompromised patients. We present here data for the spread of Pseudomonas fluorescens caused by a contaminated drinking water dispenser in a bone marrow transplant unit. Over a 1-month period we observed a sharp increase in the isolation of P. fluorescens from weekly pharyngeal surveillance swabs. Environmental samples were taken from a variety of water sources throughout the unit. These samples were cultured on cetrimide agar medium, and isolates were epidemiologically characterized by antibiotic susceptibility patterns and molecular typing methods. Nine patients became colonized with P. fluorescens, and six out of the nine developed febrile neutropenia. P. fluorescens was cultured after the filtration of 100 ml of drinking water from one of two stand-alone chiller units supplying cooled bottled water to the bone marrow transplant unit. All other environmental samples were negative. There were no further cases of P. fluorescens colonization after the contaminated dispenser was removed. Molecular typing showed that all P. fluorescens isolates were identical by both random amplification of polymorphic DNA PCR and pulsed-field gel electrophoresis. We recommend that such bottled water supplies not be used in high-risk areas or be subject to regular microbiological monitoring. PMID:21450958

  5. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation.

    PubMed

    Ribaud, P; Chastang, C; Latgé, J P; Baffroy-Lafitte, L; Parquet, N; Devergie, A; Espérou, H; Sélimi, F; Rocha, V; Espérou, H; Sélimi, F; Rocha, V; Derouin, F; Socié, G; Gluckman, E

    1999-02-01

    To determine prognostic factors for survival in bone marrow transplant recipients with invasive aspergillosis (IA), we retrospectively reviewed 27 IA cases observed in our bone marrow transplantation unit between January 1994 and October 1994. On 30 September 1997, six patients were alive and disease-free. The median survival after IA diagnosis was 36 days. Of eight variables found to be related to survival according to the univariate analysis, graft-versus-host disease (GVHD) status at IA diagnosis (P = .0008) and the cumulative prednisolone dose taken during the week preceding IA diagnosis (CPDlw) (P < .0001) were selected by a backward stepwise Cox regression model. A three-stage classification was established: CPD1w of < or =7 mg/kg (3 of 8 patients died; 60-day survival rate, 88%), CPD1w of >7 mg/kg and no GVHD (9 of 10 patients died; 60-day survival rate, 20%), and CPD1w of >7 mg/kg and active acute grade 2 or more or extensive chronic GVHD (9 of 9 patients died; 30-day survival rate, 0) (P < .0001). PMID:10064251

  6. Serial bone marrow transplantation reveals in vivo expression of the pCLPG retroviral vector

    PubMed Central

    2010-01-01

    Background Gene therapy in the hematopoietic system remains promising, though certain aspects of vector design, such as transcriptional control elements, continue to be studied. Our group has developed a retroviral vector where transgene expression is controlled by p53 with the intention of harnessing the dynamic and inducible nature of this tumor suppressor and transcription factor. We present here a test of in vivo expression provided by the p53-responsive vector, pCLPG. For this, we used a model of serial transplantation of transduced bone marrow cells. Results We observed, by flow cytometry, that the eGFP transgene was expressed at higher levels when the pCLPG vector was used as compared to the parental pCL retrovirus, where expression is directed by the native MoMLV LTR. Expression from the pCLPG vector was longer lasting, but did decay along with each sequential transplant. The detection of eGFP-positive cells containing either vector was successful only in the bone marrow compartment and was not observed in peripheral blood, spleen or thymus. Conclusions These findings indicate that the p53-responsive pCLPG retrovirus did offer expression in vivo and at a level that surpassed the non-modified, parental pCL vector. Our results indicate that the pCLPG platform may provide some advantages when applied in the hematopoietic system. PMID:20096105

  7. The fate of transplanted xenogeneic bone marrow-derived stem cells in rat intervertebral discs.

    PubMed

    Wei, Aiqun; Tao, Helen; Chung, Sylvia A; Brisby, Helena; Ma, David D; Diwan, Ashish D

    2009-03-01

    Intervertebral disc degeneration is a major cause and a risk factor for chronic low back pain. The potential of using stem cells to treat disc degeneration has been raised. The aims of our study were to assess whether xenogeneic bone-marrow derived stem cells could survive in a rat disc degeneration model and to determine which cell types, if any, survived and differentiated into disc-like cells. Human bone-marrow derived CD34(+) (hematopoietic progenitor cells) and CD34(-) (nonhematopoietic progenitor cells, including mesenchymal stem cells) cells were isolated, fluorescent-labeled, and injected into rat coccygeal discs. The rats were sacrificed at day 1, 10, 21, and 42. Treated discs were examined by histological and immunostaining techniques and compared to control discs. The survival of transplanted cells was further confirmed with a human nuclear specific marker. Fluorescent labeled CD34(-) cells were detected until day 42 in the nucleus pulposus of the injected discs. After 3 weeks these cells had differentiated into cells expressing chondrocytic phenotype (Collagen II and Sox-9). In contrast, the fluorescent labeled CD34(+) cells could not be detected after day 21. No fluorescence-positive cells were detected in the noninjected control discs. Further, no inflammatory cells infiltrated the nucleus pulposus, even though these animals had not received immunosuppressive treatment. Our data provide evidence that transplanted human BM CD34(-) cells survived and differentiated within the relative immune privileged nucleus pulposus of intervertebral disc degeneration. PMID:18853431

  8. 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.

  9. Kinetics of destruction and regeneration of the haemopoietic system after administration of busulphan and cyclophosphamide followed by bone marrow transplantation. Peripheral blood parameters.

    PubMed

    Szczylik, C; Ratajczak, M Z; Urbanowska, E; Jedrzejczak, W W

    1989-01-01

    The kinetics of restoration of haemopoiesis was studied in 10 patients prepared for allogenic bone marrow transplantation with busulphan combined with cyclophosphamide. The morphology of peripheral blood after administration of these drugs and transplantation of allogenic bone marrow was similar to that reported elsewhere after irradiation, cyclophosphamide administration and bone marrow transplantation, the cell counts falling almost to zero within several days after the end of the pharmacological preparation, and later rising to normal values within the period from several weeks to several months after transplantation. PMID:2519630

  10. Wild Type Bone Marrow Transplant Partially Reverses Neuroinflammation in Progranulin-Deficient Mice

    PubMed Central

    Yang, Yue; Aloi, Macarena S.; Cudaback, Eiron; Josephsen, Samuel R.; Rice, Samantha J.; Jorstad, Nikolas L.; Keene, C. Dirk; Montine, Thomas J.

    2014-01-01

    Frontotemporal dementia (FTD) is a neurodegenerative disease with devastating changes in behavioral performance and social function. Mutations in the progranulin gene (GRN) are one of the most common causes of inherited FTD due to reduced progranulin expression or activity, including in brain where it is expressed primarily by neurons and microglia. Thus, efforts aimed at enhancing progranulin levels might be a promising therapeutic strategy. Bone marrow-derived cells are able to engraft in the brain and adopt a microglial phenotype under myeloablative irradiation conditioning. This ability makes bone marrow (BM)-derived cells a potential cellular vehicle for transferring therapeutic molecules to the central nervous system. Here, we utilized BM cells from Grn+/+ (wild type or wt) mice labeled with green fluorescence protein for delivery of progranulin to progranulin deficient (Grn−/−) mice. Our results showed that wt bone marrow transplantation (BMT) partially reconstituted progranulin in the periphery and in cerebral cortex of Grn−/− mice. We demonstrated a pro-inflammatory effect in vivo and in ex vivo preparations of cerebral cortex of Grn−/− mice that was partially to fully reversed five months after BMT. Our findings suggest that BMT can be administered as a stem cell-based approach to prevent or to treat neurodegenerative diseases. PMID:25199051

  11. The fate of cells with chromosome aberrations after total-body irradiation and bone marrow transplantation

    SciTech Connect

    Carbonell, F.; Ganser, A.; Fliedner, T.M.; Arnold, R.; Kubanek, B.

    1983-03-01

    Cytogenetic studies were done on bone marrow cells and peripheral lymphocytes of four patients (three with acute nonlymphocytic leukemia, one with aplastic anemia) at various intervals up to 861 days after total-body X irradiation (TBI) at doses between 4.5 and 10 Gy (450-1000 rad) followed by syngeneic or allogeneic bone marrow transplantation. Whereas no radiation-induced aberrations could be found in the bone marrow, apart from a transient finding in the patient with the lowest radiation dose, aberrant metaphases were seen in the peripheral lymphocytes of three patients in the range from 2.5 to 46% even at 861 days after the exposure. There were no demonstrable aberrations related to TBI in the only patient developing graft-versus-host disease. The dicentric yield as determined in the aberrant metaphases with 46 centromeres ranged between 3.4 +/- 1.3 and 4.9 +/- 0.4. In one patient it was demonstrated by BUdR-labeling that after 10 Gy (1000 rad) TBI the surviving and heavily damaged lymphocytes can go into cell cycle and reach at least the third mitosis. The percentage of aberrant cells diminished by about 25% at each mitotic division.

  12. 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

  13. An economic evaluation of peripheral blood stem cell transplantation as an alternative to autologous bone marrow transplantation in multiple myeloma.

    PubMed

    Duncan, N; Hewetson, M; Powles, R; Raje, N; Mehta, J

    1996-12-01

    Autologous peripheral blood stem cell transplantation (PBSCT) is increasingly being utilised as an alternative to autologous bone marrow transplantation (ABMT) in the treatment of malignant diseases. We have performed a pharmacoeconomic study using cost-minimisation analysis to evaluate the two techniques in a population of multiple myeloma patients undergoing PBSCT (n = 37) or ABMT (n = 14). In the PBSCT group, the time to > 0.5 x 10(9)/l neutrophils was significantly shorter (16 vs 22 days; P = 0.0019) as was the time to > 50 x 10(9)/l platelets (19 vs 27 days; P = 0.0019). The faster haematopoietic recovery resulted in a reduced period of intravenous antibiotic therapy (12 vs 19 days; P < 0.0001), reduced requirements for platelet transfusions (12 vs 31.5 units; P = 0.0005), and ultimately, a significant reduction in duration of hospitalisation (19 vs 27.5 days; P < 0.0001). These clinical benefits translated into economic benefits such that the total cost in the PBSCT group was 27.5% less than in the ABMT group (< Pounds 7995 vs < Pounds 11026; P = 0.0001). We conclude that the use of PBSCT as an alternative to ABMT in patients with multiple myeloma is associated with demonstrable economic advantages in addition to clinical benefits. PMID:8971391

  14. Less Graft-Versus-Host Disease after Rabbit Antithymocyte Globulin Conditioning in Unrelated Bone Marrow Transplantation for Leukemia and Myelodysplasia: Comparison with Matched Related Bone Marrow Transplantation

    PubMed Central

    Atta, Elias Hallack; de Oliveira, Danielli Cristina Muniz; Bouzas, Luis Fernando; Nucci, Márcio; Abdelhay, Eliana

    2014-01-01

    One of the major drawbacks for unrelated donor (UD) bone marrow transplantation (BMT) is graft-versus-host disease (GVHD). Despite results from randomized trials, antithymocyte globulin (ATG) is not routinely included for GVHD prophylaxis in UD BMT by many centers. One of ways to demonstrate the usefulness of rabbit ATG in UD BMT is to evaluate how its results approximate to those observed in matched related (MRD) BMT. Therefore, we compared the outcomes between UD BMT with rabbit ATG (Thymoglobulin) for GVHD prophylaxis (n = 25) and MRD BMT (n = 91) for leukemia and myelodysplasia. All but one patient received a myeloablative conditioning regimen. Grades II–IV acute GVHD were similar (39.5% vs. 36%, p = 0.83); however, MRD BMT recipients developed more moderate-severe chronic GVHD (36.5% vs. 8.6%, p = 0.01) and GVHD-related deaths (32.5% vs. 5.6%, p = 0.04). UD BMT independently protected against chronic GVHD (hazard ratio 0.23, p = 0.04). The 6-month transplant-related mortality, 1-year relapse incidence, and 5-year survival rates were similar between patients with non-advanced disease in the MRD and UD BMT groups, 13.8% vs. 16.6% (p = 0.50), 20.8% vs. 16.6% (p = 0.37), and 57% vs. 50% (p = 0.67), respectively. Stable full donor chimerism was equally achieved (71.3% vs. 71.4%, p = 1). Incorporation of rabbit ATG in UD BMT promotes less GVHD, without jeopardizing chimerism evolution, and may attain similar survival outcomes as MRD BMT for leukemia and myelodysplasia especially in patients without advanced disease. PMID:25188326

  15. Preliminary Study of Autologous Bone Marrow Nucleated Cells Transplantation in Children With Spinal Cord Injury

    PubMed Central

    Jarocha, Danuta; Milczarek, Olga; Kawecki, Zdzislaw; Wendrychowicz, Anna; Kwiatkowski, Stanislaw

    2014-01-01

    The objective of this study was to assess the safety and efficacy of transplanting bone marrow nucleated cells (BMNCs) to treat children with complete interruption of spinal cord (SC) continuity. The present study was conducted from 2005 to 2011. The inclusion criteria were a magnetic resonance imaging-confirmed complete interruption of SC continuity and no improvement in neurological status within 6 months after standard therapy. Bone marrow was isolated from the iliac ala and submitted to BMNC isolation. Subsequently, the cell suspension was administered into the SC cavity and intravenously. In total, 18 of 19 intraspinal and intravenous BMNC transplantation procedures performed caused no adverse events. One case was connected with transient bradycardia. The experimental therapy showed no late complications in the 1- to 6-year follow-up evaluation period. Neurological improvement was observed in two patients who received multiple implantations. One patient demonstrated improved superficial sensation from Th3 to Th12/L1 and a restored bladder-filling sensation. In the other case, superficial sensation was improved from C2 to C5, and the respiratory drive, the swallowing reflex, and tongue movements were restored. Spasticity and quality of life were improved in three of five patients. In addition, skin pressure ulcers healed and did not recur. Our preliminary results demonstrate the safety and feasibility of BMNC transplantation in children with complete SC injury. The results indicate that a certain degree of neurological and quality-of-life improvement can be attained by children with chronic complete SC injury who receive multiple BMNC implantations. PMID:24493853

  16. Immunosuppression prior to marrow transplantation for sensitized aplastic anemia patients: comparison of TLI with TBI

    SciTech Connect

    Shank, B.; Brochstein, J.A.; Castro-Malaspina, H.; Yahalom, J.; Bonfiglio, P.; O'Reilly, R.J.

    1988-06-01

    From May 1980 through July 1986, 26 patients with severe aplastic anemia, sensitized with multiple transfusions of blood products, were treated on either of two immunosuppressive regimens in preparation for bone marrow transplantation from a matched donor. There were 10 patients treated with total body irradiation (TBI), 200 cGy/fraction X 4 daily fractions (800 cGy total dose), followed by cyclophosphamide, 60 mg/kg/d X 2 d. An additional 16 patients were treated with total lymphoid irradiation (TLI) (or, if they were infants, a modified TLI or thoracoabdominal irradiation (TAI)), 100 cGy/fraction, 3 fractions/d X 2 d (600 cGy total dose), followed by cyclophosphamide, 40 mg/kg/d X 4 d. The extent of immunosuppression was similar in both groups as measured by peripheral blood lymphocyte depression at the completion of the course of irradiation (5% of initial concentration for TBI and 24% for TLI), neutrophil engraftment (10/10 for TBI and 15/16 for TLI), and time to neutrophil engraftment (median of 22 d for TBI and 17 d for TLI). Marrow and peripheral blood cytogenetic analysis for assessment of percent donor cells was also compared in those patients in whom it was available. 2/2 patients studied with TBI had 100% donor cells, whereas 6/11 with TLI had 100% donor cells. Of the five who did not, three were stable mixed chimeras with greater than or equal to 70% donor cells, one became a mixed chimera with about 50% donor cells, but became aplastic again after Cyclosporine A cessation 5 mo post-transplant, and the fifth reverted to all host cells by d. 18 post-transplant. Overall actuarial survival at 2 years was 56% in the TLI group compared with 30% in the TBI group although this was not statistically significant. No survival decrement has been seen after 2 years in either group.

  17. Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant

    SciTech Connect

    Lawton, C.A.; Barber-Derus, S.; Murray, K.J.; Casper, J.T.; Ash, R.C.; Gillin, M.T.; Wilson, J.F. )

    1989-08-01

    The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months).

  18. 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

  19. 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

  20. 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

  1. 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

  2. Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models

    PubMed Central

    Cornejo, Melanie G.; Kharas, Michael G.; Werneck, Miriam B.; Bras, Séverine Le; Moore, Sandra A.; Ball, Brian; Beylot-Barry, Marie; Rodig, Scott J.; Aster, Jon C.; Lee, Benjamin H.; Cantor, Harvey; Merlio, Jean-Philippe

    2009-01-01

    The tyrosine kinase JAK3 plays a well-established role during normal lymphocyte development and is constitutively phosphorylated in several lymphoid malignancies. However, its contribution to lymphomagenesis remains elusive. In this study, we used the newly identified activating JAK3A572V mutation to elucidate the effect of constitutive JAK3 signaling on murine lymphopoiesis. In a bone marrow transplantation model, JAK3A572V induces an aggressive, fatal, and transplantable lymphoproliferative disorder characterized by the expansion of CD8+TCRαβ+CD44+CD122+Ly-6C+ T cellsthat closely resemble an effector/memory T-cell subtype. Compared with wild-type counterparts, these cells show increased proliferative capacities in response to polyclonal stimulation, enhanced survival rates with elevated expression of Bcl-2, and increased production of interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), correlating with enhanced cytotoxic abilities against allogeneic target cells. Of interest, the JAK3A572V disease is epidermotropic and produces intraepidermal microabscesses. Taken together, these clinical features are reminiscent of those observed in an uncommon but aggressive subset of CD8+ human cutaneous T-cell lymphomas (CTCLs). However, we also observed a CD4+ CTCL-like phenotype when cells are transplanted in an MHC-I–deficient background. These data demonstrate that constitutive JAK3 activation disrupts T-cell homeostasis and induces lymphoproliferative diseases in mice. PMID:19139084

  3. Chronic myeloid leukemia relapsing ten years after allogenic bone marrow transplantation.

    PubMed

    Hino, Yutaro; Doki, Noriko; Yamamoto, Keita; Senoo, Yasushi; Sasajima, Satoshi; Sakaguchi, Masahiro; Hattori, Keiichiro; Kaito, Satoshi; Kurosawa, Shuhei; Harada, Kaito; Ikegawa, Shuntaro; Watanabe, Daisuke; Hagino, Takeshi; Yoshioka, Kosuke; Watakabe, Kyoko; Igarashi, Aiko; Najima, Yuho; Kobayashi, Takeshi; Kakihana, Kazuhiko; Sakamaki, Hisashi; Ohashi, Kazuteru

    2016-05-01

    A 58-year-old female was diagnosed with Philadelphia chromosome positive chronic myeloid leukemia (CML) in blast crisis (BC) in 2004. The patient received imatinib, which quickly induced molecular remission, and subsequently underwent bone marrow transplantation (BMT) from an unrelated human leukocyte antigen (HLA)-identical donor. The post-transplant clinical course was essentially uneventful. In 2014, ten years after the BMT, the patient was admitted to our hospital complaining of lymphadenopathy, and blasts were observed in peripheral blood. The patient was diagnosed as having a CML relapse in myeloid BC, with leukemic infiltration in lymph nodes, and was treated with dasatinib. Subsequently, pleural effusion developed and nilotinib was administered, which induced normal blood counts without blasts and partial cytogenetic remission, one month after administration. Six months after the relapse, this patient underwent a second BMT from an HLA-matched unrelated donor. Recent studies have demonstrated the cumulative incidence of CML relapse more than five years after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to be higher than in acute myeloid leukemia. Although rare, the possibility of late relapse should be considered in patients diagnosed with CML after allo-HSCT. PMID:27263786

  4. 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

  5. Pulmonary, Gonadal, and Central Nervous System Status after Bone Marrow Transplantation for Sickle Cell Disease

    PubMed Central

    Walters, Mark C.; Hardy, Karen; Edwards, Sandie; Adamkiewicz, Thomas; Barkovich, James; Bernaudin, Francoise; Buchanan, George R.; Bunin, Nancy; Dickerhoff, Roswitha; Giller, Roger; Haut, Paul R.; Horan, John; Hsu, Lewis L.; Kamani, Naynesh; Levine, John E.; Margolis, David; Ohene-Frempong, Kwaku; Patience, Melinda; Redding-Lallinger, Rupa; Roberts, Irene A. G.; Rogers, Zora R.; Sanders, Jean E.; Scott, J. Paul; Sullivan, Keith M.

    2010-01-01

    We conducted a prospective, multicenter investigation of human-leukocyte antigen (HLA) identical sibling bone marrow transplantation (BMT) in children with severe sickle cell disease (SCD) between 1991 and 2000. To determine if children were protected from complications of SCD after successful BMT, we extended our initial study of BMT for SCD to conduct assessments of the central nervous system (CNS) and of pulmonary function 2 or more years after transplantation. In addition, the impact on gonadal function was studied. After BMT, patients with stroke who had stable engraftment of donor cells experienced no subsequent stroke events after BMT, and brain magnetic resonance imaging (MRI) exams demonstrated stable or improved appearance. However, 2 patients with graft rejection had a second stroke after BMT. After transplantation, most patients also had unchanged or improved pulmonary function. Among the 11 patients who had restrictive lung changes at baseline, 5 were improved and 6 had persistent restrictive disease after BMT. Of the 2 patients who had obstructive changes at baseline, 1 improved and 1 had worsened obstructive disease after BMT. There was, however, significant gonadal toxicity after BMT, particularly among female recipients. In summary, individuals who had stable donor engraftment did not experience sickle-related complications after BMT, and were protected from progressive CNS and pulmonary disease. PMID:19822218

  6. Increased incidence of murine graft-versus-host disease after allogeneic bone marrow transplantation by previous infusion of syngeneic bone marrow cells

    SciTech Connect

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

    1984-10-01

    Different groups of BALB/c mice received supralethal total-body irradiation (TBI; 8.5 Gy, day 0). When 30 x 10(6) allogeneic (C57B1) bone marrow (BM) cells were infused with or without 10 x 10(6) syngeneic (BALB/c) bM cells on day 1, many animals (60%) died from graft-versus-host disease (GVHD). Typing of peripheral blood leukocytes for donor antigens showed that, respectively, 22/22 and 17/21 of the mice in both groups became chimeric. When syngeneic bone marrow was given on day 1 and allogeneic bone marrow on day 2 after TBI, a similar number of animals (21/23) became chimeric, but GVHD occurred more frequently in this group (25/26 mice, P less than 0.01). When the syngeneic bone marrow cells were replaced by spleen cells, or when the transplantation of allogeneic bone marrow was delayed till days 3 or 6 after TBI, almost all mice rejected the allogeneic BM graft and became long-term survivors. BALB/c mice receiving 30 x 10(6) C57B1 BM cells after 17 daily fractions of 0.2 Gy of total lymphoid irradiation (TLI), showed a high incidence of chimerism (15/17) and in none of the latter animals was GVHD observed. Despite the high incidence of GVHD in the mice receiving allogeneic BM after TBI and syngeneic BM transplantation, as compared with mice prepared with TLI which do not develop GVHD, suppressor cells were as easily induced after TBI and syngeneic BM transplantation as after TLI.

  7. Autologous bone marrow stem cell transplantation in patients with liver failure: a meta-analytic review.

    PubMed

    Wang, Kewei; Chen, Xiaopan; Ren, Jinma

    2015-01-15

    Autologous bone marrow stem cell (ABMSC) transplantation has been utilized in clinical practice to treat patients with liver failure, but the therapeutic effect remains to be defined. A meta-analysis is essential to assess clinical advantages of ABMSC transplantation in patients with liver failure. A systematic search of published works [eg, PubMed, Medline, Embase, Chin J Clinicians (Electronic edition), and Science Citation Index] was conducted to compare clinical outcomes of ABMSC transplantation in patients with liver failure. Meta-analytic results were tested by fixed-effects model or random-effects model, dependent on the characteristics of variables. A total of 534 patients from seven studies were included in final meta-analysis. Subsequent to ABMSC transplantation, there was no significant improvement in general symptom and signs such as loss of appetite, fatigue, and ascites. Activities of serum ALT were not significantly decreased with weighted mean difference (WMD) of -19.36 and 95% confidence interval (CI) -57.53 to 18.80 (P=0.32). Postoperative level of albumin (ALB) was expectedly enhanced by stem cell transplantation (WMD 2.97, 95% CI 0.52 to 5.43, P<0.05, I(2)=84%). Coagulation function was improved as demonstrated by a short prothrombin time (PT) (WMD -1.18, 95% CI -2.32 to -0.03, P<0.05, I(2)=6%), but was not reflected by prothrombin activity (PTA) (P=0.39). Total bilirubin (TBIL) was drastically diminished after ABMSC therapy (WMD -14.85, 95% CI -20.39 to -9.32, P<0.01, I(2)=73%). Model for end-stage liver disease (MELD) scores were dramatically reduced (WMD -2.27, 95% CI -3.53 to -1.02, P<0.01, I(2)=0%). The advantage of ABMSC transplantation could be maintained more than 24 weeks as displayed by time-courses of ALB, TBIL, and MELD score. ABMSC transplantation does provide beneficial effects for patients with liver failure. Therapeutic effects can last for 6 months. However, long-term effects need to be determined. PMID:25356526

  8. A comparison between regimens containing chemotherapy alone (busulfan and cyclophosphamide) and chemotherapy (V. RAPID) plus total body irradiation on marrow engraftment following allogeneic bone marrow transplantation.

    PubMed

    Reynolds, M; McCann, S R

    1989-10-01

    The effect of two conditioning regimens given prior to allogeneic bone marrow transplantation (BMT) on the kinetics of engraftment were compared. 5 patients received busulfan and cyclophosphamide: 7 patients received daunorubicin, vincristine, cytosine arabinoside, methylprednisone and VM-26 plus total body irradiation (TBI). Bone marrow progenitors (BFU-E, CFU-E, CFU-GM, CFU-F) were assayed up to 3 months post-BMT. All progenitors were severely depressed in spite of peripheral blood recovery. There was no stromal recovery in any adult patient post-BMT. There was no significant difference in time to engraftment, or colony forming units, or between patients conditioned with chemotherapy alone or chemotherapy plus TBI. We were unable to detect effects of graft-versus-host disease or cytomegalic viral infection on bone marrow progenitors or peripheral blood recovery in this study. PMID:2684682

  9. Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation

    PubMed Central

    Gussoni, Emanuela; Bennett, Richard R.; Muskiewicz, Kristina R.; Meyerrose, Todd; Nolta, Jan A.; Gilgoff, Irene; Stein, James; Chan, Yiu-mo; Lidov, Hart G.; Bönnemann, Carsten G.; von Moers, Arpad; Morris, Glenn E.; den Dunnen, Johan T.; Chamberlain, Jeffrey S.; Kunkel, Louis M.; Weinberg, Kenneth

    2002-01-01

    Duchenne muscular dystrophy (DMD) is a severe progressive muscle-wasting disorder caused by mutations in the dystrophin gene. Studies have shown that bone marrow cells transplanted into lethally irradiated mdx mice, the mouse model of DMD, can become part of skeletal muscle myofibers. Whether human marrow cells also have this ability is unknown. Here we report the analysis of muscle biopsies from a DMD patient (DMD-BMT1) who received bone marrow transplantation at age 1 year for X-linked severe combined immune deficiency and who was diagnosed with DMD at age 12 years. Analysis of muscle biopsies from DMD-BMT1 revealed the presence of donor nuclei within a small number of muscle myofibers (0.5-0.9%). The majority of the myofibers produce a truncated, in-frame isoform of dystrophin lacking exons 44 and 45 (not wild-type). The presence of bone marrow-derived donor nuclei in the muscle of this patient documents the ability of exogenous human bone marrow cells to fuse into skeletal muscle and persist up to 13 years after transplantation. PMID:12235112

  10. Outbreak of Stenotrophomonas maltophilia bacteremia among patients undergoing bone marrow transplantation: association with faulty replacement of handwashing soap.

    PubMed

    Klausner, J D; Zukerman, C; Limaye, A P; Corey, L

    1999-11-01

    Using molecular typing methods, we confirmed an outbreak of Stenotrophomonas maltophilia among bone marrow transplant patients. The likely source was a healthcare worker who may have washed with moisturizer instead of soap between patients. Hospital epidemiologists need to go beyond antibiograms when evaluating outbreaks and be vigilant about all aspects of hand washing. PMID:10580627

  11. Hurler syndrome: a case report of a 5-year follow-up of dental findings after bone marrow transplantation.

    PubMed

    Wadenya, Rose O; Stout, Angela M; Gupta, Avin; Monge, Janet

    2010-01-01

    Hurler syndrome is a rare autosomal recessive disorder of mucopolysaccharide metabolism. It results from a deficiency in lysosomal enzymes responsible for the breakdown of glycosaminoglycans. Affected individuals may show progressive physical and mental deterioration as glycosaminoglycans are deposited in the organs of the body. Bone marrow transplantation (BMT) is effective in improving some of the clinical manifestations of Hurler syndrome. Death is caused by cardiorespiratory failure and usually occurs before the second decade of life. In this case report, the course of dental development was followed over 5 years, from the primary dentition into the permanent dentition, of a child who was successfully treated with a bone marrow transplant in infancy. The timing of bone marrow therapy has significant and variable effect on the stages of tooth development with implications for the long-term maintenance of the dentition. PMID:20051069

  12. Early predictors of transplant-related mortality (TRM) after allogeneic bone marrow transplants (BMT): blood urea nitrogen (BUN) and bilirubin.

