Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Nine patients underwent allogeneic bone-marrow transplantation as treatment for chronic granulocytic leukaemia (CGL) during the accelerated phase, a point in the course of the disease when it has progressed beyond the stable chronic phase but before the onset of blast crisis. After bone-marrow transplantation, haematological and cytogenetic studies showed ablation of all evidence of leukaemia, successful engraftment, and persistence of normal haemopoiesis in all patients. In one patient severe myelofibrosis and osteosclerosis disappeared after bone-marrow transplantation. Two patients have died of complications related to graft-versus-host disease (GvHD) but with no evidence of CGL. In one patient haematological and cytogenetic evidence of recurrent disease developed after bone-marrow transplantation, and she survives in chronic phase. Six patients are free of disability, do not require transfusions, possess normal marrow chromosomes, and have persistent clinical and haematological evidence of complete remission from CGL. Intervention with allogeneic bone-marrow transplantation during the accelerated phase of CGL can eradicate the disease and can provide normal haemopoiesis with acceptably low early morbidity and mortality. The long-term efficacy of bone-marrow transplantation as treatment for CGL, and the most effective timing of the transplantation with regard to the course of disease have yet to be determined.
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PMID:Successful allogeneic bone-marrow transplantation for patients in the accelerated phase of chronic granulocytic leukaemia. 612 74

Eighteen patients with chronic granulocytic leukemia underwent allogeneic marrow transplantation from HLA-identical sibling donors. The preparative regimen included cyclophosphamide and 1000-1500 rad total body irradiation in either single or fractionated doses. Eleven patients were transplanted in blast crisis. One died too early to evaluate. Five had recurrent leukemia, three died of interstitial pneumonia (IP), and two are living in remission after 20 and 39 months. One additional patient with blast crisis was transplanted while in remission after chemotherapy and is living in remission 28 months after transplantation. Two patients were transplanted in the accelerated phase; one died early of infection and one died of IP. Four were transplanted in the chronic phase; one died of IP, one with graft-versus-host disease, and two are living in remission 11 and 25 months after transplantation.
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PMID:Allogeneic bone marrow transplantation for chronic granulocytic leukemia. 703 Jul 67

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.
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PMID:CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. 749 95

The effect of donor/recipient histocompatibility on relapse in patients receiving T-cell-depleted (TCD) grafts for chronic myelogenous leukemia (CML) was evaluated. Specifically, we sought to determine whether TCD results in an attenuation of the graft-versus-leukemia (GVL) effect on recipients of unrelated marrow grafts similar to that observed in HLA-identical sibling marrow transplantations. This question was addressed by comparative analysis of the relapse rates in marrow grafts who otherwise received identical preparative regimens and graft-versus-host disease (GVHD) prophylaxis schedules (T-cell depletion with T10B9 monoclonal antibody and complement plus posttransplant cyclosporine) and by serial molecular analyses using the polymerase chain reaction (PCR) to detect the bcr/abl RNA transcript in patients transplanted with unrelated donor grafts. Patients transplanted with advanced disease (accelerated phase or blast crisis) had equally high relapse rates, regardless of whether they received HLA-identical sibling (56%;95% confidence interval [CI], 29% to 82%) or unrelated marrow grafts (8%; 95% CI, 0% to 28%) had a significantly lower incidence of relapse than did patients transplanted with HLA-identical marrow grafts (47%; 95% CI, 23% to 71%; P = .002). Because all patients were similarly treated, these data indicate that the lower relapse rate in these unrelated patients was caused by an augmented GVL effect that was most likely attributable to increased HLA disparity between donor and recipient. The probability of developing both acute and chronic GVHD was significantly increased in chronic-phase recipients of unrelated marrow grafts, suggesting that the enhanced GVL effect was at least partly GVHD-associated. The lack of such a finding in advanced disease patient receiving unrelated marrow grafts raises the possibility that clinically significant GVL effect after TCD marrow transplantation was limited and confined to patients with more indolent disease. Serial PCR analyses for the presence of the bcr/abl RNA transcript showed that the vast majority of patients transplanted in chronic phase with unrelated marrow grafts were persistently PCR-negative, indicating that the GVL effect was durable in these patients. Most of these patients were observed to become PCR negative within 1 to 2 months after transplantation, showing that early eradication of leukemia was possible with TCD marrow grafts. This study shows that the use of unrelated marrow grafts compensates for reduced GVL reactivity associated with TCD in patients transplanted for CML. Furthermore, these data indicate that, in selected patient populations with CML, TCD can be used to reduce GVHD without a commensurate compromise in the GVL effect.
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PMID:Use of unrelated marrow grafts compensates for reduced graft-versus-leukemia reactivity after T-cell-depleted allogeneic marrow transplantation for chronic myelogenous leukemia. 757 70

