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  1. Bone marrow transplant

    MedlinePlus

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

  2. Bone marrow transplant - discharge

    MedlinePlus

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

  3. Marrow transplantation for leukemia

    SciTech Connect

    Thomas, E.D.

    1981-07-01

    Marrow transplantation for selected patients with leukemia, as for patients with severe combined immunologic deficiency or severe aplastic anemia, has now become an accepted clinical procedure. For patients with acute leukemia who have relapsed after achieving a remission of chemotherapy, marrow grafting from an identical twin or an HLA-identical sibling has now been demonstrated to produce median remissions as long as or longer than any reported for combination chemotherapy. In contrast to chemotherapy, marrow transplantation offers the possibility of cure for a small but significant fraction of these patients. Marrow transplantation for patients with ANL in first remission has now resulted in median survivals much longer than any reported with chemotherapy. Although it now appears that more than 50% of these patients can be cured with marrow transplantation, a much longer follow-up is indicated since some patients who achieve a complete remission with combination chemotherapy are now living for a long time, and some of these patients (less than 20%) may also be cured. Current intensive research with new modalities such as interferon, Acyclovir, Cyclosporin A, and monoclonal antibodies can reasonably be expected to improve the overall results of marrow transplantation.

  4. Tuberculosis in pediatric oncology and bone marrow transplantation patients.

    PubMed

    Cruz, Andrea T; Airewele, Gladstone; Starke, Jeffrey R

    2014-08-01

    Five children with malignancies (3 hematologic, 1 medulloblastoma, 1 hepatoblastoma) and one bone marrow transplant patient were treated for tuberculosis over a 30-year period. Three had pulmonary disease, 3 disseminated tuberculosis, and 1 had scrofula. Four of five had positive tuberculin skin tests, cultures were positive in 5/6 children. One child died of disseminated TB after engraftment, and one child had hepatotoxicity likely related to tuberculosis therapy. All cases were potentially preventable had they been screened due to established risk factors of foreign birth (4/6) or parental foreign birth (2/6). All children should be screened for latent tuberculosis before chemotherapy.

  5. Allogeneic Marrow Transplantation in Patients With Severe Systemic Sclerosis

    PubMed Central

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

    2010-01-01

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

  6. Coping patterns among bone marrow transplant patients: a hermeneutical inquiry.

    PubMed

    Shuster, G F; Steeves, R H; Onega, L; Richardson, B

    1996-08-01

    Bone marrow transplantation (BMT) has recently become the treatment of choice for a number of malignancies. This procedure is highly technical, involving the use of radiation and chemotherapy to destroy the patient's diseased bone marrow and with it functions of the entire immune system. It is a process with toxic effects that are experienced by all patients to varying degrees. A great deal of research related to the physiological aspects of this procedure has already been done, but considerably fewer studies have examined the psychosocial aspects of the BMT procedure from the patient's perspective. Knowledge about how BMT patients understand this process and cope with its effects is important information for nurses taking care of these patients. The purpose of the study was to describe in depth the patterns of meaning employed by patients in the hospital as they coped with the experience of their BMT. Eleven patients were interviewed from one to four times a week throughout their hospitalization. Hermeneutic analysis was used to identify five major themes: physiological functioning, alertness, attitude, social relationships, and spirituality. Implications from the findings for nursing practice are discussed.

  7. Overview of marrow transplantation

    SciTech Connect

    Thomas, E.D.

    1985-12-01

    Bone marrow transplantation is now an accepted form of therapy for many hematologic disorders including aplastic anemia, genetically determined diseases and malignant diseases, particularly leukemia, and for rescue of patients given intensive chemoradiotherapy for malignant disease. The donor may be a healthy identical twin, a family member or even an unrelated person. Selection is made on the basis of human leukocyte antigen tissue typing. Intensive chemoradiotherapy is used to suppress patients' immune systems to facilitate engraftment and destroy diseased marrow. Transfusion of platelets, erythrocytes and granulocytes (or all of these), antibiotic coverage and protection from infection are necessary during the pancytopenic period. Survival rates vary considerably depending on a patient's disease, clinical state and age. Patients with aplastic anemia transplanted early in the course of their disease have a survival rate of approximately 80%. Patients with acute lymphoblastic leukemia are usually transplanted in a second or subsequent remission and have a survival rate of 25% to 40%. Patients with acute nonlymphoblastic leukemia in remission have survivals ranging from 45% to 70%. More than 200 patients in the chronic phase of chronic granulocytic leukemia have been transplanted with survival ranging from 50% to 70%. Complications of marrow transplantation include marrow graft rejection, graft-versus-host disease, immunologic insufficiency and the possibility of recurrence of the leukemia. 14 references.

  8. A patient with progressive multiple myeloma treated successfully with arsenic trioxide after allogeneic bone marrow transplantation.

    PubMed

    Gesundheit, B; Shapira, M Y; Ackerstein, A; Resnik, I B; Bitan, M; Or, R

    2007-01-01

    Multiple myeloma (MM) is an incurable progressive disease. Many therapeutic options are available to delay progression, including autologous and allogeneic bone marrow transplantation. At advanced stages, MM is often refractory to treatment. We report a heavily pretreated patient with graft-versus-host disease after bone marrow transplantations, treated at a terminal stage with a modified protocol for arsenic trioxide (ATO). This patient with poor clinical status tolerated the treatment very well. He had a remarkable clinical response and achieved complete remission. The mechanisms of ATO are presented and the potential role of ATO for MM is discussed.

  9. Busulfan and total body irradiation as antihematopoietic stem cell agents in the preparation of patients with congenital bone marrow disorders for allogenic bone marrow transplantation

    SciTech Connect

    Parkman, R.; Rappeport, J.M.; Hellman, S.; Lipton, J.; Smith, B.; Geha, R.; Nathan, D.G.

    1984-10-01

    The capacity of busulfan and total body irradiation to ablate hematopoietic stem cells as preparation for the allogeneic bone marrow transplantation of patients with congenital bone marrow disorders was studied. Fourteen patients received 18 transplants; busulfan was used in the preparatory regimen of eight transplants and total body irradiation in the regimens of six transplants. Sustained hematopoietic ablation was achieved in six of eight patients prepared with busulfan and in all six patients prepared with total body irradiation. Three patients prepared with total body irradiation died with idiopathic interstitial pneumonitis, whereas no patients receiving busulfan developed interstitial pneumonitis. The optimal antihematopoietic stem cell agent to be used for the preparation of patients with congenital bone marrow disorder for bone marrow transplantation is not certain.

  10. 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

  11. Special considerations for the patient undergoing allogeneic or autologous bone marrow transplantation.

    PubMed

    Hiemenz, J W; Greene, J N

    1993-10-01

    Improvements in the diagnosis, treatment, and prevention of infectious complications of bone marrow transplantation over the past two decades have markedly reduced the morbidity and mortality of this procedure. We are now able to begin early empiric antibiotic coverage with less toxic, but equally effective, antibacterial agents. Once believed to be uniformly fatal, complications such as CMV pneumonia are now considered treatable in at least half the cases with a combination of intravenous immunoglobulin and ganciclovir. Although probably the most controversial, prophylactic therapy has improved the outcome of patients undergoing bone marrow transplantation. The appropriate setting, agents to use, dose, and dose intervals will require further study in coming years. In the introduction to this article, we attempted to outline what is known about the immunobiology of bone marrow transplantation. A clear understanding of this process helps us recognize and anticipate the infectious complications encountered in this population of patients. It may also allow clinicians to focus more on immune augmentation as a means of prevention, as has been attempted with the newly available cytokines and the use of intravenous immunoglobulin infusions. Despite improvements in diagnosis, treatment, and prevention, infectious complications remain the leading cause of morbidity and mortality in the patient undergoing bone marrow transplantation. Future studies are required in this area to build on the successes of the last two decades.

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

    PubMed

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

    2001-12-15

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

  13. Neurologic complications of bone marrow, stem cell, and organ transplantation in patients with cancer.

    PubMed

    Rosenfeld, Myrna R; Pruitt, Amy

    2006-06-01

    Bone marrow and peripheral blood stem cell transplantation are part of the standard of care for a variety of oncologic and non-oncologic disorders and are associated with a large spectrum of neurologic complications. These complications may arise at any time during and after the transplantation process, especially in subjects requiring chronic immunosuppression, and are most frequently related to infections, cerebrovascular or metabolic events, and toxicity from radiation or chemotherapy. Due to the unique circumstances and treatments surrounding each step in the transplantation process, there is a higher incidence of some neurologic complications during discrete time periods. Being aware of the temporal relationship of the neurologic disorder within the transplantation process can therefore facilitate diagnosis and institution of appropriate therapy. Neurologic complications after solid organ transplantation are often due to similar mechanisms as in patients after bone marrow and stem cell transplantation although there are several complications unique to these patients such as transmission of infectious agents by the donated organ. For these patients, the clinician needs to have a high index of suspicion that the neurologic problem is related to the transplant.

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

    PubMed

    Wonitzki, C; Hoffmann, F A

    1989-01-01

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

  15. 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.

  16. Longitudinal neurophysiologic studies in a patient with metachromatic leukodystrophy following bone marrow transplantation.

    PubMed

    Dhuna, A; Toro, C; Torres, F; Kennedy, W R; Krivit, W

    1992-10-01

    We describe a girl with late infantile metachromatic leukodystrophy. The patient has been followed up with serial neurologic and neurophysiologic examinations for 8 years following bone marrow transplantation, which she underwent when she was 4 3/4 years old. Her older sister died from metachromatic leukodystrophy at the age of 8 years, whereas our patient has retained significant cognitive and motor skills. Serial neurophysiologic studies initially demonstrated continued deterioration after the bone marrow transplantation, but since then, most results have remained stable or improved. Although, to our knowledge, there have been no previous serial studies of metachromatic leukodystrophy, individual case studies suggest that these findings in our patient are very unusual. With the advent of possible treatment for this condition, there is a need for further serial neurophysiologic studies to characterize the natural progression and the possible detection of progression or reversal with treatment.

  17. 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.

  18. Multiple Eruptive Sebaceous Hyperplasia Secondary to Cyclosporin in a Patient with Bone Marrow Transplantation

    PubMed Central

    Cortés, Begonia; Kaya, Gürkan

    2016-01-01

    Many cutaneous complications have been described in patients treated with cyclosporin. Alterations of the pilosebaceous unit such as hypertrichosis are particularly frequent. However, the occurrence of sebaceous hyperplasia is exceptional. These lesions seem to be specific to cyclosporin rather than secondary to immunosuppression. Here, we report an exceptional case of eruptive and disseminated sebaceous hyperplasia arising in a bone marrow transplant recipient only a few months after starting immunosuppressive treatment with cyclosporin. PMID:27990417

  19. 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 ...

  20. Evaluating the patients with thalassemia major for long-term endocrinological complications after bone marrow transplantation.

    PubMed

    Aldemir-Kocabaş, Bilge; Tezcan-Karasu, Gülsün; Bircan, Iffet; Bircan, Oğuz; Aktaş-Samur, Anıl; Yeşilipek, Mehmet Akif

    2014-10-01

    The aim of this study was to evaluate the endocrinological complications of the patients with thalassemia major (TM) who underwent bone marrow transplantation (BMT) and followed-up more than two years in our center, prospectively. "BMT group" consisted of 41 patients with TM. The mean age was 12.4 ± 5.4 years and transplantation age was mean 7.5 ± 4.9 years. Post-BMT follow-up lasted from 24 to 122 months (mean 65.07 months). Also, 32 TM patients with similar age group and same history of transfusion and chelation therapy were recruited for the study as "control (C) group". The weight SDS score after transplantation was found better than before transplantation (p = 0.010). There was a negative correlation between height SDS and BMT age (p = 0.008). The height SDS scores were better in patients whose BMT age was under seven years old compared to those older than seven years old (p = 0.02). Z-scores of femur neck and L2-4 vertebrae DEXA were decreased (p = 0.032, p = 0.0001) and incidence of insulin resistance increased (p = 0.01) in patients with increased BMT age. The risk of gonadal insufficiency was significantly lower in the patients who underwent BMT <7 years of age (p = 0.009). There was no statistically significant relationship between BMT age and complications such as hypothyroidism, hypoparathyroidism, and adrenal insufficiency. The patients with TM should be evaluated for transplantation in early stage of the disease, especially before the age of seven years. Because the BMT cannot correct the endocrinological complications of TM completely, the patients should be followed up regularly after the transplantation.

  1. Disseminated Fusariosis in a Bone Marrow Transplant Patient

    PubMed Central

    De Pinho, Debora Braga; Fernandes, Louise Leal; Carvalho Barreiros, Maria Da Gloria; Quintella, Leonardo Pereira

    2012-01-01

    The authors present a case report involving an immunocompromised patient with fusariosis, an often fatal fungal infection in this group of patients. This mycosis needs to be recognized and treated in the initial phases, although this does not guarantee improvement. PMID:23277804

  2. 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.

  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. Autologous bone marrow transplantation in patients with subacute and chronic spinal cord injury.

    PubMed

    Syková, Eva; Homola, Ales; Mazanec, Radim; Lachmann, Hynek; Konrádová, Simona Langkramer; Kobylka, Petr; Pádr, Radek; Neuwirth, Jirí; Komrska, Vladimír; Vávra, Vladimir; Stulík, Jan; Bojar, Martin

    2006-01-01

    Stem cell transplants into spinal cord lesions may help to improve regeneration and spinal cord function. Clinical studies are necessary for transferring preclinical findings from animal experiments to humans. We investigated the transplantation of unmanipulated autologous bone marrow in patients with transversal spinal cord injury (SCI) with respect to safety, therapeutic time window, implantation strategy, method of administration, and functional improvement. We report data from 20 patients with complete SCI who received transplants 10 to 467 days postinjury. The follow-up examinations were done at 3, 6, and 12 months after implantation by two independent neurologists using standard neurological classification of SCI, including the ASIA protocol, the Frankel score, the recording of motor and somatosensory evoked potentials, and MRI evaluation of lesion size. We compared intra-arterial (via catheterization of a. vertebralis) versus intravenous administration of all mononuclear cells in groups of acute (10-30 days post-SCI, n=7) and chronic patients (2-17 months postinjury, n=13). Improvement in motor and/or sensory functions was observed within 3 months in 5 of 6 patients with intra-arterial application, in 5 of 7 acute, and in 1 of 13 chronic patients. Our case study shows that the implantation of autologous bone marrow cells appears to be safe, as there have been no complications following implantation to date (11 patients followed up for more than 2 years), but longer follow-ups are required to determine that implantation is definitively safe. Also, we cannot yet confirm that the observed beneficial effects were due to the cell therapy. However, the outcomes following transplantation in acute patients, and in one chronic patient who was in stable condition for several months prior to cell implantation, are promising. It is evident that transplantation within a therapeutic window of 3-4 weeks following injury will play an important role in any type of stem cell

  5. 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.

  6. Kinetics of erythrogenesis after bone marrow transplantation.

    PubMed

    Lazarus, H M; Chahine, A; Lacerna, K; Wamble, A; Iaffaldano, C; Straight, M; Rabinovitch, A; Schimenti, K J; Jacobberger, J

    1992-04-01

    To determine the kinetics of bone marrow erythrogenesis after bone marrow transplantation, the authors counted reticulocytes (by blood smear and flow cytometry) and compared those data with neutrophil and platelet recovery in 23 consecutive bone marrow transplant patients. The earliest indication of marrow recovery after allogeneic and autologous bone marrow transplantation was defined as the second increasing cell count after the lowest recorded count, provided that the trend continued upward. Recovery of marrow function was detected earlier in 10 of 23 patients using reticulocyte counts than by either neutrophil or platelet count alone. Specifically, in 8 of these 10 patients, recovery of erythropoiesis was determined earlier by flow cytometric examination than by the blood smear method. On the other hand, combining the data using the earliest value of platelet, neutrophil, and reticulocyte counts indicated that the mean day of recovery in our patient population was determined to be 12.1 +/- 4 days after marrow infusion. In patients undergoing autologous and allogeneic bone marrow transplantation, serial neutrophil and reticulocyte count determinations are complementary in early clinical detection of successful engraftment.

  7. 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.

  8. Origin of enriched regulatory t cells in patients receiving combined kidney/bone marrow transplantation to induce transplantation tolerance.

    PubMed

    Sprangers, Ben; DeWolf, Susan; Savage, Thomas M; Morokata, Tatsuaki; Obradovic, Aleksandar; LoCascio, Samuel A; Shonts, Brittany; Zuber, Julien; Lau, Sai Ping; Shah, Ravi; Morris, Heather; Steshenko, Valeria; Zorn, Emmanuel; Preffer, Frederic I; Olek, Sven; Dombkowski, David M; Turka, Laurence A; Colvin, Robert; Winchester, Robert; Kawai, Tatsuo; Sykes, Megan

    2017-03-01

    We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ) and, in one tolerant subject, conversion from non-Tregs. Among recovering conventional T cells, central memory CD4(+) and CD8(+) cells predominated. A large fraction of the T cell clones detected in post-transplant biopsy specimens by TCR sequencing were detected in the peripheral blood and were not donor-reactive. Our results suggest that enrichment of Tregs by new thymic emigration and lymphopenia-driven peripheral proliferation in the early post-transplant period may contribute to tolerance following CKBMT. Furthermore, most conventional T cell clones detected in immunologically quiescent post-transplant biopsies appear to be circulating cells in the microvasculature rather than infiltrating T cells. This article is protected by copyright. All rights reserved.

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

    PubMed

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

    2000-01-01

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

  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.

  11. Allogeneic and Autologous Bone Marrow Transplantation in CHAMPUS 1989-1993 A Total Patient Treatment Episode Analysis.

    DTIC Science & Technology

    1993-10-22

    AUTOLOGOUS BONE MARROW TRANSPLANTATION IN CHAMPUS 1989-1993 A TOTAL PATIENT TREATMENT EPISODE ANALYSIS DR. SCOTT A. OPTENBERG, GM-15 Chief, Health Care...Analysis Division Directorate of Health Care Studies and Analyses DR. JAMES M. THOMPSON, LTC, USAF, MC (RET) Former Director, Bone Marrow...Department of the Air Force position unless so designated by other authorized documents. Authors’ current addresses: Directorate of Health Care

  12. 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.

  13. The platelet-refractory bone marrow transplant patient: prophylaxis and treatment of bleeding.

    PubMed

    Benson, K; Fields, K; Hiemenz, J; Zorsky, P; Ballester, O; Perkins, J; Elfenbein, G

    1993-10-01

    Refractoriness to platelet transfusions remains a significant problem for oncology patients, occurring in 30% to 70% of multiply transfused recipients with bone marrow failure. Nonimmune causes are often present and include disseminated intravascular coagulation, concurrent use of amphotericin B, infection, presence of palpable spleen, use of antibacterial antibiotics, bleeding, veno-occlusive disease, and fever. Immune causes are also commonly responsible for refractoriness, with HLA alloimmunization dominating the list of immune factors. HLA antibodies can be identified in 25% to 30% of transfused leukemia patients and can be present in as many as 80% of aplastic anemia patients. Developing a consistent approach to managing these refractory patients is essential to preventing and treating bleeding manifestations. An HLA type should be obtained for all patients anticipated to have chronic transfusion requirements. Screening for lymphocytotoxic antibodies can confirm suspected HLA alloimmunization. Histocompatible platelets (cross-match compatible and HLA matched) should be provided for all patients with HLA antibodies. A number of other therapeutic modalities have been used in an effort to manage the alloimmunized patient; most of these methods have had little or no proven benefit. When bleeding develops in the alloimmunized patient, there are few therapeutic choices. If histocompatible platelets are unavailable or unsuccessful, massive platelet transfusions of pooled platelet concentrates are commonly used, although this practice is of no proven benefit. While antifibrinolytic agents have been available for over 30 years, they are only recently being applied to control bleeding in chronic thrombocytopenia. We have successfully managed bleeding episodes in thrombocytopenic bone marrow transplant recipients with the use of epsilon aminocaproic acid. A number of these patients were platelet refractory with demonstrable platelet antibodies. Platelet refractoriness

  14. Long term Outcome of Non-Ablative Booster Bone Marrow Transplantation in Patients with Severe Combined Immunodeficiency

    PubMed Central

    Teigland, Claire L.; Parrott, Roberta E.; Buckley, Rebecca H.

    2013-01-01

    Severe combined immunodeficiency (SCID) is a fatal syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T-cells. Immune reconstitution can be achieved through non-ablative related donor bone marrow transplantation. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7 percent of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63 percent) are alive for up to 28 years. Age at initial transplantation was found to have a significant effect on outcome (mean of 194 days old for patients currently alive, versus a mean of 273 days old for those now deceased, p=0.0401). Persistent viral infection was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T and B cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Non-ablative booster bone marrow transplantation can be life-saving for SCID. PMID:23396406

  15. Bone marrow transplant – children - discharge

    MedlinePlus

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

  16. Pituitary abscess after autologous bone marrow transplantation.

    PubMed

    Leff, R S; Martino, R L; Pollock, W J; Knight, W A

    1989-05-01

    The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

  17. Allogeneic bone marrow mesenchymal stem cell transplantation in patients with UDCA-resistant primary biliary cirrhosis.

    PubMed

    Wang, Li; Han, Qin; Chen, Hua; Wang, Ke; Shan, Guang-liang; Kong, Fang; Yang, Yun-jiao; Li, Yong-zhe; Zhang, Xuan; Dong, Fen; Wang, Qian; Xu, Dong; Hu, Zhao-jun; Wang, Shi-hua; Keating, Armand; Bi, Ya-lan; Zhang, Feng-chun; Zhao, Robert Chun-hua

    2014-10-15

    The objective of this study was to evaluate the safety and efficacy of allogeneic bone marrow mesenchymal stromal/stem cell transplantation (BM-MSCT) for patients with ursodeoxycholic acid (UDCA)-resistant primary biliary cirrhosis (PBC). Ten patients were enrolled in this trial of BM-MSCT. All patients were permitted to concurrently continue their previous UDCA treatment. The efficacy of BM-MSCT in UDCA-resistant PBC was assessed at various time points throughout the 12-month follow up. No transplantation-related side effects were observed. The life quality of the patients was improved after BM-MSCT as demonstrated by responses to the PBC-40 questionnaire. Serum levels of ALT, AST, γ-GT, and IgM significantly decreased from baseline after BM-MSCT. In addition, the percentage of CD8+ T cells was reduced, while that of CD4+CD25+Foxp3+ T cells was increased in peripheral lymphocytic subsets. Serum levels of IL-10 were also elevated. Notably, the optimal therapeutic outcome was acquired in 3 to 6 months and could be maintained for 12 months after BM-MSCT. In conclusion, allogeneic BM-MSCT in UDCA-resistant PBC is safe and appears to be effective.

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

    PubMed

    Bolaños-Meade, Javier; Fuchs, Ephraim J; Luznik, Leo; Lanzkron, Sophie M; Gamper, Christopher J; Jones, Richard J; Brodsky, Robert A

    2012-11-22

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

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

    PubMed Central

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

    2012-01-01

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

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

    SciTech Connect

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

    2014-05-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

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

    PubMed

    Piras, A; Poddigue, M; Angelucci, E

    2010-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

    Fitchett, George; Berry, Donna L.

    2016-01-01

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

  6. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    PubMed Central

    Lin, Shih-Chiang; Hsieh, Pei-Ying; Shueng, Pei-Wei; Tien, Hui-Ju; Wang, Li-Ying

    2013-01-01

    To compare the outcomes of melphalan 200 mg/m2 (HDM200) and 8 Gy total marrow irradiation (TMI) delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy) in newly diagnosed symptomatic multiple myeloma (MM) Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT) were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD) regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP). In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P = 0.048). However, hematologic recovery (except for neutrophils), transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P = 0.387). As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200. PMID:24089671

  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. 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…

  9. Stem cell bone marrow transplantation in patients with metabolic storage diseases.

    PubMed

    Krivit, William

    2002-01-01

    In 1984, an initial report was published on the use of BMT for inborn errors of metabolism. Our first BMT patient had a diagnosis of Maroteaux-Lamy syndrome. She had end-stage cardiopulmonary disease at the time of the transplant and was considered likely to die within months. (69) She is still alive 2 decades later, albeit with limited pulmonary function. In 1992, experimental data demonstrated the prevention of CNS deterioration in fucosidase-deficient dogs after BMT.70 These findings have been noted in many other similar studies. (46) Ample data indicate that BMT can reconstitute the CNS in several of these diseases. Progress is continuing in reducing the morbidity and mortality. In the near future, additional advances may allow for no loss of life and no illness during the bone marrow transplantation process. There is hope that by using neonatal screening techniques, infants at risk can have metabolic storage diseases diagnosed before the diseases progress so that effective treatment can be provided. The combination of all of these advances should result in a logarithmic improvement within the next 2 decades. The plan will be to avoid any mortality or morbidity and to always provide complete engraftment that is permanent and enters all tissues completely.

  10. Catheter-Related Candidemia Caused by Candida lipolytica in a Patient Receiving Allogeneic Bone Marrow Transplantation

    PubMed Central

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

    2002-01-01

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

  11. [Acute renal failure secondary to hepatic veno-occlusive disease in a bone marrow transplant patient].

    PubMed

    Borrego, F J; Viedma, G; Pérez del Barrio, P; Gil, J M; de Santis-Scoccia, C; Ramírez Huerta, J M; Alcalá, A; Pérez Bañasco, V

    2003-01-01

    Acute renal failure following bone marrow transplantation is a frequent complication with an incidence ranging 15-30% and with high rates of morbidity and mortality. Numerous potential etiologies can be implicated as chemotherapy regimen, use of nephrotoxic antibiotics, sepsis-induced damage, cyclosporine toxicity and other especific pathologies as graft-v-host disease or veno-occlusive disease of the liver. We report the case of a 41-year-old man who underwent autologous peripheral blood stem cell transplantation and developed and acute renal failure secondary to a fatal veno-occlusive disease of the liver. Incidence, potential predisposing factors, outcome and possibilities of treatment are reviewed.

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

    PubMed

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

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

  13. The kinetics of cyclosporine and its metabolites in bone marrow transplant patients.

    PubMed Central

    Schwinghammer, T L; Przepiorka, D; Venkataramanan, R; Wang, C P; Burckart, G J; Rosenfeld, C S; Shadduck, R K

    1991-01-01

    1. The pharmacokinetics of cyclosporine (CsA) and the time course of CsA metabolites were studied in five bone marrow transplant patients after intravenous (i.v.) administration on two separate occasions and once after oral CsA administration. 2. Cyclosporine and cyclosporine metabolites were measured in whole blood by h.p.l.c. 3. Cyclosporine clearance after i.v. administration decreased from 3.9 +/- 1.7 ml min-1 kg-1 to 2.0 +/- 0.6 ml min-1 kg-1 after 14 days of treatment. The mean +/- s.d. absolute oral bioavailability of cyclosporine was 17 +/- 11%. 4. Hydroxylated CsA (M-17) was the major metabolite in blood. There were no significant differences in the mean metabolite/CsA AUC ratios between the first and second i.v. studies. 5. After oral administration, the metabolite to CsA AUC ratios were higher for most metabolites compared to those observed in the second i.v. study, suggesting a contribution of intestinal metabolism to the clearance of CsA. PMID:1777368

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

    SciTech Connect

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

    1994-09-01

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

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

    MedlinePlus

    ... and Bone Marrow Transplant Also known as hematopoietic stem cell transplant, hematopoietic cell transplant, autologous transplant, or allogeneic ... or bone marrow transplant replaces abnormal blood-forming stem cells with healthy cells. When the healthy stem cells ...

  16. Intraventricular Transplantation of Autologous Bone Marrow Mesenchymal Stem Cells via Ommaya Reservoir in Persistent Vegetative State Patients after Haemorrhagic Stroke: Report of Two Cases & Review of the Literature

    PubMed Central

    Fauzi, Asra Al; Suroto, Nur Setiawan; Bajamal, Abdul Hafid; Machfoed, Moh. Hasan

    2016-01-01

    Background: One of the most devastating diseases, stroke, is a leading cause of death and disability worldwide with severe emotional and economic consequences. The purpose of this article is mainly to report the effect of intraventricular transplantation via an Ommaya reservoir using autologous bone marrow mesenchymal stem cells (BM-MSCs) in haemorrhagic stroke patients. Case Presentations: Two patients, aged 51 and 52, bearing sequels of haemorrhagic stroke were managed by intraventricular transplantation of BM-MSCs obtained from their own bone marrow. Before the procedure, both patients were bedridden, tracheostomised, on nasogastric (NG) tube feeding and in hemiparesis. The cells were transplanted intraventricularly (20 x 106 cells/2.5 ml) using an Ommaya reservoir, and then repeated transplantations were done after 1 and 2 months consecutively. The safety and efficacy of the procedures were evaluated 3, 6 and 12 months after treatment. The National Institute of Health Stroke Scale (NIHSS) was used to evaluate the patients’ neurological status before and after treatment. No adverse events derived from the procedures or transplants were observed in the one-year follow-up period, and the neurological status of both patients improved after treatment. Conclusions: Our report demonstrates that the intraventricular transplantation of BM-MSCs via an Ommaya reservoir is safe and it improves the neurological status of post-haemorrhagic stroke patients. The repeated transplantation procedure is easier and safer to perform via a subcutaneously implanted Ommaya reservoir. Key Words: Haemorrhagic stroke, bone marrow mesenchymal stem cells (BM-MSCs), intraventricular transplantation PMID:28096634

  17. Second allogeneic hematopoietic cell transplantation for Patients with Fanconi anemia and Bone Marrow Failure

    PubMed Central

    Ayas, Mouhab; Eapen, Mary; Le-Rademacher, Jennifer; Carreras, Jeanette; Abdel-Azim, Hisham; Alter, Blanche P.; Anderlini, Paolo; Battiwalla, Minoo; Bierings, Marc; Buchbinder, David K.; Bonfim, Carmem; Camitta, Bruce M.; Fasth, Anders L.; Gale, Robert Peter; Lee, Michelle A.; Lund, Troy C.; Myers, Kasiani C.; Olsson, Richard F.; Page, Kristin M.; Prestidge, Tim D.; Radhi, Mohamed; Shah, Ami J.; Schultz, Kirk R.; Wirk, Baldeep; Wagner, John E.; Deeg, H. Joachim

    2015-01-01

    Second allogeneic hematopoietic cell transplantation (HCT) is the only salvage option for those for develop graft failure after their first HCT. Data on outcomes after second HCT in Fanconi anemia (FA) are scarce. We report outcomes after second allogeneic HCT for FA (n=81). The indication for second HCT was graft failure after the first HCT. Transplants occurred between 1990 and 2012. The timing of second transplantation predicted subsequent graft failure and survival. Graft failure was high when the second transplant occurred less than 3 months from the first. The 3-month probability of graft failure was 69% when the interval between first and second transplant was less than 3 months compared to 23% when the interval was longer (p<0.001). Consequently, survival rates were substantially lower when the interval between first and second transplant was less than 3 months, 23% at 1-year compared to 58%, when the interval was longer (p=0.001). The corresponding 5-year probabilities of survival were 16% and 45%, respectively (p=0.006). Taken together, these data suggest that fewer than half of FA patients undergoing a second HCT for graft failure are long-term survivors. There is an urgent need to develop strategies to lower graft failure after first HCT. PMID:26116087

  18. Common Cold Can Be Dangerous After Bone Marrow Transplant

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164206.html Common Cold Can Be Dangerous After Bone Marrow Transplant Rhinovirus ... 2017 TUESDAY, March 21, 2017 (HealthDay News) -- The common cold can be deadly for patients recovering from bone ...

  19. Screening for Y Chromosome Microdeletion in a Nonobstructive Azoospermic Male Patient with Allogeneic Bone Marrow Transplantation from His Sister

    PubMed Central

    Gurkan, Hakan; Kucukdurmaz, Faruk; Akman, Tolga; Aydın, Filiz; Kadioglu, Ates

    2010-01-01

    Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells. PMID:21209805

  20. Good functional outcome after prolonged postanoxic comatose myoclonic status epilepticus in a patient who had undergone bone marrow transplantation.

    PubMed

    Accardo, Jennifer; De Lisi, Domenico; Lazzerini, Paola; Primavera, Alberto

    2013-01-01

    In anoxic coma, myoclonic status epilepticus and other nonreactive epileptiform patterns are considered as signs of poor prognosis. We report the case of a good recovery in a prolonged comatose myoclonic status epilepticus (MSE) after a cardiac arrest (CA) treated with mild therapeutic hypothermia (TH) in a patient who had undergone a bone marrow transplantation for Hodgkin's lymphoma. This case emphasizes the opportunity of performing an electroencephalogram (EEG) in the acute period after an hypoxic-ischemic insult and underlines the diagnostic difficulties between MSE and Lance-Adams syndrome, which classically occurs after the patient has regained consciousness, but can also begin while the patient is still comatose or sedated. Major problems in prognostication for postarrest comatose patients will also be pointed out.

  1. [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.

  2. Allogeneic peripheral blood stem cell rescue of late graft failure after bone marrow transplantation in patients with aplastic anemia.

    PubMed Central

    Chung, Ik-Joo; Lee, Je-Jung; Park, Moo-Rim; Kook, Hoon; Cho, Sang-Hee; Hwang, Tai-Ju; Kim, Hyeoung-Joon

    2002-01-01

    We investigated the effect and outcome of allogeneic peripheral blood stem cell (PBSC) rescue for aplastic anemia (AA) patients with graft failure after allogeneic bone marrow transplantation (BMT). Seven (28%) of 25 AA patients who received BMT from HLA-identical sibling donors developed late graft failure at a median of 7 months (range, 2.0-9.3 months) after transplantation. The patients with graft failure were treated with PBSC collected from the original donor after mobilization with granulocyte-colony stimulating factor (G-CSF). The median boost dose of peripheral blood mononuclear cells was 3.1 x 10(8)/kg (range, 1.4-11.9 x 10(8)/kg). Median times to reach an absolute neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 50 x 10(9)/L were 7 days (range, 4-14 days) and 9 days (range, 3-41 days), respectively. There was sustained graft function in 6 of 7 patients, with a median follow-up duration of 3.3 yr (range, 1.0-6.2 yr). Grade-I acute graft-versus-host disease (GVHD) occurred in 2 patients, while extensive chronic GVHD developed in 3 patients. This report shows that G-CSF-mobilized allogeneic PBSC rescue is very effective in achieving complete and sustained engraftment in patients with AA after graft failure. However, more efficacious measures to prevent extensive chronic GVHD remain to be developed. PMID:12172040

  3. Catheter–Based Transendocardial Delivery of Autologous Bone-Marrow-Derived Mononuclear Cells in Patients Listed for Heart Transplantation

    PubMed Central

    Silva, Guilherme V.; Perin, Emerson C.; Dohmann, Hans F.R.; Borojevic, Radovan; Silva, Suzana A.; Sousa, Andre L.S.; Assad, Joao A.R.; Vaughn, William K.; Mesquita, Claudio T.; Belém, Luciano; Carvalho, Antonio C.; Dohmann, Hans J.F.; do Amaral, Ellen Barroso; Coutinho, Joaquim; Branco, Rodrigo; Oliveira, Edie; Willerson, James T.

    2004-01-01

    Growing evidence suggests that transplantation of autologous bone-marrow mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of ischemic myocardium. This procedure could potentially benefit transplant candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC injection, we performed a prospective, nonrandomized, open-label study in 5 heart transplant candidates with severe ischemic heart failure. Each patient underwent baseline single-photon emission computed tomography, a ramp treadmill protocol, 2-dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged electrocardiography, which were repeated at 2 and 6 months. Transendocardial delivery of ABMMNCs was done with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc each. There were no deaths, significant arrhythmias, or other major complications. The ABMMNC injection reduced the amount of ischemic myocardium (not statistically significant). More important, exercise test results improved significantly. Myocardial volume oxygen consumption increased from 10.6 ± 3 mL/kg/min (baseline) to 16.3 ± 7 mL/kg/min (2 months) and 23 ± 7 mL/kg/min (6 months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the patients were no longer eligible for cardiac transplantation. In addition, metabolic equivalents improved from 3.03 ± 0.66 (baseline) to 4.65 ± 1.99 (2 months) and 6.5 ± 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections were performed safely and resulted in improved exercise capacity. This technique may hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization. PMID:15562839

  4. Effects on oral and intestinal microfloras of norfloxacin and pefloxacin for selective decontamination in bone marrow transplant patients.

    PubMed Central

    Giuliano, M; Pantosti, A; Gentile, G; Venditti, M; Arcese, W; Martino, P

    1989-01-01

    We monitored the modifications of oral and intestinal microfloras of 10 allogeneic bone marrow recipients who received randomly either norfloxacin or pefloxacin (400 mg three times a day) as selective decontamination for infection prevention. After 1 week of treatment, in all patients members of the family Enterobacteriaceae were no longer detectable and in all but one pefloxacin-treated patient enterococci were also eliminated in the intestine. The anaerobic flora was not affected, with the exception of Bacteroides spp., markedly reduced after treatment with pefloxacin. In most patients the most striking effect was the increase in staphylococcal counts. These strains were found to be resistant to both quinolones in the study. Less consistent changes were observed in oral flora. No relevant difference could be demonstrated between the two regimens on bacterial counts either in feces or in saliva. This study shows the efficacy of both quinolones in eradicating gram-negative bacilli in the alimentary tract of bone marrow transplant patients; however, the finding of the overgrowth of resistant gram-positive organisms during treatment with these agents deserves further evaluation. PMID:2686547

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

    SciTech Connect

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

    1995-11-01

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

  6. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C.; Forman, Stephen; Somlo, George; Liu An; Schultheiss, Timothy; Radany, Eric; Palmer, Joycelynne; Stein, Anthony

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  7. 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.

  8. Safety and feasibility of transendocardial autologous bone marrow cell transplantation in patients with advanced heart disease.

    PubMed

    Fuchs, Shmuel; Kornowski, Ran; Weisz, Giora; Satler, Lowell F; Smits, Peter C; Okubagzi, Petros; Baffour, Richard; Aggarwal, Anita; Weissman, Neil J; Cerqueira, Manuel; Waksman, Ron; Serrruys, Parrick; Battler, Alexander; Moses, Jeffrey W; Leon, Martin B; Epstein, Stephen E

    2006-03-15

    The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.

  9. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation

    PubMed Central

    Zeidan, Amer M; Forde, Patrick M; Symons, Heather; Chen, Allen; Smith, B Douglas; Pratz, Keith; Carraway, Hetty; Gladstone, Douglas E; Fuchs, Ephraim J; Luznik, Leo; Jones, Richard J; Bolaños-Meade, Javier

    2014-01-01

    Background Treatment of relapse after related HLA-haploidentical T-cell replete bone marrow transplantation (haploBMT) with post-transplantation cyclophosphamide (PTCy) using haploidentical donor lymphocyte infusion (haploDLI) is not documented. Methods All patients who received haploDLI after haploBMT with PTCy between 6/2003 and 10/2012 were identified and assessed for graft-versus-host disease (GvHD) and outcomes. Results 40 patients received 52 haploDLI doses. Sixteen patients had acute myeloid leukemia, 11 had lymphomas, and 34 had nonmyeloablative conditioning prior to haploBMT. The median time from haploBMT to relapse was 183 (range, 0–1,399) days. The median age at haploDLI was 48 (range, 3–70) years. The first haploDLI doses were 1×105 CD3+ cells/kg with subsequent escalation. The most commonly used first haploDLI dose was 1×106 CD3+ cells/kg. The median follow-up after haploDLI was 7 (mean, 15.4, range, 0.5–96) months for the entire cohort, and 17.5 (mean, 28 range, 2.4–96) months for the responders. Acute GvHD developed in 10 patients (25%), 6 patients had grade 3–4, and 3 developed chronic GvHD. Twelve (30%) patients achieved a complete response (CR) with a median duration of 11.8 (mean, 22.5, range, 0.4–94) months. At last follow-up, 8 responders were alive in CR; 6 for over a year. Conclusions HaploDLI for relapse after haploBMT is associated with acceptable toxicities and can result in durable responses. PMID:24296490

  10. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation.

    PubMed

    Zeidan, Amer M; Forde, Patrick M; Symons, Heather; Chen, Allen; Smith, B Douglas; Pratz, Keith; Carraway, Hetty; Gladstone, Douglas E; Fuchs, Ephraim J; Luznik, Leo; Jones, Richard J; Bolaños-Meade, Javier

    2014-03-01

    Treatment of relapse after related HLA-haploidentical T cell-replete bone marrow transplantation (haploBMT) with post-transplantation cyclophosphamide (PTCy) using haploidentical donor lymphocyte infusion (haploDLI) is not documented. All patients who received haploDLI after haploBMT with PTCy between June 2003 and October 2012 were identified and assessed for graft-versus-host disease (GVHD) and outcomes. Forty patients received 52 haploDLI doses. Sixteen patients had acute myeloid leukemia, 11 had lymphomas, and 34 had nonmyeloablative conditioning before haploBMT. The median time from haploBMT to relapse was 183 (range, 0 to 1399) days. The median age at haploDLI was 48 (range, 3 to 70) years. The first haploDLI doses were 1 × 10(5) CD3(+) cells/kg with subsequent escalation. The most commonly used first haploDLI dose was 1 × 10(6) CD3(+) cells/kg. The median follow-up after haploDLI was 7 (mean, 15.4; range, .5 to 96) months for the entire cohort, and 17.5 (mean, 28; range, 2.4 to 96) months for the responders. Acute GVHD developed in 10 patients (25%), 6 patients had grade 3 to 4, and 3 developed chronic GVHD. Twelve (30%) patients achieved a complete response (CR) with a median duration of 11.8 (mean, 22.5; range, .4 to 94) months. At last follow-up, 8 responders were alive in CR; 6 for over a year. HaploDLI for relapse after haploBMT is associated with acceptable toxicities and can result in durable responses.

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

    PubMed Central

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

    2015-01-01

    The goal of this clinical trial was to assess the feasibility and safety of transplanting autologous bone marrow mononuclear cells into patients suffering severe embolic stroke. Major inclusion criteria included patients with cerebral embolism, age 20–75 years, National Institute of Health Stroke Scale (NIHSS) score displaying improvement of ≤5 points during the first 7 days after stroke, and NIHSS score of ≥10 on day 7 after stroke. Bone marrow aspiration (25 or 50 mL; N = 6 patients in each case) was performed 7–10 days poststroke, and bone marrow mononuclear cells were administrated intravenously. Mean total transplanted cell numbers were 2.5 × 108 and 3.4 × 108 cells in the lower and higher dose groups, respectively. No apparent adverse effects of administering bone marrow cells were observed. Compared with the lower dose, patients receiving the higher dose of bone marrow cells displayed a trend toward improved neurologic outcomes. Compared with 1 month after treatment, patients receiving cell therapy displayed a trend toward improved cerebral blood flow and metabolic rate of oxygen consumption 6 months after treatment. In comparison with historical controls, patients receiving cell therapy had significantly better neurologic outcomes. Our results indicated that intravenous transplantation of autologous bone marrow mononuclear cells is safe and feasible. Positive results and trends favoring neurologic recovery and improvement in cerebral blood flow and metabolism by cell therapy underscore the relevance of larger scale randomized controlled trials using this approach. PMID:26176265

  12. [Increased efficacy of allogenic bone marrow transplantation].

    PubMed

    Fedotenkov, A G; Danilova, L A; Ignasheva, L P

    1982-08-01

    Experiments made in vivo and vitro have demonstrated that conservation of allogeneic hemopoietic tissue with glycerin brings about a decrease in transplatation, homologous activity of T lymphocytes. Allogeneic bone marrow conserved with glycerin compares very favourably with freshly prepared allogeneic bone marrow since the transplant-versus-host reaction is attenuated under the effect of glycerin. Moreover, it shows a higher proliferative activity. The glycerin-induced reduction of the inactivating effect of lymphocytes against non-syngeneic colony-forming units enables the conserved bone marrow to be transplanted from several donors.

  13. Kinetics and biodistribution of In-111 platelets in patients with bone marrow transplants, refractory to platelet transfusions

    SciTech Connect

    Civelek, C.; Braine, H.; Scheffel, U.; Drew, H.; Koester, A.; LaFrance, N.; Kasecamp, W.; Wagner, H. Jr.

    1984-01-01

    The kinetics and biodistribution of HLA identical In-111 labeled platelets was studied in 10 leukemic patients with bone marrow transplants refractory to HLA matched platelet transfusions. Platelet survival time was short (x-bar +- SEM =1.64 +- 0.83 days). The mean recovery (extrapolated to zero time) was 29.9%, ranging from 14.2 to 63.0%. The deposition of the In-111 platelets in the liver and spleen was quantified by the geometric mean method using anterior and posterior imaging. In 3 patients liver uptake was significantly increased. The highest hepatic accumulation of In-111 occurred 2 hrs after injection (x-bar=76 +- 6% dose (SEM); at 48 hrs 62% of the dose remained in the liver. In 7 patients the spleen was the organ with the highest labeled platelet deposition. The splenic uptake of In-111 platelets in this group correlated with the spleen size (r=+0.95). At 30 min after injection 75+-6% of the dose was found in the spleen. Splenic activity decreased to 62% after 48 hrs. At the same time, In-111 liver accumulation increased from 14 to 31%. This finding suggests that In-111 may be released from the spleen and subsequently sequestered by the liver. Two patients with high splenic uptake underwent splenectomy after the In-111 platelet study. Both benefited from splenectomy in terms of platelet survival after transfusion.

  14. The costs and cost-effectiveness of allogeneic peripheral blood stem cell transplantation versus bone marrow transplantation in pediatric patients with acute leukemia.

    PubMed

    Lin, Yu-Feng; Lairson, David R; Chan, Wenyaw; Du, Xianglin L; Leung, Kathryn S; Kennedy-Nasser, Alana A; Martinez, Caridad A; Gottschalk, Stephen M; Bollard, Catherine M; Heslop, Helen E; Brenner, Malcolm K; Krance, Robert A

    2010-09-01

    In a retrospective study, we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) (n = 30) compared with bone marrow transplantation (BMT) (n = 110) in children with acute leukemia after 1 year of follow-up. Treatment success was defined as disease-free survival at 1 year posttransplantation. For patients at standard risk for disease, the treatment success rate was 57.1% for PBSCT recipients and 80.3% for BMT recipients (P = not significant [NS]). The average total cost per treatment success at 1 year in the standard-risk disease group was $512,294 for PBSCT recipients and $352,885 for BMT recipients (P = NS). For patients with high-risk disease, the treatment success rate was 18.8% for PBSCT recipients and 23.5% for BMT recipients (P = NS). The cumulative average cost was $457,078 in BMT recipients and $377,316 in PBSCT recipients (P = NS). Point estimates of the incremental cost-effectiveness ratio (ICER) indicate that in patients with standard-risk disease, allogeneic BMT had lower costs and greater effectiveness than PBSCT (ICER, -$687,108; 95% confidence interval [CI], $2.4 million to dominated). For patients with high-risk disease, BMT was more effective and more costly, and it had an ICER of $1.69 million (95% CI, $29.7 million to dominated) per additional treatment success. The comparative economic evaluation provides support for BMT in standard-risk patients, but much uncertainty precludes a clear advantage of either treatment option in patients with high-risk disease. More studies using larger and randomized controlled trials are needed to confirm the long-term cost-effectiveness of each procedure.

  15. Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia.

    PubMed

    Stein, Anthony; Palmer, Joycelynne; Tsai, Ni-Chun; Al Malki, Monzr M; Aldoss, Ibrahim; Ali, Haris; Aribi, Ahmed; Farol, Len; Karanes, Chatchada; Khaled, Samer; Liu, An; O'Donnell, Margaret; Parker, Pablo; Pawlowska, Anna; Pullarkat, Vinod; Radany, Eric; Rosenthal, Joseph; Sahebi, Firoozeh; Salhotra, Amandeep; Sanchez, James F; Schultheiss, Tim; Spielberger, Ricardo; Thomas, Sandra H; Snyder, David; Nakamura, Ryotaro; Marcucci, Guido; Forman, Stephen J; Wong, Jeffrey

    2017-04-01

    Current conditioning regimens provide insufficient disease control in relapsed/refractory acute leukemia patients undergoing hematopoietic stem cell transplantation (HSCT) with active disease. Intensification of chemotherapy and/or total body irradiation (TBI) is not feasible because of excessive toxicity. Total marrow and lymphoid irradiation (TMLI) allows for precise delivery and increased intensity treatment via sculpting radiation to sites with high disease burden or high risk for disease involvement, while sparing normal tissue. We conducted a phase I trial in 51 patients (age range, 16 to 57 years) with relapsed/refractory acute leukemia undergoing HSCT (matched related, matched unrelated, or 1-allele mismatched unrelated) with active disease, combining escalating doses of TMLI (range, 1200 to 2000 cGy) with cyclophosphamide (CY) and etoposide (VP16). The maximum tolerated dose was declared at 2000 cGy, as TMLI simulation studies indicated that >2000 cGy might deliver doses toxic for normal organs at or exceeding those delivered by standard TBI. The post-transplantation nonrelapse mortality (NRM) rate was only 3.9% (95% confidence interval [CI], .7 to 12.0) at day +100 and 8.1% (95% CI, 2.5 to 18.0) at 1 year. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 43.1% (95% CI, 29.2 to 56.3) and for grade III and IV, it was 13.7% (95% CI, 6.9 to 27.3). The day +30 complete remission rate for all patients was 88% and was 100% for those treated at 2000 cGy. The overall 1-year survival was 55.5% (95% CI, 40.7 to 68.1). The TMLI/CY/VP16 conditioning regimen is well tolerated at TMLI doses up to 2000 cGy with a low 100-day and 1-year NRM rate and no increased risk of GVHD with higher doses of radiation.