    PubMed

    Bacigalupo, A; Oneto, R; Bruno, B; Soracco, M; Lamparelli, T; Gualandi, F; Occhini, D; Raiola, A; Mordini, N; Berisso, G; Bregante, S; Dini, G; Lombardi, A; Lint, M V; Brand, R

    1999-09-01

    Transplant-related mortality (TRM) following allo- geneic bone marrow transplantation (BMT) remains a major concern and early identification of patients at risk may be clinically relevant. In this study we describe a predictive score based on bilirubin and blood urea nitrogen (BUN) levels on day +7 after BMT. The patient population consisted of 309 consecutive patients who underwent BMT from sibling (n = 263) or unrelated donors (n = 46) for hematologic disorders between December 1990 and December 1996. Of 27 laboratory tests taken on day +7 after BMT, serum bilirubin (P = 0.02) and BUN (P = 0.007) were found to be independent predictors of TRM in multivariate analysis. The median levels of bilirubin (0.9 mg/dl) and of BUN (21 mg/dl) were then used as a cut-off and a score of 1 was given for values equal/greater than the median. There were 216 patients with scores 0-1 (low risk) on day +7 (bilirubin <0.9 and/or BUN <21) and 93 patients with score 2 (high risk) (bilirubin >/=0.9 and BUN >/=21): the latter had more grade III-IV acute graft-versus-host disease (P = 0.03), slower neutrophil (P = 0.02) and slower platelet engraftment (P = 0.002). The actuarial 5 year TRM is 22% for low risk vs44% for high risk patients (P = 0.0003). For HLA-identical siblings TRM is 20% vs35% (P = 0.01), for unrelated donors it is 20% vs 65% (P = 0.01). Day +7 score was highly predictive of TRM on multivariate analysis (hazard ratio 1.9, P < 0.01), after adjustment for year of transplant (P < 0.00001), unrelated vs sibling donors (P = 0.001), patient age (P = 0.01) and diagnosis (P = 0.01). These results were validated on an independent group of 82 allogeneic BMT recipients in a pediatric Unit who showed an actuarial TRM of 16% for low risk vs 46% for high risk patients (P = 0.002). This study suggests that it may be possible to identify patients with different risks of TRM on day +7 after BMT: high risk patients could be eligible for programs designed to intensify prophylaxis of post-transplant

  13. MNGIE Syndrome: Liver Cirrhosis Should Be Ruled Out Prior to Bone Marrow Transplantation.

    PubMed

    Finkenstedt, Armin; Schranz, Melanie; Bösch, Sylvia; Karall, Daniela; Bürgi, Sabine Scholl; Ensinger, Christian; Drach, Mathias; Mayr, Johannes A; Janecke, Andreas R; Vogel, Wolfgang; Nachbaur, David; Zoller, Heinz

    2013-01-01

    Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is an autosomal recessive mitochondriopathy caused by loss-of-function mutations in the thymidine phosphorylase gene. The disease leads to premature death and is characterized by gastrointestinal dysmotility and cachexia, external ophthalmoplegia, a sensorimotor neuropathy, and leukoencephalopathy. Bone marrow transplantation (BMT) is the only potentially curative treatment that can achieve a sustained biochemical correction of the metabolic imbalances.We report a 23-year-old male homozygous for the c.866A > C, p.Glu289Ala mutation of the TYMP gene, who presented with fatty liver and cachexia. Laboratory examinations were unremarkable except for increased transaminase activities. Grade II fibrosis and steatosis was found in an initial and a follow-up liver biopsy 4 years later. Myeloablative conditioning and BMT was performed 10 years after initial presentation due to the progressive weight loss and polyneuropathy. Pre-transplant liver staging was normal except for an elevated transient elastography of 31.6 kPa. Severe ascites developed after transplantation and liver function deteriorated progressively to liver failure. Despite engraftment on day +15, the patient died on day +18 from liver failure. Autopsy revealed micronodular liver cirrhosis, and postmortem diagnosis of acute-on-chronic liver failure was done.This case illustrates the difficulties and importance of diagnosing liver cirrhosis in MNGIE. Before BMT, patients must be carefully evaluated by transient elastography, liver biopsy, or assessment of hepatic venous pressure gradient. In patients with liver cirrhosis, further studies should evaluate if liver transplantation may be an alternative to BMT. Considerable amounts of thymidine phosphorylase are expressed in liver tissue which may prevent accumulation of toxic metabolites. PMID:23430799

  14. Transplanted human bone marrow progenitor subtypes stimulate endogenous islet regeneration and revascularization.

    PubMed

    Bell, Gillian I; Broughton, Heather C; Levac, Krysta D; Allan, David A; Xenocostas, Anargyros; Hess, David A

    2012-01-01

    Transplanted murine bone marrow (BM) progenitor cells recruit to the injured pancreas and induce endogenous beta cell proliferation to improve islet function. To enrich for analogous human progenitor cell types that stimulate islet regeneration, we purified human BM based on high-aldehyde dehydrogenase activity (ALDH(hi)), an enzymatic function conserved in hematopoietic, endothelial, and mesenchymal progenitor lineages. We investigated the contributions of ALDH(hi) mixed progenitor cells or culture-expanded, ALDH-purified multipotent stromal cell (MSC) subsets to activate endogenous programs for islet regeneration after transplantation into streptozotocin-treated NOD/SCID mice. Intravenous injection of uncultured BM ALDH(hi) cells improved systemic hyperglycemia and augmented insulin secretion by increasing islet size and vascularization, without increasing total islet number. Augmented proliferation within regenerated endogenous islets and associated vascular endothelium indicated the induction of islet-specific proliferative and pro-angiogenic programs. Although cultured MSC from independent human BM samples showed variable capacity to improve islet function, and prolonged expansion diminished hyperglycemic recovery, transplantation of ALDH-purified regenerative MSC reduced hyperglycemia and augmented total beta cell mass by stimulating the formation of small beta cell clusters associated with the ductal epithelium, without evidence of increased islet vascularization or Ngn3(+) endocrine precursor activation. Thus, endogenous islet recovery after progenitor cell transplantation can occur via distinct regenerative mechanisms modulated by subtypes of progenitor cells administered. Further, understanding of how these islet regenerative and pro-angiogenic programs are activated by specific progenitor subsets may provide new approaches for combination cellular therapies to combat diabetes. PMID:21417581

  15. The effect of rat bone marrow derived mesenchymal stem cells transplantation for restoration of olfactory disorder.

    PubMed

    Jo, Hyogyeong; Jung, Minyoung; Seo, Dong Jin; Park, Dong Joon

    2015-11-13

    The purpose of the study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on olfactory epithelium (OE) of morphologic and functional restoration following neural Sensorineural Disorder in rats. Except the Normal group, twenty-one rats underwent Triton X-100 (TX-100) irrigation to induce degeneration of OE, and then BMSCs and PBS were treated from the both medial canthus to the rear part of the both nasal cavity into the experimental group and then were observed for restoration according to time point. At two and four weeks after transplantation with BMSCs, restoration of OE was observed with olfactory marker protein (OMP) and behavioral test. And we observed the expression of OMP, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). After TX-100 irrigation, the OE almost disappeared in 3 days. At four weeks after transplantation with BMSCs, the thickness and cellular composition of OE was considerably restored to normal group and expression of OMP was markedly increased when compared with PBS group and reduced the searching time in the behavioral test. Furthermore at two weeks after treatment with BMSCs, expression of NGF and BDNF was greatly increased when compared with PBS group. However at four weeks after treatment with BMSCs, expression of NGF and BDNF was slightly decreased. Our results suggest the BMSCs transplantation affect restoration of OE and olfaction, most likely via regulation of the neurotrophic factor expression, especially the expression of NGF and BDNF and has a possibility of a new therapeutic strategy for the treatment of olfactory disorder caused by the degeneration of OE. PMID:26427869

  16. 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

  17. 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.

  18. 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

  19. Successful pregnancy after total body irradiation and bone marrow transplantation for acute leukaemia.

    PubMed

    Giri, N; Vowels, M R; Barr, A L; Mameghan, H

    1992-07-01

    We report successful pregnancies in two young women (aged 24 and 20 years) following allogeneic bone marrow transplantation (BMT) for acute non-lymphoblastic leukaemia. Conditioning therapy consisted of cyclophosphamide (120 mg/kg) and total body irradiation (TBI, 12 Gy) in 2 Gy fractions once daily for 6 days or twice daily for 3 days. Graft-versus-host disease prophylaxis was with methotrexate alone. Both women were amenorrhoeic after BMT and gonadal testing indicated hypergonadotrophic hypogonadism. Both women had normal pregnancies (2 years and 5 years after BMT) resulting in normal healthy infants. Previously successful pregnancy has been reported after TBI in three women in whom the TBI dose was less than 8 Gy. Our cases illustrate that normal outcome of pregnancy is possible at even higher doses of TBI. PMID:1515886

  20. Mitochondrial neurogastrointestinal encephalomyopathy treated with peritoneal dialysis and bone marrow transplantation.

    PubMed

    Ariaudo, Claudia; Daidola, Germana; Ferrero, Bruno; Guarena, Cesare; Burdese, Manuel; Segoloni, Giuseppe Paolo; Biancone, Luigi

    2015-02-01

    Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disease caused by thymidine phosphorylase deficiency which leads to toxic accumulations of thymidine (dThd) and deoxyuridine (dUrd). It lacks an established treatment and the prognosis is traditionally poor. We report a case of a young female patient with normal renal function and MNGIE treated by peritoneal dialysis (PD) and allogeneic bone marrow transplantation (BMT). PD was effective in reducing dThd and dUrd plasma levels and in improving clinical symptoms. To our knowledge, this is the first report on the beneficial effects of PD regarding MNGIE neurological symptoms. PD, therefore, should be considered especially in medically compromised patients as a supportive treatment to improve clinical conditions before BMT. PMID:24599829

  1. 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

  2. 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

  3. 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. PMID:1607569

  4. BET bromodomain inhibition suppresses graft-versus-host disease after allogeneic bone marrow transplantation in mice

    PubMed Central

    Sun, Yaping; Wang, Ying; Toubai, Tomomi; Oravecz-Wilson, Katherine; Liu, Chen; Mathewson, Nathan; Wu, Julia; Rossi, Corinne; Cummings, Emily; Wu, Depei; Wang, Shaomeng

    2015-01-01

    Acute graft-versus-host disease (GVHD) is the major obstacle of allogeneic bone marrow transplantation (BMT). Bromodomain and extra-terminal (BET) protein inhibitors selectively block acetyl-binding pockets of the bromodomains and modulate histone acetylation. Here, we report that inhibition of BET bromodomain (BRD) proteins with I-BET151 alters cytokine expression in dendritic cells (DCs) and T cells, including surface costimulatory molecules, in vitro and in vivo cytokine secretion, and expansion. Mechanistic studies with I-BET151 and JQ1, another inhibitor, demonstrate that these effects could be from disruption of association between BRD4 and acetyl-310 RelA of nuclear factor kappa B. Short-term administration early during BMT reduced GVHD severity and improved mortality in two different allogeneic BMT models but retained sufficient graft-versus-tumor effect. Thus inhibiting BRD proteins may serve as a novel approach for preventing GVHD. PMID:25778533

  5. 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. PMID:25698614

  6. Dendritic Cell Depletion and Repopulation in the Lung after Irradiation and Bone Marrow Transplantation in Mice

    PubMed Central

    Hahn, Ines; Klaus, Anna; Maus, Regina; Christman, John W.; Welte, Tobias

    2011-01-01

    Dendritic cells (DCs) are essential for innate and adaptive immunity, but are purported to exhibit variable radiosensitivity in response to irradiation in various bone marrow transplantation (BMT) protocols. To address this controversy, we analyzed the magnitude of depletion and repopulation of both lung CD11bpos DC and CD103pos DC subsets in response to irradiation and BMT in a murine model. In our study, CD45.2pos donor bone marrow cells were transplanted into irradiated CD45.1pos recipient mice to examine the depletion of recipient DC subsets and the repopulation of donor DC subsets. We observed an apoptosis-mediated and necrosis-mediated depletion (> 90%) of the recipient CD103pos DC subset, and only a 50–60% depletion of recipient CD11bpos DCs from lung parenchymal tissue on Days 3 and 5, whereas recipient alveolar and lung macrophages were much less radiosensitive, showing an approximately 50% depletion by Days 14–21 after treatment. A repopulation of lung tissue with donor DC subsets had occurred by Days 10 and 28 for CD11bpos DCs and CD103pos DCs, whereas alveolar and lung macrophages were repopulated by 6 and 10 weeks after treatment. Furthermore, the infection of mice with Streptococcus pneumoniae further accelerated the turnover of lung DCs and lung macrophage subsets. Our data illustrate the vulnerability of lung CD103pos DCs and CD11bpos DCs to irradiation, and indicate that an accelerated turnover of lung DC subsets occurs, relative to pulmonary and lung macrophages. Our findings may have important implications in the development of adjuvant immune-stimulatory protocols that could reduce the risk of opportunistic infections in patients undergoing BMT. PMID:21177980

  7. Perivascular, but not Parenchymal, Cerebral Engraftment of Donor Cells after Non-Myeloablative Bone Marrow Transplantation

    PubMed Central

    Yang, Yue; Jorstad, Nikolas L.; Shiao, Christine; Cherne, Makenzie K.; Khademi, Shawn B.; Montine, Kathleen S.; Montine, Thomas J.; Keene, C. Dirk

    2013-01-01

    Myeloablative (MyA) bone marrow transplantation (BMT) results in robust engraftment of BMT-derived cells in the central nervous system (CNS) and is neuroprotective in diverse experimental models of neurodegenerative diseases of brain and retina. However, MyA irradiation is associated with significant morbidity and mortality and does not represent a viable therapeutic option for the elderly. Non-myeloablative (NMyA) BMT is less toxic, but it is not known if the therapeutic efficacy observed with MyA BMT is preserved. As a first step to address this important gap in knowledge, we evaluated and compared engraftment characteristics of BMT-derived monocytes/microglia using several clinically relevant NMyA pretransplant conditioning regimens in C57BL/6 mice. These included chemotherapy (fludarabine and cyclophosphamide) with or without 2 Gy irradiation, and 5.5 Gy irradiation alone. Each regimen was followed by transplantation of whole bone marrow from green fluorescent protein-expressing wild type (wt) mice. While stable hematopoietic engraftment occurred, to varying degrees, in all NMyA regimens, only 5.5 Gy irradiation resulted in significant engraftment of BMT-derived cells in brain, where these cells were exclusively localized to perivascular, leptomeningeal, and related anatomic regions. Engraftment in retina under 5.5 Gy NMyA conditions was significantly reduced compared to MyA, but robust engraftment was identified in optic nerve. Advancing the therapeutic applications of BMT to neurodegenerative diseases will require identification of the barrier mechanisms MyA, but not NMyA, is able to overcome. PMID:23567123

  8. 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

  9. Genetic tracing of arterial graft flow surface endothelialization in allogeneic marrow transplanted dogs.

    PubMed

    Shi, Q; Wu, M H; Fujita, Y; Ishida, A; Wijelath, E S; Hammond, W P; Wechezak, A R; Yu, C; Storb, R F; Sauvage, L R

    1999-01-01

    In order to trace genetically the source of fallout endothelialization on arterial grafts, six beagle dogs with successful autologous bone marrow transplantation received composite tandem aortic grafts with an isolated, totally impervious Dacron graft and a porous Dacron graft for 12 weeks. For impervious segments, five of 12 fresh tissue samples were Factor VIII/von Willebrand factor + (FVIII/vWF) and seven had faint or negative signals; three of the FVIII/vWF + samples had alpha-actin + smooth muscle cells. Polymerase chain reaction (PCR) study showed eight had a pure donor DNA genotype and four had donor/host mixed, with the donor predominant. Of 12 AgNO3-stained samples, 11 showed pure donor type and one had donor/host mixed, with the donor predominant. For porous segments, all 12 fresh samples had positive flow surface FVIII/vWF and alpha-actin cells. PCR showed all these samples and all 12 AgNO3-stained samples had donor/host mixed type, but the host pattern was predominant. Porous graft healing appears to involve both cellular fallout and tissue ingrowth, and bone-marrow-derived cells may be a source for fallout. PMID:10073768

  10. Graft-versus-host disease and sialodacryoadenitis viral infection in bone marrow transplanted rats

    SciTech Connect

    Rossie, K.M.; Sheridan, J.F.; Barthold, S.W.; Tutschka, P.J.

    1988-06-01

    The effect of a localized viral infection on the occurrence of graft-vs.-host disease (GVHD) was examined in allogeneic rat bone marrow chimeras (ACI/LEW). Animals without clinical evidence of GVHD, 62 days after bone marrow transplant, were infected in salivary and lacrimal glands with sialodacryoadenitis virus (SDAV), and sacrificed 8-25 days postinfection. Using established histologic criteria, GVHD was found more frequently in salivary and lacrimal glands of SDAV-infected chimeras than uninfected chimeras. Skin and oral mucosa, tissues not infected by the virus, showed no differences in occurrence of GVHD, suggesting that the viral infection induced only local and not systemic GVHD. GVHD and SDAV infection, which are histologically similar, were differentiated by examining tissues for SDAV antigen using immunoperoxidase technique. Histologic changes were present for at least 1 week longer than viral antigen, suggesting they represented GVHD rather than viral infection. GVHD and SDAV infection were also differentiated by looking for a histologic feature characteristic of GVHD and not found in SDAV infection (periductal lymphocytic infiltrate). This was found in SDAV-infected chimeras more frequently than uninfected chimeras, suggesting that the viral infection somehow induced GVHD. Results showed a localized increase in the occurrence of GVHD subsequent to localized viral infection.

  11. Transfusion Induced Bone Marrow Transplant Rejection Due to Minor Histocompatibility Antigens

    PubMed Central

    Patel, Seema R; Zimring, James C

    2014-01-01

    Traditionally, alloimmunization to transfused blood products has focused exclusively upon recipient antibodies recognizing donor alloantigens present on the cell surface. Accordingly, the immunological sequelae of alloimmunization have been antibody mediated effects (i.e. hemolytic transfusion reactions, platelet refractoriness, anti-HLA and anti-HNA effects, etc.). However, in addition to the above sequelae, there is also a correlation between the number of antecedent transfusions in humans and the rate of bone marrow transplant (BMT) rejection - under reduced intensity conditioning with HLA matched or HLA identical marrow. BMT of this nature is the only existing cure for a series of non-malignant hematological diseases (e.g. sickle cell disease, thalassemias, etc.); however, rejection remains a clinical problem. It has been hypothesized that transfusion induces subsequent BMT rejection through immunization. Studies in animal models have observed the same effect and have demonstrated that transfusion induced BMT rejection can occur in response to alloimmunization. However, unlike traditional antibody responses, sensitization in this case results in cellular immune effects, involving populations such as T cell or NK cells. In this case, rejection occurs in the absence of alloantibodies, and would not be detected by existing immune-hematological methods. We review human and animal studies in light of the hypothesis that, for distinct clinical populations, enhanced rejection of BMT may be an unappreciated adverse consequence of transfusion which current blood bank methodologies are unable to detect. PMID:24090731

  12. The role of the professional nurse in a bone marrow transplantation programme.

    PubMed

    Wood, L; Richards, J; Jacobs, P

    1990-12-01

    Two different methods of transplantation are available. The allogeneic procedure is the transfer of bone marrow between compatible siblings, whereas in autografting the patient's own haematopoietic stem cells are collected, stored, and subsequently reinfused. Both forms have become established in the treatment of the leukaemias, aplastic anaemia, the malignant lymphomas, myeloma and certain immunologic diseases. Similarly, these techniques are being used in solid tumour oncology to reconstitute bone marrow function after high doses of chemotherapy, which would otherwise result in irreversible myelotoxicity. The success of such programmes depends upon a well developed multidisciplinary approach, prominently involving experienced and dedicated nursing staff. The latter individuals will establish contact with the patient typically during the first admission for chemotherapy and this will be consolidated during subsequent outpatient visits. Then follows the highly specialised care of central venous lines and management of radiation or chemotherapy-related side effects, often with intensive care needed for safe reversal of sepsis that may, however, be associated with renal or cardiorespiratory dysfunction. Most importantly, and again centrally involving the professional nurse, is responsibility for all aspects of maintaining and operating the protected environment, together with laminar air-flow rooms. Additional interaction is also necessary with dieticians, social workers, liaison psychiatrists, occupational therapists and frequently the infectious disease, cardiovascular, respiratory and renal services. Furthermore, achievement of optimal results presupposes the availability of a dedicated cell support section, as well as the competence to cryopreserve haematopoietic stem cells and monitor the safety of this step with in vitro bone marrow culture--another role for the specialised or academic nurse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2091866

  13. 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.

  14. Bone Marrow Mesenchymal Stem Cell Transplantation Retards the Natural Senescence of Rat Hearts

    PubMed Central

    Zhang, Mingyu; Liu, Di; Li, Shuang; Chang, Lingling; Zhang, Yu; Liu, Ruixue; Sun, Fei; Duan, Wenqi; Du, Weijie; Wu, Yanping; Zhao, Tianyang; Xu, Chaoqian

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging hearts. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations. Monocultured NRVCs displayed the senescence-associated phenotypes, characterized by an increase in the number of β-galactosidase-positive cells and decreases in the degradation and disappearance of cellular organelles in a time-dependent manner. The levels of reactive oxygen species and malondialdehyde were elevated, whereas the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased, along with upregulation of p53, p21Cip1/Waf1, and p16INK4a in the aging cardiomyocytes. These deleterious alterations were abrogated in aging NRVCs cocultured with BMSCs. Qualitatively, the same senescent phenotypes were consistently observed in aging rat hearts. Notably, BMSC transplantation significantly prevented these detrimental alterations and improved the impaired cardiac function in the aging rats. In summary, BMSCs possess strong antisenescence action on the aging NRVCs and hearts and can improve cardiac function after transplantation in aging rats. The present study, therefore, provides an alternative approach for the treatment of heart failure in the elderly population. PMID:25855590

  15. Evaluation of APP695 Transgenic Mice Bone Marrow Mesenchymal Stem Cells Neural Differentiation for Transplantation

    PubMed Central

    Li, Qian; Jia, Yanjie; Zhang, John; Yang, Jun

    2015-01-01

    Objective. Even though there is a therapeutic potential to treat Alzheimer's disease (AD) with neural cell replenishment and replacement, immunological rejections of stem cell transplantation remain a challenging risk. Autologous stem cells from AD patients however may prove to be a promising candidate. Therefore, we studied the neuronal differentiation efficiency of bone marrow mesenchymal stem cells (MSCs) from APP695 transgenic mice, which share features of human AD. Method. Cultured MSCs from APP695 transgenic mice are used; neuronal differentiation was assessed by immunocytochemistry and Western blot. Correlation with Notch signaling was examined. Autophage flux was assessed by western blot analysis. Results. MSCs from APP695 mice have higher neuronal differentiation efficiency than MSCs from wild type mice (WT MSCs). The expression of Notch-1 signaling decreased during the differentiation process. However, autophagy flux, which is essential for neuronal cell survival and neuronal function, was impaired in the neuronally differentiated counterparts of APP695 MSCs (APP695 MSCs–n). Conclusion. These results suggested autologous MSCs of APP690 mice may not be a good candidate for cell transplantation. PMID:26491658

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

    PubMed Central

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

    2015-01-01

    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. PMID:25298037

  17. 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. PMID:25298037

  18. 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

  19. Interstitial pneumonitis following bone marrow transplantation after low dose rate total body irradiation

    SciTech Connect

    Barrett, A.; Depledge, M.H.; Powles, R.L.

    1983-07-01

    Idiopathic and infective interstitial pneumonitis (IPn) is a common complication after bone marrow transplantation (BMT) in many centers and carries a high mortality. We report here a series of 107 patients with acute leukemia grafted at the Royal Marsden Hospital in which only 11 (10.3%) developed IPn and only 5 died (5%). Only one case of idiopathic IPn was seen. Factors which may account for this low incidence are discussed. Sixty of 107 patients were transplanted in first remission of acute myeloid leukemia (AML) and were therefore in good general condition. Lung radiation doses were carefully monitored and doses of 10.5 Gy were not exceeded except in a group of 16 patients in whom a study of escalating doses of TBI (up to 13 Gy) was undertaken. The dose rate used for total body irradiation (TBI) was lower than that used in other centers and as demonstrated elsewhere by ourselves and others, reduction of dose rate to <0.05 Gy/min may be expected to lead to substantial reduction in lung damage. Threshold doses of approximately 8 Gy for IPn have been reported, but within the dose range of 8 to 10.5 Gy we suggest that dose rate may significantly affect the incidence. Data so far available suggest a true improvement in therapeutic ratio for low dose rate single fraction TBI compared with high dose rate.

  20. Cataracts after total body irradiation and marrow transplantation: a sparing effect of dose fractionation

    SciTech Connect

    Deeg, H.J.; Flournoy, N.; Sullivan, K.M.; Sheehan, K.; Buckner, C.D.; Sanders, J.E.; Storb, R.; Witherspoon, R.P.; Thomas, E.D.

    1984-07-01

    Two hundred seventy-seven patients, who have been followed for 1 to 12 years after marrow transplantation, have been examined for cataract development. In preparation for transplantation, 96 patients with aplastic anemia were conditioned with chemotherapy only, while 181 patients (two with aplastic anemia and 179 with a hematologic malignancy) were conditioned with a regimen of total body irradiation (TBI) and chemotherapy. TBI was delivered from two opposing /sup 60/Co sources at an exposure rate of 4 to 8 cGy/min, either as a single dose of 10 Gy (105 patients) or in fractions (76 patients). To date, 86 patients have developed cataracts. Kaplan-Meier product limit estimates of the incidence of cataracts for patients given chemotherapy only and no TBI, single-dose TBI, and fractionated TBI are 19, 80, 18%, respectively. On the basis of proportional hazards regression analyses, patients given single-dose TBI had a relative risk of developing cataracts that was 4.7-fold higher than in patients given fractionated TBI or chemotherapy only, suggesting a significant sparing effect with use of TBI dose fractionation.

  1. Transplanted murine long-term repopulating hematopoietic cells can differentiate to osteoblasts in the marrow stem cell niche.

    PubMed

    Hofmann, Ted J; Otsuru, Satoru; Marino, Roberta; Rasini, Valeria; Veronesi, Elena; Murgia, Alba; Lahti, Jill; Boyd, Kelli; Dominici, Massimo; Horwitz, Edwin M

    2013-06-01

    Bone marrow transplantation (BMT) can give rise to donor-derived osteopoiesis in mice and humans; however, the source of this activity, whether a primitive osteoprogenitor or a transplantable marrow cell with dual hematopoietic and osteogenic potential, has eluded detection. To address this issue, we fractionated whole BM from mice according to cell surface immunophenotype and assayed the hematopoietic and osteopoietic potentials of the transplanted cells. Here, we show that a donor marrow cell capable of robust osteopoiesis possesses a surface phenotype of c-Kit(+) Lin(-) Sca-1(+) CD34(-/lo), identical to that of the long-term repopulating hematopoietic stem cell (LTR-HSC). Secondary BMT studies demonstrated that a single marrow cell able to contribute to hematopoietic reconstitution in primary recipients also drives robust osteopoiesis and LT hematopoiesis in secondary recipients. These findings indicate that LTR-HSC can give rise to progeny that differentiate to osteoblasts after BMT, suggesting a mechanism for prompt restoration of the osteoblastic HSC niche following BM injury, such as that induced by clinical BMT preparative regimens. An understanding of the mechanisms that regulate this differentiation potential may lead to novel treatments for disorders of bone as well as methods for preserving the integrity of endosteal hematopoietic niches. PMID:23587920

  2. 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

  3. Simultaneous bone marrow and composite tissue transplantation in rats treated with nonmyeloablative conditioning promotes tolerance1

    PubMed Central

    Xu, Hong; Ramsey, Deborah M.; Wu, Shengli; Bozulic, Larry D.; Ildstad, Suzanne T.

    2012-01-01

    Background Approaches to safely induce tolerance in vascularized composite allotransplantation (VCA) with chimerism through bone marrow transplantation (BMT) are currently being pursued. However, the VCA were historically performed sequentially after donor chimerism was established. Delayed VCA is not clinically applicable due to the time constraints associated with procurement from deceased donors. A more clinically relevant approach to perform both the BMT and VCA simultaneously was evaluated. Methods WF (RT1Au) rats were treated with a short course of immunosuppressive therapy (anti-αβ-TCR mAb, FK-506, and anti-lymphocyte serum). One day prior to BMT, rats were treated with varying doses of total body irradiation (TBI) followed by transplantation of heterotopic osteomyocutaneous flaps from hind limbs of ACI (RT1Aabl) rats. Results 80% of rats conditioned with 300 cGy TBI and 40% of rats receiving 400 cGy TBI accepted the VCA. Mixed chimerism was detected in peripheral blood at one month post-VCA, but chimerism was lost in all transplant recipients by 4 months. The majority of peripheral donor cells originated from the BMT and not the VCA. Acceptors of VCA were tolerant of a donor skin graft challenge and no anti-donor antibodies were detectable, suggesting a central deletional mechanism for tolerance. Regulatory T cells (Treg) from spleens of acceptors more potently suppressed lymphocyte proliferation than Treg from rejectors in the presence of donor stimulator cells. Conclusions These studies suggest that simultaneous BMT and VCA may establish indefinite allograft survival in rats through Treg-mediated suppression and thymic deletion of alloreactive T cells. PMID:23250336

  4. 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

  5. Technical modifications in hyperfractionated total body irradiation for T-lymphocyte deplete bone marrow transplant.

    PubMed

    Lawton, C A; Barber-Derus, S; Murray, K J; Casper, J T; Ash, R C; Gillin, M T; Wilson, J F

    1989-08-01

    The Medical College of Wisconsin implemented a major bone marrow transplant (BMT) program in July 1985. The type of transplants to be focused on were allogeneic T-lymphocyte deplete. Total body irradiation (TBI) was initially patterned after the Memorial method. Patients received total body irradiation in a sitting position at a dose rate of 20-25 cGy/minute with 50% attenuation lung blocks used both anterior/posterior and posterior/anterior. Electron boosting was utilized for the ribs beneath the lung blocks. Occasionally, lower extremity boosting was required because of the sitting position. A dose of 14 Gy was chosen since T-lymphocyte deplete bone marrow transplant data suggest the need for higher total doses to consistently obtain engraftment. This dose was given in 3 equal daily fractions over 3 days following conditioning chemotherapy. Six of 11 patients treated in this manner developed lethal pulmonary events. In response to the pulmonary toxicity, partial lung shielding was increased to 60% attenuation. In the next 107 patients receiving this program of total body irradiation there was a reduced incidence of fatal pulmonary events (10 cases of fatal idiopathic interstitial pneumonitis and 12 cases of fatal pulmonary infections) after a median follow-up of 9 months. This was an obvious improvement over the initial group. A significant level of hepato-renal toxicity was also observed with 14 Gy total body irradiation when no liver or kidney blocking was used. Of the first 20 patients treated, three cases of fatal veno-occlusive disease resulted. Subsequently, a 10% attenuation right sided liver block was added. Five of 98 patients treated with this block have developed fatal hepatic dysfunction, (median follow-up of 7.2 months). This incidence is not statistically different from the initial group but favors the use of the liver block. Some renal toxicity was also detected with the earlier regimen, especially in pediatric patients. Partial kidney blocking has

  6. [Allogenic hematopoietic stem cell transplantation in acquired aplastic anemia: first experience of the National Center for Bone Marrow Grafting].

