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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone marrow transplantation (BMT) after supralethal cytoreductive therapy in the acute leukemias, chronic myelogenous leukemia (CML), and the lymphomas may be curative in 50% to 60% of patients. The donor may be a human leukocyte antigen (HLA) matched family member (allogeneic), an identical twin (syngeneic), or the patient (autologous). In general, the outcome is best in younger patients and those transplanted early in their disease (i.e., in the first remission for acute leukemia and in the chronic phase of the disease in CML). Solutions to the major problems of allogeneic BMT, such as graft-versus-host disease and viral infections, are being actively pursued. Syngeneic and autologous BMT avoids some of the above problems, but relapses appear to be greater. Despite this problem, a significant number of cures have been accomplished. Newer methods of purging autologous marrow and newer preparative regimens promise to reduce the problem of relapses.
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PMID:Bone marrow transplantation in hematologic malignancies. Current status. 240 2

One hundred and four patients with acute leukemia treated by allogeneic bone marrow transplantation in Japan were analysed for the incidence of interstitial pneumonitis (IP). Thirty-six (35%) of 104 marrow graft recipients developed IP. Cytomegalovirus (CMV) was the most frequent organism (61%). Using multivariate analysis, remission at transplant (P = 0.0001) and use of cyclosporin A to prevent graft-versus-host disease (P = 0.0363) were found to be significant factors associated with a decreased incidence of IP. For preventing IP, anti-CMV hyperimmune globulin was effective, while interferon and acyclovir were not.
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PMID:Interstitial pneumonitis in allogeneic bone marrow transplantation: a report from the Japanese BMT Study Group. 245 86

Utilization of bone marrow transplantation as a therapeutic modality continues to increase. More and more institutions are initiating bone marrow transplant programs. During the 33-year period between 1955 and 1987, more than 20,000 patients received allogeneic bone marrow transplants; more than 50% of these were performed in the 3 years, 1985-1987. Transplantation is an effective therapy for acute leukemia; in some instances it is the preferred treatment. In chronic myelogenous leukemia, severe aplastic anemia, and some genetic and immune deficiency diseases, bone marrow transplantation provides the only possibility for cure. Bone marrow transplantation is associated with serious problems such as graft-versus-host disease (GvHD), graft failure, interstitial pneumonitis and, until recently, the requirement for an HLA-identical sibling donor. In the past few years, an increasing number of transplants have been performed using HLA-partially matched related or unrelated donors with some success, the level of which is yet to be determined. The development of acute GvHD (8) and interstitial pneumonitis (9, 10) can often be predicted by risk factor assessment. Special precautions can then be taken for patients at high risk of these complications. In this report, current data from the International Bone Marrow Transplant Registry were summarized and several risk factors affecting outcome were identified.
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PMID:Current status of bone marrow transplantation. 248 30

We determined the serum levels of tumor necrosis factor-alpha (TNF) in allogeneic bone marrow transplant recipients in order to evaluate the relationship between TNF and graft-versus-host disease (GVHD). Eight patients with acute leukemia receiving an HLA-identical marrow graft were studied. Samples from healthy subjects and pretransplant recipients were all negative for TNF. Six of eight patients had detectable levels of TNF in serum after transplantation. All three patients with acute GVHD, and three of five patients without acute GVHD had elevated TNF levels in serum. Among the patients with increased TNF levels, documented infection was demonstrated in only one patient, with a clinical diagnosis of B19 parvovirus infection. Serum TNF levels were elevated when the WBC counts were more than 2,000/microliters. However, serum concentrations of TNF significantly correlated with body temperature. Although we could not conclude definitely that serum TNF levels correlated with severity of GVHD, it was suggested that TNF may be produced as a result of latent infections or immunological reaction against non-HLA allogeneic antigens.
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PMID:Serum tumor necrosis factor-alpha levels in allogeneic bone marrow transplant recipients with acute leukemia. 262 65