  16. Long-term clinical results of autologous bone marrow CD 133+ cell transplantation in patients with ST-elevation myocardial infarction

    NASA Astrophysics Data System (ADS)

    Kirgizova, M. A.; Suslova, T. E.; Markov, V. A.; Karpov, R. S.; Ryabov, V. V.

    2015-11-01

    The aim of the study was investigate the long-term results of autologous bone marrow CD 133+ cell transplantation in patients with primary ST-Elevation Myocardial Infarction (STEMI). Methods and results: From 2006 to 2007, 26 patients with primary STEMI were included in an open randomized study. Patients were randomized to two groups: 1st - included patients underwent PCI and transplantation of autologous bone marrow CD 133+ cell (n = 10); 2nd - patients with only PCI (n = 16). Follow-up study was performed 7.70±0.42 years after STEMI and consisted in physical examination, 6-min walking test, Echo exam. Total and cardiovascular mortality in group 1 was lower (20% (n = 2) vs. 44% (n = 7), p = 0.1 and 22% (n = 2) vs. 25% (n = 4), (p=0.53), respectively). Analysis of cardiac volumetric parameters shows significant differences between groups: EDV of 100.7 ± 50.2 mL vs. 144.40±42.7 mL, ESV of 56.3 ± 37.8 mL vs. 89.7 ± 38.7 mL in 1st and 2nd groups, respectively. Data of the study showed positive effects of autologous bone marrow CD 133+ cell transplantation on the long-term survival of patients and structural status of the heart.

  17. National Marrow Donor Program. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2014-11-30

    event. 3. Immunogenetic Studies: Increase understanding of the immunologic factors important in HSC transplantation. 4. Clinical Research... Immunology , and Transplantation DaSH Data Standards Hackathon DC Donor Center National Marrow Donor Program® N00014-13-1-0039 HLA Typing for Bone...Management Strategy ImmPort Immunology Database and Analysis Portal IND Investigational New Drug IND Improvised Nuclear Device IPR Immunobiology Project

  18. Nocardiosis after bone marrow transplantation: a retrospective study.

    PubMed

    van Burik, J A; Hackman, R C; Nadeem, S Q; Hiemenz, J W; White, M H; Flowers, M E; Bowden, R A

    1997-06-01

    To evaluate the spectrum of nocardiosis after marrow transplantation, we reviewed the medical records of 27 patients with nocardiosis who were treated at three centers, and we reviewed the findings of three cases reported in the literature. Nocardial involvement was defined as invasive nocardiosis (n = 25), colonization (n = 4), or contamination (n = 1). The median time to the diagnosis of nocardiosis after marrow transplantation was 210 days. Nocardia asteroides complex accounted for 96% of isolates. All 25 invasive infections occurred in allogeneic marrow recipients. Ten (40%) of 25 patients with invasive nocardiosis were receiving double-strength oral trimethoprimsulfamethoxazole twice weekly as prophylaxis for Pneumocystis carinii pneumonia. Treatment regimens for nocardiosis included sulfonamides; synergistic agents were also often added. The overall survival rate at 6 years was 34%; survival from the infection itself was 84%. Two of four nocardiosis-related deaths also involved other pathogens. The incidence of nocardiosis among allogeneic marrow recipients averaged 0.3% over 25 years. We conclude that nocardiosis is a rare infection that occurs later after marrow transplantation than other infections and that is marginally associated with increased mortality among long-term survivors of allogeneic marrow transplantation.

  19. Bone marrow-derived mesenchymal stem cells remain host-derived despite successful hematopoietic engraftment after allogeneic transplantation in patients with lysosomal and peroxisomal storage diseases.

    PubMed

    Koç, O N; Peters, C; Aubourg, P; Raghavan, S; Dyhouse, S; DeGasperi, R; Kolodny, E H; Yoseph, Y B; Gerson, S L; Lazarus, H M; Caplan, A I; Watkins, P A; Krivit, W

    1999-11-01

    Human bone marrow contains mesenchymal stem cells (MSCs) that can differentiate into various cells of mesenchymal origin. We developed an efficient method of isolating and culture expanding a homogenous population of MSCs from bone marrow and determined that MSCs express alpha-L-iduronidase, arylsulfatase-A and B, glucocerebrosidase, and adrenoleukodystrophy protein. These findings raised the possibility that MSCs may be useful in the treatment of storage disorders. To determine if donor derived MSCs are transferred to the recipients with lysosomal or peroxisomal storage diseases by allogeneic hematopoietic stem cell (HSC) transplantation, we investigated bone marrow derived MSCs of 13 patients 1-14 years after allogeneic transplantation. Highly purified MSCs were genotyped either by fluorescence in situ hybridization using probes for X and Y-chromosomes in gender mis-matched recipients or by radiolabeled PCR amplification of polymorphic simple sequence repeats. Phenotype was determined by the measurement of disease specific protein/enzyme activity in purified MSCs. We found that MSCs isolated from recipients of allogeneic HSC transplantation are not of donor genotype and have persistent phenotypic defects despite successful donor type hematopoietic engraftment. Whether culture expanded normal MSCs can be successfully transplanted into patients with storage diseases and provide therapeutic benefit needs to be determined.

  20. Non-myeloablative bone marrow transplantation.

    PubMed

    Ruiz-Argüelles, Guillermo J

    2003-01-01

    As a result of the evolution of knowledge in the area of allogeneic hematopoietic stem cells (HSC) transplantation, several dogmata have been broken. We now have the following information: a) successful engraftment if allogeneic HSC bone marrow ablation of the recipient is not required; b) HSC create their own space through graft-vs.-host reactions; c) several malignancies are eradicated by the graft-vs.-tumor effect; d) allografting can be conducted on an out-patient basis; e) allografting can be done in aged or debilitated individuals; f) allografting can be achieved without transfusion of blood products, and g) costs of the allografting procedures can be substantially diminished. Breaking all these dogmata has resulted in availability of HSC allografting to a larger number of individuals, thus offering true curative therapeutic options to patients who otherwise would not qualify to receive these opportunities.

  1. Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation

    SciTech Connect

    Pino Y Torres, J.L.; Bross, D.S.; Lam, W.C.; Wharam, M.D.; Santos, G.W.; Order, S.E.

    1982-08-01

    Total body irradiation is part of the preparatory regimen for allogeneic bone marrow transplantation because of its cytotoxic and immunosuppressive properties. A major toxicity of bone marrow transplantation has been interstitial pneumonitis, which may be, in part, related to the lung irradiation. One hundred and sixty-one consecutive patients receiving allogeneic bone marrow transplantation for leukemia and aplastic anemia at Johns Hopkins Hospital (1968-1979) were retrospectively studied. The present study demonstrated that lung shielding to 600 rad maximum in single dose total body irradiation, fractionation of total body irradiation in comparison to single dose total body irradiation, and absence of graft versus host disease in the leukemia patients, each reduced the risk of interstitial pneumonitis. Total body irradiation significantly reduced the leukemia recurrence rate and/or the failure of remission induction.

  2. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia.

    PubMed

    Atsuta, Yoshiko; Suzuki, Ritsuro; Nagamura-Inoue, Tokiko; Taniguchi, Shuichi; Takahashi, Satoshi; Kai, Shunro; Sakamaki, Hisashi; Kouzai, Yasushi; Kasai, Masaharu; Fukuda, Takahiro; Azuma, Hiroshi; Takanashi, Minoko; Okamoto, Shinichiro; Tsuchida, Masahiro; Kawa, Keisei; Morishima, Yasuo; Kodera, Yoshihisa; Kato, Shunichi

    2009-02-19

    We made a disease-specific comparison of unrelated cord blood (CB) recipients and human leukocyte antigen allele-matched unrelated bone marrow (BM) recipients among 484 patients with acute myeloid leukemia (AML; 173 CB and 311 BM) and 336 patients with acute lymphoblastic leukemia (ALL; 114 CB and 222 BM) who received myeloablative transplantations. In multivariate analyses, among AML cases, lower overall survival (hazard ratio [HR]=1.5; 95% confidence interval [CI], 1.0-2.0, P= .028) and leukemia-free survival (HR=1.5; 95% CI, 1.1-2.0, P= .012) were observed in CB recipients. The relapse rate did not differ between the 2 groups of AML (HR=1.2; 95% CI, 0.8-1.9, P= .38); however, the treatment-related mortality rate showed higher trend in CB recipients (HR=1.5; 95% CI, 1.0-2.3, P= .085). In ALL, there was no significant difference between the groups for relapse (HR=1.4, 95% CI, 0.8-2.4, P= .19) and treatment-related mortality (HR=1.0; 95% CI, 0.6-1.7, P= .98), which contributed to similar overall survival (HR=1.1; 95% CI, 0.7-1.6, P= .78) and leukemia-free survival (HR=1.2; 95% CI, 0.9-1.8, P= .28). Matched or mismatched single-unit CB is a favorable alternative stem cell source for patients without a human leukocyte antigen-matched related or unrelated donor. For patients with AML, decreasing mortality, especially in the early phase of transplantation, is required to improve the outcome for CB recipients.

  3. A randomized trial of roxithromycin in patients with acute leukemia and bone marrow transplant recipients receiving fluoroquinolone prophylaxis.

    PubMed Central

    Kern, W V; Hay, B; Kern, P; Marre, R; Arnold, R

    1994-01-01

    Fluoroquinolone prophylaxis in patients with profound neutropenia may be useful for preventing gram-negative bacterial infection, but it is ineffective against gram-positive bacterial infections in the bloodstream, particularly those caused by streptococci and coagulase-negative staphylococci, which appear to have emerged as significant causes of morbidity, decreased treatment efficacy, and the increased costs of empiric antimicrobial therapy. In a prospective, randomized, open trial, we evaluated the efficacy and safety of oral roxithromycin (150 mg twice daily) as additional antibacterial prophylaxis in 131 adult patients with acute leukemia and bone marrow transplant recipients receiving oral ofloxacin. In comparison with patients given ofloxacin alone, fewer patients receiving ofloxacin plus roxithromycin developed bacteremia caused by viridans group streptococci (incidence, 9 versus 0%; P = 0.03), while the incidence of bacteremia caused by other organisms, the incidence of febrile episodes from any cause, the risk of infection-associated complications (including prolonged or secondary fever, pneumonia, septic shock, need for mechanical ventilation, and/or infection-related death), and antimicrobial usage for therapy were comparable between both groups. Adverse events possibly related to the study drugs were slightly more common among the patients receiving the combination treatment (P = 0.05). Although effective for the prevention of streptococcal bacteremia, the addition of roxithromycin to a fluoroquinolone should not be used routinely as a prophylactic regimen in patients with profound neutropenia, but it might be considered and may be useful for cancer patients with a particularly high risk of streptococcal infection and related complications. PMID:8203838

  4. Serial monitoring of Mucorales DNA load in serum samples of a patient with disseminated mucormycosis after allogeneic bone marrow transplantation.

    PubMed

    Shigemura, Tomonari; Nakazawa, Yozo; Matsuda, Kazuyuki; Sano, Kenji; Yaguchi, Takashi; Motobayashi, Mitsuo; Saito, Shoji; Noda, Shunsuke; Kobayashi, Norimoto; Agematsu, Kazunaga; Honda, Takayuki; Koike, Kenichi

    2014-08-01

    Mucormycosis is a fatal complication in immunocompromised patients, and is additionally difficult to diagnose due to the lack of useful serum biomarkers. Using a quantitative PCR approach, we retrospectively analyzed Mucorales DNA load in sera collected serially from a 3-year-old patient with chronic granulomatous disease, who died of multi-organ failure probably due to dissemination of Rhizomucor pusillus, which was detected from necropsy specimens. Mucorales DNA load was below the detection limit on days 9, 2, and 4 after unrelated bone marrow transplantation. Rhizomucor DNA was first detected on day 14 (1.6 × 10(3) copies/mL), and subsequently fluctuated between 1.3 × 10(3) and 37.2 × 10(3) copies/mL until day 43. Rhizomucor achieved a peak value of 940.0 × 10(3) copies/mL on day 48 the day before death. The detection or fluctuation of Rhizomucor DNA appeared to be associated with corticosteroid dosages or C-reactive protein levels. This specific, noninvasive, and highly quantitative assay may be useful for the early diagnosis of mucormycosis and prediction of disease progression.

  5. [Rapid tapering of cyclosporine for cytogenetic relapse shortly after bone marrow transplantation in a patient with chronic myeloid leukemia].

    PubMed

    Kobayashi, Y; Nakata, M; Sato, N; Kamiya, Y; Maeda, A; Togitani, K; Kawahigashi, N; Murayama, T; Yokozawa, T; Takeyama, K; Narabayashi, M; Takenaka, T; Tobinai, K

    1998-06-01

    A 53-year-old female case of cytogenetically relapsed chronic myeloid leukemia after allogeneic bone marrow transplantation (BMT) who achieved remission by withdrawal of immunosuppressant is reported. On day 690 of this presentation she is well and alive with performance status of 100%. She had episodes of cyclic oscillation of her neutrophil count during hydroxyurea therapy lasting 1 year before transplantation. Increase of the neutrophils at the time of BMT might have contributed to her early relapse on day 207. Withdrawal of immunosuppressant was successful at least in this case.

  6. Myeloablative allogeneic hematopoietic stem cell transplantation in patients who experience relapse after autologous stem cell transplantation for lymphoma: a report of the International Bone Marrow Transplant Registry.

    PubMed

    Freytes, César O; Loberiza, Fausto R; Rizzo, J Douglas; Bashey, Asad; Bredeson, Christopher N; Cairo, Mitchell S; Gale, Robert Peter; Horowitz, Mary M; Klumpp, Thomas R; Martino, Rodrigo; McCarthy, Philip L; Molina, Arturo; Pavlovsky, Santiago; Pecora, Andrew L; Serna, Derek S; Tsai, Tsuong; Zhang, Mei-Jie; Vose, Julie M; Lazarus, Hillard M; van Besien, Koen

    2004-12-01

    Myeloablative allogeneic hematopoietic stem cell transplantation (allo-HSCT) is increasingly used in patients with lymphoma who experience disease relapse after autologous hematopoietic stem cell transplantation (auto-HSCT) because the allograft is tumor free and may induce a graft-versus-tumor effect. We analyzed 114 patients treated with this approach from 1990 to 1999 to assess disease progression, progression-free survival (PFS), and overall survival (OS). Cumulative incidence of disease progression at 3 years was 52%, whereas treatment-related mortality was 22%, lower than previously reported. Three-year probabilities of OS and PFS were 33% and 25%, respectively. With prolonged follow-up, however, nearly all patients experienced disease progression, and 5-year probabilities were 24% and 5%, respectively. Complete remission at the time of allo-HSCT and use of total body irradiation (TBI) in patients with non-Hodgkin lymphoma (NHL) were associated with lower rates of disease progression and higher rates of OS. In summary, allo-HSCT is feasible for patients with lymphoma who have relapses after auto-HSCT and can result in prolonged survival for some, but it is usually not curative. Most likely to benefit are patients who have HLA-matched sibling donors, are in remission, and have good performance status.

  7. Transplantation of umbilical cord and bone marrow-derived mesenchymal stem cells in a patient with relapsing-remitting multiple sclerosis

    PubMed Central

    Hou, Zong-liu; Liu, Ying; Mao, Xi-Hong; Wei, Chuan-yu; Meng, Ming-yao; Liu, Yun-hong; Zhuyun Yang, Zara; Zhu, Hongmei; Short, Martin; Bernard, Claude; Xiao, Zhi-cheng

    2013-01-01

    There is currently great interest in the use of mesenchymal stem cells as a therapy for multiple sclerosis with potential to both ameliorate inflammatory processes as well as improve regeneration and repair. Although most clinical studies have used autologous bone marrow-derived mesenchymal stem cells, other sources such as allogeneic umbilical cord-derived cells may provide a more accessible and practical supply of cells for transplantation. In this case report we present the treatment of aggressive multiple sclerosis with multiple allogenic human umbilical cord-derived mesenchymal stem cell and autologous bone marrow-derived mesenchymal stem cells over a 4 y period. The treatments were tolerated well with no significant adverse events. Clinical and radiological disease appeared to be suppressed following the treatments and support the expansion of mesenchymal stem cell transplantation into clinical trials as a potential novel therapy for patients with aggressive multiple sclerosis. PMID:24192520

  8. Flow cytometric evaluation of red blood cell chimerism after bone marrow transplantation in Iranian patients: a preliminary study.

    PubMed

    Shaiegan, Mojgan; Hadjati, Esmerdis; Aghaiipour, Mahnaz; Iravani, Masoud; David, Gaelle; Bernard, Daniel

    2006-10-01

    The aim of this study was to evaluate mixed red cells population and red blood cell chimerism after hematopoietic stem cell transplantation. Red blood cell chimerism after hematopoietic stem cell transplantation was analyzed using a series of fluorescein isothiocyanate-conjugated monoclonal antibodies (BioAtlantic, France) directed against ABH, Rh (D, C, E, c, e), Kell, Duffy, Kidd, and Ss antigens on blood samples of 14 patients with hematologic disorders undergoing hematopoietic stem cell transplantation, by flow cytometric method on days 15, 30, and 60 after transplantation. All patients showed expression of donor red cell antigens within days 15 - 30 after hematopoietic stem cell transplantation. Graft versus host disease and ABO incompatibility did not affect the expression of chimerism. Flow cytometric analysis is a simple, accurate, and valuable test which is of significant help in monitoring chimerism in allogeneic hematopoietic stem cell transplantation.

  9. Usefulness of bone marrow transplantation in the Hurler syndrome.

    PubMed

    Braunlin, Elizabeth A; Stauffer, Nanci R; Peters, Charles H; Bass, John L; Berry, James M; Hopwood, John J; Krivit, William

    2003-10-01

    The Hurler syndrome, an autosomal recessive storage disease of childhood, leads to death within the first decade of life from progressive deposition of glycosaminoglycans within the myointima of the coronary arteries and airways. Cardiac ultrasound findings of patients with this syndrome >10 years after successful bone marrow transplantation are described.

  10. Enteral nutrition after bone marrow transplantation

    PubMed Central

    Papadopoulou, A; MacDonald, A; Williams, M; Darbyshire, P; Booth, I

    1997-01-01

    Accepted 16 April 1997
 Nutritional insult after bone marrow transplantation (BMT) is complex and its nutritional management challenging. Enteral nutrition is cheaper and easier to provide than parenteral nutrition, but its tolerance and effectiveness in reversing nutritional depletion after BMT is poorly defined. Nutritional status, wellbeing, and nutritional biochemistry were prospectively assessed in 21 children (mean age 7.5 years; 14 boys) who received nasogastric feeding after BMT (mean duration 17 days) and in eight children (mean age 8 years, four boys) who refused enteral nutrition and who received dietetic advice only.
 Enteral nutrition was stopped prematurely in eight patients. Greater changes in weight and mid upper arm circumference were observed in the enteral nutrition group, while positive correlations were found between the duration of feeds and increase in weight and in mid upper arm circumference. Vomiting and diarrhoea had a similar incidence in the two groups, while fever and positive blood cultures occurred more frequently in the dietetic advice group. Diarrhoea occurring during enteral nutrition was not associated with fat malabsorption, while carbohydrate malabsorption was associated with rotavirus infection only. Enteral feeding did not, however, affect bone marrow recovery, hospital stay, general wellbeing, or serum albumin concentrations. Hypomagnesaemia, hypophosphataemia, zinc and selenium deficiency were common in both groups. In conclusion, enteral nutrition, when tolerated, is effective in limiting nutritional insult after BMT. With existing regimens nutritional biochemistry should be closely monitored in order to provide supplements when required.

 PMID:9301351

  11. The bone marrow microenvironment is similarly impaired in allogeneic hematopoietic stem cell transplantation patients with early and late poor graft function.

    PubMed

    Kong, Y; Wang, Y-T; Hu, Y; Han, W; Chang, Y-J; Zhang, X-H; Jiang, Z-F; Huang, X-J

    2016-02-01

    Poor graft function (PGF), including early and late PGF, is a serious complication following allotransplant. We recently reported that bone marrow microenvironment abnormalities may occur in cases of late PGF. Whether these abnormalities occur in early PGF remains unknown. To answer this question, we performed a nested case-control study comparing cellular elements of the bone marrow microenvironment in 10 subjects with early PGF, 30 subjects with late PGF and 40 subjects without PGF. Bone marrow endosteal cells, perivascular cells and endothelial cells were analyzed by flow cytometry and by hematoxylin-eosin and immunohistochemical staining in situ. Subjects with early and late PGF had similar abnormalities in these cell types compared with transplant recipients without PGF. However, none of the aforementioned elements of the bone marrow microenvironment were significantly different between early and late PGF patients. Our data suggest that similar abnormalities in the bone marrow microenvironment may occur in early and late PGF post allotransplant. Cellular approaches, such as the administration of mesenchymal stem cells, promise to be beneficial therapeutic strategies in patients with early or late PGF.

  12. A Melanoma Brain Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: First Evidence for Fusion in Human Cancer

    PubMed Central

    Duvall, Eric; Spoelstra, Nicole; Klump, Vincent; Sznol, Mario; Cooper, Dennis; Spritz, Richard A.; Chang, Joseph T.; Pawelek, John M.

    2013-01-01

    Background Tumor cell fusion with motile bone marrow-derived cells (BMDCs) has long been posited as a mechanism for cancer metastasis. While there is much support for this from cell culture and animal studies, it has yet to be confirmed in human cancer, as tumor and marrow-derived cells from the same patient cannot be easily distinguished genetically. Methods We carried out genotyping of a metastatic melanoma to the brain that arose following allogeneic bone-marrow transplantation (BMT), using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor cells were isolated free of leucocytes by laser microdissection, and tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 14 autosomal STR loci and the sex chromosomes. Results All alleles in the donor and patient pre-BMT lymphocytes were found in tumor cells. The alleles showed disproportionate relative abundances in similar patterns throughout the tumor, indicating the tumor was initiated by a clonal fusion event. Conclusions Our results strongly support fusion between a BMDC and a tumor cell playing a role in the origin of this metastasis. Depending on the frequency of such events, the findings could have important implications for understanding the generation of metastases, including the origins of tumor initiating cells and the cancer epigenome. PMID:23840523

  13. 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.

  14. 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.

  15. Lenalidomide After Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancers

    ClinicalTrials.gov

    2016-12-26

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Alkylating Agent-Related Acute Myeloid Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Post-Transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Richter Syndrome; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  16. 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.

  17. Treatment of complete spinal cord injury patients by autologous bone marrow cell transplantation and administration of granulocyte-macrophage colony stimulating factor.

    PubMed

    Park, Hyung Chun; Shim, Yoo Shik; Ha, Yoon; Yoon, Seung Hwan; Park, So Ra; Choi, Byung Hyune; Park, Hyun Seon

    2005-01-01

    Transplantation of bone marrow cells into the injured spinal cord has been found to improve neurologic functions in experimental animal studies. However, it is unclear whether bone marrow cells can similarly improve the neurologic functions of complete spinal cord injury (SCI) in human patients. To address this issue, we evaluated the therapeutic effects of autologous bone marrow cell transplantation (BMT) in conjunction with the administration of granulocyte macrophage-colony stimulating factor (GM-CSF) in six complete SCI patients. BMT in the injury site (1.1 x 10(6) cells/microL in a total of 1.8 mL) and subcutaneous GM-CSF administration were performed on five patients. One patient was treated with GM-CSF only. The follow-up periods were from 6 to 18 months, depending on the patients. Sensory improvements were noted immediately after the operations. Sensory recovery in the sacral segment was noted mainly 3 weeks to 7 months postoperatively. Significant motor improvements were noted 3 to 7 months postoperatively. Four patients showed neurologic improvements in their American Spiral Injury Association Impairment Scale (AIS) grades (from A to C). One patient improved to AIS grade B from A and the last patient remained in AIS grade A. No immediate worsening of neurologic symptoms was found. Side effects of GMCSF treatment such as a fever (>38 degrees C) and myalgia were noted. Serious complications increasing mortality and morbidity were not found. The follow-up study with magnetic resonance imaging 4-6 months after injury showed slight enhancement within the zone of BMT. Syrinx formation was not definitely found. BMT and GM-CSF administration represent a safe protocol to efficiently manage SCI patients, especially those with acute complete injury. To demonstrate the full therapeutic value of this protocol, long-term and more comprehensive case-control clinical studies are required.

  18. Blood and Bone Marrow Hematopoietic Stem Cells for Transplantation: A Comparative Review.

    PubMed

    Janssen; Hiemenz; Fields; Zorsky; Ballester; Goldstein; Elfenbein

    1994-05-01

    Classical bone marrow transplantation collects bone marrow from a normal individual. This is infused into a patient rendered aplastic by high-dose chemoradiotherapy. Shortcomings include a limited donor pool and morbidity and mortality from graft-vs-host and graft rejection phenomena. Autologous marrow transplantation, in which the marrow of the patient to be transplanted is harvested, cryopreserved, and stored until needed, is not so constrained. Although marrow cannot be collected from some individuals due to hypocellularity, fibrosis, or infiltration with malignant disease, the presence of peripheral blood stem cells in the circulation allows these individuals to be treated with autologous transplantation therapy. It has been postulated that these hematopoietic progenitors have advantages over bone marrow collected stem cells, including safer and less expensive collections and accelerated rates of hematopoietic recovery following high-dose therapy and stem cell reinfusion.

  19. Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia.

    PubMed

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

    2011-07-01

    We compared outcomes of patients with severe aplastic anemia (SAA) who received granulocyte-colony stimulating factor (G-CSF)-stimulated bone marrow (G-BM) (n = 78), unstimulated bone marrow (BM) (n = 547), or peripheral blood progenitor cells (PBPC) (n = 134) from an HLA-matched sibling. Transplantations occurred in 1997 to 2003. Rates of neutrophil and platelet recovery were not different among the 3 treatment groups. Grade 2-4 acute graft-versus-host disease (aGVHD) (relative risk [RR] = 0.82, P = .539), grade 3-4 aGVHD (RR = 0.74, P = .535), and chronic GVHD (cGVHD) (RR = 1.56, P = .229) were similar after G-BM and BM transplants. Grade 2-4 aGVHD (RR = 2.37, P = .012) but not grade 3-4 aGVHD (RR = 1.66, P = .323) and cGVHD (RR = 5.09, P < .001) were higher after PBPC transplants compared to G-BM. Grade 2-4 (RR = 2.90, P < .001), grade 3-4 (RR = 2.24, P = .009) aGVHD and cGVHD (RR = 3.26, P < .001) were higher after PBPC transplants compared to BM. Mortality risks were lower after transplantation of BM compared to G-BM (RR = 0.63, P = .05). These data suggest no advantage to using G-BM and the observed higher rates of aGVHD and cGVHD in PBPC recipients warrants cautious use of this graft source for SAA. Taken together, BM is the preferred graft for HLA-matched sibling transplants for SAA.

  20. Immunological analysis of a patient with hepatitis B virus (HBV) reactivation after bone marrow transplantation.

    PubMed

    Kowazaki, Yuka; Osawa, Yosuke; Imamura, Jun; Ohashi, Kazuteru; Sakamaki, Hisashi; Kimura, Kiminori

    2015-01-01

    Patients with resolved hepatitis B virus (HBV) infection undergoing chemo- or immunosuppressive therapy are at potential risk for HBV reactivation. To determine whether the host immune response contributes to liver injury, we performed an immunological analysis of a patient with HBV reactivation. Consistent with the detection of HBV DNA in the sera, the number of polyclonal HBV-specific cytotoxic T lymphocytes (CTLs) gradually increased; however, the number of CD4(+)CD25(+) regulatory T cells (Treg) decreased. The interaction between HBV-specific CTLs and CD4(+)CD25(+) Treg is an important determinant of liver injury during HBV reactivation. Therefore, monitoring the number of these cells might be a useful modality for the diagnosis of acute hepatitis resulting from HBV reactivation.

  1. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation

    PubMed Central

    Mohty, M; Malard, F; Abecassis, M; Aerts, E; Alaskar, A S; Aljurf, M; Arat, M; Bader, P; Baron, F; Bazarbachi, A; Blaise, D; Ciceri, F; Corbacioglu, S; Dalle, J-H; Dignan, F; Fukuda, T; Huynh, A; Masszi, T; Michallet, M; Nagler, A; NiChonghaile, M; Okamoto, S; Pagliuca, A; Peters, C; Petersen, F B; Richardson, P G; Ruutu, T; Savani, B N; Wallhult, E; Yakoub-Agha, I; Duarte, R F; Carreras, E

    2016-01-01

    Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation. PMID:27183098

  2. Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation.

    PubMed

    Mohty, M; Malard, F; Abecassis, M; Aerts, E; Alaskar, A S; Aljurf, M; Arat, M; Bader, P; Baron, F; Bazarbachi, A; Blaise, D; Ciceri, F; Corbacioglu, S; Dalle, J-H; Dignan, F; Fukuda, T; Huynh, A; Masszi, T; Michallet, M; Nagler, A; NiChonghaile, M; Okamoto, S; Pagliuca, A; Peters, C; Petersen, F B; Richardson, P G; Ruutu, T; Savani, B N; Wallhult, E; Yakoub-Agha, I; Duarte, R F; Carreras, E

    2016-07-01

    Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.

  3. Post-5-fluorouracil human marrow: stem cell characteristics and renewal properties after autologous marrow transplantation.

    PubMed

    Stewart, F M; Temeles, D; Lowry, P; Thraves, T; Grosh, W W; Quesenberry, P J

    1993-05-01

    The effect of 5-fluorouracil (5-FU) pretreatment on human bone marrow (BM) progenitor/stem cells and recovery of hematopoiesis after autologous marrow transplant was studied. Twenty-one patients were treated with 5-FU (15 mg/kg to 45 mg/kg) intravenously (IV) for 1 to 3 days administered 6 to 22 days before BM harvest. Post-FU marrow was infused into 15 patients after high-dose cyclophosphamide, carmustine (BCNU), and VP-16 (CBV). Seventeen patients (historical controls) were treated with CBV and autologous BM transplantation but did not receive 5-FU before marrow harvest. The groups were comparable for diagnosis and prior therapy. In the 5-FU-treated group and control group, median recovery times for platelet count to 50,000/mm3 were 20 and 30 days, respectively (P = .007), and for platelet count to 100,000/mm3, 23 and 38 days, respectively (P = .007), while neutrophil recovery was not significantly altered. In vitro cultures with 1 to 7 growth factors (interleukin-1 [IL-1], IL-3, IL-4, IL-6, colony-stimulating factor-1 [CSF-1], granulocyte-macrophage colony-stimulating factor [GM-CSF], and G-CSF) were performed. In 8 of 10 patients whose marrow was studied before and after 5-FU treatment, the numbers of CFU-C responsive to the combination of GM-CSF and IL-3 was increased 6.15-fold by 5-FU pretreatment. In 4 of these patients, thymidine suicide of GM-CSF- and IL-3-stimulated CFU-C ranged from 17% to 42%. High proliferative potential colony-forming cell (HPP-CFC) was observed in low frequency in normal marrow and patient's marrow before 5-FU treatment. In 11 of 16 patients pretreated with 5-FU, increased numbers of HPP-CFC were noted. GM-CSF and IL-3 interacted synergistically to stimulate HPP-CFC. Multifactor combinations, especially GM-CSF + G-CSF + IL-3 + IL-6 + IL-1 + CSF-1 did not increase total colony count or classic HPP-CFC but did result in altered morphology, producing huge, loose colonies. The marrow from patients pretreated with 5-FU is enriched with

  4. Ultrasound imaging as the basis of a clinical diagnosis of systemic bartonellosis in a patient after bone marrow transplantation. A case report

    PubMed Central

    Goździk, Jolanta; Woźniak, Magdalena; Czogała, Wojciech

    2016-01-01

    Infections in immunocompromised patients after hematopoietic stem cell transplantation can have a severe and atypical course. Some opportunistic pathogens are difficult to detect in microbiological tests, and that is why treatment success depends on an accurate clinical diagnosis. This article presents a case of a 7-year-old girl with severe aplastic anemia treated with bone marrow transplantation with post-transplantation period complicated by persistent, hectic fever, with peak episodes of 39–40°C, lasting several weeks. Repeated microbiological tests failed to reveal the etiological agent, and empirical anti-infective treatment was ineffective. In the fourth week of fever, imaging showed multiple foci resembling abscesses in the patient's internal organs and, subsequently, in soft tissues. The characteristics of these changes and data concerning environmental exposure led to the clinical diagnosis of cat scratch disease (bartonellosis) with multi-organ involvement and enabled the targeted treatment to be implemented. Fever subsided and organ lesions regressed. In this case, repeated ultrasound imaging was the basic diagnostic tool that helped arrive at a correct diagnosis and implement effective treatment of this life-threatening complication after hematopoietic stem cell transplantation. PMID:27446604

  5. Successful pregnancy and delivery via in vitro fertilization with cryopreserved and thawed embryo transfer in an acute myeloid leukemia patient after allogeneic bone marrow transplantation.

    PubMed

    Nakajima, Yuki; Kuwabara, Hideyuki; Kishimoto, Kumiko; Numata, Ayumi; Motohashi, Kenji; Tachibana, Takayoshi; Tanaka, Masatsugu; Yamashita, Naoki; Ishigatsubo, Yoshiaki; Fujisawa, Shin

    2015-04-01

    As the number of young long-term survivors of hematopoietic stem cell transplantation (HSCT) for acute leukemia continues to increase, post-transplant infertility is becoming a significant concern. HSCT, particularly with cyclophosphamide and total body irradiation conditioning, is known to cause secondary premature ovarian failure, resulting in infertility. To preserve post-transplant fertility, several methods have been proposed, including in vitro fertilization (IVF) with embryo cryopreservation. Due to the aggressiveness of acute leukemia, however, patients have little chance to undergo egg harvesting and IVF before they must begin receiving chemotherapy. To the best of our knowledge, there have been no detailed reports of successful pregnancy after HSCT using IVF with embryo cryopreservation and transfer in a patient with acute myeloid leukemia. Here, we report the case of a 42-year-old woman with acute myeloid leukemia who became pregnant 2 years and 2 months after allogeneic bone marrow transplantation via IVF-embryo transfer with an egg collected after induction therapy and delivered a full-term healthy infant.

  6. 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.

  7. Opportunistic infections after blood and marrow transplantation.

    PubMed

    Wingard, J R

    1999-03-01

    Opportunistic infections are major causes of morbidity and mortality following bone marrow transplantation. Technological advances in stem cell procurement, the introduction of hematologic growth factors to speed engraftment, the development of new immunosuppressive regimens to control graft-versus-host disease (GVHD), the development of technology to perform graft engineering with removal of T lymphocytes in toto or subpopulations of T lymphocytes, the use of molecular techniques to optimize donor and recipient matching, advances in blood banking, and development of international donor registries, are among the various factors that have led to tremendous changes in transplant practices. Because of such changes in transplant practices, along with the advent of new antimicrobial agents, and development of infection control measures affecting pathogen exposure, alterations in the interplay between host and potential pathogens have occurred. Shifts in the incidence and types of opportunistic pathogens are taking place. Several historically important infectious syndromes are today well controlled; others have diminished in importance early after transplant but are more problematic at a later time; new emerging pathogens are being recognized due to selection pressures from antimicrobial usage and new hosts, such as recipients of alternate donor allogeneic transplant procedures, with even more profound and prolonged immune suppression. Such shifts and new syndromes pose continuing new challenges to the transplant clinician.

  8. Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older.

    PubMed

    Konuma, Takaaki; Tsukada, Nobuhiro; Kanda, Junya; Uchida, Naoyuki; Ohno, Yuju; Miyakoshi, Shigesaburo; Kanamori, Heiwa; Hidaka, Michihiro; Sakura, Toru; Onizuka, Makoto; Kobayashi, Naoki; Sawa, Masashi; Eto, Tetsuya; Matsuhashi, Yoshiko; Kato, Koji; Ichinohe, Tatsuo; Atsuta, Yoshiko; Miyamura, Koichi

    2016-05-01

    Older recipient and donor age were associated with higher incidences of severe graft-versus-host disease (GVHD) and mortality after allogeneic hematopoietic stem cell transplantation from matched sibling donors (MSDs) and matched unrelated donors. Since a lower incidence of severe GVHD is advantageous in unrelated cord blood transplantation (CBT), a higher incidence of GVHD using older MSDs could be overcome using cord blood for older patients. We retrospectively analyzed Japanese registration data of 2,091 patients with acute myeloid leukemia, acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome aged 50 years or older who underwent MSD bone marrow transplantation (BMT) (n = 319), MSD peripheral blood stem cell transplantation (PBSCT) (n = 462), or unrelated CBT (n = 1,310) between 2007 and 2012. Median age of MSD was 56 (range, 38-74) years. Compared with CBT, the risk of developing extensive chronic GVHD was higher after BMT (hazard ratio [HR], 2.00; P = 0.001) or PBSCT (HR, 2.38; P < 0.001), and transplant-related mortality was lower after BMT (HR, 0.61; P < 0.001) or PBSCT (HR, 0.63; P < 0.001). Relapse rates were not significant difference between three groups. Although overall mortality was lower after BMT (HR, 0.67; P < 0.001) or PBSCT (HR, 0.75; P = 0.002) compared with CBT, the rates of a composite endpoint of GVHD-free, relapse-free survival (GRFS) were not significant difference between three groups. These data showed that MSDs remain the best donor source for older patients, but CBT led to similar GRFS to BMT and PBSCT.

  9. 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

  10. Overcoming psychosocial and developmental barriers to blood and marrow transplantation (BMT) in an adolescent/young adult (AYA) transgender patient with chronic myelogenous leukemia.

    PubMed

    Khazal, Sajad; Abdel-Azim, Hisham; Kapoor, Neena; Mahadeo, Kris M

    2014-11-01

    Adolescents/young adults (AYAs) afflicted with cancer face unique barriers to potentially standard curative therapies, such as blood and marrow transplantation (BMT). Transgender AYAs face additional barriers and there is a dearth of published literature regarding their oncology-related experience. We present the case of an AYA male-to-female (MTF) transgender patient on cross-sex hormone therapy, with a history of Chronic Myelogenous Leukemia (CML) and significant psychosocial barriers, which initially served as a barrier to BMT at two different centers; we modified our standard consent and education process and was able to successfully proceed with BMT and subsequently cure her CML. Despite unique challenges, AYA and transgender patients with significant psychosocial barriers may achieve successful outcomes with BMT. Research is needed regarding guidelines for cross-sex hormone therapy administration for patients undergoing BMT and other issues, which may be unique to the transgender experience.

  11. Infections and immunodeficiency in bone marrow transplantation.

    PubMed

    Tutschka, P J

    1988-05-01

    After allogeneic bone marrow transplantation certain patterns of infectious complications emerge that follow the clinical course, are correlated to the immunobiology of transplantation and are almost predictable in their character and expression. The preparative regimen, designed to generate complete aplasia, will be associated with severe and sometimes life-threatening bacterial infections, predominantly with Gram-negative organisms derived from bowel flora, but also Gram-positive skin saprophytes. In this early aplastic phase, life-threatening viral infections are less common, consisting mainly of herpes simplex and possibly Epstein-Barr stomatitis and BK papovavirus cystitis. Systemic infections with invasive filamentous fungi are rare and are seen only when the induced aplasia is markedly prolonged. Once early marrow recovery has been achieved, systemic infections will generally disappear unless acute graft-vs.-host disease develops. This complication, which will lead to the breakdown of natural barriers such as skin and gastrointestinal epithelium and the marked impairment of all systemic defense mechanisms, can cause polymicrobial infections as well as set the stage for life-threatening viral infections. Such opportunistic viral infections, leading to either interstitial pneumonia or hemorrhagic gastroenteritis, are the major threat in the early recovery phase after engraftment has taken place. Usually caused by cytomegalovirus and rotavirus, respectively, these infections are the primary expression of the severe combined immunodeficiency post transplant, statistically associated with the presence of acute graft-vs.-host disease and amenable to immunologic manipulations. With the recovery of cellular and humoral immune function derived from transplanted donor lymphoid cells, the third phase of infectious complications is reached, covering 3 months to 2 years post grafting.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Patient and healthcare perspectives on the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic: a qualitative study

    PubMed Central

    Sinclair, Shane; McConnell, Shelagh; Raffin Bouchal, Shelley; Ager, Naree; Booker, Reanne; Enns, Bert; Fung, Tak

    2015-01-01

    Objectives The purpose of this study was to use a qualitative approach to better understand the importance and efficacy of addressing spiritual issues within an interdisciplinary bone marrow transplant clinic from the perspectives of patients and healthcare providers. Setting Participants were recruited from the bone marrow transplant clinic of a large urban outpatient cancer care centre in western Canada. Participants: Focus groups were conducted with patients (n=7) and healthcare providers (n=9) to explore the importance of addressing spiritual issues across the treatment trajectory and to identify factors associated with effectively addressing these needs. Results Data were analysed using the qualitative approach of latent content analysis. Addressing spiritual issues was understood by patients and healthcare providers, as a core, yet under addressed, component of comprehensive care. Both sets of participants felt that addressing basic spiritual issues was the responsibility of all members of the interdisciplinary team, while recognising the need for specialised and embedded support from a spiritual care professional. While healthcare providers felt that the impact of the illness and treatment had a negative effect on patients’ spiritual well-being, patients felt the opposite. Skills, challenges, key time points and clinical indicators associated with addressing spiritual issues were identified. Conclusions Despite a number of conceptual and clinical challenges associated with addressing spiritual issues patients and their healthcare providers emphasised the importance of an integrated approach whereby basic spiritual issues are addressed by members of the interdisciplinary team and by an embedded spiritual care professional, who in addition also provides specialised support. The identification of clinical issues associated with addressing spiritual needs provides healthcare providers with clinical guidance on how to better integrate this aspect of care into

  13. Allogeneic stem cell transplantation in patients with atypical chronic myeloid leukaemia: a retrospective study from the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation.

    PubMed

    Onida, Francesco; de Wreede, Liesbeth C; van Biezen, Anja; Eikema, Diderik-Jan; Byrne, Jenny L; Iori, Anna P; Schots, Rik; Jungova, Alexandra; Schetelig, Johannes; Finke, Jürgen; Veelken, Hendrik; Johansson, Jan-Erik; Craddock, Charles; Stelljes, Matthias; Theobald, Matthias; Holler, Ernst; Schanz, Urs; Schaap, Nicolaas; Bittenbring, Jörg; Olavarria, Eduardo; Chalandon, Yves; Kröger, Nicolaus

    2017-03-28

    Atypical chronic myeloid leukaemia (aCML) is an aggressive malignancy for which allogeneic haematopoietic stem cell transplantation (allo-HSCT) represents the only curative option. We describe transplant outcomes in 42 patients reported to the European Society for Blood and Marrow Transplantation (EBMT) registry who underwent allo-HSCT for aCML between 1997 and 2006. Median age was 46 years. Median time from diagnosis to transplant was 7 months. Disease status was first chronic phase in 69%. Donors were human leucocyte antigen (HLA)-identical siblings in 64% and matched unrelated (MUD) in 36%. A reduced intensity conditioning was employed in 24% of patients. T-cell depletion was applied in 87% and 26% of transplants from MUD and HLA-identical siblings, respectively. According to the EBMT risk-score, 45% of patients were 'low-risk', 31% 'intermediate-risk' and 24% 'high-risk'. Following allo-HSCT, 87% of patients achieved complete remission. At 5 years, relapse-free survival was 36% and non-relapse mortality (NRM) was 24%, while relapse occurred in 40%. Patient age and the EBMT score had an impact on overall survival. Relapse-free survival was higher in MUD than in HLA-identical sibling HSCT, with no difference in NRM. In conclusion, this study confirmed that allo-HSCT represents a valid strategy to achieve cure in a reasonable proportion of patients with aCML, with young patients with low EBMT risk score being the best candidates.

  14. Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.

    PubMed

    Coda, B A; O'Sullivan, B; Donaldson, G; Bohl, S; Chapman, C R; Shen, D D

    1997-09-01

    A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute

  15. Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

    SciTech Connect

    Wong, Jeffrey Y.C. Rosenthal, Joseph; Liu An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

    2009-01-01

    Purpose: Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Methods and Materials: Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. Results: For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. Conclusions: This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches.

  16. Late effects of blood and marrow transplantation.

    PubMed

    Inamoto, Yoshihiro; Lee, Stephanie J

    2017-04-01

    Hematopoietic cell transplantation is a curative treatment for a variety of hematologic diseases. Advances in transplantation technology have reduced early transplant-related mortality and expanded application of transplantation to older patients and to a wider variety of diseases. Management of late effects after transplantation is increasingly important for a growing number of long-term survivors that is estimated to be half a million worldwide. Many studies have shown that transplant survivors suffer from significant late effects that adversely affect morbidity, mortality, working status and quality of life. Late effects include diseases of the cardiovascular, pulmonary, and endocrine systems, dysfunction of the thyroid gland, gonads, liver and kidneys, infertility, iron overload, bone diseases, infection, solid cancer, and neuropsychological effects. The leading causes of late mortality include recurrent malignancy, lung diseases, infection, secondary cancers and chronic graft-versus-host disease. The aim of this review is to facilitate better care of adult transplant survivors by summarizing accumulated evidence, new insights, and practical information about individual late effects. Further research is needed to understand the biology of late effects allowing better prevention and treatment strategies to be developed.

  17. Multiorgan WU Polyomavirus Infection in Bone Marrow Transplant Recipient.

    PubMed

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

    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.

  18. Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa

    PubMed Central

    Wagner, John E.; Ishida-Yamamoto, Akemi; McGrath, John A.; Hordinsky, Maria; Keene, Douglas R.; Riddle, Megan J.; Osborn, Mark J.; Lund, Troy; Dolan, Michelle; Blazar, Bruce R.; Tolar, Jakub

    2010-01-01

    Background Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7−/− mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans. Methods Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography. Results One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal–epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies. Conclusions Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National

  19. Assessment of nephrotoxicity of high-cumulative dose of liposomal amphotericin B in a pediatric patient who underwent allogeneic bone marrow transplantation.

    PubMed

    Cesaro, Simone; Zignol, Matteo; Burlina, Alberto B; Tridello, Gloria; Visintin, Gianluca; Messina, Chiara

    2006-03-01

    We describe a 9-yr-old boy who received the highest cumulative dose so far reported of liposomal amphotericin B. The patient underwent an allogeneic bone marrow transplantation (BMT) for adrenoleucodystrophy, after a conditioning regimen with busulfan, thiothepa and cyclophosphamide. Rabbit antithymoglobulin, cyclosporin and prednisone were used as prophylaxis against graft vs. host disease (GVHD). Post-transplant Epstein-Bar-virus-related lymphoma was diagnosed on day +68 and was treated with donor-derived lymphocytes. The patient developed a severe form of GVHD, and a progressive worsening of his neurological status because of progression of his underlying disease. Death from septic shock occurred 23 months after BMT. During prolonged hospitalization, 19,750 mg of liposomal amphotericin B, about 1000 mg/kg, were given for prophylactic or empirical therapeutic purposes without significant nephrotoxicity. This case suggests that liposomal amphotericin B is safe and well-tolerated even if is administered for long periods and a cumulative dose fivefold greater than the nephrotoxic threshold of amphotericin B deoxycholate is achieved.

  20. 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.

  1. Disseminated histoplasmosis in allogeneic bone marrow transplant: a diagnosis not to be missed.

    PubMed

    Haydoura, S; Wallentine, J; Lopansri, B; Ford, C D; Saad, D; Burke, J P

    2014-10-01

    Immunosuppressed patients are at highest risk for disseminated histoplasmosis, but only a few cases have been reported in hematopoietic stem cell transplant recipients. We report a case of disseminated histoplasmosis in an allogeneic bone marrow transplant recipient residing in a non-endemic area. Diagnosis was first suspected based on a peripheral blood smear.

  2. In vitro assessment of bone marrow endothelial colonies (CFU-En) in non-Hodgkin's lymphoma patients undergoing peripheral blood stem cell transplantation.

    PubMed

    Lanza, F; Campioni, D; Punturieri, M; Moretti, S; Dabusti, M; Spanedda, R; Castoldi, G

    2003-12-01

    The distribution and functional characteristics of in vitro bone marrow (BM) endothelial colonies (CFU-En) were studied in 70 non-Hodgkin's lymphoma (NHL) patients in different phases of the disease to explore the association between CFU-En growth and angiogenesis, and between the number of CFU-En and the presence of hematopoietic and mesenchymal progenitor cells. The mean number of CFU-En/10(6) BM mononuclear cells seen in remission patients was significantly higher than that seen in newly diagnosed patients (P=0.04), and in normal subjects (P=0.008). Patients with low-grade NHL in remission displayed a higher CFU-En value compared with high-grade NHL (P=0.04). In the autograft group (40 patients), a significant reduction of CFU-En number was detected in the first 4-6 months after transplantation. In remission patients, the CFU-En number positively correlated with the incidence of BM colony-forming unit granulocyte-macrophage (CFU-GM) (P=0.013) and CFU-multilineage (CFU-GEMM) hematopoietic colonies (P=0.044). These in vitro data show that CFU-En numbers increase following standard-dose chemotherapy, thus providing a rationale for further investigating the effects of different cytostatic drugs on BM endothelial cells growth and function.