    PubMed

    Abdelkefi, A; Ladeb, S; Ben Othman, T; Torjman, L; Jeddi, R; Ben Abdeladhim, A

    2001-10-01

    Bone marrow transplantation from HLA-identical sibling offers cure and leads to restoration of normal hematopoiesis and long-term survival in 60-80% of recipients. From february 1998 to october 1999, seven patients with aplastic anemia (2 very severe aplastic anemia and 5 severe aplastic anemia), with a median age of 22 years (14-39), received a transplant from an HLA-identical sibling donor. All patients had sustained engraftment. Only one patient developed grade IV acute graft-versus-host disease. One patient died in the 22th day of systemic mycobacterial infection and one in the 79th day of acute graft-versus-host disease. The remaining 5 patients are alive and have a complete hematological recovery, with a median follow-up of 6 months (1,5-12). There are at least two reasons for the improved survival of patients with aplastic anemia who where treated by HLA-indentical bone marrow transplantation. One is the decreased incidence of graft rejection that has resulted from the more judicious use of transfusions before bone marrow transplantation, and improvements in the immunosuppressive qualities of the conditioning programs. Another reason for improved survival is the decrease in the incidence and severity of acute graft-versus-host disease. PMID:11910688

  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. Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

    PubMed Central

    Lyra, Andre Castro; Soares, Milena Botelho Pereira; da Silva, Luiz Flavio Maia; Fortes, Marcos Fraga; Silva, André Goyanna Pinheiro; Mota, Augusto César de Andrade; Oliveira, Sheilla A; Braga, Eduardo Lorens; de Carvalho, Wilson Andrade; Genser, Bernd; dos Santos, Ricardo Ribeiro; Lyra, Luiz Guilherme Costa

    2007-01-01

    AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 ± 0.9) and 4 mo (2.10 ± 1.0) after cell transplantation that baseline levels (2.78 ± 1.2). Albumin levels 4 mo after BMC infusion (3.73 ± 0.5) were higher than baseline levels (3.47 ± 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease. PMID:17373741

  9. Allogeneic bone marrow transplantation for chronic myeloid leukemia using HLA identical sibling donors primed with G-CSF.

    PubMed

    Chen, Hui-Ren; Ji, Shu-Quan; Wang, Hang-Xiang; Yan, Hong-Ming

    2002-08-01

    Many studies have shown that G-CSF mobilized peripheral blood progenitor cell transplants (PBPCT) manifests faster recovery kinetics than conventional bone marrow transplants. This potential advantage of PBPCT still needs to be balanced against the risk of acute and chronic GVHD associating with the infusion of 10 - 15 fold higher donor lymphocyte number in unmanipulated allogeneic PBPCT than the marrow graft. To evaluate the effect of G-CSF primed bone marrow as a source of stem cells in the HLA-matched sibling transplantation, G-CSF primed with non-primed donor marrow in engraftment and incidence of GVHD for a homogenous group of patients with chronic myeloid leukemia (CML) were compared. Fifty patients with CML underwent bone marrow transplant, thirty-two donors (study group) were given G-CSF 3 - 4 micro g/kg per day for seven days prior to marrow harvest and eighteen donors (control group) had marrow harvest without G-CSF stimulation. Conditioning regimen consisted of total body irradiation and cyclophosphamide (CY), busulfan and CY, or busulfan, total body irradiation and CY. Both groups received same post-grafting GVHD prophylaxis and postgrafting G-CSF treatment. It was found that G-CSF primed donor marrow yielded with significantly higher number of total nucleated cells as well as CD34(+) cells and CFU-GM compared to non-G-CSF primed marrow (P = 0.001). The median engraftment time for absolute neutrophil (ANC > 0.5 x 10(9)/L) was day 15 (range 10 - 22) in the group of G-CSF primed vs day 21 in the non-primed donor group (P = 0.001). The median time for platelets (> 20 x 10(9)/L) was day 17.5 (range 13 - 28) in the group of G-CSF primed vs day 24 in non-primed group (P = 0.001). The incidence of acute GVHD grade II - IV in G-CSF primed donor group was surprisingly as low,as only two cases of thirty-two transplants (6.3%) with acute GVHD grade II limited to the skin. Whereas, five of eighteen patients (27.8%) in the control group developed acute GVHD grade II

  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. Enhancement of the grafting efficiency of transplanted marrow cells by preincubation with interleukin-3 and granulocyte-macrophage colony-stimulating factor

    SciTech Connect

    Tavassoli, M.; Konno, M.; Shiota, Y.; Omoto, E.; Minguell, J.J.; Zanjani, E.D.

    1991-04-01

    To improve the grafting efficiency of transplanted murine hematopoietic progenitors, we briefly preincubated mouse bone marrow cells with interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) ex vivo before their transplantation into irradiated recipients. This treatment was translated into an increase in the seeding efficiency of colony-forming unit-spleen (CFU-S) and CFU-GM after transplantation. Not only was the concentration of CFU-S in the tibia increased 2 and 24 hours after transplantation, but the total cell number and CFU-S and CFU-GM concentrations were persistently higher in IL-3- and GM-CSF-treated groups 1 to 3 weeks after transplantation. In addition, the survival of animals as a function of transplanted cell number was persistently higher in IL-3- and GM-CSF-treated groups compared with controls. The data indicate that the pretreatment of marrow cells with IL-3 and GM-CSF before transplantation increases the seeding efficiency of hematopoietic stem cells and probably other progenitor cells after transplantation. This increased efficiency may be mediated by upward modulation of homing receptors. Therefore, ex vivo preincubation of donor marrow cells with IL-3 and GM-CSF may be a useful tactic in bone marrow transplantation.

  12. Recovery from CMV esophagitis after allogeneic bone marrow transplantation using non-myeloablative conditioning: the role of immunosuppression.

    PubMed

    Fiegl, Michael; Gerbitz, Armin; Gaeta, Antonia; Campe, Hartmut; Jaeger, Gundula; Kolb, Hans-Jochem

    2005-11-01

    Cytomegalovirus (CMV) positive recipients of CMV negative bone marrow bear a significantly higher risk of developing CMV disease compared to all other constellations. Here, we report a case of severe CMV induced esophagitis after allogeneic bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. The patient developed the first symptoms between day 10 and 20 after dose reduced conditioning and HLA-matched unrelated stem cell transplantation. Esophageal tissue biopsies as well as peripheral blood proved positive for CMV DNA by PCR. Treatment with acyclovir, ganciclovir, foscarnet, cidofovir, and immunoglobulines resulted in elimination of CMV in peripheral blood but not in clinical improvement. Only tapering of cyclosporine at day +120 eventually led to the development of CMV-specific T-cells and resolution of esophagitis. PMID:16129661

  13. Cytomegalovirus Viral Load and Virus-specific Immune Reconstitution after Peripheral Blood Stem Cell versus Bone Marrow Transplantation

    PubMed Central

    Guerrero, A.; Riddell, S.R.; Storek, J.; Stevens-Ayers, T.; Storer, B.; Zaia, J. A.; Forman, S.; Negrin, R.S.; Chauncey, T.; Bensinger, W.; Boeckh, M.

    2011-01-01

    Peripheral blood stem cell (PBSC) products contain more T cells and monocytes when compared to bone marrow (BM), leading to fewer bacterial and fungal infections. CMV viral load and disease as well as CMV-specific immune reconstitution were compared in patients enrolled in a randomized trial comparing PSBC and BM transplantation. There was a higher rate of CMV infection and disease during the first 100 days after transplantation among PBSC recipients (any antigenemia/DNAemia: PBSC, 63% vs. BM, 42%, P=0.04; CMV disease: PBSC, 17% vs. BM, 4%, P=0.03). By two years, CMV disease rates were similar. The early increase in CMV events correlated temporarily with lower CMV-specific CD4+ T helper and CD8+ cytotoxic T lymphocyte function at 30 days after transplantation in PBSC recipients. By 3 months after transplantation and thereafter, CMV-specific immune responses were similar between BM and PBSC recipients. In conclusion, higher CMV infection and disease rates occurred in PBSC transplant recipients early after transplantation. These differences may be due to a transient delay in CMV specific immune reconstitution following PBSC transplantation. PMID:21664286

  14. 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

  15. 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.

  16. 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

  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. 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

  19. An asymptomatic 61-year-old man with BCR-ABL-positive bone marrow following autologous transplantation for multiple myeloma

    PubMed Central

    Roper, Nitin; Deangelo, Daniel; Kuo, Frank; Cin, Paola dal; Ghobrial, Irene; Aster, Jon C.

    2010-01-01

    A 61-year-old man treated with an autologous transplant for multiple myeloma was incidentally found to have a high level of BCR-ABL fusion gene-positive cells in his bone marrow. We describe the clinical decision-making process that led us to initiate therapy with imatinib, despite the absence of any clinical evidence of chronic myelogenous leukemia or other BCR-ABL associated hematologic malignancy. PMID:20730794

  20. 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

  1. 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

  2. Osteoanagenesis after transplantation of bone marrow-derived mesenchymal stem cells using polyvinylidene chloride film as a scaffold.

    PubMed

    Hamajima, Soichiro; Hayashi, Tatsuhide; Sato, Yamato; Sasaki, Keisuke; Kawai, Tatsushi

    2011-01-01

    The aim of this study was to develop a new cell transplantation technique for osteoanagenesis at bone defect sites. Polyvinylidene chloride (PVDC) film was evaluated because of its good biocompatibility and flexibility. We used this film as both a cell scaffold and a barrier membrane. Initially, the cell compatibility of the PVDC film for fibroblast-like cells and osteoblast-like cells was confirmed. Subsequently, bone marrow cells were obtained from rats and cultured on PVDC films in two kinds of medium. The PVDC films with bone marrow-derived mesenchymal stem cells (MSCs) were then applied to critical-sized bone defects in the calvarial bone of rats. After the transplantation, the surgical sites were dissected out and evaluated by soft X-ray radiography, micro-CT analysis and histological examinations. The bone marrow-derived MSC-transplanted rats showed greater bone regeneration than the control rats. Therefore, PVDC film is considered to be useful as a scaffold for bone regeneration. PMID:21946492

  3. 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.

  4. A novel explanation of corneal clouding in a bone marrow transplant-treated patient with Hurler syndrome.

    PubMed

    Yuan, Ching; Bothun, Erick D; Hardten, David R; Tolar, Jakub; McLoon, Linda K

    2016-07-01

    One common complication of mucopolysaccharidosis I-Hurler (MPS1-H) is corneal clouding, which occurs despite current treatments, including bone marrow transplantation. Human corneas were obtained from a 14 year old subject with MPS1-H and visual disability from progressive corneal clouding despite a prior bone marrow transplant at age 2. This was compared to a cornea from a 17 year old donated to our eye bank after his accidental death. The corneas were analyzed microscopically after staining with Alcian blue, antibodies to collagen I, IV, VI, and α-smooth muscle actin. Differences in levels of expression of the indicated molecules were assessed. Corneas from Hurler and control mice were examined similarly to determine potential mechanistic overlap. The MPS1-H subject cornea showed elevations in mucopolysaccharide deposition. The MPS1-H and Hurler mice corneas showed increased and disorganized expression of collagen I and IV relative to the control corneas. The MPS1-H corneas also showed increased and disordered expression of collagen VI. Positive expression of α-smooth muscle actin indicated myofibroblast conversion within the MPS1-H cornea in both the patient and mutant mouse material compared to normal human and control mouse cornea. Increased deposition of collagens and smooth muscle actin correlate with corneal clouding, providing a potential mechanism for corneal clouding despite bone marrow transplantation in MPS1-H patients. It might be possible to prevent or slow the onset of corneal clouding by treating the cornea with drugs known to prevent myofibroblast conversion. PMID:27235795

  5. 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

  6. Long-term therapeutic efficacy of allogenic bone marrow transplantation in a patient with mucopolysaccharidosis IVA

    PubMed Central

    Chinen, Yasutsugu; Higa, Takeshi; Tomatsu, Shunji; Suzuki, Yasuyuki; Orii, Tadao; Hyakuna, Nobuyuki

    2014-01-01

    Mucopolysaccharidosis IVA (MPS IVA) is one of the lysosomal storage diseases. It is caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of the specific glycosaminoglycans keratan sulfate and chondroitin-6-sulfate. This accumulation has a direct impact on cartilage and bone development, resulting in systemic skeletal dysplasia. There is no curative therapy for this skeletal dysplasia. This report describes long-term therapeutic efficacy in a 15-year-old boy with a severe form of MPS IVA who received successful allogeneic bone marrow transplantation (BMT) from his HLA-identical carrier sister. The level of the GALNS enzyme in the recipient’s lymphocytes reached almost half of normal level within two years after BMT. For the successive 9+ years post-BMT, GALNS activity in his lymphocytes maintained the same level as the donor’s, and the level of urinary uronic acid was reduced. Lumbar bone mineral density increased around 50% one year later post-BMT and was kept consistent. Radiographs showed that the figures of trochanter major and minor appeared, while the epiphyseal dysplasia in the femoral cap was almost unchanged. Loud snoring and apnea disappeared. Vital capacity increased to around 20% for the first two years and was maintained. Activity of daily life (ADL) was improved in work/study efficacy, respiratory status, sleep, joint pain, and frequency of infection. In conclusion, the long-term study of hematopoetic stem cell transplantation has shown clinical improvements in respiratory function, radiograph findings, ADL, and biochemical findings, suggesting that it is a potential therapeutic option for patients with MPS IVA. PMID:25593792

  7. 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

  8. Dynamic of bone marrow fibrosis regression predicts survival after allogeneic stem cell transplantation for myelofibrosis.

    PubMed

    Kröger, Nicolaus; Zabelina, Tatjana; Alchalby, Haefaa; Stübig, Thomas; Wolschke, Christine; Ayuk, Francis; von Hünerbein, Natascha; Kvasnicka, Hans-Michael; Thiele, Jürgen; Kreipe, Hans-Heinrich; Büsche, Guntram

    2014-06-01

    We correlate regression of bone marrow fibrosis (BMF) on day 30 and 100 after dose- reduced allogeneic stem cell transplantation (allo-SCT) in 57 patients with primary or post-essential thrombocythemia/polycythemia vera myelofibrosis with graft function and survival. The distribution of International Prognostic Scoring System (IPSS) risk score categories was 1 patient with low risk, 5 patients with intermediate-1 risk, 18 patients with intermediate-2 risk, and 33 patients with high risk. Before allo-SCT, 41 patients (72%) were classified as XXX [myclofibrosis (MF)]-3 and 16 (28%) were classified as MF-2 according to the World Health Organization criteria. At postengraftment day +30 (±10 days), 21% of the patients had near-complete or complete regression of BMF (MF-0/-1), and on day +100 (±20 days), 54% were MF-0/-1. The 5-year overall survival rate at day +100 was 96% in patients with MF-0/-1 and 57% for those with MF-2/-3 (P = .04). There was no difference in BMF regression at day +100 between IPSS high-risk and low/intermediate-risk patients. Complete donor cell chimerism at day +100 was seen in 81% of patients with MF-0/-1 and in 31% of those with MF-2/-3. Patients with MF-2/-3 at day +100 were more likely to be transfusion-dependent for either RBCs (P = .014) or platelets (P = .018). Rapid BMF regression after reduced-intensity conditioning allo-SCT resulted in a favorable survival independent of IPSS risk score at transplantation. PMID:24589549

  9. The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras. These results raise the possibility that the fulminant GVHD seen in human marrow transplantation is in part due to the major contamination of bone marrow with peripheral blood that results from the techniques currently used for human bone marrow harvest.

  10. Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

    SciTech Connect

    Sanders, J.E.; Buckner, C.D.; Leonard, J.M.; Sullivan, K.M.; Witherspoon, R.P.; Deeg, H.J.; Storb, R.; Thomas, E.D.

    1983-09-01

    One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

  11. Evaluation of dose homogenization and radiation carcinogenesis risk in total body irradiation for bone marrow transplantation.

    PubMed

    Oysul, K; Dirican, B; Beyzadeoglu, M; Sürenkok, S; Arpaci, F; Pak, Y

    2003-01-01

    The purpose of this study is to report on the dose homogeneity in total body irradiated patients undergoing Bone Marrow Transplantation (BMT), and carcinogenic risk in surviving patients. Between 1987 and 2001, 105 patients received hyperfractionated (6 fractions in 3 days) 12 Gy Total Body Irradiation (TBI) in our institution with lateral opposed fields. All the patients had measurements with thermoluminiscence dosimetry (TLD100) placed on seven bilateral body sites in vivo, controlled by the randophantom measurements to verify reasonable dose homogeneity achievement. The comorbid effects in the whole TBI conditioning group with at least three months post BMT follow-up were noted and surviving patients who had a minimum 5-year and maximum 14-year follow-up (median 7.8 years) have been evaluated for carcinogenic radiation risk on the basis of tissue weighting factors as defined by ICRP 60. Reasonable dose homogeneity by lateral opposed beam TBI has been obtained in all 105 patients in whom lateral TLD100 measurement means were within +5% of the planned doses. Calculated carcinogenesis risk factor was 11.34% for males and 12.40% for females, and no second-cancer has been detected whilst radiation-induced 5 cataracts and 10 interstitial pneumonia comorbidities were noted. Dose homogenization can be well achieved for hyperfractionated lateral-beam TBI with acceptable comorbidities and estimated second-cancer risk is significant but relatively low compared to the risk from the clinical indications for TBI. PMID:14628091

  12. 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

  13. Plasma pharmacokinetics of high-dose oral busulfan in children and adults undergoing bone marrow transplantation.

    PubMed

    Bostrom, Bruce; Enockson, Karen; Johnson, Amy; Bruns, Alyssa; Blazar, Bruce

    2003-01-01

    We have analyzed the plasma pharmacokinetics of busulfan in 272 patients receiving high-dose oral busulfan and intravenous cyclophosphamide in conjunction with allogeneic or autologous bone marrow transplantation. The patients ranged in age from 2 months to 59 yr (mean 10, median 12 yr) and had the following diagnoses: thalassemia or sickle cell anemia (n = 74); leukemia or myelodysplasia (n = 112); inborn errors of metabolism (n = 41) or immunodeficiency (n = 45). Plasma specimens were collected following the first dose for each patient which ranged from 1 to 4 mg/kg (mean +/- SD, 1.21 +/- 0.41, median 1.15). Busulfan was quantitated using ultraviolet absorbance detection after derivatization and HPLC separation. Pharmacokinetic parameters were derived by modeling the raw data to fit first-order single compartment kinetics. The kinetic parameters showed wide interpatient variability independent of age and diagnosis. There was a statistically significant correlation of age with the following parameters: area under the curve (AUC); maximal concentration; minimum concentration; clearance; volume of distribution and absorption half-time. The coefficients of determination (i.e. correlation coefficient squared) were low ranging from 0.04 to 0.12 implying only a small part (i.e. 4-12%) of the variance was explained by age. Although busulfan pharmacokinetics are age-related most of the variability is not explained by age or diagnosis. PMID:12603688

  14. Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice.

    PubMed

    Norflus, F; Tifft, C J; McDonald, M P; Goldstein, G; Crawley, J N; Hoffmann, A; Sandhoff, K; Suzuki, K; Proia, R L

    1998-05-01

    The GM2 gangliosidoses are a group of severe, neurodegenerative conditions that include Tay-Sachs disease, Sandhoff disease, and the GM2 activator deficiency. Bone marrow transplantation (BMT) was examined as a potential treatment for these disorders using a Sandhoff disease mouse model. BMT extended the life span of these mice from approximately 4.5 mo to up to 8 mo and slowed their neurologic deterioration. BMT also corrected biochemical deficiencies in somatic tissues as indicated by decreased excretion of urinary oligosaccharides, and lower glycolipid storage and increased levels of beta-hexosaminidase activity in visceral organs. Even with neurologic improvement, neither clear reduction of brain glycolipid storage nor improvement in neuronal pathology could be detected, suggesting a complex pathogenic mechanism. Histological analysis revealed beta-hexosaminidase-positive cells in the central nervous system and visceral organs with a concomitant reduction of colloidal iron-positive macrophages. These results may be important for the design of treatment approaches for the GM2 gangliosidoses. PMID:9576752

  15. Hurler's syndrome: dental findings in a case treated with bone marrow transplantation in infancy.

    PubMed

    Hingston, E J; Hunter, M L; Hunter, B; Drage, N

    2006-05-01

    Hurler's syndrome, also known as mucopolysaccharidosis I (MPS I-H), is a rare condition inherited as an autosomal recessive trait. It is caused by a deficiency in alpha-L-iduronidase, an enzyme that participates in the degradation of the glycosaminoglycans (GAGs) heparin sulphate and dermatan sulphate. Children with Hurler's syndrome appear nearly normal at birth but, left untreated, show a progressive mental and physical deterioration caused by a build-up of GAGs in all organs of the body. Death is often caused by cardiac or respiratory failure and usually occurs before the second decade of life. In recent years, bone marrow transplantation (BMT) has been employed in the management of patients with Hurler's syndrome. However, the dental findings observed in these cases have not previously been reported in the dental literature. Here we report a patient aged 11 years and 6 months, presented to a Specialist Paediatric Dentistry Unit, who was successfully treated by BMT at 18 months of age. PMID:16643543

  16. 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

  17. Keratinocyte growth factor enhances DNA plasmid tumor vaccine responses after murine allogeneic bone marrow transplantation

    PubMed Central

    Jenq, Robert R.; King, Christopher G.; Volk, Christine; Suh, David; Smith, Odette M.; Rao, Uttam K.; Yim, Nury L.; Holland, Amanda M.; Lu, Sydney X.; Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Diab, Adi; Alpdogan, Onder; Penack, Olaf; Na, Il-Kang; Kappel, Lucy W.; Wolchok, Jedd D.; Houghton, Alan N.; Perales, Miguel-Angel

    2009-01-01

    Keratinocyte growth factor (KGF), which is given exogenously to allogeneic bone marrow transplantation (allo-BMT) recipients, supports thymic epithelial cells and increases thymic output of naive T cells. Here, we demonstrate that this improved T-cell reconstitution leads to enhanced responses to DNA plasmid tumor vaccination. Tumor-bearing mice treated with KGF and DNA vaccination have improved long-term survival and decreased tumor burden after allo-BMT. When assayed before vaccination, KGF-treated allo-BMT recipients have increased numbers of peripheral T cells, including CD8+ T cells with vaccine-recognition potential. In response to vaccination, KGF-treated allo-BMT recipients, compared with control subjects, generate increased numbers of tumor-specific CD8+ cells, as well as increased numbers of CD8+ cells producing interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). We also found unanticipated benefits to antitumor immunity with the administration of KGF. KGF-treated allo-BMT recipients have an improved ratio of T effector cells to regulatory T cells, a larger fraction of effector cells that display a central memory phenotype, and effector cells that are derived from a broader T-cell–receptor repertoire. In conclusion, our data suggest that KGF can function as a potent vaccine adjuvant after allo-BMT through its effects on posttransplantation T-cell reconstitution. PMID:19011222

  18. 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

  19. Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow Mononuclear Cell Transplantation.

    PubMed

    Sharma, Alok; Sane, Hemangi; Kulkarni, Pooja; D'sa, Myola; Gokulchandran, Nandini; Badhe, Prerna

    2015-01-01

    Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child's development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve conduction. Cell therapy is being explored as an alternate therapeutic strategy as there is no treatment currently available for CP. To study the benefits of this treatment we have administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand functions, walking stability, balance, posture and coordination improved. His ability to perform activities of daily living improved. On repeating the Functional Independence Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography-computed tomography (PET-CT) scan of the brain six months after intervention showed progression of the mean standard deviation values towards normalization which correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a potential for treatment of CP. PMID:26199918

  20. Extramedullary relapse after allogeneic bone marrow transplantation plus buffy-coat in two high risk patients.

    PubMed

    Salutari, P; Sica, S; Micciulli, G; Rutella, S; Di Mario, A; Leone, G

    1996-01-01

    In order to obtain an additional graft versus leukemia effect (GVL) and rapid engraftment, donor leukocyte infusion (DLI) was added to unseparated, sex-mismatched allogeneic bone marrow transplantation in two male patients (age 21, 26) affected by high risk hematological malignancies (refractory T-ALL, refractory B-LBL in leukemic phase). Graft versus host disease (GVHD) prophylaxis consisted of methotrexate (MTX) alone. DLI were obtained after G-CSF 16 ug/kg/day sc. A total of 2.36 and 5.8 x 10(6)/kg MNC, 5.4 and 11 x 10(6)/kg CD34+ cells, 1.3 and 1.3 x 10(6)/kg CD3+ lymphocytes, respectively, were infused. Hemopoietic recovery occurred promptly. Complete chimerism was detected by cytogenetic examination. One patient developed an extramedullary relapse that first involved the cranial nerves, and then the testes, soft tissue and skin; the other patient developed central nervous system disease and then bilateral paravertebral masses with progressive paraplegia. Despite complete medullary remission with normal female karyotype, both patients died from extramedullary progression of their disease. Our observation shows that, at least in high risk patients, no additional GVHD or GVL effect was evident after donor leukocyte infusion. Extramedullary relapse was not prevented despite good control of medullary disease. PMID:8641654

  1. Aging accentuates and bone marrow transplantation ameliorates metabolic defects in Fabry disease mice.

    PubMed

    Ohshima, T; Schiffmann, R; Murray, G J; Kopp, J; Quirk, J M; Stahl, S; Chan, C C; Zerfas, P; Tao-Cheng, J H; Ward, J M; Brady, R O; Kulkarni, A B

    1999-05-25

    Fabry disease is an X-linked metabolic disorder caused by a deficiency of alpha-galactosidase A (alpha-Gal A). The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide (Gb3). In patients with this disorder, glycolipid deposition in endothelial cells leads to renal failure and cardiac and cerebrovascular disease. Recently, we generated alpha-Gal A gene knockout mouse lines and described the phenotype of 10-week-old mice. In the present study, we characterize the progression of the disease with aging and explore the effects of bone marrow transplantation (BMT) on the phenotype. Histopathological analysis of alpha-Gal A -/0 mice revealed subclinical lesions in the Kupffer cells in the liver and macrophages in the skin with no gross lesions in the endothelial cells. Gb3 accumulation and pathological lesions in the affected organs increased with age. Treatment with BMT from the wild-type mice resulted in the clearance of accumulated Gb3 in the liver, spleen, and heart with concomitant elevation of alpha-Gal A activity. These findings suggest that BMT may have a potential role in the management of patients with Fabry disease. PMID:10339603

  2. 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

  3. Improved Quality of Life in A Case of Cerebral Palsy after Bone Marrow Mononuclear Cell Transplantation

    PubMed Central

    Sharma, Alok; Sane, Hemangi; Kulkarni, Pooja; D’sa, Myola; Gokulchandran, Nandini; Badhe, Prerna

    2015-01-01

    Cerebral palsy (CP) is a non progressive, demyelinating disorder that affects a child’s development and posture and may be associated with sensation, cognition, communication and perception abnormalities. In CP, cerebral white matter is injured resulting in the loss of oligodendrocytes. This causes damage to the myelin and disruption of nerve conduction. Cell therapy is being explored as an alternate therapeutic strategy as there is no treatment currently available for CP. To study the benefits of this treatment we have administered autologous bone marrow mononuclear cells (BMMNCs) to a 12-year-old CP case. He was clinically re-evaluated after six months and found to demonstrate positive clinical and functional outcomes. His trunk strength, upper limb control, hand functions, walking stability, balance, posture and coordination improved. His ability to perform activities of daily living improved. On repeating the Functional Independence Measure (FIM), the score increased from 90 to 113. A repeat positron emission tomography-computed tomography (PET-CT) scan of the brain six months after intervention showed progression of the mean standard deviation values towards normalization which correlated to the functional changes. At one year, all clinical improvements have remained. This indicated that cell transplantation may improve quality of life and have a potential for treatment of CP. PMID:26199918

  4. The value of immunohistochemistry and in situ hybridization in detecting cytomegalovirus in bone marrow transplant recipients.

    PubMed

    Rasing, L A; De Weger, R A; Verdonck, L F; van der Bij, W; Compier-Spies, P I; De Gast, G C; Van Basten, C D; Schuurman, H J

    1990-06-01

    Autopsy tissues of 19 patients with complications after bone marrow transplantation (BMT) were analysed for the presence of cytomegalovirus (CMV) using histochemical methods. CMV antigens were detected by antibodies to CMV Immediate Early Antigen (IEA) or CMV Late Antigen (LA). CMV-DNA was detected by DNA in situ hybridization (DISH). IEA was detected in one or more tissues in 79% of 14 patients from whom frozen tissue was available. CMV-DNA was detected on paraffin sections in 84% of all 19 patients. CMV components were present in all organs studied; the highest incidence was found in lung, gastrointestinal tract and kidney. In histology, only 37% of patients showed signs of CMV infection by the presence of cytomegalic cells with nuclear inclusions (or so called "owl eye cells"). In tissue culture, only 33% of 15 patients were CMV positive. Serologically, 68% of all patients had active CMV infection, as indicated by a rise in antibody titres. We conclude that the quick detection of CMV IEA and CMV-DNA has a high sensitivity and predictive value, which is comparable to or exceeds the serological detection of CMV. PMID:2166539

  5. Patient perceptions of an art-making experience in an outpatient blood and marrow transplant clinic.

    PubMed

    Mische Lawson, L; Glennon, C; Amos, M; Newberry, T; Pearce, J; Salzman, S; Young, J

    2012-05-01

    This study explored blood and marrow transplantation (BMT) patients' perceptions of an art-making experience during BMT treatment. Participants including patients receiving BMT for a variety of cancers (10 men/10 women, aged 20-68) were offered a 1 hour tile-painting activity during treatment. Participants with cognitive impairment and respiratory precautions were excluded from the study. Researchers followed immune precaution protocols for the safety of participants. Data were collected through semi-structured, in-depth interviews with 20 participants to gather information about their perceptions of the art-making experience in a BMT clinic setting. Interview recordings were transcribed verbatim and analysed. Researchers coded transcripts independently and discussed outcomes together to achieve agreement on themes. Twelve themes emerged from the data, with the three most prevalent themes being Occupying Time (20.5%), Creative Expression (13.5%), and Reactions to Tile Painting (13.5%). Other themes included Support (12.2%), Side Effects (7.3%), Other Activities Suggested by Patients (7%), BMT Treatment Process (6.2%), Shared Painting Experience (5.9%), Life Outlook (5.2%), BMT Life Changes (3.8%), Spirituality (3%) and Barriers (1.9%). Through analysis of these themes, researchers have identified this art-making experience as a diversional or meaningful way to spend time during treatment, a medium for creative expression, and a distraction from negative side effects of the BMT process. PMID:22150782

  6. Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction

    PubMed Central

    Protti, Andrea; Mongue-Din, Heloise; Mylonas, Katie J.; Sirker, Alexander; Sag, Can Martin; Swim, Megan M.; Maier, Lars; Sawyer, Greta; Dong, Xuebin; Botnar, Rene; Salisbury, Jon; Gray, Gillian A.; Shah, Ajay M.

    2016-01-01

    Background Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. Methods and results Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. Conclusions The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI. PMID:26688473

  7. "A day in my life" photography project: the silent voice of pediatric bone marrow transplant patients.

    PubMed

    Breitwieser, Carrie L; Vaughn, Lisa M

    2014-01-01

    A photovoice project was conducted with pediatric bone marrow transplant (BMT) patients to examine their coping skills and interpretation of their experience during a BMT, especially when hospitalized. We also wanted to determine how photovoice could be used within a pediatric BMT unit. Sixteen children (ages 4-14) and 2 young adults (ages 22 and 25) from a pediatric BMT unit participated in the project. Six BMT outpatients participated in the data analysis and evaluation phase. Fourteen clinical staff evaluated the impact of the project on their practice. Three primary themes emerged from the pre- and post-BMT photos, accompanying detailed notes, and BMT outpatient analysis of the photos: (a) BMT is "torture," (b) BMT is "time slipping away," and (c) BMT requires normalization, comfort, distraction, and support. BMT patients and staff concluded that photovoice helped express and release emotions regarding the challenges of BMT. BMT staff noted that the results of this project reminded them of the importance of being patient-centered and mindful of patient experience and the therapeutic relationship. PMID:25013004

  8. 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.