Detection of the chronic myelogenous leukemia (CML)-related marker, the bcr/abl m-RNA transcript, in blood or bone marrow of patients with CML in hematologic remission after allogeneic bone marrow transplantation (allo-BMT) may be associated with the presence of minimal residual disease but does not uniformly predict hematologic relapse. In contrast, when there is cytogenetic reappearance of the Philadelphia (Ph1) translocation [t(9;22)(q34;q11)] along with additional cytogenetic abnormalities, especially more than 2 years after BMT, progression to hematologic relapse and acceleration of CML usually occur. An exception to this rule may be our patient, who was a 29-year old white woman diagnosed with Ph1-positive CML by cytogenetics. She was initially treated with hydroxyurea. An allo-BMT was performed 4 months after the diagnosis, while the patient was still in the first chronic phase of her disease, her HLA-identical brother serving as bone marrow (BM) donor. The conditioning regimen for BMT consisted of cytosine arabinoside, cyclophosphamide, total body irradiation, splenic irradiation, and intrathecal methotrexate. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A and methotrexate. Her hospital course was unremarkable and without evidence of acute GVHD. Six months after transplantation, the patient had mild chronic GVHD and was treated with azathioprine and prednisone for 6 months. A year later, she recurred with mild chronic GVHD. She was treated with azathioprine alone for 5 months. Subsequently, she received cyclosporin A and prednisone for 8 months, with resolution of her symptoms. Serial BM cytogenetic studies showed normal male donor karyotypes 12 and 24 months after BMT. At 36, 42, and 50 months after BMT, reappearance of the Ph1 was noted along with some cells with additional cytogenetic abnormalities, including t(6;14)(p21;q32). The breakpoint involvement of 14q32, the heavy chain Ig locus, in the new clone may be indicative of B-lymphoid lineage-based evolution. The abnormal clones disappeared 56 months from BMT and remained absent through 69 months after BMT. The patient has remained in hematologic remission during her entire post-BMT course. Clinically, she continues to do well without immunosuppressants at presently 69 months after BMT. The reappearance of the Ph1 chromosome could be associated with the immunosuppressive therapy given for chronic GVHD. This case supports the concept that immunologic mechanisms may be important in the eradication of CML after allo-BMT, and even cytogenetic evidence of blast crisis CML may spontaneously remit after allo-BMT.
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PMID:Case report of spontaneous remission of cytogenetic relapse of chronic myelogenous leukemia suggestive of progression to blast crisis after allogeneic bone marrow transplantation. 782 5

Between January 1988 and March 1993, 48 patients received T-cell-depleted marrow grafts from unrelated donors as treatment for chronic myelogenous leukemia (CML). The median age of the population was 31.7 years (range 5.4 to 53) with 17 of 48 patients greater than 40 years of age. Twenty-seven patients were transplanted in chronic phase, 17 in accelerated phase, and 4 in blast crisis. All patients received a standardized preparative regimen of cyclophosphamide, high-dose cytosine arabinoside, methylprednisolone, and total body irradiation. Marrow grafts were depleted of mature T cells with the alpha beta T-cell receptor antibody T10B9 as graft-versus-host disease (GVHD) prophylaxis. All patients also received posttransplant cyclosporine therapy. Twenty-eight of 48 patients were mismatched with their donors for one or more HLA-A, B, DR, or DQ loci by either serology or high-resolution oligonucleotide genotyping. Nine of 28 were mismatched at multiple HLA loci. Durable engraftment was achieved in 94% (45/48) of patients. The actuarial probability of developing grades II to IV and grades III to IV acute GVHD were 39.6% (95% confidence interval (CI) 26.9 to 53.0) and 8.3% (95% CI 6.1 to 10.9) for the entire cohort. There was no difference in the incidence of grades II to IV acute GVHD between patients receiving matched (36.8%) or mismatched (41.4%) marrow grafts (P = .77). The actuarial probability of relapse at 2 years was 8.8% (95% CI 2.1 to 21.6) for the entire cohort and 18% (95% CI 4 to 41) for patients transplanted in either the accelerated or blast crisis phase (advanced disease). One cytogenetic relapse has occurred among patients transplanted in the chronic phase. The probability of disease-free survival at 2 years was 52% (95% CI 24 to 70) for patients transplanted in chronic phase and 46% (95% CI 25 to 73) for patients transplanted with advanced disease. No difference in disease-free survival was observed between patients receiving matched (49%) or mismatched (51%) marrow grafts (P = .90). This study shows that patients receiving unrelated T-cell-depleted marrow grafts for CML can achieve durable engraftment with a low incidence of severe GVHD and apparent preservation of graft-versus-leukemia reactivity. These data also suggest that T-cell depletion may allow patients who might otherwise experience unacceptable toxicity from GVHD-related complications caused by older age or increased HLA disparity to benefit from unrelated marrow grafts.
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PMID:Effect of T-cell depletion as graft-versus-host disease prophylaxis on engraftment, relapse, and disease-free survival in unrelated marrow transplantation for chronic myelogenous leukemia. 814 64