  3. 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

  4. Impact of the intensity of the pretransplantation conditioning regimen in patients with prior invasive aspergillosis undergoing allogeneic hematopoietic stem cell transplantation: a retrospective survey of the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Martino, Rodrigo; Parody, Rocio; Fukuda, Takahiro; Maertens, Johan; Theunissen, Koen; Ho, Aloysius; Mufti, Ghulam J.; Kroger, Nicolaus; Zander, Arnold R.; Heim, Dominik; Paluszewska, Monika; Selleslag, Dominik; Steinerova, Katerina; Ljungman, Per; Cesaro, Simone; Nihtinen, Anna; Cordonnier, Catherine; Vazquez, Lourdes; López-Duarte, Monica; Lopez, Javier; Cabrera, Rafael; Rovira, Montserrat; Neuburger, Stefan; Cornely, Oliver; Hunter, Ann E.; Marr, Kieren A.; Dornbusch, Hans Jürgen; Einsele, Hermann

    2006-01-01

    In this retrospective study, we analyzed the outcomes of 129 patients who underwent an allogeneic hematopoietic stem cell transplantation (allo-HSCT) and had a history of probable or proven invasive aspergillosis (IA), of whom 57 (44%) received a reduced-intensity conditioning (RIC). Overall, 27 patients with IA progressed after the allo-HSCT (cumulative incidence [CumInc] at 2 years, 22%). The variables that increased the 2-year CumInc of IA progression were (1) longer duration of neutropenia after transplantation; (2) advanced status of the underlying disease; and (3) less than 6 weeks from start of systemic anti-Aspergillus therapy and the allo-HSCT. In addition, (4) conventional myeloablative conditioning increased the risk of progression early after transplantation (before day 30) only, while 3 variables increased the risk beyond day 30 were (5) cytomegalovirus disease; (6) bone marrow or cord blood as source of stem cells; and (7) grades II to IV acute graft-versus-host disease (GVHD). A risk model for progression was generated, defined as low (0-1 risk factors, 6% incidence), intermediate (2-3 risk factors, 27% incidence), or high risk (≥ 3 risk factors, 72% incidence [P < .001]). These findings may help in the interpretation and design of future studies on secondary prophylaxis of IA after an allo-HSCT. PMID:16720833

  5. Intensive care outcomes in bone marrow transplant recipients: a population-based cohort analysis

    PubMed Central

    Scales, Damon C; Thiruchelvam, Deva; Kiss, Alexander; Sibbald, William J; Redelmeier, Donald A

    2008-01-01

    Introduction Intensive care unit (ICU) admission for bone marrow transplant recipients immediately following transplantation is an ominous event, yet the survival of these patients with subsequent ICU admissions is unknown. Our objective was to determine the long-term outcome of bone marrow transplant recipients admitted to an ICU during subsequent hospitalizations. Methods We conducted a population-based cohort analysis of all adult bone marrow transplant recipients who received subsequent ICU care in Ontario, Canada from 1 January 1992 to 31 March 2002. The primary endpoint was mortality at 1 year. Results A total of 2,653 patients received bone marrow transplantation; 504 of which received ICU care during a subsequent hospitalization. Patients receiving any major procedure during their ICU stay had higher 1-year mortality than those patients who received no ICU procedure (87% versus 44%, P < 0.0001). Death rates at 1 year were highest for those receiving mechanical ventilation (87%), pulmonary artery catheterization (91%), or hemodialysis (94%). In combination, the strongest independent predictors of death at 1 year were mechanical ventilation (odds ratio, 7.4; 95% confidence interval, 4.8 to 11.4) and hemodialysis (odds ratio, 8.7; 95% confidence interval, 2.1 to 36.7), yet no combination of procedures uniformly predicted 100% mortality. Conclusion The prognosis of bone marrow transplant recipients receiving ICU care during subsequent hospitalizations is very poor but should not be considered futile. PMID:18547422

  6. 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

  7. Successful Repigmentation of Vitiligo after Allogeneic Bone Marrow Transplantation for Hodgkin's Lymphoma by Autologous Noncultured Melanocyte-keratinocyte Transplantation

    PubMed Central

    Tang, Huijuan; Wang, Cui; Fu, Lifang; Xu, Ai-e

    2015-01-01

    The treatment of vitiligo is derisory since the pathogenesis of vitiligo is not clear at present. Most conservative treatments are difficult to approach satisfactory therapy. So transplantation is the only way left when the disease becomes insensitive to those conservative treatments. Here we describe an 18-year-old patient who developed vitiligo, which was triggered by graft-versus-host disease after a allogeneic bone marrow transplantation for the treatment of Hodgkin's lymphoma from his sister. In the following treatment to vitiligo, the patient successfully performed the transplantation of autologous uncultured melanocyte on the premise of poor reaction to other conservative methods. We infer that transplantation can be a treatment of the vitiligo after allogeneic bone marrow transplantation. PMID:26538694

  8. Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation.

    PubMed

    van Gelder, M; de Wreede, L C; Bornhäuser, M; Niederwieser, D; Karas, M; Anderson, N S; Gramatzki, M; Dreger, P; Michallet, M; Petersen, E; Bunjes, D; Potter, M; Beelen, D; Cornelissen, J J; Yakoub-Agha, I; Russell, N H; Finke, J; Schoemans, H; Vitek, A; Urbano-Ispízua, Á; Blaise, D; Volin, L; Chevallier, P; Caballero, D; Putter, H; van Biezen, A; Henseler, A; Schönland, S; Kröger, N; Schetelig, J

    2017-03-01

    Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25-31), 35% (95% CI, 32-38) and 40% (95% CI, 37-42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73-85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.

  9. Intracoronary autologous bone marrow-derived mononuclear cell transplantation improves coronary collateral vessel formation and recruitment capacity in patients with ischemic cardiomyopathy: a combined hemodynamic and scintigraphic approach.

    PubMed

    Tayyareci, Yelda; Sezer, Murat; Umman, Berrin; Besisik, Sevgi; Mudun, Ayse; Sanli, Yasemin; Oncul, Aytac; Gurses, Nuray; Sargin, Deniz; Meric, Mehmet; Nisanci, Yilmaz

    2008-01-01

    This study investigated the effects of intracoronary autologous bone marrow-derived mononuclear cell (BMC) transplantation on coronary microcirculation. Fifteen patients with ischemic cardiomyopathy were treated by intracoronary infusion of BMCs via the patent infarct-related artery. The thermodilution-derived coronary flow reserve, index of microvascular resistance, pressure-derived collateral flow index, and coronary wedge pressure were measured at baseline and at 6 months. Successive balloon inflations during BMC transplantation were performed to observe the recruitment in pressure-derived collateral flow index and coronary wedge pressure, and the percentage changes between baseline and 6 months were calculated. The mean (SD) coronary flow reserve increased from 1.3 (0.4) to 2.1 (0.5), and the mean (SD) index of microvascular resistance decreased from 44.9 (24.4) to 21.2 (14.1) (P = .001 for both). The mean (SD) improvement in pressure-derived collateral flow index (from 0.14 [0.05] to 0.22 [0.08]) was also statistically significant (P = .001). Similarly, the percentage improvements in pressure-derived collateral flow index and coronary wedge pressure were statistically significant (P = .01 for both). The percentage improvement in perfusion assessed by single-photon emission computed tomography strongly correlated with the percentage changes in pressure-derived collateral flow index (r = 0.88, P = .001) and coronary wedge pressure (r = 0.69, P = .01). These results demonstrate for the first time (to our knowledge) that intracoronary autologous BMC transplantation improves coronary collateral vessel formation and recruitment capacity in human subjects.

  10. Long-term cryopreservation of bone marrow for autologous transplantation.

    PubMed

    Attarian, H; Feng, Z; Buckner, C D; MacLeod, B; Rowley, S D

    1996-03-01

    Little is known about the effect of long-term cryopreservation on the viability of hematopoietic stem cells (HSC) or on the success of autologous bone marrow transplantation. Although progenitor cell assays such as culture of CFU-GM after thawing can be predictive of engraftment, the most rigorous assay for the cryosurvival of HSC is engraftment after reinfusion of stem cells. We retrospectively evaluated the engraftment data for 36 patients with hematologic malignancies or solid tumors treated at the Fred Hutchinson Cancer Research Center between 1981 and 1993 who received bone marrows stored for 2 years or more. The median duration of cryopreservation for this study group was 2.7 years (range 2.0-7.8). Ninety-seven percent of patients in the study group achieved a granulocyte count of > or = 0.5 x 1.0(9)/1 at a median of 19 days (range 10-115) vs 86% of control group (selected by diagnosis and date of storage) at a median of 20 days (P = 0.14). Seventy percent of patients in the study group achieved a platelet count > or = 20 x 10(9)/1 at a median of 27 days (range 9-69) vs 74% of control group at a median of 23 days (P = 0.47). Also, samples of 28 marrows cryopreserved for a median of 4.4 years (range 2.0-7.8) were cultured to determine if a loss of hematopoietic progenitors relative to duration of storage could be detected. The storage length was not predictive for the quantity of colonies formed (P = 0.57 for BFU-E-derived colonies; P = 0.65 for CFU-GM-derived colonies). We found no consistent detrimental effect of long-term cryopreservation on the success rate of autologous bone marrow transplantation. This report confirms previous reports that marrow cells cryopreserved for several years are capable of engrafting. Therefore, bone marrow cells may be stored at an early appropriate time before the side-effects of multiple cycles of chemotherapy and radiotherapy on hematopoietic tissues are incurred.

  11. 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.

  12. Cardiac resynchronization therapy and bone marrow cell transplantation in patients with ischemic heart failure and electromechanical dyssynchrony: a randomized pilot study.

    PubMed

    Pokushalov, Evgeny; Romanov, Alexander; Corbucci, Giorgio; Prohorova, Darya; Chernyavsky, Alexander; Larionov, Petr; Terekhov, Igor; Artyomenko, Sergey; Kliver, Elena; Shirokova, Natalya; Karaskov, Alexander; Dib, Nabil

    2011-12-01

    Most studies have confirmed the beneficial effects of autologous bone marrow mononuclear cell (BMMC) transplantation on angina, myocardial perfusion, regional wall motion, and LV ejection fraction (LVEF). Cardiac resynchronization therapy (CRT) has also shown a beneficial effect in patients with heart failure (HF) and electrical/mechanical dyssynchrony. However, the relative contribution of BMMC and CRT in patients with ischemic HF and electromechanical dyssynchrony has never been investigated. The aim of this study was to evaluate the benefit of combining BMMC transplantation with CRT in patients with severe ischemic HF, left bundle branch block (LBBB), and mechanical dyssynchrony. Patients with ischemic HF, LVEF < 35%, LBBB, and mechanical dyssynchrony underwent intramyocardial transplantation of BMMC and CRTD system implantation. This randomized, single-blind, crossover study compared clinical and echocardiographic parameters during two follow-up periods: 6 months of active CRT (BMMC + CRTact) and 6 months of inactive CRT (BMMC + CRTinact). Physical performance was assessed by means of a 6-min walking test. Myocardial perfusion was evaluated by SPECT. Quality of Life (QoL) was assessed through the Minnesota Living with HF Questionnaire (MLwHFQ). Twenty-six patients (64 ± 7 years) were enrolled in the study. The distance covered by the patients during the 6-min walking test significantly increased in the BMMC + CRTinact phase (BMMC therapy only) in comparison with the baseline (269 ± 68 vs 206 ± 51; p = 0.007) and in the BMMC + CRTact phase (BMMC therapy + CRT) in comparison with the BMMC + CRTinact (378 ± 59 vs 269 ± 68; p < 0.001). The summed rest and stress score (SPECT) decreased significantly in the BMMC + CRTact and BMMC + CRTinact phases in comparison with the baseline (p ≤ 0.03). Both phases showed equivalent myocardial perfusion in the segments into which BMMC had been injected. QoL score was significantly lower in the BMMC

  13. In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

    SciTech Connect

    Lum, L.G.; Seigneuret, M.C.; Storb, R.F.; Witherspoon, R.P.; Thomas, E.D.

    1981-09-01

    Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation.

  14. 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.

  15. Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment.

    PubMed

    Lee, J H; Lee, K H; Choi, J S; Zang, D Y; Kim, S B; Kim, S W; Suh, C; Lee, J S; Kim, W K; Lee, Y S; Kim, S H

    1996-04-01

    Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt

  16. Reversible posterior leucoencephalopathy syndrome associated with bone marrow transplantation.

    PubMed

    Teive, H A; Brandi, I V; Camargo, C H; Bittencourt, M A; Bonfim, C M; Friedrich, M L; de Medeiros, C R; Werneck, L C; Pasquini, R

    2001-09-01

    Reversible posterior leucoencephalopathy syndrome (RPLS) has previously been described in patients who have renal insufficiency, eclampsia, hypertensive encephalopathy and patients receiving immunosuppressive therapy. The mechanism by which immunosuppressive agents can cause this syndrome is not clear, but it is probably related with cytotoxic effects of these agents on the vascular endothelium. We report eight patients who received cyclosporine A (CSA) after allogeneic bone marrow transplantation or as treatment for severe aplastic anemia (SSA) who developed posterior leucoencephalopathy. The most common signs and symptoms were seizures and headache. Neurological dysfunction occurred preceded by or concomitant with high blood pressure and some degree of acute renal failure in six patients. Computerized tomography studies showed low-density white matter lesions involving the posterior areas of cerebral hemispheres. Symptoms and neuroimaging abnormalities were reversible and improvement occurred in all patients when given lower doses of CSA or when the drug was withdrawn. RPLS may be considered an expression of CSA neurotoxicity.

  17. REDUCED INTENSITY HEMATOPOIETIC CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY MYELOFIBROSIS: A COHORT ANALYSIS FROM THE CENTER FOR INTERNATIONAL BLOOD AND MARROW TRANSPLANT RESEARCH

    PubMed Central

    Gupta, Vikas; Malone, Adriana K.; Hari, Parameswaran N.; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K.; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T.; Waller, Edmund K.; Costa, Luciano J.; Antin, Joseph H.; Kamble, Rammurti T.; van Besien, Koen M.; Savani, Bipin N.; Schouten, Harry C.; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J.; Wirk, Baldeep; Aljurf, Mahmoud D.; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R.; Norkin, Maxim; Lewis, Ian D.; Hale, Gregory A.; Woolfrey, Ann E.; Miller, Alan M.; Ustun, Celalettin; Jagasia, Madan H.; Lill, Michael; Maziarz, Richard T.; Cortes, Jorge; Kalaycio, Matt E.; Saber, Wael

    2014-01-01

    We evaluated the outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced intensity conditioning (RIC). Median age at HCT was 55 years. Donors were: matched sibling donor (MSD), 34%; HLA-well-matched unrelated donors (URD), 45%; and partially/mismatched URD, 21%. Risk stratification according to Dynamic International Prognostic Scoring System (DIPSS): low, 12%; intermediate-1, 49%; intermediate-2, 37%; and high, 1%. The probability of survival at 5-years was 47% (95% CI 40–53). In a multivariate analysis, donor type was the only independent factor associated with survival. Adjusted probabilities of survival at 5-years for MSD, well matched URD and partially matched/mismatched URD were 56% (95% CI 44–67), 48% (95% CI 37–58), and 34% (95% CI 21–47), respectively (p=0.002). Relative risks (RR) for NRM for well-matched URD and partially matched/mismatched URD were 3.92 (p=0.006) and 9.37 (p<0.0001), respectively. A trend towards increased NRM (RR 1.7, p=0.07) and inferior survival (RR 1.37, p=0.10) was observed in DIPSS-intermediate-2/high-risk patients compared to DIPSS-low/intermediate-1 risk patients. RIC HCT is a potentially curative option for patients with MF, and donor type is the most important factor influencing survival in these patients. PMID:24161923

  18. CT analysis of lung density changes in patients undergoing total body irradiation prior to bone marrow transplantation

    SciTech Connect

    Lee, J.Y.; Shank, B.; Bonfiglio, P.; Reid, A.

    1984-10-01

    Sequential changes in lung density measured by CT are potentially sensitive and convenient monitors of lung abnormalities following total body irradiation (TBI). Methods have been developed to compare pre- and post-TBI CT of lung. The average local features of a cross-sectional lung slice are extracted from three peripheral regions of interest in the anterior, posterior, and lateral portions of the CT image. Also, density profiles across a specific region may be obtained. These may be compared first for verification of patient position and breathing status and then for changes between pre- and post-TBI. These may also be compared with radiation dose profiles through the lung. A preliminary study on 21 leukemia patients undergoing total body irradiation indicates the following: (a) Density gradients of patients' lungs in the antero-posterior direction show a marked heterogeneity before and after transplantation compared with normal lungs. The patients with departures from normal density gradients pre-TBI correlate with later pulmonary complications. (b) Measurements of average peripheral lung densities have demonstrated that the average lung density in the younger age group is substantially higher: pre-TBI, the average CT number (1,000 scale) is -638 +/- 39 Hounsfield unit (HU) for 0-10 years old and -739 +/- 53 HU for 21-40 years old. (c) Density profiles showed no post-TBI regional changes in lung density corresponding to the dose profile across the lung, so no differentiation of a radiation-specific effect has yet been possible. Computed tomographic density profiles in the antero-posterior direction are successfully used to verify positioning of the CT slice and the breathing level of the lung.

  19. The national marrow donor program 20 years of unrelated donor hematopoietic cell transplantation.

    PubMed

    Ballen, Karen K; King, Roberta J; Chitphakdithai, Pintip; Bolan, Charles D; Agura, Edward; Hartzman, Robert J; Kernan, Nancy A

    2008-09-01

    In the 20 years since the National Marrow Donor Program (NMDP) facilitated the first unrelated donor transplant, the organization has grown to include almost 7 million donors, and has facilitated over 30,000 transplants on 6 continents. This remarkable accomplishment has been facilitated by the efforts of over 600 employees, and an extensive international network including 171 transplant centers, 73 donor centers, 24 cord blood banks, 97 bone marrow collection centers, 91 apheresis centers, 26 HLA typing laboratories, and 26 Cooperative Registries. In this article, we review the history of the NMDP, and cite the major trends in patient demographics, graft sources, and conditioning regimens over the last 20 years.

  20. Aspergillus antigen testing in bone marrow transplant recipients

    PubMed Central

    Williamson, E; Oliver, D; Johnson, E; Foot, A; Marks, D; Warnock, D

    2000-01-01

    Aims—To assess the clinical usefulness of a commercial aspergillus antigen enzyme linked immunosorbent assay (ELISA) in the diagnosis of invasive aspergillosis (IA) in bone marrow transplant recipients, and to compare it with a commercial latex agglutination (LA) test. Methods—In total, 2026 serum samples from 104 bone marrow transplant recipients were tested. These comprised 67 sera from seven patients who had died with confirmed IA, 268 sera from nine patients who had died with suspected IA, and 1691 sera from 88 patients with no clinical, radiological, or microbiological signs of IA. Results—The ELISA was more sensitive than the LA test. All patients who were ELISA positive were also LA positive, and a positive LA result never preceded a positive ELISA. Twelve of 16 patients with confirmed or suspected IA were ELISA positive on two or more occasions, compared with 10 of 15 who were LA positive. ELISA was positive before LA in five patients (range, 2–14 days), and became positive on the same day in the remainder. Aspergillus antigen was detected by ELISA a median of 15 days before death (range, 4–233). Clinical and/or radiological evidence of IA was noted in all patients, and a positive ELISA was never the sole criterion for introduction of antifungal treatment. Two samples (one from each of two patients without IA) gave false positive results. Conclusions—The aspergillus ELISA is a specific indicator of invasive aspergillosis if the criterion of two positive samples is required to confirm the diagnosis. However, the test is insufficiently sensitive to diagnose aspergillosis before other symptoms or signs are apparent, and hence is unlikely to lead to earlier initiation of antifungal treatment. It is therefore unsuitable for screening of asymptomatic patients at risk of invasive aspergillosis, but does have a useful role in confirming the diagnosis in symptomatic patients. Key Words: invasive aspergillosis • aspergillus antigen • Platelia enzyme

  1. Autologous Pancreatic Islet Transplantation in Human Bone Marrow

    PubMed Central

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

    2013-01-01

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

  2. Rapid autologous marrow recovery and eradication of infectious mononucleosis despite severe immunosuppression following second transplantation for aplastic anemia.

    PubMed

    Rossbach, H C; Hosler, K M; Chamizo, W; Mueller, T; Grana, N H; Lacson, A G; Barbosa, J L

    1999-01-01

    A patient with aplastic anemia failed to respond to immunosuppressive therapy and first marrow transplantation (BMT). Recovery of autologous hematopoiesis was rapid following a second stem cell transplant with a non-myeloablative preparatory regimen. The autologous immune response to infectious mononucleosis (IM) 4 weeks post-transplant was normal despite recent and ongoing severe immunosuppression.

  3. Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research.

    PubMed

    Gupta, Vikas; Malone, Adriana K; Hari, Parameswaran N; Ahn, Kwang Woo; Hu, Zhen-Huan; Gale, Robert Peter; Ballen, Karen K; Hamadani, Mehdi; Olavarria, Eduardo; Gerds, Aaron T; Waller, Edmund K; Costa, Luciano J; Antin, Joseph H; Kamble, Rammurti T; van Besien, Koen M; Savani, Bipin N; Schouten, Harry C; Szer, Jeffrey; Cahn, Jean-Yves; de Lima, Marcos J; Wirk, Baldeep; Aljurf, Mahmoud D; Popat, Uday; Bejanyan, Nelli; Litzow, Mark R; Norkin, Maxim; Lewis, Ian D; Hale, Gregory A; Woolfrey, Ann E; Miller, Alan M; Ustun, Celalettin; Jagasia, Madan H; Lill, Michael; Maziarz, Richard T; Cortes, Jorge; Kalaycio, Matt E; Saber, Wael

    2014-01-01

    We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients.

  4. 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.

  5. Australian Dental Research Fund Trebitsch Scholarship. Efficacy of antifungal prophylaxis in bone marrow transplantation.

    PubMed

    Quirk, P C; Osborne, P J; Walsh, L J

    1995-08-01

    Oral candidal infection is a common problem in bone marrow transplantation. This prospective study compared the effectiveness of antifungal prophylaxis with topical antifungals (nystatin and amphotericin B suspensions) versus oral fluconazole in 196 patients undergoing bone marrow transplantation. Oral candidosis occurred frequently in the group receiving topical antifungals (61/113, 54%), but was rare in the group receiving fluconazole (6/83, 7%). The difference in efficacy between the two groups was highly significant (p < 0.00001). There was no difference in the incidence of suspected systemic fungal infection between the two groups. While nausea was a problem with antifungal suspensions, no significant adverse reactions to fluconazole occurred. Because of greater efficacy in preventing oral candidosis and better patient tolerance, oral fluconazole is preferred to antifungal suspensions for prophylactic use in patients undergoing bone marrow transplantation.

  6. Toxoplasma gondii infection in marrow transplant recipients: a 20 year experience.

    PubMed

    Slavin, M A; Meyers, J D; Remington, J S; Hackman, R C

    1994-05-01

    Twelve of 3803 consecutive marrow allograft patients treated at this center over the past 20 years have had a post-transplant tissue diagnosis of toxoplasmosis: 10 at autopsy and 2 by brain biopsy. This infection was identified in none of 509 autologous marrow recipients. Occurrence of toxoplasmosis was 0.31 cases per 100 allogeneic transplants and 1.0 per 100 autopsies. An estimated 15% of allogeneic transplant recipients were seropositive for Toxoplasma gondii and 2% of seropositive patients developed toxoplasmosis. Pre-transplant serology was positive by both dye and agglutination tests in 11 infected patients tested. Sequential IgG, IgM, IgA, IgE antibody titers to T. gondii and the differential agglutination ratio were not helpful in diagnosing toxoplasmosis. Median day of clinical presentation was day 59 post-transplant (35-97 days) and of diagnosis, day 62 after transplant (37-143 days). Eleven patients had graft-versus-host disease (GVHD) of grades II-IV. All 12 patients died. Infection was diagnosed prior to death in only 16% of patients and contributed to death in at least 40%. Histopathology revealed tachyzoites of T. gondii most prevalent in brain (100%), heart (67%) and lungs (33%), and toxoplasma cysts alone in heart (33%) and lungs (22%). Toxoplasma infection was diagnosed in two patients receiving trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia prophylaxis suggesting this was insufficient prophylaxis for toxoplasmosis. Toxoplasmosis appeared to occur by reactivation within the first 6 months after marrow transplant. Infection developed in patients who were seropositive for T. gondii pre-transplant, had received allogeneic marrow and had severe GVHD.

  7. Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation.

    PubMed

    Molrine, D C; Guinan, E C; Antin, J H; Wheeler, C; Parsons, S K; Weinstein, H J; McGarigle, C; Blanding, P; Phillips, N R; Ciamarra, A; George, S; Ambrosino, D M

    1996-06-01

    Immune reconstitution following autologous bone marrow transplantation (ABMT) is characterized by defects in B cell and T cell function and loss of specific antibody. In the late post-transplant period, patients are at risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We examined whether immunizing ABMT patients before bone marrow (BM) harvest enhanced the early recovery of specific antibody. Twelve patients were immunized before BM harvest with Haemophilus influenzae type b (HIB)-conjugate, tetanus toxoid and polysaccharide pneumococcal vaccines. Forty-one comparable ABMT patients not immunized prior to BM harvest were also studied. Following ABMT, both groups of patients were immunized with HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12 and 24 months and with pneumococcal vaccine at 12 and 24 months. Patients immunized before BM harvest had higher HIB antibody concentrations during the first 2 years post-transplant, the differences reaching significance at 3 months (P = 0.0001) and following the 24-month dose (P = 0.048). Tetanus toxoid antibody concentrations were also significantly higher at 3 months (P = 0.001) and 6 months (P = 0.032) in patients immunized before BM harvest. There were no differences in pneumococcal antibody concentrations between the two groups. Immunization of patients before bone marrow harvest resulted in higher anti-HIB antibody concentrations following ABMT and may be an effective strategy to prevent infectious complications.

  8. Parentage testing implications of male fertility after allogeneic bone marrow transplantation.

    PubMed

    Lipton, J H; Marshall, W H; Waye, J S

    1999-01-01

    Fertility is expected to be reduced after the extensive chemotherapy and/or radiotherapy that is needed for conditioning prior to bone marrow transplantation. However, a male patient can be fertile, and in very rare situations such as reported here, this may confuse subsequent paternity testing. The patient, initially excluded as the biological father by red cell types but not by HLA, was subsequently included after the history of his previous marrow transplant was revealed, a review of the HLA results and further RFLP testing on buccal mucosal cells. This case points to the need for good history taking before performing paternity testing.

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

    PubMed Central

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

    2010-01-01

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

  10. The future for treatment by bone marrow transplantation for adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome.

    PubMed

    Krivit, W; Lockman, L A; Watkins, P A; Hirsch, J; Shapiro, E G

    1995-01-01

    Within the past decade, bone marrow transplantation has been applied to over 200 patients worldwide with the intention of treating storage diseases. Bone marrow transplantation has provided a method for treatment of adrenoleukodystrophy, metachromatic leukodystrophy, globoid cell leukodystrophy and Hurler syndrome. After engraftment, significant improvement in the clinical course of each of these diseases occurs. Survival data of engrafted patients are superior to those of non-transplanted. Engraftment and the resulting enzymatic reconstitution are concordant. Outcomes based on neuropsychological tests indicate continued maintenance and in some cases increase in cognitive function. Magnetic resonance imaging as well as spectroscopic examinations of the brain provide further evidence that positive changes occur in the central nervous system following long-term engraftment. A better quality of life follows engraftment. Greater gains from use of bone marrow transplantation for these particular storage diseases will occur in the future. Earlier diagnosis will allow bone marrow transplantation in the presymptomatic stage at a younger age, providing an enhancement of positive effects noted from such treatment. At the same time, advances in bone marrow technology will serve to reduce the risk factors involved with the bone marrow transplantation process itself. These two factors taken together will be more than additive in providing benefits from use of bone marrow transplantation.

  11. 16S rRNA gene pyrosequencing reveals shift in patient faecal microbiota during high-dose chemotherapy as conditioning regimen for bone marrow transplantation.

    PubMed

    Montassier, Emmanuel; Batard, Eric; Massart, Sébastien; Gastinne, Thomas; Carton, Thomas; Caillon, Jocelyne; Le Fresne, Sophie; Caroff, Nathalie; Hardouin, Jean Benoit; Moreau, Philippe; Potel, Gilles; Le Vacon, Françoise; de La Cochetière, Marie France

    2014-04-01

    Gastrointestinal disturbances are a side-effect frequently associated with haematological malignancies due to the intensive cytotoxic treatment given in connection with bone marrow transplantation (BMT). However, intestinal microbiota changes during chemotherapy remain poorly described, probably due to the use of culture-based and low-resolution molecular methods in previous studies. The objective of our study was to apply a next generation DNA sequencing technology to analyse chemotherapy-induced changes in faecal microbiota. We included eight patients with non-Hodgkin's lymphoma undergoing one course of BMT conditioning chemotherapy. We collected a prechemotherapy faecal sample, the day before chemotherapy was initiated, and a postchemotherapy sample, collected 1 week after the initiation of chemotherapy. Total DNA was extracted from faecal samples, denaturing high-performance liquid chromatography based on amplification of the V6 to V8 region of the 16S ribosomal RNA (rRNA) gene, and 454-pyrosequencing of the 16 S rRNA gene, using PCR primers targeting the V5 and V6 hypervariable 16S rRNA gene regions were performed. Raw sequence data were screened, trimmed, and filtered using the QIIME pipeline. We observed a steep reduction in alpha diversity and significant differences in the composition of the intestinal microbiota in response to chemotherapy. Chemotherapy was associated with a drastic drop in Faecalibacterium and accompanied by an increase of Escherichia. The chemotherapy-induced shift in the intestinal microbiota could induce severe side effects in immunocompromised cancer patients. Our study is a first step in identifying patients at risk for gastrointestinal disturbances and to promote strategies to prevent this drastic shift in intestinal microbiota.

  12. 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.

  13. A simple technique for red blood cell removal in major ABO-incompatible bone marrow transplantation.

    PubMed

    Mayer, G; Wernet, D; Northoff, H; Schneider, W

    1994-01-01

    A simple technique for red blood cell (RBC) removal in major ABO-incompatible bone marrow transplantation is reported requiring two centrifugation steps, special blood bags and a mechanical device to separate the buffy coat from RBCs within the bag. In 42 transplantations an average of 84% of nucleated cells was recovered with an average contamination of 7.5 ml packed RBCs. The preparations were well tolerated in all patients whose isoagglutinin titers had not been reduced. Bone marrow engraftment was not significantly different from control groups.

  14. Oral administration of cyclosporin A for recipients of allogeneic marrow transplants: implications of clinical gut dysfunction.

    PubMed

    Atkinson, K; Biggs, J C; Britton, K; Short, R; Mrongovius, R; Concannon, A; Dodds, A

    1984-02-01

    Cyclosporin A (CyA) was used to minimize graft-versus-host disease (GVHD) in 28 recipients of allogeneic marrow transplants. When given orally, the absorption of CyA was markedly dependent on normal gut function. Patients without gut dysfunction showed normal serum concentration-time curves while those with diarrhoea from any cause (chemo-radiation enteritis, acute GVHD of the gut, infectious enteritis) showed minimal absorption of the drug. These data indicate the desirability of the intravenous administration of CyA during periods of gut dysfunction in marrow transplant recipients.

  15. Current status of unrelated-donor bone marrow transplantation. The International Marrow Unrelated Search and Transplant (IMUST) Study.

    PubMed

    Bradley, B A; Hows, J M; Gore, S M; Bidwell, J L; Clay, T; Downie, T R; Gluckman, E; Howard, M R; Laundy, G J

    1992-01-01

    1. The International Marrow Unrelated Search and Transplant (IMUST) Study 1 provides novel prognostic data on outcome of unrelated-donor (UD) searches for patients with well-defined clinical characteristics. Case-types analyzed by multifactorial methods reveal the importance of HLA phenotype, ethnic mismatching, and stage of disease at search request, in predicting search outcome. White patients, with common HLA types and early disease, were least likely to suffer search failure. In contrast, searches for non-White patients with unusual HLA phenotypes and advanced disease were most likely to fail. Of importance, 70% of patients had HLA phenotypes defined as uncommon. 2. Overall donor yield at the 2 UK registries between 1989 and 1991 was 7%, significantly below expectations. Reasons for this shortfall are that theoretical predictions did not consider ethnic mismatch and logistical delays incurred by outdated UD search routines and most importantly HLA-typing inaccuracies. 3. IMUST Study 2 is a prospective multicenter-controlled cohort study comparing HLA-identical sibling donor (ID) and UD-bone marrow transplantation (BMT) for factors affecting BMT outcome. Generous support was provided by 83 BMT centers worldwide. An interim analysis of 165 UD- and 368 ID-BMT, with at least 6 months follow-up after BMT, is described. Unifactorial analysis showed a probability of engraftment at day 100 of 89% after UD- compared with 98% after ID-BMT (p < 0.001). Probability of Grades II-IV acute graft-versus-host disease (AGvHD) at 100 days was 52% after UD- compared with 42% after ID-BMT (p < 0.01). Probability of overall survival at day 400 was 42% after UD- compared with 63% after ID-BMT (p < 0.001). Survival on day 400 of those patients receiving UD-BMT for early disease was encouraging at 52%. 4. Multifactorial analysis was performed on combined data from UD- and ID-BMT cohorts to identify various factors predicting engraftment, AGvHD, and overall survival. Survival after UD

  16. Mycoses in the transplanted patient.

    PubMed

    Dictar, M O; Maiolo, E; Alexander, B; Jacob, N; Verón, M T

    2000-01-01

    The incidence of invasive fungal infection (IFI) has increased considerably over the past 20 years, and transplant recipients are at especially high risk for fungal infections owing to their overall immunosuppressed condition. Organ transplantation procedures were incorporated as a therapeutic option for many patients who lacked the normal functions of organs such as the heart, liver, kidney, lung, pancreas and small bowel. The prevalence of IFI in solid organ transplant (SOTR) patients ranges from 5 to 50% in kidney and liver transplants, respectively. In bone marrow transplant (BMT) patients, IFI are major causes of morbidity and mortality due to the protracted neutropenic period and graft-versus-host disease. Candida spp. and Aspergillus spp. account for >80% of fungal episodes in both SOTR and BMT. The development of new immunosuppressive agents, new prophylaxis strategies (as pre-emptive therapy) and the improvement in surgical techniques led to increase survival of transplant recipients. In this session, a clear and concise update of the recent advances in the laboratory diagnosis of candidiasis and aspergillosis in this kind of patients was presented. However, we still need to establish more rapid, sensitive and specific methods for IFI diagnosis. Representatives of the 'Subcomision de Infecciones en el Paciente Neutropenico y Transplantado (SIPNYT)' de la Sociedad Argentina de Infectologia (SADI), presented the results of an unusual multicenter study both retrospective and descriptive studies of IFI in SOTR and BMT patients in Argentina. In addition, a study of IFI in 1,861 SOTR patients from four centers and the analysis of IFI in 2,066 BMT patients from all 12 BMT centers from Argentina was presented. From these studies it can be concluded that 'all transplant recipients are not the same' and that they should be stratified according to their different risk degrees in order to determine the best prophylaxis and treatment strategies.

  17. Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome.

    PubMed

    Krivit, W; Aubourg, P; Shapiro, E; Peters, C

    1999-11-01

    Bone marrow transplantation protocols for inherited metabolic storage diseases are unique for each disorder treated. Differences depend also upon how old the patient was when onset occurred and rate of progression of disease. Treatment is directed to prevent or ameliorate the inexorable neurological deterioration that is the major pathophysiological event in all of these inherited metabolic storage diseases.

  18. Cytomegalovirus sinusitis in a child with chronic myelogenous leukemia following bone marrow transplantation.

    PubMed

    Rayes, Ahmad; Sahni, Kiren; Hanna, Christian; Suryadevara, Manika; Goyal, Parul; Cherrick, Irene

    2011-07-01

    Cytomegalovirus (CMV) is a common opportunistic pathogen. CMV sinusitis has been described in acquired immunodeficiency syndrome (AIDS) patients, but not in other immune compromising conditions. In this report, we describe CMV sinusitis in a child with chronic myelogenous leukemia (CML) following bone marrow transplantation.

  19. Fatal 2009 pandemic influenza A (H1N1) in a bone marrow transplant recipient.

    PubMed

    Abdo, Anselmo; Alfonso, Carlos; Diaz, Guillermo; Wilford, Mario; Rocha, Maykel; Verdecia, Niurka

    2011-03-02

    Conditions characterized by immunosuppression have been recently reported as risk factors for severe novel swine-origin influenza A (H1N1) virus (S-OIV) infection during the current 2009 pandemic.  We report clinical and virological findings, antiviral therapy, and post-mortem study of S-OIV in an adult bone marrow transplant recipient. The viral genome was amplified by real time reverse transcriptase polymerase chain reaction (RT-PCR) from a nasopharyngeal swab specimen. The patient developed acute respiratory distress syndrome, septic shock, and eventually succumbed with a severe pulmonary haemorrhage. To the best of our knowledge, the entire clinical/therapy management and pathological examination in a transplant recipient infected with the S-OIV has not been previously documented. The fatal ending in this bone marrow transplant recipient supports recommendations that call for education measures, S-OIV vaccination, early diagnosis and aggressive treatment in the transplant population.

  20. Probable graft-vs-graft reaction in an infant after exchange transfusion and marrow transplantation.

    PubMed

    Lauer, B A; Githens, J H; Hayward, A R; Conrad, P D; Yanagihara, R T; Tubergen, D G

    1982-07-01

    A newborn with graft-vs-host (GVH) disease following an exchange transfusion was treated by attempting to eradicate the incompatible graft and to reconstitute the child hematologically and immunologically with a bone marrow transplant. The patient was a female term infant (blood group B, Rh+ Coombs test positive) who received a one-unit group O, Rh- exchange transfusion from an unrelated female donor for hyperbilirubinemia due to ABO incompatibility on day 2. Signs of acute GVH disease began on day 8 and the clinical diagnosis was supported by skin biopsy. With antithymocyte globulin and high dose dexamethasone, the GVH reaction improved somewhat. Cyclophosphamide, 200 mg/kg total dose, was given over four days followed by a marrow graft from a brother who was HLA-A, B identical, and probably also D locus compatible in mixed lymphocyte culture. All signs of GVH resolved with cyclophosphamide treatment and hematologic reconstitution was evident by 14 days after transplant. Two weeks later the GVH reaction and aplastic anemia recurred and Y chromatin was detected in only 6% of marrow cells. The infant died on day 80. Autopsy showed disseminated candidiasis, disseminated cytomegalovirus infection, thymic dysplasia, hypoplastic marrow, and other histopathologic changes consistent with GVH disease. The persistence of female cells in blood and bone marrow and the destruction of the reconstituted marrow suggest that the original incompatible transfusion-derived graft was not eliminated and that it ultimately rejected the histocompatible marrow graft.

  1. Twenty years of unrelated donor bone marrow transplantation for pediatric acute leukemia facilitated by the National Marrow Donor Program.

    PubMed

    MacMillan, Margaret L; Davies, Stella M; Nelson, Gene O; Chitphakdithai, Pintip; Confer, Dennis L; King, Roberta J; Kernan, Nancy A

    2008-09-01

    The National Marrow Donor Program (NMDP) has facilitated unrelated donor hematopoietic cell transplants for more than 20 years. In this time period, there have been many changes in clinical practice, including improvements in HLA typing and supportive care, and changes in the source of stem cells. Availability of banked unrelated donor cord blood (incorporated into the NMDP registry in 2000) as a source of stem cells has become an important option for children with leukemia, offering the advantages of immediate availability for children with high-risk disease, the need for a lesser degree of HLA match, and expanding access for those with infrequent HLA haplotypes. Overall survival (OS) in children with acute leukemia transplanted with unrelated donor bone marrow (BM) is markedly better in more recent years, largely attributable to less treatment-related mortality (TRM). Within this cohort, 2-year survival was markedly better for patients with acute lymphoblastic leukemia (ALL) in first complete response (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease (33%). Similar findings are observed with patients with AML, suggesting earlier referral to bone marrow transplant (BMT) is optimal for survival. Notably, this improvement over time was not observed in unmodified peripheral blood stem cell (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell source for children.

  2. 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.

  3. 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.

  4. HLA Typing for Bone Marrow Transplantation

    DTIC Science & Technology

    2007-10-31

    storage of the first product at the apheresis center. It is also common, particularly if products arrive late in the business day, for either PBSC or marrow...over time with products stored at 20°C whereas no notable change was observed with products stored at 4’C (p ɘ.0003). However for BM, platelet

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

    PubMed

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

    2010-04-01

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

  6. Acute parkinsonian syndrome with demyelinating leukoencephalopathy in bone marrow transplant recipients.

    PubMed

    Lockman, L A; Sung, J H; Krivit, W

    1991-01-01

    A syndrome of rigidity, bradykinesia, spasticity, and often myoclonus and dementia developed acutely in 5 patients who had undergone successful engraftment of bone marrow transplants for the treatment of various hematologic diseases. Magnetic resonance imaging demonstrated widespread changes in white matter; brain biopsy disclosed mild demyelination associated with active phagocytosis of myelin. One patient, who was not treated, remains severely demented. Patients treated with very high-dose methylprednisolone had complete clinical recovery.

  7. Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies.

    PubMed

    Chang, Ying-Jun; Zhao, Xiang-Yu; Huo, Ming-Rui; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Huang, Xiao-Jun

    2011-02-01

    Currently, limited information is available regarding the effects of early lymphocyte recovery on transplant outcomes in pediatric patients with hematological malignancies after unmanipulated haploidentical transplantation. In this study, we evaluated the association of Day 30 absolute lymphocyte count (ALC-30) with transplant outcomes in 60 consecutive pediatric patients with hematological malignancies receiving T-cell-repleted transplantation from an haploidentical related donors. After median follow-up of 36 months (range, 1.4-75 months), higher relapse rate was observed in patients with an ALC-30 < 300 cells/μL compared to patients with an ALC-30 ≥ 300 cells/μL (35.5% vs. 13.8%, P = 0.049). More patients died of infections in those with an ALC-30 < 300 cells/μL compared with patients with an ALC-30 ≥ 300 cells/μL (25.8% vs. 3.4%, P = 0.015). The ALC-30 above the cutoff value 300 cells/μL was associated with improved overall-survival (HR 0.301, 95% CI 0.117-0.771; P = 0.012), leukemia free survival (HR 0.195, 95% CI 0.078-0.498; P=0.002), less relapse (HR 0.224 95% CI 0.070-0.717; P = 0.012), and less transplant- related mortality (HR=0.166; 95%CI 0.037-0.750; P = 0.020). Our results suggest that a higher ALC-30 ≥ 300 cells/μL) could be a useful and simple tool to predict pediatric patients with a superior outcome after unmanipulated haploidentical transplantation.

  8. A history of bone marrow transplantation.

    PubMed

    de la Morena, M Teresa; Gatti, Richard A

    2010-02-01

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

  9. 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.

  10. 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.

  11. Allogeneic Hematopoietic Cell Transplantation for Aggressive NK Cell Leukemia. A Center for International Blood and Marrow Transplant Research Analysis.

    PubMed

    Hamadani, Mehdi; Kanate, Abraham S; DiGilio, Alyssa; Ahn, Kwang Woo; Smith, Sonali M; Lee, Jong Wook; Ayala, Ernesto; Chao, Nelson; Hari, Parameswaran; Bolaños-Meade, Javier; Gress, Ronald; Smedegaard Anderson, Niels; Chen, Yi-Bin; Farooq, Umar; Schiller, Gary; Yared, Jean; Sureda, Anna; Fenske, Timothy S; Olteanu, Horatiu

    2017-02-01

    Aggressive NK cell leukemia (ANKL) is an exceedingly rare form of leukemia and carries a poor prognosis, with a median survival of only 2 months. Using the Center for International Blood and Marrow Transplant Research database, we evaluated outcomes of allogeneic hematopoietic cell transplantation (alloHCT) in patients with ANKL. Twenty-one patients with a centrally confirmed diagnosis of ANKL were included. Median patient age was 42 years and 15 patients (71%) were Caucasian. Fourteen patients (67%) were in complete remission (CR) at the time of alloHCT, and 5 patients had active disease. Median follow-up of survivors was 25 months (range, 12 to 116). The 2-year estimates of nonrelapse mortality, relapse/progression, progression-free (PFS), and overall survival (OS) were 21%, 59%, 20%, and 24%, respectively. The 2-year PFS of patients in CR at the time of alloHCT was significantly better than that of patients with active disease at transplantation (30% versus 0%; P = .001). The 2-year OS in similar order was 38% versus 0% (P < .001). In conclusion, this registry analysis that included majority non-Asian patient population shows that alloHCT can provide durable disease control in a subset of ANKL patients. Achieving CR before transplantation appears to be a prerequisite for successful transplantation outcomes.

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

    PubMed

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

    2014-12-01

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

  13. Prevention of diabetes in rats by bone marrow transplantation.

    PubMed

    Alinaji; Silvers, W K; Bellgrau, D; Anderson, A O; Plotkin, S; Barker, C F

    1981-09-01

    Hyperglycemia, hypoinsulinemia and ketonemia often develop abruptly in previously normal young "BB" rats. The syndrome mimics human juvenile diabetes closely and is, thus, appropriate for assessing pancreatic transplantation. Transplantation of islet cells from closely histocompatible Wistar Furth (WF) donor resulted in permanent normoglycemia when immunosuppression with ALS was given. However, when islet cells from nondiabetic "BB" donors were transplanted to nonimmunosuppressed diabetic "BB" recipients, only transient normoglycemia followed. Transplantation of WF islets cells also failed in diabetic "BB" rats which were tolerant of WF antigens, again suggesting destruction of transplanted islet cells by the original disease process-possibly autoimmunity. Evidence for autoimmunity was strengthened by the finding that newly diabetic "BB" rats could be rendered normoglycemic by immunosuppression. Since genetic susceptibility to spontaneous autoimmune diabetes is unique to some members of the "BB" stock, an attempt was made to alter their vulnerability by modifying their cellular immune system. Accordingly, 50 million bone marrow cells from WF donors were inoculated into half the newborn members of "BB" litters, leaving the littermates as unmodified controls. Most bone marrow recipients were protected, only four of 37 (10.8%) ever becoming diabetic, while the incidence of diabetes in noninoculated littermates was 22 of 39 (56.4%). The ultimate goal in human diabetes, which also seems very likely to be an autoimmune disease, may not be replacement of destroyed islet cells but identification of potentially susceptible children and prevention of islet destruction by immunologic manipulation.

  14. Mouse Models in Bone Marrow Transplantation and Adoptive Cellular Therapy

    PubMed Central

    Arber, Caroline; Brenner, Malcolm K.; Reddy, Pavan

    2014-01-01

    Mouse models of transplantation have been indispensable to the development of bone marrow transplantation (BMT). Their role in the generation of basic science knowledge is invaluable and is subject to discussion below. However, this article focuses on the direct role and relevance of mouse models towards the clinical development and advances in BMT and adoptive T-cell therapy for human diseases. The authors aim to present a thoughtful perspective on the pros and cons of mouse models while noting that despite imperfections these models are obligatory for the development of science-based medicine. PMID:24216170

  15. T cell regeneration after allogenic bone marrow transplantation

    PubMed Central

    Favrot, Marie; Janossy, G.; Tidman, N.; Blacklock, Hilary; Lopez, Elisa; Bofill, Margarita; Lampert, I.; Morgenstein, G.; Powles, R.; Prentice, H. G.; Hoffbrand, A. V.

