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)

From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ("matched"). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ("mismatched"). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 X 10(9)/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], +/- 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P less than .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, +/- 9%) for the entire group at 2 1/2 years.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Therapy for chronic myelogenous leukemia with unrelated donor bone marrow transplantation: results in 102 cases. 232 22

In a multicenter study (seven University clinics) in the German Federal Republic bone marrow transplants from HLA-identical donors were performed in 177 patients (113 men, 64 women, mean age 32 [1.3-50] years) with Philadelphia chromosome-positive chronic myeloid leukaemia from 1982 to 1988. The survival rate among the 144 patients in whom the transplant had been carried out during the first chronic phase amounted to 58.4 +/- 11.4% after a median observation period of 3 years; survival rate among the 24 patients who underwent transplantation during the acceleration phase was 29.2 +/- 20.4%. All nine patients who received bone marrow transplants in the second chronic phase or during a blast crisis died during the period of observation (after median periods of 4 and 2 months, respectively). The most frequent causes of death among the group as a whole (82/177 patients) were interstitial pneumonia, acute and chronic graft versus host reactions (GVHD), recurrences and the toxic effects of previous treatment. The risk factors which significantly diminished survival rate were moderate to severe acute GVHD, chronic GVHD and age over 30 years.
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PMID:[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The results of HLA-identical transplants in the Federal Republic of Germany]. 235 28

Bone marrow transplantation (BMT) offers potentially curable treatment for patients with high-risk hematologic malignancies. However, relapse remains the major cause for failure of autologous BMT in these diseases and of allogeneic BMT in subsets of patients with these diseases. With our current preparative regimens, relapse rates following autologous BMT are over 30% for patients with intermediate or high-grade non-Hodgkin lymphoma and relapsed Hodgkin's disease in sensitive relapse and over 50% following autologous BMT for patients with acute non-lymphoblastic leukemia (ANLL) and acute lymphoblastic leukemia (ALL). Relapse rates exceed 80% in patients treated with autologous BMT for non-Hodgkin lymphomas and Hodgkin's disease in drug-resistant relapse. We also see a relapse rate over 50% in patients given allogeneic BMT for ANLL in second or third remission or early relapse, for ALL in third or subsequent remission or early relapse, and for chronic myelogenous leukemia (CML) in accelerated phase or blast crisis. We have explored two new approaches for improving the anti-tumor activity of our BMT preparative regimens. One involves combining etoposide, a chemotherapeutic agent that has excellent activity against leukemias and lymphomas, has shown synergistic activity with cyclophosphamide in vitro, and can be substantially dose-escalated, with busulfan and cyclophosphamide. The other approach attempts to induce graft-versus-host disease (GVHD), which appears to provide a clinical anti-tumor effect following allogeneic BMT, in recipients of autologous BMT. A syndrome similar to mild GVHD has been reported to occur spontaneously in a small number of patients receiving autologous or syngeneic transplants. GVHD can also be induced in rats undergoing syngeneic BMT by treatment with cyclosporine (CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New conditioning regimens for high risk marrow transplants. 262 18

To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA-identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.
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PMID:Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. 265 60

Bone marrow transplantations in four patients (aged 8-28 years, median 27 years) with chronic myeloid leukaemia (CML) were performed from unrelated donors who were HLA-identical and MLC-negative. One patient was in the stage of refractory blast crisis, one in a chronic phase, and two in the second chronic phase. Conditioning treatment consisted of fractionated radiation and administration of cyclophosphamide; in the patients with their second chronic phase additionally etoposide. Cyclosporin A and methotrexate were administered to prevent graft versus host reaction. The patient in the blast crisis died on day 12 after transplantation of Candida pneumonia. The other three patients are still alive 128, 306 and 530 days, respectively, after transplantation, only a mild form of graft versus host disease having occurred. It is suggested that for patients younger then 50 years with CML in the chronic phase an unrelated donor should be searched for in the absence of a familial donor.
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PMID:[Transplantation of bone marrow from unrelated donors in chronic myeloid leukemia]. 266 Nov 85

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

Between August 1979 and April 1986, we treated 70 patients with chronic myeloid leukemia by supralethal chemoradiotherapy followed by bone marrow transplantation (BMT) from HLA identical sibling donors (65 patients) or from identical twins (5 patients). All patients were splenectomized before BMT. To prevent graft versus host disease Cyclosporin alone or associated with Methotrexate was given; in addition 13 patients received a T cell depleted marrow. All patients showed engraftment. Of the 5 patients treated by syngenic BMT, 2 patients relapsed but all are alive in remission, 2 of them after a successful second BMT. Of the 36 patients treated by allogeneic BMT in the chronic phase, 20 are alive in unmaintained remission after a median follow-up of 24 months (range 6 to 58). No patients have relapsed. The actuarial survival at 2 years was 60%. Of the 29 patients with more advanced disease, 19 have survived with the actuarial survival at 2 years 50%. We conclude that the probability of cure after BMT is very high, especially if BMT is performed while the patient remains in the chronic phase. Only 3 patients grafted in accelerated or blast phase died with relapse. The main cause of death was interstitial pneumonitis (15 patients) and 10 patients died from other transplant-related complications.
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PMID:[Allogenic bone marrow grafts in chronic myeloid leukemia]. 329 74

