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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)

Inadequate leukemic ablative therapy ending in leukemic relapse is the source of most failures following bone marrow transplantation. Attempting to improve pretransplant leukemic ablative therapy, we report on a pilot regimen that includes teniposide, the principal chemotherapy, and total-body irradiation. Ten patients with acute lymphoblastic leukemia in relapse underwent allogeneic bone marrow transplantation. All patients engrafted. Toxicity, primarily mucositis, was manageable. Two patients have survived for 1547 and 1988 days in continued remission. Eight patients have died: three from sepsis in the immediate posttransplant period, four with recurrent leukemia, and one with chronic graft-versus-host disease and pneumonia. We believe that these results support further trials with teniposide in pretransplant leukemic ablative therapies.
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PMID:Total-body irradiation and high-dose teniposide: a pilot study in bone marrow transplantation for patients with relapsed acute lymphoblastic leukemia. 355 90

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

One hundred fourteen children with acute lymphoblastic leukemia were treated with allogeneic marrow transplantation from HLA-identical siblings after conditioning with cyclophosphamide and total body irradiation. Methotrexate was given posttransplantation for prophylaxis of graft-versus-host disease. The minimum follow-up after transplantation was 2 years. Sixteen of 51 patients transplanted in marrow remission survive from 2.1 to 8.9 years (median 2.7), 13 in continuous remission, one in remission following testicular relapse, and two after marrow relapse. Sixty-three were transplanted in relapse and eight survived 3-10 years (median 5.7), five in continuous remission, and three in remission following testicular relapse. In a multivariate analysis, factors significantly related to increased survival were marrow remission at transplant (p less than 0.007) and chronic graft-versus-host disease (p less than 0.005). Factors associated with increased relapse were marrow relapse at transplant (p less than 0.002) and absence of significant graft-versus-host disease (p less than 0.004). The development of acute graft-versus-host disease was associated with high marrow cell doses (p less than 0.04). These data suggest that some children with acute lymphoblastic leukemia and a poor prognosis with conventional chemotherapy may be cured with marrow transplantation.
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PMID:Marrow transplant experience in children with acute lymphoblastic leukemia: an analysis of factors associated with survival, relapse, and graft-versus-host disease. 389 60

5 patients underwent bone marrow transplantation for severe aplastic anemia (2) and acute leukemia (ALL) in first remission (3). Graft versus host disease prophylaxis was performed by depleting T lymphocytes in the donor bone marrow with the rat monoclonal Campath-1 and autologous complement. In addition, patients received cyclosporin A. Engraftment occurred normally in all 5 patients but 1 patient (SAA) had a late graft failure. Two patients suffered mild degrees of GvHD. All patients are currently in complete remission, one having undergone a second transplantation.
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PMID:[Transplantation of allogeneic bone marrow treated in vitro with Campath-1 monoclonal antibody]. 390 87

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. Use of a Hickman catheter facilitates maintenance of adequate nutritional intake and provides easy access for drawing blood and intravenous administration. 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. The risk of death from these complications must be balanced against the possibility of cure.
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PMID:Overview of marrow transplantation. 391 95

Two patients undergoing marrow transplantation for acute lymphocytic leukaemia in third remission received from histocompatible siblings marrow pretreated with a mixture of three anti-T-cell immunotoxins, consisting of murine monoclonal antibodies covalently linked to ricin. This marrow processing effectively eliminated functional T-cell responses while preserving the marrow precursors necessary for sustained haematoimmunopoietic engraftment. No post-transplant immunoprophylaxis was administered. Both patients showed prompt peripheral engraftment and were discharged from hospital within a month of transplantation. No toxic effects or graft-versus-host disease were apparent after the administration of immunotoxin-treated marrow. Ex-vivo immunotoxin pretreatment appears a safe and simple procedure which deserves further clinical testing as a sole method of graft-versus-host disease prophylaxis.
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PMID:Ex-vivo treatment of donor bone marrow with anti-T-cell immunotoxins for prevention of graft-versus-host disease. 614 6