    1983-01-01

    Various T cell subsets were characterized by double immunofluorescent staining using monoclonal antibodies (MoAb) in blood, bone marrow (BM) and tissues of 29 patients after allogeneic BM transplantation (BMT). In an attempt to prevent graft versus host disease (GvHD), 15 patients received cyclosporin A (Cy A). In the remaining 14 patients the BM was pre-incubated with a MoAb, OKT3. The regeneration of T4+ subset was delayed and the level of T8+ cells was abnormally high even 1 year after engraftment. This did not have any predictive value for the appearance of complications such as GvHD or severe viral infections. The number of T8+ cells was lower in the group of patients who received Cy A than in the OKT3 group (0·7±0·2 vs 1·5±0·3×109/1 at day 90). In contrast to normal individuals, the T4/T8 ratio in both blood and regenerating BM of BMT patients was <1. A sizeable subset of circulating T cells expressed the phenotype T8+,T10+,HNK-1+,DR+. Circulating cells of this phenotype were transiently very high (up to 50%) in patients with active GvHD or suffering from severe viral infection. This subpopulation of lymphocytes was not found in the epidermal infiltrate that accompanied GvHD where the predominant phenotype was T8+,T1-,T10-,HNK-1-,DR-. We conclude therefore that after BMT the number and phenotype of circulating T cells reflects the T cell distribution seen in the regenerating BM. PMID:6352107

  16. Fatal Hemorrhagic Gastrointestinal Angioectasia after Bone Marrow Transplantation for Dyskeratosis Congenita

    PubMed Central

    Imai, Jin; Suzuki, Takayoshi; Yoshikawa, Marie; Dekiden, Makiko; Nakae, Hirohiko; Nakahara, Fumio; Tsuda, Shingo; Mizukami, Hajime; Koike, Jun; Igarashi, Muneki; Yabe, Hiromasa; Mine, Tetsuya

    2016-01-01

    Dyskeratosis congenita (DC) is a rare inherited disease in which the telomere complex cannot be maintained. Shortened telomeres can cause a number of clinical conditions. We herein report a case of unrelated bone marrow transplantation due to aplastic anemia associated with DC. The patient died of uncontrollable refractory intestinal bleeding. Three cases of DC with life-threatening hemorrhaging after transplantation have been reported; however, the bleeding origin could not be determined. Our case is the only patient in which a gastrointestinal bleeding point, jejunal multiple angioectasia, was determined. PMID:27904106

  17. Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains

    PubMed Central

    Weimann, James M.; Charlton, Carol A.; Brazelton, Timothy R.; Hackman, Robert C.; Blau, Helen M.

    2003-01-01

    We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-mismatched) or female (sex-matched, control) bone marrow transplants. Cerebella were evaluated in 10-μm-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to ≈50% of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons. PMID:12576546

  18. No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET

    PubMed Central

    Tossios, Paschalis; Müller-Ehmsen, Jochen; Schmidt, Matthias; Scheid, Christof; Ünal, Nermin; Moka, Detlef; Schwinger, Robert HG; Mehlhorn, Uwe

    2006-01-01

    Background We tested the hypothesis, that intramyocardial injection of mononuclear bone marrow cells combined with coronary artery bypass grafting (CABG) surgery improves tissue viability or function in infarct regions with non-viable myocardium as assessed by nuclear imaging techniques. Methods Thus far, 7 patients (60 ± 10 [SD] years) undergoing elective CABG surgery after a myocardial infarction were included in this study. Prior to sternotomy, bone marrow was harvested by sternal puncture. Mononuclear bone marrow cells were isolated by gradient centrifugation and resuspended in 2 ml volume of Hank's buffered salt solution. At the end of CABG surgery 10 injections of 0.2 ml each were applied to the core area and borderzones of the infarct. Global and regional perfusion and viability were evaluated by ECG-gated 99mTc-tetrofosmin myocardial single-photon emission computed tomograph (SPECT) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in all study patients < 6 days before and 3 months after the intervention. Results Non-viable segments indicating transmural defects were identified in 5 patients. Two patients were found to have non-transmural defects before surgery. Concomitant surgical revascularisation and bone marrow cell injection was performed in all patients without major complications. The median total injected mononuclear cell number was 7.0 × 107 (range: 0.8–20.4). At 3 months 99mTc-tetrofosmin SPECT and 18F-FDG-PET scanning showed in 5 patients (transmural defect n = 4; non-transmural defect n = 1) no change in myocardial viability and in two patients (transmural defect n = 1, non-transmural defect n = 1) enhanced myocardial viability by 75%. Overall, global and regional LV ejection fraction was not significantly increased after surgery compared with the preoperative value. Conclusion In CABG surgery patients with non-viable segments the concurrent use of intramyocardial cell transfer did not show any clear improvement in

  19. The intra-bone marrow injection of cord blood cells extends the possibility of transplantation to the majority of patients with malignant hematopoietic diseases.

    PubMed

    Frassoni, Francesco; Varaldo, Riccardo; Gualandi, Francesca; Bacigalupo, Andrea; Sambuceti, GianMario; Sacchi, Nicoletta; Podestà, Marina

    2010-06-01

    Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35-5.4)×10(7)/kg; the HLA disparity was: 12 cases=5/6, 62 cases=4/6 and 1 case=3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500×10(9)/L and platelets (PLT) >20 000×10(9)/L was: 23 (14-44) and 35 (16-70) days respectively. The outcomes at 2 years according to Kaplan-Meier are: OS=46%±5; RI=18%±2; NRM=39%±5. Acute GVHD incidence/severity was: grade 0-I=64%, II=14%, III-IV=0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival.

  20. [Current status of allogenic bone marrow transplantation in chronic myelocytic leukemia].

    PubMed

    Speck, B; Gratwohl, A; Osterwalder, B; Nissen, C; Buser, U; Reusser, P; Tichelli, A; Würsch, A; Jeannet, M

    1984-10-06

    Bone marrow transplants were carried out in 18 patients with chronic myelogenous leukemia (CML) in the chronic phase (CP). 12 (67%) are still alive, 11 without evidence of leukemia after a mean observation period of 24 (3-44) months, 1 relapsed and 6 died. The most frequent cause of death was GvHD and interstitial pneumonia (5). 1 patient died of septicemia. 2 grafts were performed in patients with CML in the accelerated phase (AP); both died, one from leukemic relapse and one from GvHD. The authors also participated in an international study in which 117 patients were evaluated. In CP there was a survival plateau at 63%, in AP at 36% and in blastic crisis at 12%. In CP mortality was primarily age-dependent and relapses occurred in only 7%. It is concluded that bone marrow transplantation (BMT) is a highly successful treatment for CML, with the CP the optimum moment for grafting. Longlasting cytogenetic and clinical remissions with potential for cure are possible in a high percentage of patients. The incidence of transplant-related mortality is acceptable. The incidence of leukemic relapse is low in CP. Patients under age 40 with HLA-identical siblings should be transplanted in CP. At present BMT is the only treatment with curative potential for CML.

  1. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.

    PubMed

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W C J; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.

  2. High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation

    PubMed Central

    Cook, Gordon; Iacobelli, Simona; van Biezen, Anja; Ziagkos, Dimitris; LeBlond, Veronique; Abraham, Julie; McQuaker, Grant; Schoenland, Stefan; Rambaldi, Alessandro; Halaburda, Kazimierz; Rovira, Maria; Sica, Simona; Byrne, Jenny; Sanz, Ramon Garcia; Nagler, Arnon; van de Donk, Niels W.C.J.; Sinisalo, Marjatta; Cook, Mark; Kröger, Nicolaus; De Witte, Theo; Morris, Curly; Garderet, Laurant

    2017-01-01

    POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997–2010 with a median age of 50 years (range 26–69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome. PMID:27634201

  3. Haematopoietic stem cell transplantation for Shwachman-Diamond disease: a study from the European Group for blood and marrow transplantation.

    PubMed

    Cesaro, Simone; Oneto, Rosi; Messina, Chiara; Gibson, Brenda E; Buzyn, Agnes; Steward, Colin; Gluckman, Eliane; Bredius, Robbert; Breddius, Robbert; Boogaerts, Marc; Vermylen, Christiane; Veys, Paul; Marsh, Judith; Badell, Isabel; Michel, Gerard; Güngör, Tayfun; Niethammer, Dietrich; Bordigoni, Pierre; Oswald, Cecilia; Favre, Claudio; Passweg, Jakob; Dini, Giorgio

    2005-10-01

    This report assessed the results of allogeneic stem cell transplantation (allo-SCT) in 26 patients with Shwachman-Diamond disease (SDS) and severe bone marrow abnormalities. The conditioning regimen was based on busulphan (54%), total body irradiation (23%), fludarabine (15%) or other chemotherapy combinations (8%). Standard prevention of graft versus host disease (GVHD) with cyclosporin +/- methotrexate was adopted in 54% of the patients whilst in vivo or in vitro T-cell depletion was used in 17 and four patients respectively. Neutrophil and platelet engraftment were achieved in 21 (81%) and 17 (65%) of 26 patients after a median time of 18 days and 29 days respectively. The incidence of grade III and IV acute GVHD was 24% and of chronic GVHD 29%. Nine patients died after a median time of 70 d, post-SCT. After a median follow-up of 1.1 years, the transplant-related mortality was 35.5% (95% CI 17-54) whilst the overall survival was 64.5% (95% CI 45.7-83.2). Allo-SCT was found to be successful in more than half of SDS patients with severe bone marrow dysfunction. Further improvements would be anticipated by a better definition of the optimum time in the course of disease to transplant and by the adoption of less toxic conditioning regimens.

  4. Haemopoietic recovery in spleen and marrow after transplantation of bone marrow from either normal or hydroxyurea treated mice.

    PubMed

    Hasthorpe, S; Hodgson, G S

    1977-09-01

    Haemopoietic regeneration was studied following x-irradiation and transplantation of bone marrow from either normal or hydroxyurea-treated donor mice, to ascertain the contribution of proliferating progenitor cells to regeneration. With transplantation of equivalent numbers of CFU-S, total DNA and 3HTdR uptake into DNA in spleen and femoral bone marrow and the erythroid, granulocytic and mononuclear cell populations were not significantly different between normal (NBM) and hydroxyurea-treated (HUBM) marrow. The response of hypertransfused x-irradiated mice to erythropoietin (EPO) administration was also not significantly different in spleens of mice receiving normal or hydroxyurea-treated marrow.

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2014-02-01

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

  7. Bone marrow transplant cure for beta-thalassaemia major: initial experience from a developing country.

    PubMed

    Ullah, Khalil; Khan, Badshah; Raza, Shahid; Ahmed, Parvez; Satti, Tariq M; Butt, Tariq; Tariq, Waheed Z; Kamal, Muhammad K

    2008-08-01

    Between July 2001 and June 2007, 48 consecutive patients with beta-thalassaemia major received allogeneic haematopoietic stem cell transplants (allo HSCT) from human-leukocyte-antigen-matched siblings at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, using standard conditioning regimens. The median age of the patient cohort was 4 years (range, 1-14 years). Thirty-one patients were in risk class I, 11 in class II and six patients were in class III. Engraftment was achieved in all patients. Survival was calculated from the date of transplant to death or last follow-up. Major post-transplant complications encountered were acute graft versus host disease (Ac GvHD) (grades II-IV), 35.4%; chronic GvHD, 8.3%; haemorrhagic cystitis, 12.5%; veno-occlusive disease (VOD) of the liver, 6.2%; bacterial infections, 37.5%; fungal infections, 19%; cytomegalovirus (CMV) infection, 6.2%; herpes infection, 6.2%; and tuberculosis in 2% of patients. Graft rejection was observed in five patients. Three patients received second transplants. Mortality was observed in 20.8% of patients. Major fatal complications included GvHD, VOD, intracranial haemorrhage, septicaema, CMV disease and disseminated tuberculosis. Overall survival and disease-free survival were 79% and 75%, respectively, at 6 years post-HSCT.

  8. Blood and marrow transplantation for sickle cell disease: is less more?

    PubMed

    Bolaños-Meade, Javier; Brodsky, Robert A

    2014-11-01

    Blood and marrow transplantation is a curative therapy for patients with sickle cell disease yet this option is 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.

  9. 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

  10. 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.

  11. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, the Center for International Blood and Marrow Transplant Research, and the American Society of Blood and Marrow Transplantation.

    PubMed

    Rizzo, J Douglas; Wingard, John R; Tichelli, Andre; Lee, Stephanie J; Van Lint, Maria Teresa; Burns, Linda J; Davies, Stella M; Ferrara, James L M; Socié, Gérard

    2006-02-01

    More than 40000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers, and many community health care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Bone Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.

  12. Pharmacokinetic and Maximum Tolerated Dose Study of Micafungin in Combination with Fluconazole versus Fluconazole Alone for Prophylaxis of Fungal Infections in Adult Patients Undergoing a Bone Marrow or Peripheral Stem Cell Transplant

    PubMed Central

    Hiemenz, J.; Cagnoni, P.; Simpson, D.; Devine, S.; Chao, N.; Keirns, J.; Lau, W.; Facklam, D.; Buell, D.

    2005-01-01

    In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose. PMID:15793107

  13. Pharmacokinetic and maximum tolerated dose study of micafungin in combination with fluconazole versus fluconazole alone for prophylaxis of fungal infections in adult patients undergoing a bone marrow or peripheral stem cell transplant.

    PubMed

    Hiemenz, J; Cagnoni, P; Simpson, D; Devine, S; Chao, N; Keirns, J; Lau, W; Facklam, D; Buell, D

    2005-04-01

    In this dose escalation study, 74 adult cancer patients undergoing bone marrow or peripheral blood stem cell transplantation received fluconazole (400 mg/day) and either normal saline (control) (12 subjects) or micafungin (12.5 to 200 mg/day) (62 subjects) for up to 4 weeks. The maximum tolerated dose (MTD) of micafungin was not reached, based on the development of Southwest Oncology Group criteria for grade 3 toxicity; drug-related toxicities were rare. Commonly occurring adverse events considered related to micafungin were headache (6.8%), arthralgia (6.8%), hypophosphatemia (4.1%), insomnia (4.1%), maculopapular rash (4.1%), and rash (4.1%). Pharmacokinetic profiles for micafungin on days 1 and 7 were similar. The mean half-life was approximately 13 h, with little variance after repeated or increasing doses. Mean maximum concentrations of the drug in serum and areas under the concentration-time curve from 0 to 24 h were approximately proportional to dose. There was no clinical or kinetic evidence of interaction between micafungin and fluconazole. Five of 12 patients (42%) in the control group and 14 of 62 (23%) in the micafungin-plus-fluconazole groups had a suspected fungal infection during treatment which resulted in empirical treatment with amphotericin B. The combination of micafungin and fluconazole was found to be safe in this high-risk patient population. The MTD of micafungin was not reached even at doses up to 200 mg/day for 4 weeks. The pharmacokinetic profile of micafungin in adult cancer patients with blood or marrow transplants is consistent with the profile in healthy volunteers, and the area under the curve is proportional to dose.

  14. 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.

  15. Pure red-cell aplasia of long duration after major ABO-incompatible bone marrow transplantation.

    PubMed

    Volin, L; Ruutu, T

    1990-01-01

    We describe a patient with an exceptionally long-lasting red-cell aplasia of 330 days following ABO-incompatible bone marrow transplantation (BMT). Before BMT, the anti-B titre was high, 1:1,024, and it was only temporarily reduced by extensive plasma exchange. The anti-B titre remained above the level of 1:64 for 270 days, and host-derived isoagglutinin could still be detected 3 years after BMT. In vitro bone marrow cultures during the red-cell aplasia showed greatly reduced numbers or total absence of CFU-E, while the number of BFU-E colonies was only moderately subnormal. Six years after BMT, bone marrow and peripheral-blood cell counts are normal.

  16. [Haploidentical hematopoietic stem cell transplantation: Guidelines from the Francophone society of marrow transplantation and cellular therapy (SFGM-TC)].

    PubMed

    Nguyen, Stéphanie; Chalandon, Yves; Lemarie, Claude; Simon, Sophie; Masson, Dominique; Dhedin, Nathalie; Suarez, Felipe; Renaud, Barbara; Charbonnier, Amandine; Yafour, Nabil; François, Sylvie; Duléry, Rémy; Blaise, Didier; Yakoub-Agha, Ibrahim; Rubio, Marie-Thérèse

    2016-11-01

    Haploidentical hematopoietic stem cell transplantation (HSCT) is being increasingly used due to improvement of the transplantation procedures allowing a reduction of graft-versus-host-disease (GVHD) and of transplant-related mortality (TRM). Such improvements have been particularly observed after administration of T-replete HSCT graft associated to an in vivo T cell depletion by the administration of high-doses of cyclophosphamide (HD-Cy) after transplantation. Here, we have analyzed the results of haplo-identical T replete HSC transplants, in particular, when performed with post-transplant HD-Cy in order to provide recommendations for the clinical practice. Criteria of choice for a haploidentical donor by priority order are absence of donor-specific antibodies (DSA) and to prioritize: CMV seronegative recipient/donor couples, ABO matching in case of deserythrocytation, male donor for a male recipient, the youngest donor. There is no clear argument in favor of the use of bone marrow versus peripheral blood stem cells (PBSC) after non myeloablative conditioning regimen, while after ablative conditioning PBSC seem to be associated with higher risks of GVHD without obvious impact on survival. Results of haploidentical HSCT, confirmed by several groups, are interesting in lymphomas (in particular Hodgkin disease) and for acute leukemia. Outcomes of patients rely on age, disease status at transplant and conditioning intensity. At equivalent disease risk, results of haploidentical HSCT seem comparable to those of HLA matched HSCT, raising the question of the classification of such transplants as alternatives. In all cases, we recommend to include patients in prospective clinical trials.

  17. 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

  18. Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

    PubMed

    Couban, Stephen; Aljurf, Mahmoud; Lachance, Sylvie; Walker, Irwin; Toze, Cynthia; Rubinger, Morel; Lipton, Jeffrey H; Lee, Stephanie J; Szer, Richard; Doocey, R; Lewis, Ian D; Huebsch, Lothar; Howson-Jan, Kang; Lalancette, Michel; Almohareb, Fahad; Chaudhri, Nadeem; Ivison, Sabine; Broady, Raewyn; Levings, Megan; Fairclough, Diane; Devins, Gerald; Szwajcer, David; Foley, Ronan; Smith, Clayton; Panzarella, Tony; Kerr, Holly; Kariminia, Amina; Schultz, Kirk R

    2016-08-01

    In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

  19. Composite vascularized skin/bone transplantation models for bone marrow-based tolerance studies.

    PubMed

    Ozmen, Selahattin; Ulusal, Betul G; Ulusal, Ali E; Izycki, Dariusz; Siemionow, Maria

    2006-03-01

    There is an ongoing need to understand the mechanisms of bone marrow-based allograft tolerance. This is important in clarifying the diverse variables influencing the ultimate outcome of the solid organ and composite tissue transplants. To establish bone marrow transplantation as a routine clinical application, further experimental studies should be conducted to overcome the obstacles related to the bone marrow transplantation. These obstacles include graft versus host disease, immunocompetence, and toxicity of the conditioning regimens. For these purposes, novel experimental models are needed. In an attempt to provide a reliable research tool for bone marrow-based tolerance induction studies, we introduced different experimental models of modified vascularized skin/bone marrow (VSBM) transplantation technique for tolerance induction, monitoring, and maintenance studies. In this skin/bone transplantation model, the technical feasibility of concurrent or consecutive transplantation of the combination of bilateral vascularized skin, vascularized bone marrow, or vascularized skin/bone marrow transplants was investigated. Isograft transplantations were performed between genetically identical Lewis (LEW, RT1) rats. Five different experimental designs in 5 groups of 5 animals each were studied. Group I: Bilateral vascularized skin (VS) transplantation; group II: bilateral vascularized skin/bone transplantation; group III: vascularized skin transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group IV: vascularized bone transplantation on one side and vascularized skin/bone transplantation on the contralateral side; group V: vascularized bone transplantation on one side and vascularized skin transplantation on the contralateral side. Successful transplantations were performed in all groups. The survival of the isograft transplants was evaluated clinically and histologically. All skin flaps remained pink and pliable and grew new

  20. Blood and marrow transplantation: a perspective from the University of Minnesota.

    PubMed

    Kersey, John H

    2007-01-01

    On the occasion of the first meeting of the Robert A. Good Immunology Society in June of 2006, I was asked to provide a perspective on the history and progress of the field of bone marrow transplantation. I was honored to provide this perspective at that meeting and subsequently in this manuscript. This review has a strong University of Minnesota bias, as Minneapolis is a place where important roots in this field were developed. Minnesota is also where I have spent my career in this field learning the excitement of laboratory research beginning as a medical student under Bob Good and Carlos Martinez in 1960, and clinical research in pediatrics under Bill Krivit and Mark Nesbit beginning in 1970. This review is dedicated to two of my recently deceased mentors: Bob Good was a pioneer in so many ways and a true giant in immunology and blood and marrow transplantation. Bill Krivit taught me a great deal about genetic diseases and the critical role of compassion and understanding patients and their families in dealing with fatal illness and new treatments such as bone marrow transplantation that are often risky and themselves may result in suffering and death. My affection for Bob Good and Bill Krivit is unending.

  1. Prolonged survival in mice with advanced tumors treated with syngeneic or allogeneic intra-bone marrow-bone marrow transplantation plus fetal thymus transplantation.

    PubMed

    Hosaka, Naoki; Cui, Wenhao; Zhang, Yuming; Takaki, Takashi; Inaba, Muneo; Ikehara, Susumu

    2010-07-01

    Thymic function decreases in line with tumor progression in patients with cancer, resulting in immunodeficiency and a poor prognosis. In the present study, we attempted to restore thymic function by BALB/c (H-2(d)) syngeneic (Syn), or B6 (H-2(b)) allogeneic (Allo) bone marrow transplantation (BMT) using intra-bone marrow-bone marrow transplantation (IBM-BMT) plus Syn-, Allo- or C3H (H-2(k)) 3rd-party fetal thymus transplantation (TT). Although the BALB/c mice with advanced tumors (Meth-A sarcoma; H-2(d), >4 cm(2)) treated with either Syn- or Allo-BMT alone showed a slight improvement in survival compared with non-treated controls, the mice treated with BMT + TT showed a longer survival. The mice treated with Allo-BMT + Allo-TT or 3rd-party TT showed the longest survival. Interestingly, although there was no difference in main tumor size among the BMT groups, lung metastasis was significantly inhibited by Allo-BMT + Allo-TT or 3rd-party TT. Numbers of CD4(+) and CD8(+) T cells, Con A response, and IFN-gamma production increased significantly, whereas number of Gr-1(+)/CD11b(+) myeloid suppressor cells and the percentage of FoxP3(+) cells in CD4(+) T cells significantly decreased in these mice. Furthermore, there was a positive correlation between survival days and the number of T cells or T cell function, while there was a negative correlation between survival days and lung metastasis, the number of Gr-1(+)/CD11b(+) cells, or the percentage of FoxP3(+) cells. These results suggest that BMT + TT, particularly Allo-BMT + Allo-TT or 3rd-party TT, is most effective in prolonging survival as a result of the restoration of T cell function in hosts with advanced tumors.

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

    PubMed

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

    2015-11-01

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

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

    PubMed

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

    1991-11-01

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

  4. B- and T-lymphocyte number and function in HIV+/HIV− lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

    PubMed Central

    Bertoli, Diego; Re, Alessandro; Chiarini, Marco; Sottini, Alessandra; Serana, Federico; Giustini, Viviana; Roccaro, Aldo M.; Cattaneo, Chiara; Caimi, Luigi; Rossi, Giuseppe; Imberti, Luisa

    2016-01-01

    Combination of anti-retroviral therapy, high-dose chemotherapy (HCT) and autologous stem cell transplantation (ASCT) has led to an improved survival of HIV+ non-Hodgkin lymphoma (NHL) patients. We compared T- and B-cell subset recovery and related capability to respond to in-vitro stimulation, as well as T-cell repertoire modifications of HIV+ and HIV− NHL patients undergoing HCT and ASCT as first-line consolidation or salvage treatment, using sequential blood samples obtained before and at 3, 6, 12 and 24 months after ASCT. B lymphocyte recovery occurred earlier, reaching higher levels in HIV+ patients as compared to HIV− patients and healthy controls; in particular, immature and naïve B cells were significantly higher in HIV+ patients who had received rituximab in the pre-ASCT period. These lymphocytes equally responded to in-vitro stimulation. Newly produced T cells similarly increased in HIV+ and HIV− NHL patients, but their levels remained constantly lower than in healthy controls. T lymphocytes showed a reduced proliferative capacity, but their repertoire was reassorted by the treatment. The functional and numeric B-cell recovery and the qualitative modifications of T-cell receptor repertoire may explain, at least in part, the success of this aggressive therapeutic approach in HIV+ patients. PMID:27905485

  5. High-dose melphalan and total body irradiation with bone marrow transplantation for refractory malignancies.

    PubMed

    Spitzer, G; Jagannath, S; Dicke, K A; Armitage, J; Zander, A R; Vellekoop, L; Horwitz, L; Cabanillas, F; Zagars, G K; Velasquez, W S

    1986-06-01

    We investigated if high dose melphalan and total body irradiation could be administered to adult patients with acceptable toxicity. Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m2-140 mg/m2) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). An occasional patient may be cured by this approach. The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. The combination warrants further investigation in a less heavily pretreated population to determine more accurately the complete response rate.

  6. Sirolimus Pharmacokinetics in Early Postmyeloablative Pediatric Blood and Marrow Transplantation

    PubMed Central

    Goyal, Rakesh K.; Han, Kelong; Wall, Donna A.; Pulsipher, Michael A.; Bunin, Nancy; Grupp, Stephan A.; Mada, Sripal R.; Venkataramanan, Raman

    2014-01-01

    This study examined the pharmacokinetics of sirolimus in pediatric allogeneic blood and marrow transplantation (BMT) recipients in the presence and absence of concomitant fluconazole. Forty pediatric BMT recipients received a daily oral dose of sirolimus and a continuous i.v. infusion of tacrolimus for graft-versus-host disease prophylaxis. Fluconazole was administered i.v. to 19 patients and orally to 6 patients. Full pharmacokinetic profiles of sirolimus within a single dosing interval were collected. Whole-blood sirolimus concentrations were measured by HPLC/mass spectrometry. Noncompartmental analysis was performed using WinNonlin. Nonlinear mixed-effects pharmacokinetic models were developed using NONMEM following standard procedures. The mean ± SD sirolimus trough level before the dose (C0) was 8.0 ± 4.6 ng/mL (range, 1.8–21.6 ng/mL). The peak concentration was 19.9 ± 11.8 ng/mL (range, 3.9–46.1 ng/mL), and the trough level 24 hours later (C24) was 9.1 ± 5.3 ng/mL (range, 1.0–19.1 ng/mL). The terminal disposition half-life (T1/2) was 24.5 ± 11.2 hours (range, 5.8–53.2 hours), and the area under the concentration-versus-time curve (AUC0–24) was 401.1 ± 316.3 ng·h/mL (range, 20.7–1332.3 ng·h/mL). In patients at steady state, C0 and C24 were closely correlated (R2 = 0.77) with a slope of 0.99, indicating the achievement of steady state. C24 was 1.7-fold greater (P = .036) and AUC0–24 was 2-fold greater (P = .012) in Caucasian patients (n = 22) compared with Hispanic patients (n = 9). The average apparent oral clearance was 3-fold greater (P = .001) and the apparent oral volume of distribution was 2-fold greater (P = .018) in patients age ≤12 years compared with those age >12 years. C24 was significantly lower in patients (n = 10) who developed grade III–IV aGVHD (n = 10) than in those with grade 0-II aGVHD (n = 22) (6.1 ± 2.9 ng/mL versus 9.4 ± 5.5 ng/mL; P = .044). Dose-normalized sirolimus trough concentrations were significantly

  7. Cutaneous and bone marrow histoplasmosis after 18 years of renal allograft transplant.

    PubMed

    Ibrahim, K Y; Carvalho, N B; Mimicos, E V; Yeh-Li, H; Sotto, M N; França, F O S

    2014-10-01

    The frequency of histoplasmosis among solid organ transplant (SOT) recipients appears to be low where there are only a few case series, mostly among renal and liver transplant recipients. Herein we report a case of a 44-year-old woman who underwent a living-related renal transplant 18 years prior to evaluation, developed a nodule after followed by ulceration upon her posterior right leg and a second one upon her left leg 3 months and 2 months before her hospitalisation, respectively. The biopsy of lesion revealed the presence of Histoplasma spp. Bone marrow aspiration was performed and also revealed the same organism. She had initially received itraconazole without improvement of lesions, while a new lesion appeared on her left arm. Healing of all lesions could be observed after 40 days of liposomal amphotericin B when she was submitted to skin grafts on the legs and a surgical treatment on the arms, and the myelosuppression improved simultaneously. Histoplasmosis seems to be very uncommon among patients who underwent to organ solid transplantation. Most cases occur within 12-18 months after transplantation, although unusual cases have been presented many years post-transplant. There are cases reported in the literature, occurring from 84 days to 18 years after organ transplantation, but without cutaneous involvement. Our patient developed lesions on limbs and myelosuppression after 18 years of chronic immunosuppression medication. This case suggests that besides cutaneous histoplasmosis is an uncommon infection following iatrogenic immunosuppression and even rarer over a long period after the transplantation. Clinicians who care SOT recipient patients must bear in mind histoplasmosis infection as differential diagnosis in any case of cutaneous injury with prolonged fever and try to use as many tools as possible to make the diagnosis, once this disease presents a good prognosis if it is diagnosed and treated promptly.

  8. Allogeneic marrow transplantation following cyclophosphamide and escalating doses of hyperfractionated total body irradiation in patients with advanced lymphoid malignancies: A phase I/II trial

    SciTech Connect

    Demirer, T.; Petersen, F.B.; Appelbaum, F.R.

    1995-07-15

    The purpose of this investigation was to define the maximum tolerated dose (MTD) of unshielded total body irradiation (TBI) delivered from dual {sup 60}C sources at an exposure rate of 0.08 Gy/min and given in thrice daily fractions of 1.2 Gy in patients with advanced lymphoid malignancies. Forty-four patients with a median age of 28 (range 6-48) years were entered into a Phase I/II study. All patients received cyclophosphamide (Cy), 120 mg/kg administered over 2 days before TBI. Marrow from human leukocyte antigen (HLA) identical siblings was infused following the last dose of TBI. An escalation-deescalation schema designed to not exceed an incidence of 25% of Grade 3-4 regimen-related toxicities (RRTs) was used. The first dose level tested was 13.2 Gy followed by 14.4 Gy. None of the four patients at the dose level of 13.2 Gy developed Grade 3-4 RRT. Two of the first eight patients receiving 14.4 Gy developed Grade 3-4 RRT, establishing this as the MTD. An additional 32 patients were evaluated at the 14.4 Gy level to confirm these initial observations. Of 40 patients receiving 14.4 Gy, 13 (32.5%) developed Grade 3-4 RRTs; 46% in adults and 12% in children. The primary dose limiting toxicity was Grade 3-4 hepatic toxicity, which occurred in 12.5% of patients. Noninfectious Grade 3-4 interstitial pneumonia syndrome occurred in 5% of patients. The actuarial probabilities of event-free survival, relapse, and nonrelapse mortality at 2 years were 0.10, 0.81, and 0.47, respectively, for patients who received 14.4 Gy of TBI. The outcome for patients receiving 14.4 Gy of TBI was not different from previous studies of other CY and TBI regimens in patients with advanced lymphoid malignancies. These data showed that the incidence of Grade 3-4 RRTs in adults was greater than the 25% maximum set as the goal of this study, suggesting that 13.2 Gy is a more appropriate dose of TBI for adults, while 14.4 Gy is an appropriate dose for children. 36 refs., 1 fig., 3 tabs.

  9. 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.

  10. A Melanoma Lymph Node Metastasis with a Donor-Patient Hybrid Genome following Bone Marrow Transplantation: A Second Case of Leucocyte-Tumor Cell Hybridization in Cancer Metastasis

    PubMed Central

    Duvall, Eric; Grasmick, Zachary; Haedicke, Kay

    2017-01-01

    Background Metastatic disease is the principal cause of mortality in cancer, yet the underlying mechanisms are not fully understood. Macrophage-cancer cell fusion as a cause of metastasis was proposed more than a century ago by German pathologist Prof. Otto Aichel. Since then this theory has been confirmed in numerous animal studies and recently in a patient with metastatic melanoma. Methods Here we analyzed tumor DNA from a 51-year-old man who, 8 years following an allogeneic BMT from his brother for treatment of chronic myelogenous leukemia (CML), developed a nodular malignant melanoma on the upper back with spread to an axillary sentinal lymph node. We used laser microdissection to isolate FFPE tumor cells free of leucocytes. They were genotyped using forensic short tandem repeat (STR) length-polymorphisms to distinguish donor and patient genomes. Tumor and pre-transplant blood lymphocyte DNAs were analyzed for donor and patient alleles at 15 autosomal STR loci and the sex chromosomes. Results DNA analysis of the primary melanoma and the nodal metastasis exhibit alleles at each STR locus that are consistent with both the patient and donor. The doses vary between these samples indicative of the relative amounts of genomic DNA derived from the patient and donor. Conclusion The evidence supports fusion and hybridization between donor and patient cells as the initiator of metastasis in this patient. That this phenomenon has now been seen in a second case suggests that fusion is likely to play a significant role for melanoma and other solid tumor metastasis, perhaps leading to new avenues of treatment for this most problematic disease. PMID:28146572

  11. Unmanipulated haploidentical bone marrow transplantation and post-transplant cyclophosphamide for hematologic malignanices following a myeloablative conditioning: an update.

    PubMed

    Bacigalupo, A; Dominietto, A; Ghiso, A; Di Grazia, C; Lamparelli, T; Gualandi, F; Bregante, S; Van Lint, M T; Geroldi, S; Luchetti, S; Grasso, R; Pozzi, S; Colombo, N; Tedone, E; Varaldo, R; Raiola, A M

    2015-06-01

    This is a report of 148 patients with hematologic malignancies who received an unmanipulated haploidentical bone marrow transplant (BMT), followed by post-transplant high-dose cyclophosphamide (PT-CY). All patients received a myeloablative conditioning consisting of thiotepa, busulfan, fludarabine (n=92) or TBI, fludarabine (n=56). The median age was 47 years (17-74); 47 patients were in first remission (CR1), 37 in second remission (CR2) and 64 had an active disease; all patients were first grafts. The diagnosis was acute leukemia (n=75), myelodisplastic syndrome (n=24), myelofibrosis (n=16), high-grade lymphoma (n=15) and others (n=18). GVHD prophylaxis consisted in PT-CY on days +3 and +5, cyclosporine (from day 0), and mycophenolate (from day +1). The median day for neutrophil engraftment was day +18 (13-32). The cumulative incidence of grades II-IV acute GVHD was 24%, and of grades III-IV GVHD 10%. The incidence of moderate-severe chronic GVHD was 12%. With a median follow-up for the surviving patients of 313 days (100-1162), the cumulative incidence of transplant-related mortality (TRM) is 13%, and the relapse-related death is 23%. The actuarial 22 months overall survival is 77% for CR1 patients, 49% for CR2 patients and 38% for patients grafted in relapse (P<0.001). Major causes of death were relapse (22%), GVHD (2%) and infections (6%). We confirm our initial results, suggesting that a myeloablative conditioning regimen followed by unmanipulated haploidentical BMT with PT-CY, results in a low risk of acute and chronic GVHD and encouraging rates of TRM and overall survival, also for patients with active disease at the time of transplant.

  12. Cytomegalovirus pneumonia in transplant patients: CT findings

    SciTech Connect

    Eun-Young Kang; Patz, E.F. Jr.; Mueller, N.L.

    1996-03-01

    Our goal was to assess the CT findings of cytomegalovirus (CMV) pneumonia in transplant patients. The study included 10 transplant patients who had chest CT scan and pathologically proven isolated pulmonary CMV infection. Five patients had bone marrow transplant and five had solid organ transplant. The CT scans were retrospectively reviewed for pattern and distribution of disease and the CT findings compared with the findings on open lung biopsy (n = 9) and autopsy (n = 1). Nine of 10 patients had parenchymal abnormalities apparent at CT and I had normal CT scans. The findings in the nine patients included small nodules (n = 6), consolidation (n = 4), ground-glass attenuation (n = 4), and irregular lines (n = 1). The nodules had a bilateral and symmetric distribution and involved all lung zones. The consolidation was most marked in the lower lung zones. The CT findings of CMV pneumonia in transplant patients are heterogeneous. The most common patterns include small nodules and areas of consolidation. 13 refs., 4 figs., 1 tab.

  13. Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.

    PubMed

    Wen, Yanting; Ouyang, Jian; Yang, Rong; Chen, Junhao; Liu, Yong; Zhou, Xiaojun; Burt, Richard K

    2008-09-19

    Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n=20) and recipients (n=20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P<0.001), maintain normal blood insulin levels (P<0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P<0.01), increased Foxp3 mRNA expression (P<0.01) and increased Foxp3 protein expression (P<0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

  14. 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.

  15. 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.

  16. Plasma concentrations of 4-hydroxycyclophosphamide and phosphoramide mustard in patients repeatedly given high doses of cyclophosphamide in preparation for bone marrow transplantation.

    PubMed

    Sladek, N E; Doeden, D; Powers, J F; Krivit, W

    1984-10-01

    Plasma half-life and area under the curve (AUC) values for cyclophosphamide were determined in patients given this agent iv at doses of 50-60 mg/kg/infusion. Apparent plasma half-life and AUC values for the metabolites 4-hydroxycyclophosphamide and phosphoramide mustard were also determined in some of these patients. Disappearance from the plasma of the parent compound as well as that of the metabolites was approximately first-order. Plasma half-life values for cyclophosphamide ranged from 45 to 480 mins; AUC values ranged from 10 to 188 mM X min. As expected, AUC values for cyclophosphamide increased approximately linearly with an increase in its plasma half-life. Apparent plasma half-life values for 4-hydroxycyclophosphamide and phosphoramide mustard increased approximately linearly with an increase in plasma half-life values for cyclophosphamide; the slopes of these relationships were 1.35 and 1.97, respectively, but did not quite extrapolate to zero. AUC values for 4-hydroxycyclophosphamide and phosphoramide mustard remained approximately constant at about 5 and 15 mM X min, respectively, over the relatively wide range of plasma half-life and AUC values obtained for cyclophosphamide. On the basis of these observations we suggest that (a) changes in the rate of cyclophosphamide hydroxylation, effected by whatever means, will not alter the systemic therapeutic and toxic responses to a given dose of cyclophosphamide, given that the cytotoxic effects of this agent are directly proportional to AUC values of 4-hydroxycyclophosphamide and/or phosphoramide mustard, and (b) in most cases, 4-hydroxycyclophosphamide, and not phosphoramide mustard, is likely to be the circulating metabolite of therapeutic importance in humans since the AUC values for phosphoramide mustard exceeded those for 4-hydroxycyclophosphamide by only a factor of 3 and tumor and bone marrow cells proliferating in culture are generally substantially (8-25-fold) more sensitive to 4

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

  19. [Erythrocyte substitution and isoagglutinin titer following ABO-incompatible bone marrow transplantation].

    PubMed

    Henneberg-Quester, K B; Luboldt, W; Schaefer, U W; Beelen, D W; Quabeck, K

    1990-01-01

    About 2 or 3 weeks after transplantation, even ABO-Incompatible bone marrow shows a successful graft. Haemopoiesis is not always free of problems. Suppression of erythropoiesis is caused by persistently incompatible agglutinins. Patient's well-being is limited by longer periods of low levels of haemoglobin concentration. Long-lasting need for transfusions is related to the well-known risk of infections. A procedure to eliminate the residual titers of alloantibodies should be discussed in time with the staff of the transfusion department.

  20. Clinical and histological study of permanent alopecia after bone marrow transplantation*

    PubMed Central

    Basilio, Flávia Machado Alves; Brenner, Fabiane Mulinari; Werner, Betina; Rastelli, Graziela Junges Crescente

    2015-01-01

    BACKGROUND Permanent alopecia after bone marrow transplantation is rare, but more and more cases have been described, typically involving high doses of chemotherapeutic agents used in the conditioning regimen for the transplant. Busulfan, classically described in cases of irreversible alopecia, remains associated in recent cases. The pathogenesis involved in hair loss is not clear and there are few studies available. In addition to chemotherapeutic agents, another factor that has been implicated as a cause is chronic graft-versus-host disease. However, there are no histopathological criteria for defining this diagnosis yet. OBJECTIVE the study aims to evaluate clinical and histological aspects in cases of permanent alopecia after bone marrow transplantation, identifying features of permanent alopecia induced by myeloablative chemotherapy and alopecia as a manifestation of chronic graft-versus-host disease. METHODS data were collected from medical records of 7 patients, with description of the clinical features and review of slides and paraffin blocks of biopsies. RESULTS Two distinct histological patterns were found: one similar to androgenetic alopecia, non-scarring pattern, and other similar to lichen planopilaris, scarring alopecia. CONCLUSION The first pattern corroborates the literature cases of permanent alopecia induced by chemotherapeutic agents, and the second is compatible with manifestation of chronic graft-versus-host disease on scalp, that has never been described yet. The results contribute to the elucidation of the factors involved in these cases, including the development of therapeutic methods PMID:26734861

  1. Bone marrow transplantation in hindlimb muscles of motoneuron degenerative mice reduces neuronal death and improves motor function.

    PubMed

    Pastor, Diego; Viso-León, Mari Carmen; Botella-López, Arancha; Jaramillo-Merchan, Jesus; Moraleda, Jose M; Jones, Jonathan; Martínez, Salvador

    2013-06-01

    Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis.

  2. Bone Marrow Transplantation in Hindlimb Muscles of Motoneuron Degenerative Mice Reduces Neuronal Death and Improves Motor Function

    PubMed Central

    Viso-León, Mari Carmen; Botella-López, Arancha; Jaramillo-Merchan, Jesus; Moraleda, Jose M.; Jones, Jonathan; Martínez, Salvador

    2013-01-01

    Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis. PMID:23282201

  3. Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: Case series of 14 patients

    PubMed Central

    Amr, Sherif M.; Gouda, Ashraf; Koptan, Wael T.; Galal, Ahmad A.; Abdel-Fattah, Dina Sabry; Rashed, Laila A.; Atta, Hazem M.; Abdel-Aziz, Mohammad T.

    2014-01-01

    Objective To investigate the effect of bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells. Methods In 14 patients with chronic paraplegia caused by spinal cord injury, cord defects were grafted and stem cells injected into the whole construct and contained using a chitosan-laminin paste. Patients were evaluated using the International Standards for Classification of Spinal Cord Injuries. Results Chitosan disintegration leading to post-operative seroma formation was a complication. Motor level improved four levels in 2 cases and two levels in 12 cases. Sensory-level improved six levels in two cases, five levels in five cases, four levels in three cases, and three levels in four cases. A four-level neurological improvement was recorded in 2 cases and a two-level neurological improvement occurred in 12 cases. The American Spinal Impairment Association (ASIA) impairment scale improved from A to C in 12 cases and from A to B in 2 cases. Although motor power improvement was recorded in the abdominal muscles (2 grades), hip flexors (3 grades), hip adductors (3 grades), knee extensors (2–3 grades), ankle dorsiflexors (1–2 grades), long toe extensors (1–2 grades), and plantar flexors (0–2 grades), this improvement was too low to enable them to stand erect and hold their knees extended while walking unaided. Conclusion Mesenchymal stem cell-derived neural stem cell-like cell transplantation enhances recovery in chronic spinal cord injuries with defects bridged by sural nerve grafts combined with a chitosan-laminin scaffold. PMID:24090088

  4. Minor histocompatibility antigens on transfused leukoreduced units of red blood cells induce bone marrow transplant rejection in a mouse model.

    PubMed

    Desmarets, Maxime; Cadwell, Chantel M; Peterson, Kenneth R; Neades, Renee; Zimring, James C

    2009-09-10

    When successful, human leukocyte antigen (HLA)-matched bone marrow transplantation with reduced-intensity conditioning is a cure for several nonmalignant hematologic disorders that require chronic transfusion, such as sickle cell disease and aplastic anemia. However, there are unusually high bone marrow transplant (BMT) rejection rates in these patients. Rejection correlates with the number of transfusions before bone marrow transplantation, and it has been hypothesized that preimmunization to antigens on transfused blood may prime BMT rejection. Using a novel mouse model of red blood cell (RBC) transfusion and major histocompatibility complex-matched bone marrow transplantation, we report that transfusion of RBC products induced BMT rejection across minor histocompatibility antigen (mHA) barriers. It has been proposed that contaminating leukocytes are responsible for transfusion-induced BMT rejection; however, filter leukoreduction did not prevent rejection in the current studies. Moreover, we generated a novel transgenic mouse with RBC-specific expression of a model mHA and demonstrated that transfusion of RBCs induced a CD8(+) T-cell response. Together, these data suggest that mHAs on RBCs themselves are capable of inducing BMT rejection. Cellular immunization to mHAs is neither monitored nor managed by current transfusion medicine practice; however, the current data suggest that mHAs on RBCs may represent an unappreciated and significant consequence of RBC transfusion.

  5. Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Stem Cell Transplantation (HCT) for Severe Combined Immunodeficiency Patients: A Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT.

    PubMed

    Heimall, Jennifer; Puck, Jennifer; Buckley, Rebecca; Fleisher, Thomas A; Gennery, Andrew R; Neven, Benedicte; Slatter, Mary; Haddad, Elie; Notarangelo, Luigi D; Baker, K Scott; Dietz, Andrew C; Duncan, Christine; Pulsipher, Michael A; Cowan, Mort J

    2017-03-01

    Severe combined immunodeficiency (SCID) is 1 of the most common indications for pediatric hematopoietic cell transplantation (HCT) in patients with primary immunodeficiency. Historically, SCID was diagnosed in infants who presented with opportunistic infections within the first year of life. With newborn screening (NBS) for SCID in most of the United States, the majority of infants with SCID are now diagnosed and treated in the first 3.5 months of life; however, in the rest of the world, the lack of NBS means that most infants with SCID still present with infections. The average survival for SCID patients who have undergone transplantation currently is >70% at 3 years after transplantation, although this can vary significantly based on multiple factors, including age and infection status at the time of transplantation, type of donor source utilized, manipulation of graft before transplantation, graft-versus-host disease prophylaxis, type of conditioning (if any) utilized, and underlying genotype of SCID. In at least 1 study of SCID patients who received no conditioning, long-term survival was 77% at 8.7 years (range out to 26 years) after transplantation. Although a majority of patients with SCID will engraft T cells without any conditioning therapy, depending on genotype, donor source, HLA match, and presence of circulating maternal cells, a sizable percentage of these will fail to achieve full immune reconstitution. Without conditioning, T cell reconstitution typically occurs, although not always fully, whereas B cell engraftment does not, leaving some molecular types of SCID patients with intrinsically defective B cells, in most cases, dependent on regular infusions of immunoglobulin. Because of this, many centers have used conditioning with alkylating agents including busulfan or melphalan known to open marrow niches in attempts to achieve B cell reconstitution. Thus, it is imperative that we understand the potential late effects of these agents in this patient

  6. Pseudomonas aeruginosa sepsis in stem cell transplantation patients.

    PubMed

    Fanci, Rosa; Pecile, Patrizia; Casalone, Enrico; Mengoni, Alessio; Tamburini, Elena; Guidi, Stefano; Cecconi, Daniela; Bosi, Alberto; Nicoletti, Pierluigi; Mastromei, Giorgio

    2006-07-01

    We report the epidemiological investigation of an outbreak of Pseudomonas aeruginosa infection in 6 patients who shared, during different periods, the same 2 rooms of a bone marrow transplantation unit. Phenotypic and molecular analysis of isolates from patients and from the environment strongly suggested a single, environmental source of infection.

  7. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation.

    PubMed

    Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

    2013-11-01

    Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source.

  8. Pulmonary, gonadal, and central nervous system status after bone marrow transplantation for sickle cell disease.

    PubMed

    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

    2010-02-01

    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.

  9. Immunophenotypic and ultrastructural study in peripheral blood neutrophil granulocytes following bone marrow transplantation.

    PubMed

    Masat, T; Feliu, E; Villamor, N; Castellsagué, J; Ordi, J; Fabregues, M; Rozman, C

    1997-08-01

    Neutrophil studies after bone marrow transplantation (BMT) describe chemotactic and phagocytotic alterations and dyshaemopoiesis. Neutrophil granulocytes (NG) in peripheral blood after BMT were analysed in 28 patients. 14 patients (six receiving GM-CSF) underwent autologous BMT and 14 underwent allogeneic BMT. Immunophenotypic and electron microscopic studies were performed during post-BMT granulopoietic regeneration. Results were compared with NG from 15 healthy bone marrow donors (control group A) and from six patients receiving intensive chemotherapy before autologous BMT (control group B). A significant increase in CD15 and a decrease in 8C7 antigen expression was observed in peripheral blood NG from BMT patients compared with controls A. MPO-7 in NG after BMT did not differ from control group A. Autologous BMT patients showed a lower percentage of NG expressing 13F6, 31D8 and CD16 (Leu 11a) than allogeneic BMT patients, and a significant decrease in 8C7 antigen expression compared with patients receiving intensive chemotherapy. Ultrastructurally, a marked decrease of azurophilic granules was observed in NG from BMT patients compared with control groups A and B. These data indicate that repopulation after BMT was made by phenotypically less mature NG with dysgranulopoietic features. Differences between autologous and allogeneic BMT patients may be partly related to GM-CSF usage. In conclusion, NG present immunophenotypic and ultrastructural changes after BMT which may be involved in abnormal NG response against bacterial infections, although further investigation is needed.