Between January 1983 and December 1986 16 patients (8 f, 8 m, median age 31.5 years, 14-41) with chronic myelocytic leukaemia (CML) received bone marrow grafts from their HLA compatible sibling donors. 11 patients were in the chronic and 4 in the accelerated phase. 1 patient was in lymphatic blast crisis. The patients were pretreated with busulfan (n = 15, total dose: 100-1000 mg, median: 225), mitobromitol (1 pat.), hydroxyurea (2 pats.), pre-irradiation of the spleen with 800 rad (1 pat.) and one patient had received 3 cycles of vincristin and prednisolone. The conditioning regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation (1000 rad, lung 800 rad). The prophylaxis against graft versus host disease (GVH-D) consisted of methotrexate (MTX) in 14 patients and of MTX in combination with cyclosporin-A in 2. At present (January 15th 1987) 9 patients survive 30 to 1210 days (median 1009) post graft (6/11 grafted in chronic, 2 of 4 in accelerated phase and 1/1 grafted in blast crisis. The causes of death were interstitial pneumonitis (CMV-associated, 2 pats.), venoocclusive disease of the liver (2 pats.), acute GVH-D and septicemia (2 pat.) and relapse (1 pat.). The Karnovsky score of 8/9 survivors is 100%, one patient has a score of 70% due to chronic GVH-D. Bone marrow transplantation for CML bears a high risk of early mortality but offers the unique option of permanent eradication of leukaemic haemopoiesis with subsequent long term survival.
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PMID:[Bone marrow transplantation in chronic myeloid leukemia--experiences in 16 patients]. 329 69

The current use of allogeneic bone marrow transplantation in various hematologic diseases is reviewed. Bone marrow transplantation (BMT) involves infusion of bone marrow from a suitable donor into a properly conditioned recipient. Most BMT is allogeneic, in which the donor is genetically dissimilar but shares some common tissue antigens with the recipient. Almost all patients undergoing allogeneic BMT must be "prepared" with high-dose cyclophosphamide to prevent graft rejection. Most patients with hematologic malignancy also receive total body irradiation to eradicate malignant cells located in areas inaccessible to the systemic circulation. Bone marrow transplantation is the treatment of choice for severe aplastic anemia. In acute myelogenous leukemia, the best results are observed in young patients undergoing BMT in first remission. In acute lymphoblastic leukemia, BMT is usually reserved for patients in second or subsequent remission. Early results are promising in patients with chronic myelogenous leukemia who receive BMT before the accelerated phase or blast crisis of this disease. Allogeneic BMT offers an opportunity for cure in some patients with relapses of Hodgkin's disease or those with certain subtypes of non-Hodgkin's lymphoma. Other diseases for which BMT has been used include severe combined immune deficiency disease, Fanconi's anemia, and multiple myeloma. Complications of BMT include graft failure or rejection, acute and chronic graft-versus-host disease, and infectious complications; late complications, such as restrictive and obstructive pulmonary disease, cataracts, sterility, and secondary malignancies, may also occur. Bone marrow transplantation has become an important treatment for many hematologic diseases, but it will probably remain a treatment reserved for only a few highly specialized centers. If morbidity and mortality caused by transplant-related complications can be reduced, BMT may be offered to older patients and those without HLA-identical sibling donors.
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PMID:Allogeneic bone marrow transplantation in the treatment of hematologic diseases. 388 73

Twenty-one patients with chronic granulocytic leukaemia underwent marrow transplantation. The donors were human-lymphocyte antigen-identical siblings in 19 cases. In the remaining 2 cases the donor was a parent in one and an identical twin in the other. The preparatory regimen included cyclophosphamide and 8.6 Gy total body irradiation given at either a dose of 0.1 Gy/min or 0.04 Gy/min. Five patients were in the accelerated phase of the disease, one was in remission following blast crisis, and the rest were all in the chronic phase. After chemotherapy and irradiation, all patients received bone marrow transplants. To date, nine patients are still alive, with a median survival of 64 days (range 28-683 days). One patient continued to have leukaemic cells and in another, the leukaemia recurred 18 months following transplantation. Interstitial pneumonitis was the cause of death of eight patients (38%). Graft-versus-host disease occurred in ten patients (47%).
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PMID:Bone marrow transplantation for chronic granulocytic leukaemia. 389 94


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