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)

Thirty-three patients with acute leukemia (15 with lymphoblastic leukemia and 18 with myeloblastic leukemia) were entered into a program of high-dose radiochemotherapy followed by allogeneic bone-marrow transplantation. These patients were in various clinical stages of disease. Of 10 in complete hematologic remission at the time of transplantation, seven were alive without maintenance therapy at the time of evaluation, eight to 35 months after grafting; one was in relapse. Of 11 who received transplants during partial remission, six were in remission without further treatment eight to 33 months after transplantation. In 12 the disease was refractory to chemotherapy when preparation for transplantation was started, and only one of them was alive and free of disease after 10 months. Recurrent leukemia, graft-versus-host disease, viral pneumonia, and early therapy-related toxicity were the major causes of failure. High-dose chemotherapy and total-body irradiation followed by allogeneic marrow transplantation performed during complete or partial remission can produce long-term remission of acute leukemia.
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PMID:Bone-marrow ablation and allogeneic marrow transplantation in acute leukemia. 624 59

Nearly one-half of marrow transplant recipients who survive at least 6 months develop varicella-zoster virus (VZV) infection. Of 92 cases studied, 82 occurred within the first 12 months after transplant. Only one patient had recurrent infection. Seventy-seven patients had herpes zoster, 22 with subsequent cutaneous dissemination, and 15 had varicella. The overall mortality rate was 8%, and all deaths occurred within 9 months of transplant. Twenty-six of 32 patients studied had significant rises in VZV antibody during recovery. Among patients with acute leukemia, those with syngeneic transplants had a significantly lower incidence of VZV infection than those with allogeneic transplants. Incidence was slightly, but not significantly, decreased among patients with aplastic anemia. In contrast to other infections, the incidence of VZV infection was not influenced by graft-versus-host disease or predicted by the results of dinitrochlorobenzene skin testing.
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PMID:Varicella-zoster virus infection after marrow transplantation for aplastic anemia or leukemia. 624 86

Seven patients with acute leukemia were treated by allogenic bone marrow transplantation from HLA matched sibling. The conditioning regimen was classical using cyclophosphamide and Total Body Irradiation, followed by methotrexate. All patients were given ketoconazole (400 mg per day in a single dose) as antifungal prophylaxis for 6 months. Serum ketoconazole levels were measured using the inhibition assay of mycotic culture in gelose, and they were studied at 0, 1, 2, 4 and 6 h after ketoconazole ingestion, and repeated serially after bone marrow transplantation. In these transplanted patients, absorption of ketoconazole could be delayed, with the maximum levels at 4 h or 6 h after ingestion. Most measurements showed appropriate levels (maximum levels greater than 1 mg/l) even after the third week post transplantation. With the exception of severe acute GVH disease (1 patient), the ketoconazole absorption was adequate in minor or mild GVH disease (6 patients) and in chronic GVH disease (2 patients). In four patients ketoconazole absorption was compared with gut absorption tests (Schilling's test, Iron absorption test, xylose test): In all patients the maximum serum levels of ketoconazole were correct, even in three patients with abnormal gut absorption tests. In this series, no life-threatening mycotic infection occurred, and the three deaths observed showed no mycotic infection.
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PMID:Serum levels of ketoconazole in bone marrow transplanted patients. 631 9

In a review of allogeneic bone marrow transplantation (BMT) for leukemia the following points proved to be of crucial importance: (1) combination of cyclophosphamide (Cy) and total body irradiation (TBI) for conditioning, (2) early BMT for acute leukemia (AL) in first remission and for chronic granulocytic leukemia (CGL) in chronic phase, (3) prophylaxis of graft-versus-host disease (GvHD) with cyclosporin-A (CyA). 50 successive BMT for leukemia performed in Basel between July 1979 and September 1982 are analyzed. 7 of 13 acute myelogenous leukemias (AML) and 8 of 9 acute lymphatic leukemias (ALL) grafted in first remission, and 7 of 10 CGL, are alive without signs of leukemia and without chronic problems. Of the patients grafted for AL in second remission or later, 3 of 6 AML and 6 of 12 ALL are alive. Severe GvHD was seen in 5 of 43 BMT between HLD identical siblings, in three of them combined with interstitial pneumonia. Thus the incidence of these two serious complications of allogeneic BMT has been drastically reduced with CyA compared to our previous experience with prophylactic methotrexate (MTX). 4 grafts were performed between HLA-haploidentical siblings. 3 of the 4 patients developed fatal GvHD. This implies that in this histocompatibility setting CyA alone is not sufficient. No problems were encountered in 3 syngeneic BMT. 12 leukemic relapses were observed. Relapse never occurred in ALL in first remission and never in CGL. 4 recurrences were seen in AML in first remission. All other relapses were in patients with AL grafted in stages other than first remission. In 86 successive patients with severe aplastic anemia (SAA) the following important advances were made: (1) it was shown that the majority of patients have sufficient hemopoietic stem cells and that after treatment with antilymphocyte globulin (ALG) over 70% have long-lasting remissions, (2) the combined treatment with ALG and high dose prednisone increases the remission rates to 90% and in addition shortens the supportive care period significantly. These developments are of crucial importance for patients without an HLA-identical sibling, (3) success rates of marrow transplants between HLA-identical siblings could be increased from 36% with prophylactic MTX to 67% using CyA.
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PMID:[Bone marrow transplantation in leukemia and aplastic anemia]. 634 83