  9. 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. PMID:25957389

  10. 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

  11. Localized bone marrow transplantation leads to skin allograft acceptance in nonmyeloablated recipients: comparison of intra-bone marrow and isolated limb perfusion.

    PubMed

    Askenasy, Nadir

    2002-01-01

    It has been shown that engraftment of allogeneic bone marrow cells (BMC) induces tolerance to antigen-matched organs, and infusion of a megadose of cells improves the success of engraftment of T-cell-depleted BMC. This study explores intra-bone marrow injection (IB) and isolated limb perfusion (IL) as means of localized bone marrow transplantation (BMT) and assesses their tolerogenic effect. Intravenous (i.v.), IB, and IL infusion of syngeneic and allogeneic whole BMC rescued 90%-100% of myeloablated recipients. Tracing of PKH-labeled cells revealed early systemic dissipation after IB injection, indicating that it was equivalent to i.v. transplantation. In contrast, IL perfusion led to initial localization of donor BMC. BALB/c recipients conditioned with 70 microg/g busulfan had 58% +/- 5% and 44% +/- 4% donor lymphocytes at 4 weeks after i.v. and IL infusion, respectively, of 10(7) whole BMC from B10 donors. This suggests that cells migrated out of the IL femur and seeded other bones. All recipients accepted donor-matched skin grafts and acutely rejected third party grafts. T-cell depletion lowered the engraftment efficiency of i.v.-BMT by 35% (p < 0.001 versus whole BMC), but not when infused IL (p < 0.001). It is concluded that IL-BMT is a procedure for initial localization of donor cells, which is as efficient as i.v.- and IB-BMT in rescue of myeloablated mice, induction of hemopoietic chimerism, and donor-specific immune nonresponsiveness to secondary skin grafts without myeloablative conditioning. The megadose effect achieved by inoculation of a small hemopoietic space improved engraftment of T-cell-depleted BMC. This approach may have clinical applications. PMID:11796926

  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. PMID:26901703

  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. PMID:26718665

  14. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia.

    PubMed

    Rocha, V; Cornish, J; Sievers, E L; Filipovich, A; Locatelli, F; Peters, C; Remberger, M; Michel, G; Arcese, W; Dallorso, S; Tiedemann, K; Busca, A; Chan, K W; Kato, S; Ortega, J; Vowels, M; Zander, A; Souillet, G; Oakill, A; Woolfrey, A; Pay, A L; Green, A; Garnier, F; Ionescu, I; Wernet, P; Sirchia, G; Rubinstein, P; Chevret, S; Gluckman, E

    2001-05-15

    In order to compare the outcomes of unrelated umbilical cord blood transplants (UCBTs) or bone marrow transplants, 541 children with acute leukemia (AL) transplanted with umbilical cord blood (n = 99), T-cell-depleted unrelated bone marrow transplants (T-UBMT) (n = 180), or nonmanipulated (UBMT) (n = 262), were analyzed in a retrospective multicenter study. Comparisons were performed after adjustment for patient, disease, and transplant variables. The major difference between the 3 groups was the higher number in the UCBT group of HLA mismatches (defined by serology for class I and molecular typing for DRB1). The donor was HLA mismatched in 92% of UCBTs, in 18% of UBMTs, and in 43% of T-UBMTs (P <.001). Other significant differences were observed in pretransplant disease characteristics, preparative regimens, graft-versus-host disease (GVHD) prophylaxis, and number of cells infused. Nonadjusted estimates of 2-year survival and event-free survival rates were 49% and 43%, respectively, in the UBMT group, 41% and 37% in the T-UBMT group, and 35% and 31% in the UCBT group. After adjustment, differences in outcomes appeared in the first 100 days after the transplantation. Compared with UBMT recipients, UCBT recipients had delayed hematopoietic recovery (Hazard ratio [HR] = 0.37; 95% confidence interval [95CI]: 0.27-0.52; P <.001), increased 100 day transplant-related mortality (HR = 2.13; 95CI: 1.20-3.76; P <.01) and decreased acute graft-versus-host disease (aGVHD) (HR = 0.50; 95CI: 0.34-0.73; P <.001). T-UBMT recipients had decreased aGVHD (HR = 0.25; 95CI: 0.17-0.36; P <.0001) and increased risk of relapse (HR = 1.96; 95CI: 1.11-3.45; P =.02). After day 100 posttransplant, the 3 groups achieved similar results in terms of relapse. Chronic GVHD was decreased after T-UBMT (HR = 0.21; 95CI: 0.11-0.37; P <.0001) and UCBT (HR = 0.24; 95CI: 0.01-0.66; P =.002), and overall mortality was higher in T-UBMT recipients (HR = 1.39; 95CI: 0.97-1.99; P <.07). In conclusion, the

  15. 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.

  16. Eradication of Epstein-Barr virus by allogeneic bone marrow transplantation: implications for sites of viral latency.

    PubMed Central

    Gratama, J W; Oosterveer, M A; Zwaan, F E; Lepoutre, J; Klein, G; Ernberg, I

    1988-01-01

    Wild-type strains of Epstein-Barr virus (EBV) can be distinguished on the basis of variations in the molecular weight of virus-encoded, growth transformation-associated proteins. This approach was used to study the persistence of EBV in two seropositive recipients of allogeneic bone marrow transplants. The first patient received marrow from her EBV-seronegative brother, became EBV seronegative after grafting, and remained so for greater than 1200 days. Subsequently, she became infected with a new EBV strain that differed from her pretransplant strain but was indistinguishable from the virus isolated from her husband. The second patient received marrow from his EBV-seropositive brother. This patient showed only a transient decrease in IgG antibodies to EBV capsid antigen. His pretransplant strain differed from the virus of his donor. On days 252 and 915 after transplantation, lymphoblastoid cell lines were grown from the peripheral blood of the patient and were found to carry exclusively the virus of the donor. These results suggest that the latently EBV-infected host cells reside in a cellular compartment that can be destroyed by graft-versus-host reactivity, irradiation, or cytotoxic drugs. Hemopoietic tissue is the most likely candidate. Images PMID:2847171

  17. Booster irradiation to the spleen following total body irradiation. A new immunosuppressive approach for allogeneic bone marrow transplantation

    SciTech Connect

    Lapidot, T.; Singer, T.S.; Salomon, O.; Terenzi, A.; Schwartz, E.; Reisner, Y.

    1988-10-15

    Graft rejection presents a major obstacle for transplantation of T cell-depleted bone marrow in HLA-mismatched patients. In a primate model, after conditioning exactly as for leukemia patients, it was shown that over 99% of the residual host clonable T cells are concentrated in the spleen on day 5 after completion of cytoreduction. We have now corroborated these findings in a mouse model. After 9-Gy total body irradiation (TBI), the total number of Thy-1.2+ cells in the spleen reaches a peak between days 3 and 4 after TBI. The T cell population is composed of both L3T4 (helper) and Lyt-2 (suppressor) T cells, the former being the major subpopulation. Specific booster irradiation to the spleen (5 Gy twice) on days 2 and 4 after TBI greatly enhances production of donor-type chimera after transplantation of T cell-depleted allogeneic bone marrow. Similar enhancement can be achieved by splenectomy on day 3 or 4 after TBI but not if splenectomy is performed 1 day before TBI or 1 day after TBI, strengthening the hypothesis that, after lethal TBI in mice, the remaining host T cells migrate from the periphery to the spleen. These results suggest that a delayed booster irradiation to the spleen may be beneficial as an additional immunosuppressive agent in the conditioning of leukemia patients, in order to reduce the incidence of bone marrow allograft rejection.

  18. Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation

    PubMed Central

    Zhang, Wen; Shen, Zhong-Yang; Song, Hong-Li; Yang, Yang; Wu, Ben-Juan; Fu, Nan-Nan; Liu, Tao

    2014-01-01

    AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model. METHODS: BM MSCs were isolated from male Lewis rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. The HIT models were divided into a non-rejection group, saline-treated rejection group (via penile vein), and BM MSC–treated group (via penile vein). Intestinal mucosal barrier injury was estimated by diamine oxidase (DAO) and D-lactic acid (D-LA) expression levels. Tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) were detected by enzyme-linked immunosorbent assay. Ultrastructural change of tight junctions (TJs) was observed under transmission electron microscope. Expression levels of the TJ proteins occludin and zona occludens (ZO)-1, affected by the inflammatory factors, were measured using real-time polymerase chain reaction and Western blotting. RESULTS: The pathological score at each time point after surgery indicated significantly less serious injury in the BM MSCs-treated group than in the rejection group (P < 0.05). In the former, graft levels of DAO and D-LA were reduced, and TNF-α and INF-γ production was inhibited (at day 7: 10.6473 ± 0.0710 vs 17.2128 ± 0.4991, P < 0.05; 545.1506 ± 31.9416 vs 810.2637 ± 25.1175, P < 0.05). IL-10 and TGF-β production was increased greatly (at day 7: 125.7773 ± 4.7719 vs 80.3756 ± 2.5866, P < 0.05; 234.5273 ± 9.3980 vs 545.1506 ± 31.9416, P < 0.05). There was increased expression of occludin and ZO-1 protein (at day 7: 0.2674 ± 0.0128 vs 0.1352 ± 0.0142, P < 0.05; at day 5: 0.7189 ± 0.0289 vs 0.4556 ± 0.0242, P < 0.05) and mRNA (at day 7: 0.3860 ± 0.0254 vs 0.1673 ± 0.0369, P < 0.05; at day 5: 0.5727 ± 0.0419 vs 0.3598 ± 0.0242, P < 0.05). CONCLUSION: BM MSCs can improve intestinal barrier permeability

  19. 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

  20. Effect on lifespan of high yield non-myeloablating transplantation of bone marrow from young to old mice

    PubMed Central

    Kovina, Marina V.; Zuev, Viktor A.; Kagarlitskiy, German O.; Khodarovich, Yuriy M.

    2013-01-01

    Tissue renewal is a well-known phenomenon by which old and dying-off cells of various tissues of the body are replaced by progeny of local or circulating stem cells (SCs). An interesting question is whether donor SCs are capable to prolong the lifespan of an aging organism by tissue renewal. In this work, we investigated the possible use of bone marrow (BM) SC for lifespan extension. To this purpose, chimeric C57BL/6 mice were created by transplanting BM from young 1.5-month-old donors to 21.5-month-old recipients. Transplantation was carried out by means of a recently developed method which allowed to transplant without myeloablation up to 1.5 × 108 cells, that is, about 25% of the total BM cells of the mouse. As a result, the mean survival time, counting from the age of 21.5 months, the start of the experiment, was +3.6 and +5.0 (±0.1) months for the control and experimental groups, respectively, corresponding to a 39 ± 4% increase in the experimental group over the control. In earlier studies on BM transplantation, a considerably smaller quantity of donor cells (5 × 106) was used, about 1% of the total own BM cells. The recipients before transplantation were exposed to a lethal (for control animals) X-ray dose which eliminated the possibility of studying the lifespan extension by this method. PMID:23967009

  1. 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

  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. Outcome of aplastic anemia in adolescence: a survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Dufour, Carlo; Pillon, Marta; Passweg, Jakob; Socié, Gerard; Bacigalupo, Andrea; Franceschetto, Genny; Carraro, Elisa; Oneto, Rosi; Risitano, Antonio Maria; Peffault de Latour, Regis; Tichelli, André; Rovo, Alicia; Peters, Christina; Hoechsmann, Britta; Samarasinghe, Sujith; Kulasekararaj, Austin G; Schrezenmeier, Hubert; Aljurf, Mahmoud; Marsh, Judith

    2014-10-01

    We analyzed the outcome of 537 adolescents (age 12-18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14). Event-free survival in the same groups was respectively 83%, 64% and 71% (P=0.04). Cumulative incidence of rejection was 8% in matched family donor hematopoietic stem cell transplantation and 9% in transplants post failed front-line immunosuppression (P=0.62). Cumulative incidence of acute graft-versus-host disease was 12% in matched family donor transplants and 18% in transplants post failed immunosuppression (P=0.18). Chronic graft-versus-host disease was higher in matched family donor hematopoietic stem cell transplantation (8%) than in transplants post failed immunosuppressive therapy (20%) (P=0.0009). Cumulative incidence of post-therapy malignancies was 0.7% in matched family donor transplantations, 7% in transplantations post failed immunosuppression and 21% after front-line immunosuppression (P=0.0017). In the whole cohort, under multivariate analysis, the diagnosis to treatment interval of two months or under positively affected overall survival whereas up-front immunosuppression alone (with no subsequent

  4. Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation.

    PubMed

    Lieschke, G J; Ramenghi, U; O'Connor, M P; Sheridan, W; Szer, J; Morstyn, G

    1992-11-01

    Patients are at risk of mucositis and infections in the oral cavity during the neutropenic period after chemotherapy, which are significant causes of morbidity. In phase I/II studies with the haemopoietic growth factor granulocyte colony stimulating factor (G-CSF), a reduction in post-chemotherapy mucositis has been observed in addition to haematologic effects. To understand this phenomenon better in patients receiving G-CSF following high-dose chemotherapy with autologous bone marrow transplantation (ABMT), we studied the effects of G-CSF on levels of neutrophils recoverable from the oral cavity using a quantitative mouthrinse assay. In normal subjects, mouthrinses contained 472 +/- 329 x 10(3) neutrophils/mouthrinse. After chemotherapy followed by ABMT, mouthrinse neutrophil levels decreased to undetectable levels during the neutropenic period, but recovered 1-2 and 3-9 d before circulating neutrophil levels reached 0.1 and 1 x 10(9)/l respectively, whether or not patients received G-CSF. In patients who received G-CSF, the mean cumulative mucositis score was reduced from 35 +/- 9 to 21 +/- 12 (P < 0.05), and the maximum mean daily mucositis score was reduced from 2.8 +/- 0.5 to 1.7 +/- 0.9 (P < 0.01), compared to patients who did not receive G-CSF after ABMT. These studies provide in vivo evidence that neutrophils produced during G-CSF therapy are available to leave the circulation and enter tissues where their function is required for host defence. Since the usual temporal relationship between oral and peripheral blood neutrophil recovery was preserved during G-CSF administration after ABMT, these data support the hypothesis that the reduction in post-ABMT mucositis observed with G-CSF therapy may reflect a beneficial effect of G-CSF on the kinetics of oral mucosal neutrophil recovery in addition to the effect of G-CSF to accelerate peripheral blood neutrophil recovery. PMID:1283080

  5. Long-term effects of bone marrow transplantation in dogs with mucopolysaccharidosis I.

    PubMed Central

    Breider, M. A.; Shull, R. M.; Constantopoulos, G.

    1989-01-01

    The therapeutic effects of allogeneic bone marrow transplantation (BMT) in a canine model of mucopolysaccharidosis I (MPS I) were investigated. Long-term post-BMT pathologic and biochemical studies were performed on three groups of dogs: 1) MPS I-affected dogs that did not receive BMT, 2) MPS I-affected dogs that received total body irradiation followed by an allogeneic BMT, and 3) normal, unaffected dogs that served as BMT donors. All dogs were necropsied at approximately 20 months after BMT. The severity of MPS I-related lesions in the dogs receiving BMT was greatly diminished. These dogs had only slight cardiac valvular thickening, no meningeal thickening, no renal tubular epithelial vacuolation, decreased neuronal vacuolation, decreased corneal stromal vacuolation, and greatly diminished arterial medial thickening. The severity and incidence of degenerative arthropathy also were decreased in BMT dogs, however, vertebral lesions were similar to nontransplanted, affected dogs. Chondrocytes of both MPS I-BMT and MPS I-no BMT groups had similar marked cytoplasmic vacuolation, except for MPS I-BMT chondrocytes near the articular surface, which had more normal morphology. Ultrastructurally, the liver and kidney tissue in BMT recipients had no appreciable lysosomal accumulation of GAGs. These morphologic findings were supported by near normal levels and electrophoretic patterns of glycosaminoglycans (GAG) in most tissues of BMT recipient dogs. This study demonstrates that BMT is capable of substantially diminishing the severity of MPS I-related lesions in this canine model. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:2493739

  6. Living with the unknown: Posttraumatic stress disorder in pediatric bone marrow transplantation survivors and their mothers.

    PubMed

    Taskıran, Gülseren; Sürer Adanır, Aslı; Özatalay, Esin

    2016-04-01

    Bone marrow transplantation (BMT) is used to treat children with various hematologic, oncologic, and metabolic diseases. Although the treatment can be lifesaving, it is also physically and psychologically demanding for both the child and caregivers. In previous studies, BMT is found to be related with anxiety, posttraumatic stress disorder (PTSD), depression, and psychosocial problems both in children and parents. The aim of this study was to investigate PTSD in pediatric BMT survivors and their mothers compared with the healthy controls. Twenty-seven BMT survivors and their mothers and 28 healthy peers and their mothers were recruited as the study group and as the comparison group, respectively. All children were interviewed using Child Posttraumatic Stress Disorder-Reaction Index (CPTSD-RI) for assessing posttraumatic stress responses. As for mothers, Clinician-Administered PTSD Scale (CAPS) was used. In healthy children and mothers, instead of BMT, the most important traumatic event reported by them was included. All data were analyzed by a neutral statistician from the Department of Biostatistics of the university. The BMT group, both children and mothers, obtained significantly higher PTSD rates than the control group (66.5% and 17.8%, respectively, in children; 57.6% and 7%, respectively, in mothers). However, there was a weak correlation between survivors' and mothers' posttraumatic stress responses. These findings suggest that BMT is a significant stressor for both children and mothers. Clinicians should be aware of psychiatric symptoms of children who underwent such a life-threatening condition. Combination of medical treatment with psychosocial support is imperative. PMID:26949991

  7. DLA-DQB1 alleles and bone marrow transplantation experiments in narcoleptic dogs.

    PubMed

    Wagner, J L; Storb, R; Storer, B; Mignot, E

    2000-09-01

    Human narcolepsy is a neurological disorder known to be tightly associated with HLA-DQB1*0602. A clinically similar disorder has been described in various dog breeds. The canine form of the disease is inherited as an autosomal recessive disorder in Labrador retrievers and Doberman pinschers (canarc-1) but occurs sporadically in other breeds, most typically dachshunds and poodles. In this study, we have examined if there is a relationship between the development of narcolepsy and specific dog leukocyte antigen (DLA)-DQB1 alleles. Ninety-nine dogs were typed for DLA-DQB1-31 with narcolepsy and 68 control animals. Recent studies have linked the development of autosomal recessive canine narcolepsy to a disruption of the hypocretin receptor 2 (Hcrtr2) gene on the same chromosome as the canine MHC region (CFA12), but not close to the DLA. Four Hcrtr2-positive families (two Doberman pinscher families, one Labrador retriever family, one dachshund family) were analyzed at the DLA-DQ level. No relationship was found between narcolepsy and DLA in Hcrtr2-mediated narcolepsy but loose genetic linkage was observed (Zmax=2.3 at theta=25%, m= 40). Bone marrow transplantation between two DLA identical affected (Hcrtr2-/-) and unaffected (Hcrtr2+/-) siblings was also performed and found not to be successful neither in transmitting narcolepsy nor in relieving the symptoms in Doberman pinschers. DLA-DQB1 was next studied in 11 dogs with sporadic (non-familial) narcolepsy and in unrelated control animals of the same and different breeds. The allelic and carrier frequencies of various DLA-DQB1 alleles were analyzed. There was no strong positive or negative correlation between the development of narcolepsy and specific DLA-DQB1 alleles. These results do not support the involvement of DLA-DQ in canine narcolepsy, whether of sporadic or familial origin. PMID:11034558

  8. 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

  9. GST-pi gene-transduced hematopoietic progenitor cell transplantation overcomes the bone marrow toxicity of cyclophosphamide in mice.

    PubMed

    Matsunaga, T; Sakamaki, S; Kuga, T; Kuroda, H; Kusakabe, T; Akiyama, T; Konuma, Y; Hirayama, Y; Kobune, M; Kato, J; Sasaki, K; Kogawa, K; Koyama, R; Niitsu, Y

    2000-08-10

    Autologous transplantation of bone marrow cells (BMCs) transduced with the multidrug resistance 1 (MDR1) gene or dihydrofolate reductase (DHFR) gene has already been applied in clinical chemoprotection trials. However, anticancer drugs frequently used in high-dose chemotherapy (HDC), such as alkylating agents, are not relevant to MDR1 or DHFR gene products. In this context, we have previously reported that glutathione S-transferase-pi (GST-pi) gene-transduced human CD34(+) cells showed resistance in vitro against 4-hydroperoxicyclophosphamide, an active form of cyclophosphamide (CY). In the present study, a subsequent attempt was made in a murine model to evaluate the effectiveness of transplantation of GST-pi-transduced BMCs to protect bone marrow against high-dose CY. The gene transfection was carried out retrovirally, employing a recombinant fibronectin fragment. Transfection efficiency into CFU-GM was 30%. After the transplantation, recipient mice (GST-pi mice) received three sequential courses of high-dose CY. As the chemotherapy courses advanced, both shortening of recovery period from WBC nadir and shallowing of WBC nadir were observed. In contrast to the fact that three of seven control mice died, possibly due to chemotoxicity, all seven GST-pi mice were alive after the third course, at which point the vector GST-pi gene was detected in 50% of CFU-GM derived from their BMCs and peripheral blood mononuclear cells. When BMCs obtained from these seven mice were retransplanted into secondary recipient mice, 20% of CFU-GM from BMCs showed positive signals for vector GST-pi DNA after 6 months. These data indicate that the GST-pi gene can confer resistance to bone marrow against CY by being transduced into long-term repopulating cells. PMID:10954901

  10. 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

  11. Same sibling marrow following cord allogeneic transplantation as therapy for second relapse acute promyelocytic leukemia in a pediatric patient.

    PubMed

    De Oliveira, Satiro N; Kao, Roy L; Pham, Andrew; Smith, LaMarr Taylor; Kempert, Pamela; Moore, Theodore B

    2016-03-01

    Optimal therapy for relapsed APL in pediatric patients is controversial. Allogeneic HSCT is an alternative, with event-free survival of 70-75%. We report a pediatric patient with APL who relapsed 28 months after CBT from her sibling and then was treated with BMT from the same donor. Bone marrow was selected for higher cell dose, donor availability, and partial donor chimerism. Persistent molecular remission was achieved, currently at 65 months after BMT. This case suggests the potential role of GVL activity in APL and illustrates the use of different cell sources from the same donor in allogeneic transplantation for pediatric patients. PMID:26849401

  12. Advances and Challenges in Immunotherapy for Solid Organ and Bone Marrow Transplantation

    PubMed Central

    McDonald-Hyman, Cameron; Turka, Laurence A.; Blazar, Bruce R.

    2015-01-01

    Although major advances have been made in hematopoietic stem cell transplantation (HSCT) and solid organ transplantation in the last 50 years, big challenges remain. This Review outlines the current immunological limitations for HSCT and solid organ transplantation, and discusses new immune-modulating therapies in clinical trials and under pre-clinical development that may allow these obstacles to be overcome. PMID:25810312

  13. Early-second-trimester use of acyclovir in treating herpes zoster in a bone marrow transplant patient. A case report.

    PubMed

    Horowitz, G M; Hankins, G D

    1992-03-01

    Bone marrow transplantation from a human leukocyte antigen (HLA)-identical sibling for treatment of severe aplastic anemia among women of reproductive age is becoming more common. Successful pregnancy has been reported to occur in several such patients. A woman delivered a healthy, term, female infant 18 months after a transplant from her HLA-identical sister. Her pregnancy was complicated by disseminated herpes zoster, treated with intravenous acyclovir at 14 weeks' gestation, before the diagnosis of pregnancy. While there have been several case reports involving the use of acyclovir in the third trimester, primarily in the treatment of varicella infections, there have been no previous reports of such an early utilization of this antiviral drug. PMID:1564715

  14. [Information theory of ageing: studying the effect of bone marrow transplantation on the life span of mice].

    PubMed

    Karnaukhov, A V; Karnaukhova, E V; Sergievich, L A; Karnaukhova, N A; Karnaukhova, N A; Bogdanenko, E V; Smirnov, A A; Manokhina, I A; Karnaukhov, V N

    2014-01-01

    In this paper the method of life span extension of multicellular organisms (human) using the reservation of stem cells followed by autotransplantation has been proposed. As the efficiency of this method results from the information theory of ageing, it is important to verify it experimentally testing the basic concepts of the theory. Taking it into consideration, the experiment on the bone marrow transplantation to old mice from young closely-related donors of the inbred line was carried out. It has been shown, that transplanted animals exhibited a survival advantage, a mean life span increased by 34% as compared to the control. This result not only demonstrates the efficiency of the proposed method for life span extension of multicellular organisms, but also confirms the basis of the information theory of ageing. PMID:25707248

  15. Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

    PubMed Central

    Jang, Dong-Kyu; Park, Sang-In; Han, Young-Min; Jang, Kyung-Sool; Park, Moon-Seo; Chung, Young-An; Kim, Min-Wook; Maeng, Lee-So; Huh, Pil-Woo; Yoo, Do-Sung; Jung, Seong-Whan

    2011-01-01

    This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway. PMID:21772790

  16. Diagnostic Value of Bronchoalveolar Lavage in Leukemic and Bone Marrow Transplant Patients: The Impact of Antimicrobial Therapy

    PubMed Central

    Yacoub, Abraham Tareq; Thomas, Dani; Yuan, Carol; Collazo, Carolina; Greene, John; Walsh, Frank; Solomon, David; Schwartz, Skai; Andrews, Arthur

    2015-01-01

    There is significant morbidity and mortality from pneumonia in leukemic and bone marrow transplant patients. We sought to explore the diagnostic yield of bronchoalveolar lavage (BAL) in these patients with new pulmonary infiltrates. A retrospective chart review of approximately 200 Non- human immunodeficiency virus (HIV) leukemic and Hematopoietic stem cell transplantation (HSCT) patients who underwent bronchoscopy at a single academic cancer center was performed. Antimicrobial use for less than 24 hours at the time of BAL was associated with a higher yield in this population (56.8% versus 32.8%, p<0.001). This supports performing bronchoscopy with BAL within 24 hours of antimicrobial therapy in leukemic and HSCT patients. PMID:25574361

  17. 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. PMID:26854937

  18. Etoposide in combination with cyclophosphamide and total body irradiation or busulfan as conditioning for marrow transplantation in adults and children

    SciTech Connect

    Spitzer, T.R.; Ortlieb, M.; Tefft, M.C.; Torrisi, J.; Cahill, R.; Deeg, H.J. ); Peters, C.; Gadner, H. ); Urban, C. )

    1994-04-30

    In an attempt to intensify conditioning therapy for bone marrow transplantation of hematologic malignancies, a retrospective three center evaluation of escalating doses of etoposide added to cyclophosphamide and either total body irradiation or busulfan was undertaken. Seventy-six patients who received etoposide (25-65 mg/kg) added to cyclophosphamide (60-120 mg/kg) and either total body irradiation (12.0-13.2 Gy) or busulfan (12-16 mg/kg) were evaluable for toxicity. Fifty-one of the evaluable patients received allogeneic transplants, while twenty-six received autologous transplants. A comparative analysis of toxicities according to conditioning regimen, donor source and etoposide dose was made. Similar toxicities were observed among the treatment groups with the exception of more frequent skin (p = 0.03) and life threatening hepatic toxicities (p = 0.01) in the busulfan treated patients. Life threatening or fatal toxicities were not influenced by donor source, either when analyzed by treatment group or etoposide dose. Etoposide at a dose of 60-65 mg/kg in combination with TBI and cyclophosphamide was associated with a significantly increased incidence of life threatening or fatal toxicities compared with a combination using a dose of 25-50 mg/kg (15 of 24 vs. 5 of 20; p = 0.013). The maximally tolerated dose of etoposide in combination with busulfan and cyclophosphamide cannot be definitively established in this analysis in part due to the heterogeneity of the patient population and treatment schemes. Although toxicities with bone marrow transplant preparative regimens containing etoposide in combination with cyclophosphamide and total body irradiation or busulfan were frequently severe, treatment related mortality risk was believed to be acceptably low. 27 refs., 3 tabs.

  19. Direct bone marrow HSC transplantation enhances local engraftment at the expense of systemic engraftment in NSG mice

    PubMed Central

    Futrega, Kathryn; Lott, William B.; Doran, Michael R.

    2016-01-01

    Direct bone marrow (BM) injection has been proposed as a strategy to bypass homing inefficiencies associated with intravenous (IV) hematopoietic stem cell (HSC) transplantation. Despite physical delivery into the BM cavity, many donor cells are rapidly redistributed by vascular perfusion, perhaps compromising efficacy. Anchoring donor cells to 3-dimensional (3D) multicellular spheroids, formed from mesenchymal stem/stromal cells (MSC) might improve direct BM transplantation. To test this hypothesis, relevant combinations of human umbilical cord blood-derived CD34+ cells and BM-derived MSC were transplanted into NOD/SCID gamma (NSG) mice using either IV or intrafemoral (IF) routes. IF transplantation resulted in higher human CD45+ and CD34+ cell engraftment within injected femurs relative to distal femurs regardless of cell combination, but did not improve overall CD45+ engraftment at 8 weeks. Analysis within individual mice revealed that despite engraftment reaching near saturation within the injected femur, engraftment at distal hematopoietic sites including peripheral blood, spleen and non-injected femur, could be poor. Our data suggest that the retention of human HSC within the BM following direct BM injection enhances local chimerism at the expense of systemic chimerism in this xenogeneic model. PMID:27065210

  20. A quality of life study in 20 adult long-term survivors of unrelated donor bone marrow transplantation.

    PubMed

    Marks, D I; Gale, D J; Vedhara, K; Bird, J M

    1999-07-01

    There are few specific data available concerning quality of life (QOL) of survivors of unrelated donor bone marrow transplantation (UD-BMT). The procedure is expensive, difficult and is being employed increasingly yet we have little information concerning the QOL of survivors to justify this intervention. In this study, 20 long-term (>1 year post-BMT) survivors were studied with four self report questionnaires designed to assess quality of life, satisfaction with life, social support and employment status. Overall, satisfaction with life measures was above average but there was dissatisfaction with physical strength and appearance. The post-transplant employment data indicates that 60% of long-term survivors returned to full-time work and 15% to part-time work. Failure to return to work was not correlated with graft-versus-host disease (GVHD), relapse, age at or time since transplant. In general, there was a good correlation between the clinician's and patient's view of their health but the clinician's assessment of the patients mental health and energy was higher than the patients reported. Further research is required in the area of QOL post-UD-BMT. This will enable transplant physicians to counsel patients better pre-BMT and to evaluate fully the results achieved by different centres performing the procedure. PMID:10455348

  1. 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

  2. Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment

    PubMed Central

    Liang, Fan; Wamala, Isaac; Scalea, Joseph; Tena, Aseda; Cormack, Taylor; Pratts, Shannon; Struuck, Raimon Duran; Elias, Nahel; Hertl, Martin; Huang, Christene A.; Sachs, David H.