Recently, treatment of leukemia has shown remarkable progress. Development of new antileukemic drugs, improvements in supportive care and rapid progress in bone marrow transplantation have resulted in considerable changes in responses in refractory leukemia. Chemotherapy for Acute leukemia: By the introduction of Mitoxantrone and etoposide and a new combination chemotherapy including them, a high remission rate of acute leukemia is obtained, but because of the high relapse rate the 5-year survival rates in our center were 20% for adult ALL and 18% for ANL. In order to reduce the relapse rate, a new regimen containing intensive consolidation treatments is now being studied in a nation-wide cooperative study. BMT: In 1987, 160 BMTs including 75 acute leukemia and 28 CML, were registered in Japan. The improvements in the management of graft versus host disease (GVHD) and infections in the granulocytopenic period has contributed to the marked increase in the long-term survival rate after BMT. In our center the long-term survival rate rose from 20% before 1984 to 85% after 1985. Colony stimulating factor: Macrophage-colony stimulating factor (M-CSF) and granulocyte colony stimulating factor (G-CSF) were studied in Japan. In the double-blind placebo controlled study of M-CSF, a significantly shorter duration of granulocytopenia, as well as a significantly lower rate of failure of BMT (i.e., death or retransplant) was observed. In the phase II study of G-CSF, a rapid recovery of granulocytes after chemotherapy or BMT and marked efficacy on infection in granulocytopenic patients were observed.
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PMID:[Multidisciplinary treatment of leukemia]. 265 20

Data from 3113 patients receiving HLA-identical sibling bone marrow transplants for leukemia were analysed to determine the time course of the major causes of treatment failure. The median interval from transplant to onset of acute graft-versus-host disease (GVHD) was 17 days, interstitial pneumonitis 63 days, and chronic GVHD 111 days. The median interval from transplant to relapse was 3.3 months for patients transplanted in relapse of acute leukemia or blast phase of chronic myelogenous leukemia (CML), 6.4 months when transplants were performed in second or subsequent remission of acute leukemia or accelerated phase of CML, and 7.8 months for patients transplanted during first remission of acute leukemia or while in the first chronic phase of CML. Shorter intervals from transplant to onset of interstitial pneumonitis or chronic GVHD were associated with a significantly lower probability of 2-year survival. The temporal relationships between these complications are displayed graphically and demonstrate the overlapping and competing causes of death following allogeneic bone marrow transplantation.
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PMID:Temporal relationships between the major complications of bone marrow transplantation for leukemia. 267 53

In mammalian ontogeny, the liver constitutes the primary hematopoietic organ for some time. Fetal liver cells (FLC) are rich in hematopoietic stem cells with a high proliferative potential but contain few post-thymic T cells. In animal studies, FLC restored hematopoiesis without severe graft-versus-host disease. However, genetic disparity between donor and host frequently limited durable engraftment and prevented or protracted complete immune reconstitution in most fully allogeneic recipients. Some children with severe combined immunodeficiency have been cured by FLC infusion, whereas favorable effects in aplastic anemia, acute leukemia, and inborn errors of metabolism have been limited and badly understood. Fetal liver transplantation in animals may serve as a model for the analysis and management of complications associated with the transfer of purified hematopoietic stem cell grafts and aid in the development of future therapeutic strategies requiring rapidly proliferating stem cell populations.
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PMID:The fetal liver as an alternative stem cell source for hemolymphopoietic reconstitution. 287 17