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

The data on 1480 bone marrow transplants for chronic myeloid leukemia (CML), performed between 1979 and 1990 were reported to the registry of the European Group for Bone Marrow Transplantation (EBMT). Of these, 1082 patients were transplanted in first chronic phase, 88 in subsequent chronic phase, 251 in accelerated phase and 59 during blast crisis. For these four disease stages leukemia-free survival (LFS) at 5 years is 39%, 22%, 22% and 0%, respectively. A more detailed analysis was performed for 947 patients receiving a first transplant in first chronic phase of their disease from an HLA-identical sibling donor. Survival at 8 years is 47%. At 5 years, relapse incidence (RI) is 33% and the transplant-related mortality rate (TRM) is 42%. The major prognostic factors are patient age (LFS, TRM), T cell depletion (LFS, RI), time from diagnosis to transplant (LFS, TRM), white blood cell count (RI) and donor-recipient sex combination (LFS, TRM). This first report on long-term results of a large cohort of transplanted CML patients confirms and extends previous findings. Stage of disease at time of transplant is the most important prognostic factor. Fifty per cent of all patients transplanted for CML in chronic phase can be expected to be alive at 8 years post-transplant, 40% alive and free of the disease. This number increases to > 60% for patients given cyclosporin and methotrexate without T cell depletion as GVHD prophylaxis. However, there is no plateau phase and late relapses and late transplant-related deaths occur in all subcategories.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone marrow transplantation for chronic myeloid leukemia: long-term results. Chronic Leukemia Working Party of the European Group for Bone Marrow Transplantation. 829 62

Eight patients who had hematologic relapse of chronic myelogenous leukemia (CML) after undergoing allogeneic bone marrow transplantation (BMT) were treated with leukocyte infusions from the original bone marrow donors. All patients had previously received marrow grafts from HLA-identical siblings. Six patients were in the accelerated phase of their disease and two were in blast crisis. Each patient received a predetermined T-cell dose within a narrow range of 2.5 to 5.0 x 10(8) T cells/kg. Three patients also received short courses of therapy with alpha interferon to control elevated white blood cell counts within the first several weeks after leukocyte transfusions. Seven of eight evaluable patients developed graft-versus-host disease (GVHD) at a median of 32 days after the initial infusion. One patient had fatal GVHD. A second patient had grade 3 acute GVHD, which has responded to immunosuppressive therapy. The remaining patients all had mild grade I GVHD. Six patients continue to require modest doses of prednisone more than 6 months after infusion. Four patients developed marrow aplasia, which in three patients required marrow boosts from the original donors. Two of these three patients have normal hematopoietic function, whereas the third patient remains growth factor and transfusion dependent. Both patients treated in blast crisis have died, one from GVHD and one from disease progression. All six patients in the accelerated phase are alive and in cytogenetic remission at a median of 42 weeks after infusion. Five of these six patients are in molecular remission. This study demonstrates that leukocyte infusions that administered a defined T-cell dose can exert a profound graft-versus-leukemia effect and are an effective form of salvage immunotherapy in allogeneic marrow transplant recipients. This therapeutic approach appears to be a viable alternative to existing chemotherapeutic and immunomodulatory strategies for the treatment of relapsed CML.
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PMID:Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. 840 Feb 84

In the interval from December 1987 to November 1990, 196 consecutive patients with chronic myelogenous leukemia (CML) received unrelated donor marrow transplantation using marrow procured by the National Marrow Donor Program (NMDP) at 21 NMDP-affiliated marrow transplant centers. Baseline donor and recipient data as well as follow-up data were obtained systematically in all cases by the NMDP. The median interval from the initiation of a search for an unrelated donor to bone marrow transplantation was 8.4 months (range, 1.7 to 34.6 months). Median age of the recipients was 33.3 years (4.5 to 54.5 years). Seventy-five recipients were female and 121 were male. At time of transplant, 115 patients were in chronic phase, 51 in accelerated phase, 14 in blast crisis, and 16 in a second or subsequent chronic phase. In 133 cases, donors and recipients were identical at the HLA A, B, and DR loci using standard serologic typing, and in 63 cases, there was nonidentity at one HLA locus. Patients were prepared for transplantation with a combination of high-dose chemotherapy and total body irradiation (N = 169) or with high-dose chemotherapy only (N = 27). Thirty-five patients received marrow depleted ex vivo of T lymphocytes, whereas 161 patients received non-T-depleted marrow. One hundred seventy-four of 196 patients engrafted (absolute neutrophil count > or = 500/mm3 for 3 consecutive days). The median time to engraftment was 22 days (6 to 69 days). Twenty-two patients failed to engraft, and an additional 10 patients experienced late graft failure. The incidence of grades III or IV acute graft-versus-host disease (GVHD) was 0.54 +/- 0.10, and that of extensive chronic GVHD was 0.52 +/- 0.12. A lower incidence of both grades III and IV acute GVHD (P = .0003) and of extensive chronic GVHD (P = .01) were independently associated with use of T-depleted marrow. The actuarial incidence of hematologic relapse at 2 years is 0.11 +/- 0.06. The 2-year actuarial incidence of disease-free survival for patients transplanted in first chronic phase within 1 year of diagnosis is 0.45 +/- 0.21, in chronic phase more than 1 year from diagnosis is 0.36 +/- 0.11, in accelerated phase is 0.27 +/- 0.12, in second or subsequent chronic phase is 0.22 +/- 0.21, and in blast crisis is 0. Fifteen of 55 patients transplanted at 40 to 50 years of age survive.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program. 842 71


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