    2013-01-01

    Background The development of genetically modified pigs which lack the expression of alpha 1–3 galactosyl transferase, (GalT-KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre-existing antibodies against the Gal epitope. However, antibodies against other antigens (anti-non-Gal antibodies), are found at varying levels in the pre-transplant sera of most primates. We have previously found that baboons with high levels of pre-transplant anti-non-Gal IgG, conditioned with a non-myeloablative conditioning regimen, failed to engraft following pig-to-baboon bone marrow transplantation [8]. Two baboons with low levels of pre-transplant anti-non-Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor-specific hypo-responsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre-transplant anti-non-Gal IgG levels might improve engraftment levels following GalT-KO pig-to-baboon bone marrow transplantation. Methods Five baboons, with low pre-transplant anti-non-Gal IgG levels, received transplantation of bone marrow cells (1–5 × 10^9/kg of recipient weight) from GalT-KO pigs. They received a non-myeloablative conditioning regimen consisting of low-dose total body irradiation (150cGy), thymic irradiation (700cGy), anti-thymocyte globulin (ATG) and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra-corporeal immunoadsorption using GalT-KO pig livers. Bone marrow engraftment was assessed by porcine-specific PCR on colony forming units (CFU) of day 28 bone marrow aspirates. Anti-non-Gal antibody levels were assessed by serum binding towards GalT-KO PBMC using flow cytometry (FACS). Peripheral macro-chimerism was measured by FACS using pig and

  3. 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

  4. 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.

  5. Hematopoietic Cell Transplantation in 2020: Summary of Year 2 Recommendations of the National Marrow Donor Program’s System Capacity Initiative

    PubMed Central

    Denzen, Ellen M.; Majhail, Navneet S.; Ferguson, Stacy Stickney; Anasetti, Claudio; Bracey, Arthur; Burns, Linda; Champlin, Richard; Chell, Jeffrey; Leather, Helen; Lill, Michael; Maziarz, Richard T.; Medoff, Erin; Neumann, Joyce; Schmit-Pokorny, Kim; Snyder, Edward L.; Wiggins, Laura; Yolin Raley, Deborah S.; Murphy, Elizabeth A.

    2013-01-01

    The National Marrow Donor Program, in partnership with the American Society for Blood and Marrow Transplantation, sponsored and organized a series of symposia to identify complex issues affecting the delivery of hematopoietic cell transplantation (HCT) and to collaboratively develop options for solutions. “Hematopoietic Cell Transplantation in 2020: A System Capacity Initiative” used a deliberative process model to engage professional organizations, experts, transplant centers, and stakeholders in a national collaborative effort. Year 2 efforts emphasized data analysis and identification of innovative ideas to increase HCT system efficiency, address future capacity requirements, and ensure adequate reimbursement for HCT programs to meet the projected need for HCT. This report highlights the deliberations and recommendations of Year 2 and the associated symposium held in September 2011. PMID:23078785

  6. Prospective Validation of the Predictive Power of the Hematopoietic Cell Transplantation Comorbidity Index: A Center for International Blood and Marrow Transplant Research Study.

    PubMed

    Sorror, Mohamed L; Logan, Brent R; Zhu, Xiaochun; Rizzo, J Douglas; Cooke, Kenneth R; McCarthy, Philip L; Ho, Vincent T; Horowitz, Mary M; Pasquini, Marcelo C

    2015-08-01

    Prospective validation of the hematopoietic cell transplantation-comorbidity index (HCT-CI) using contemporary patients treated with hematopoietic cell transplantation (HCT) across the Unites States is necessary to confirm its widespread applicability. We performed a prospective observational study including all patients (8115 recipients of allogeneic and 11,652 recipients of autologous HCT) who underwent a first HCT that was reported to the Center for International Blood and Marrow Transplant Research between 2007 and 2009. In proportional hazards models, increased HCT-CI scores were independently associated with increases in hazard ratios for nonrelapse mortality (NRM) (P < .0001) and overall mortality (P < .0001) among recipients of allogeneic HCT. HCT-CI scores of ≥3 were uniformly associated with higher risks for outcomes in both allogeneic and autologous HCT and in all subgroups, regardless of diagnoses, age, and conditioning intensity. Recipients of allogeneic HCT with scores of 1 and 2 who were ages < 18 years or were treated with lower intensity conditioning regimens had similar outcomes compared with those with a score of 0. Higher risks for overall mortality, but not for NRM, were observed among recipients of autologous HCT with scores of 1 and 2 versus 0. Our results confirm the validity the HCT-CI in both allogeneic and autologous HCT. The index should be used as a valid standard-of-care health measure in counseling patients for HCT, in clinical trial design, and in adjusting outcome analyses. PMID:25862591

  7. HLA-matched family hematopoetic stem cell transplantation in children with beta thalassemia major: the experience of the Turkish Pediatric Bone Marrow Transplantation Group.

    PubMed

    Yesilipek, M Akif; Ertem, Mehmet; Cetin, Mualla; Öniz, Haldun; Kansoy, Savas; Tanyeli, Atila; Anak, Sema; Kurekci, Emin; Hazar, Volkan

    2012-12-01

    From January 1991 to June 2009, 245 children with beta thalassemia major who underwent their first allogeneic HSCT in Turkey and who were followed for a minimum of one yr post-transplantation were enrolled this study. The median age of the patients was 6.6 yr old (range, 1-22 yr). The distribution of Pesaro risk class I, II, and III categories was 41, 130, and 63 children, respectively. The median serum ferritin level was 2203 ng/mL. Eighty-eight patients received bone marrow (BM) stem cells; 137, peripheral blood (PB) stem cells; and 20, cord blood (CB) stem cells. The donors were HLA-matched siblings or parents. Median engraftment times were shorter in PBSCT patients compared with the BMT group (p < 0.001). Grade II-IV acute GvHD was observed in 33 children (13.5%), while cGvHD was observed in 28 patients (12.5%), eight of whom had the extensive form. Thalassemic reconstitution was observed in 43 (17%) of the transplant patients. Post-transplant aplasia occurred in three patients, and the TRM rate was 7.75%. Seventeen patients were lost after 100 days. The thalassemia-free survival and OS rates were 68% (95% CI, 61.8-74.2) and 85.0% (95% CI, 80.2-89.8), respectively. We believe that this study is important because it is the first multicenter national data for children with beta thalassemia major receiving HSCT. PMID:22931438

  8. B lymphocyte reconstitution after human bone marrow transplantation. Leu-1 antigen defines a distinct population of B lymphocytes.

    PubMed Central

    Antin, J H; Ault, K A; Rappeport, J M; Smith, B R

    1987-01-01

    Differences in the expression of Leu-1 (CD5) define two populations of recovering B cells after human marrow transplantation, Leu-1+ and Leu-1- B cells. The Leu-1+ B cells were polyclonal, of donor origin, and did not express detectable interleukin 2 receptor. Leu-1+ B cells generally appeared 2-4 wk after marrow grafting and often preceded the recovery of Leu-1- B cells. Acute and chronic graft vs. host disease (GvHD) resulted in the recovery of significantly fewer Leu-1+ B cells, whereas Leu-1- B cells were only decreased in acute GvHD. Multivariate analysis showed no significant effect of age, disease, prednisone or azathioprine, or ex vivo treatment of the marrow with anti-Leu-1 and complement on recovery of Leu-1+ and Leu-1- B cells, independent of the effects of GvHD. Leu-1+ B cells are a major lymphocyte population posttransplant. They may reflect a stage of differentiation of normal B cells or a separate B cell lineage. PMID:3112184

  9. Nonresponsive lymphocytes from bone marrow transplant patients proliferate in vitro following exposure to rIL-2

    SciTech Connect

    Hank, J.A.; Sondel, P.M.; Flynn, B.; Hong, R.; Kohler, P.C.

    1986-03-01

    In vitro T-cell responses are depressed following bone marrow transplantation (BMT). Normal proliferative responses to mitogens, alloantigens and soluble antigens do not return for many months. Despite poor T-cell responses following EMT, peripheral blood lymphocytes respond readily to human rIL-2 as measured by /sup 3/H-thymidine incorporation. Lymphocytes from 8 patients have been studied following BMT. Six received whole marrow and 2 received marrow depleted of T-cells. While these patients were still unable to respond to mitogens, soluble antigens or in MLC following engraftment, their responses to rIL-2 were remarkable. These responses were often greater than the responses of the patients own cryopreserved remission cells, donor cells, or lymphocytes from healthy controls to either rIL-2 or antigens. Whether these IL-2 responsive cells are lymphocytes that have been activated in vivo by alloantigens, and thus express their IL-2 receptor, or are lymphokine activated killer (LAK) precursors, or are a primitive regenerating cell remains to be determined. Preliminary results indicate that these cells mediate nonspecific cytotoxicity.

  10. Ultrasound-mediated microbubble destruction enhances the therapeutic effect of intracoronary transplantation of bone marrow stem cells on myocardial infarction

    PubMed Central

    Chang, Xuefeng; Liu, Jiaqing; Liao, Xudong; Liu, Guohui

    2015-01-01

    Objective: The combination of intracoronary transplantation and ultrasound-mediated microbubble destruction may promote effective and accurate delivery of bone marrow stem cells (BMSCs) into the infarct zone. To test this hypothesis in this study we examined the effectiveness of ultrasound-mediated microbubble destruction in combination with intracoronary transplantation of BMSCs for the treatment of myocardial infarction in canine model of acute myocardial infarction. Method: The dogs were randomly assigned to four groups: PBS, ultrasound-mediated microbubble destruction, BMSCs, BMSCs together with ultrasound-mediated microbubble destruction. At 28 days post-surgery, cardiac function and the percentage of perfusion defect area to total left ventricular perfusion area (DA%) were determined by myocardial contrast echocardiography. Nitro blue tetrazolium staining was performed to determine myocardial infarct size, hematoxylin and eosin staining for assessing microvascular injury, Masson’s staining for analyzing myocardial tissue collagen, immunohistochemical analysis of α-actin to measure cardiac contractile function and of BrdU-labeled myocardial cells to measure the number of the BMSCs homing to the infarcted region. Results: The transplantation of BMSCs significantly improved heart function and DA% (P < 0.05). The group that received ultrasound-mediated microbubble destruction with BMSCs transplantation showed the most improvement in heart function and DA% (P < 0.05). This group also showed a denser deposition of BMSCs in the coronary artery and more BrdU positive cells in the infarcted region, had the maximum number of α-actin positive cells, showed the smallest myocardial infarct area compared to other groups (P< 0.05). Conclusion: Ultrasound-mediated microbubble destruction increases the homing of BMSCs in the target area following intracoronary transplantation, which allows more BMSCs to differentiate into functional cardiomyocytes, thereby reducing

  11. 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

  12. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    SciTech Connect

    Clave, E.; Socie, G.; Carosella, E.

    1995-11-01

    Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3{minus}, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation. 20 refs., 3 figs., 1 tab.

  13. 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

  14. Thiotepa-associated cardiomyopathy during blood or marrow transplantation: association with the female sex and cardiac risk factors.

    PubMed

    Alidina, A; Lawrence, D; Ford, L A; Baer, M R; Bambach, B; Bernstein, S H; Czuczman, M S; Slack, J L; Spangenthal, E; Wetzler, M; Barcos, M P; Proulx, G M; Anderson, B; McCarthy, P L

    1999-01-01

    Thiotepa (TT) has not been reported to cause cardiomyopathy, whereas cyclophosphamide (Cy)-related cardiomyopathy is well characterized. To search for cases of acute onset cardiomyopathy associated with TT, we retrospectively reviewed 171 patients who received TT-containing conditioning regimens for blood or marrow transplantation (BMT). Nine of 171 patients (5.3%) developed clinical congestive heart failure in the post-BMT period. The median time to onset of heart failure was 15 days after BMT (range 5-30). The median pre-BMT left ventricular ejection fraction (LVEF) was 50% (range 42-65%) as determined by two-dimensional echocardiogram, or gated blood pool scan. At the time of cardiomyopathy onset, LVEF was 30%. Six patients died of causes unrelated to heart failure. All affected patients who developed congestive heart failure following administration of TT had some evidence of cardiac dysfunction prior to transplantation. Significant risk factors for the development of cardiomyopathy included low pre-BMT-LVEF and female sex--particularly in females receiving allogeneic transplantation. The incidence of congestive heart failure with TT-containing regimens was similar to the incidence using other regimens with and without Cy. The mean time to clinical evidence of TT-associated cardiomyopathy was longer than the mean time reported with Cy. We recommend caution in using high-dose TT-containing regimens for patients with histories of cardiac dysfunction. PMID:10534063

  15. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation.

    PubMed

    Hägglund, H; Remberger, M; Klaesson, S; Lönnqvist, B; Ljungman, P; Ringdén, O

    1998-12-15

    In this single-center study, we retrospectively analyzed incidence and risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation between January 1990 and June 1995. Twenty-four of the 249 transplanted patients developed VOD. The probabilities of developing VOD were 17% among women and 7% in men (P =.01). In women treated with norethisterone, the incidence was 27% compared with 3% in women without this treatment (P =.007). One-year survival rates were 17% and 73% in patients with (n = 24) or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, the following risk factors were significant: norethisterone treatment (P <.001), bilirubin >26 micromol/L before bone marrow transplantation (BMT) (P =.002), one HLA-antigen mismatch (P =.003), previous abdominal irradiation (P =.02), and conditioning with busulphan (P =.02). Our conclusion is that norethisterone treatment should not be used in patients undergoing BMT and heparin prophylaxis did not affect the incidence or mortality of VOD. PMID:9845522

  16. Recurrent adult choroid plexus carcinoma treated with high-dose chemotherapy and syngeneic stem cell (bone marrow) transplant.

    PubMed

    Samuel, Thomas A; Parikh, Jigarkumar; Sharma, Suash; Giller, Cole A; Sterling, Kristen; Kapoor, Suraj; Pirkle, Christen; Jillella, Anand

    2013-12-01

    Choroid plexus carcinomas (CPCs) are rare epithelial central nervous system tumors. CPC occurs mainly in infants and young children, comprising ≈ 1 to 4% of all pediatric brain neoplasms. There is very limited information available regarding tumor biology and CPC treatment due to its rarity. There have been various case reports and meta-analyses of reported cases with CPC. Surgical resection is often challenging but remains a well-established treatment option. Chemotherapy is often reserved for recurrent or refractory cases, but the goal of treatment is usually palliative. We present a case of recurrent, adult CPC with disseminated leptomeningeal involvement treated with salvage chemotherapy including high-dose ifosfamide, carboplatin, and etoposide; once a remission was achieved, this response was consolidated with a syngeneic stem cell (bone marrow) transplant after a preparative regimen of high-dose chemotherapy with carboplatin, etoposide, and thiotepa. Although the patient tolerated the transplant well and remained disease-free for 12 months, she subsequently succumbed to relapsed disease 18 months posttransplant. We believe that this is the first report of using syngeneic stem cell transplant in CPC to consolidate a remission achieved by salvage chemotherapy. PMID:23427033

  17. The Treatment of Osteochondral Lesions of the Talus with Autologous Osteochondral Transplantation and Bone Marrow Aspirate Concentrate

    PubMed Central

    Kennedy, John G.; Murawski, Christopher D.

    2011-01-01

    Objective: To present the functional results after autologous osteochondral transplantation with bone marrow aspirate concentrate in 72 patients, while placing an emphasis on the surgical technique. Methods: Between 2005 and 2009, 72 patients underwent autologous osteochondral transplantation under the care of the senior author. The mean patient age at the time of surgery was 34.19 years (range, 16-85 years). All patients were followed for a minimum of 1 year after surgery. The mean follow-up time was 28.02 months (range, 12-64 months). Patient-reported outcome measures were taken preoperatively and at final follow-up using the Foot and Ankle Outcome Score (FAOS) and Short Form–12 (SF-12) general health questionnaire. Identical questionnaires were used in all instances. Results: The mean FAOS scores improved from 52.67 points preoperatively to 86.19 points postoperatively (range, 71-100 points). The mean SF-12 scores also improved from 59.40 points preoperatively to 88.63 points postoperatively (range, 52-98 points). Three patients reported donor site knee pain after surgery, and one patient required the decompression of a cyst that developed beneath the graft site approximately 2 years after the index procedure. Conclusion: Autologous osteochondral transplantation is a reproducible and primary treatment strategy for large osteochondral lesions of the talus. PMID:26069591

  18. 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.

  19. Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders.

    PubMed

    Larochelle, Antoine; Bellavance, Marc-André; Michaud, Jean-Philippe; Rivest, Serge

    2016-03-01

    The central nervous system (CNS) is a very unique system with multiple features that differentiate it from systemic tissues. One of the most captivating aspects of its distinctive nature is the presence of the blood brain barrier (BBB), which seals it from the periphery. Therefore, to preserve tissue homeostasis, the CNS has to rely heavily on resident cells such as microglia. These pivotal cells of the mononuclear lineage have important and dichotomous roles according to various neurological disorders. However, certain insults can overwhelm microglia as well as compromising the integrity of the BBB, thus allowing the infiltration of bone marrow-derived macrophages (BMDMs). The use of myeloablation and bone marrow transplantation allowed the generation of chimeric mice to study resident microglia and infiltrated BMDM separately. This breakthrough completely revolutionized the way we captured these 2 types of mononuclear phagocytic cells. We now realize that microglia and BMDM exhibit distinct features and appear to perform different tasks. Since these cells are central in several pathologies, it is crucial to use chimeric mice to analyze their functions and mechanisms to possibly harness them for therapeutic purpose. This review will shed light on the advent of this methodology and how it allowed deciphering the ontology of microglia and its maintenance during adulthood. We will also compare the different strategies used to perform myeloablation. Finally, we will discuss the landmark studies that used chimeric mice to characterize the roles of microglia and BMDM in several neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. PMID:26432480

  20. 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

  1. Prolongation of survival for high-grade malignant gliomas with adjuvant high-dose BCNU and autologous bone marrow transplantation.

    PubMed

    Johnson, D B; Thompson, J M; Corwin, J A; Mosley, K R; Smith, M T; de los Reyes, R A; Daly, M B; Petty, A M; Lamaster, D; Pierson, W P

    1987-05-01

    Employment of postoperative brain irradiation in the initial management of high-grade malignant glial tumors has now become standard. The addition of conventional chemotherapy to irradiation has not significantly improved median survival beyond 1 year. We treated 25 consecutive patients (13 pilot patients and 12 protocol patients) with histologically confirmed unresectable grade 3 or 4 malignant gliomas with high-dose BCNU (carmustine) followed by autologous bone marrow transplantation and whole brain irradiation. Within 3 weeks of initial surgery, each patient had autologous bone marrow stored (median 2 X 10(8) nucleated cells/kg), and then received BCNU 1,050 mg/m2 intravenously (IV). Peripheral granulocytes recovered (greater than 500/microL) at a median of 19 days (range, 10 to 37 days), and platelets recovered (greater than 20,000/microL) at a median of 18 days (range, 13 to 40 days), following bone marrow infusion. Patients received 60 Gy whole brain irradiation when granulocytes were greater than 1,500/microL. Toxicity was well tolerated. Nausea occurred in 19 patients (76%); however, only eight patients (32%) experienced vomiting (mild in three, moderate in five). Eleven patients (44%) did not require empiric antibiotics, six of whom never developed an absolute granulocyte count less than 500/microL. Three patients with a poor performance status died early (one seizure with vomiting and asphyxiation; one, klebsiella urinary tract infection (UTI) with bacteremia; one, candidal pneumonia), and one additional patient who was performing well died of pulmonary hemorrhage. The 13 pilot patients have now been followed for a median of 23 months, with a significant survival advantage compared with the 52 consecutive historical control patients who received similar surgery and radiotherapy without high-dose BCNU (P = .037). The overall study group of 25 patients also has a significant survival advantage when compared with the same historical control group, with a

  2. Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation.

    PubMed

    Fioredda, Francesca; Iacobelli, Simona; van Biezen, Anja; Gaspar, Bobby; Ancliff, Phil; Donadieu, Jean; Aljurf, Mahmoud; Peters, Christina; Calvillo, Michaela; Matthes-Martin, Susanne; Morreale, Giuseppe; van 't Veer-Tazelaar, Nelleke; de Wreede, Liesbeth; Al Seraihy, Amal; Yesilipek, Akif; Fischer, Alain; Bierings, Marc; Ozturk, Gulyuz; Smith, Owen; Veys, Paul; Ljungman, Per; Peffault de Latour, Régis; Sánchez de Toledo Codina, José; Or, Reuven; Ganser, Arnold; Afanasyev, Boris; Wynn, Robert; Kalwak, Krzysztof; Marsh, Judith; Dufour, Carlo

    2015-10-15

    Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken. PMID:26185129

  3. Comparative Analysis of Busulfan and Cyclophosphamide versus Cyclophosphamide and Total Body Irradiation in Full Intensity Unrelated Marrow Donor Transplantation for Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia and Myelodysplasia

    PubMed Central

    Uberti, Joseph P.; Agovi, Manza-A.; Tarima, Sergey; Haagenson, Michael; Gandham, Sharavi; Anasetti, Claudio; Baker, K. Scott; Bolwell, Brian J.; Bornhauser, Martin; Chan, Ka Wah; Copelan, Edward; Davies, Stella M.; Finke, Juergen; Hale, Gregory A.; Kollman, Craig; McCarthy, Philip L.; Ratanatharathorn, Voravit; Ringdén, Olle; Weisdorf, Daniel J.; Rizzo, J. Douglas

    2011-01-01

    We retrospectively compared clinical outcomes in 1593 T-repleted URD marrow transplant recipients with AML, MDS and CML who received myeloablative conditioning regimens of either busulfan and cyclophosphamide (BuCy), standard-dose Cy/TBI (1,000-1,260 cGy) or high-dose Cy/TBI (1,320-1,500 cGy). Subjects were drawn from patients transplanted between 1991 and 1999 facilitated by the National Marrow Donor Program (NMDP). Patients who received high-dose Cy/TBI regimens were slightly younger, more likely to receive a mismatched transplant and to have intermediate or advanced disease compared to patients in the BuCy or standard-dose TBI group. Neutrophil recovery was significantly higher in the standard dose CY/TBI group compared to the high-dose Cy/TBI or BuCy group. Patients who received the high-dose Cy/TBI regimen had an increased risk of developing grade III-IV aGVHD when compared to the control group who received BuCy (p=0.011). Overall survival (OS), disease free survival (DFS), transplant-related mortality (TRM) and relapse were not significantly different between any of the regimens. We conclude that BuCy, standard-dose and high dose Cy/TBI regimens have equivalent efficacy profiles for OS, DFS, TRM and relapse risk in patients undergoing T-replete URD marrow transplantation for AML, CML and MDS. PMID:20400989

  4. 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 ...

  5. Prophylactic antithymocyte globulin reduces the risk of chronic graft-versus-host disease in alternative-donor bone marrow transplants.

    PubMed

    Bacigalupo, A; Lamparelli, T; Gualandi, F; Bregante, S; Raiola, A M; Di Grazia, C; Dominietto, A; Bruno, B; Galbusera, V; Frassoni, F; Podesta, M; Tedone, E; Occhini, D; Van Lint, M T

    2002-01-01

    We studied the impact of preparative regimens with or without antithymocyte globulin (ATG) on chronic GVHD in 160 patients undergoing marrow transplants from unrelated donors (n = 127) or partially mismatched related donors (n = 33). A conditioning regimen that included rabbit ATG, 7.5 to 15 mg/kg (Thymoglobuline; Sangstat, Lyon, France), was given to 102 patients, whereas a conditioning regimen without ATG was given to 58 patients. The median patient age was 34 years for the ATG group and 29 years for the non-ATG group (P = .002); otherwise the 2 groups were matched for disease phase, diagnosis, donor age, interval from diagnosis to transplantation, and number of cells infused at the time of transplant. Median follow-up for surviving patients was 4.5 years (range, l.5-9 years). The conditioning regimen was cyclophosphamide (CY) and total body irradiation (TBI) in 95 patients and CY-thiotepa in 65 patients; the source of stem cells was bone marrow for all patients. Acute GVHD grades II-IV and grades III-IV were reduced in patients receiving ATG compared to patients not receiving ATG (51% versus 74%, P = .004 and 14% versus 28%, P = .03, respectively). There were significantly fewer patients with chronic GVHD in the ATG group than in the non-ATG group at 6 months (14% versus 30%, P = .03), 1 year (7% versus 41%, P = .0001), 2 years (16% versus 36%, P = .02), and 4 years (5% versus 34%, P = .002) and beyond 4 years (0% in 19 patients at risk versus 29% in 24 patients at risk, P = .01). More patients in the ATG group than in the non-ATG group had a performance status (Karnowski score) greater than 90 at last follow-up (93% versus 56%, P = .01) and had discontinued cyclosporin treatment 2 years posttransplant (28% versus 3%, P = .003). Survival rates were comparable in the ATG and non-ATG groups for patients who received TBI (56% versus 59%, P = .7) and those who received thiotepa (33% versus 18%, P = .3). Transplant mortality and relapse rates were also comparable in

  6. Marrow Ablative and Immunosuppressive Effects of I-131-anti-CD45 Antibody in Congenic and H2-Mismatched Murine Transplant Models

    SciTech Connect

    Matthews, D. C.; Martin, P J.; Nourigat, C.; Appelbaum, F. R.; Fisher, Darrell R. ); Bernstein, I. D.

    1998-12-01

    Targeted hematopoietic irradiation delivered by I-131-anti-CD45 antibody has been combined with conventional marrow transplant preparative regimens in an effort to decrease relapse. Before increasing the proportion of therapy delivered by radiolabeled antibody, the myeloablative and immunosuppressive effects of such low dose rate irradiation must be quantitated. We have examined the ability of I-131-anti-CD45 antibody to facilitate engraftment in Ly5-congenic and H2-mismatched murine marrow transplant models. Recipient B6-Ly5-a mice were treated with 30F11 antibody labeled with 0.1 to 1.5 mCi I-131 and/or total body irradiation (TBI), followed by T-cell-depleted marrow from Ly5-b-congenic (C57BL/6) or H2-mismatched (BALB/c) donors. Engraftment was achieved readily in the Ly5-congenic setting, with greater than 80% donor granulocytes and T cells after 0.5 mCi I-131 (estimated 17 Gy to marrow) or 8 Gy TBI. A higher TBI dose (14 Gy) was required to achieve engraftment of H2-mismatched mar row, and engraftment occurred in only 3 of 11 mice receiving 1.5 mCi I-131 delivered by anti-CD45 antibody. Engraftment of H2-mismatched marrow was achieved in 22 of 23 animals receiving 0.75 mCi I-131 delivered by anti-CD45 antibody combined with 8 Gy TBI. Thus, targeted radiation delivered via I-131-anti-CD45 antibody can enable engraftment of congenic marrow and can partially replace TBI when transplanting T-cell-depleted H2-mismatched marrow.

  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. Detection of minimal residual disease by polymerase chain reaction in patients with different hematologic diseases treated by bone marrow transplantation.

    PubMed

    Stuppia, L; Calabrese, G; Guanciali Franchi, P; Di Bartolomeo, P; Antonucci, A; Peila, R; Torlontano, G; Palka, G

    1993-02-01

    Thirteen male patients affected by different hematologic diseases who underwent bone marrow transplantation (BMT) with female donors were investigated by cytogenetic analysis and polymerase chain reaction (PCR) amplification of a DNA sequence specific for the Y chromosome. In six of these patients, PCR showed the presence of the Y chromosome-related sequence; in only three of these did cytogenetic analysis confirm the presence of mixed chimerism. In the remaining three patients, the results of the PCR were confirmed by in situ hybridization on cell nuclei with a probe for the alpha-satellite of the Y chromosome. We compare results obtained with the two methods and discuss the meaning of the minimal residual disease detected by PCR in patients submitted to BMT. PMID:8453609

  9. Long-term immunity to measles, mumps and rubella after MMR vaccination among children with bone marrow transplants.

    PubMed

    Spoulou, V; Giannaki, M; Vounatsou, M; Bakoula, C; Grafakos, S

    2004-06-01

    Measles, mumps and rubella (MMR) vaccine-induced long-term immunity was studied in 30 children with bone marrow transplants (BMT). Immunity at baseline for MMR was 13.3, 33.3 and 66.6%, respectively. MMR vaccination failed to induce adequate and persistent responses to measles and mumps; seropositivity at 1 and 12 months for measles was 26.6 and 23.3% and for mumps 46.6 and 36.6%, respectively. In contrast, 27 of 30 children with a BMT were immune to rubella 1 month after immunization and retained protective antibody levels at 12 months. The MMR-induced anamnestic responses to rubella among all responders were associated with the production of high avidity antibodies. We conclude that a single dose of MMR given at 2 years after BMT induces suboptimal and short-lived immune responses to measles and mumps; a second dose should be recommended for paediatric BMT recipients. PMID:15077129

  10. Frequent occurrence of new hepatobiliary abnormalities after bone marrow transplantation: results of a prospective study using scintigraphy and sonography.

    PubMed

    Jacobson, A F; Teefey, S A; Lee, S P; Hollister, M S; Higano, C A; Bianco, J A

    1993-07-01

    With hepatobiliary scintigraphy and sonography, we prospectively studied the occurrence of new hepatobiliary abnormalities in 18 patients before, and from 1 to 103 days after, bone marrow transplantation (BMT). Prior to BMT, all patients had normal hepatic uptake and visualization of the gallbladder by 60 min on scintigraphy, and no sludge, stones, or other abnormalities on sonography. After BMT, 16 patients (89%) developed new scintigraphic and/or sonographic hepatobiliary abnormalities. Fifteen patients had impaired liver uptake of mebrofenin, while 11 developed gallbladder uptake of mebrofenin, while 11 developed gallbladder sludge and/or stones, and 10 had gallbladder nonvisualization at 60 min. Nevertheless, no patient developed clinical or laboratory evidence of acute cholecystitis. New hepatobiliary abnormalities are more common during the first months post-BMT than clinically suspected, probably reflecting the combined effects of hepatotoxic chemoradiation therapy, graft-versus-host disease, and prolonged administration of parenteral alimentation. Evidence of acute cholecystitis is generally not found. PMID:8317403

  11. Excess of veno-occlusive disease in a randomized clinical trial on a higher trigger for red blood cell transfusion after bone marrow transplantation: a canadian blood and marrow transplant group trial.

