Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.1.1.69 (BMT)
 2,655 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.
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PMID:European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 923 50

Thirty-two adults (median age 36 years) with leukemia (15 AML, eight CML, six ALL, three CLL) persisting or relapsing 1-40 months (median 4) after allogeneic BMT (20 matched siblings, eight unrelated, four family mismatch) underwent immunotherapy to elicit GVHD. This comprised one or more of: infusion of donor cells (n = 22), stopping cyclosporine (n = 14), and administration of interferon-alpha2b (n = 15) or interleukin-2 (n = 4). Eight acute leukemia patients received chemotherapy as well. The time from relapse to immunotherapy was 0-1344 days (median 4). Acute and/or chronic GVHD developed in 17 patients. Response was not evaluable in three patients due to early toxic death. There was no response in 10 patients, whereas 19 showed objective response. Nine patients died due to toxicity and 10 due to progressive disease. Thirteen patients are alive 4-58 months (median 14) after immunotherapy; 12 in remission (five AML, four chronic phase CML, one ALL, one accelerated phase CML, one CLL) and one with progressive disease (accelerated phase CML). Eleven of 13 patients who are alive had GVHD compared with six of 19 who died (P = 0.005, Fisher's exact test). We conclude that with the exception of CML in myeloid blast crisis, immunotherapy is active in most types of acute and chronic leukemia relapsing after allogeneic BMT. It is associated with considerable toxicity. Clinically obvious GVHD, especially chronic GVHD, results in a higher probability of survival.
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PMID:Induction of graft-versus-host disease as immunotherapy of leukemia relapsing after allogeneic transplantation: single-center experience of 32 adult patients. 924 16

Twelve patients (9 males and 3 females) with chronic myelogenous leukemia, underwent CD8+ T cell depleted allogeneic bone marrow transplantation with a sex-mismatched donor. To assess chimerism we performed fluorescent in-situ hybridization for the X and Y chromosome at different time points after BMT. Patient median age was 33 years (range, 27-48); median time to transplant was 28 months (range, 5-87). All patients received thiotepa 10 mg/kg; cyclophosphamide 120 mg/kg and 12.0 Gy of fractionated total body irradiation. CD8+ cells were depleted from the normal donor marrow with anti-CD8 murine monoclonal antibodies and immunomagnetic beads. Bone marrow aspirates were studied at <60, 60-140, 140-300, and >300 days post BMT. Hybridization was done on mononuclear cells and a median of 518 cells were counted per slide with a fluorescent microscope. The median percentage of donor cells was 99.04%, 98.21%, 98.15%, and 99.52% at <60, 60-140, 140-300, and >300 days after BMT. Mixed chimerism was a rare occurrence after CD8 depleted allogeneic BMT and occured only at low levels. Inhibition of repopulation by host hematopoietic cells may be associated with the graft-versus-leukemia effect against CML.
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PMID:Analysis of chimerism following allogeneic bone marrow transplantation by fluorescent-in-situ hybridization. 925 Aug 16

Pulmonary alveolar proteinosis (PAP) is a disease of unknown etiopathogenesis sometimes associated with malignant haematological disorders. The potential reversibility of the process in these cases seems to be related to recovery from the underlying disease. GM-CSF has acquired an important, potentially pathogenic role and BMT presents one therapeutic option effective in certain forms of human PAP. We present the case of a 43-year-old female patient with Ph+ CML. During pretransplantation evaluation, unexpected pulmonary infiltrates were noted in the chest X-ray, PAP being diagnosed on biopsy. In view of the progressive respiratory symptomatology and her CML being in accelerated phase, the patient underwent haematopoietic transplantation. She died on day +12 from invasive pulmonary aspergillosis before a response could be observed. Pathogenic implications in PAP and the role of haematopoietic transplantation in this disease are discussed.
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PMID:Haematopoietic transplantation in pulmonary alveolar proteinosis associated with chronic myelogenous leukaemia. 931 86

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.
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PMID:Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. 933 56

A 46-year-old woman with Ph-positive CML received an unmanipulated BMT from an HLA-identical brother, conditioned with busulfan-cyclophosphamide. Five months after BMT, cytogenetic relapse occurred, and CsA was decreased and then discontinued. Mild acute GVHD occurred, but gradually improved with no immunosuppression. Forty days after CsA discontinuation, both cytogenetic and fluorescence in situ hybridization analyses showed a host-derived normal karyotype, 46,XX, and no evidence of leukemic cells or donor graft. The sustained host-derived hematopoiesis lasted for 2 years until sudden recurrence of CML. In this case, the discontinuation of CsA led to GVHD and also suppression of the relapsed leukemia, presumably by a 'specific' GVL effect. There was also graft failure. The observation that subsequent hematologic recovery was of host origin implies that, at least in this case, the GVL effect was not directed against normal host-type hematopoiesis.
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PMID:Complete cytogenetic response with host-derived hematopoiesis induced by cyclosporin A discontinuation in a patient with relapsed chronic myelogenous leukemia after bone marrow transplantation. 933 67