A non-complement-binding monoclonal antibody, TA-1, recognizing determinants on human T lymphocytes, was linked to the plant seed toxin ricin, either the intact molecule or purified ricin A chain. Peripheral blood lymphocytes were pretreated with conjugate for 2 hr, washed, and then measured in vitro for T cell proliferation. Studies showed that antibody-intact ricin conjugates were up to 39-fold more inhibitory than antibody-A-chain conjugates. Killing was selective because an unreactive control antibody linked to toxin had minimal inhibitory effect. Dose response curves obtained in human studies were nearly identical to curves obtained in an animal model n which a monoclonal anti-murine T cell antibody (anti-Thy 1.1) was linked to ricin and ricin A chain. In the human system, longer exposures of peripheral blood cells to conjugates did not alter our findings. TA-1-ricin conjugates were tested against human ALL cell lines. KOPN-1, a cell line bearing the determinant reactive with TA-1 was selectively eliminated within 2 days after pretreatment with 500 ng/ml. Even 10-fold greater concentrations of TA-1-A chain were not adequate for leukemic cell destruction. These findings (1) show for the first time in a human model that monoclonal antibodies, directed against certain differentiation antigens when linked to ricin A chain are not as effective in normal or malignant cell killing as when linked to intact ricin; (2) contribute to the growing body of evidence showing that monoclonal antibody A chain conjugates do not permit the acquisition of levels of toxin sufficient to destroy target cells; and (3) are important relative to increasing interest in use of antibody-toxin conjugates for graft-versus-host disease prophylaxis in allogeneic bone marrow transplantation.
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PMID:Monoclonal antibody-toxin conjugates reactive against human T lymphocytes. A comparison of antibody linked to intact ricin toxin with antibody linked to ricin A chain. 623 50

Fifteen patients with acute lymphocytic leukemia (ALL) in second or subsequent remission received intensive therapy with cyclophosphamide and single dose, rapid rate (26 cGy/min) total body irradiation (TBI) followed by bone marrow transplantation (BMT) from a histocompatible sibling match. Outcome was compared to that of 23 conventionally treated control patients in second ALL remission who presented to the same institution during the same time period but had no available transplant donor. The 15 BMT patients and 23 control patients had similar characteristics, with the exception that the BMT patients were significantly older at the time of ALL diagnosis (12.6 yr versus 5.7 yr, p = 0.01). BMT patients had a significantly increased chance of remaining disease-free for 36 mo from time on study (43% actuarial versus 5%, p = 0.004) and a greater overall survival rate at 48 mo (47% actuarial versus 9%, p = 0.27) than the conventionally treated patients. In all, 5 of the bone marrow transplant patients (33%) remain alive and free of disease 24-48 + mo from transplantation. Several pre- and posttransplant characteristics were analyzed to determine predictive factors for a successful BMT outcome for patients with ALL in second or subsequent remission. Significant risk factors for predicting leukemic relapse included initial white blood count (WBC) greater than 50,000/microliters at ALL diagnosis (100% relapse rate versus 37% for patients with lower WBCs, p = 0.001) and presence of any extramedullary disease pre-BMT (100% relapse rate versus 37% for patients without extramedullary disease, p = 0.03). All 5 disease-free BMT survivors had initial WBCs less than 50,000/microliters and no evidence of extramedullary disease pretransplantation. Maintenance chemotherapy with 6-mercaptopurine (6MP) and methotrexate was given to four patients starting 100 days after bone marrow transplantation. Use of maintenance chemotherapy was associated with a significantly increased chance of remaining disease free (100% of patients surviving leukemia-free versus 17% for patients not receiving maintenance chemotherapy, p = 0.02). Presence of graft-versus-host disease (GVHD) did not influence leukemia-free survival. These results confirm that intensive therapy followed by bone marrow transplantation is the treatment of choice for patients with ALL in second or subsequent remission who have a histocompatible sibling match. Furthermore, the data suggest that a controlled trial to evaluate the efficacy of maintenance chemotherapy post-BMT for ALL patients is warranted.
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PMID:Intensive therapy followed by bone marrow transplantation for patients with acute lymphocytic leukemia in second or subsequent remission: determination of prognostic factors (a report from the University of Minnesota Bone Marrow Transplantation Team). 634 Jul 56

To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.
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PMID:Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow. 637 95

Twenty-one patients with acute leukemia in second to fifth remission were treated with bone marrow transplantation: 19 patients with transplants from HLA-matched siblings and two with transplants from identical twins. Twelve patients survived from 15 to 1,625 days after transplantation: six of 11 in the ALL group and six of 10 in the AML group. Recurrence of leukemia after marrow transplantation occurred in five patients. The cause of death in five patients was infection, in two patients combined with graft-versus-host disease. Long-term disease-free survival can probably be achieved in 30%-35% of all patients with acute leukemia who receive a marrow transplant in second or subsequent remission.
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PMID:Bone marrow transplantation for acute leukemia in second or subsequent remission. 639 27


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