Science.gov

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. 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

  14. 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

  15. 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

  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. 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

  1. 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

  2. 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

  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. 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

  5. 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

  6. 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

  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. 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

  18. 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

  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. 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.

  2. 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.

  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. 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

  8. 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

  9. 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

  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. 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

  17. [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

  18. 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.

  19. 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

  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. [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

  5. 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

  6. 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…

  7. 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,…

  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. 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

  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. 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

  8. 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

  9. 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.

  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. 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

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

    SciTech Connect

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

    2013-04-15

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

  14. 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. 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

  17. 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

  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. [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

  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. 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

  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. 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

  14. 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.

  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. 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

  17. 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

  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. 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

  3. 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

  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. 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)

  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. 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

  10. 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

  11. 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

  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. 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.

  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. 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

  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. 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

  2. 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

  3. 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

  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. 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

  8. 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

  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. 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

  14. 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.

  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. 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

  18. 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

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  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. 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.

  16. 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).

  17. 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

  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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  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. 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

  14. 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

  15. 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

  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. 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

  20. 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

  1. 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

  2. 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

  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. 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

  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. 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.

  10. 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