IL-10 plays an important role in the control of immune reactions during systemic infection. Here, IL-10 serum levels were investigated in patients after BMT. The IL-10 levels correlated with the clinical course of the patients and with serum levels of C-reactive protein (CRP) and neopterin (NP). A total of 26 patients with AML (7), ALL (12), CML (2), NHL (3) and multifocal Ewing's sarcoma (2) had received autologous (10) or allogeneic (16) BMT from related (9) or unrelated donors (7). Routine serum samples were obtained prior to BMT and at days 46 and 100 after BMT. However, in patients with severe complications additional samples were drawn at individual points in time. Prior to BMT, IL-10 serum levels were not detectable in 24/24 patients. Post-BMT, 11 patients developed elevated IL-10 levels, of these eight died of complications (DOC), whereas only one of 15 patients with undetectable IL-10 died of complications, indicating that high IL-10 levels were significantly correlated with severe life-threatening complications (chi2, P < 0.01). To determine the pathomechanism and role of the increased IL-10 levels, they were correlated to the respective NP and CRP serum concentrations. CRP and NP concentrations were found significantly elevated in patients with detectable IL-10, indicating a severe acute phase reaction associated with macrophage activation. In conclusion, high IL-10 serum levels in patients after BMT were significantly associated with fatal outcome. Since IL-10 is a strong suppressor of T cell immunity, high IL-10 production in patients with severe complications such as septic shock or GVHD > grade II after BMT might lead to functional immunodeficiency contributing to the poor prognosis of these patients.
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PMID:High interleukin-10 serum levels are associated with fatal outcome in patients after bone marrow transplantation. 933 50

We treated 12 patients with leukemia relapse after allogenic bone marrow transplantation with a combination of interferon-alpha (IFN-alpha) ((2.5-5.0) x 10(6) u/m2 subcutaneously three times a week) and interleukin-2 (IL-2) ((1.8-3.6) x 10(6) IU/m2 subcutaneously five times a week) to determine the toxicity and efficacy of combination cytokine therapy in this setting. The median age of the patients was 39 years (range: 16-50). There were nine females and three males. The median time to relapse from BMT was 98 days (range: 0-963). At the time of relapse, six patients had AML, four patients had CML (two in blast crisis and two in chronic phase with clonal evolution), and one patient had lymphoblastic lymphoma. Combination cytokine therapy was started a median of 108 days post BMT (range: 37-2404). Nine patients treated at the higher dose level required a 50% dose reduction because of toxicity or GVHD (three CNS, two GVHD, one high fever, one diarrhoea with hypotension, and one pericarditis). At a lower dose level, 2 of 10 patients had their treatment discontinued because of toxicity or GVHD. Six patients developed clinical findings consistent with acute GVHD while on combination cytokine therapy. Two patients responded to combination cytokine therapy: one with CML and one with AML. Combination cytokine therapy is feasible in the setting of relapse post allogeneic BMT. The combination of IL-2 1.8 x 10(6) IU/m2 five times a week with IFN-2 2.5 x 10(6) U/m2 three times a week seems to be tolerable, and merits further study in this setting.
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PMID:Interferon-alpha and interleukin-2 as treatment for leukemia relapse after allogeneic bone marrow transplantation. 938 68

In a retrospective single centre study we examined the outcome of five different therapy approaches in 48 patients in whom a relapse of CML (13 cytogenetic relapses, 35 hematological relapses: 10 chronic phase (CP), nine accelerated phase, 16 blast crisis) occurred after allogeneic BMT. Cyclosporin A (CsA) withdrawal, interferon alpha-2b (IFN-alpha) therapy, donor leukocyte transfusions (DLT), second transplantation (2nd BMT), and chemotherapy (CTX) alone were used and studied for their response rates. Patients who achieved a complete hematologic and cytogenetic remission (CR) were studied for BCR-ABL transcripts and for their chimerism status by PCR. A strong antileukemic effect was observed after abrupt CsA withdrawal, with 10 of 20 patients achieving a CR (50%). All 10 patients with early stage (nine cytogenetic and one CP), but none of the patients with advanced disease recurrence, responded to CsA withdrawal. IFN-alpha induced in five of 11 patients (45%) a stable cytogenetic remission, whereas treatment with DLT induced a CR in only two of 14 patients (14%). A second transplant was performed in six patients. Three of six patients (50%) survive disease-free at a median of 19 months after the 2nd BMT (range 10-25). The use of CTX alone did not induce a remission.
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PMID:A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation. 946 77

We report the clinical course of five adult patients with chronic Chagas' disease (Cd) who underwent BMT. Two patients with non-Hodgkin's lymphoma and one with ALL received an ABMT. Allogeneic BMT was performed in two patients with AML and CML respectively. One donor had chronic Cd. Samples of peripheral blood for parasite investigation by the Strout method, blood culture, and immunological studies by indirect immunofluorescent assay, ELISA and indirect hemagglutination tests were performed weekly from the start of chemotherapy until day +60 for ABMT and during the period of immunosuppression for allogeneic BMT. No prophylaxis was given to any of these patients. In only one ABMT patient were trypomastigotes detected early by blood culture without symptoms of reactivation. Benznidazole as preemptive treatment was administered at 5-8 mg/kg/daily for 30 days. Parasitemia was rapidly cleared and at the end of therapy xenodiagnosis was negative. The other Cd patients showed no evidence of relapse of parasitemia or signs and symptoms of reactivation. In brief, evidence of Cd should be sought in all BMT patients coming from endemic areas because parasitemia and reactivation are potential complications during the period of neutropenia and immunosuppression. The strategy used for early detection and treatment of parasitemia and reactivation was safe and effective.
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PMID:Recipients and donors of bone marrow transplants suffering from Chagas' disease: management and preemptive therapy of parasitemia. 950 74


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