  10. Allogeneic bone marrow transplantation for severe aplastic anemia: the Vancouver experience.

    PubMed

    Cuthbert, R J; Shepherd, J D; Nantel, S H; Barnett, M J; Reece, D E; Klingemann, H G; Chan, K W; Spinelli, J J; Sutherland, H J; Phillips, G L

    1995-04-01

    We report a retrospective analysis of the experience of a single centre in treating severe aplastic anemia (SAA) with allogeneic bone marrow transplant (BMT). Between 1982 and 1992, we transplanted 21 patients with SAA (14 males, 7 females); median age at BMT was 15 y (range 2-40 y); median time from diagnosis of SAA to BMT was 29 d (range 6 d-5.5 y). Thirteen patients had received multiple transfusions before BMT. Patients were conditioned with cyclophosphamide 50 mg/kg for 4 d, +/- total body irradiation 300-500 cGy as a single fraction; 1 patient received total nodal irradiation (750 cGy) plus antithymocyte globulin. Sixteen patients received bone marrow from human leucocyte antigen (HLA)-identical siblings, 3 from haplo-identical parents, and 2 from unrelated volunteer donors; graft-versus-host disease (GVHD) prophylaxis was variable. Three patients failed to fully engraft following BMT; 2 achieved successful engraftment following a second BMT. Six of 20 evaluable patients (30%) developed grade II-IV acute GVHD, of whom 3 died; 3 patients developed limited and 5 patients (31%) developed extensive chronic GVHD, of whom 1 died. Fourteen patients (67%) are alive and well following BMT with a median follow-up of 6 y (range 2.1-11 y). Survival was superior in patients receiving sibling-donor BMT (75%) compared with those receiving parent- or unrelated-donor BMT (40%). We conclude that allogeneic BMT remains an important mode of treatment for SAA, but long-term survival remains limited by graft failure and GVHD.

  11. Myelodysplastic syndrome after autologous bone marrow transplantation: an additional late complication of curative cancer therapy.

    PubMed

    Miller, J S; Arthur, D C; Litz, C E; Neglia, J P; Miller, W J; Weisdorf, D J

    1994-06-15

    Myelodysplastic syndrome (MDS) is a complication of conventional antineoplastic therapy but has rarely been reported after autologous bone marrow transplantation (ABMT). We reviewed records of 206 patients who underwent ABMT for lymphoma at the University of Minnesota (Minneapolis, MN) between 1974 and 1993. Of 206 patients who underwent ABMT for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD), 9 patients developed an MDS or secondary acute leukemia between 5 and 60 months (median 34 months) post-BMT. Two patients had relapsed after transplant and received additional therapy before the diagnosis of MDS. They were censored from the statistical analysis, resulting in a cumulative incidence of 14.5% +/- 11.6% (95% confidence interval) at 5 years. Three patients (15.2% +/- 18.0%) had HD, and four (14.0% +/- 14.7%) had NHL. In vitro BM purging had no affect on the incidence of MDS, although patients receiving peripheral blood stem cells had a projected MDS incidence of 31% +/- 33% versus 10.5% +/- 12% if BM cells were used (p = .0035). The patients had received a median of 14 cycles (range, 6 to 40) of chemotherapy before autologous transplantation; Five of nine patients received radiation therapy before BMT conditioning, and all patients received radiation before the diagnosis of MDS. No BM cytogenetic abnormalities were evident pretransplant in three of three patients studied, and all nine had normal pretransplant BM morphology. All patients had morphologic BM findings typical of MDS, and six of six studied had clonal cytogenetic abnormalities. At the diagnosis of MDS, all nine patients were without clinical, radiographic, or autopsy evidence of recurrent lymphoma; Three of the nine patients have died from complications of cytopenias at 23, 36, and 45 months after transplant (3 to 10 months after the diagnosis of MDS), whereas 6 survive 8 to 63 months after transplantation (1 to 34 months post-MDS). These data emphasize the cumulative leukemogenic potential of

  12. 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.

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

    PubMed

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

    2016-02-01

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

  14. Prevention of transmission of hepatitis C virus in bone marrow transplantation by treating the donor with alpha-interferon.

    PubMed

    Vance, E A; Soiffer, R J; McDonald, G B; Myerson, D; Fingeroth, J; Ritz, J

    1996-11-15

    Transmission of hepatitis C virus (HCV) in the setting of allogeneic bone marrow transplantation can occur through an infected marrow donor. Prevention of transmission may reduce the risks of peritransplant complications. We describe a 43-year-old patient with chronic myelogenous leukemia whose HLA-identical donor was found to be HCV antibody positive and HCV RNA positive by polymerase chain reaction (PCR). The patient was HCV antibody negative and HCV RNA negative by PCR of the serum. For 6 months before bone marrow transplantation, the donor was treated with alpha-interferon at a standard dose. After 3 months, HCV RNA was no longer detectable by PCR. Interferon was discontinued 1 week before harvest. Bone marrow cellularity was normal. Engraftment was prompt. The recipient's serum remained negative for HCV RNA at 1, 3, 5, and 10 months after transplantation. Hepatitis C transmission from a viremic donor to an HCV-seronegative recipient may be preventable by treating the donor with alpha-interferon.

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

    SciTech Connect

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

    1984-07-01

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

  16. Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome.

    PubMed

    Depil, S; Deconinck, E; Milpied, N; Sutton, L; Witz, F; Jouet, J P; Damaj, G; Yakoub-Agha, I

    2004-03-01

    Donor lymphocyte infusion has become established as a salvage therapy for patients with hematological disorders relapsing after allogeneic bone marrow transplantation (BMT). The role of donor lymphocyte infusion for patients with myelodysplastic syndrome (MDS) remains to be established. Between July 1993 and October 2001, 14 patients with MDS relapsing after allogeneic BMT received DLI as salvage therapy. At the time of BMT, one patient had RA, nine had RAEB, of whom three were in CR after induction-type chemotherapy, two had RAEB-T, one had CMML and one had AML. Donors were HLA-matched siblings (n=12), HLA-matched other relative (n=1) and unrelated (n=1). At the time of relapse, the median marrow blast count was 9%. The median CD3+ cell dose administered was 6.3 x 10(7)/kg. With a median follow-up of 49 months, six patients were alive, of whom two were in CR after DLI alone and remained disease-free, two were in CR after a second BMT and two had active disease. Eight patients died of disease progression. Although DLI alone seems to be effective in a small number of patients with MDS, other treatment strategies, including prior debulking chemotherapy, deserve investigation.

  17. CCN1 enhances angiogenic potency of bone marrow transplantation in a rat model of hindlimb ischemia.

    PubMed

    Yin, Cunping; Liang, Yuan; Guo, Shuguang; Zhou, Xingli; Pan, Xinghua

    2014-09-01

    Implantation of autologous bone marrow mononuclear cells (BM-MNCs) has been performed in ischemic tissues, for stimulation of angiogenesis, but the limited number of BM-MNCs in patients with hindlimb ischemia disease may offset their overall therapeutic efficacy. CCN1 is a novel and essential regulator during angiogenesis. We evaluated whether CCN1 and BM-MNC are capable of promoting angiogenesis in hindlimb ischemia. In this study, we created the rat model of hindlimb ischemia, and then the rats were randomly divided into four groups: CCN1 infusion plus BM-MNC transplantation (CCN1 + BM-MNCs group), CCN1 infusion plus PBS injection (CCN1 group), vehicle infusion plus BM-MNC transplantation (BM-MNCs group) and vehicle infusion plus PBS injection (control group). The combination of CCN1 and BM-MNC therapy could increase blood perfusion, capillary/muscle fiber ratio and tissue oxygenation in ischemic hindlimb. Moreover, CCN1 could not only inhibit the apoptosis of BM-MNCs, but also enhance the adhesiveness of BM-MNCs to HUVEC. Taken together, CCN1 enhanced angiogenesis of BM-MNC transplantation, and combining CCN1 with BM-MNC transplantation is a useful alternative for ischemic limbs.

  18. Epstein-Barr virus-related lymphoproliferative disorders following bone marrow transplantation: an immunologic and genotypic analysis.

    PubMed

    Davey, D D; Kamat, D; Laszewski, M; Goeken, J A; Kemp, J D; Trigg, M E; Purtilo, D T; Davis, J; Dick, F R

    1989-01-01

    Four patients from 1.5 to 18 yr of age who had received partially matched T-cell-depleted bone marrow transplants for acute leukemia succumbed to a widespread lymphoproliferative disorder (LPD) at 56 to 147 days after transplant. Premortem diagnosis of LPD was suggested in two because plasmacytoid cells were observed in the blood and bone marrow, and in the cerebrospinal fluid of one of these patients. Serum clonal immunoglobulins (Igs) were also demonstrated in these two patients premortem, while the other two had clonal Igs in serum obtained at autopsy. Autopsies revealed a plasmacytoid infiltrate or immunoblastic lymphoma involving lymph nodes, spleen, liver, lungs, gastrointestinal tract, and kidneys. Immunoglobulin gene rearrangement studies performed in three revealed B-cell clonality. Both immunohistochemical and DNA gene rearrangement studies were useful in differentiating the LPD from the pretransplant leukemia. Epstein-Barr virus (EBV) genome was found in the tissues of the three patients studied. The diagnosis of EBV-induced LPD must be considered in bone marrow transplant patients who deteriorate and who exhibit serum clonal Igs or prominent plasmacytoid cells in laboratory specimens.

  19. LRBA is Essential for Allogeneic Responses in Bone Marrow Transplantation

    PubMed Central

    Park, Mi Young; Sudan, Raki; Srivastava, Neetu; Neelam, Sudha; Youngs, Christie; Wang, Jia-Wang; Engelman, Robert W.; Kerr, William G.

    2016-01-01

    The PH-BEACH-WD40 (PBW) protein family members play a role in coordinating receptor signaling and intracellular vesicle trafficking. LPS-Responsive-Beige-like Anchor (LRBA) is a PBW protein whose immune function remains elusive. Here we show that LRBA-null mice are viable, but exhibit compromised rejection of allogeneic, xenogeneic and missing self bone-marrow grafts. Further, we demonstrate that LRBA-null Natural Killer (NK) cells exhibit impaired signaling by the key NK activating receptors, NKp46 and NKG2D. However, induction of IFN-γ by cytokines remains intact, indicating LRBA selectively facilitates signals by receptors for ligands expressed on the surface of NK targets. Surprisingly, LRBA limits immunoregulatory cell numbers in tissues where GvHD is primed or initiated, and consistent with this LRBA-null mice also demonstrate resistance to lethal GvHD. These findings demonstrate that LRBA is redundant for host longevity while being essential for both host and donor-mediated immune responses and thus represents a unique and novel molecular target in transplant immunology. PMID:27824136

  20. 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

  1. Wolman disease successfully treated by bone marrow transplantation.

    PubMed

    Krivit, W; Peters, C; Dusenbery, K; Ben-Yoseph, Y; Ramsay, N K; Wagner, J E; Anderson, R

    2000-09-01

    Wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with Wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. Diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. Liver function is normal. This is the first long-term continued remission reported for Wolman disease.

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

    PubMed Central

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

    2013-01-01

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

  3. Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation.

    PubMed

    Martini, E; Gorin, N C; Gastal, C; Doinel, C; Roquin, H; Najman, A; Salmon, C

    1988-01-01

    Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself.

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

    PubMed

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

    2014-05-01

    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 × 10(6) 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.

  5. 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

  6. [Insights into auto-transplantation--the unexpected discovery of transdifferentiation systems in bone marrow stromal cells and its application].

    PubMed

    Dezawa, Mari

    2007-05-01

    Many kinds of cells, including embryonic stem cells and tissue stem cells, have been considered candidates for cell transplantation therapy for muscle-degenerative diseases. Bone marrow stromal cells (MSCs) also have great potential as therapeutic agents since they are easily isolated and can be expanded from patients without serious ethical or technical problems. Recently, new methods for the highly efficient and specific induction of functional skeletal muscle cells have been found in MSCs. Induced cells differentiate into muscle fibers upon transplantation into degenerated muscles of rats and mdx-nude mice. Furthermore, the induced population contained Pax7-positive cells that contribute to subsequent regeneration of muscle upon repetitive damage without additional transplantation of cells. Here I describe the discovery of these induction systems and focus on the potential use of MSC-derived cells for "auto-cell transplantation therapy" in muscle-degenerative diseases.

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

    PubMed

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

    1987-08-01

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

  8. JACIE accreditation for blood and marrow transplantation: past, present and future directions of an international model for healthcare quality improvement.

    PubMed

    Snowden, J A; McGrath, E; Duarte, R F; Saccardi, R; Orchard, K; Worel, N; Kuball, J; Chabannon, C; Mohty, M

    2017-03-27

    Blood and marrow transplantation (BMT) is a complex and evolving medical speciality that makes substantial demands on healthcare resources. To meet a professional responsibility to both patients and public health services, the European Society for Blood and Marrow Transplantation (EBMT) initiated and developed the Joint Accreditation Committee of the International Society for Cellular Therapy and EBMT-better known by the acronym, JACIE. Since its inception, JACIE has performed over 530 voluntary accreditation inspections (62% first time; 38% reaccreditation) in 25 countries, representing 40% of transplant centres in Europe. As well as widespread professional acceptance, JACIE has become incorporated into the regulatory framework for delivery of BMT and other haematopoietic cellular therapies in several countries. In recent years, JACIE has been validated using the EBMT registry as an effective means of quality improvement with a substantial positive impact on survival outcomes. Future directions include development of Europe-wide risk-adjusted outcome benchmarking through the EBMT registry and further extension beyond Europe, including goals to faciliate access for BMT programmes in in low- and middle-income economies (LMIEs) via a 'first-step' process.Bone Marrow Transplantation advance online publication, 27 March 2017; doi:10.1038/bmt.2017.54.

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

    PubMed Central

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

    2015-01-01

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

  10. Chagas disease in bone marrow transplantation: an approach to preemptive therapy.

    PubMed

    Altclas, J; Sinagra, A; Dictar, M; Luna, C; Verón, M T; De Rissio, A M; García, M M; Salgueira, C; Riarte, A

    2005-07-01

    The efficacy of preemptive therapy was evaluated in bone marrow transplantation (BMT) recipients associated with Chagas disease (CD). The criterion to include patients in the protocol was the serological reactivity for CD in recipients and/or donors before transplant. After BMT, the monitoring was performed using the direct Strout method (SM), which detects clinical levels of Trypanosome cruzi parasitemia, and CD conventional serological tests. Monitoring took place during 60 days in ABMT and throughout the immunosuppressive period in allogeneic BMT. Reactivation of CD was diagnosed by detecting T. cruzi parasites in blood or tissues. In primary T. cruzi infection, an additional diagnostic criterion was the serological conversion. A total of 25 CD-BMT patients were included. Two ABMT and four allogeneic BMT recipients showed CD recurrences diagnosed by SM. One patient also showed skin lesions with T. cruzi amastigotes. Benznidazole treatment (Roche Lab), an antiparasitic drug, was prescribed at a dose of 5 mg/kg/day during 4-8 weeks with recovery of patients. Primary T. cruzi infection was not observed. This report proves the relevance of monitoring CD in BMT patients and demonstrates that preemptive therapy was able to abrogate the development of clinical and systemic disease.

  11. Chronic neutrophilic leukemia with congenital Robertsonian translocation successfully treated with allogeneic bone marrow transplantation in a young man.

    PubMed

    Goto, Hideko; Hara, Takeshi; Tsurumi, Hisashi; Tanabashi, Shinobu; Moriwaki, Hisataka

    2009-01-01

    We present a 23-year-old man with chronic neutrophilic leukemia (CNL). Physical examination revealed hepatosplenomegaly. Leukocytosis was evident with predominance of mature neutrophils with basophilic granules. Bone marrow aspiration revealed mature myeloid hyperplasia. Congenital Robertsonian translocation [45,XY,der(13;22)(q10;q10), in all of analyzed 20 cells] was detected; however, cytogenetic and molecular studies for 9:22 translocation were negative. He was diagnosed with CNL and hydroxyurea was started to control his symptoms and white blood cell count. He was then successfully treated with allogeneic bone marrow transplantation (BMT). Although the prognosis of CNL was not determined, curative therapy including allogeneic hematopoietic stem cell transplantation should be attempted in young patients with CNL.

  12. Successful treatment of multi-resistant Pseudomonas aeruginosa osteomyelitis after allogeneic bone marrow transplantation with a combination of colistin and tigecycline.

    PubMed

    Stanzani, Marta; Tumietto, Fabio; Giannini, Maria Benedetta; Bianchi, Giuseppe; Nanetti, Anna; Vianelli, Nicola; Arpinati, Mario; Giovannini, Maddalena; Bonifazi, Francesca; Bandini, Giuseppe; Baccarani, Michele

    2007-12-01

    A case of osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa is reported in a patient who underwent allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The patient was successfully treated by prolonged administration of a full dose of colistin and tigecycline, and surgical curettage with the positioning of resorbable calcium sulfate pellets loaded with colistin.

  13. Seizure Treatment in Transplant Patients

    PubMed Central

    Shepard, Paul W.

    2013-01-01

    Opinion statement Solid organ transplantation is frequently complicated by a spectrum of seizure types, including single partial-onset or generalized tonic-clonic seizures, acute repetitive seizures or status epilepticus, and sometimes the evolution of symptomatic epilepsy. There is currently no specific evidence involving the transplant patient population to guide the selection, administration, or duration of antiepileptic drug (AED) therapy, so familiarity with clinical AED pharmacology and application of sound judgment are necessary for successful patient outcomes. An initial detailed search for symptomatic seizure etiologies, including metabolic, infectious, cerebrovascular, and calcineurin inhibitor treatment-related neuro-toxic complications such as posterior reversible encephalopathy syndrome (PRES), is imperative, as underlying central nervous system disorders may impose additional serious risks to cerebral or general health if not promptly detected and appropriately treated. The mainstay for post-transplant seizure management is AED therapy directed toward the suspected seizure type. Unfavorable drug interactions could place the transplanted organ at risk, so choosing an AED with limited interaction potential is also crucial. When the transplanted organ is dysfunctional or vulnerable to rejection, AEDs without substantial hepatic metabolism are favored in post-liver transplant patients, whereas after renal transplantation, AEDs with predominantly renal elimination may require dosage adjustment to prevent adverse effects. Levetiracetam, gabapentin, pregabalin, and lacosamide are drugs of choice for treatment of partial-onset seizures in post-transplant patients given their efficacy spectrum, generally excellent tolerability, and lack of drug interaction potential. Levetiracetam is the drug of choice for primary generalized seizures in post-transplant patients. When intravenous drugs are necessary for acute seizure management, benzodiazepines and

  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

    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.

  15. Growth velocity in pediatric bone marrow transplantation: significance of donor type and treatment factors.

    PubMed

    Anderson, Lynnette; Schmidt, Debra; Bingen, Kristin; Kupst, Mary Jo; Warwick, Anne

    2009-01-01

    Children who have undergone bone marrow transplantation (BMT) often have decreased growth. Growth is a multifactorial process, and the factors that influence growth after BMT are not completely understood. The authors hypothesized that donor type may be a factor influencing growth. Sixty-five children and adolescents who underwent BMT (32 related matched, 33 unrelated matched) were evaluated. Growth velocity (height standard deviation) was assessed prior to and 2 years following BMT. The results indicated that children and adolescents who underwent unrelated matched transplants had lower growth velocity (P < .059) than those with related matched transplants. Those who received the standard conditioning regimen that included total body irradiation (TBI) had a significantly lower growth velocity (P < .045) than those with chemotherapy-only regimens. Significant correlates of growth velocity included younger age at BMT and pre-BMT growth velocity. Thus, donor type, age at BMT, prior treatment, and BMT conditioning regimens that include TBI may all affect growth post-BMT. Careful monitoring of growth velocity is required for patients who have received an unrelated donor BMT.

  16. Infections following Transplantation of Bone Marrow or Peripheral-Blood Stem Cells from Unrelated Donors

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-10-01

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

  18. Circulating angiogenic factors associated with response and survival in patients with acute graft-versus-host disease: results from Blood and Marrow Transplant Clinical Trials Network 0302 and 0802.

    PubMed

    Holtan, Shernan G; Verneris, Michael R; Schultz, Kirk R; Newell, Laura F; Meyers, Gabrielle; He, Fiona; DeFor, Todd E; Vercellotti, Gregory M; Slungaard, Arne; MacMillan, Margaret L; Cooley, Sarah A; Blazar, Bruce R; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J

    2015-06-01

    Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration versus those mediating damage/inflammation would have improved outcomes. Circulating AF known predominantly for repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, and vascular endothelial growth factor-A [VEGF-A], -C, and -D) and for damage/inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, and placental growth factor [PlGF]) were measured in a discovery set of hematopoietic cell recipients with grade III and IV aGVHD and compared with controls, then validated in 2 aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (n = 105, serum) and 0802 (n = 158, plasma) versus controls without aGVHD (n = 53, serum). Levels of EGF and VEGF-A were lower than in controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio, 9.3 in CTN 0302; 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and, thus, may contribute to both pathogenesis and recovery.

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

    PubMed Central

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

    2016-01-01

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

  20. Pregnancy after allogeneic hematopoietic stem cell transplantation in a Fanconi anemia patient

    PubMed Central

    Atashkhoei, Simin; Fakhari, Solmaz; Bilehjani, Eissa; Farzin, Haleh

    2017-01-01

    Pregnancy in patients with Fanconi anemia (FA) is rare. However, there are reports of successful pregnancy in Fanconi patients after bone marrow transplantation (BMT, hematopoietic stem cell transplantation). We describe the case of a term pregnant woman with FA who was treated with BMT 2 years earlier. She underwent successful delivery with cesarean section using spinal anesthesia without any complications. PMID:28138266

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

    PubMed

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

    2014-06-01

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

  2. Birth order and transplantation outcome in HLA-identical sibling stem cell transplantation: an analysis on behalf of the Center for International Blood and Marrow Transplantation.

    PubMed

    Dobbelstein, Christiane; Ahn, Kwang Woo; Haagenson, Michael; Hale, Gregory A; van Rood, Jon J; Miklos, David; Waller, Edmund K; Spellman, Stephen R; Fernandez-Vina, Marcelo; Ganser, Arnold; Aljurf, Mahmoud; Bornhaeuser, Martin; Gupta, Vikas; Marino, Susan R; Pollack, Marilyn S; Reddy, Vijay; Eder, Matthias; Lee, Stephanie J

    2013-05-01

    Allogeneic stem cell transplantation (SCT) is the most effective treatment option for many hematologic malignancies, but graft-versus-host disease (GVHD) remains a major cause of treatment failure. Along with well-established risk factors for transplantation outcomes, recent single-center studies have identified a birth order effect in HLA-identical sibling SCT, with lower rates of acute and chronic GVHD and improved overall survival when the donor is younger than the recipient. One hypothesized mechanism for this effect is microchimerism due to fetomaternal and transmaternal sibling cell trafficking during pregnancy as the donor is exposed to recipient antigens in utero. The aim of the present study was to validate previously reported single-center data in a large, multicenter cohort provided by the Center for International Blood and Marrow Transplantation. All adult and pediatric patients (n = 11,365) with a hematologic malignancy who underwent allogeneic SCT with a graft from an HLA-identical sibling donor between 1990 and 2007 were included. When donors were younger than recipients, there was a significantly lower rate of acute GVHD grade II-IV and chronic GVHD in children, as well as a lower rate of chronic GVHD in adolescents. However, the hypothesized overall positive effect of lower relapse and better survival when donors are younger than recipients was not observed. Our data suggest that if otherwise equally matched, a graft from a younger sibling may be superior to a graft from an older sibling for children and adolescents undergoing SCT.

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

    SciTech Connect

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

    1983-07-01

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

  4. Kidney transplantation in obese patients

    PubMed Central

    Tran, Minh-Ha; Foster, Clarence E; Kalantar-Zadeh, Kamyar; Ichii, Hirohito

    2016-01-01

    The World Health Organization estimated that in 2014, over 600 million people met criteria for obesity. In 2011, over 30% of individuals undergoing kidney transplant had a body mass index (BMI) 35 kg/m2 or greater. A number of recent studies have confirmed the relationship between overweight/obesity and important comorbidities in kidney transplant patients. As with non-transplant surgeries, the rate of wound and soft tissue complications are increased following transplant as is the incidence of delayed graft function. These two issues appear to contribute to longer length of stay compared to normal BMI. New onset diabetes after transplant and cardiac outcomes also appear to be increased in the obese population. The impact of obesity on patient survival after kidney transplantation remains controversial, but appears to mirror the impact of extremes of BMI in non-transplant populations. Early experience with (open and laparoscopic) Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy support excellent weight loss (in the range of 50%-60% excess weight lost at 1 year), but experts have recommended the need for further studies. Long term nutrient deficiencies remain a concern but in general, these procedures do not appear to adversely impact absorption of immunosuppressive medications. In this study, we review the literature to arrive at a better understanding of the risks related to renal transplantation among individuals with obesity. PMID:27011911

  5. The meaning of adolescents' eating experiences during bone marrow transplant recovery.

    PubMed

    Rodgers, Cheryl; Young, Anne; Hockenberry, Marilyn; Binder, Brenda; Symes, Lene

    2010-01-01

    Bone marrow transplant (BMT) is a common treatment option for adolescents with various diseases; however, the aggressive therapy often causes significant side effects that can lead to poor eating. There is little documentation of eating experiences and necessary support needed after the initial BMT hospitalization. This phenomenological study, guided by Martin Heidegger's philosophical influences, revealed the meaning of adolescents' eating experiences, eating strategies, and the impact of eating on the adolescents' quality of life during the first 100 days post-BMT. Individual interviews were conducted at 50 and 100 days post-BMT. Data analysis used the hermeneutic circle and revealed 5 themes. Adolescents discussed the slow return of eating, barriers that affected their eating, personal eating strategies, significance of eating, and feelings regarding eating. Eating issues do not end when a BMT patient is discharged from the hospital, and caregivers need to have a better understanding of the ongoing issues affecting adolescents throughout the BMT recovery phase.

  6. Optimal Threshold and Time of Absolute Lymphocyte Count Assessment for Outcome Prediction after Bone Marrow Transplantation.

    PubMed

    Bayraktar, Ulas D; Milton, Denái R; Guindani, Michele; Rondon, Gabriela; Chen, Julianne; Al-Atrash, Gheath; Rezvani, Katayoun; Champlin, Richard; Ciurea, Stefan O

    2016-03-01

    The recovery pace of absolute lymphocyte count (ALC) is prognostic after hematopoietic stem cell transplantation. Previous studies have evaluated a wide range of ALC cutoffs and time points for predicting outcomes. We aimed to determine the optimal ALC value for outcome prediction after bone marrow transplantation (BMT). A total of 518 patients who underwent BMT for acute leukemia or myelodysplastic syndrome between 1999 and 2010 were divided into a training set and a test set to assess the prognostic value of ALC on days 30, 60, 90, 120, 180, as well as the first post-transplantation day of an ALC of 100, 200, 300, 400, 500, and 1000/μL. In the training set, the best predictor of overall survival (OS), relapse-free survival (RFS), and nonrelapse mortality (NRM) was ALC on day 60. In the entire patient cohort, multivariable analyses demonstrated significantly better OS, RFS, and NRM and lower incidence of graft-versus-host disease (GVHD) in patients with an ALC >300/μL on day 60 post-BMT, both including and excluding patients who developed GVHD before day 60. Among the patient-, disease-, and transplant-related factors assessed, only busulfan-based conditioning was significantly associated with higher ALC values on day 60 in both cohorts. The optimal ALC cutoff for predicting outcomes after BMT is 300/μL on day 60 post-transplantation.

  7. Quality of harvest and role of cell dose in unrelated bone marrow transplantation: an Italian Bone Marrow Donor Registry-Gruppo Italiano Trapianto di Midollo Osseo Study.

    PubMed

    Fagioli, Franca; Quarello, Paola; Pollichieni, Simona; Lamparelli, Teresa; Berger, Massimo; Benedetti, Fabio; Barat, Veronica; Marciano, Renato; Rambaldi, Alessandro; Bacigalupo, Andrea; Sacchi, Nicoletta

    2014-01-01

    In this study, we investigated the factors affecting cell dose harvest and the role of cell dose on outcome. We analysed data from a cohort of 703 patients who underwent unrelated bone marrow transplantation facilitated by IBMDR in GITMO centers between 2002 and 2008. The median-infused cell doses is 3.7 × 10(8)/kg, the correlation between the nucleated cells requested from transplant centers and those harvested by collection centers was adequate. A harvested/requested cells ratio lower than 0.5 was observed only in 3% of harvests. A volume of harvested marrow higher than the median value of 1270 ml was related to a significant lower infused cell dose (χ(2): 44.4; P < 0.001). No patient- or donor-related variables significantly influenced the cell dose except for the recipient younger age (χ(2): 95.7; P < 0.001) and non-malignant diseases (χ(2): 33.8; P < 0.001). The cell dose resulted an independent predictor factor for a better outcome in patients affected by non-malignant disease (P = 0.05) while early disease malignant patients receiving a lower cell dose showed a higher risk of relapse (P = 0.05).

  8. Transplanted bone marrow-derived circulating PDGFRα+ cells restore type VII collagen in recessive dystrophic epidermolysis bullosa mouse skin graft.

    PubMed

    Iinuma, Shin; Aikawa, Eriko; Tamai, Katsuto; Fujita, Ryo; Kikuchi, Yasushi; Chino, Takenao; Kikuta, Junichi; McGrath, John A; Uitto, Jouni; Ishii, Masaru; Iizuka, Hajime; Kaneda, Yasufumi

    2015-02-15

    Recessive dystrophic epidermolysis bullosa (RDEB) is an intractable genetic blistering skin disease in which the epithelial structure easily separates from the underlying dermis because of genetic loss of functional type VII collagen (Col7) in the cutaneous basement membrane zone. Recent studies have demonstrated that allogeneic bone marrow transplantation (BMT) ameliorates the skin blistering phenotype of RDEB patients by restoring Col7. However, the exact therapeutic mechanism of BMT in RDEB remains unclear. In this study, we investigated the roles of transplanted bone marrow-derived circulating mesenchymal cells in RDEB (Col7-null) mice. In wild-type mice with prior GFP-BMT after lethal irradiation, lineage-negative/GFP-positive (Lin(-)/GFP(+)) cells, including platelet-derived growth factor receptor α-positive (PDGFRα(+)) mesenchymal cells, specifically migrated to skin grafts from RDEB mice and expressed Col7. Vascular endothelial cells and follicular keratinocytes in the deep dermis of the skin grafts expressed SDF-1α, and the bone marrow-derived PDGFRα(+) cells expressed CXCR4 on their surface. Systemic administration of the CXCR4 antagonist AMD3100 markedly decreased the migration of bone marrow-derived PDGFRα(+) cells into the skin graft, resulting in persistent epidermal detachment with massive necrosis and inflammation in the skin graft of RDEB mice; without AMD3100 administration, Col7 was significantly supplemented to ameliorate the pathogenic blistering phenotype. Collectively, these data suggest that the SDF1α/CXCR4 signaling axis induces transplanted bone marrow-derived circulating PDGFRα(+) mesenchymal cells to migrate and supply functional Col7 to regenerate RDEB skin.

  9. 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.

  10. Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation.

    PubMed

    Cesaro, S; Pillon, M; Tridello, G; Aljurf, M; Martino, R; Schroyens, W; Nozzoli, C; Barba, P; Faraci, M; Fagioli, F; Cappelli, B; Cordonnier, C; Al-Mohareb, F; Floisand, Y; Greil, J; Panizzolo, I S; Santarone, S

    2013-06-01

    To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62. The median number of CDV doses was 3, range 1-8, and the treatment lasted for a median of 3 weeks, range 1-10. Clinical improvement of HC was observed in 27 patients (84%). In 12 of 32 episodes (37.5%), BK viremia was determined before every CDV administration and a complete clinical response was observed in 10 of 12 patients (83%), the reduction of BK viremia load being 1 log by 2 weeks after starting CDV. Nephrotoxicity related to CDV was observed in nine patients. Among 26 patients with 100-day follow-up, 4 of 4 patients who had a complete clinical response by 30 days were alive vs 16 of 22 (73%) who did not have the resolution of HC in this time frame. We conclude that in patients with HC, the response to CDV treatment is usually associated with a significant reduction of BK viremia load.

  11. Graft-versus-Host Disease-Associated Vulvovaginal Symptoms after Bone Marrow Transplantation.

    PubMed

    Chung, Christopher P; Sargent, Rachel E; Chung, Nadia T; Lacey, James V; Wakabayashi, Mark T

    2016-02-01

    We conducted a retrospective review to assess the prevalence of graft-versus-host disease (GVHD)-associated gynecologic conditions among bone marrow transplantation (BMT) patients at City of Hope Medical Center. We calculated the associations among the estimated risks of various gynecologic complications, including vaginal stenosis, by performing chi-square tests and t-test statistics. Between 2010 and 2014, 180 patients were referred to the gynecologic clinic after their BMT. One hundred twenty-four patients (69%) had GVHD; among these patients, 51 (41%) experienced dyspareunia and 43 (35%) had vaginal stenosis. GVHD patients were significantly more likely to have vaginal stenosis (P < .0001), more likely to have used a vaginal dilator (P = .0008), and less likely to have urinary incontinence (UI) than those without GVHD (P < .001). There was no difference in developing pelvic organ prolapse (POP) in patients with or without GVHD (P = .4373). GVHD was a common complication after allogenic BMT. Patients with BMT were more likely to have vulvovaginal symptoms, such as dyspareunia and pelvic pain. Patients with GVHD are at high risk for vaginal stenosis requiring the use of a vaginal dilator. However, they are at low risk for developing UI and POP.

  12. 2013 report from the Center for International Blood and Marrow Transplant Research (CIBMTR): current uses and outcomes of hematopoietic cell transplants for blood and bone marrow disorders.

    PubMed

    Pasquini, Marcelo; Wang, Zhiwei; Horowitz, Mary M; Gale, Robert Peter

    2013-01-01

    Data reported herein indicate increasing use of hematopoietic cell transplants for persons with blood and bone marrow disorders. Recent trends include increasing use of alternative donors including human leukocyte antigen (HLA)-matched unrelated persons and HLA-matched umbilical cord blood cells, increasing use of blood cell rather than bone marrow grafts, and increasing use of reduced-intensity pretransplant conditioning regimens. Many of these shifts are driven by logistical considerations such as the need for donors in persons without an HLA-identical sibling or expanding use of allotransplants to older persons. Many changes in transplant practices are not supported by results of large randomized trials. More data are needed to critically-assess the impact of these changes.

  13. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury.

    PubMed

    Dai, Guanghui; Liu, Xuebin; Zhang, Zan; Yang, Zhijun; Dai, Yiwu; Xu, Ruxiang

    2013-10-02

    Neuronal injuries have been a challenging problem for treatment, especially in the case of complete and chronic cervical spinal cord injury (SCI). Recently, particular attention is paid to the potential of stem cell in treating SCI, but there are only few clinical studies and insufficient data. This study explored the efficacy of autologous bone marrow mesenchymal stem cells (BMMSCs) transplantation in the treatment of SCI. Forty patients with complete and chronic cervical SCI were selected and randomly assigned to one of the two experimental groups, treatment group and control group. The treatment group received BMMSCs transplantation to the area surrounding injury, while the control group was not treated with any cell transplantation. Both the transplant recipients and the control group were followed up to 6 months, postoperatively. Preoperative and postoperative neurological functions were evaluated with AIS grading, ASIA score, residual urine volume and neurophysiological examination. Results showed that in the treatment group 10 patients had a significant clinical improvement in terms of motor, light touch, pin prick sensory and residual urine volume, while nine patients showed changes in AIS grade. Neurophysiological examination was consistent with clinical observations. No sign of tumor was evident until 6 months postoperatively. In the control group, no improvement was observed in any of the neurological functions specified above. BMMSCs transplantation improves neurological function in patients with complete and chronic cervical SCI, providing valuable information on applications of BMMSCs for the treatment of SCI.

  14. Fludarabine Phosphate, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, Total-Body Irradiation, and Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

    ClinicalTrials.gov

    2014-02-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma

  15. [Cell transplantation for periodontal diseases. A novel periodontal tissue regenerative therapy using bone marrow mesenchymal stem cells].

    PubMed

    Kawaguchi, Hiroyuki; Hayashi, Hideaki; Mizuno, Noriyoshi; Fujita, Tsuyoshi; Hasegawa, Naohiko; Shiba, Hideki; Nakamura, Shigeo; Hino, Takamune; Yoshino, Hiroshi; Kurihara, Hidemi; Tanaka, Hideo; Kimura, Akiro; Tsuji, Koichiro; Kato, Yukio

    2005-07-01

    A major goal of periodontal therapy is to reconstruct healthy periodontium destroyed by periodontal diseases. Basic studies have revealed that transplantation of mesenchymal stem cells (MSC) into periodontal defects promotes regeneration of periodontal tissue. We have developed a novel method for periodontal therapy using MSC. Human bone marrow cells are obtained from the iliac crest and expanded in vitro at Cell and Tissue Engineering Center in Hiroshima University Hospital. MSC are, then, isolated and mixed with Atelocollagen at final concentrations of 2 x 10(7) cells/mL. These MSC in Atelocollagen are transplanted into periodontal osseous defects at the periodontal surgery. The results in all seven patients who received the own MSC transplantation have shown good clinical course. Further basic studies and the continuous clinical trial are needed to prove the effectiveness of the clinical application.

  16. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report.

    PubMed

    Passweg, J R; Baldomero, H; Bader, P; Bonini, C; Duarte, R F; Dufour, C; Gennery, A; Kröger, N; Kuball, J; Lanza, F; Montoto, S; Nagler, A; Snowden, J A; Styczynski, J; Mohty, M

    2017-03-13

    Hematopoietic stem cell transplantation (HSCT) is an established procedure for many acquired and congenital disorders of the hematopoietic system. A record number of 42 171 HSCT in 37 626 patients (16 030 allogeneic (43%), 21 596 autologous (57%)) were reported by 655 centers in 48 countries in 2015. Trends include continued growth in transplant activity over the last decade, with the highest percentage increase seen in middle-income countries but the highest absolute growth in the very-high-income countries in Europe. Main indications for HSCT were myeloid malignancies 9413 (25%; 96% allogeneic), lymphoid malignancies 24 304 (67%; 20% allogeneic), solid tumors 1516 (4%; 3% allogeneic) and non-malignant disorders 2208 (6%; 90% allogeneic). Remarkable is the decreasing use of allogeneic HSCT for CLL from 504 patients in 2011 to 255 in 2015, most likely to be due to new drugs. Use of haploidentical donors for allogeneic HSCT continues to grow: 2012 in 2015, a 291% increase since 2005. Growth is seen for all diseases. In AML, haploidentical HSCT increases similarly for patients with advanced disease and for those in CR1. Both marrow and peripheral blood are used as the stem cell source for haploidentical HSCT with higher numbers reported for the latter.Bone Marrow Transplantation advance online publication, 13 March 2017; doi:10.1038/bmt.2017.34.

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

    SciTech Connect

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

    1988-10-15

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

  18. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources.

    PubMed

    Walker, Christopher M; van Burik, Jo-Anne H; De For, Todd E; Weisdorf, Daniel J

    2007-09-01

    Cytomegalovirus (CMV) infection is an important complication following allogeneic hematopoietic stem cell transplant (HSCT), but the natural history in the cord blood setting has not been well studied. We assessed CMV infection episodes in 753 consecutive allogeneic HSCT recipients at the University of Minnesota between January 1, 1998 and December 31, 2003. The 6-month cumulative incidence of viremia/antigenemia was 22% by day +182: 21% (95% confidence interval 16%-26%) in cord blood recipients (UCB), 24% (20%-28%) in marrow (BM), and 22% (16%-28%) using peripheral blood grafts (PBSC). CMV disease incidence was 6% (2%-10%) in UCB, 8% (5%-11%) in BM, and 9% (6%-12%) in PBSC. In multivariate analysis, CMV infection (viremia/antigenemia and disease) was significantly more likely in patients who were seropositive to CMV, in those with acute graft versus host disease, and in those receiving T cell-depleted grafts. Graft source did not independently contribute to the risk of CMV infection and did not impact survival after CMV infection. These data confirm that recipient CMV serostatus remains the dominant risk factor for CMV infection. Recipients of UCB have similar risks of CMV infection, responses to antiviral therapy, and survival following CMV infection as recipients of either marrow or PBSC.

  19. Autologous bone marrow transplantation in poor-risk high-grade non-Hodgkin's lymphoma in first complete remission. Newcastle and Northern Lymphoma Group.

    PubMed Central

    Jackson, G. H.; Lennard, A. L.; Taylor, P. R.; Carey, P.; Angus, B.; Lucraft, H.; Evans, R. G.; Proctor, S. J.

    1994-01-01

    We report the safety and efficacy of autologous bone marrow transplantation (ABMT) in 30 patients with high-grade non-Hodgkin's lymphoma (NHL) in first complete remission (CR1) following remission induction chemotherapy. Two patients relapsed prior to ABMT. All patients were conditioned with high-dose melphalan. In Addition, ten received fractionated total body irradiation, one hemi-body irradiation and four high-dose etoposide. Unmanipulated non-cryopreserved autologous marrow was reinfused within 56 h of harvesting. Engraftment occurred in all patients with a median of 11 days of neutropenia (< 0.5 x 10(9) l-1), a median requirement for platelet transfusion of 3 days and packed red cell transfusion of 2 units, with a median hospital stay of 18 days post transplant. There was no procedure-related mortality and only minor morbidity was observed. Two patients relapsed at 1 and 2 months post transplantation, and one patient died of carcinoma of the lung 33 months after transplantation. The remaining 25 patients remain alive, well and in CR1 with a median follow-up of 44 months. The event-free survival at 3 years for all patients considered for ABMT was 83%. We conclude that ABMT for high-grade NHL in CR1 with non-cryopreserved marrow results in rapid haematological recovery without growth factor support. It is safe and is associated with high survival when used as consolidation of CR in high-risk patients. PMID:7521662

  20. Fluctuating lymphocyte chimerism, tolerance and anti-tumor response in a patient with refractory lymphoma receiving nonmyeloablative conditioning and a haploidentical related allogeneic bone marrow transplant.

    PubMed

    Toh, Han C; Spitzer, Thomas R; Preffer, Frederic; Alexander, Stephen I; McAfee, Steve; Dombkowski, David; Clark, Jeffrey S; Colby, Christine; Saidman, Susan; Sackstein, Robert; Sykes, Megan

    2002-12-01

    A 51-year-old patient with refractory non-Hodgkin lymphoma (NHL) received non-myeloablative conditioning and a two of six (A, B, DR) human leucocyte antigen (HLA) mismatched donor BMT. Post-BMT lymphocytes showed fluctuating T- and natural killer (NK)-cell chimerism, which culminated in mainly donor lymphocytes by Day + 100. Changes in lymphocyte chimerism correlated with anti-donor and anti-host responses in mixed lymphocyte reaction (MLR). On Day + 100, a strong anti-host response was observed in MLR in the absence of graft-versus-host disease (GVHD), together with near complete regression of the patient's lymphoma. A mild chronic GVHD later developed and, eventually, by 680 days post-BMT, the lymphoma had relapsed and MLR reflected a state of global immune unresponsiveness. These observations demonstrate evolving host-versus-graft and graft-versus-host tolerance that correlates with fluctuating lymphoid chimerism and graft-versus-lymphoma (GVL) effects, in the absence of severe GVHD. Eventual lymphoma relapse temporally correlated with a generalised immunosuppressed state.

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

    PubMed

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

    2013-01-01

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

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

    PubMed

    Rowland, Chris; Kaste, Sue; Owens, Amber

    2013-01-01

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

  3. Transfusion problems associated with transplantation

    SciTech Connect

    Storb, R.; Weiden, P.L.

    1981-04-01

    Researchers have reviewed the role of blood transfusions in renal and marrow graft recipients. Striking contrasts are evident: while transfusions may promote successful kidney grafting, any transfusions before initiation of the transplant conditioning regimen may jeopardize the treatment of severe aplastic anemia by marrow transplantation. Researchers have suggested guidelines for the transfusion support of transplant candidates before transplantation and for marrow graft recipients after transplantation. It is important to recognize that after conditioning for marrow transplantation, all patients will be profoundly pancytopenic for a limited period of time, and intensive transfusion support is vital to patient survival.

  4. Blood and Marrow Transplant Clinical Trials Network: progress since the State of the Science Symposium 2007.

    PubMed

    Ferrara, James L M

    2014-02-01

    Outcomes of hematopoietic cell transplantation continue to improve. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from related and unrelated donors. In June 2007, the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) convened a State of the Science Symposium (SOSS) in Ann Arbor and identified 11 high priority clinical trials for the network to pursue. This article reviews both the status of those trials and the record of achievement of the BMT CTN as it convenes another SOSS in Grapevine, Texas in February 2014.

  5. Autologous transplantation in poor risk Hodgkin's disease using high dose melphalan/etoposide conditioning with non-cryopreserved marrow rescue. The Newcastle and Northern Region Lymphoma Group.

    PubMed Central

    Taylor, P. R.; Jackson, G. H.; Lennard, A. L.; Lucraft, H.; Proctor, S. J.

    1993-01-01

    This study aimed to assess the safety and efficacy of using high dose melphalan and etoposide followed by autologous, non-cryopreserved marrow rescue in advanced Hodgkin's disease (HD). Seventeen patients with poor risk Hodgkin's disease from a single centre underwent autologous bone marrow transplant (ABMT) using high dose melphalan and etopside conditioning. Two patients had primary progressive resistant disease (PD), two were in fourth relapse, six in second or third complete remission (CR), one patient had good partial response (GPR) (> 75% reduction in initial bulk) to primary therapy and six were in first complete remission. The patients transplanted in first CR all has a Scotland and Newcastle Lymphoma Group (SNLG) Prognostic Index (Proctor et al., 1991) which indicated they were in a poor risk prognostic group. Melphalan and etoposide both have a short half life enabling ABMT to be accomplished using unmanipulated marrow stored at 4 degrees C. The marrow was returned to the patient within 56 h of harvest. Complete haematological reconstitution occurred in 16/17 patients, the rate of engraftment reflecting the amount of previous chemotherapy. One patient died of progressive Hodgkin's disease before full engraftment could occur. In patients autografted in first remission, the median number of days with neutropenia (< 0.5 x 10(9) l-1 neutrophils) was 19 (range 9-33) and, in those in subsequent remission, 27 days (range 18-36). The median number of days to 50 x 10(9) l-1 platelets in the same groups were 29 (21-80) and 50 (41-74) respectively. The number of days in hospital post transplant in both groups was similar; median 22 (15-27) and 23 (17-37) respectively. There were no procedural deaths and none of the patients transplanted in first, second or third CR have relapsed (median follow up 21 months). The two patients transplanted with progressive disease showed only temporary responses. The two patients transplanted in fourth relapse went into CR; one is

  6. 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

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

    PubMed Central

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

    2014-01-01

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

  8. The Syndrome of Veno-occlusive Disease After Blood or Marrow Transplantation.

    PubMed

    Carreras, E; Rozman, C

    1998-01-01

    Veno-occlusive disease of the liver (VOD) was originally described in patients who drank infusions made with plants containing pyrrolizidine alkaloids [1]. This disease was characterized, histologically, by a progressive and concentric non-thrombotic narrowing of the lumina of small intrahepatic veins. Later, VOD was related to other pathogens such as alcohol, contraceptives, toxic oil, liver radiation and several antineoplastic drugs [2-3]. The first case of veno-occlusive disease following bone marrow transplantation (BMT) was reported in 1979 [4]. Since then, BMT has proved to be the main cause of VOD which is one of the leading causes of morbidity and mortality after transplant [5-7]. Clinical manifestations of VOD are very characteristic (jaundice, painful hepatomegaly and fluid retention) but indistinguishable from those produced by other regime-related morphological changes on zone 3 of the liver acinus. For this reason, the term "syndrome of veno-occlusive disease of the liver" has been adopted to designate the clinical manifestations of conditioning regimen toxicity on this zone [8]. This review focuses on the present knowledge of VOD syndrome after BMT.

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

    PubMed Central

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

    2015-01-01

    Neonatal bone marrow transplantation (BMT) could offer a novel therapeutic opportunity for genetic disorders by providing sustainable levels of the missing protein at birth, thus preventing tissue damage. We tested this concept in mucopolysaccharidosis type I (MPS IH; Hurler syndrome), a lysosomal storage disorder caused by deficiency of α-l-iduronidase. MPS IH is characterized by a broad spectrum of clinical manifestations, including severe progressive skeletal abnormalities. Although BMT increases the life span of patients with MPS IH, musculoskeletal manifestations are only minimally responsive if the timing of BMT delays, suggesting already irreversible bone damage. In this study, we tested the hypothesis that transplanting normal BM into newborn MPS I mice soon after birth can prevent skeletal dysplasia. We observed that neonatal BMT was effective at restoring α-l-iduronidase activity and clearing elevated glycosaminoglycans in blood and multiple organs. At 37 weeks of age, we observed an almost complete normalization of all bone tissue parameters, using radiographic, microcomputed tomography, biochemical, and histological analyses. Overall, the magnitude of improvements correlated with the extent of hematopoietic engraftment. We conclude that BMT at a very early stage in life markedly reduces signs and symptoms of MPS I before they appear. PMID:25298037

  10. High-dose therapy and autologous bone marrow transplantation in first complete or partial remission for poor prognosis Hodgkin's disease.