    PubMed

    Robitaille, Nancy; Lacroix, Jacques; Alexandrov, Lubomir; Clayton, Lucy; Cortier, Marion; Schultz, Kirk R; Bittencourt, Henrique; Duval, Michel

    2013-03-01

    Previous studies have shown that maintaining high hemoglobin levels in patients after chemotherapy reduced the length of neutropenia. Thus, we undertook a randomized, controlled, clinical trial in children undergoing allogeneic bone marrow transplantation after receiving a myeloablative conditioning regimen to compare 2 hemoglobin thresholds as triggers for red blood cell transfusion: 120 g/L in the experimental arm and 70 g/L in the control arm. The Data and Safety Monitoring Board closed the study after enrollment of the sixth patient because 3 patients in the experimental arm contracted veno-occlusive disease, but none in the control arm did (P = .05). Ascites was present in all 3 patients, pleura effusion in 2, and portal vein thrombosis in 2. One patient experienced hepatic failure and required treatment with the molecular adsorbent recycling system. Another patient required hemodialysis for renal failure. No major imbalance between groups was seen with regard to risk factors for veno-occlusive disease. Therefore, maintaining the hemoglobin at higher levels should be avoided after hematopoietic stem cell transplantation. PMID:23220014

  12. High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease--a pragmatic prognostic index.

    PubMed Central

    O'Brien, M. E.; Milan, S.; Cunningham, D.; Jones, A. L.; Nicolson, M.; Selby, P.; Hickish, T.; Hill, M.; Gore, M. E.; Viner, C.

    1996-01-01

    High-dose chemotherapy with autologous bone marrow transplantation is used in the treatment of relapsed or high-risk Hodgkin's disease. As prospective randomised studies have proved difficult to accrue to, current recommendations are based on the reports of large series of prospectively collected data. We have looked at the outcome of 89 patients treated in this way at a single institution and have developed an index to predict outcome. Of 89 patients, with a median age of 29 years (range 15-51 years), eight patients were in first complete remission/partial remission (CR/PR), 17 in second or later CR, 37 were responding relapses, 13 resistant relapses, 11 primary refractory and three untested relapses. Combinations of melphalan, BCNU and etoposide were given in all cases except in ten patients who received melphalan alone. The median follow-up was 43 months (range 6-77 months). A total of 24 patients were in CR at the time of autologous bone marrow transplantation (ABMT), 33 achieved CR with ABMT, 16 PR, to give a response rate to ABMT of 49/65 = 74% (95% CI 60-83%) with a CR rate of 51% (CI 36-62%). In a Cox's multivariate analysis the most important factors in predicting outcome after ABMT were response to treatment before entry, number of previous treatments and previous chemosensitivity. Using these factors we devised a prognostic index which reliably selects a group of patients (65%) with at least a 70% chance of being progression free from 1 year onwards. Patients who have never achieved a CR and have received three or more chemotherapy regimens do not benefit from high-dose chemotherapy as used in this study. PMID:8630292

  13. Bone marrow transplantation for T-B- severe combined immunodeficiency disease in Athabascan-speaking native Americans.

    PubMed

    O'Marcaigh, A S; DeSantes, K; Hu, D; Pabst, H; Horn, B; Li, L; Cowan, M J

    2001-04-01

    A distinct form of autosomal recessive T-B- severe combined immunodeficiency disease occurs with a high frequency among Athabascan-speaking Native Americans (SCIDA), including Navajo and Apache Indians from the southwestern US and Dene Indians from the Canadian Northwest Territories. The SCIDA gene has been linked to markers on chromosome 10p although its identity and role in the pathogenesis of this disease are unknown. We report our experience in treating 18 Navajo and Dene children with SCIDA between 1984 and 1999; 16 underwent bone marrow transplants (BMT). All children were symptomatic within 2 months of birth, had the T-B- NK(+)SCID phenotype and 67% presented with oral and/or genital ulcers. Three children had evidence of maternal engraftment prior to transplant. Two children died shortly after diagnosis. Three children required more than one BMT and 12 are alive with T cell reconstitution at a median follow-up of 7 years. Three children developed normal B cell immunity, two of whom received ablative conditioning therapy with either radiation or busulfan. Three of the four children who died received therapy with either radiation or busulfan and two of eight long-term survivors who were also recipients of cytotoxic chemotherapy have failed to develop secondary teeth. These results demonstrate the efficacy of BMT in treating infants with this distinct form of SCID, although B cell reconstitution remains a problem even with HLA-matched donors. Without conditioning, T cell engraftment is likely when closely HLA-matched donors are used. With T cell depletion of haplocompatible marrow, conditioning with immunosuppressive therapy may be necessary; however, children with SCIDA who were treated with intensive immunosuppressive and myeloablative therapy had a poor outcome. PMID:11360109

  14. Prevention of lethal graft vs Host disease following bone marrow transplantation (pretreatment of the inoculum with purine metabolic enzyme inhibitors)

    SciTech Connect

    Kennedy, D.W.

    1983-01-01

    A correlation between lymphocyte function and enzymes of the purine metabolic pathway has been shown. Abnormal levels of three of these enzymes - adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), and purine nucleoside phosphorylase (PNP) - have been associated with defective lymphoid functions. Selective inhibition of one or more of these enzymes may result in elimination of specific lymphocyte populations from a bone marrow (BM) graft and thus prevent graft-vs-host disease (GVHD). To test this hypothesis, BM and spleen cells were pretreated with inhibitors of ADA or PNP before transplant to histoincompatible recipients. Germfree (GF) mice approximately 11 weeks of age were lethally X-irradiated with 1000 Rads. At 24 hours post irradiation the mice received 5 x 10/sup 6/ BM cells and 5 x 10/sup 6/ BM cells and 5 x 10/sup 6/ spleen cells i.v. from syngeneic donors or allogeneic donors. Prior to injection the mice were divided into 5 groups: (1) the inoculum was treated with a final concentration of 10 ..mu..M deoxycoformycin (dCF), and ADA inhibitor, and 100 ..mu..M deoxyadenosine (dAdo); (2) the inoculum was treated with a final concentration of 100 ..mu..M 8-aminoguanosine (8AGuo), an inhibitor of PNP, and 100 ..mu..M 2'-deoxyguanosine (2'dGuo); (3) allogenic controls; (4) syngeneic controls; and (5) radiation controls. In vitro experiments utilizing human peripheral blood and bone marrow demonstrated a severe immunosuppressive effect by the combination of 2'dCF and dAdo which was quick acting and not easily washed away. Treatment with 8A Guo + 2'dGuo also was immunosuppressive, but not as effective as the dCF and dAdo treatment. Both groups of drugs deserve further investigation for possible clinical application to BM transplantation.

  15. Leukocytes expressing green fluorescent protein as novel reagents for adoptive cell transfer and bone marrow transplantation studies.

    PubMed

    Manfra, D J; Chen, S C; Yang, T Y; Sullivan, L; Wiekowski, M T; Abbondanzo, S; Vassileva, G; Zalamea, P; Cook, D N; Lira, S A

    2001-01-01

    Transgenic mice expressing green fluorescent protein (GFP) were generated to provide a source of labeled leukocytes for cell transfer studies. The transgene comprises the GFP coding region under the transcriptional control of the chicken ss-actin promoter and human cytomegalovirus enhancer. Mice expressing this GFP transgene were generated in the B6D2 and in the 129SvEv backgrounds. Flow cytometric analysis of cells from the blood, spleen, and bone marrow of these transgenic mice revealed that most leukocytes, including dendritic cells and memory T cells, express GFP. In allogeneic cell transfers, donor GFP+ splenocytes were detected in the spleen and mesenteric lymph nodes of recipient mice within 2 hours after transfer and for at least 9 days thereafter. In syngeneic experiments using 129-derived GFP+ donor splenocytes, donor cells were detected in multiple tissues of 129 recipients from 2 hours to 3 weeks after transfer. In bone-marrow transplantation experiments using irradiated allogeneic recipients, the percent of GFP+ donor cells in recipients at 3 weeks was comparable to that seen in similar tissues of GFP+ donor mice. These data demonstrate that GFP+ transgenic mice provide a ready source of GFP-expressing primary cells that can be easily monitored after their transfer to recipient animals. PMID:11141477

  16. Leukocytes Expressing Green Fluorescent Protein as Novel Reagents for Adoptive Cell Transfer and Bone Marrow Transplantation Studies

    PubMed Central

    Manfra, Denise J.; Chen, Shu-Cheng; Yang, Tong-Yuan; Sullivan, Lee; Wiekowski, Maria T.; Abbondanzo, Susan; Vassileva, Galya; Zalamea, Petronio; Cook, Donald N.; Lira, Sergio A.

    2001-01-01

    Transgenic mice expressing green fluorescent protein (GFP) were generated to provide a source of labeled leukocytes for cell transfer studies. The transgene comprises the GFP coding region under the transcriptional control of the chicken β-actin promoter and human cytomegalovirus enhancer. Mice expressing this GFP transgene were generated in the B6D2 and in the 129SvEv backgrounds. Flow cytometric analysis of cells from the blood, spleen, and bone marrow of these transgenic mice revealed that most leukocytes, including dendritic cells and memory T cells, express GFP. In allogeneic cell transfers, donor GFP+ splenocytes were detected in the spleen and mesenteric lymph nodes of recipient mice within 2 hours after transfer and for at least 9 days thereafter. In syngeneic experiments using 129-derived GFP+ donor splenocytes, donor cells were detected in multiple tissues of 129 recipients from 2 hours to 3 weeks after transfer. In bone-marrow transplantation experiments using irradiated allogeneic recipients, the percent of GFP+ donor cells in recipients at 3 weeks was comparable to that seen in similar tissues of GFP+ donor mice. These data demonstrate that GFP+ transgenic mice provide a ready source of GFP-expressing primary cells that can be easily monitored after their transfer to recipient animals. PMID:11141477

  17. Analysis of beta-globin mutations shows stable mixed chimerism in patients with thalassemia after bone marrow transplantation.

    PubMed

    Kapelushnik, J; Or, R; Filon, D; Nagler, A; Cividalli, G; Aker, M; Naparstek, E; Slavin, S; Oppenheim, A

    1995-10-15

    Beta-thalassemia major (TM) is caused by any of approximately 150 mutations within the beta-globin gene. To establish the degree of chimerism after bone marrow transplantation (BMT), we have performed molecular analysis of beta-globin mutations in 14 patients with TM over a period of 10 years. All patients underwent T cell-depleted allogeneic BMT from HLA-identical related donors, using either in vitro T-cell depletion with CAMPATH 1M and complement or in vivo depletion using CAMPATH 1G in the bone marrow collection bag. To date, at different time periods after BMT, seven patients have some degree of chimerism; six of these patients, all blood transfusion-independent, have donor cells in the range of 70% to 95%, with stable mixed chimerism (MC). The seventh patient has less than 10% donor cells with, surprisingly, only minimal transfusion requirements. The detection of beta-globin gene point mutation, as used here, is a highly specific and sensitive marker for engraftment and MC in patients with thalassemia. In light of its specificity, the method is applicable in all cases of TM, as it is independent of sex and other non-globin-related DNA markers. The high incidence of MC found in our patients may be a consequence of the pre-BMT T-cell depletion. Because MC was associated with transfusion independence, complete eradication of residual host cells for effective treatment of TM and possibly other genetic diseases may prove not to be essential. PMID:7579421

  18. 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

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

    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 ...

  20. Burden of morbidity in 10+ year survivors of hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study

    PubMed Central

    Sun, Can-Lan; Kersey, John H.; Francisco, Liton; Armenian, Saro H.; Baker, K. Scott; Weisdorf, Daniel J.; Forman, Stephen J.; Bhatia, Smita

    2013-01-01

    Long-term morbidity after hematopoietic cell transplantation (HCT) is unknown. The risk of physical and psychological health in 324 patients who had survived 10 or more years after HCT, and a sibling comparison group (n=309) was evaluated. Using the CTCAE v3.0, the 15-year cumulative incidence of severe/life-threatening/fatal conditions was 41% (95%CI, 34–48%). HCT survivors were 5.7 times as likely to develop a severe/life-threatening condition (p<0.001), and 2.7 times as likely to report somatic distress (p<0.001) compared with siblings. Compared with allogeneic HCT recipients with no chronic GvHD, those with active chronic GvHD were at a 1.8-fold higher risk of severe/life-threatening health conditions (p=0.006), and 4.5-fold higher risk of somatic distress (p=0.04); allogeneic HCT recipients with resolved chronic GvHD were not at increased risk of morbidity compared with those with no chronic GvHD. Only 27% of the HCT survivors returned to the transplant center for their cancer-related care. The burden of long-term physical and emotional morbidity borne by survivors remains substantial, even beyond 10 years after HCT; however, specialized healthcare is underutilized. Patients, families and healthcare providers need to be made aware of the high burden, such that they can plan for post-HCT care, even many years after HCT. PMID:23583827

  1. Group medical appointments: organization and implementation in the bone marrow transplantation clinic.

    PubMed

    Meehan, Kenneth R; Hill, John M; Root, Lynn; Kimtis, Elizabeth; Patchett, Linda; Noffsinger, Edward B

    2006-01-01

    Group medical appointments provide patients with prompt access to care, greater attention to their psychosocial needs, and increased time with their medical team. Care providers evaluate more patients with similar needs in a shorter period. Eligible patients (between 100 days and 3 years after autologous stem cell transplantation) were contacted to participate. The laboratory and radiographic results of each patient's completed reevaluation were entered into the electronic template office note before their visit. A group medical visit model, called a Physical Shared Medical Appointment (PSMA), was employed because this uses individual patient examinations followed by a group meeting. On the day of the visit, brief physical examinations were performed on each patient. A transplantation physician then met with the group of patients and answered questions. Patient satisfaction surveys were distributed upon completion of the group session. Each PSMA was limited to 10 patients to facilitate patient participation. Questions during the group meeting were general and applicable to all patients. At completion of the 2-hour visit, patient surveys indicated an extremely high level of satisfaction and the preference to attend a future PSMA. Issues discussed during the group meeting were pertinent to all transplant recipients, regardless of diagnosis. The PSMA model allows the patient to spend extended time with their care providers while providing the care providers an opportunity to discuss health issues with numerous patients during 1 appointment. The Dartmouth Transplant PSMA model is expanding to pretransplantation and postallogeneic transplant recipients. PMID:18632444

  2. 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. PMID:10516675

  3. Evaluation of a cryopreservation procedure to set up a new bone marrow transplant unit using lymphocyte proliferation test.

    PubMed

    Wong, Peerapon; Pongcharoen, Sutatip; Pangwangthong, Kullanit; Supalap, Kwansuda; Tapprom, Akamon; Deoisares, Rawisut

    2012-01-01

    A bone marrow transplant (BMT) is one kind of standard treatment modality in advanced hemato-oncology. In order to set up a BMT unit, one of the important steps before starting a clinical program is to evaluate the cryopreservation procedure for stem cell storage. Twenty one bags of buffy coat were used to be the testing specimens. They were processed and frozen according to cryopreservation protocol and kept in liquid nitrogen for 2 weeks. The evaluation process was carried out with a lymphocyte proliferation test together with trypan blue staining. By measuring the optical density of each lymphocyte containing well after stimulation, the lymphocyte proliferation value (LPV) could be obtained. When comparing them before and after cryopreservation, the LPV was 2.064 ± 0.379 (mean ± SD) and 1.913 ± 0.546, (p = 0.314), respectively. At 2 weeks after cryopreservation, comparing between the frozen group and the unfrozen control, the LPV was 1.913 ± 0.546 and 0.486 ± 0.453, (p < 0.05), respectively. The LPV showed clear efficacy of the procedure, especially for preserving the cellular proliferation function. Our model of the cryopreservation procedure evaluation at pre-clinical phase by use of a buffy coat and lymphocyte proliferation test seems feasible for newly-established small BMT units. With these results, clinical transplantations can be performed with more confidence. PMID:21649473

  4. Role of reduced intensity conditioning in T-cell and B-cell immune reconstitution after HLA-identical bone marrow transplantation in ADA-SCID

    PubMed Central

    Cancrini, Caterina; Ferrua, Francesca; Scarselli, Alessia; Brigida, Immacolata; Romiti, Maria Luisa; Barera, Graziano; Finocchi, Andrea; Roncarolo, Maria Grazia; Caniglia, Maurizio; Aiuti, Alessandro

    2010-01-01

    The treatment of choice for severe combined immunodeficiency is bone marrow transplantation from an HLA-identical donor sibling without conditioning. However, this may result in low donor stem cell chimerism, leading to reduced long-term immune reconstitution. We compared engraftment, metabolic, and T-cell and B-cell immune reconstitution of HLA-identical sibling bone marrow transplantation performed in 2 severe combined immunodeficiency infants with adenosine deaminase deficiency from the same family treated with or without a reduced intensity conditioning regimen (busulfan/fludarabine). Only the patient who received conditioning showed a stable mixed chimerism in all lineages, including bone marrow myeloid and B cells. The use of conditioning resulted in higher thymus-derived naïve T cells and T-cell receptor excision circles, normalization of the T-cell repertoire, and faster and complete B-cell and metabolic reconstitution. These results suggest the utility of exploring the use of reduced intensity conditioning in bone marrow transplantation from HLA-identical donor in severe combined immunodeficiency to improve long-term immune reconstitution. PMID:20460637

  5. Allogeneic bone marrow transplantation in models of experimental autoimmune encephalomyelitis: evidence for a graft-versus-autoimmunity effect.

    PubMed

    Van Wijmeersch, Bart; Sprangers, Ben; Rutgeerts, Omer; Lenaerts, Caroline; Landuyt, Willy; Waer, Mark; Billiau, An D; Dubois, Bénédicte

    2007-06-01

    Autologous hematopoietic stem cell transplantation (HSCT) is being explored in the treatment of severe multiple sclerosis (MS), and is based on the concept of "resetting" the immune system. The use of allogeneic HSCT may offer additional advantages, such as the replacement of the autoreactive immune compartment by healthy allogeneic cells and development of a graft-versus-autoimmunity (GVA) effect. However, in clinical practice, the genetic susceptibility to MS of allogeneic stem cell donors is generally unknown, and GVA may therefore be an important mechanism of action. Experimental autoimmune encephalomyelitis (EAE)-susceptible and -resistant mouse strains were used to determine the roles of genetic susceptibility, level of donor-chimerism, and alloreactivity in the therapeutic potential of syngeneic versus allogeneic bone marrow transplant (BMT) for EAE. After transplantation and EAE induction, animals were evaluated for clinical EAE and ex vivo myelin oligodendrocyte glycoprotein-specific proliferation. Early after BMT, both syngeneic and allogeneic chimeras were protected from EAE development. On the longer term, allogeneic but not syngeneic BMT conferred protection, but this required high-level donor-chimerism from EAE-resistant donors. Importantly, when EAE-susceptible donors were used, robust protection from EAE was obtained when active alloreactivity, induced by donor lymphocyte infusions, was provided. Our findings indicate the requirement of a sufficient level of donor-chimerism from a nonsusceptible donor in the therapeutic effect of allogeneic BMT. Importantly, the data indicate that, independently of genetic susceptibility, active alloreactivity is associated with a GVA effect, thereby providing new evidence to support the potential role of allogeneic BMT in the treatment of MS. PMID:17531772

  6. 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.

  7. HLA-Haploidentical Bone Marrow Transplantation for Hematologic Malignancies Using Nonmyeloablative Conditioning and High-Dose, Posttransplantation Cyclophosphamide

    PubMed Central

    Luznik, Leo; O’Donnell, Paul V.; Symons, Heather J.; Chen, Allen R.; Leffell, M. Susan; Zahurak, Marianna; Gooley, Ted A.; Piantadosi, Steve; Kaup, Michele; Ambinder, Richard F.; Huff, Carol Ann; Matsui, William; Bolaños-Meade, Javier; Borrello, Ivan; Powell, Jonathan D.; Harrington, Elizabeth; Warnock, Sandy; Flowers, Mary; Brodsky, Robert A.; Sandmaier, Brenda M.; Storb, Rainer F.; Jones, Richard J.; Fuchs, Ephraim J.

    2008-01-01

    We evaluated the safety and efficacy of high-dose, posttransplantation cyclophosphamide (Cy) to prevent graft rejection and graft-versus-host disease (GVHD) after outpatient nonmyeloablative conditioning and T cell-replete bone marrow transplantation from partially HLA-mismatched (haploidentical) related donors. Patients with advanced hematologic malignancies (n = 67) or paroxysmal nocturnal hemoglobinuria (n = 1) received Cy 50 mg/kg i.v. on day 3 (n = 28) or on days 3 and 4 (n 5 40) after transplantation. The median times to neutrophil (>500/µL) and platelet recovery (>20,000/µL) were 15 and 24 days, respectively. Graft failure occurred in 9 of 66 (13%) evaluable patients, and was fatal in 1. The cumulative incidences of grades II–IV and grades III–IV acute (aGVHD) by day 200 were 34% and 6%, respectively. There was a trend toward a lower risk of extensive chronic GVHD (cGVHD) among recipients of 2 versus 1 dose of posttransplantation Cy (P = .05), the only difference between these groups. The cumulative incidences of nonrelapse mortality (NRM) and relapse at 1 year were 15% and 51%, respectively. Actuarial overall survival (OS) and event-free survival (EFS) at 2 years after transplantation were 36% and 26%, respectively. Patients with lymphoid malignancies had an improved EFS compared to those with myelogenous malignancies (P = .02). Nonmyeloablative HLA-haploidentical BMT with posttransplantation Cy is associated with acceptable rates of fatal graft failure and severe aGVHD or cGVHD. PMID:18489989

  8. In utero transplantation of adult bone marrow decreases perinatal lethality and rescues the bone phenotype in the knockin murine model for classical, dominant osteogenesis imperfecta.

    PubMed

    Panaroni, Cristina; Gioia, Roberta; Lupi, Anna; Besio, Roberta; Goldstein, Steven A; Kreider, Jaclynn; Leikin, Sergey; Vera, Juan Carlos; Mertz, Edward L; Perilli, Egon; Baruffaldi, Fabio; Villa, Isabella; Farina, Aurora; Casasco, Marco; Cetta, Giuseppe; Rossi, Antonio; Frattini, Annalisa; Marini, Joan C; Vezzoni, Paolo; Forlino, Antonella

    2009-07-01

    Autosomal dominant osteogenesis imperfecta (OI) caused by glycine substitutions in type I collagen is a paradigmatic disorder for stem cell therapy. Bone marrow transplantation in OI children has produced a low engraftment rate, but surprisingly encouraging symptomatic improvements. In utero transplantation (IUT) may hold even more promise. However, systematic studies of both methods have so far been limited to a recessive mouse model. In this study, we evaluated intrauterine transplantation of adult bone marrow into heterozygous BrtlIV mice. Brtl is a knockin mouse with a classical glycine substitution in type I collagen [alpha1(I)-Gly349Cys], dominant trait transmission, and a phenotype resembling moderately severe and lethal OI. Adult bone marrow donor cells from enhanced green fluorescent protein (eGFP) transgenic mice engrafted in hematopoietic and nonhematopoietic tissues differentiated to trabecular and cortical bone cells and synthesized up to 20% of all type I collagen in the host bone. The transplantation eliminated the perinatal lethality of heterozygous BrtlIV mice. At 2 months of age, femora of treated Brtl mice had significant improvement in geometric parameters (P < .05) versus untreated Brtl mice, and their mechanical properties attained wild-type values. Our results suggest that the engrafted cells form bone with higher efficiency than the endogenous cells, supporting IUT as a promising approach for the treatment of genetic bone diseases. PMID:19414862

  9. 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.

  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. PMID:15701723

  11. [The transplantability of bone marrow and spleen cells after filtration through silon tissue].

    PubMed

    Fiala, J

    1976-01-01

    Investigations were carried out on the separation of haematopoietic stem cells from suspensions of the bone-marrow and spleen by means of filtration with silon tissue. The presence of stem cells in the filtrates was determined by the spleen colony test according to the method of Till and McCulloch in irradiated mice. The investigations revealed that a selective separation of haematopoietic stem cells could not be achieved when proceeding in this way. From the results of further test series, in which suspensions were also used which had been gained from haematopoietic tissues of hypersplenic mice, the conclusion could be drawn that the haematopoietic stem cells obtained by filtrating the bone-marrow will have another affinity to the spleen tissue of irradiated mice than the haematopoietic stem cells gained by filtrating the spleen tissue. PMID:64407

  12. Facilitation of allogeneic bone marrow transplantation by a T cell-specific immunotoxin containing daunomycin

    SciTech Connect

    Xie, S.S.; Inazawa, M.; Sinha, N.; Sawada, S.; Vergidis, R.; Diener, E.

    1987-12-01

    Daunomycin coupled via an acid-sensitive spacer to monoclonal Thy-1.2-specific antibody was used to purge T lymphocytes from a 1:1 mixture of murine C57BL/6J bone marrow and spleen cells prior to engraftment in fully allogeneic, irradiated BALB/c recipients. Treatment of bone marrow with the immunotoxin at a concentration used for purging had no effect on the viability of committed hematopoietic progenitor or multipotent stem cells. All of the recipients of purged bone marrow were at least 80% chimeric for donor peripheral blood cells and none developed graft-versus-host disease. Out of 50 chimeras, 49 were still alive more than 200 days posttransplantation. The chimeras were shown to be tolerant to donor tissue as tested by mixed lymphocyte reactivity, cell-mediated cytotoxicity, and skin grafting. The same tests revealed full immunocompetence of chimeras to third-party alloantigens. In vivo IgM and IgG antibody responses to sheep red blood cells were similar in magnitude in allogeneically and syngeneically reconstituted mice.

  13. Challenges and potential solutions for recruitment and retention of hematopoietic cell transplantation physicians: the National Marrow Donor Program's System Capacity Initiative Physician Workforce Group report.

    PubMed

    Burns, Linda J; Gajewski, James L; Majhail, Navneet S; Navarro, Willis; Perales, Miguel-Angel; Shereck, Evan; Selby, George B; Snyder, Edward L; Woolfrey, Ann E; Litzow, Mark R

    2014-05-01

    Hematopoietic cell transplantation (HCT) remains the only known curative therapy for many patients with hematologic, metabolic, and immunologic disorders. Furthermore, the use of HCT has increased with the emergence of HCT as a viable therapeutic option for older patients, those with significant comorbidities, and, with the demonstrated clinical effectiveness of alternative allogeneic donor sources, for those patients without a suitable sibling donor. The National Marrow Donor Program (NMDP) estimates that by 2020, it will facilitate 10,000 transplantations per year, double the number in 2010. To understand the needs of the HCT infrastructure to facilitate this number of transplantations, the NMDP organized the System Capacity Initiative 2020, centered on 6 working groups representing a diverse group of stakeholders. The Physician Workforce Group was tasked with addressing issues relating to recruitment and retention of transplantation physicians. We report here the results of our efforts and future initiatives. PMID:24508838

  14. Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation.

    PubMed

    Bacigalupo, A; Oneto, R; Bruno, B; Socié, G; Passweg, J; Locasciulli, A; Van Lint, M T; Tichelli, A; McCann, S; Marsh, J; Ljungman, P; Hows, J; Marin, P; Schrezenmeier, H

    2000-01-01

    We have analyzed 2,002 patients grafted in Europe between 1976 and 1998 from an identical twin (n = 34), from an HLA-identical sibling (n = 1,699) or from an alternative donor (n = 269), which included unrelated and family mismatched donors. The proportions of patients surviving in these three groups are, respectively, 91, 66 and 37%: major causes of failure were acute graft-versus host disease (GvHD) (11%), infection (12%), pneumonitis (4%), rejection (4%). In multivariate Cox analysis, factors predicting outcome were patient's age (p < 0.0001), donor type (p < 0.0001), interval between diagnosis and bone marrow transplantation (BMT) (p < 0.0005), year of BMT (p = 0.0005) and female donor for a male recipient (p = 0.02). Patients were then divided in two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24% (p < 0.00001). Improvements were seen mostly for grafts from identical siblings (from 54 to 75%, p < 0.0001), and less so for alternative-donor grafts (from 28 to 35%; p = 0.07). Major changes have occurred in the BMT protocol: decreasing use of radiotherapy in the conditioning regimen (from 35 to 24%; p < 0.0001) and increasing use of cyclosporin (with or without methotrexate) for GvHD prophylaxis (from 70 to 98%; p < 0.0001). In conclusion, the outcome of allogeneic BMT for patients with severe aplastic anemia has considerably improved over the past two decades: young patients, grafted early after diagnosis from an identical sibling, have currently an over 80% chance of long-term survival. Transplants from twins are very successful as well. The risk of complications with alternative donor transplants is still high. PMID:10705155

  15. Influence of severe combined immunodeficiency phenotype on the outcome of HLA non-identical, T-cell-depleted bone marrow transplantation: a retrospective European survey from the European group for bone marrow transplantation and the european society for immunodeficiency.