Autologous bone marrow transplantation (ABMT), which was developed in the past decade, is currently under investigation for the treatment of leukemias, lymphomas, and a few solid tumors. It consists of engrafting a patient, after ablative chemotherapy and/or total-body irradiation (TBI), with marrow taken from the patient at a propitious time in the history of the disease and usually cryopreserved. This technique has two major consequences: ABMT by reducing the length and variability of posttreatment aplasia can be considered a super hematologic support. It allows the use of chemotherapeutic agents and/or TBI at doses that surpass the dose for effecting the threshold of myelotoxicity. Therefore, a greater tumor cell kill can be expected at a reasonably low cost in terms of toxicity. In patients with acute leukemia (AL), however, the contribution of ABMT may go far beyond. In the initial trials (1974-79), the marrow of patients with AL was collected during complete remission and cryopreserved, with the idea of preserving "the remission status." At relapse this marrow was re-infused after high-dose chemotherapy and/or TBI, for achieving another complete remission. The result could be considered a chronologic chimera; the autograft, which had stem cells younger than those of the organism, reproduced, over the course of a few months or years, the evolution of the remission during which it was collected. As predicted, however, all patients who received this treatment eventually relapsed. For a more aggressive technique, some teams gave autografts to patients earlier, during remission, to allow ablative therapy in the consolidation mode; the whole procedure, including the pretransplant cytoreductive regimen, was modeled on that of allografting. Because allogeneic bone marrow transplantation currently offers the best chance of long-term survival but remains severely restricted, by age and availability of an HLA-identical donor, to less than 10% of the patients, ABMT may be considered an alternative source of stem cells to the other patients. In addition, ABMT avoids the risks of graft-versus-host disease with its associated immunosuppression. However, one major impediment to effective ABMT may be the persistence of leukemia cells in the marrow autograft, although the marrow was collected during earlier remission. The recent development of numerous techniques to cleanse the marrow prior to ABMT has considerably increased the possibility of ABMT becoming a major tool in the cure of leukemia. This report reviews the early data and essentially focuses on recent results of ABMT effected in or done in remission with use of cleansed and uncleansed marrow.
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PMID:Autologous bone marrow transplantation in acute leukemia. 294 Apr

We report here the results of a phase I clinical trial using counterflow centrifugal elutriation (CCE) for the removal of donor T lymphocytes before allogeneic bone marrow transplantation (BMT). Thirty-eight patients received lymphocyte-depleted allografts from HLA-identical, MLR-nonreactive sibling donors. The patients entered onto the study were either at high risk on the basis of age (median, 39 years) or disease status (acute leukemia in early relapse [ER], chronic myelogenous leukemia [CML] in accelerated phase [AP], or therapy resistant [RES] lymphoma). All patients received a standard lymphocyte dose of 1 x 10(6) morphologic lymphocytes per kilogram ideal body weight (BW) and were maintained on cyclosporine A (CsA) for 170 days after BMT. Prompt engraftment occurred in 37 of 38 patients with a median time to absolute neutrophil count (ANC) greater than 500/microL of 18 days. Although acute graft-v-host disease (GVHD; clinical stage I or greater) was observed in 45%, it was limited to the skin in all but five patients. Survival was related to disease status at the time of BMT. Among patients with acute leukemia in first or second remission, CML in chronic phase (CP) or lymphoma in partial remission (PR), 64% are currently alive, in contrast to 31% of patients with acute leukemia in third remission or early relapse, CML in second CP or AP, or RES lymphoma. Median follow-up for all patients was 351 days (range, 105 to 711 days). We conclude that this procedure is safe and warrants further evaluation in a randomized efficacy trial.
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PMID:Lymphocyte depletion of donor bone marrow by counterflow centrifugal elutriation: results of a phase I clinical trial. 304 36

T cell depletion reduces the incidence and severity of graft-versus-host disease (GVHD) following bone marrow transplantation in man. Graft-versus-host disease of more than grade 2 severity is decreased from about 45% to about 10% in recipients of HLA-identical transplants. However, T cell depletion also increases the frequency of graft failure and leukemia relapse. Graft failure increases from about 1 to 10% following HLA-identical transplants. In patients with acute leukemia in first remission or with chronic myelogenous leukemia in chronic phase, leukemia relapse increases from about 20% to about 40%. Thus, although T cell depletion decreases GVHD, it increases graft failure and leukemia relapse such that survival is not convincingly improved. Several approaches to these problems are possible including increased pre- or post-transplant immune suppression, more effective antileukemia therapy or selective T cell depletion. Preliminary results of these approaches are discussed and new directions suggested.
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PMID:T cell depletion in bone marrow transplantation for leukemia: current results and future directions. 304 85


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