    PubMed

    Fleury, J; Legros, M; Colombat, P; Cure, H; Travade, P; Tortochaux, J; Dionet, C; Chollet, P; Linassier, C; Lamagnere, J P; Blaise, D; Viens, P; Maraninchi, D; Plagne, R

    1996-01-01

    We report the experience of three French centres which evaluated high-dose therapy (HDT) as consolidation therapy for poor prognosis Hodgkin's disease (HD). From March 1986 to April 1990, 23 consecutive patients with poor prognosis stage IV HD underwent HDT followed by autologous bone marrow transplantation (ABMT) after achieving either complete remission (CR1) or good partial response (GPR1) (reduction mass> 75%). The median age was 31 years (range 18 to 55 years), 14 were male. All patients except one initially had at least 2 poor prognosis factors such as: systemic symptoms (n = 19), bulky tumor (n = 16), more than one extranodal site (n = 9), bone marrow involvement (n = 5), lymphocyte count < or = 1.10(9)/1 (n = 8) and biological stage B (n = 21). All patients had previously been treated with alternating MOPP/ABVD. Ten patients were in GPR1 and 13 in CR1 before transplant. The conditioning regimens were: CBV (n = 17), BEAM (n = 5), BEAC (n = 1) followed by bone marrow rescue. Radiotherapy was introduced just before the conditioning regimen for 6 patients or after ABMT for 5 patients. Nine of 10 patients in GPR1 achieved CR after ABMT but one died early of treatment-related toxicity. Five of 22 patients who were in CR posttransplant, relapsed (3, 4, 4, 18, 36 months). Seventeen patients remain alive in continuous CR with a median follow-up of 60 months (range: 30-100 months). The overall survival (OS) and disease-free survival (DFS) projected at 5 years are 92% and 77% respectively. Consolidation by HDT and ABMT proved to be well tolerated. An international trial is currently underway to attempt to demonstrate a clear benefit on survival for this subset of poor prognosis HD patients.

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

    SciTech Connect

    Himeno, K.; Good, R.A.

    1988-04-01

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

  12. Oral manifestations in transplant patients

    PubMed Central

    Nappalli, Deepika; Lingappa, Ashok

    2015-01-01

    Organ transplantation is a widely undertaken procedure and has become an important alternative for the treatment of different end-stage organ diseases that previously had a poor prognosis. The field of organ transplant and hematopoietic stem cell transplant is developing rapidly. The increase in the number of transplant recipients also has an impact on oral and dental services. Most of the oral problems develop as a direct consequence of drug-induced immunosuppression or the procedure itself. These patients may present with oral complaints due to infections or mucosal lesions. Such lesions should be identified, diagnosed, and treated. New treatment strategies permit continuous adaptation of oral care regimens to the changing scope of oral complications. The aim of this review is to analyze those oral manifestations and to discuss the related literature. PMID:26005458

  13. Bone-marrow transplantation in the Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI). Biochemical and clinical status 24 months after transplantation.

    PubMed

    Krivit, W; Pierpont, M E; Ayaz, K; Tsai, M; Ramsay, N K; Kersey, J H; Weisdorf, S; Sibley, R; Snover, D; McGovern, M M

    1984-12-20

    A 13-year-old girl with the severe form of the Maroteaux-Lamy syndrome (mucopolysaccharidosis Type VI, arylsulfatase B deficiency) has had successful reconstitution with bone marrow from her HLA-MLC-matched sister who had normal arylsulfatase B activity. Full engraftment has been present for 24 months. The following biochemical and clinical changes have occurred: arylsulfatase B activity in peripheral lymphocytes and granulocytes increased to normal levels, and the activity in serial liver-biopsy specimens increased from about 3 per cent of the mean normal level 43 days after transplantation to about 16 per cent at 600 days. Urinary excretion of acid mucopolysaccharide decreased. Ultrastructural evidence of accumulated dermatan sulfate was no longer detectable in bone-marrow cells; in peripheral-blood lymphocytes, granulocytes, or platelets; or in Ito cells of liver. Twenty-four months after engraftment, hepatosplenomegaly was substantially decreased and cardiopulmonary function was normal. Visual acuity and joint mobility were also improved. The patient returned to school and continued to perform well in academic studies. Thus, bone-marrow transplantation provided a source of enzymatically normal cells, which have altered the metabolic and clinical course of the disease.

  14. Combinatorial Treatment of Bone Marrow Transplantation and Regulatory T Cells Improves Glycemia in Streptozotocin-diabetic Mice.

    PubMed

    Min, H; Ding, J; Wen, Y; Ma, X; Gao, Q

    2015-11-01

    Autologous hematopoietic stem cell transplantation (HSCT) has limited benefits in patients with a long-duration of diabetes. To test whether a T regulatory cells (Tregs) and syngeneic bone marrow transplantation (syn-BMT) co-transplantation regimen will be effective, BMT±Tregs infusion was performed in streptozotocin-diabetic mice with a long-duaration of diabetes. Diabetic status, pancreata morphometry and Tregs/Th17 balancing were tested on day 100 after transplantation. While hyperglycemia relapsed in mice receiving BMT monotherapy about 6 weeks after transplantation, combined therapy with BMT+Tregs improved hyperglycemia and C-peptides, preserved islet cell mass within 100 days after BMT. Although both groups BMT and BMT+Tregs induced Tregs/Th17 rebalancing, combined treatment of BMT+Tregs synergistically elevated TGF-β1 and FoxP3 expression compared with BMT monotherapy. The sustained rebalance of Tregs/Th17 may be one possible explanation for the longer benefits of the combined treatment of BMT+Tregs over BMT monotherapy to mice with a long-duaration of diabetes. This observation of the therapeutic potential of BMCs+Tregs treatment may have important implications for clinical therapy for patients with a long-duration of diabetes.

  15. Haematuria in Postrenal Transplant Patients

    PubMed Central

    Wang, Ziting; Vathsala, Anantharaman; Tiong, Ho Yee

    2015-01-01

    Haematuria has a prevalence of 12% in the postrenal transplant patient population. It heralds potentially dangerous causes which could threaten graft loss. It is important to consider causes in light of the unique, urological, and immunological standpoints of these patients. We review the literature on common causes of haematuria in postrenal transplant patients and suggest the salient approach to the evaluation of this condition. A major cause of haematuria is urinary tract infections. There should be a higher index of suspicion for mycobacterial, fungal, and viral infection in this group of immunosuppressed patients. Measures recommended in the prevention of urinary tract infections include early removal of foreign bodies as well as prophylactic antibiotics during the early transplant phase. Another common cause of haematuria is that of malignancies, in particular, renal cell carcinomas. When surgically managing cancer in the setting of a renal transplant, one has to be mindful of the limited retropubic space and the need to protect the anastomoses. Other causes include graft rejections, recurrences of primary disease, and calculus formation. It is important to perform a comprehensive evaluation with the aid of an experienced multidisciplinary transplant team. PMID:25918706

  16. Haematuria in postrenal transplant patients.

    PubMed

    Wang, Ziting; Vathsala, Anantharaman; Tiong, Ho Yee

    2015-01-01

    Haematuria has a prevalence of 12% in the postrenal transplant patient population. It heralds potentially dangerous causes which could threaten graft loss. It is important to consider causes in light of the unique, urological, and immunological standpoints of these patients. We review the literature on common causes of haematuria in postrenal transplant patients and suggest the salient approach to the evaluation of this condition. A major cause of haematuria is urinary tract infections. There should be a higher index of suspicion for mycobacterial, fungal, and viral infection in this group of immunosuppressed patients. Measures recommended in the prevention of urinary tract infections include early removal of foreign bodies as well as prophylactic antibiotics during the early transplant phase. Another common cause of haematuria is that of malignancies, in particular, renal cell carcinomas. When surgically managing cancer in the setting of a renal transplant, one has to be mindful of the limited retropubic space and the need to protect the anastomoses. Other causes include graft rejections, recurrences of primary disease, and calculus formation. It is important to perform a comprehensive evaluation with the aid of an experienced multidisciplinary transplant team.

  17. A review of the current status and techniques of allogeneic bone marrow transplantation for treatment of leukaemia.

    PubMed Central

    Prentice, H G

    1983-01-01

    Bone marrow transplantation is now an accepted component in the overall therapy of acute and chronic (myeloid) leukaemia for some selected patients. Some of the obstacles to success have been partially overcome. Many advances in supportive care have been made. Pneumocystis carinii and herpes simplex infections are preventable. Effective decontamination of the gastrointestinal tract for bacteria and fungi is now readily achievable and may have reduced the risk of serious systemic infections. New antibiotics which, in combination, are effective in life-threatening infections are under study. Recent developments in the prevention or amelioration of graft versus host disease (GvHD) have included T lymphocyte depletion in the donor marrow and the use of the fungal polypeptide cyclosporin A. Less than 10% of patients would now be expected to succumb to this complication. Outstanding problems remaining to be resolved are the improvement in the antileukaemic conditioning prior to transplantation and the prevention or treatment of cytomegalovirus infection in the seropositive recipient. This infection can cause pneumonitis and is currently the single most frequent transplant related cause of mortality. PMID:6355192

  18. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

    PubMed

    Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

    2014-12-01

    The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.

  19. Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

    2013-01-01

    Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source. PMID:23894010

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2013-03-01

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

  2. Monitoring of leukocyte cytomegalovirus DNA in bone marrow transplant recipients by nested PCR.

    PubMed Central

    Yuen, K Y; Lo, S K; Chiu, E K; Wong, S S; Lau, Y L; Liang, R; Chan, T K; Ng, M H

    1995-01-01

    A nested PCR assay for the detection of human cytomegalovirus (CMV) DNA was evaluated by weekly monitoring of blood samples taken from 101 bone marrow transplant (BMT) recipients. When peripheral blood leukocytes were used as the source of CMV DNA, even a modified assay with stringent temperature-cycling conditions was as sensitive as the standard assay. The sensitivity, specificity, and positive predictive value of two consecutively positive leukocytic PCR results with this modified assay in predicting CMV disease of 101 patients submitting 1,441 peripheral blood leukocyte samples were found to be 92.1, 63.5, and 60.3%, respectively. The positive predictive value of patients' seropositivity for CMV was 40%, while that of viremia was 72%. However, viremia followed CMV disease by a median of 1.5 days, while the first leukocytic positive PCR assay preceded disease by a median of 14 days. By use of the criteria of two consecutively positive PCR results instead of recipient CMV seropositivity for starting preemptive ganciclovir treatment, 38 of the 43 recipients with isolated single positive or negative assays (groups I and II) would be spared unnecessary ganciclovir treatment. Moreover, two other findings support the use of antiviral prophylaxis before engraftment in high-risk cases and subsequent preemptive treatment of patients with two consecutively positive PCR assays. First, for 7.9% of 76 patients with positive assays (groups II and III), the first positive PCR assay occurred before engraftment, which implied the presence of viral DNA in the blood (DNAemia) soon after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8567878

  3. [Information and consent forms for hematopoietic stem cell transplantation donors and recipients: Guidelines from the Franchophone society of bone marrow transplantation and cellular therapy (SFGM-TC)].

    PubMed

    Bruno, Bénédicte; Thibert, Jean-Baptiste; Bancillon, Nelly; Desbos, Anna; Fawaz, Abir; Fournier, Isabelle; Genty, Carole; Issarni, Dominique; Leveille, Sandrine; Premel, Christelle; Polomeni, Alice; Renault, Myriam; Tarillon, Sylvie; Wallart, Anne; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Within the context of the SFGM-TC's 6th workshop series on the harmonization of clinical practices, our workshop proposes a standardization of the informed consent process for hematopoietic stem cell donors and recipients leading up to an autologous or allogenic transplantation. All informed consent was for bone marrow or peripheral stem cell donors, and mononuclear/lymphocyte donors according to usual procedures. The informed consent for autologous and allogenic related or unrelated adults and pediatric transplantation patients have been included. A first step has been conducted for collecting in advance the informed consent forms used routinely in all francophone transplantation centers. In a second step, a comprehensive version has been re-written by a multidisciplinary team. For the purposes of understanding the risks and advantages, language has been carefully considered and streamlined. In the third step, texts were sent to stem cell transplantation experts, experts at the French biomedical agency (agence de la biomédecine [ABM]), law specialists, members of the ethical committee of the French society of hematology and several transplant recipients to be edited and proofread.

  4. Transplanted bone marrow mononuclear cells and MSCs impart clinical benefit to children with osteogenesis imperfecta through different mechanisms.

    PubMed

    Otsuru, Satoru; Gordon, Patricia L; Shimono, Kengo; Jethva, Reena; Marino, Roberta; Phillips, Charlotte L; Hofmann, Ted J; Veronesi, Elena; Dominici, Massimo; Iwamoto, Masahiro; Horwitz, Edwin M

    2012-08-30

    Transplantation of whole bone marrow (BMT) as well as ex vivo-expanded mesenchymal stromal cells (MSCs) leads to striking clinical benefits in children with osteogenesis imperfecta (OI); however, the underlying mechanism of these cell therapies has not been elucidated. Here, we show that non-(plastic)-adherent bone marrow cells (NABMCs) are more potent osteoprogenitors than MSCs in mice. Translating these findings to the clinic, a T cell-depleted marrow mononuclear cell boost (> 99.99% NABMC) given to children with OI who had previously undergone BMT resulted in marked growth acceleration in a subset of patients, unambiguously indicating the therapeutic potential of bone marrow cells for these patients. Then, in a murine model of OI, we demonstrated that as the donor NABMCs differentiate to osteoblasts, they contribute normal collagen to the bone matrix. In contrast, MSCs do not substantially engraft in bone, but secrete a soluble mediator that indirectly stimulates growth, data which provide the underlying mechanism of our prior clinical trial of MSC therapy for children with OI. Collectively, our data indicate that both NABMCs and MSCs constitute effective cell therapy for OI, but exert their clinical impact by different, complementary mechanisms. The study is registered at www.clinicaltrials.gov as NCT00187018.

  5. Does location matter? Rural vs urban outcomes after blood and marrow transplantation in a population-based Canadian cohort.

    PubMed

    Paulson, K; Lambert, P; Bredeson, C; Demers, A; Nowatzki, J; Richardson, E; Rubinger, M; Szwajcer, D; Seftel, M D

    2010-07-01

    Specialized health services, such as blood and marrow transplantation (BMT), are usually based in large urban centers. Previous research has suggested that rural patients undergoing BMT have a higher risk of death. We performed a cohort study using data from both the Manitoba BMT Program and the provincial Cancer Registry to determine whether patients from the rural areas would have inferior survival after BMT and whether rural patients have reduced access to BMT. A total of 463 adult Manitobans, who underwent BMT between January 1990 and December 2006, were assessed. We analyzed area of residence (rural vs urban), disease and BMT characteristics, and calculated the OS. Patients undergoing autologous and allogeneic transplants were analyzed separately. When adjusted for gender, age at BMT and year of BMT, area of residence was not a significant predictor of mortality. A relative survival analysis was also conducted, and area of residence was again not a significant predictor of mortality. To measure access to BMT in urban vs rural patients, we evaluated all patients with newly diagnosed Hodgkin's Lymphoma (HL) during this same period. Of 432 Manitobans diagnosed with HL, 182 (42%) were rural and 250 (58%) were urban. In contrast, 69% of patients undergoing transplant for HL were urban. In conclusion, using population-based data from a Canadian province, we were unable to show a survival disadvantage for rural patients after controlling for other variables. BMT utilization in rural populations deserves further study.

  6. Role of patient-support groups in the Thailand transplant program.

    PubMed

    Luvira, U; Supaporn, T

    2004-09-01

    Thailand started kidney transplantation in 1972 when vascular and nonvascular transplant programs were first established. Presently, we have 27 kidney, 6 liver, and 6 intrathoracic private or governmental transplantation centers, all approved and members of the Organ Donation Centres Thai Red Cross Society (ODC). They also provide organ procurement teams to the ODC. The Thai Medical Council has issued and supervised the criterion of brain death and ethical rules of transplantation to all practicing physicians since 1989. All recipients must register at these selected transplantation centers and at the ODC. When the potential donor arrives from any hospital in Thailand, the donor hospital notifies the ODC and organ procurement teams are sent out to harvest organs and transfer them to the recipient transplantation centers. The ODC computerizes and shares organs according to ABO, HLA typing, and crossmatching results. After transplantation all patients register with the Thai Transplantation Society (TTS) and the ODC. The TTS, the Thai Transplant Coordinator Society, and the ODC are responsible for the education of surgeons, physicians, nurses, patients, the public, and mass media to improve our transplant program. Bone marrow transplantation has separate regulations. Pooled, nonrelated bone marrow donors are registered at the blood-bank of the Thai Red Cross Society to provide donors for bone marrow transplantation. Financially, government support recipients only if they are state enterprise workers or civil servants. Public fund support through the ODC for organ procurement and the Kidney Foundation of Thailand is available for kidney transplantation. The ODC and the transplantation centers are the main patient-support groups for transplant programs in Thailand.

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

    SciTech Connect

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

    1994-04-30

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

  8. Stem Cell Transplant Patients and Fungal Infections

    MedlinePlus

    ... Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and Fungal Infections Recommend on Facebook ... Mold . Top of Page Preventing fungal infections in stem cell transplant patients Fungi are difficult to avoid because ...

  9. Successful treatment of renal failure caused by multiple myeloma with HLA-identical living kidney and bone marrow transplantation: a case report.

    PubMed

    Wagner, L; Lengyel, L; Mikala, G; Reményi, P; Piros, L; Csomor, J; Fábry, L; Tordai, A; Langer, R M; Masszi, T

    2013-01-01

    Here we have described a successful HLA-identical living allogeneic kidney transplantation after bone marrow transplantation in a patient with end-stag liver disease caused by multiple myeloma (MM). Our case is unique, because this combined transplantation is rarely possible and because of our unique immunosuppressive and management strategies. A 45-year-old man with ESRD MM and κ light-chain nephropathy was diagnosed. Cytostatic treatment resulted in partial remission, so autologous peripheral stem cell transplantation (SCT) was performed leading to a complete remission; however the patient remained anuric. The patient's HLA-identical brother offered to be a donor of peripheral stem cells for collection and cryopreservation. Kidney transplantation was performed with a combination of tacrolimus sirolimuns, and methylprednisolone. With a well-functioning kidney graft, allogeneic SCT was performed in the incipient relapse phase of MM, after total body irradiation. Severe oropharyngeal infections, diarrhea, sepsis, and renal failure. Fearing acute renal rejection, we administered steroid bolus. He experienced therapy with gradual restoration of kidney function. Then, steroid-responsive acute graft-versus-host disease (grade II, predominantly bowel) was diagnosed on the background of diarrhea, which returned once. Later he experienced a left subclavian vein thrombosis at the site of a central venous catheter and sepsis. Having recovered from these events, the patient enjoys good health, with stable kidney function and normal protein excretion. After the steroid was stopped, a bone marrow biopsy revealed full-donor type normocellular hemopoiesis. Because of the chimerism, we gradually discontinued the immunosuppression including, sirolimus and finally tacrolimus, since with minimal trough levels there were no complications. Bone marrow biopsy showed a complete remission. In MM with ESRD HLA-identical combined kidney and bone marrow transplantation from a living donor

  10. Effect of antithymocyte globulin source on outcomes of bone marrow transplantation for severe aplastic anemia.

    PubMed

    Kekre, Natasha; Zhang, Ying; Zhang, Mei-Jie; Carreras, Jeanette; Ahmed, Parvez; Anderlini, Paolo; Atta, Elias Hallack; Ayas, Mouhab; Boelens, Jaap Jan; Bonfim, Carmem; Deeg, H Joachim; Kapoor, Neena; Lee, Jong-Wook; Nakamura, Ryotaro; Pulsipher, Michael A; Eapen, Mary; Antin, Joseph H

    2017-03-24

    For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using HLA-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, p<0.001) and chronic (20% versus 9%, p<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3 year overall survival, 87% and 92%, p=0.76. Among recipients of unrelated donor transplants acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, p<0.001) but not chronic graft-versus-host disease (38% versus 32%, p=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, p=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

  11. Bone marrow derived mesenchymal stem cell transplantation in cerebellar degeneration: a behavioral study.

    PubMed

    Edalatmanesh, Mohammad Amin; Bahrami, Ahmad Reza; Hosseini, Ebrahim; Hosseini, Mahmoud; Khatamsaz, Saeid

    2011-11-20

    In addition to its key role in complex motor function, the cerebellum is increasingly recognized to have a role in cognition. Thus, motor and cognitive deficits can be associated with cerebellar degeneration. After unilateral lesion in cerebellum (folia VI) was caused by Quinolinic acid, CM-DiI labeled mesenchymal stem cells (MSCs), which were isolated and purified from bone marrow, were transplanted into the damaged folium. Motor function was assessed using the cylinder test, rotarod, hanging wire and beam balance during 6 weeks after transplantation. Cognitive function was assessed using the Morris water maze learning paradigm in 3 weeks after transplantation. Six weeks after transplantation surviving MSCs were detectable in QA-treated animals. The MSC-transplanted group showed markedly improved functional performance in spatial memory, motor learning, locomotor asymmetry, dysmetria, abnormality in neuromuscular strength and equilibrium 2-6 weeks compared with the controls. We found that cerebellar lesions produced deficits (folia VI) in motor and cognitive aspects of a spatial task. The results indicate that transplantation of MSCs can significantly reduce the behavioral abnormalities of these animals during six weeks after engraftment. According to results of this assay, cell therapy by means of bone marrow derived adult stem cells promises for treatment of cerebellar diseases.

  12. Lung damage following bone marrow transplantation. I. The contribution of irradiation. [Rats

    SciTech Connect

    Cardozo, B.L.; Zoetelief, H.; van Bekkum, D.W.; Zurcher, C.; Hagenbeek, A.

    1985-05-01

    High dose whole body irradiation is commonly included in conditioning regimens for bone marrow transplantation for treatment of patients with hematological malignancies. Interstitial pneumonitis is a major complication after BMT. When no infectious cause is found, it is classified as idiopathic IP (IIP). Total body irradiation is often associated with the induction of IIP; however, extrapolation of animal data from the experiments presented indicates that this is not the only factor contributing to IIP in man. Brown Norway (BN/Bi) rats were bilaterally irradiated to the lungs with 300 kV X rays at a high dose rate (HDR; 0.8 Gy/min) and at low dose rate (LDR; 0.05 Gy/min). The LD50 at 180 days was 13.3 Gy for HDR and 22.7 Gy for LDR. The ratios of LD/sub 50/180/ at 0.05 Gy/min to that at 0.8 Gy/min is 1.7, which indicates a great repair capacity of the lungs. Extrapolation of animal data to patient data leads to an estimated dose of about 15-16 Gy at a 50% radiation pneumonitis induction for low dose rate TBI. As the absorbed dose in the lungs of BMT patients rarely exceeds 10 Gy, additional factors might be involved in the high incidence of HP in man after BMT.

  13. Cryotherapy effect on oral mucositis severity among recipients of bone marrow transplantation: a literature review.

    PubMed

    Tayyem, Abdel-Qader Mahmoud

    2014-08-01

    Oral mucositis is a distressing toxic effect of cancer therapy and one of the major side effects of the myeloablative conditioning used to prepare patients for bone marrow transplantation (BMT). Oral cryotherapy is one of the recent modalities used to prevent and manage oral mucositis. The purpose of this review is to clarify the cryotherapy effect on oral mucositis severity among patients receiving myeloablative conditioning followed by BMT. A literature search was performed using six different electronic databases: CINAHL®, MEDLINE®, Nursing Ovid, PubMed, Springer, and Science Direct. Six articles were deemed relevant and included in this review. Oral mucositis increases mortality rate, length of hospital stay, opioid use, and the need for parenteral nutrition usage. It also decreases patient's quality of life and his or her desire to complete treatment. However, oral cryotherapy significantly minimizes the incidence and severity of oral mucositis and decreases secondary oral mucositis complications. Using oral cryotherapy concurrently with a regular oral care protocol can improve its efficacy for preventing and managing oral mucositis. Additional studies should be conducted to create standard oral cryotherapy protocols.

  14. The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus.

    PubMed

    Hahn, B H

    1997-05-01

    Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized.

  15. 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

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

    PubMed

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

    2015-01-01

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

  17. Impact of total body irradiation on successful neutrophil engraftment in unrelated bone marrow or cord blood transplantation.

    PubMed

    Nakasone, Hideki; Fuji, Shigeo; Yakushijin, Kimikazu; Onizuka, Makoto; Shinohara, Akihito; Ohashi, Kazuteru; Miyamura, Koichi; Uchida, Naoyuki; Takanashi, Minoko; Ichinohe, Tatsuo; Atsuta, Yoshiko; Fukuda, Takahiro; Ogata, Masao

    2017-02-01

    Total body irradiation (TBI) has been thought to promote donor cell engraftment in allogeneic hematopoietic cell transplantation (HCT) from alternative donors. However, recent progress in HCT strategies may affect the clinical significance of TBI on neutrophil engraftment. With the use of a Japanese transplant registry database, we analyzed 3933 adult recipients (>15 y.o.) who underwent HCT between 2006 and 2013 from an 8/8 HLA-matched unrelated bone marrow donor (MUD, n = 1367), an HLA-mismatched unrelated bone marrow donor (MMUD, n = 1102), or unrelated cord blood (CBT, n = 1464). Conditioning regimens were divided into five groups: High-TBI-(>8Gy), Low-TBI- (≤8Gy), and no-TBI-myeloablative conditioning (MAC), and Low-TBI- and no-TBI-reduced-intensity conditioning (RIC). In both MUD and MMUD, neutrophil engraftment rate was >90% in each of the five conditioning groups, and TBI was not associated with prompt neutrophil engraftment in multivariate analyses. Conversely, in CBT, TBI regimens had a higher rate of day-30 neutrophil engraftment than no-TBI-regimens: 78% in High-TBI-MAC, 83% in Low-TBI-MAC, and 76% in Low-TBI-RIC versus 65% in No-TBI-MAC, and 68% in No-TBI-RIC (P < .001). Multivariate analyses in CBT demonstrated that TBI-regimens were significantly associated with a higher rate of neutrophil engraftment. Subsequently focusing on CBT patients alone, TBI-regimens were significantly associated with a higher rate of neutrophil engraftment in patients who received CBT with a 4/6 or less HLA allele-match, or who had anti-HLA antibodies. In summary, TBI-regimens had no impact on neutrophil engraftment in the current practice of unrelated bone marrow transplantation. However, in CBT, TBI is still necessary to enhance engraftment.

  18. Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation.

    PubMed

    Li, Ming; Abraham, Nader G; Vanella, Luca; Zhang, Yuming; Inaba, Muneo; Hosaka, Naoki; Hoshino, Sho-Ichi; Shi, Ming; Ambrosini, Yoko Miyamoto; Gershwin, M Eric; Ikehara, Susumu

    2010-12-01

    There is increasing evidence that both autoimmune and autoinflammatory mechanisms are involved in the development of not only type 1 diabetes mellitus (T1 DM), but also type 2 diabetes mellitus (T2 DM). Our laboratory has focused on this concept, and in earlier efforts replaced the bone marrow cells (BMCs) of leptin receptor-deficient (db/db) mice, an animal model of T2DM, with those of normal C57BL/6 (B6) mice by IBM-BMT. However, the outcome was poor due to incomplete recovery of T cell function. Therefore, we hypothesized that intra-bone marrow-bone marrow transplantation plus thymus transplantation (IBM-BMT + TT) could be used to treat T2 DM by normalizing the T cell imbalance. Hence we addressed this issue by using such dual transplantation and demonstrate herein that seven weeks later, recipient db/db mice manifested improved body weight, reduced levels of blood glucose, and a reduction of plasma IL-6 and IL-1β. More importantly, this treatment regimen showed normal CD4/CD8 ratios, and increased plasma adiponectin levels, insulin sensitivity, and the number of insulin-producing cells. Furthermore, the expression of pancreatic pAKT, pLKB1, pAMPK and HO-1 was increased in the mice treated with IBM-BMT + TT. Our data show that IBM-BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM-BMT + TT is a viable therapeutic option in the treatment of T2 DM.

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

    PubMed Central

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

    2014-01-01

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

  20. Increased presence of anti-HLA antibodies early after allogeneic granulocyte colony-stimulating factor-mobilized peripheral blood hematopoietic stem cell transplantation compared with bone marrow transplantation.

    PubMed

    Lapierre, Valérie; Aupérin, Anne; Tayebi, Hakim; Chabod, Jacqueline; Saas, Philippe; Michalet, Mauricette; François, Sylvie; Garban, Frédéric; Giraud, Christine; Tramalloni, Dominique; Oubouzar, Nadia; Blaise, Didier; Kuentz, Matthieu; Robinet, Eric; Tiberghien, Pierre

    2002-08-15

    We have recently shown that the use of allogeneic granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood hematopoietic stem cell transplantation (PBHSCT), as compared with bone marrow transplantation (BMT), is associated with increased titers of antibodies (Abs) directed against red blood cell ABO antigens. To further evaluate the influence of a G-CSF-mobilized PBHSCT graft on alloimmune Ab responses, we examined the frequency of anti-HLA Abs after transplantation in the setting of the same randomized study, comparing PBHSCT with BMT in adults. Anti-HLA Ab presence was determined by complement-dependent cytotoxicity assay (CDC) and flow cytometry in the recipient before and 30 days after transplantation as well as in the donor before graft donation. The use of PBHSCT was significantly associated with increased detection of anti-HLA immunoglobulin G (IgG) Abs early after transplantation as evidenced by flow cytometry (11 of 24 versus 4 of 27 transplant recipients, P =.03) and, less so, by CDC (5 of 24 versus 1 of 27 transplant recipients, P =.09). The difference between PBHSCT and BMT was further heightened when analysis was restricted to anti-HLA IgG Ab-negative donor/recipient pairs. In such a setting, early anti-HLA Ab was never detected after BMT but was repeatedly detected after PBHSCT (flow cytometry, 6 of 18 versus 0 of 17 transplant recipients, P =.02; CDC, 4 of 23 versus 0 of 26 transplant recipients, P =.04). Importantly, the PBHSCT-associated increase in anti-HLA Ab detection was observed despite a reduction in the median number of platelet-transfusion episodes per patient in PBHSC transplant versus BM transplant recipients (3 platelet-transfusion episodes [range, 1-21] in PBHSCT group vs 6 platelet-transfusion episodes [range, 3-33] in the BMT group; P =.02). In conclusion, this study strongly suggests that G-CSF-mobilized PBHSCT results in an increased incidence of circulating anti-HLA Abs and further confirms that the use of such a

  1. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation.

    PubMed

    Ho, Vincent T; Cutler, Corey; Carter, Shelly; Martin, Paul; Adams, Roberta; Horowitz, Mary; Ferrara, James; Soiffer, Robert; Giralt, Sergio

    2005-08-01

    The syndrome of microangiopathic hemolysis associated with renal failure, neurologic impairment, or both is a recognized complication of hematopoietic stem cell transplantation. This entity is often called hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP), yet it is clear that the pathophysiology of transplant-associated HUS/TTP is different from that of classic HUS or TTP. Furthermore, the incidence of this syndrome varies from 0.5% to 76% in different transplant series, primarily because of the lack of a uniform definition. The toxicity committee of the Blood and Marrow Transplant Clinical Trials Network has reviewed the current literature on transplant-related HUS/TTP and recommends that it be henceforth renamed posttransplantation thrombotic microangiopathy (TMA). An operational definition for TMA based on the presence of microangiopathic hemolysis and renal and/or neurologic dysfunction is proposed. The primary intervention after diagnosis of TMA should be withdrawal of calcineurin inhibitors. Plasma exchange, although frequently used in this condition, has not been proven to be effective. In the absence of definitive trials, plasma exchange cannot be considered a standard of care for TMA. It is hoped that these positions will improve the identification and reporting of this devastating complication after hematopoietic stem cell transplantation and facilitate future clinical studies for its prevention and treatment.

  2. Composite vascularized skin/bone graft model: a viable source for vascularized bone marrow transplantation.

    PubMed

    Siemionow, Maria; Ulusal, Betul G; Ozmen, Selahattin; Ulusal, Ali E; Ozer, Kagan

    2004-01-01

    In this study, we introduce a new model for vascularized skin and bone marrow transplantation. Twenty-five Lewis (RT1(1)) rats were studied. Anatomic dissection studies were performed in 5 animals. In the experimental group, 10 isograft transplantations were performed between Lewis rats. Combined groin skin and femoral bone flaps were transplanted based on the femoral artery and vein. Transplants were evaluated on a daily basis. All flaps survived without problems over 100 days posttransplant. The skin component remained pink and pliable, and grew new hair. Histological examination of the femoral bone (except the femoral head) revealed active hematopoiesis with a viable compact and cancellous bone components on day 100 posttransplant. This model can be applied to tolerance induction studies across the major Histocompatibility (MHC) barrier, where bone will serve as donor of stem and progenitor cells, and the skin flap will serve as a monitor of graft rejection.

  3. [Changes in the bone marrow in cancer patients. 61 bone marrow biopsies].

    PubMed

    Marsan, C; Henon, P; Cywiner-Golenzer, C; Zitouna, M M; Girardi, P

    1976-01-01

    The authors studied 61 bone marrow biopsies carried out in cancerous patients, presumably suffering from a bone metastasis and before any treatment. They feel that quantitative and qualitative changes in the bone marrow may be considered to be an indirect diagnostic indication of metastatic spread.

  4. Severe papillomavirus infection progressing to metastatic squamous cell carcinoma in bone marrow-transplanted X-linked SCID dogs.

    PubMed

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

    2006-07-01

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

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

    SciTech Connect

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

    2005-11-01

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

  6. Oocyte donation in women cured of cancer with bone marrow transplantation including total body irradiation in adolescence.

    PubMed

    Larsen, E C; Loft, A; Holm, K; Müller, J; Brocks, V; Andersen, A N

    2000-07-01

    Female survivors of cancer in childhood and adolescence who have been treated with bone marrow transplantation including total body irradiation (TBI) are at high risk of developing ovarian follicular depletion and infertility. The lack of oocytes may be compensated for by oocyte donation but these patients also seem to have a uterine factor. Even though oestrogen replacement therapy is given, the growth of the uterus during adolescence is impaired. To our knowledge there have been no earlier reports of live births after oocyte donation in such patients. We report three cases of oocyte donation in women who, at a young age, were cured of haematological malignancies with bone marrow transplantation including TBI. In adolescence they developed ovarian failure and uterine volumes were assessed by ultrasonography. One woman with a uterus of almost normal size delivered a healthy child in the 37th week of gestation. Another woman with severely diminished uterine volume miscarried in the 17th week of gestation. The third woman has not yet conceived. Pregnancy achieved by oocyte donation is possible despite TBI in adolescence. However, the uterine factor is a concern and complications during pregnancy and preterm birth may be expected in these patients.

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

    SciTech Connect

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

    2008-08-01

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

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

    PubMed Central

    Ohshima, Toshio; Schiffmann, Raphael; Murray, Gary J.; Kopp, Jeffrey; Quirk, Jane M.; Stahl, Stefanie; Chan, Chi-Chao; Zerfas, Patricia; Tao-Cheng, Jung-Hwa; Ward, J. M.; Brady, Roscoe O.; Kulkarni, Ashok B.

    1999-01-01

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

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

    SciTech Connect

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

    1983-09-01

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

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

    PubMed

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

    2016-10-01

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

  11. Successful treatment of refractory acquired pure red cell aplasia (PRCA) by allogeneic bone marrow transplantation.

    PubMed

    Müller, B U; Tichelli, A; Passweg, J R; Nissen, C; Wodnar-Filipowicz, A; Gratwohl, A

    1999-06-01

    This case describes a 16-year-old woman treated successfully by a bone marrow transplant from her HLA-identical brother for refractory acquired pure red cell aplasia. Conditioning was as for severe aplastic anaemia with cyclophosphamide 4 x 50 mg/kg and antithymocyte globulin. Complete donor type engraftment at 3 months reversed to full autologous reconstitution at 2 years with normal haemopoiesis. The potential implications on pathogenesis of the disease as well as on treatment of autoimmune disorders by stem cell transplantation are discussed.

  12. Haploidentical Bone Marrow Transplantation in 2015 and Beyond.

    PubMed

    Ruiz-Argüelles, Guillermo J; Ruiz-Delgado, Guillermo J; González-Llano, Oscar; Gómez-Almaguer, David

    2015-12-01

    On the face of the lack of HLA-identical sibling stem cell donors for all individuals needing an allograft, the use of alternative donors is gaining popularity. Matched unrelated donors and cord bloods have become very expensive and unaffordable for most people living in developing countries. Grafting allogeneic haploidentical stem cells has become an option with a great future, mainly if the procedure is conducted in a way to cut down expenses, such as the use of reduced-intensity conditioning regimens, outpatient conduction of the procedures, and use of post-transplant cyclophosphamide. The long-term results of allografting haploidentical stem cells seem to be similar to those of grafting cord blood stem cells. The improvement of the procedures to conduct haploidentical stem cell transplantation will most likely result in more individuals gaining access to this type of treatments, critical in the current practice of hematology.

  13. Relapse after non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: early transplantation, use of an unrelated donor, and chronic graft-versus-host disease are protective.

    PubMed

    Enright, H; Davies, S M; DeFor, T; Shu, X; Weisdorf, D; Miller, W; Ramsay, N K; Arthur, D; Verfaillie, C; Miller, J; Kersey, J; McGlave, P

    1996-07-15

    We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host disease (CGVHD) had a decreased risk of relapse (RR, 0.24; P = .005). Only two of 106 unrelated-donor transplant recipients relapsed following transplant (5-year Kaplan-Meier estimate of relapse, 3%; 95% CI, 0% to 7%). When both related- and unrelated-donor recipients were considered, the use of an unrelated donor was independently associated with a decreased risk of relapse (RR, 0.24; P = .07). Twelve of 16 relapsing patients who received further therapy (nine of 13 who underwent second transplant and three of three who received donor leukocyte infusions) remain alive. This analysis shows that relapse, sometimes occurring long after transplant, is an important adverse outcome in allogeneic transplantation for CML. Early transplant, posttransplant CGVHD, and use of an unrelated donor are associated with a reduced incidence of relapse, perhaps due to allogeneic disparities enhancing the graft-versus-leukemia effect.

  14. Effects of mixed hematopoietic chimerism in a mouse model of bone marrow transplantation for sickle cell anemia.

    PubMed

    Iannone, R; Luznik, L; Engstrom, L W; Tennessee, S L; Askin, F B; Casella, J F; Kickler, T S; Goodman, S N; Hawkins, A L; Griffin, C A; Noffsinger, L; Fuchs, E J

    2001-06-15

    Sickle cell anemia (SCA) is an inherited disorder of beta-globin, resulting in red blood cell rigidity, anemia, painful crises, organ infarctions, and reduced life expectancy. Allogeneic blood or marrow transplantation (BMT) can cure SCA but is associated with an 8% to 10% mortality rate, primarily from complications of marrow-ablative conditioning. Transplantation of allogeneic marrow after less intensive conditioning reduces toxicity but may result in stable mixed hematopoietic chimerism. The few SCA patients who inadvertently developed mixed chimerism after BMT remain symptom free, suggesting that mixed chimerism can reduce disease-related morbidity. However, because the effects of various levels of mixed chimerism on organ pathology have not been characterized, this study examined the histologic effects of an increasing percentage of normal donor hematopoiesis in a mouse model of BMT for SCA. In lethally irradiated normal mice that were reconstituted with varying ratios of T-cell-depleted marrow from normal and transgenic "sickle cell" mice, normal myeloid chimerism in excess of 25% was associated with more than 90% normal hemoglobin (Hb). However, 70% normal myeloid chimerism was required to reverse the anemia. Organ pathology, including liver infarction, was present in mice with sickle Hb (HbS) levels as low as 16.8% (19.6% normal myeloid chimerism). Histologic abnormalities increased in severity up to 80% HbS, but were less severe in mice with more than 80% HbS than in those with 40% to 80% HbS. Therefore, stable mixed chimerism resulting from nonmyeloablative BMT may reduce the morbidity from SCA, but prevention of all disease complications may require minimizing the fraction of circulating sickle red cells. (Blood. 2001;97:3960-3965)

  15. 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.

  16. 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.

  17. The topologic and chronologic patterns of hematopoietic cell seeding in host femoral bone marrow after transplantation.

    PubMed

    Askenasy, Nadir; Stein, Jeremiah; Yaniv, Isaac; Farkas, Daniel L

    2003-08-01

    The early stages of homing, seeding, and engraftment of hematopoietic stem and progenitor cells are poorly characterized. We have developed an optical technique that allows in vivo tracking of transplanted, fluorescent-tagged cells in the host femurs. In this study we used fluorescence microscopy to monitor the topologic and chronologic patterns of hematopoietic cell seeding in the femoral bone marrow (BM) of mice. PKH-labeled cells homed to the femur within minutes after injection into a peripheral vein. Most cells drifted within the marrow space and gradually seeded in clusters close to the endosteal surface of the epiphyseal cortex. Three days after transplantation 85% to 94% (14%) of PKH-labeled cells in the femoral marrow were located within 100 microm of the epiphyseal bone surface (P <.001 versus the more central cells), whereas labeled cells were absent in the femoral diaphysis. Primary seeding of juxtaendosteal, epiphyseal marrow occurred independently of recipient conditioning (myeloablated and nonconditioned hosts), donor-recipient antigen disparity, or the phenotype of the injected cells (whole BM and lineage-negative cells) and was consistently observed in secondary recipients of BM-homed cells. Seeding in regions close to the epiphyseal bone was also observed in freshly excised femurs perfused ex vivo and in femurs assessed without prior placement of optical windows, indicating that the site of primary seeding was not affected by surgical placement of optical windows. Four to 5 days after transplantation, cellular clusters appeared in the more central regions of the epiphyses and in the diaphyses. Centrally located cells showed decreased PKH fluorescence, suggesting that they were progeny of the seeding cells, and brightly fluorescent cells (quiescent first-generation seeding cells) were observed close to the bone surface for as long as 24 days after transplantation. These data indicate that the periphery of the femoral marrow hosts primary seeding

  18. Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party.

    PubMed

    Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D'aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; Peffault de Latour, Regis

    2016-07-01

    Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia.

  19. Unrelated alternative donor transplantation for severe acquired aplastic anemia: a study from the French Society of Bone Marrow Transplantation and Cell Therapies and the EBMT Severe Aplastic Anemia Working Party

    PubMed Central

    Devillier, Raynier; Dalle, Jean-Hugues; Kulasekararaj, Austin; D’aveni, Maud; Clément, Laurence; Chybicka, Alicja; Vigouroux, Stéphane; Chevallier, Patrice; Koh, Mickey; Bertrand, Yves; Michallet, Mauricette; Zecca, Marco; Yakoub-Agha, Ibrahim; Cahn, Jean-Yves; Ljungman, Per; Bernard, Marc; Loiseau, Pascale; Dubois, Valérie; Maury, Sébastien; Socié, Gérard; Dufour, Carlo; de Latour, Regis Peffault

    2016-01-01

    Unrelated allogeneic transplantation for severe aplastic anemia is a treatment option after immunosuppressive treatment failure in the absence of a matched sibling donor. Age, delay between disease diagnosis and transplantation, and HLA matching are the key factors in transplantation decisions, but their combined impact on patient outcomes remains unclear. Using the French Society of Bone Marrow Transplantation and Cell Therapies registry, we analyzed all consecutive patients (n=139) who underwent a first allogeneic transplantation for idiopathic severe aplastic anemia from an unrelated donor between 2000 and 2012. In an adjusted multivariate model, age over 30 years (Hazard Ratio=2.39; P=0.011), time from diagnosis to transplantation over 12 months (Hazard Ratio=2.18; P=0.027) and the use of a 9/10 mismatched unrelated donor (Hazard Ratio=2.14; P=0.036) were independent risk factors that significantly worsened overall survival. Accordingly, we built a predictive score using these three parameters, considering patients at low (zero or one risk factors, n=94) or high (two or three risk factors, n=45) risk. High-risk patients had significantly shorter survival (Hazard Ratio=3.04; P<0.001). The score was then confirmed on an independent cohort from the European Group for Blood and Marrow Transplantation database of 296 patients, with shorter survival in patients with at least 2 risk factors (Hazard Ratio=2.13; P=0.005) In conclusion, a simple score using age, transplantation timing and HLA matching would appear useful to help physicians in the daily care of patients with severe aplastic anemia. PMID:27056924

  20. Reduction of Acute Rejection by Bone Marrow Mesenchymal Stem Cells during Rat Small Bowel Transplantation

    PubMed Central

    Zhang, Wen; Wu, Ben-Juan; Fu, Nan-Nan; Zheng, Wei-Ping; Don, Chong; Shen, Zhong-Yang

    2014-01-01

    Background Bone marrow mesenchymal stem cells (BMMSCs) have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats. Methods Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control), isogeneically transplanted rats (BN-BN) and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg) cells were assessed at each time point. Results Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th)1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL)-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ while upregulating IL-10 and transforming growth factor (TGF)-β expression and increasing Treg levels. Conclusion BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation. PMID:25500836

  1. Evaluation of a quantitative plasma PCR plate assay for detecting cytomegalovirus infection in marrow transplant recipients.

    PubMed Central

    Gallez-Hawkins, G M; Tegtmeier, B R; ter Veer, A; Niland, J C; Forman, S J; Zaia, J A

    1997-01-01

    A plasma PCR test, using a nonradioactive PCR plate assay, was evaluated for detection of human cytomegalovirus reactivation. This assay was compared to Southern blotting and found to perform well. As a noncompetitive method of quantitation, it was similar to a competitive method for detecting the number of genome copies per milliliter of plasma in marrow transplant recipients. This is a technically simplified assay with potential for adaptation to automation. PMID:9041438

  2. Therapeutic benefits in thalassemic mice transplanted with long term cultured bone marrow cells

    PubMed Central

    Hatada, Seigo; Walton, William; Hatada, Tomoko; Wofford, Anne; Fox, Raymond; Liu, Naiyou; Lill, Michael C.; Fair, Jeffery H.; Kirby, Suzanne L.; Smithies, Oliver

    2011-01-01

    Objective Autologous bone marrow (BM) cells with a faulty gene corrected by gene targeting could provide a powerful therapeutic option for patients with genetic blood diseases. Achieving this goal is hindered by the low abundance of therapeutically useful BM cells and the difficulty of maintaining them in tissue culture long enough for completing gene targeting without them differentiating. Our objective was to devise a simple long-term culture system, using unfractioned BM cells, that maintains and expands therapeutically useful cells for ≥4 weeks. Materials and Methods From 2 to 60 million BM cells from wild-type (WT) mice, or from mice carrying a truncated erythropoietin receptor transgene (tEpoR-tg), were plated with or without irradiated fetal-liver derived AFT024 stromal cells in 25 cm2 culture flasks. Four-week cultured cells were analyzed and transplanted into sublethally irradiated thalassemic mice (1 million cells / mouse). Results After 4 weeks, the cultures with AFT024 cells had extensive “cobblestone” areas. Optimum expansion of Sca-1 positive cells was 5.5-fold with 20 × 106 WT cells/flask and 27-fold with 2 × 106 tEpoR-tg cells. More than 85% of thalassemic mice transplanted with either type of cells had almost complete reversal of their thalassemic phenotype for at least 6 months, including blood smear dysmorphology, reticulocytosis, high ferritin plasma levels and hepatic/renal hemosiderosis. Conclusion When plated at high cell densities on irradiated fetal-liver derived stromal cells, BM cells from WT mice maintain their therapeutic potential for 4 weeks in culture, which is sufficient time for correction of a faulty gene by targeting. PMID:21184801

  3. Hematopoietic stem cell transplantation for patients with sickle cell disease: progress and future directions.

    PubMed

    Fitzhugh, Courtney D; Abraham, Allistair A; Tisdale, John F; Hsieh, Matthew M

    2014-12-01

    Research has solidified matched sibling marrow, cord blood, or mobilized peripheral blood as the best source for allogeneic hematopoietic stem cell transplantation for patients with sickle cell disease, with low graft rejection and graft-versus-host disease (GVHD) and high disease-free survival rates. Fully allelic matched unrelated donor is an option for transplant-eligible patients without HLA-matched sibling donors. Unrelated cord transplant studies reported high GVHD and low engraftment rates. Haploidentical transplants have less GVHD, but improvements are needed to increase the low engraftment rate. The decision to use unrelated cord blood units or haploidentical donors depends on institutional expertise.

  4. [General and ethical considerations for the informed consent process: Guidelines from the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    PubMed

    Thibert, Jean-Baptiste; Polomeni, Alice; Yakoub-Agha, Ibrahim; Bordessoule, Dominique

    2016-11-01

    Informed consent is not restricted to clinical research and must be applied to high-risk care such as hematopoietic stem cell transplantation. If standardized informed consent might improve inequalities in medical practices between different transplantation centers, it is strongly recommended that it be adapted with an honest dialogue between physicians and patients and physicians and donors. In an attempt to harmonize clinical practices among French hematopoietic stem cell transplantation centers, the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) held its sixth annual workshop series in September 2015 in Lille. This event brought together practitioners from across the country. The purpose of this paper is to highlight the French law concerning patients' rights and ethical practices for an informed consent process to be applied to care or research.