    PubMed

    Bertrand, Y; Landais, P; Friedrich, W; Gerritsen, B; Morgan, G; Fasth, A; Cavazzana-Calvo, M; Porta, F; Cant, A; Espanol, T; Müller, S; Veys, P; Vossen, J; Haddad, E; Fischer, A

    1999-06-01

    We analyzed the outcomes of 214 HLA non-identical T-cell-depleted bone marrow transplantations (BMTs), performed in 178 consecutive patients for treatment of severe combined immunodeficiencies (SCID). Patients were treated in 18 European centers between 1981 and March 1995. SCID variants, that is, absence of T and B lymphocytes (B-) or absence of T cells with presence of B lymphocytes (B+) were found to have a major influence on outcome. The disease-free survival was significantly better for patients with B+ SCID (60%) as compared with patients with B- SCID (35%) (P =.002), with a median follow-up of 57 months and 52 months, respectively. Other factors associated with a poor prognosis were the presence of a lung infection before BMT (odds ratio = 2.47 [1.99-2.94]) and the use of monoclonal antibodies for T-cell depletion of the graft (odds ratio = 1.67 [1. 18-2.15]). Additional factors influencing outcome were age at BMT (<6 months) and period during which BMT was performed. Better results were achieved after 1991. Reduced survival of patients with B- SCID was associated with a higher incidence of early deaths from infection, a diminished rate of marrow engraftment, a trend to a higher incidence of chronic graft-versus-host disease, and slower kinetics of T/B immune function development. In both groups of patients, the use of busulfan (8 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose) as a conditioning regimen provided the best cure rate (74% for patients with B+ SCID and 43% for patients with B- SCID, respectively), although results were not statistically significantly different from other regimens. This retrospective analysis should lead to the design of adapted measures to the performance of HLA non-identical BMT in patients with distinct SCID conditions. PMID:10356144

  16. Immune Tolerance in Recipients of Combined Haploidentical Bone Marrow and Kidney Transplantation

    PubMed Central

    Sykes, Megan

    2016-01-01

    The success of allogeneic HCT has been limited by transplant-associated toxicities related to the conditioning regimens used and to graft-vs-host disease (GVHD). The frequency and severity of GVHD observed when extensive HLA barriers are transgressed has greatly impeded the routine use of extensively HLA-mismatched HCT. Allogeneic HCT also has potential as an approach to organ allograft tolerance induction, but this potential has not been previously realized because of the toxicity associated with traditional conditioning. This paper reviews an approach to HCT involving reduced intensity conditioning that demonstrated sufficient safety in patients with hematologic malignancies, even in the HLA-mismatched transplant setting, to be applied for the induction of kidney allograft tolerance in humans with no other indication for HCT. These studies provided the first successful example of intentional organ allograft tolerance induction across HLA barriers in humans. Current data and hypotheses on the mechanisms of tolerance in these patients are reviewed. PMID:26039215

  17. Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation

    PubMed Central

    McDermott, David H.; Conway, Susan E.; Wang, Tao; Ricklefs, Stacy M.; Agovi, Manza A.; Porcella, Stephen F.; Tran, Huong Thi Bich; Milford, Edgar; Spellman, Stephen

    2010-01-01

    Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen–matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. PMID:20068218

  18. Comparison of Outcomes after Transplantation of G-CSF Stimulated Bone Marrow Grafts versus Bone Marrow or Peripheral Blood Grafts from HLA-Matched Sibling Donors for Patients with Severe Aplastic Anemia

    PubMed Central

    Chu, Roland; Brazauskas, Ruta; Kan, Fangyu; Bashey, Asad; Bredeson, Christopher; Camitta, Bruce; Chiang, Kuang-Yueh; Frangoul, Haydar; Gale, Robert Peter; Gee, Adrian; George, Biju; Goldman, Frederick D.; Gross, Thomas G.; Gupta, Vikas; Hale, Gregory A.; Isola, Luis; Ispizua, Alvaro Urbano; Lazarus, Hillard; Marsh, Judith; Russell, James; Sabloff, Mitchell; Waller, Edmund K.; Eapen, Mary

    2010-01-01

    We compared outcomes of patients with severe aplastic anemia (SAA) who received G-CSF stimulated bone marrow (G-BM) (n=78), unstimulated bone marrow (BM) (n=547), or peripheral blood progenitor cells (PBPC) (n=134) from an HLA-matched sibling. Transplantations occurred in 1997–2003. Rates of neutrophil and platelet recovery were not different among the three treatment groups. Grade 2–4 acute graft-versus-host disease (GVHD) (RR 0.82, p=0.539), grade 3–4 acute GVHD (RR 0.74, p=0.535) and chronic GVHD (RR 1.56, p=0.229) were similar after G-BM and BM transplants. Grade 2–4 acute GVHD (RR 2.37, p=0.012) but not grade 3–4 acute GVHD (RR 1.66, p=0.323) and chronic GVHD (RR 5.09, p<0.001) were higher after PBPC transplants compared to G-BM. Grade 2–4 (RR 2.90, p<0.001), grade 3–4 (RR 2.24, p=0.009) acute GVHD and chronic GVHD (RR 3.26, p<0.001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR 0.63, p=0.05). These data suggest no advantage to using G-BM and the observed higher rates of acute and chronic GVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA matched sibling transplants for SAA. PMID:21034842

  19. Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation

    SciTech Connect

    Ikehara, S.; Yasumizu, R.; Inaba, M.; Izui, S.; Hayakawa, K.; Sekita, K.; Toki, J.; Sugiura, K.; Iwai, H.; Nakamura, T. )

    1989-05-01

    Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x NZW)F1 (B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted greater than 5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+ Ly-1+ cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, resids in abnormalities present in stem cells.

  20. Evaluation of the survival of bone marrow-derived mononuclear cells and the growth factors produced upon intramedullary transplantation in rat models of acute spinal cord injury.

    PubMed

    Arai, Kiyotaka; Harada, Yasuji; Tomiyama, Hiroyuki; Michishita, Masaki; Kanno, Nobuo; Yogo, Takuya; Suzuki, Yoshihisa; Hara, Yasushi

    2016-08-01

    Intramedullary bone marrow-derived mononuclear cell (BM-MNC) transplantation has demonstrated neuroprotective effects in the chronic stage of spinal cord injury (SCI). However, no previous study has evaluated its effects in the acute stage, even though cell death occurs mainly within 1week after injury in all neuronal cells. Moreover, the mechanism underlying these effects remains unclear. We aimed to investigate the survival of intramedullary transplanted allogeneic BM-MNCs and the production of growth factors after transplantation to clarify the therapeutic potential of intramedullary transplanted BM-MNCs and their protective effects in acute SCI. Sprague-Dawley rats were subjected to traumatic SCI and received intramedullary transplantation of EGFP(+)BM-MNCs (n=6), BM-MNCs (n=10), or solvent (n=10) immediately after injury. To evaluate the transplanted BM-MNCs and their therapeutic effects, immunohistochemical evaluations were performed at 3 and 7days post-injury (DPI). BM-MNCs were observed at the injected site at both 3 (683±83 cells/mm(2)) and 7 DPI (395±64 cells/mm(2)). The expression of hepatocyte growth factor was observed in approximately 20% transplanted BM-MNCs. Some BM-MNCs also expressed monocyte chemotactic protein-1 or vascular endothelial growth factor. The demyelinated area and number of cleaved caspase-3-positive cells were significantly smaller in the BM-MNC-transplanted group at 3 DPI. Hindlimb locomotor function was significantly improved in the BM-MNC-transplanted group at 7 DPI. These results suggest that intramedullary transplantation of BM-MNCs is an efficient method for introducing a large number of growth factor-producing cells that can induce neuroprotective effects in the acute stage of SCI. PMID:27473980

  1. An In Vivo Characterization of Trophic Factor Production Following Neural Precursor Cell or Bone Marrow Stromal Cell Transplantation for Spinal Cord Injury

    PubMed Central

    Hawryluk, Gregory W.J.; Mothe, Andrea; Wang, Jian; Wang, Shelly; Tator, Charles

    2012-01-01

    Cellular transplantation strategies for repairing the injured spinal cord have shown consistent benefit in preclinical models, and human clinical trials have begun. Interactions between transplanted cells and host tissue remain poorly understood. Trophic factor secretion is postulated a primary or supplementary mechanism of action for many transplanted cells, however, there is little direct evidence to support trophin production by transplanted cells in situ. In the present study, trophic factor expression was characterized in uninjured, injured-untreated, injured-treated with transplanted cells, and corresponding control tissue from the adult rat spinal cord. Candidate trophic factors were identified in a literature search, and primers were designed for these genes. We examined in vivo trophin expression in 3 paradigms involving transplantation of either brain or spinal cord-derived neural precursor cells (NPCs) or bone marrow stromal cells (BMSCs). Injury without further treatment led to a significant elevation of nerve growth factor (NGF), leukemia inhibitory factor (LIF), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β1 (TGF-β1), and lower expression of vascular endothelial growth factor isoform A (VEGF-A) and platelet-derived growth factor-A (PDGF-A). Transplantation of NPCs led to modest changes in trophin expression, and the co-administration of intrathecal trophins resulted in significant elevation of the neurotrophins, glial-derived neurotrophic factor (GDNF), LIF, and basic fibroblast growth factor (bFGF). BMSCs transplantation upregulated NGF, LIF, and IGF-1. NPCs isolated after transplantation into the injured spinal cord expressed the neurotrophins, ciliary neurotrophic factor (CNTF), epidermal growth factor (EGF), and bFGF at higher levels than host cord. These data show that trophin expression in the spinal cord is influenced by injury and cell transplantation, particularly when combined with intrathecal trophin infusion

  2. Remarkably reduced transplant-related complications by dibromomannitol non-myeloablative conditioning before allogeneic bone marrow transplantation in chronic myeloid leukemia.

    PubMed

    Barta, A; Dénes, R; Masszi, T; Reményi, P; Bátai, A; Torbágyi, E; Sipos, A; Lengyel, L; Jakab, K; Gyódi, E; Réti, M; Földi, J; Páldi-Haris, P; Avalos, M; Pálóczi, K; Fekete, S; Török, J; Hoffer, I; Jakab, J; Váradi, G; Kelemen, E; Petrányi, G

    2001-01-01

    A non-myeloablative conditioning protocol containing dibromomannitol (DBM/cytosine arabinoside/cyclophosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from sibling donors. Risk factors include: accelerated phase (10 patients), older age (17 patients over >40 years) and long interval between diagnosis and BMT (27 months on average). Severe mucositis did not occur. Venoocclusive liver disease was absent. Infectious complications were rare. Although grade II-IV acute graft-versus-host disease (GVHD) was present in 9 (25%) cases, there were only 2 serious (III-IV) ones. Chronic GVHD occurred in 25 (69%) cases, preceded by acute GVHD in 9 of the 25 affected patients. Early hematological relapse, 7-29 weeks after BMT, developed in 6 patients (17.6%). No relapse was noted in the completely chimeric patients, however molecular genetic residual disease was observed in 6 patients, in most of them after transient short-term mixed chimeric state. Overall actual survival rate is 83.3% for the 36 cases, and leukemia-free survival is 72.2% for the 34 engrafted patients. PMID:11408706

  3. Leukemia prevention and long-term survival of AKR mice transplanted with MHC-matched or MHC-mismatched bone marrow

    SciTech Connect

    Longley, R.E.; Good, R.A.

    1986-09-01

    The current studies were designed to evaluate the effectiveness of marrow transplantation within and outside the major histocompatibility complex (MHC) on the long-term survival and occurrence of spontaneous leukemia in AKR mice. AKR mice, which were lethally irradiated and received MHC-matched marrow from CBA/J mice (CBA----AKR), never developed leukemia and were alive and remained healthy for up to 280 days post-transplant. These long-term surviving chimeras possessed substantial immune vigor when both cell-mediated and humoral responses were tested. Lethally irradiated AKR mice, which had received MHC-mismatched marrow (anti-Thy-1.2 treated or nontreated) from C57BL/6J mice (B6----AKR), never developed leukemia and survived up to 170 days post-transplant. However, both groups of these chimeras began dying 180 to 270 days post-transplant due to a disease process which could not be readily identified. Histological analysis of B6----AKR chimeras revealed severe lymphoid cell depletion in thymus and spleen; however, none of these chimeras exhibited classical features of acute graft versus host disease. Concanavalin A mitogenesis, primary antibody responses to sheep red blood cells and the production of interleukin 2 (IL-2) were suppressed in B6----AKR chimeras. IL-2 treatment of B6----AKR chimeras was shown to partially correct these deficiencies without stimulating mixed lymphocyte responsiveness to donor or host lymphocytes. These studies indicate that the use of MHC-mismatched marrow for the prevention of spontaneous AKR leukemia may rely on augmentative IL-2 therapy for complete immune reconstitution of leukemia-free chimeras.

  4. 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

  5. Exposure of Early Pediatric Trainees to Blood and Marrow Transplantation Leads to Higher Recruitment to the Field

    PubMed Central

    Shereck, Evan; Shenoy, Shalini; Pulsipher, Michael; Burns, Linda; Bracey, Arthur; Chell, Jeffrey; Snyder, Edward; Nemecek, Eneida

    2013-01-01

    The National Marrow Donor Program (NMDP) projects the need for allogeneic unrelated blood and marrow transplants (BMT) in the United States is 10,000 per year. While the NMDP is preparing to facilitate that number by 2015, there are a number of barriers to meeting this need including recruiting additional health care personnel including BMT providers. To learn how best to recruit BMT physicians, we sought to understand why practicing BMT physicians chose to enter BMT, and why others did not. We conducted a web-based survey amongst Pediatric Hematology/Oncology (PHO) and BMT physician providers and trainees to determine the factors influencing their decision to choose or not choose a career in BMT. There were 259 respondents (48% male, 74% of Caucasian origin); 94 identified as BMT physicians, 112 as PHO physicians and 53 as PHO trainees. PHO and BMT providers spent an average of 53% of their time in clinical activities. More than 2/3 of PHO providers stated that they provide BMT services at their institutions, most commonly for inpatient coverage (73%). The proportion of providers exposed to BMT early in their training was significantly higher amongst BMT providers than PHO providers (51% vs. 18% during medical school [p<0.0001] and 70% vs. 50% during residency [p < 0.005]). Exposure during fellowship (94%) did not differ amongst groups. The decision to pursue a career in BMT was made before fellowship (medical school or residency) in 50% of the respondents. A lower proportion of BMT providers reported currently being involved in education of medical students and residents compared to PHO providers (98% vs. 76%, p<0.0001). Of 53 trainees, 64% reported that they were not contemplating a career in BMT. Of these, 68% stated that inadequate exposure to BMT prior to PHO fellowship was the reason. Only 26% reported BMT exposure in medical school and 43% during residency. The two most common reasons for the choice of a BMT career were the degree of intellectual and

  6. The relative roles of MHC and non-MHC antigens in bone marrow transplantation in rats. Graft acceptance and antigenic expression on donor red blood cells.

    PubMed

    Pinto, M; Gill, T J; Kunz, H W; Dixon-McCarthy, B D

    1983-06-01

    In order to investigate the influence of MHC and non-MHC genes in bone marrow transplantation, various combinations of congenic and inbred strains of rats were used as donors and recipients. A standard regimen of busulfan and cyclophosphamide treatment was used to condition the recipients. The resultant survival patterns of the animals indicated that: (1) a difference across the entire RT1 (MHC) complex is sufficient for the induction of fatal graft-versus-host disease (GVHD) in 100% of the engrafted animals; and (2) the blood group antigens RT2 and RT3, which are controlled by non-MHC genes, do not cause bone marrow graft rejection or GVHD. There were sequential changes of expression in surface alloantigens on the red cells in different donor-recipient combinations without other hematologic changes in the busulfan-cyclophosphamide conditioned bone marrow chimeras. PMID:6346598

  7. Remission With Donor Lymphocyte Infusion in a Child With Marrow Relapse After Haploidentical Stem Cell Transplantation for Relapsed Stage 4 Neuroblastoma.

    PubMed

    Liu, A P Y; Leung, R Y Y; Cheuk, K L; Lee, P P W; Chiang, A K S; Ha, S Y; Chan, G C F

    2016-08-01

    A 7-year-old male with Stage 4 neuroblastoma was treated with chemotherapy and autologous hematopoietic stem cell transplantation (HSCT), resulting in partial response with residual bone and marrow disease. He proceeded to haploidentical-HSCT with his mother as donor and achieved remission. The patient developed marrow relapse 2 years after haploidentical-HSCT with cytopenia and dropping donor chimerism. Donor lymphocyte infusion (DLI) using mother's whole blood was given resulting in clearance of marrow disease, resolution of cytopenia, and full donor chimerism. This is the first report of successful treatment for neuroblastoma relapse after haploidentical-HSCT using DLI alone, supporting the role of adoptive cell therapy post-HSCT in neuroblastoma. PMID:27100283

  8. Bone marrow transplantation for patients with acquired severe aplastic anemia using cyclophosphamide and antithymocyte globulin: the experience from a single center.

    PubMed

    Abdelkefi, Abderrahman; Ben Othman, Tarek; Ladeb, Saloua; Torjman, Lamia; Hsaïri, Mohamed; Ben Abdeladhim, Abdeladhim

    2003-01-01

    Between 1998 and 2001, 31 (24 male, 7 female) patients with severe aplastic anemia (SAA) and a median age of 19 years (range, 4-39 years) received an allogeneic bone marrow transplantation. Marrow donors were genotypically HLA-identical siblings in 30 cases and a monozygous twin in one case. The median time from diagnosis to bone marrow transplantation was 1 month (range, 0.5-5 months). Conditioning regimen consisted of cyclophosphamide (CY) combined with antithymocyte globulin (ATG), in all patients. For graft-versus-host disease (GvHD) prophylaxis, all patients received methotrexate and cyclosporin. A total of 84% of patients had sustained grafts, whereas 16% rejected grafts between 3 and 20 months after transplantation. Of the five rejecting patients, three are alive with successful second engraftments and two died from infections. Acute grade II-IV GvHD was seen in only 11% of patients. A limited chronic GvHD was seen in one patient. With a median follow-up of 18 months (range, 5-42 months), survival rate was 86% and Karnofsky score was at least 90%. This study confirms the high success rate of the CY/ATG regimen in SAA allografted from an HLA-identical sibling. Early and late graft failure remains a problem and may require modification of this regimen. PMID:12764353

  9. 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.

  10. A Phase II Trial of Autologous Transplantation of Bone Marrow Stem Cells for Critical Limb Ischemia: Results of the Naples and Pietra Ligure Evaluation of Stem Cells Study

    PubMed Central

    Maione, Ciro; Botti, Chiara; Marino, Gennaro; Lillo, Stefano; Garrone, Alberto; Lanza, Lorella; Pagliari, Stefano; Silvestroni, Andrea; Signoriello, Giuseppe

    2012-01-01

    Critical limb ischemia (CLI) is a vascular disease affecting lower limbs, which is going to become a demanding challenge because of the aging of the population. Despite advances in endovascular therapies, CLI is associated with high morbidity and mortality. Patients without direct revascularization options have the worst outcomes. To date, 25%–40% of CLI patients are not candidates for surgical or endovascular approaches, ultimately facing the possibility of a major amputation. This study aimed to assess the safety and efficacy of autologous bone marrow (BM) transplantation performed in “no-option” patients, in terms of restoring blood perfusion by collateral flow and limb salvage. A multicenter, prospective, not-controlled phase II study for no-option CLI patients was performed. Patients were subjected to intra-arterial infusion of autologous bone marrow and followed for 12 months after the treatment. Variation of blood perfusion parameters, evaluated by laser Doppler flowmetry or transcutaneous oximetry, was set as the primary endpoint at 12 months after treatment and amputation-free survival as the secondary endpoint. Sixty patients were enrolled and treated with BM transplantation, showing improvement in objective and subjective measures of perfusion. Furthermore, survival analysis demonstrated improved amputation-free survival rates (75.2%) at 12 months after the treatment. This study provides further evidence that autologous bone marrow transplantation is well tolerated by CLI patients without adverse effects, demonstrating trends toward improvement in perfusion and reduced amputation rate, confirming the feasibility and safety of the procedure. PMID:23197862

  11. 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

  12. B-cell proliferative and differentiative responses after autologous peripheral blood stem cell or bone marrow transplantation.

    PubMed

    Kiesel, S; Pezzutto, A; Moldenhauer, G; Haas, R; Körbling, M; Hunstein, W; Dörken, B

    1988-08-01

    In this study the authors have evaluated B-cell function after autologous peripheral-blood stem cell transplantation (ABSCT) and autologous bone marrow (ABMT) transplantation. The B-enriched fractions of peripheral blood from ten normal subjects and 22 autografted patients (11 patients after ABMT, eight patients after ABSCT, and three patients after ABSCT followed by ABMT) were investigated. Time postgrafting ranged from 1 to 34 months. Proliferative responses to anti-mu antibody, Staphylococcus aureus Cowan 1 (SAC), and low molecular weight (mol wt) 12-Kd B-cell growth factor (BCGF) were measured. Differentiative responses to the same factors were assessed by quantifying in vitro immunoglobulin (IgG/IgM) production. The authors found no difference in B-cell function between the ABMT and the ABSCT patient groups. Compared to the B cells of normal subjects, only five out of 22 autografted patients showed a normal proliferative response to all agents used, while nine out of 22 did not respond to any signals. Eight out of 22 patients displayed various defects of B-cell response. However, in vitro IgG/IgM secretion of predominantly IgG subclass was normal in 19 out of 22 patients. This in vitro ability to produce Ig was reflected by the patients' normal serum IgG/IgM levels, whereas serum IgA levels were low. The authors speculate that there may be 2 B-cell populations: the normal in vitro Ig production and in vivo serum IgG may come from the stimulation of a small number of re-infused pre-committed memory B cells while, in parallel, immature B cells develop from autografted hematopoietic progenitor cells. PMID:2900031

  13. Cells of origin of squamous epithelium, dysplasia and cancer in the head and neck region after bone marrow transplantation.

    PubMed

    Kano, Yoshihiro; Ishii, Hideshi; Konno, Masamitsu; Yamasaki, Makoto; Miyata, Hiroshi; Nishikawa, Shimpei; Hamabe, Atsushi; Ogawa, Hisataka; Takahashi, Hidekazu; Ohta, Katsuya; Hasegawa, Shinichiro; Tanaka, Kouji; Fukusumi, Takahito; Otsuka, Masahisa; Kawamoto, Koichi; Haraguchi, Naotsugu; Fujimoto, Rika; Isobe, Masaharu; Tomita, Yasuhiko; Matsuura, Nariaki; Takiguchi, Shuji; Mori, Masaki; Doki, Yuichiro

    2014-02-01

    Secondary solid tumors that occur after hematopoietic stem cell transplantation (HSCT) are late complications of HSCT. Previously, secondary solid tumors were considered to be recipient-derived cells because transplanted cells do not contain epithelial cells. Recently, however, not only donor‑derived epithelial cells but also donor-derived secondary solid tumors have also been reported in mice and humans. It means that circulating bone marrow-derived stem cells (BMDCs) including hematopoietic stem cells include the stem cells of many tissue types and the precancerous cells of many solid tumors. In most reports of donor-derived secondary solid tumors, however, tumors contained a low proportion of BMDC-derived epithelial cells in mixed solid tumor tissues. To our knowledge, there are only five known cases of completely donor-derived tumor tissues, i.e., four oral SCCs and a pharyngeal SCC. In this study, we analyzed five human clinical samples of solid tumors, i.e., two esophageal squamous cell carcinomas (SCCs), two oral SCCs and a tongue carcinoma. In the oral and tongue, completely donor-derived tissues were not observed, but in esophagus a completely donor-derived esophageal epidermis and SCC were observed for the first time. In addition, in another esophageal SCC patient, a completely donor-derived dysplasia region of esophageal epidermis was observed near recipient-derived SCC. This study suggests that BMDC-derived cells include the stem cells of esophageal epidermis and the precancerous cells of esophageal SCC and can differentiate into esophageal epithelium and esophageal SCC. PMID:24317739

  14. Mycobacterium avium complex-associated peritonitis with CAPD after unrelated bone marrow transplantation.

    PubMed

    Miyashita, Emiko; Yoshida, Hisao; Mori, Daisuke; Nakagawa, Natsuki; Miyamura, Takako; Ohta, Hideaki; Seki, Masafumi; Tomono, Kazunori; Hashii, Yoshiko; Ozono, Keiichi

    2014-12-01

    Peritonitis remains an important complication of peritoneal dialysis and is mostly caused by aerobic enteric bacteria. Non-tuberculous mycobacteria (NTM)-associated peritonitis is an unusual but serious infection, requiring special culture techniques to avoid delay in diagnosis. We report the case of an 11-year-old girl with aplastic anemia on ambulatory peritoneal dialysis who had Mycobacterium avium complex-associated peritonitis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case emphasizes that we should be constantly cautious about NTM infection in allo-HSCT recipients, especially when standard cultures are negative and the infection is refractory to empirical antibiotic therapy. PMID:25521993

  15. 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

  16. Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children's Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry.

    PubMed

    Mitchell, R; Nivison-Smith, I; Anazodo, A; Tiedemann, K; Shaw, P J; Teague, L; Fraser, C J; Carter, T L; Tapp, H; Alvaro, F; O'Brien, T A

    2013-09-01

    We report a retrospective analysis of 53 haematopoietic stem cell transplants for inherited metabolic disorders performed at ANZCHOG transplant centres between 1992 and 2008. Indications for transplant included Hurler syndrome, ALD, and MLD. The majority of transplants utilized unrelated donor stem cells (66%) with 65% of those being unrelated cord blood. Conditioning therapy was largely myeloablative, with Bu plus another cytotoxic agent used in 89% of recipients. Primary graft failure was rare, occurring in three patients, all of whom remain long-term survivors following the second transplant. The CI of grade II-IV and grade III-IV acute GVHD at day +100 was 39% and 14%, respectively. Chronic GVHD occurred in 17% of recipients. TRM was 12% at day +100 and 19% at one yr post-transplant. OS at five yr was 78% for the cohort, 73% for patients with ALD and 83% for patients with Hurler syndrome. There was no statistically significant difference in overall survival between unrelated marrow and unrelated cord blood donor groups. The development of interstitial pneumonitis was an independent variable shown to significantly impact on TRM and OS. In summary, we report a large cohort of patients with inherited metabolic disorders with excellent survival post-allogeneic transplant. PMID:23802616

  17. Bone Marrow Transplantation for Peripheral T-Cell Non-Hodgkins' Lymphoma in First Remission.

    PubMed

    Sharma, Manish; Pro, Barbara

    2015-07-01

    Opinion statement: Peripheral T-cell lymphomas (PTCLs) are rare and heterogeneous diseases that carry, with the exception of anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma, a poor prognosis when treated with conventional chemotherapy. Historically, PTCL was treated like aggressive B-cell lymphomas, and to date cyclophosphamide, prednisone, vincristine, and doxorubicin (CHOP) remains the most commonly used regimen, despite disappointing results. Given the poor outcomes of PTCL patients, a number of studies have investigated the role of high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in the upfront setting, with different results. However, there are no prospective randomized trials, and the clinical benefit appears to be restricted to patients who achieve an objective response after induction chemotherapy. Nevertheless, with the exception of low-risk ALK+ anaplastic large cell lymphoma, in light of the available data, HDT/ASCT for consolidation should be recommended for patients deemed eligible. The results of phase II trials showed that allogeneic stem cell transplantation can cure some relapsed/refractory patients, and few studies have evaluated this strategy in the frontline setting. With the availability of recently approved new drugs as well as new targeted agents under investigation, a number of ongoing studies are testing novel combinations aiming to improve rate and durability of responses to induction chemotherapy. PMID:26076798

  18. 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

  19. Non-myeloablative bone marrow transplant and platelet infusion can transiently improve the clinical outcome of mitochondrial neurogastrointestinal encephalopathy: a case report.

    PubMed

    Hussein, Eiman

    2013-10-01

    Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is caused by deficiency in thymidine phosphorylase (TP), that regulates thymidine (dThd) and deoxyuridine (dUrd). Toxic levels of dThd and dUrd can lead to mitochondrial dysfunction by impairing mitochondrial DNA replication, causing GI and neurologic deterioration. We studied the impact of bone marrow transplant (BMT) and platelets, as a source of TP on the clinical outcome of MNGIE. We report a case of MNGIE, who presented with severe vomiting. Over time, he was non-ambulatory and his GI symptoms got progressively worse with severe dysphagia, abdominal pain episodes, persistent vomiting and diarrhea. Being unfit for intense conditioning regimen, he received a mini BMT, with mild conditioning regimen. Bone marrow was obtained from his HLA fully matched brother. One month after transplantation, donor chimerism in peripheral blood was 33%. Excellent clinical responses were achieved 3 months after transplantation and circulating donor cell chimerism decreased to 24% with a significant increase in platelet TP activity. Ten months post transplant the patient's symptoms recurred and fresh single donor platelets were infused, with a significant increase in platelet TP activity. Mini BMT and platelet transfusion can transiently increase circulating TP activity and might prevent progress of this fatal disease. PMID:23410918

  20. Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia.

    PubMed

    Pawlowska, A B; Blazar, B R; Angelucci, E; Baronciani, D; Shu, X O; Bostrom, B

    1997-12-01

    We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg. Three sets of parameters were examined in this homogenous patient population: (1) factors that affect the plasma kinetics of busulfan, such as age and pre-transplant liver status defined by liver function tests, ferritin levels and liver biopsy; (2) busulfan-related toxicity: occurrence of veno-occlusive disease, seizures and idiopathic interstitial pneumonitis; and (3) the relationship between busulfan exposure and transplant outcome: engraftment delay or rejection, aplasia, occurrence of mixed chimeras and mortality. Kinetic analysis of first and 10th dose (using area under the curve (AUC), maximum and minimum concentration) as comparable, showing no sign of accumulation or decline in busulfan plasma levels over time. Age and liver status did not influence busulfan metabolism. No relationship was found between busulfan exposure and toxicities or transplant outcome. We conclude that busulfan monitoring is not predictive in children and young adults with homozygous beta-thalassemia receiving busulfan and high-dose cyclophosphamide along with histocompatable sibling donor marrow. PMID:9422469

  1. Combined model of the EBMT score modified model and the HCT-CI improves the stratification of high-risk patients undergoing unmanipulated haploidentical blood and marrow transplantation.

    PubMed

    Chang, Ying-Jun; Wang, Hong-Tao; Xu, Lan-Ping; Wang, Yu; Liu, Kai-Yan; Zhang, Xiao-Hui; Liu, Dai-Hong; Chen, Huan; Chen, Yu-Hong; Wang, Feng-Rong; Han, Wei-; Sun, Yu-Qian; Yan, Chen-Hua; Tang, Fei-Fei; Mo, Xiao-Dong; Huang, Xiao-Jun

    2016-09-01

    Both European Group for blood and marrow transplantation risk score (EBMT score modified model) and hematopoietic cell transplantation comorbidity index (HCT-CI) are suitable for evaluating patients undergoing unmanipulated haploidentical blood and marrow transplantation (HBMT), while the predictive capacity of the combined model following haploidentical transplantation is still unknown. In this study, we calculated and validated 322 consecutive unmanipulated HBMT patients. Patients in groups with HCT-CI scores of 0 or 1-2 exhibited similar overall survival (OS), non-relapse mortality (NRM), and relapse rates, independent of their EBMT score modified model. In the group in which patients' HCT-CI scores were ≥3, patients with high EBMT score modified model showed lower OS (p = 0.003) and higher NRM (p = 0.001) than did patients with low EBMT score. In conclusion, this combined model can be used to predict outcomes and may improve the stratification of high-risk patients following unmanipulated HBMT. PMID:26857549

  2. 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

  3. 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.

  4. Glutathione S-transferase activity influences busulfan pharmacokinetics in patients with beta thalassemia major undergoing bone marrow transplantation.

    PubMed

    Poonkuzhali, B; Chandy, M; Srivastava, A; Dennison, D; Krishnamoorthy, R

    2001-03-01

    Busulfan, at a dose of 16 mg/kg, is widely used in combination with cyclophosphamide as a conditioning regimen for patients undergoing bone marrow transplantation. Wide interindividual variation in busulfan kinetics and rapid clearance of the drug have been reported, especially in children. Some of the factors contributing to interpatient variability have been identified. They include circadian rhythms, age, disease, drug interaction, changes in hepatic function, and busulfan bioavailability. In this study, we demonstrate that hepatic glutathione S-transferase (GST) activity correlates negatively with busulfan maximum and minimum concentrations (Pearson's correlation r = -0.74 and -0.77, respectively) and positively with busulfan clearance (Pearson's correlation r = 0.728) in children with thalassemia major in the age range of 2 to 15 years. We also found that plasma alpha GST levels were 5 to 10 times higher in patients with thalassemia than in normal controls and age-matched leukemic patients, either reflecting extensive liver damage, elevated expression of the enzyme, or both in thalassemic patients. Plasma alpha GST concentrations showed a similar correlation with busulfan kinetic parameters to that observed for hepatic GST. The status of hepatic GST activity accounts, at least in part, for the observed interindividual variation in busulfan kinetics, while the observed association with plasma alpha GST is difficult to explain at present. PMID:11181493

  5. Evaluation of existing limited sampling models for busulfan kinetics in children with beta thalassaemia major undergoing bone marrow transplantation.