  5. The mechanism of recurrence of mouse myeloid leukaemia after total body irradiation and bone marrow transplantation.

    PubMed

    Poljak-Blazi, M; Popović, M; Majić, T

    1994-01-01

    RFM mice were X-irradiated (9.5 Gy) 3, 4, 5, 6 or 7 days after inoculation of a transplantable strain-specific myeloid leukaemia (ML) and were reconstituted or not with syngeneic or allogeneic bone marrow cells. Recurrent leukaemia was observed in mice with either type of the bone marrow transplant, indicating that ML cells survived the dose of 9.5 Gy of X-rays. ML cells exposed in vitro to high doses of X-rays (20, 30, 40, 50, 60 Gy) and injected into lethally irradiated syngeneic recipients were still capable of forming leukaemic colonies on the spleens. Higher doses (70, 80, 90 and 100 Gy) abolished the colony formation completely. Irradiated ML cells were also capable of causing leukaemia (hepatosplenomegaly) if inoculated into lethally irradiated CBA mice reconstituted with bone marrow cells of CBA or RFM mice. That was attributed to the release of a leukaemogenic factor from the ML cells, capable of transforming transplanted normal cells.

  6. 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.

  7. 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.

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

    PubMed Central

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

    2011-01-01

    GVHD causes extensive morbidity and mortality in patients who receive alloHCT. Predictive and reliable markers for GVHD are currently lacking but required to improve the safety and accessibility of alloHCT. We present an experimental rat model of myeloablative total body irradiation and fully mismatched major and minor histoincompatible, T cell-depleted BMT, followed by delayed infusion of donor lymphocytes. This treatment, in contrast to marrow transplantation alone, resulted in severe aGVHD and 100% lethality within 2–6 weeks. We investigated the reconstitution kinetics and phenotypes of donor leukocyte subpopulations as well as the histopathology of selected organs that may correlate with GVHD, with the goal to find potential disease-related markers. We observed histological changes mainly confined to the skin, with degenerative changes in the basal layer. LNs and spleen showed deranged architecture with markedly increased accumulation of lymphocytes, whereas the gut, liver, and lungs appeared normal. Of the lymphocyte markers tested, donor-derived CD62L+ T cells were markedly decreased in animals suffering from GVHD. Furthermore, we observed peripheral depletion of CD4+CD25hiFoxP3+ Treg, which was in contrast to controls. The relative frequency of these lymphocyte subpopulations in blood may therefore serve as accessible cellular markers of aGVHD. We propose that the animal model presented is instructive for the identification of clinically relevant markers of GVHD, which could improve disease diagnosis and management in alloHCT. PMID:21498586

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

    PubMed

    Peluso, Ilaria; Palmery, Maura; Vitalone, Annabella

    2016-10-25

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

  10. Diffuse alveolar hemorrhage associated with thrombotic thrombocytopenic purpura after allogeneic bone marrow transplantation.

    PubMed

    Kalayoğlu Beşışık, Sevgi; Yenerel, Mustafa; Diz Küçükkaya, Reyhan; Çalışkan, Yaşar; Sargın, Deniz

    2004-12-05

    Alveolar hemorrhage is an early complication after bone marrow transplantation (BMT) and often associated with inflammatory pulmonary processes. We present a case of diffuse alveolar hemorrhage associated with BMT associated thrombotic thrombocytopenic purpura (BMT-TTP). An 18-years-old man with acute myeloid leukaemia (FAB; M5) underwent ABO incompatible BMT from his HLA-identical sister. On the 37th day of BMT, BMT-TTP was diagnosed with the occurrence of red cell fragmentation and rise in serum lactic dehydrogenase (LDH) level with severe sudden decrease in hemoglobin and platelet levels. Cyclosporine A (CsA) was ceased and plasma infusion with plasma exchange was started. On the 42nd day of BMT, the diagnosis of diffuse alveolar hemorrhage was made by the clinical, bronchoscopic and bronchoalveolar lavage fluid findings. Alveolar hemorrhage among patients with BMT-TTP has been scarce reported. These two complications may be regarded as related, as small vessel injury is a central feature in both and they may share aetiological and pathogenetic factors.

  11. [Assessment and management of post-transplant iron overload: Guidelines of the Francophone Society of Marrow Transplantation and Cellular Therapy (SFGM-TC)].

    PubMed

    Jaspers, Aurélie; Bouhya, Salaheddine; Belaiche, Stéphanie; Chevallier, Patrice; Hermet, Eric; Hospital-Gustems, Carole; Michallet, Mauricette; Rialland, Fanny; Samsonova, Olga; Sirvent, Anne; Yakoub-Agha, Ibrahim; Rohrlich, Pierre-Simon; Beguin, Yves

    2016-11-01

    To harmonize clinical practice in hematopoietic stem cell transplantation, the Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the sixth annual series of workshops which brought together practitioners from all member centers and took place in September 2015 in Lille. The main aim of this session was to describe the impact, evaluation and treatment of post-transplant iron overload.

  12. Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy.

    PubMed

    Phillips, G L; Shepherd, J D; Barnett, M J; Lansdorp, P M; Klingemann, H G; Spinelli, J J; Nevill, T J; Chan, K W; Reece, D E

    1991-10-01

    Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year

  13. Aspergillus Infections in Transplant and Non-Transplant Surgical Patients

    PubMed Central

    Guidry, Christopher; Politano, Amani; Rosenberger, Laura; McLeod, Matthew; Hranjec, Tjasa; Sawyer, Robert

    2014-01-01

    Background: Aspergillus infections are associated commonly with immunocompromised states, such as transplantation and hematologic malignant disease. Although Aspergillus infections among patients having surgery occur primarily in transplant recipients, they are found in non-recipients of transplants, and have a mortality rate similar to that seen among transplant recipients. Methods: We conducted a retrospective analysis of a prospective data base collected from 1996 to 2010, in which we identified patients with Aspergillus infections. We compared demographic data, co-morbidities, and outcomes in non-transplant patients with those in abdominal transplant recipients. Continuous data were evaluated with the Student t-test, and categorical data were evaluated through χ2 analysis. Results: Twenty-three patients (11 transplant patients and 12 non-transplant patients) were identified as having had Aspergillus infections. The two groups were similar with regard to their demographics and co-morbidities, with the exceptions of their scores on the Acute Physiology and Chronic Health Evaluation II (APACHE II), of 23.6±8.1 points for transplant patients vs. 16.8±6.1 points for non-transplant patients (p=0.03); Simplified Acute Physiology Score (SAPS) of 16.6±8.3 points vs. 9.2±4.1 points, respectively (p=0.02); steroid use 91.0% vs. 25.0%, respectively (p=0.003); and percentage of infections acquired in the intensive care unit (ICU) 27.3% vs. 83.3%, respectively (p=0.01). The most common site of infection in both patient groups was the lung. The two groups showed no significant difference in the number of days from admission to treatment, hospital length of stay following treatment, or mortality. Conclusions: Although Aspergillus infections among surgical patients have been associated historically with solid-organ transplantation, our data suggest that other patients may also be susceptible to such infections, especially those in an ICU who are deemed to be critically ill

  14. Electrocardiographic and other cardiac anomalies in beta-glucuronidase-null mice corrected by nonablative neonatal marrow transplantation.

    PubMed

    Schuldt, A J T; Hampton, T J; Chu, V; Vogler, C A; Galvin, N; Lessard, M D; Barker, J E

    2004-01-13

    Cardiovascular manifestations of lysosomal storage disease (LSD) are a significant health problem for affected patients. Infantile-onset cardiac disease, because of its rapid progression, is usually treated symptomatically. Therapy in older patients includes valve replacement and bone marrow (BM) transplantation, both of which are life threatening in the already debilitated patients. Enzyme replacement therapy has potential benefit but has not yet been demonstrated to provide long-term relief for cardiac disease. Here, we demonstrate prevention of severe cardiac manifestations in beta-glucuronidase (GUSB) null mice BM-transplanted i.v. as neonates without myeloablative pretreatment. The mice, a model of mucopolysaccharidosis type VII (MPSVII, Sly syndrome), develop progressive LSD unless provided with GUSB early in life. The BM recipients retained GUSB+ donor cells in the peripheral blood and heart until necropsy at > or = 11 months of age. The enzyme beta-hexosamindase increased in tissues of GUSB null MPSVII mice was reduced significantly (P = 0.001) in treated MPSVII hearts. Electrocardiography demonstrated normalization of heart rate, PR, PQ, and QRS intervals in BM recipients. Storage was markedly reduced in the stroma of heart valves, adventitial cells of the aortic root, perivascular and interstitial cells of the myocardium, and interstitial cells of the conduction tissue. Heart/body weight ratio normalized. The aortic root was still grossly distended, and the conductive myocytes retained storage, suggesting neither plays a major role in ECG normalization. We conclude that transplantation of MPSVII neonates without toxic intervention can prevent many of the cardiovascular manifestations of LSD.

  15. Bone marrow-derived stem cell transplantation for the treatment of insulin-dependent diabetes.

    PubMed

    Fotino, Carmen; Ricordi, Camillo; Lauriola, Vincenzo; Alejandro, Rodolfo; Pileggi, Antonello

    2010-01-01

    The bone marrow is an invaluable source of adult pluripotent stem cells, as it gives rise to hematopoietic stem cells, endothelial progenitor cells, and mesenchymal cells, amongst others. The use of bone marrow-derived stem cell (BMC) transplantation (BMT) may be of assistance in achieving tissue repair and regeneration, as well as in modulating immune responses in the context of autoimmunity and transplantation. Ongoing clinical trials are evaluating the effects of BMC to preserve functional beta-cell mass in subjects with type 1 and type 2 diabetes, and to favor engraftment and survival of transplanted islets. Additional trials are evaluating the impact of BMT (i.e., mesenchymal stem cells) on the progression of diabetes complications. This article reviews the progress in the field of BMC for the treatment of subjects with insulin-dependent diabetes, and summarizes clinical data of pilot studies performed over the last two decades at our research center by combining allogeneic islet transplantation with donor-specific BMC. Clinical data is summarized from pilot studies performed at our research center over the last two decades.

  16. Bone Marrow Derived Hematopoietic Stem and Progenitor Cells Infiltrate Allogeneic and Syngeneic Transplants

    PubMed Central

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

    2015-01-01

    Lineage (CD3e, CD11b, GR1, B220 and Ly-76) negative hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) infiltrate islet allografts within 24 h posttransplantation. In fact, lineagenegative Sca-1+cKit+ (“LSK”) cells, a classic signature for HSCs, were also detected among these graft infiltrating cells. Lineage negative graft infiltrating cells are functionally multi-potential as determined by a standard competitive bone marrow transplant (BMT) assay. By 3 months post-BMT, both CD45.1 congenic, lineage negative HSCs/HPCs and classic “LSK” HSCs purified from islet allograft infiltrating cells, differentiate and repopulate multiple mature blood cell phenotypes in peripheral blood, lymph nodes, spleen, bone marrow and thymus of CD45.2 hosts. Interestingly, “LSK” HSCs also rapidly infiltrate syngeneic islet transplants as well as allogeneic cardiac transplants and sham surgery sites. It seems likely that an inflammatory response, not an adaptive immune response to allo-antigen, is responsible for the rapid infiltration of islet and cardiac transplants by biologically active HSCs/HPCs. The pattern of hematopoietic differentiation obtained from graft infiltrating HSCs/HPCs, cells that are recovered from inflammatory sites, as noted in the competitive BMT assay, is not precisely the same as that of intra-medullary HSCs. This does not refute the obvious multi-lineage potential of graft infiltrating HSCs/HPCs. PMID:25387427

  17. In Vivo Functional and Transcriptional Profiling of Bone Marrow Stem Cells after Transplantation into Ischemic Myocardium

    PubMed Central

    Sheikh, Ahmad Y.; Huber, Bruno C.; Narsinh, Kazim H.; Spin, Joshua M.; van der Bogt, Koen; de Almeida, Patricia E.; Ransohoff, Katherine J.; Kraft, Daniel L.; Fajardo, Giovanni; Ardigo, Diego; Ransohoff, Julia; Bernstein, Daniel; Fischbein, Michael P.; Robbins, Robert C.; Wu, Joseph C.

    2011-01-01

    Objective Clinical trials of bone marrow-derived stem cell therapy for the heart have yielded variable results. The basic mechanism(s) that underlie their potential efficacy remains unknown. In the present study, we evaluate the survival kinetics, transcriptional response, and functional outcome of intramyocardial bone marrow mononuclear cell (BMMC) transplantation for cardiac repair in murine myocardial infarction model. Methods and Results We utilized molecular-genetic bioluminescence imaging and high throughput transcriptional profiling to evaluate the in vivo survival kinetics and gene expression changes of transplanted BMMCs after their engraftment into ischemic myocardium. Our results demonstrate short-lived survival of cells following transplant, with less than 1% of cells surviving by 6 weeks post-transplantation. Moreover, transcriptomic analysis of BMMCs revealed non-specific upregulation of various cell regulatory genes with a marked downregulation of cell differentiation and maturation pathways. BMMC therapy caused limited improvement of heart function as assessed by echocardiography, invasive hemodynamics, and positron emission tomography (PET). Histological evaluation of cell fate further confirmed findings of the in vivo cell tracking and transcriptomic analysis. Conclusions Collectively, these data suggest that BMMC therapy, in its present iteration, may be less efficacious than once thought. Additional refinement of existing cell delivery protocols should be considered to induce better therapeutic efficacy. PMID:22034515

  18. Bone marrow stromal cell transplantation preserves gammaaminobutyric acid receptor function in the injured spinal cord.

    PubMed

    Yano, Shunsuke; Kuroda, Satoshi; Shichinohe, Hideo; Seki, Toshitaka; Ohnishi, Takako; Tamagami, Hiroshi; Hida, Kazutoshi; Iwasaki, Yoshinobu

    2006-11-01

    A surprising shortage of information surrounds the mechanisms by which bone marrow stromal cells (BMSC) restore lost neurologic functions when transplanted into the damaged central nervous system. In the present study, we sought to elucidate whether BMSCs express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into injured spinal cord. To examine this, we harvested and cultured rat femoral BMSCs. We then subjected Sprague-Dawley rats to thoracic spinal cord injury (SCI) with a pneumatic impact device. Fluorescence-labeled BMSCs (n = 7) were transplanted stereotactically or the vehicle in which these cells were cultured (n = 4) was introduced stereotactically into the rostral site of SCI at 7 days after injury. We evaluated GABA receptor function by measuring the binding potential for 125I-iomazenil (125I-IMZ) through in vitro autoradiography at 4 weeks after BMSC transplantation and simultaneously examined the fate of the transplanted BMSCs by immunocytochemistry. We found that the transplanted BMSC migrated toward the core of the injury and were densely distributed in the marginal region at 4 weeks after transplantation. BMSC transplantation significantly increased the binding potential for 125I-IMZ (p = 0.0376) and increased the number of GABA receptor-positive cells (p = 0.0077) in the marginal region of the injury site. Some of the transplanted BMSCs were positive for microtubule-associated protein-2 and the alpha1 subunit of GABA(A) receptor in the region of injury. These findings suggest that BMSCs have the potential to support the survival of neurons in the marginal region of SCI and can partly differentiate into neurons, regenerating spinal cord tissue at the site of injury.

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

    PubMed

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

    2015-02-01

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

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

    PubMed

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

    2013-03-01

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

  1. 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.

  2. Pneumonia in renal transplant patients.

    PubMed Central

    Bowie, D. M.; Marrie, T. J.; Janigan, D. T.; MacKeen, A. D.; Belitsky, P.; MacDonald, A. S.; Lannon, S. G.; Cohen, A. D.

    1983-01-01

    Between January 1976 and March 1982, 28 episodes of pneumonia occurred in 26 renal transplant patients. The overall mortality rate was 46%. Of the 16 patients with nosocomial pneumonia 9 (56%) died, whereas of the 12 patients with community-acquired pneumonia 4 (33%) died. In all 9 cases of unknown cause the response to empiric treatment was prompt, whereas in 4 of the 10 cases of monomicrobial pneumonia and 8 of the 9 cases of polymicrobial pneumonia the patient died. Cytomegalovirus was the sole cause of the pneumonia in two patients and a contributing cause, along with aerobic gram-negative bacteria, in another five, four of whom also had a fungal infection. Two patients, both of whom survived, had nosocomial Legionnaires' disease. PMID:6342741

  3. Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury

    PubMed Central

    Dong, Yuzhen; Yang, Libin; Yang, Lin; Zhao, Hongxing; Zhang, Chao; Wu, Dapeng

    2014-01-01

    Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesenchymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury. PMID:25317169

  4. DNA-based HLA typing of nonhematopoietic tissue used to select the marrow transplant donor for successful treatment of transfusion-associated graft-versus-host disease.

    PubMed Central

    Friedman, D F; Kwittken, P; Cizman, B; Argyris, E; Kearns, J; Yang, S Y; Zmijewski, C; Bunin, N; Douglas, S D; Monos, D

    1994-01-01

    Transfusion-associated graft-versus-host disease (TAGVHD) is a rare and usually fatal complication of blood transfusion which can arise when immunocompetent lymphocytes from the donor of a cellular blood product are transfused into a severely immunocompromised recipient. We describe the case of an 8-month-old male with a severe combined immunodeficiency syndrome who developed TAGVHD after receiving an unirradiated transfusion. Serologic HLA typing of the parents, the patient, and the blood donor demonstrated the foreign origin of circulating lymphocytes, confirming the diagnosis of TAGVHD. The manifestations of TAGVHD did not respond to medical immunosuppressive therapy, and bone marrow transplantation was planned to treat the underlying immunodeficiency as well as the TAGVHD. By using DNA-based class I and class II HLA typing, the child's HLA type was determined from nonhematopoietic tissues. This information proved critical in selecting the bone marrow donor. The child received immunosuppression, myeloablation, and a T-depleted, maternal bone marrow graft mismatched at one HLA class II allele. Trilineage hematopoietic engraftment occurred within 3 weeks, and the child remains clinically stable with no evidence of TAGVHD more than 2 years after the transplant. This case illustrates that TAGVHD can be successfully treated by allogeneic bone marrow transplantation and that DNA-based HLA typing can play a unique role in the diagnosis and management of TAGVHD. PMID:8556506

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

    PubMed

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

    2010-10-01

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

  6. Gene therapy/bone marrow transplantation in ADA-deficient mice: roles of enzyme-replacement therapy and cytoreduction.

    PubMed

    Carbonaro, Denise A; Jin, Xiangyang; Wang, Xingchao; Yu, Xiao-Jin; Rozengurt, Nora; Kaufman, Michael L; Wang, Xiaoyan; Gjertson, David; Zhou, Yang; Blackburn, Michael R; Kohn, Donald B

    2012-11-01

    Gene therapy (GT) for adenosine deaminase-deficient severe combined immune deficiency (ADA-SCID) can provide significant long-term benefit when patients are given nonmyeloablative conditioning and ADA enzyme-replacement therapy (ERT) is withheld before autologous transplantation of γ-retroviral vector-transduced BM CD34+ cells. To determine the contributions of conditioning and discontinuation of ERT to the therapeutic effects, we analyzed these factors in Ada gene knockout mice (Ada(-/-)). Mice were transplanted with ADA-deficient marrow transduced with an ADA-expressing γ-retroviral vector without preconditioning or after 200 cGy or 900 cGy total-body irradiation and evaluated after 4 months. In all tissues analyzed, vector copy numbers (VCNs) were 100- to 1000-fold greater in mice receiving 900 cGy compared with 200 cGy (P < .05). In mice receiving 200 cGy, VCN was similar whether ERT was stopped or given for 1 or 4 months after GT. In unconditioned mice, there was decreased survival with and without ERT, and VCN was very low to undetectable. When recipients were conditioned with 200 cGy and received transduced lineage-depleted marrow, only recipients receiving ERT (1 or 4 months) had detectable vector sequences in thymocytes. In conclusion, cytoreduction is important for the engraftment of gene-transduced HSC, and short-term ERT after GT did not diminish the capacity of gene-corrected cells to engraft and persist.

  7. 660 nm red light-enhanced bone marrow mesenchymal stem cell transplantation for hypoxic-ischemic brain damage treatment.

    PubMed

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

    2014-02-01

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

  8. Whole blood tissue factor procoagulant activity remains detectable during severe aplasia following bone marrow and peripheral blood stem cell transplantation.

    PubMed

    Ozcan, M; Morton, C T; Solovey, A; Dandelet, L; Bach, R R; Hebbel, R P; Slungaard, A; Key, N S

    2001-02-01

    Using a novel whole blood assay, we recently demonstrated that tissue factor procoagulant activity (TF PCA) is present in normal individuals. Preliminary experiments suggested that this activity is localized in the mononuclear cell fraction. Postulating that whole blood TF PCA would therefore be undetectable when monocytes and neutrophils are absent from peripheral blood, we assayed TF PCA during the peri-transplant period in 15 consecutive patients undergoing allogeneic (n = 12) or autologous (n = 3) bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). Baseline (pre-transplant) mean TF PCA was higher in patients compared to normal controls (P <0.005). Unexpectedly, although TF PCA during the period of profound aplasia was significantly reduced compared to baseline (p <0.05), fully 55% of the initial activity remained detectable. During the engraftment phase, TF PCA returned to pre-transplant levels, with a linear correlation between monocyte counts and TF PCA (r = 0.63). In contrast to normal whole blood, incubation of aplastic samples with E. Coli lipopolysaccharide ex vivo failed to induce TF PCA. Throughout the period of study--but especially during the aplastic phase--the absolute number of circulating endothelial cells (CECs) that were TF antigen-positive was increased compared to normals (P <0.001). However, removal of these cells from whole blood samples failed to significantly diminish total TF PCA indicating that CECs alone could not account for the detectable TF PCA during aplasia. We conclude that neither circulating mature myelo-monocytic cells nor endothelial cells can account for all the functionally intact TF in peripheral blood. Further studies are needed to identify the other source(s) of TF PCA.

  9. Total body irradiation as preparation for bone marrow transplantation in treatment of acute leukemia and aplastic anemia

    SciTech Connect

    Serota, F.T.; Burkey, E.D.; August, C.S.; D'Angio, G.J.

    1983-12-01

    In an attempt to improve survival while minimizing toxicity, many bone marrow transplant centers are now studying the use of cytoreduction regimens with an increased amount of radiation in single-dose or fractionated-exposure schedules for patients with leukemia and aplastic anemia. In order to review the current results, the literature prior to September, 1982 was surveyed and data were tabulated for each transplant center regarding the number of patients receiving transplants, diagnoses, cytoreduction regimen, clinical status, remission duration, relapse rate, causes of death and incidence of interstitial pneumonia. The incidence and severity of cataracts, growth failure, hypothyroidism and second malignant neoplasms were noted, and the data obtained from the literature search were updated and expanded by telephone questionnaire when possible. Marked variation in the technique of tranplantation was found among the participating institutions, making it difficult to determine the contribution of the various TBI doses, dose rates and fractionation schedules to the efficacy and toxicity of the combined regimen. In order to define the risk-benefit ratio of the various TBI regimens more clearly, prospective controlled, randomized studies will be required.

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

    PubMed

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

    2013-09-01

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

  11. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with B-precursor acute lymphoblastic leukemia in a second remission: a collaborative study of the Children's Oncology Group and the Center for International Blood and Marrow Transplant Research

    PubMed Central

    Eapen, Mary; Raetz, Elizabeth; Zhang, Mei-Jie; Muehlenbein, Catherine; Devidas, Meenakshi; Abshire, Thomas; Billett, Amy; Homans, Alan; Camitta, Bruce; Carroll, William L.; Davies, Stella M.

    2006-01-01

    The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)–containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (≥ 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse. PMID:16493003

  12. Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation1

    PubMed Central

    Goldberg, Gabrielle L.; King, Christopher G.; Nejat, Rebecca A.; Suh, David Y.; Smith, Odette M.; Bretz, Jamison C.; Samstein, Robert M.; Dudakov, Jarrod A.; Chidgey, Ann P.; Chen-Kiang, Selina; Boyd, Richard L.; van den Brink, Marcel R. M.

    2009-01-01

    Posttransplant immunodeficiency, specifically a lack of T cell reconstitution, is a major complication of allogeneic bone marrow transplantation. This immunosuppression results in an increase in morbidity and mortality from infections and very likely contributes to relapse. In this study, we demonstrate that sex steroid ablation using leuprolide acetate, a luteinizing hormone-releasing hormone agonist (LHRHa), increases the number of lymphoid and myeloid progenitor cells in the bone marrow and developing thymocytes in the thymus. Although few differences are observed in the peripheral myeloid compartments, the enhanced thymic reconstitution following LHRHa treatment and allogeneic bone marrow transplantation leads to enhanced peripheral T cell recovery, predominantly in the naive T cell compartment. This results in an increase in T cell function in vivo and in vitro. Graft-versus-host-disease is not exacerbated by LHRHa treatment and graft-versus-tumor activity is maintained. Because LHRHa allows for reversible (and temporary) sex steroid ablation, has a strong safety profile, and has been clinically approved for diseases such as prostate and breast cancer, this drug treatment represents a novel therapeutic approach to reversal of thymic atrophy and enhancement of immunity following immunosuppression. PMID:19380833

  13. Veno-occlusive disease prophylaxis with fresh frozen plasma and heparin in bone marrow transplantation.

    PubMed

    Batsis, Ioannis; Yannaki, Evangelia; Kaloyannidis, Panayotis; Sakellari, Ioanna; Smias, Christos; Georgoulis, Ioannis; Fassas, Athanasios; Anagnostopoulos, Achilles

    2006-01-01

    Fresh frozen plasma (FFP) contains natural anticoagulants, such as antithrombin (AT) and Protein C (Prot-C). We hypothesized that FFP given in addition to heparin, could potentially replace the consumption of endogenous anticoagulants occurring during conditioning and moreover, corrected AT levels could augment heparin's anticoagulant function. This could therefore result in an effective anti-VOD prophylaxis. In this study, we retrospectively analyzed the incidence of hepatic VOD in 403 consecutive bone marrow transplants (BMTs) comparing 2 prophylactic regimens and no prophylaxis. Patients received no prophylaxis (70/403), heparin-only (27/403) or heparin+2FFP daily during conditioning (306/403). VOD was significantly lower in the heparin+FFP group (5.9%) compared to heparin (20%) and no prophylaxis group (15.7%) [p<0.01]. Day 8 AT and Prot-C levels, were lower in the VOD- compared to the non-VOD group (AT: 69+/-26% vs. 89+/-19%, Prot-C:68+/-26% vs. 91+/-29%, respectively, p=0.001). In a multivariate logistic regression, risk factors for developing VOD were: the administration of >2 hepato-nephrotoxic drugs, previous history of hepatitis B or C and number of BMT. Multivariate analysis in a subset of 198 patients (all having recorded AT, Prot-C), demonstrated as VOD-related factors, the low day 8 Prot-C, number of BMT>1 and prior abdominal radiotherapy. Our study implies that FFP during conditioning, in addition to heparin, potentially has an anti-VOD prophylactic effect, presumably by minimizing the drop of natural anticoagulants around day 8. In order to evaluate if there truely is a beneficial effect of heparin+FFP in VOD prophylaxis, we have initiated a prospective randomized trial.

  14. Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

    PubMed Central

    D'Souza, Anita; Dispenzieri, Angela; Wirk, Baldeep; Zhang, Mei-Jie; Huang, Jiaxing; Gertz, Morie A.; Kyle, Robert A.; Kumar, Shaji; Comenzo, Raymond L.; Peter Gale, Robert; Lazarus, Hillard M.; Savani, Bipin N.; Cornell, Robert F.; Weiss, Brendan M.; Vogl, Dan T.; Freytes, César O.; Scott, Emma C.; Landau, Heather J.; Moreb, Jan S.; Costa, Luciano J.; Ramanathan, Muthalagu; Callander, Natalie S.; Kamble, Rammurti T.; Olsson, Richard F.; Ganguly, Siddhartha; Nishihori, Taiga; Kindwall-Keller, Tamila L.; Wood, William A.; Mark, Tomer M.; Hari, Parameswaran

    2015-01-01

    Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality

  15. 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

  16. Efficacy and outcome of allogeneic transplantation in IgD and nonsecretory myeloma. A report on behalf of the Myeloma Subcommittee of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Morris, Curly; Iacobelli, Simona; Gahrton, Gösta; van Biezen, Anja; Drake, Mary; Garderet, Laurent; Potter, Michael; Schattenberg, Anton V; Cornelissen, Jan J; Hamladji, Rose-Marie; Martelli, Massimo; Petersen, Eefke; Rovira, Montserrat; Bandini, Giuseppe; Kroger, Nicolaus; de Witte, Theo

    2015-06-01

    We have recently reported on the outcome of autologous transplantation in the rare myelomas (IgD, IgE, IgM, and nonsecretory [NS]) but there is no real information on the outcome of these conditions after allogeneic transplantation. We used the European Group for Blood and Marrow Transplantation myeloma database to compare the outcomes after allogeneic transplantation of 1354 common myelomas (IgG, IgA, and light chain myeloma) with the outcome in 26 IgD myelomas and 52 NS myelomas. There was little difference between common and the IgD and NS myeloma patients with respect to prognostic factors although the IgD group had a higher beta 2 microglobulin at diagnosis, shorter time to transplantation, and more T cell depletion. IgD and NS patients had a significantly greater achievement of complete remission at conditioning but this did not translate into equivalent progression-free survival and overall survival for the IgD patients although the NS outcome was very similar to that of common myeloma. The PFS and OS of IgD, common, and NS myelomas appear similar after allogeneic transplantation, despite a tendency for higher early relapse rate in IgD myeloma. Allogeneic transplantation may, therefore, be an option to investigate in prospective observational studies.

  17. Allogenic stem cell transplantation as salvage therapy for patients relapsing after autologous transplantation: experience from a single institution.

    PubMed

    Martínez, C; Carreras, E; Rovira, M; Urbano-Ispizua, A; Esteve, J; Fernández-Avilés, F; Perales, M; Rives, S; Gómez, M; Montserrat, E

    2001-05-01

    The prognosis of patients relapsing after an autologous transplant (autoSCT) is very poor. Allogenic stem cell transplantation (alloSCT) offers the possibility of curing some of these patients, at the cost, however, of a high transplant related mortality (TRM). The aim of this study was to analyze the outcome of 14 consecutive patients with hematologic malignancies, from a single institution, who underwent alloSCT for progressive disease after autoSCT. Patients had relapsed at a median of 11.5 months (range 2-72) after autoSCT and they underwent alloSCT at a median of 25.5 months (range 7-73) from the first transplant. Ten patients received HLA-identical related peripheral blood progenitor cells, three patients underwent matched-unrelated donor marrow transplants, and one patient received a mismatched related transplant. Conditioning regimens consisted of total body irradiation plus cyclophosphamide (n=5) or melphalan (n=1), or high-dose combination chemotherapy (n=8). Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. Eight patients (57%) developed grade II-IV acute GVHD. All evaluable patients (n=6) presented extensive chronic GVHD. Overall survival at 1 year was 16% (median 3.5 months, 95% CI 0.7-10.3). Ten patients (71%) died from transplant related complications at a median of 3.5 months (range 0.7-11). Only one patient died of recurrent disease. Three patients remain alive and in complete remission at the time of this report (4, 20 and 20 months, respectively). In conclusion, alloSCT offers the possibility of a sustained control of the disease in some patients who relapse after an autoSCT. However, the procedure is associated with a high transplant-related mortality. Better results might be obtained by carefully selecting patients and by reducing the intensity of the preparative regimen.

  18. Bone Marrow Transplantation: MedlinePlus Health Topic

    MedlinePlus

    ... response by commensal gut microbiota and potential... Article: Comparison of Patient-Reported Outcomes in 5-Year Survivors ... the sharing features on this page, please enable JavaScript. About MedlinePlus Site Map FAQs Customer Support Get ...

  19. Venocclusive disease of the liver after allogeneic bone marrow transplantation in man

    SciTech Connect

    Ganem, G.; Saint-Marc Girardin, M.F.; Kuentz, M.; Cordonnier, C.; Marinello, G.; Teboul, C.; Braconnier, F.; Vernant, J.P.; Dhumeaux, D.; Le Bourgeois, J.P.

    1988-05-01

    One hundred and fifty-one consecutive patients underwent allogeneic bone marrow transplantation (B.M.T.) following high-dose chemotherapy and single dose total body irradiation (T.B.I.) for hematologic malignancies between September 1980 and December 1985. All patients included in this study were treated using a /sup 60/Co beam to deliver a prescribed dose of 10 Gy to the mid-plane of the abdomen. Total body irradiation was performed the day before B.M.T. The mean instantaneous dose-rate was 3.5 cGy/min (range: 2.6 to 4.7). The real dose received was measured using thermoluminescent dosimeters (lithium borate). The difference between the doses delivered to the liver and to the mid-plane of the abdomen did not exceed 5%. The mean real dose delivered to the reference point was 10 Gy (range 8.3 to 11.7). Ninety five per cent of the patients received a dose ranging from 9.1 Gy to 10.9 Gy. High-dose cyclophosphamide was given to 126 patients with a standard-risk of relapse (60 mg/kg on day 5 and 4 before B.M.T.). Chemotherapy was intensified by the addition of other drugs in 25 patients with higher-risk of relapse. We analyzed the effect of the following pretransplant characteristics on the subsequent posttransplant development of V.O.D.: age, sex, ASAT and/or ALAT before conditioning regimen, diagnosis and status of malignant disease, history of liver disease, interval between diagnosis of hematologic malignancy and B.M.T., conditioning regimen (i.e., classical or intensified) and dose delivered to the liver during T.B.I. Seventeen patients were classified as having clinical V.O.D. giving a prevalence of 11.2%. In the first 2 months following B.M.T., death occurred respectively in 9 of 17 (53%) and 23 of 134 (17%) patients with and without clinical V.O.D.

  20. Outcome of conditioning intensity in acute myeloid leukemia with monosomal karyotype in patients over 45 year-old: A study from the acute leukemia working party (ALWP) of the European group of blood and marrow transplantation (EBMT).

    PubMed

    Poiré, Xavier; Labopin, Myriam; Cornelissen, Jan J; Volin, Liisa; Richard Espiga, Carlos; Veelken, J Hendrik; Milpied, Noël; Cahn, Jean-Yves; Yacoub-Agha, Ibrahim; van Imhoff, Gustaaf W; Michallet, Mauricette; Michaux, Lucienne; Nagler, Arnon; Mohty, Mohamad

    2015-08-01

    Acute myeloid leukemia with monosomal karyotype (MK AML) carries a very poor prognosis, even after allogeneic stem cell transplantation (SCT). However, SCT remains the only curative option in this high-risk population. Because myeloablative conditioning regimen (MAC) is associated with less relapse, we hypothesized that more intensive conditioning regimen might be beneficial for MK AML patients. We reviewed 303 patients over age 45 diagnosed with either de novo or secondary MK AML. One hundred and five patients received a MAC and 198 a reduced-intensity conditioning (RIC). The median age at SCT was 57-year-old, significantly lower in the MAC (53-year-old) than in the RIC group (59-year-old). The median follow-up was 42 months (range, 3 - 156 months). The 3-year overall survival (OS), leukemia-free survival (LFS), and relapse rate (RR) were not significantly different between both groups with overall values of 34%, 29%, and 51%, respectively. On the contrary, the 3-year nonrelapse mortality (NRM) was significantly higher in MAC recipients (28%) compared with RIC patients (16%, P = 0.004). The incidence of Grades II to IV acute graft-versus-host disease (GvHD) was significantly higher after a MAC (30.5%) than after a RIC (19.3%, P = 0.02). That of chronic GvHD was comparable between both groups (35%) and did not impact on LFS. Interestingly, within our MK AML cohort, hypodiploidy was significantly associated with worse outcomes. Due to reduced toxicity and comparable OS, LFS, and RR, RIC appears as a good transplant option in the very high-risk population, including older patients, diagnosed with MK AML.

  1. Patient selection for liver transplantation.

    PubMed

    Carrion, Andres F; Aye, Lydia; Martin, Paul

    2013-08-01

    Improved outcomes in liver transplant recipients reflect advances in surgical technique, post-operative care, immunosuppression as well as better selection of potential candidates. The pre-transplant evaluation is a multidisciplinary process intended to recognize and treat important comorbid conditions that may impair outcomes during the peri- and post-transplant periods. Important psychosocial issues should also be ascertained and tackled early during the pre-transplant evaluation with an overarching intention to improve the success of liver transplantation.

  2. Nonablative neonatal marrow transplantation attenuates functional and physical defects of beta-glucuronidase deficiency.

    PubMed

    Soper, B W; Lessard, M D; Vogler, C A; Levy, B; Beamer, W G; Sly, W S; Barker, J E

    2001-03-01

    The toxicity of preparative regimens render neonatal bone marrow transplantation (BMT) for progressive childhood diseases a controversial treatment. Ablative BMT in neonatal mice with or without the lysosomal storage disease mucopolysaccharidosis type VII (MPS VII) show high morbidity and developmental disruption of both brain and bone structure. In this investigation, BMT was performed with a high dose of congenic, normal bone marrow into nonablated newborn mice. Recipients had lifelong, multilineage, peripheral blood chimerism with the donor beta-glucuronidase-positive (GUS(+)) cells that was both well tolerated and therapeutic. Three daily injections of normal adult marrow increased the average life span by at least 6 months and corrected the functional breeding deficits typical of the MPS VII mice. Twelve months after injection, several structural features of femurs were more like that of normal mice than of untreated MPS VII mice. Periosteal circumference and bone cortical thickness were significantly improved in males and cortical density did not differ significantly from values in normal females. Significant reduction of lysosomal glycosaminoglycan storage corresponded directly with GUS enzyme activity and percentage of histochemically GUS(+) cells in visceral organs and hematopoietic tissues such as thymus, spleen, peripheral blood, and bone marrow. By all criteria tested, BMT into neonatal MPS VII mice in the absence of any preparative regimen is a successful therapy.

  3. Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study.

    PubMed

    Engelhard, D; Elishoov, H; Strauss, N; Naparstek, E; Nagler, A; Simhon, A; Raveh, D; Slavin, S; Or, R

    1996-02-15

    The purpose of this study was to examine coagulase-negative staphylococcal infections in bone marrow transplantation (BMT) patients with central vein catheters by investigating incidence, clinical relevance, risk factors, methicillin resistance, clinical impact of initial empiric antimicrobial therapy without vancomycin, and management of documented catheter-related infections. A 5-year prospective study was conducted with daily evaluation of 242 BMT patients during hospitalization, including clinical assessment and blood culture via the Hickman/Broviac catheter. If fever or infected appearance occurred, peripheral blood cultures or exit site cultures, respectively, were done. Results showed a septicemia incidence of 7.0%, including in 6 patients following colonization, in 1 patient with tunnel infection, in 1 patient with thrombophlebitis, in 1 patient with exit site infection, and in 8 patients with septicemia of unknown origin. Total colonization incidence was 7%, with colonization only in 11 patients who had 16 episodes; incidence of exit site infection was 3.7%. Age > or = 18 years was the only identified risk factor for developing staphylococcal infection (P = 0.03). Despite a methicillin resistance rate of 45% and omission of vancomycin from the routine initial empiric antimicrobial regimen, the clinical course of coagulase-negative staphylococcal infections was relatively benign. A single patient, who experienced marrow rejection, died on day +31 with septicemia and only one patient experienced microbiological failure with recurrent colonization. Bacteria grown in both aerobic and anaerobic bottles were more likely true bacteremia than contaminant (P = 0.03). We conclude that the hazard of coagulase-negative staphylococcal infection does not mandate inclusion of a glycopeptide in the initial empiric antimicrobial regimen in BMT patients, even during febrile neutropenia. Hickman/Broviac-related staphylococcal infections, except for tunnel infection or

  4. Alternative donor transplantation after reduced intensity conditioning: results of parallel phase 2 trials using partially HLA-mismatched related bone marrow or unrelated double umbilical cord blood grafts

    PubMed Central

    Carter, Shelly L.; Karanes, Chatchada; Costa, Luciano J.; Wu, Juan; Devine, Steven M.; Wingard, John R.; Aljitawi, Omar S.; Cutler, Corey S.; Jagasia, Madan H.; Ballen, Karen K.; Eapen, Mary; O'Donnell, Paul V.

    2011-01-01

    The Blood and Marrow Transplant Clinical Trials Network conducted 2 parallel multicenter phase 2 trials for individuals with leukemia or lymphoma and no suitable related donor. Reduced intensity conditioning (RIC) was used with either unrelated double umbilical cord blood (dUCB) or HLA-haploidentical related donor bone marrow (Haplo-marrow) transplantation. For both trials, the transplantation conditioning regimen incorporated cyclophosphamide, fludarabine, and 200 cGy of total body irradiation. The 1-year probabilities of overall and progression-free survival were 54% and 46%, respectively, after dUCB transplantation (n = 50) and 62% and 48%, respectively, after Haplo-marrow transplantation (n = 50). The day +56 cumulative incidence of neutrophil recovery was 94% after dUCB and 96% after Haplo-marrow transplantation. The 100-day cumulative incidence of grade II-IV acute GVHD was 40% after dUCB and 32% after Haplo-marrow transplantation. The 1-year cumulative incidences of nonrelapse mortality and relapse after dUCB transplantation were 24% and 31%, respectively, with corresponding results of 7% and 45%, respectively, after Haplo-marrow transplantation. These multicenter studies confirm the utility of dUCB and Haplo-marrow as alternative donor sources and set the stage for a multicenter randomized clinical trial to assess the relative efficacy of these 2 strategies. The trials are registered at www.clinicaltrials.gov under NCT00864227 (BMT CTN 0604) and NCT00849147 (BMT CTN 0603). PMID:21527516

  5. Transplanted bone marrow stromal cells protect neurovascular units and ameliorate brain damage in stroke-prone spontaneously hypertensive rats.

    PubMed

    Ito, Masaki; Kuroda, Satoshi; Sugiyama, Taku; Maruichi, Katsuhiko; Kawabori, Masahito; Nakayama, Naoki; Houkin, Kiyohiro; Iwasaki, Yoshinobu

    2012-10-01

    This study was aimed to assess whether bone marrow stromal cells (BMSC) could ameliorate brain damage when transplanted into the brain of stroke-prone spontaneously hypertensive rats (SHR-SP). The BMSC or vehicle was stereotactically engrafted into the striatum of male SHR-SP at 8 weeks of age. Daily loading with 0.5% NaCl-containing water was started from 9 weeks. MRIs and histological analysis were performed at 11 and 12 weeks, respectively. Wistar-Kyoto rats were employed as the control. As a result, T2-weighted images demonstrated neither cerebral infarct nor intracerebral hemorrhage, but identified abnormal dilatation of the lateral ventricles in SHR-SP. HE staining demonstrated selective neuronal injury in their neocortices. Double fluorescence immunohistochemistry revealed that they had a decreased density of the collagen IV-positive microvessels and a decreased number of the microvessels with normal integrity between basement membrane and astrocyte end-feet. BMSC transplantation significantly ameliorated the ventricular dilatation and the breakdown of neurovascular integrity. These findings strongly suggest that long-lasting hypertension may primarily damage neurovascular integrity and neurons, leading to tissue atrophy and ventricular dilatation prior to the occurrence of cerebral stroke. The BMSC may ameliorate these damaging processes when directly transplanted into the brain, opening the possibility of prophylactic medicine to prevent microvascular and parenchymal-damaging processes in hypertensive patients at higher risk for cerebral stroke.

  6. First report of pediatric hematopoietic stem cell transplantation activities in the eastern mediterranean region from 1984 to 2011: on behalf of the pediatric cancer working committee of the eastern mediterranean blood and marrow transplantation group.

    PubMed

    Hussein, A A; Hamidieh, A A; Elhaddad, A; Ramzi, M; Othman, T B; Hussain, F; Dennison, D; Ahmed, P; Abboud, M; Al-Ahmari, A; Wahadneh, A; Fathy, J; Bekadja, M-A; Al-Kindi, S; Benchekroun, S; Ibrahim, A; Behfar, M; Samra, M; Ladeb, S; Adil, S; El-Solh, H; Ayas, M; Aljurf, M; Ghavamzadeh, A; Al-Seraihy, A

    2017-01-01

    To describe the hematopoietic stem cell transplantation (HSCT) activities for children in the Eastern Mediterranean (EM) region, data on transplants performed for children less than 18 years of age between 1984 and 2011 in eight EM countries (Egypt, Iran, Jordan, Lebanon, Oman, Pakistan, Saudi Arabia and Tunisia) were collected. A total of 5187 transplants were performed, of which 4513 (87%) were allogeneic and 674 (13%) were autologous. Overall, the indications for transplantation were malignant diseases in 1736 (38.5%) and non-malignant in 2777 (61.5%) patients. A myeloablative conditioning regimen was used in 88% of the allografts. Bone marrow (BM) was the most frequent source of stem cells (56.2%), although an increasing use of PBSC was observed in the last decade. The stem cell source of autologous HSCT has shifted over time from BM to PBSC, and 80.9% of autologous HSCTs were from PBSCs. The donors for allogeneic transplants were matched-related in 94.5% of the cases, and unrelated transplants, mainly cord blood (99%) in 239 (5.5%) cases. This is the first report to describe the pediatric HSCT activities in EM countries. Non-malignant disorders are the main indication for allogeneic transplantation. Frequency of alternate donor transplantation is low.

  7. PEG-ADA: an alternative to haploidentical bone marrow transplantation and an adjunct to gene therapy for adenosine deaminase deficiency.

    PubMed

    Hershfield, M S

    1995-01-01

    PEG-ADA is a long-circulating form of adenosine deaminase (ADA) that has been in use for > 8 years as replacement therapy for severe combined immunodeficiency disease due to ADA deficiency. Treatment with PEG-ADA almost completely corrects metabolic abnormalities, allowing the recovery of a variable degree of immune function. Although not normal, the level of function achieved has in most cases been sufficient to protect against opportunistic and life-threatening infections. PEG-ADA has been used as an alternative for patients who lack an HLA-identical bone marrow donor, but are judged to be at too high a risk for undergoing HLA-haploidentical marrow transplantation. To date, mortality and morbidity with PEG-ADA have been less than for the latter procedure. PEG-ADA has also been an important adjunct to attempts to develop somatic cell gene therapy for ADA deficiency, although its continued use poses a problem for evaluation of the benefit of gene therapy. As a true "orphan drug" developed to treat a very small patient population, the cost per patient of PEG-ADA is very high.

  8. Navigating Survival: Quality of Life Following Bone Marrow Transplantation.

    DTIC Science & Technology

    1991-01-01

    the skin, musculoskeletal system, eyes, mouth, esophagus, gastrointestinal tract, lungs and liver. Early detection and treatment of chronic GVHD...life circumstances and express satisfaction with their lives. Laborde and Powers (1980) compared hemodialysis patients (n = 20) with osteoarthritis ... deficiencies , especially those treated for leukemia, Hodgkin’s disease, and breast cancer (Workman, 1989). Impairments of the T-lymphocytes and a decrease

  9. Long-term outcomes of myeloablation and autologous transplantation of relapsed acute myeloid leukemia in second remission: a British Society of Blood and Marrow Transplantation registry study.

    PubMed

    Chantry, Andrew D; Snowden, John A; Craddock, Charles; Peggs, Karl; Roddie, Claire; Craig, Jenny I O; Orchard, Kim; Towlson, Keiren E; Pearce, Rachel M; Marks, David I

    2006-12-01

    Relapsed acute myeloid leukemia (AML) in adults has a poor prognosis if treated with chemotherapy alone. Case series have previously supported the role of myeloablation and autologous transplantation as a potentially curative treatment. This study aimed to use the large numbers and extended follow-up data in the British Society of Blood and Marrow Transplantation (BSBMT) registry database to establish long-term outcomes and relate these to biological and procedural factors. The BSBMT registry database was used to retrospectively identify 152 adult patients (age, 16-69 years) with AML in second remission treated with autologous transplantation in 1982-2003. Cytogenetic data were available for 68% of the patients; of these, at diagnosis, 42% had good risk features, 57% had standard risk features, and 1% had poor risk features. Conditioning regimens varied; autologous rescue was provided with bone marrow (BM) (71%), peripheral blood stem cells (PBSCs) (18%), or both (11%), which were harvested during first complete remission (CR1) and/or second CR (CR2). Median follow-up was 84 months (range, 2-200 months). At 10 years, actuarial overall survival (OS) was 32%, progression-free survival (PFS) was 28%, and relapse rate (RR) was 57%. The 100-day nonrelapse mortality (NRM) was 7%, rising to 11% at 1 year and to 14% at 10 years. OS was significantly related to M3 subtype (5-year OS, 66%; P = .005), patient age at diagnosis (P = .005) and transplantation (P = .026), and length of CR1, with greatest significance if the patient was dichotomized at CR1 duration of < 8 months or > or = 8 months (P = .0001). There was no difference in OS between regimens containing total body irradiation (TBI) and chemotherapy alone (P = .7). In relation to the nature of autologous graft material, there was improved OS (P = .025) and PFS (P = .009) with the use of cells harvested entirely in CR1 compared with cells harvested in CR2 or in both CR1 and CR2. Engraftment times were significantly

  10. Successful engraftment following unrelated donor transplant in an alloimmunized patient with Kostmann syndrome.

    PubMed

    Myers, Scott N; Zeevi, Adriana; Zorich, G Phil; Pillage, Gina; Martel, Joan; Goyal, Rakesh K

    2005-05-01

    Severe chronic neutropenia (SCN) is characterized by severe recurrent bacterial infections during infancy. Blood or marrow transplantation (BMT) is the only curative option for patients with refractory disease. This report describes the case of a 4-year-old girl with refractory SCN, who received a bone marrow transplant from a highly matched donor after becoming HLA sensitized to multiple granulocyte transfusions. She is clinically well with normal blood counts and stable mixed chimerism 3 years after BMT. She experienced no graft rejection or graft versus host disease.