    PubMed

    Balasubramanian, P; Chandy, M; Krishnamoorthy, R; Srivastava, A

    2001-11-01

    Busulfan pharmacokinetic parameters are useful in predicting the outcome of allogeneic bone marrow transplantation (BMT). Standard pharmacokinetic measurements require multiple blood samples. Various limited sampling models (LSM) have been proposed for reducing the sample number required for these measurements, essentially for patients with malignant disorders undergoing BMT. This study was undertaken to evaluate the existing LSM for busulfan pharmacokinetics to find out the most suitable method for patients with thalassaemia major undergoing BMT. Busulfan levels in plasma samples were analysed by HPLC. The AUC calculated by non-compartmental analysis using the program 'TOPFIT' was compared with previously published LSMs. Our seven sample pharmacokinetic data for AUC calculation was compared with the published LSMs. The three sample models suggested by Chattergoon et al and Schuler et al showed significant agreement with AUC TOPFIT (R(2) = 0.98 and 0.94, respectively) in our clinical context. Other models resulted in significant over or under representation of observed values (Vassal's model R(2) = 0.61; Chattergoon's two sample model R(2) = 0.84; four sample model R(2) = 0.83; Schuler's two sample model R(2) = 0.79). By these data the three sample LSM proposed by Chattergoon et al and Schuler et al are suitable for calculation of the AUC in patients with thalassaemia major undergoing BMT conditioned with oral busulfan. PMID:11781641

  6. Specificity of T cells invading the skin during acute graft-vs.-host disease after semiallogeneic bone marrow transplantation.

    PubMed Central

    Gaschet, J; Mahé, B; Milpied, N; Devilder, M C; Dréno, B; Bignon, J D; Davodeau, F; Hallet, M M; Bonneville, M; Vié, H

    1993-01-01

    The mechanisms responsible for skin lesions during acute graft-vs.-host disease (aGVHD) after allogeneic bone marrow transplantation (BMT) are poorly understood. The exact role of various effector cell populations and "major" (particularly HLA-DP) or "minor" antigens as target molecules is not known. To investigate the nature of cells responsible for tissue injury, we cultured T cells from skin biopsy first with interleukin 2 (IL-2) alone and then in polyclonal activation conditions to avoid in vitro antigenic sensitization before specificity testing. We applied this method to two biopsies performed during aGVHD after semiallogeneic BMT and obtained cytotoxic T cells against four graft mismatches: CD8+ T cells against HLA-A2.2 and HLA-B27 and CD4+ T cells against HLA-DP101 and HLA-DP401. This demonstrates that T cells with documented specificity can be obtained from an aGVHD lesion without antigenic selection. Moreover, these data directly implicate DP as a potential target antigen for aGVHD. Images PMID:8423212

  7. 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

  8. Absence of P-selectin in Recipients of Allogeneic Bone Marrow Transplantation Ameliorates Experimental Graft-versus-Host-Disease

    PubMed Central

    Lu, Sydney X.; Holland, Amanda M.; Na, Il-Kang; Terwey, Theis H.; Alpdogan, Onder; Bautista, Jhoanne L.; Smith, Odette M.; Suh, David; King, Christopher; Kochman, Adam; Hubbard, Vanessa M.; Rao, Uttam K.; Yim, Nury; Liu, Chen; Laga, Alvaro C.; Murphy, George; Jenq, Robert; Zakrzewski, Johannes L.; Penack, Olaf; Dykstra, Lindsay; Bampoe, Kevin; Perez, Lia; Furie, Bruce; Furie, Barbara; van den Brink, Marcel R.M.

    2013-01-01

    Alloreactive T cells are crucial for graft-versus-host-disease (GVHD) pathophysiology, and modulating their trafficking patterns has been efficacious in ameliorating experimental disease. We report here that P-selectin, a glycoprotein found on resting and inflamed endothelium, is important for donor alloreactive T cells trafficking into GVHD target organs such as the intestines and skin. Compared with wildtype recipients of allogeneic bone marrow transplantation (allo-BMT), P-selectin−/− recipients exhibit decreased GVHD mortality and decreased GVHD of the skin, liver and small bowels. This was associated with diminished infiltration of alloactivated T cells into the Peyer's Patches and small bowels, coupled with increased numbers of donor T cells in the spleen and secondary lymphoid organs (SLO). Surprisingly however, donor T cells deficient for PSGL1, the most well-described P-selectin ligand, mediated similar GVHD as WT T cells, and accumulated in SLO and target organs in similar numbers as WT T cells. This suggests that P-selectin may be required for trafficking into inflamed tissues but not SLO, and that donor T cells may utilize multiple P-selectin ligands apart from PSGL1 to interact with P-selectin and traffic into inflamed tissues during GVHD. We conclude that targeting P-selectin may be a viable target for GVHD prophylaxis or treatment. PMID:20622117

  9. 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

  10. Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus.

    PubMed

    Ding, Lijun; Li, Xin'an; Sun, Haixiang; Su, Jing; Lin, Nacheng; Péault, Bruno; Song, Tianran; Yang, Jun; Dai, Jianwu; Hu, Yali

    2014-06-01

    Serious injuries of endometrium in women of reproductive age are often followed by uterine scar formation and a lack of functional endometrium predisposing to infertility or miscarriage. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown great promise in clinical applications. In the present study, BM-MSCs loaded onto degradable collagen membranes were constructed. Collagen membranes provided 3-dimmensional architecture for the attachment, growth and migration of rat BM-MSCs and did not impair the expression of the stemness genes. We then investigated the effect of collagen/BM-MSCs constructs in the healing of severe uterine injury in rats (partial full thickness uterine excision). At four weeks after the transplantation of collagen/BM-MSCs constructs, BM-MSCs were mainly located to the basal membrane of regenerative endometrium. The wounded tissue adjacent to collagen/BM-MSCs constructs expressed higher level of bFGF, IGF-1, TGFβ1 and VEGF than the corresponding tissue in rats receiving collagen construct alone or in spontaneous regeneration group. Moreover, the collagen/BM-MSCs system increased proliferative abilities of uterine endometrial and muscular cells, facilitated microvasculature regeneration, and restored the ability of endometrium to receive the embryo and support its development to a viable stage. Our findings indicate that BM-MSCs may support uterine tissue regeneration. PMID:24680661

  11. Autologous transplantation of CD34(+) bone marrow derived mononuclear cells in management of non-reconstructable critical lower limb ischemia.

    PubMed

    Ismail, Ahmed M; Abdou, Said M; Aty, Hassan Abdel; Kamhawy, Adel H; Elhinedy, Mohammed; Elwageh, Mohammed; Taha, Atef; Ezzat, Amal; Salem, Hoda A; Youssif, Said; Salem, Mohamed L

    2016-08-01

    Patients with a decrease in limb perfusion with a potential threat to limb viability manifested by ischemic rest pain, ischemic ulcers, and/or gangrene are considered to have critical limb ischemia (CLI). Because of this generally poor outcome, there is a strong need for attempting any procedure to save the affected limb. The aim of this work is to evaluate the possibility to use stem cell therapy as a treatment option for patients with chronic critical lower limb ischemia with no distal run off. This study includes 20 patients with chronic critical lower limb ischemia with no distal run off who are unsuitable for vascular or endovascular option. These patients underwent stem cell therapy (SCT) by autologous transplantation of bone marrow derived mononuclear cells. 55 % of patients treated with SCT showed improvement of the rest pain after the first month, 60 % continued improvement of the rest pain after 6 months, 75 % after 1 year and 80 % after 2 years and continued without any deterioration till the third year. Limb salvage rate after STC was 80 % after the first year till the end of the second and third years. SCT can result in angiogenesis in patients with no-option CLI, providing a foundation for the application of this therapy to leg ischemia. PMID:25511801

  12. 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

  13. 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

  14. [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. PMID:7534002

  15. STAT3 mutations identified in human hematologic neoplasms induce myeloid malignancies in a mouse bone marrow transplantation model

    PubMed Central

    Couronné, Lucile; Scourzic, Laurianne; Pilati, Camilla; Valle, Véronique Della; Duffourd, Yannis; Solary, Eric; Vainchenker, William; Merlio, Jean-Philippe; Beylot-Barry, Marie; Damm, Frederik; Stern, Marc-Henri; Gaulard, Philippe; Lamant, Laurence; Delabesse, Eric; Merle-Beral, Hélène; Nguyen-Khac, Florence; Fontenay, Michaëla; Tilly, Hervé; Bastard, Christian; Zucman-Rossi, Jessica; Bernard, Olivier A.; Mercher, Thomas

    2013-01-01

    STAT3 protein phosphorylation is a frequent event in various hematologic malignancies and solid tumors. Acquired STAT3 mutations have been recently identified in 40% of patients with T-cell large granular lymphocytic leukemia, a rare T-cell disorder. In this study, we investigated the mutational status of STAT3 in a large series of patients with lymphoid and myeloid diseases. STAT3 mutations were identified in 1.6% (4 of 258) of patients with T-cell neoplasms, in 2.5% (2 of 79) of patients with diffuse large B-cell lymphoma but in no other B-cell lymphoma patients (0 of 104) or patients with myeloid malignancies (0 of 96). Functional in vitro assays indicated that the STAT3Y640F mutation leads to a constitutive phosphorylation of the protein. STA21, a STAT3 small molecule inhibitor, inhibited the proliferation of two distinct STAT3 mutated cell lines. Using a mouse bone marrow transplantation assay, we observed that STAT3Y640F expression leads to the development of myeloproliferative neoplasms with expansion of either myeloid cells or megakaryocytes. Together, these data indicate that the STAT3Y640F mutation leads to constitutive activation of STAT3, induces malignant hematopoiesis in vivo, and may represent a novel therapeutic target in some lymphoid malignancies. PMID:23872306

  16. 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

  17. Autologous peripheral blood stem cell transplantation in malignancies involving bone marrow.

    PubMed

    Sica, S; Leone, G; Teofili, L; Pierelli, L; Menichella, G; Di Mario, A; Paoloni, A; Iovino, M S; Bizzi, B

    1991-03-01

    Six patients suffering from refractory malignancies (3 NHL, 1 MM, 1 AML, 1 neuroblastoma) received high dose of chemotherapy and autologous peripheral blood stem cell transplantation (APBSCT). The recruitment of PBSC was performed using conventional salvatage schedules of therapy. The patients received a median of 8.69 MNC/kg bw and 20.87 CFU-GM x 10(4)/kg bw. Prompt engraftment occurred in all patients and the median number of days to achieve WBC greater than 1 x 10(9)/l was 16.5 (range 7-26), PMN greater than 0.5 x 10(9)/l was 21.5 (range 6-37) and PLTs greater than 50 x 10(9)/l was 17.5 (range 4-31). Four patients achieved a complete remission. One patient (neuroblastoma) died of progressive disease after a partial response. One patient died in relapse because of drug related toxicity. PMID:1677914

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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. PMID:9498711

  4. 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

  5. Pneumonitis in bone marrow transplant recipients results from a local immune response.

    PubMed Central

    Milburn, H J; Du Bois, R M; Prentice, H G; Poulter, L W

    1990-01-01

    Eighteen recipients of allogeneic T cell-depleted bone marrow who developed 22 episodes of interstitial pneumonitis were investigated by bronchoalveolar lavage for the cause of pneumonitis. The cells obtained were examined using a panel of monoclonal antibodies with immunocytochemical techniques to identify lymphocyte subsets and the presence of surface molecules indicative of lymphocyte activation. The majority of patients had an excess of lymphocytes in lavage and most of these cells were positively stained with the McAb recognizing the CD8 antigen (suppressor/cytotoxic type T cells). Although the proportions of CD4+ (helper type) T cells were below normal, the absolute numbers were within normal limits, thus the CD4:CD8 ratio was consistently 1:1 or less. A large proportion of the CD8+ cells displayed HLA-DR molecules (RFDR1+), interleukin-2 (IL-2) receptors (CD25+) and high concentration of CD7 antigen (RFT2+). Further analysis revealed that most CD8+ cells were CD5+ (RFT1+) yet a large proportion (20-40%) were CD5-. A majority of CD8+ cells was also CD38+ (RFT10+) and Leu7+. No clear correlation between the emergence of a raised proportion of activated CD8+ cells and diagnosed cytomegalovirus infection was found. These results demonstrate, however, that cells with the phenotype of the resident T cells of the bronchial epithelium (CD8+CD5-) emerge to the air spaces and express activation markers. This raises the intriguing paradox of an aggressive local immune response occurring in an otherwise immunosuppressed group of patients. PMID:2201468

  6. Autologous Bone Marrow Mononuclear Cell Transplantation in Patients with Decompensated Alcoholic Liver Disease: A Randomized Controlled Trial

    PubMed Central

    Spahr, Laurent; Chalandon, Yves; Terraz, Sylvain; Kindler, Vincent; Rubbia-Brandt, Laura; Frossard, Jean-Louis; Breguet, Romain; Lanthier, Nicolas; Farina, Annarita; Passweg, Jakob; Becker, Christoph D.; Hadengue, Antoine

    2013-01-01

    Objective Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD). We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT) improved liver function in decompensated ALD. Design 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy) were randomized early after hospital admission to standard medical therapy (SMT) alone (n = 30), including steroids in patients with a Maddrey’s score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28). Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC) compartment. Results Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64%) from the BMMCT group and 18 patients (53%) from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49–5.4) in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001), and proliferating HPC tended to decrease in both groups (−35 and −33%, respectively). Conclusion Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. Trial Registration

  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. Low-dose irradiation prior to bone marrow transplantation results in ATM activation and increased lethality in Atm-deficient mice.

    PubMed

    Pietzner, J; Merscher, B M; Baer, P C; Duecker, R P; Eickmeier, O; Fußbroich, D; Bader, P; Del Turco, D; Henschler, R; Zielen, S; Schubert, R

    2016-04-01

    Ataxia telangiectasia is a genetic instability syndrome characterized by neurodegeneration, immunodeficiency, severe bronchial complications, hypersensitivity to radiotherapy and an elevated risk of malignancies. Repopulation with ATM-competent bone marrow-derived cells (BMDCs) significantly prolonged the lifespan and improved the phenotype of Atm-deficient mice. The aim of the present study was to promote BMDC engraftment after bone marrow transplantation using low-dose irradiation (IR) as a co-conditioning strategy. Atm-deficient mice were transplanted with green fluorescent protein-expressing, ATM-positive BMDCs using a clinically relevant non-myeloablative host-conditioning regimen together with TBI (0.2-2.0 Gy). IR significantly improved the engraftment of BMDCs into the bone marrow, blood, spleen and lung in a dose-dependent manner, but not into the cerebellum. However, with increasing doses, IR lethality increased even after low-dose IR. Analysis of the bronchoalveolar lavage fluid and lung histochemistry revealed a significant enhancement in the number of inflammatory cells and oxidative damage. A delay in the resolution of γ-H2AX-expression points to an insufficient double-strand break repair capacity following IR with 0.5 Gy in Atm-deficient splenocytes. Our results demonstrate that even low-dose IR results in ATM activation. In the absence of ATM, low-dose IR leads to increased inflammation, oxidative stress and lethality in the Atm-deficient mouse model. PMID:26752140

  9. 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

  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. Transplantation of bone marrow stromal cells enhances infiltration and survival of CNP and Schwann cells to promote axonal sprouting following complete transection of spinal cord in adult rats

    PubMed Central

    Ding, Peng; Yang, Zhiyong; Wang, Weimin; Wang, Jinkun; Xue, Liping

    2014-01-01

    This study aimed to investigate the roles of bone marrow stromal cells (BMSCs) in promoting axonal regeneration after complete transection of spinal cord in adult rats. Transplantation was done 9 days after injury. Only a few BMSCs were detected at the injury site 8 weeks after transplantation, yet there was robust growth of axons. The scarcity of surviving BMSCs may attribute to the adverse conditions in their ambient environment. In this connection, the immediate accumulation of a large number of macrophages/reactive microglia following BMSCs transplantation and subsequent cavitation of tissues may be detrimental to their survival. An unexpected finding following BMSCs transplantation was the marked increase in the nestin, GFAP, NF200, olig 3 and CNP positive cells at the injury site. Immunoelectron microscopy showed CNP cells were oval or fibroblast-like and had multiple perineurial-like compartments with long extending filopodia. The spatial relationship between regenerating axons and CNP-positive cells was also confirmed by double immunofluorescence staining. Our results suggest that transplantation of BMSCs elicits the influx and survival of local cells including CNP positive cells and Schwann cells into injury site, which provide structural support for the axon regeneration and remyelination after spinal cord injury. PMID:24936216

  12. The effect of a polyurethane-based reverse thermal gel on bone marrow stromal cell transplant survival and spinal cord repair

    PubMed Central

    Ritfeld, Gaby J; Rauck, Britta; Novosat, Tabitha L; Park, Daewon; Patel, Pavan; Roos, Raymund AC; Wang, Yadong; Oudega, Martin

    2014-01-01

    Cell therapy for nervous tissue repair is limited by low transplant survival. We investigated the effects of a polyurethane-based reverse thermal gel, poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU) on bone marrow stromal cell (BMSC) transplant survival and repair using a rat model of spinal cord contusion. Transplantation of BMSCs in ESHU at three days post-contusion resulted in a 3.5-fold increase in BMSC survival at one week post-injury and a 66% increase in spared nervous tissue volume at four weeks post-injury. These improvements were accompanied by enhanced hindlimb motor and sensorimotor recovery. In vitro, we found that ESHU protected BMSCs from hydrogen peroxide-mediated death, resulting in a four-fold increase in BMSC survival with two-fold fewer BMSCs expressing the apoptosis marker, caspase 3 and the DNA oxidation marker, 8-Oxo-deoxyguanosine. We argue that ESHU protected BMSCs transplanted is a spinal cord contusion from death thereby augmenting their effects on neuroprotection leading to improved behavioral restoration. The data show that the repair effects of intraneural BMSC transplants depend on the degree of their survival and may have a widespread impact on cell-based regenerative medicine. PMID:24331711

  13. Successful management of EBV-PTLD in allogeneic bone marrow transplant recipient by virological-immunological monitoring of EBV infection, prompt diagnosis and early treatment.

    PubMed

    Chiereghin, Angela; Bertuzzi, Clara; Piccirilli, Giulia; Gabrielli, Liliana; Squarzoni, Diego; Turello, Gabriele; Ferioli, Martina; Sessa, Mariarosaria; Bonifazi, Francesca; Zanoni, Lucia; Sabattini, Elena; Lazzarotto, Tiziana

    2016-02-01

    Epstein-Barr virus-related post-transplant lymphoproliferative disorder (EBV-PTLD) is an uncommon, but frequently fatal, complication after allogeneic hematopoietic stem cell transplant. Prospective post-transplant virological and immunological monitoring allowed to successfully manage a patient who developed both polymorphic and monomorphic, "diffuse large B-cell lymphoma like", as an EBV-PTLD, 65days after allogeneic bone marrow transplant. Early detection of significant increase in EBV DNA level in patient's peripheral blood (peak of viral load equal to 119,039copies/mL whole blood, +56day after transplant) led to administration of pre-emptive anti-CD20 monoclonal antibody (rituximab) and close clinical monitoring. After one week, physical exam revealed laterocervical adenopathy. Histopathologic features, immunohistochemical characterization and in situ hybridization study allowed to establish a diagnosis of EBV-related PTLD. Immunological monitoring showed no EBV-specific T-cell responses during EBV replication, thus potentially explaining the occurrence of high EBV load with subsequent PTLD development. A total of four doses of anti-CD20 monoclonal antibody were administered and at the end of the treatment, EBV infection was cleared and imaging technique showed complete disease remission. In conclusion, the early use of anti-CD20 monoclonal antibody proved to be a safe and effective treatment strategy for EBV-PTLD. Moreover, combined virological-immunological monitoring of EBV infection may more accurately assess patients at higher risk for EBV-PTLD. PMID:26687013

  14. 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

  15. Transplant of bone marrow and cord blood hematopoietic stem cells in pediatric practice, revisited according to the fundamental principles of bioethics.

    PubMed

    Burgio, G R; Locatelli, F

    1997-06-01

    The two most widely used sources of hematopoietic stem cells for allogeneic transplants in pediatric practice are bone marrow (BM) and cord blood (CB). While bone marrow transplantation (BMT) is reaching its 30th year of application, human umbilical cord blood transplantation (HUCBT) is approaching its 10th. Although these procedures have basically the same purpose, a number of biological differences distinguish them. In particular, the intrinsically limited quantity of CB stem cells and their immunological naiveté confer peculiar characteristics to these hematopoietic progenitors. From a bioethical point of view, the problems which have repeatedly been raised when the BM donor is a child are well-known. Different but no less important ethical problems are raised when one considers HUCBT; in this regard the most important issues are the easier propensity of programming a CB donor in comparison with a BM donor (clearly due to the shorter time interval needed to collect the hematopoietic progenitors); the in utero HLA-typing; the implication of employing 'blood belonging to a neonate' for a third party; the need to perform a number of investigations both on the CB of the donor and on the mother and the implications that the discovery of disease may have for them, but also the need to establish banks for storing CB, with the accompanying administration and management problems. All these different aspects of UCBT will be discussed in the light of the four fundamental and traditional principles of bioethics, namely autonomy, nonmaleficence, beneficence and justice. PMID:9208108

  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. 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

  18. The origin of IgG production and homogeneous IgG components after allogeneic bone marrow transplantation.

    PubMed

    van Tol, M J; Gerritsen, E J; de Lange, G G; van Leeuwen, A M; Jol-van der Zijde, C M; Oudeman-Gruber, N J; de Vries, E; Radl, J; Vossen, J M

    1996-01-15

    Pediatric recipients (n = 25) of an allogeneic bone marrow (BM) graft were selected on the basis of informative IgG allotype (Gm) differences between the BM donor and the recipient. To investigate the kinetics of the appearance of IgG of donor origin and the disappearance of IgG of recipient origin, G1m and G2m allotype levels were quantified in sera obtained at regular intervals between 3 months and 5 years after BM transplantation (BMT). For this quantification, a dot immunobinding assay (DIBA) has been developed. In 19 of 22 informative recipients, the Gm allotype distribution had reached the range of values expected on the basis of the Gm phenotype of the donor within 6 months after BMT. Remarkably, IgG of recipient origin persisted in 15 of 18 informative recipients until last follow up, ie, for several years after BMT. In addition to the origin of total IgG production, the origin of homogeneous IgG components (H-IgG) appearing after BMT was investigated. H-IgG of donor origin could be detected as early as 3 weeks after BMT, but also H-IgG of recipient origin were present in 8 of 13 informative recipients for a period of up to 1 year after BMT. We conclude that host-type IgG-producing cells were not eradicated by the (myeloablative) conditioning regimen and persisted in a high number of graft recipients. It is our hypothesis that lack of graft-versus-host disease (GVHD) in the majority of these recipients results in the persistence of IgG-producing cells of host origin. These observations may be relevant for the evaluation of patients who received allogeneic BMT for the treatment of multiple myeloma. PMID:8555508

  19. 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

  20. 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. PMID:26301968

  1. A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis.

    PubMed Central

    Kern, W V; Hay, B; Kern, P; Marre, R; Arnold, R

    1994-01-01

    Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications. PMID:8203838

  2. 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.

  3. 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

  4. HLA-Identical Sibling Compared With 8/8 Matched and Mismatched Unrelated Donor Bone Marrow Transplant for Chronic Phase Chronic Myeloid Leukemia

    PubMed Central

    Arora, Mukta; Weisdorf, Daniel J.; Spellman, Stephen R.; Haagenson, Michael D.; Klein, John P.; Hurley, Carolyn K.; Selby, George B.; Antin, Joseph H.; Kernan, Nancy A.; Kollman, Craig; Nademanee, Auayporn; McGlave, Philip; Horowitz, Mary M.; Petersdorf, Effie W.

    2009-01-01

    Purpose Transplantation of hematopoietic stem cells from an unrelated donor (URD) is an option for many patients who do not have an HLA-identical sibling donor (MSD). Current criteria for the selection of URDs include consideration for HLA alleles determined by high resolution typing methods, with preference for allele-matched donors. However, the utility and outcome associated with transplants from URDs compared with those from MSDs remains undefined. Patients and Methods We examined clinical outcome after patients received bone marrow transplants (BMTs) from MSDs; HLA-A, -B, -C, and DRB1 allele-matched URDs (8/8); and HLA-mismatched URDs in a homogeneous population of patients with chronic myeloid leukemia (CML) in first chronic phase (CP1) where a strong allogeneic effect and hence a lower risk of relapse is anticipated. Transplantation outcomes were compared between 1,052 URD and 3,514 MSD BMT recipients with CML in CP1. Results Five-year overall survival and leukemia-free survival (LFS) after receipt of BMTs from 8/8 matched URDs were worse than those after receipt of BMTs from MSDs (5-year survival, 55% v 63%; RR, 1.35; 95% CI, 1.17 to 1.56; P < .001; LFS, 50% v 55%; RR, 1.21; 95% CI, 1.06 to 1.40; P = .006). Survival was progressively worse with greater degrees of mismatch. Similar and low risk of relapse were observed after receipt of transplant from either MSD or URD. Conclusion In this homogeneous cohort of good risk patients with CML in CP1, 5-year overall survival and LFS after receipt of transplant from 8/8 allele-matched donors were modestly though significantly worse than those after receipt of transplant from MSDs. Additive adverse effects of multilocus mismatching are not well tolerated and should be avoided if possible. PMID:19224849

  5. The Effect of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation on Allodynia and Hyperalgesia in Neuropathic Animals: A Systematic Review with Meta-Analysis.

    PubMed

    Hosseini, Mostafa; Yousefifard, Mahmoud; Aziznejad, Heidar; Nasirinezhad, Farinaz

    2015-09-01

    Stem cell transplantation has been considered a possible therapeutic method for neuropathic pain. However, no quantitative data synthesis of stem cell therapy for neuropathic pain exists. Therefore, the present systematic review and meta-analysis assessed the efficacy of bone marrow mesenchymal stem cell (BMMSC) transplantation on alleviating pain symptoms in animal models of neuropathic pain. In the present meta-analysis, controlled animal studies assessing the effect of administrating BMMSC on neuropathic pain were included through an extensive literature search of online databases. After collecting data, effect sizes were computed and the standardized mean difference (SMD) with 95% confidence interval (CI) was entered in all analyses. Random-effects models were used for data analysis. Sensitivity and subgroup analyses were performed to investigate expected or measured heterogeneity. Finally, 14 study were included. The analyses showed that BMMSC transplantation lead to significant improvement on allodynia (SMD = 2.06; 95% CI, 1.09 to 3.03; I(2) = 99.7%; P < .001). The type of neuropathy (P = .036), time between injury and intervention (P = .02), and the number of transplanted cells (P = .023) influence the improvement of allodynia after BMMSC transplantation. BMMSC transplantation has no effect on hyperalgesia (SMD = .3; 95% CI, -1.09 to 1.68; I(2) = 100%; P < .001) unless it occurs during the first 4 days after injury (P = .02). The present systematic review with meta-analysis suggests that BMMSC transplantation improves allodynia but does not have any significant effect on hyperalgesia unless it is given during the first 4 days after injury. PMID:25985918

  6. Effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation

    SciTech Connect

    Almaraz, R.; Ballinger, W.; Sachs, D.H.; Rosenberg, S.A.

    1983-02-01

    Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments. The addition of as few as 3 X 10(4) peripheral mononuclear cells to the marrow from exsanguinated donors uniformly led to lethal GVHD. /sup 51/Cr-labeled cell traffic studies revealed that prior exsanguination of marrow donors led to about a 70% reduction in the number of circulating mononuclear cells contaminating the bone marrow at the time of marrow harvest. This decrease in contaminating peripheral cells was calculated to be in the appropriate range to account for the decreased GVHD seen when marrow from exsanguinated donors was used. It thus appears that peripheral cells contaminating marrow can be an important factor in causing lethal GVHD in allogeneic radiation chimeras.

  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. 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.

  9. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT).

    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; 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

    2015-06-01

    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

  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. 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

  12. 2', 3'-Cyclic nucleotide 3'-phosphodiesterase cells derived from transplanted marrow stromal cells and host tissue contribute to perineurial compartment formation in injured rat spinal cord.

    PubMed

    Cao, Qiong; Ding, Peng; Lu, Jia; Dheen, S Thameem; Moochhala, Shabbir; Ling, Eng-Ang

    2007-01-01

    Transdifferentiation of transplanted marrow stromal cells (MSCs) and reactive changes of glial cells in a completely transected rat spinal cord were examined. Marrow stromal cells exhibited 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) at the plasma membrane and this has allowed their identification after transplantation by immunoelectron microscopy. In the control rats, the lesion site showed activated microglia/neural macrophages and some elongated cells, whose cytoplasm was immunoreactive for CNP. Cells designated as CNP1 and apparently host-derived expressed CXCR4. In experimental rats receiving MSCs transplantation, CNP1 cells were increased noticeably. This was coupled with the occurrence of a different subset of CNP cells whose plasma membrane was CNP-immunoreactive and expressed CXCR4. These cells, designated as CNP2, enclosed both myelinated and unmyelinated neurites thus assuming a spatial configuration resembling that of Schwann cells. A remarkable feature was the extensive ramifications of CNP1 cells with long filopodia processes delineating the CNP2 cells and their associated neurites, forming many perineurial-like compartments. Present results have shown that CNP2 cells considered to be MSCs-derived can transform into cells resembling Schwann cells based on their spatial relation with the regenerating nerve fibers, whereas the CNP1 glial cells participate in formation of perineurial compartments, probably serving as conduits to guide the nerve fiber growth. The chemotactic migration of CNP cells either derived from host tissue or MSCs bearing CXCR4 may be attracted by stromal derived factor-1alpha (SDF-1alpha) produced locally. The coordinated cellular interaction between transplanted MSCs and local glial cells may promote the growth of nerve fibers through the lesion site. PMID:17061258

  13. In vivo formation of bone and hematopoietic territories by transplanted human bone marrow stromal cells generated in medium with and without osteogenic supplements

    PubMed Central

    Kuznetsov, Sergei A; Mankani, Mahesh H; Robey, Pamela Gehron

    2011-01-01

    Autologous transplantation of human bone marrow stromal cells (BMSCs) has been successfully used for bone reconstruction. However, in order to advance this approach into the mainstream of bone tissue engineering, the conditions for BMSC cultivation and transplantation must be optimized. In a recent report, cultivation with dexamethasone (Dex) significantly increased bone formation by human BMSCs in vivo. Based on this important conclusion, we analyzed the data accumulated by our laboratory where human BMSCs have been routinely generated using media both with and without a combination of two osteogenic supplements: Dex at 10-8M and ascorbic acid phosphate (AscP) at 10-4M. Our data demonstrate that for 22 out of 24 donors, BMSC strains propagated with and without Dex/AscP formed similar amounts of bone in vivo. Thus, human BMSCs do not appear to need to be induced to osteogenic differentiation ex vivo prior to transplantation. Similarly, for 12 of 14 donors, BMSC strains cultured with and without Dex/AscP formed hematopoietic territories to a comparable extent. While Dex/AscP did not increase bon