  11. Anti-thymocyte globulin as graft-versus-host disease prevention in the setting of allogeneic peripheral blood stem cell transplantation: a review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

    PubMed Central

    Baron, Frédéric; Mohty, Mohamad; Blaise, Didier; Socié, Gérard; Labopin, Myriam; Esteve, Jordi; Ciceri, Fabio; Giebel, Sebastian; Gorin, Norbert Claude; Savani, Bipin N; Schmid, Christoph; Nagler, Arnon

    2017-01-01

    Allogeneic hematopoietic stem cell transplantation is increasingly used as treatment for patients with life-threatening blood diseases. Its curative potential is largely based on immune-mediated graft-versus-leukemia effects caused by donor T cells contained in the graft. Unfortunately, donor T cells are also the cause of graft-versus-host disease. The vast majority of human leukocyte antigen-matched allogeneic hematopoietic stem cell transplants are nowadays carried out with peripheral blood stem cells as the stem cell source. In comparison with bone marrows, peripheral blood stem cells contain more hematopoietic stem/progenitor cells but also one log more T cells. Consequently, the use of peripheral blood stem cells instead of bone marrow has been associated with faster hematologic recovery and a lower risk of relapse in patients with advanced disease, but also with a higher incidence of chronic graft-versus-host disease. These observations have been the basis for several studies aimed at assessing the impact of immunoregulation with anti-thymocyte globulin on transplantation outcomes in patients given human leukocyte antigen-matched peripheral blood stem cells from related or unrelated donors. After a brief introduction on anti-thymocyte globulin, this article reviews recent studies assessing the impact of anti-thymocyte globulin on transplantation outcomes in patients given peripheral blood stem cells from human leukocyte antigen-matched related or unrelated donors as well as in recipients of grafts from human leukocyte antigen haploidentical donors. PMID:27927772

  12. Autologous hematopoietic stem cell transplantation for pediatric multiple sclerosis: a registry-based study of the Autoimmune Diseases Working Party (ADWP) and Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT).

    PubMed

    Burman, J; Kirgizov, K; Carlson, K; Badoglio, M; Mancardi, G L; De Luca, G; Casanova, B; Ouyang, J; Bembeeva, R; Haas, J; Bader, P; Snowden, J; Farge, D

    2017-03-20

    Autologous hematopoietic stem cell transplantation (aHSCT) is a promising therapy for multiple sclerosis (MS), which has mainly been used in adults. The purpose of this study was to investigate efficacy and adverse events of aHSCT in the treatment of children with MS using data from the European Society for Blood and Marrow Transplantation registry. Twenty-one patients with a median follow-up time of 2.8 years could be identified. PFS at 3 years was 100%, 16 patients improved in expanded disability status scale score and only 2 patients experienced a clinical relapse. The procedure was generally well tolerated and only two instances of severe transplant-related toxicity were recorded. There was no treatment-related mortality, although one patient needed intensive care. aHSCT may be a therapeutic option for children with disease that does not respond to standard care.Bone Marrow Transplantation advance online publication, 20 March 2017; doi:10.1038/bmt.2017.40.

  13. Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome Blood and Marrow Transplant Clinical Trials Network #1102 Study Rationale, Design and Methods

    PubMed Central

    Saber, Wael; Le Rademacher, Jennifer; Sekeres, Mikkael; Logan, Brent; Lewis, Moira; Mendizabal, Adam; Leifer, Eric; Appelbaum, Frederick R.; Horowitz, Mary M; Nakamura, Ryotaro; Cutler, Corey S.

    2014-01-01

    The introduction of reduced intensity conditioning regimens (RIC) made it possible to offer allogeneic hematopoietic cell transplantation (alloHCT) to older patients with myelodysplastic syndromes (MDS). However, the relative risks and benefits of alloHCT compared to novel non-transplant therapies continue to be the source of considerable uncertainty. We will perform a prospective biologic assignment trial to compare RIC alloHCT to non-transplant therapies based on donor availability. Primary outcome is 3-year overall survival. Secondary outcomes include leukemia-free survival, quality of life, and cost-effectiveness. Four hundred patients will be enrolled over roughly 3 years. Planned subgroup analyses will evaluate key biologic questions, such as the impact of age & response to hypomethylating agents on treatment effects. Findings from this study potentially may set a new standard of care for older MDS patients who are considered candidates for alloHCT. PMID:24972249

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

    SciTech Connect

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

    1981-10-01

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

  15. Ischemic colitis as a manifestation of thrombotic microangiopathy following bone marrow transplantation.

    PubMed

    Komeno, Yukiko; Ogawa, Seishi; Ishida, Tateru; Takeuchi, Kengo; Tsujino, Shiho; Kurokawa, Mineo; Aoki, Katsunori; Kanda, Yoshinobu; Chiba, Shigeru; Motokura, Toru; Fukayama, Masashi; Hirai, Hisamaru

    2003-12-01

    Thrombotic microangiopathy (TMA) is a microvascular disorder characterized by platelet aggregation and hemolytic anemia. In the setting of bone marrow transplantation (BMT), ischemic colitis due to TMA is difficult to differentiate from acute graft-versus-host disease. We report a 32-year-old man who presented ischemic colitis due to TMA after unrelated BMT for myelodysplastic syndrome. He suffered from treatment-resistant bloody diarrhea, and died of renal failure and Aspergillus pleuritis on day 253 post-BMT. Autopsy revealed endothelial injuries of arterioles and ischemic changes in the intestines and kidneys. Clinical and pathological characteristics of ischemic colitis due to BMT-associated TMA are described.

  16. Eradication of polymerase chain reaction-detectable chronic lymphocytic leukemia cells is associated with improved outcome after bone marrow transplantation.

    PubMed

    Provan, D; Bartlett-Pandite, L; Zwicky, C; Neuberg, D; Maddocks, A; Corradini, P; Soiffer, R; Ritz, J; Nadler, L M; Gribben, J G

    1996-09-15

    In chronic lymphocytic leukemia (CLL), clonal rearrangement of the immunoglobulin heavy chain locus (IgH) provides a useful marker for the detection of minimal residual disease (MRD) after treatment. At the time of initial presentation, DNA from patients with CLL was polymerase chain reaction (PCR)-amplified using consensus Variable (VH) and Joining (JH) region primers using complementarity determining region III consensus region primers or a panel of VH family-specific framework region 1 (FR1) primers. The clonal product was directly sequenced and patient-specific probes constructed using N region nucleotide sequences. We amplified and sequenced the CDRIII region and designed patient specific oligonucleotide probes for the detection of MRD in 55 of 66 patients (84%, 90% Confidence Intervals (CI): 74% to 90%) with poor prognosis CLL referred for autologous and allogeneic bone marrow transplantation (BMT). To determine the clinical utility of this technique, PCR amplification was performed on patient samples at the time of and following autologous (21 patients) and allogeneic (10 patients) BMT in whom serial bone marrow samples obtained after BMT were available for analysis. We show that the persistence of MRD after BMT is associated with increased probability of relapse. In all cases that have relapsed to date, the IgH CDRII region was identical at the time of initial presentation and at relapse suggesting that clonal evolution of the IgH locus is unusual in this disease. The finding that a significant number of patients remain disease free and with no evidence of PCR-detectable MRD after BMT suggests that high-dose therapy may contribute to improved outcome in selected patients with CLL.

  17. The long and the short of telomeres in bone marrow recipient SCID patients.

    PubMed

    Sarzotti-Kelsoe, Marcella; Daniell, Xiaoju G; Whitesides, John F; Buckley, Rebecca H

    2011-04-01

    Telomeres are noncoding DNA regions at the end of the chromosomes that are crucial for genome stability. Since telomere length decreases with cell division, they can be used as a signature of cell proliferation history. T-cell reconstitution in severe combined immunodeficiency (SCID) subjects, recipients of T-cell-depleted, allogeneic-related bone marrow cells, is due to the development and maturation of donor T-cell precursors in the infant's vestigial thymus and to homeostatic proliferation of mature T cells in the peripheral organs. Since T-cell function, thymic output, and T-cell clonal diversity are maintained long term in these patients, we investigated whether donor T-cell engraftment resulted in increased telomere shortening. Our study of seven SCID patients, following successful bone marrow transplantation, demonstrates that the patients' peripheral T cells did not exhibit greater than normal telomere shortening.

  18. Successful non-myeloablative allogenic bone marrow transplantation in a child with severe congenital neutropenia complicated by chronic pulmonary infection.

    PubMed

    Nino, Nanako; Kozaki, Aiko; Hasegawa, Daiichiro; Ueda, Go; Takahashi, Hironobu; Miyata, Kenji; Ochi, Satoshi; Yamashita, Tatsuya; Takafuji, Satoru; Uemura, Suguru; Yokoi, Takehito; Saito, Atsuro; Ishida, Toshiaki; Kawasaki, Keiichiro; Nakamura, Kazuhiro; Kobayashi, Masao; Kosaka, Yoshiyuki

    2016-06-01

    We herein describe a 2-year-old boy with severe congenital neutropenia (SCN) who was successfully treated with reduced-intensity bone marrow transplantation (HSCT). He had suffered recurrent episodes of bacterial pneumonia from 12 months of age, and was found to have severe neutropenia with white blood cell counts below 100/μl. The patient harbored a heterozygous missense mutation in ELANE exon 4 (p.Gln134Pro, NM_001972.2: c.401A>C). This was a novel mutation. Due to intractable pneumonia and severe persistent neutropenia, reduced-intensity HSCT was performed from an HLA-matched sibling donor. The preparative regimen consisted of melphalan, fludarabine, and 4 Gy of total body irradiation. Hematopoietic engraftment was rapidly obtained, i.e., by day +14, and complete donor chimerism was subsequently achieved. The lung complications observed pre-transplantation markedly improved after neutrophil recovery, i.e., by day +60. We concluded that HSCT is a useful treatment for SCN patients, especially for those at high risk of leukemic transformation. Fludarabine-based reduced-intensity HSCT may represent a safe and effective therapeutic option for patients with SCN who need HSCT even if they have intractable infectious complications.

  19. Bone marrow infection with Mycobacterium fortuitum in a diabetic patient.

    PubMed

    Satti, Luqman; Abbasi, Shahid; Sattar, Abdul; Ikram, Aamer; Manzar, Muhammad Adnan; Khalid, Malik Muhammad

    2011-08-01

    Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin.

  20. 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.

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

    PubMed

    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(+) insulin(-) PDX-1(+) cells, Ngn3(+) cells and insulin(+) glucagon(+) 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(+) 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.

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

    PubMed

    Tassoni, Alessia; Gutteridge, Alex; Barber, Amanda C; Osborne, Andrew; Martin, Keith R

    2015-10-01

    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.

  3. Acute renal graft-versus-host disease in a murine model of allogeneic bone marrow transplantation.

    PubMed

    Schmid, Peter M; Bouazzaoui, Abdellatif; Schmid, Karin; Birner, Christoph; Schach, Christian; Maier, Lars S; Holler, Ernst; Endemann, Dierk H

    2017-03-23

    Acute kidney injury (AKI) is a very common complication after allogeneic bone marrow transplantation (BMT) and associated with poor prognosis. Generally kidneys are assumed to be no direct target of Graft-versus-Host Disease (GvHD), and renal impairment is often attributed to several other factors occurring in the early phase after BMT. Our study aimed to prove the existence of renal GvHD in a fully MHC-mismatched model of BALB/c mice conditioned and transplanted according to two different intensity protocols. Syngeneically transplanted and untreated animals served as controls. 4 weeks after transplantation, allogeneic animals developed acute GvHD that was more pronounced in the high-intensity protocol (HIP) group than in the low-intensity protocol (LIP) group. Urea and creatinine as classic serum markers of renal function could not verify renal impairment 4 weeks after BMT. Creatinine levels were even reduced as a result of catabolic metabolism and loss of muscle mass due to acute GvHD. Proteinuria, albuminuria, and urinary N-acetyl-beta-Dglucosaminidase (NAG) levels were measured as additional renal markers before and after transplantation. Albuminuria and NAG were only significantly increased after allogeneic transplantation, correlating with disease severity between HIP and LIP animals. Histological investigations of the kidneys showed renal infiltration of T-cells and macrophages with endarteriitis, interstitial nephritis, tubulitis, and glomerulitis. T-cells consisted of CD4+, CD8+, and FoxP3+ cells. Renal expression analysis of allogeneic animals showed increases in indoleamine-2,3 dioxygenase (IDO), different cytokines (TNFα, IFN-γ, IL-1α, IL2, IL-6, and IL-10), and adhesion molecules (ICAM-1 and VCAM-1), resembling findings from other tissues in acute GvHD. In summary, our study supports the entity of renal GvHD with histological features suggestive of cell-mediated renal injury. Albuminuria and urinary NAG levels may serve as early markers of renal

  4. Transient engraftment of syngeneic bone marrow after conditioning with high-dose cyclophosphamide and thoracoabdominal irradiation in a patient with aplastic anemia

    SciTech Connect

    Matsue, K.; Niki, T.; Shiobara, S.; Ueda, M.; Ohtake, S.; Mori, T.; Matsuda, T.; Harada, M. )

    1990-01-01

    We describe the clinical course of a 16 year old girl with aplastic anemia who was treated by syngeneic bone marrow transplantation. Engraftment was not obtained by simple infusion of bone marrow without immunosuppression. The patient received a high-dose cyclophosphamide and thoracoabdominal irradiation, followed by second marrow transplantation from the same donor. Incomplete but significant hematologic recovery was observed; however, marrow failure recurred 5 months after transplantation. Since donor and recipient pairs were genotypically identical, graft failure could not be attributed to immunological reactivity of recipient cells to donor non-HLA antigens. This case report implies that graft failure in some cases of aplastic anemia might be mediated by inhibitory cells resistant to cyclophosphamide and irradiation.

  5. 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

  6. Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases.

    PubMed

    Krivit, W; Sung, J H; Shapiro, E G; Lockman, L A

    1995-01-01

    Treatment and potential cure of lysosomal and peroxisomal diseases, heretofore considered fatal, has become a reality during the past decade. Bone marrow transplantation, (BMT), has provided a method for replacement of the disease-causing enzyme deficiency. Cells derived from the donor marrow continue to provide enzyme indefinitely. Several scores of patients with diseases as diverse as metachromatic leukodystrophy, adrenoleukodystrophy, globoid cell leukodystrophy, Hurler syndrome (MPS I-H), Maroteaux-Lamy (MPS VI) Gaucher disease, and fucosidosis have been successfully treated following long-term engraftment. Central nervous system (CNS) manifestations are also prevented or ameliorated in animal models of these diseases following engraftment from normal donors. The microglial cell system has been considered to be the most likely vehicle for enzyme activity following bone marrow engraftment. Microglia in the mature animal or human are derived from the newly engrafted bone marrow. Graft-v-host disease activation of the microglia is also of importance. This article will summarize some of the pertinent literature relative to the role of microglia in such transplant processes.

  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. Regulatory functions of TRAIL in hematopoietic progenitors: human umbilical cord blood and murine bone marrow transplantation.

    PubMed

    Mizrahi, K; Stein, J; Pearl-Yafe, M; Kaplan, O; Yaniv, I; Askenasy, N

    2010-07-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway has selective toxicity to malignant cells. The TRAIL receptors DR4 and DR5 are expressed at low levels in human umbilical cord blood cells (3-15%) and are upregulated by incubation with the cognate ligand, triggering apoptosis in 70-80% of receptor-positive cells (P<0.001). Apoptosis is not induced in hematopoietic progenitors, as determined from sustained severe combined immunodeficiency reconstituting potential and clonogenic activity. Furthermore, elimination of dead cells after incubation with TRAIL for 72 h results in a threefold enrichment in myeloid progenitors. Exposure to TRAIL in semisolid cultures showed synergistic activity of DR4 and granulocyte/macrophage colony-stimulating factor in recruiting lineage-negative (lin(-)) and CD34(+) progenitors and in promoting the formation of large colonies. In murine bone marrow, approximately 30% of lin(-) cells express TRAIL-R2 (the only murine receptor), and the receptor is upregulated after transplantation in cycling and differentiating donor cells that home to the host marrow. However, this receptor is almost ubiquitously expressed in the most primitive (lin(-)SCA-1(+)c-kit(+)) progenitors, and stimulates the clonogenic activity of lin(-) cells (P<0.001), suggesting a tropic function after transplantation. It is concluded that TRAIL does not trigger apoptosis in hematopoietic progenitors, and upregulation of its cognate receptors under stress conditions mediates tropic signaling that supports recovery from hypoplasia.

  9. Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation.

    PubMed

    Dietz, Andrew C; Mehta, Parinda A; Vlachos, Adrianna; Savage, Sharon A; Bresters, Dorine; Tolar, Jakub; Boulad, Farid; Dalle, Jean Hugues; Bonfim, Carmem; de la Fuente, Josu; Duncan, Christine N; Baker, K Scott; Pulsipher, Michael A; Lipton, Jeffrey M; Wagner, John E; Alter, Blanche P

    2017-05-01

    Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond Blackfan anemia (DBA) are 3 of the most common inherited bone marrow failure syndromes (IBMFS), in which the hematologic manifestations can be cured with hematopoietic cell transplantation (HCT). Later in life, these patients face a variety of medical conditions, which may be a manifestation of underlying disease or due to pre-HCT therapy, the HCT, or a combination of all these elements. Very limited long-term follow-up data exist in these populations, with FA the only IBMFS that has specific published data. During the international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium entitled "Late Effects Screening and Recommendations following Allogeneic Hematopoietic Cell Transplant (HCT) for Immune Deficiency and Nonmalignant Hematologic Disease" held in Minneapolis, Minnesota in May of 2016, a half-day session was focused specifically on the unmet needs for these patients with IBMFS. A multidisciplinary group of experts discussed what is currently known, outlined an agenda for future research, and laid out long-term follow-up guidelines based on a combination of evidence in the literature as well as expert opinion. This article addresses the state of science in that area as well as consensus regarding the agenda for future research, with specific screening guidelines to follow in the next article from this group.

  10. Quality of life-adjusted survival analysis of high-dose therapy with autologous bone marrow transplantation versus sequential chemotherapy for patients with aggressive lymphoma in first complete remission. Groupe d'Etude les Lymphomes de l'Adulte (GELA).

    PubMed

    Mounier, N; Haioun, C; Cole, B F; Gisselbrecht, C; Sebban, C; Morel, P; Marit, G; Bouabdallah, R; Ravoet, C; Salles, G; Reyes, F; Lepage, E

    2000-06-15

    Evaluating high-dose therapy (HDT) with autologous stem cell transplantation (ASCT) in term of both duration and quality of life (QOL) presents major interests for patients with non-Hodgkin lymphoma. The quality-adjusted time without symptom and toxicity (Q-TWiST) methodology was applied to the LNH87-2 trial comparing HDT with ASCT versus sequential chemotherapy in 541 patients in first complete remission (CR). Overall survival (OS) and disease-free survival (DFS) curves were used to estimate duration of 4 health states: acute short-term toxicity (Tox1), secondary toxicity (Tox2), time without symptom and toxicity (TWiST), and relapse (Rel). Areas under survival curves (AUC) were retrospectively weighted according to QOL coefficients. HDT increased, but not significantly, TWiST (+2. 4 months in AUC, P =.17) and decreased Rel (-3 months, P <.01). Survival estimates did not differ between the 2 treatments (AUC 47.7 months for OS, 39.7 months for DFS). High-risk patients treated by HDT versus chemotherapy had a significant benefit in DFS (AUC 28.8 versus 24.9 months, P <.01) but not in OS (AUC 37.3 versus 36 months, P =.27). Sensitivity analysis, performed by varying QOL coefficients, demonstrated significant quality-adjusted survival gain in high-risk patients treated by HDT. In low-risk patients, a diagram provided an aid to clinical decision-making. This analysis supports the use of HDT in these patients with adverse prognostic factors in the first CR, even after adjusting for QOL using the Q-TWiST method. (Blood. 2000;95:3687-3692)

  11. Lymphocytic infiltration and HLA-DR expression of salivary glands in bone marrow transplant recipients: a prospective study.

    PubMed Central

    Lindahl, G; Lönnquist, B; Hedfors, E

    1988-01-01

    Lymphocytic infiltration and epithelial HLA-DR expression of lip salivary glands were studied by means of an immunohistoenzymatic staining technique in patients undergoing repeated lip salivary gland biopsies before, and 12, 26, 52 and 104 weeks after bone marrow transplantation (BMT). Within 12 weeks of transplantation, lymphocytes, mainly of the anti-Leu3a+ T 'helper' phenotype, were seen infiltrating the salivary glands of all the patients, reaching a maximum between 26 and 52 weeks. Epithelial HLA-DR expression, present at the 12th week after BMT, was seen close to the lymphocytic infiltrates in all the specimens. Two years after BMT, lymphocytic infiltrates and epithelial HLA-DR expression were still noted in about half of the specimens but not seen in the remaining ones. No correlations were found between immunohistopathology and earlier or persistent chronic graft-versus-host disease or immunosuppressive treatment. The significance of the findings as well as their resemblance to idiopathic connective tissue diseases, notably Sjögren's syndrome, are discussed. Images Fig. 1 PMID:2970353

  12. Ongoing graft-versus-host disease is a risk factor for azoospermia after allogeneic hematopoietic stem cell transplantation: a survey of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Rovó, Alicia; Aljurf, Mahmoud; Chiodi, Sandra; Spinelli, Simonetta; Salooja, Nina; Sucak, Gülsan; Hunter, Ann; Kim, Tan Swee; Socié, Gérard; van Lint, Maria Teresa; Passweg, Jakob R; Arat, Mutlu; Badoglio, Manuela; Tichelli, André

    2013-03-01

    The aim of this study was to assess the degree of spermatogenesis defects in sperm analysis in long-term male survivors after allogeneic hematopoietic stem cell transplantation in order to identify the risk factors related to potential infertility after hematopoietic stem cell transplantation and to provide data on longitudinal sperm recovery after hematopoietic stem cell transplantation. Here, the Late Effects Working Party of the European Group for Blood and Marrow Transplantation reports data of sperm analysis from 224 males who underwent hematopoietic stem cell transplantation. Median time between transplantation and sperm analysis was 63 months (8-275 months). At last sperm analysis, presence of any degree of spermatozoa was reported in 70 (31%) and complete azoospermia in 154 (69%) patients. In multivariate analysis, being conditioned with total body irradiation (RR 7.1; 95% CI: 3.4-14.8) and age over 25 years at transplantation (RR 2.4; 95% CI: 1.09-5.2) were significantly associated with higher risk for azoospermia. In patients not conditioned with total body irradiation, ongoing chronic graft-versus-host disease is the main adverse factor for sperm recovery (RR of 3.11; 95% CI: 1.02-9.47; P=0.045). Already established risk factors, such as total body irradiation and age older than 25 years at hematopoietic stem cell transplantation, were seen to be the most relevant adverse risk factor for sperm production after hematopoietic stem cell transplantation. Furthermore, for the first time, ongoing graft-versus-host disease has been shown to be the most relevant adverse factor for sperm recovery, particularly in patients conditioned without total body irradiation. We also introduce a useful scoring system to predict the probability of male long-term survivors' azoospermia.

  13. Ongoing graft-versus-host disease is a risk factor for azoospermia after allogeneic hematopoietic stem cell transplantation: a survey of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation

    PubMed Central

    Rovó, Alicia; Aljurf, Mahmoud; Chiodi, Sandra; Spinelli, Simonetta; Salooja, Nina; Sucak, Gülsan; Hunter, Ann; Kim, Tan Swee; Socié, Gérard; van Lint, Maria Teresa; Passweg, Jakob R.; Arat, Mutlu; Badoglio, Manuela; Tichelli, André

    2013-01-01

    The aim of this study was to assess the degree of spermatogenesis defects in sperm analysis in long-term male survivors after allogeneic hematopoietic stem cell transplantation in order to identify the risk factors related to potential infertility after hematopoietic stem cell transplantation and to provide data on longitudinal sperm recovery after hematopoietic stem cell transplantation. Here, the Late Effects Working Party of the European Group for Blood and Marrow Transplantation reports data of sperm analysis from 224 males who underwent hematopoietic stem cell transplantation. Median time between transplantation and sperm analysis was 63 months (8–275 months). At last sperm analysis, presence of any degree of spermatozoa was reported in 70 (31%) and complete azoospermia in 154 (69%) patients. In multivariate analysis, being conditioned with total body irradiation (RR 7.1; 95% CI: 3.4–14.8) and age over 25 years at transplantation (RR 2.4; 95% CI: 1.09–5.2) were significantly associated with higher risk for azoospermia. In patients not conditioned with total body irradiation, ongoing chronic graft-versus-host disease is the main adverse factor for sperm recovery (RR of 3.11; 95% CI: 1.02–9.47; P=0.045). Already established risk factors, such as total body irradiation and age older than 25 years at hematopoietic stem cell transplantation, were seen to be the most relevant adverse risk factor for sperm production after hematopoietic stem cell transplantation. Furthermore, for the first time, ongoing graft-versus-host disease has been shown to be the most relevant adverse factor for sperm recovery, particularly in patients conditioned without total body irradiation. We also introduce a useful scoring system to predict the probability of male long-term survivors’ azoospermia. PMID:22929982

  14. A Violaceous Nodule in a Lung-transplant Patient.

    PubMed

    Milford, Emily; Winslow, Caroline; Danhof, Rebecca

    2016-06-15

    Posttransplantation lymphoproliferative disorder (PTLD) is a rare complication of solid organ or allogenic bone marrow transplantation. Cases localized to the skin are even rarer, with only around 100 cases recorded in the literature [2]. We present a case of 60 year-old-woman, a lung transplant recipient, who presented with an asymptomatic violaceous nodule on her left medial calf. Histopathology was consistent with PTLD of the B-cell subtype, EBV negative. This case is unique in that it was of the B cell subtype of cutaneous PTLD, which has been less commonly observed than the T cell subtype. In addition, the case was EBV negative, which is rare in B cell cutaneous PTLD. The patient was treated with rituximab 600 mg IV weekly for four weeks and cytomegalovirus immune globulin (Cytogam) 100 mg/kg once, with resolution of the nodule.

  15. A cure for murine sickle cell disease through stable mixed chimerism and tolerance induction after nonmyeloablative conditioning and major histocompatibility complex-mismatched bone marrow transplantation.

    PubMed

    Kean, Leslie S; Durham, Megan M; Adams, Andrew B; Hsu, Lewis L; Perry, Jennifer R; Dillehay, Dirck; Pearson, Thomas C; Waller, Edmund K; Larsen, Christian P; Archer, David R

    2002-03-01

    The morbidity and mortality associated with sickle cell disease (SCD) is caused by hemolytic anemia, vaso-occlusion, and progressive multiorgan damage. Bone marrow transplantation (BMT) is currently the only curative therapy; however, toxic myeloablative preconditioning and barriers to allotransplantation limit this therapy to children with major SCD complications and HLA-matched donors. In trials of myeloablative BMT designed to yield total marrow replacement with donor stem cells, a subset of patients developed mixed chimerism. Importantly, these patients showed resolution of SCD complications. This implies that less toxic preparative regimens, purposefully yielding mixed chimerism after transplantation, may be sufficient to cure SCD without the risks of myeloablation. To rigorously test this hypothesis, we used a murine model for SCD to investigate whether nonmyeloablative preconditioning coupled with tolerance induction could intentionally create mixed chimerism and a clinical cure. We applied a well-tolerated, nonirradiation-based, allogeneic transplantation protocol using nonmyeloablative preconditioning (low-dose busulfan) and costimulation blockade (CTLA4-Ig and anti-CD40L) to produce mixed chimerism and transplantation tolerance to fully major histocompatibility complex-mismatched donor marrow. Chimeric mice were phenotypically cured of SCD and had normal RBC morphology and hematologic indices (hemoglobin, hematocrit, reticulocyte, and white blood cell counts) without evidence of graft versus host disease. Importantly, they also showed normalization of characteristic spleen and kidney pathology. These experiments demonstrate the ability to produce a phenotypic cure for murine SCD using a nonmyeloablative protocol with fully histocompatibility complex-mismatched donors. They suggest a future treatment strategy for human SCD patients that reduces the toxicity of conventional BMT and expands the use of allotransplantation to non-HLA-matched donors.

  16. Autologous hematopoietic stem cell transplantation for autoimmune diseases: an observational study on 12 years’ experience from the European Group for Blood and Marrow Transplantation Working Party on Autoimmune Diseases

    PubMed Central

    Farge, Dominique; Labopin, Myriam; Tyndall, Alan; Fassas, Athanasios; Mancardi, Gian Luigi; Van Laar, Jaap; Ouyang, Jian; Kozak, Tomas; Moore, John; Kötter, Ina; Chesnel, Virginie; Marmont, Alberto; Gratwohl, Alois; Saccardi, Riccardo

    2010-01-01

    Background Autologous hematopoietic stem cell transplantation has been used since 1996 for the treatment of severe autoimmune diseases refractory to approved therapies. We evaluated the long-term outcomes of these transplants and aimed to identify potential prognostic factors. Design and Methods In this observational study we analyzed all first autologous hematopoietic stem cell transplants for autoimmune diseases reported to the European Group for Blood and Marrow Transplantation (EBMT) registry between 1996–2007. The primary end-points for analysis were overall survival, progression-free survival and transplant-related mortality at 100 days. Results Nine hundred patients with autoimmune diseases (64% female; median age, 35 years) who underwent a first autologous hematopoietic stem cell transplant were included. The main diseases were multiple sclerosis (n=345), systemic sclerosis (n=175), systemic lupus erythematosus (n=85), rheumatoid arthritis (n=89), juvenile arthritis (n=65), and hematologic immune cytopenia (n=37). Among all patients, the 5-year survival was 85% and the progression-free survival 43%, although the rates varied widely according to the type of autoimmune disease. By multivariate analysis, the 100-day transplant-related mortality was associated with the transplant centers’ experience (P=0.003) and type of autoimmune disease (P=0.03). No significant influence of transplant technique was identified. Age less than 35 years (P=0.004), transplantation after 2000 (P=0.0015) and diagnosis (P=0.0007) were associated with progression-free survival. Conclusions This largest cohort studied worldwide shows that autologous hematopoietic stem cell transplantation can induce sustained remissions for more than 5 years in patients with severe autoimmune diseases refractory to conventional therapy. The type of autoimmune disease, rather than transplant technique, was the most relevant determinant of outcome. Results improved with time and were associated with

  17. Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct.

    PubMed

    Ito, Masaki; Shichinohe, Hideo; Houkin, Kiyohiro; Kuroda, Satoshi

    2017-02-01

    Bone marrow stromal cells (BMSC) transplantation enhances functional recovery after cerebral infarct, but the optimal delivery route is undetermined. This study was aimed to assess whether a novel cell-sheet technology non-invasively serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell sheet was analysed histologically and then transplanted onto the ipsilateral neocortex of rats subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their behaviours and histology were compared with those in the animals treated with direct injection of BMSCs or vehicle over 4 weeks post-transplantation. The cell sheet was 27.9 ± 8.0 μm thick and was composed of 9.8 ± 2.4 × 10(5) cells. Cell sheet transplantation significantly improved motor function when compared with the vehicle-injected animals. Histological analysis revealed that the BMSCs were densely distributed to the neocortex adjacent to the cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted animals. These findings were almost equal to those for the animals treated with direct BMSC injection. The attachment of the BMSC sheet to the brain surface did not induce reactive astrocytes in the adjacent neocortex, although direct injection of BMSCs profoundly induced reactive astrocytes around the injection site. These findings suggest that the BMSCs in cell sheets preserve their biological capacity of migration and neural differentiation. Cell-sheet technology may enhance functional recovery after ischaemic stroke, using a less invasive method. Copyright © 2014 John Wiley & Sons, Ltd.

  18. Kidney transplantation in patients with Fabry disease.

    PubMed

    Cybulla, Markus; Walter, Kerstin Nanette; Schwarting, Andreas; Divito, Raffaelle; Feriozzi, Sandro; Sunder-Plassmann, Gere

    2009-04-01

    Little is known about the effects of enzyme replacement therapy (ERT) in kidney transplant recipients with Fabry disease. Clinical characteristics of transplant recipients in the Fabry Outcome Survey (FOS) were therefore examined in patients with Fabry disease with or without ERT. Of the 837 European patients in FOS (March 2006), 34 male patients and two female patients had received kidney transplants. Mean age at transplantation was 37.6 +/- 10.9 years, mean time since transplantation was 7.7 +/- 6.4 years, median estimated glomerular filtration rate (eGFR) was 44.4 ml/min/1.73 m(2), and median proteinuria was 296 mg/24 h. Of 27 patients with baseline data, 59% had hypertension, 74% had left ventricular hypertrophy, 22% had cardiac valve disease, 30% had arrhythmia, and 22% had transient ischaemic attacks and 15% stroke. Twenty patients (74%; two female patients, 18 male patients) were receiving ERT with agalsidase alfa. At enrollment or at the start of ERT, median eGFRs were 59 and 35 ml/min/1.73 m(2) (P = 0.05) and median proteinuria levels were 240 and 420 mg/24 h (not significant) in treated and untreated patients respectively. Renal function remained stable in patients receiving ERT. In conclusion, agalsidase alfa is well tolerated in patients with Fabry disease who have undergone renal transplantation.

  19. Survival of pig-to-rhesus corneal xenografts prolonged by prior donor bone marrow transplantation.

    PubMed

    Jie, Ying; Liu, Limin; Pan, Zhiqiang; Wang, Li

    2013-03-01

    The aim of the present study was to explore the survival of pig-rhesus corneal xenografts following donor bone marrow transplantation (BMT). Wuzhishan pigs were used as donors and rhesus monkeys as recipients for corneal xenotransplantation. Twelve rhesus monkeys were divided into two groups. Group 1 received intravenous injection of cyclophosphamide (CP) followed by pig bone marrow cell transplantation, while group 2 was used as a control and only received intravenous CP injection. All xenografts were evaluated using a slit-lamp microscope. The immunological status of the recipients following transplantation, including the formation of chimerism, mixed lymphocyte reaction (MLR) and immunoglobulin and complement in the serum, was analyzed. Two rhesus monkeys in each group were sacrificed for corneal histopathology examination. The mean survival time was 36.0±4.7 days in group 1 and 17.7±3.2 days in group 2. The mean chimerism percentage in group 1 at week 1 was 5.20±1.02%, but decreased with time and was <1% after week 3. MLR demonstrated that immune reactivity to donor spleen cells in group 1 was decreased following surgery. Immunoglobulin and complement levels in the serum revealed a decreasing trend. Histopathological examination demonstrated that the corneal xenografts in group 1 had minimal inflammatory cell infiltration and no eosinophil infiltration. Survival of corneal xenografts may be prolonged by prior BMT, suggesting that immune reactivity to donors is suppressed, and is highly dependent on chimerism formation.

  20. Reduction and repopulation of recipient T4+ and T8+ T-lymphocytes in allogeneic bone marrow transplantation

    SciTech Connect

    Gratama, J.W.; van den Bergh, R.L.; Naipal, A.; D'Amaro, J.; Zwaan, F.E.; Jansen, J.; de Gast, G.C.

    1986-02-01

    In eight recipients of allogeneic bone marrow grafts who had sex-mismatched donors, the reduction and subsequent repopulation of T4+ and T8+ T-lymphocytes of recipient origin were studied. The origin of the donor-recipient T4+ and T8+ T cells was studied using quinacrine staining of Y chromatin combined with T-cell typing for T4 and T8. Following chemoradiotherapy and bone marrow transplantation (BMT), T cells reached their nadir at a median of five (range 1-8) days after BMT. T8+ T cells decreased at a faster rate from the peripheral blood than T4+ T cells. The first T cells that appeared in the circulation at day 12 were predominantly T4+, and a large number of them were of recipient origin. Thereafter, they gradually decreased, and the numbers of T cells of donor origin increased. In the patients who had no or only minor complications, T4+ and T8+ T cells of donor origin repopulated the blood at similar rates. This pattern, however, was modified by severe graft-versus-host disease or by cytomegalovirus infection.

  1. Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

    PubMed

    Tiercy, J M; Bujan-Lose, M; Chapuis, B; Gratwohl, A; Gmür, J; Seger, R; Kern, M; Morell, A; Roosnek, E

    2000-08-01

    Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding

  2. Complete Suppression of the Gut Microbiome Prevents Acute Graft-Versus-Host Disease following Allogeneic Bone Marrow Transplantation

    PubMed Central

    Vossen, Jaak M.; Guiot, Harry F. L.; Lankester, Arjan C.; Vossen, Ann C. T. M.; Bredius, Robbert G. M.; Wolterbeek, Ron; Bakker, Hanny D. J.; Heidt, Peter J.

    2014-01-01

    The hypothesis that elimination of facultative and strict anaerobic microorganisms from the gastro-intestinal tract by antimicrobial drugs in the period of time around allogeneic bone marrow transplantation (BMT) prevents acute graft-versus-host disease (GVHD), was examined in a cohort of 112 children grafted between 1989 and 2002 for hematological malignancies. All patients received T-cell replete marrow from human leukocyte antigens (HLA) matched sibling donors under identical transplantation conditions. To eliminate microorganisms from the gastro-intestinal tract, total gastro-intestinal decontamination (GID) was applied by high doses of non-absorbable antimicrobial drugs while the graft recipient was maintained in strict protective isolation. About half of the children (51%) proved to be successfully decontaminated, and about half (49%) unsuccessfully. One recipient got acute GVHD in the first group and 8 in the second group (p = 0.013). The degree of success of total GID was decisive for the occurrence of acute GVHD, irrespective of the presence of other risk factors such as higher age of recipient and/or donor, female donor for male recipient and carriership or reactivation of herpesviruses. Our results demonstrate that successful total GID of the graft recipient prevents moderate to severe acute GVHD. We suppose that substantial translocation of gastro-intestinal microorganisms or parts of these, functioning as microbial-associated molecular patterns (MAMP's), triggering macrophages/dendritic cells via pattern recognizing receptors (PRR's) is prohibited. As a consequence the initiation and progression of an inflammatory process leading to acute GVHD is inhibited. PMID:25180821

  3. Kidney Transplantation in the Diabetic Patient

    PubMed Central

    Pérez-Sáez, María José; Pascual, Julio

    2015-01-01

    Diabetes mellitus is one of the most important causes of chronic kidney disease (CKD). In patients with advanced diabetic kidney disease, kidney transplantation (KT) with or without a pancreas transplant is the treatment of choice. We aimed to review current data regarding kidney and pancreas transplant options in patients with both type 1 and 2 diabetes and the outcomes of different treatment modalities. In general, pancreas transplantation is associated with long-term survival advantages despite an increased short-term morbidity and mortality risk. This applies to simultaneous pancreas kidney transplantation or pancreas after KT compared to KT alone (either living donor or deceased). Other factors as living donor availability, comorbidities, and expected waiting time have to be considered whens electing one transplant modality, rather than a clear benefit in survival of one strategy vs. others. In selected type 2 diabetic patients, data support cautious utilization of simultaneous pancreas kidney transplantation when a living kidney donor is not an option. Pancreas and kidney transplantation seems to be the treatment of choice for most type 1 diabetic and selected type 2 diabetic patients. PMID:26239558

  4. 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

  5. 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.

  6. POLYCLONAL OUTBREAK OF BLOODSTREAM INFECTIONS CAUSED BY Burkholderia cepacia COMPLEX IN HEMATOLOGY AND BONE MARROW TRANSPLANT OUTPATIENT UNITS

    PubMed Central

    Boszczowski, Icaro; do Prado, Gladys Villas Boas; Dalben, Mirian F.; Telles, Roberto C. P.; Freire, Maristela Pinheiro; Guimarães, Thaís; Oliveira, Maura S.; Rosa, Juliana F.; Soares, Robson E.; Llacer, Pedro Enrique Dorlhiac; Dulley, Frederico Luiz; Costa, Silvia F.; Levin, Anna S.

    2014-01-01

    Aim: The objective was to describe an outbreak of bloodstream infections by Burkholderia cepacia complex (Bcc) in bone marrow transplant and hematology outpatients. Methods: On February 15, 2008 a Bcc outbreak was suspected. 24 cases were identified. Demographic and clinical data were evaluated. Environment and healthcare workers' (HCW) hands were cultured. Species were determined and typed. Reinforcement of hand hygiene, central venous catheter (CVC) care, infusion therapy, and maintenance of laminar flow cabinet were undertaken. 16 different HCWs had cared for the CVCs. Multi-dose heparin and saline were prepared on counter common to both units. Findings: 14 patients had B. multivorans (one patient had also B. cenopacia), six non-multivorans Bcc and one did not belong to Bcc. Clone A B. multivorans occurred in 12 patients (from Hematology); in 10 their CVC had been used on February 11/12. Environmental and HCW cultures were negative. All patients were treated with meropenem, and ceftazidime lock-therapy. Eight patients (30%) were hospitalized. No deaths occurred. After control measures (multidose vial for single patient; CVC lock with ceftazidime; cleaning of laminar flow cabinet; hand hygiene improvement; use of cabinet to store prepared medication), no new cases occurred. Conclusions: This polyclonal outbreak may be explained by a common source containing multiple species of Bcc, maybe the laminar flow cabinet common to both units. There may have been contamination by B. multivorans (clone A) of multi-dose vials. PMID:24553612

  7. 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

  8. Bone-marrow mesenchymal stem cell transplantation to treat diabetic nephropathy in tree shrews.

    PubMed

    Pan, Xing-Hua; Yang, Xiao-Yan; Yao, Xiang; Sun, Xiao-Mei; Zhu, Lu; Wang, Jin-Xiang; Pang, Rong-Qing; Cai, Xue-Min; Dai, Jie-Jie; Ruan, Guang-Ping

    2014-07-01

    Diabetic nephropathy (DN) is a common microvascular complication of diabetes. We used a new DN model in tree shrews to validate the use of bone-marrow mesenchymal stem cell (BM-MSC) transplantation to treat DN. The DN tree shrew model was established by a high-sugar and high-fat diet and four injections of streptozotocin. 4',6-Diamidino-2-phenylindole labelled BM-MSCs were injected into tree shrews. The DN tree shrew model was successfully established. Blood glucose was significantly increased ( p < 0.01) during the entire experiment. DN tree shrews showed dyslipidemia, insulin resistance and increased 24-h proteinuria. At 21 days after BM-MSC transplantation, glucose and levels of triglycerides, total cholesterol and 24-h urine volume were lower than in tree shrews with DN alone ( p < 0.01) but were still higher than control values ( p < 0.01). Levels of creatinine and urea nitrogen as well as 24-h proteinuria were lower for DN tree shrews with BM-MSCs transplantation than DN alone ( p < 0.05). High-sugar and high-fat diet combined with STZ injection can induce a tree shrew model of DN. BM-MSCs injection can home to damaged kidneys and pancreas, for reduced 24-h proteinuria and improved insulin resistance.

  9. Successful treatment of the murine model of cystinosis using bone marrow cell transplantation.

    PubMed

    Syres, Kimberly; Harrison, Frank; Tadlock, Matthew; Jester, James V; Simpson, Jennifer; Roy, Subhojit; Salomon, Daniel R; Cherqui, Stephanie

    2009-09-17

    Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders. The defective gene is CTNS encoding the lysosomal cystine transporter, cystinosin. Cystine accumulates in every organ in the body and leads to organ damage and dysfunction, including renal defects. Using the murine model for cystinosis, Ctns(-/-) mice, we performed syngeneic bone marrow cell (BMC), hematopoietic stem cell (HSC), and mesenchymal stem cell transplantation. Organ-specific cystine content was reduced by 57% to 94% in all organs tested in the BMC-treated mice. Confocal microscopy and quantitative polymerase chain reaction revealed a large quantity of transplanted BMC in all organs tested, from 5% to 19% of the total cells. Most of these cells were not from the lymphoid lineage but part of the intrinsic structure of the organ. The natural progression of renal dysfunction was prevented, and deposition of corneal cystine crystals was significantly improved in the BMC-treated mice. HSC had the same therapeutic effect as whole BMC. In contrast, mesenchymal stem cell did not integrate efficiently in any organ. This work is a proof of concept for using HSC transplantation as a therapy for cystinosis and highlights the efficiency of this strategy for a chronic, progressive degenerative disease.

  10. Comparison of Characteristics and Outcomes of Trial Participants and Non-participants: Example of Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) 0201 Trial

    PubMed Central

    Khera, Nandita; Majhail, Navneet S.; Brazauskas, Ruta; Wang, Zhiwei; He, Naya; Aljurf, Mahmoud D.; Akpek, Görgün; Atsuta, Yoshiko; Beattie, Sara; Bredeson, Christopher N.; Burns, Linda J.; Dalal, Jignesh D.; Freytes, César O.; Gupta, Vikas; Inamoto, Yoshihiro; Lazarus, Hillard M.; LeMaistre, Charles F.; Steinberg, Amir; Szwajcer, David; Wingard, John R.; Wirk, Baldeep; Wood, William A.; Joffe, Steven; Hahn, Theresa E.; Loberiza, Fausto R.; Anasetti, Claudio; Horowitz, Mary M.; Lee, Stephanie J.

    2015-01-01

    BACKGROUND Controversy surrounds the question of whether clinical trial participants have better outcomes than comparable patients who are not treated on a trial. We explored this question using a recent large, randomized, multi-center study comparing peripheral blood (PB) with bone marrow (BM) transplantation from unrelated donors (URD), conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). METHODS AND FINDINGS We compared characteristics and outcomes of study participants (n=494) and non-participants (n=1384) who appeared eligible and received similar treatment without enrolling on the BMT CTN trial at participating centers during the study time-period. Data were obtained from the Center for International Blood and Marrow Transplant Research. Outcomes were compared between the two groups using Cox proportional hazards regression models. No significant differences in age, sex and disease distribution, race/ ethnicity, HLA matching, comorbidities and interval from diagnosis to HCT were seen between the participants and non-participants. Non-participants were more likely to have lower performance status, lower-risk disease, and older donors, and to receive myeloablative conditioning and anti-thymocyte globulin. Non-participants were also more likely to receive PB grafts, the intervention tested in the trial (66% vs. 50% p<0.001). Overall survival, transplant-related mortality, and incidences of acute or chronic GVHD were comparable between the two groups though relapse was higher (HR 1.22, 95% CI 1.02–1.46, p=0.028) in non-participants. CONCLUSION Despite differences in certain baseline characteristics, survival was comparable between study participants and non-participants. The results of the BMT CTN trial appear generalizable to the population of trial-eligible patients. PMID:26071866

  11. Intravenous transplantation of allogeneic bone marrow mesenchymal stem cells and its directional migration to the necrotic femoral head.

    PubMed

    Li, Zhang-hua; Liao, Wen; Cui, Xi-long; Zhao, Qiang; Liu, Ming; Chen, You-hao; Liu, Tian-shu; Liu, Nong-le; Wang, Fang; Yi, Yang; Shao, Ning-sheng

    2011-01-09

    In this study, we investigated the feasibility and safety of intravenous transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) for femoral head repair, and observed the migration and distribution of MSCs in hosts. MSCs were labeled with green fluorescent protein (GFP) in vitro and injected into nude mice via vena caudalis, and the distribution of MSCs was dynamically monitored at 0, 6, 24, 48, 72 and 96 h after transplantation. Two weeks after the establishment of a rabbit model of femoral head necrosis, GFP labeled MSCs were injected into these rabbits via ear vein, immunological rejection and graft versus host disease were observed and necrotic and normal femoral heads, bone marrows, lungs, and livers were harvested at 2, 4 and 6 w after transplantation. The sections of these tissues were observed under fluorescent microscope. More than 70 % MSCs were successfully labeled with GFP at 72 h after labeling. MSCs were uniformly distributed in multiple organs and tissues including brain, lungs, heart, kidneys, intestine and bilateral hip joints of nude mice. In rabbits, at 6 w after intravenous transplantation, GFP labeled MSCs were noted in the lungs, liver, bone marrow and normal and necrotic femoral heads of rabbits, and the number of MSCs in bone marrow was higher than that in the, femoral head, liver and lungs. Furthermore, the number of MSCs peaked at 6 w after transplantation. Moreover, no immunological rejection and graft versus host disease were found after transplantation in rabbits. Our results revealed intravenously implanted MSCs could migrate into the femoral head of hosts, and especially migrate directionally and survive in the necrotic femoral heads. Thus, it is feasible and safe to treat femoral head necrosis by intravenous