Peripheral blood Ia-positive (Ia+) T cells were enumerated in 52 patients who had received allogeneic or syngeneic bone marrow transplantation for the treatment of acute leukemia or severe aplastic anemia. Twenty-two normal people showed 3 +/- 2% of peripheral blood T cells to be Ia+. During the first 130 days posttransplant, all patient groups showed a moderate elevation in the percentage (mean: 21-26%) of Ia+ T cells, regardless of the type of transplant performed, and regardless of the presence or absence of acute graft-versus-host disease (GVHD). Although there was marked individual variation (range 5-76%), there was a trend towards a decrease in the percentage of Ia+ T cells with increasing time after transplantation. Long-term survivors still showed a small (range 3-20%, mean 10%) but significant elevation in the relative number of Ia+ T cells 1-3.4 years after transplantation, regardless of the presence or absence of chronic GVHD. It is not currently known why Ia+ T cells are found in these patients, but accelerated lymphopoiesis, subclinical infection, and excessive immune stimulation caused by microorganisms or other foreign antigens could be contributing factors.
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PMID:Human T lymphocyte phenotypes after bone marrow transplantation. T cells expressing Ia-like antigen. 635 69

Four patients with acute leukemia received transplants from HLA-mismatched, related donors. Marrow cells that had been depleted of T lymphocytes using a monoclonal anti-T-lymphocyte antibody and rabbit complement were used. In vitro studies showed that 80-97% of the mature T lymphocytes were removed using this procedure. Infusion of the treated marrow was accomplished without complications, and engraftment occurred in each case. Graft-versus-host disease occurred in 3 of the 4 patients. These results show that additional manipulations of the marrow will be required to allow complete T lymphocyte removal from the marrow before the feasibility of this approach in HLA-mismatched patients can be determined.
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PMID:Transplantation of T-lymphocyte-depleted bone marrow between HLA-mismatched individuals. 635 2

To study the impact of the composition of the bone-marrow graft on engraftment and graft-versus-host disease (GvHD), we analyzed the data on 29 patients with acute leukemia in remission and 11 patients with aplastic anemia. All of them received bone-marrow grafts from HLA matched, MLC nonreactive, sibling donors, were nursed in laminar down-flow isolators with selective gut decontamination, and received GvHD prophylaxis with methotrexate. The number of nucleated cells in the marrow graft/kg body weight of the recipient had no relation with the rapidity of engraftment or with the occurrence and severity of GvHD. The number of hematopoietic progenitor cells (CFUc)/kg had a weak, but significant, correlation with both the number of neutrophils at day 30 post BMT and with the day at which the reticulocytes passed the 10% level. The number of T cells/kg did not show any correlation with either the occurrence or the severity of GvHD. Our data show that the concentration of hematopoietic progenitor cells in the graft correlates with the rapidity of engraftment. However, within the range of numbers of T cells infused in this study, no correlation is present between T cells in the graft and GvHD. Therefore, nearly complete depletion of marrow grafts of T cells is probably necessary to effectively decrease the incidence of GvHD.
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PMID:The impact of the composition of the bone marrow graft on engraftment and graft-versus-host disease. 636 14

High-dose methylprednisolone (HDMP) was used to treat 18 episodes of severe (grades III and IV) acute graft-versus-host disease (GVHD) that developed after allogeneic bone marrow transplantation in 12 patients with acute leukemia and in 2 with aplastic anemia. Most of the patients showed rapid improvement in GVHD, with complete resolution of the skin and gut manifestations. However, the response of liver disease to the treatment was slow and incomplete. Complications seen were interstitial pneumonia and fungal and viral infections. Seven patients survived for more than two months following the treatment of acute GVHD. Five of these became long-term survivors with a median survival of 22+ months (range 11-38 months); all five long-term survivors developed chronic GVHD and are alive at the time of this report. It appears that HDMP is an effective treatment for severe acute GVHD. However, its true efficacy can only be ascertained in a randomized study comparing high-dose and conventional-dose methylprednisolone.
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PMID:High-dose methylprednisolone treatment for acute graft-versus-host disease after bone marrow transplantation in adults. 636 62

Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
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PMID:Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients. 637 59

Twenty patients with disseminated non-Hodgkin's lymphoma who failed conventional combination chemotherapy were treated with high-dose chemoradiotherapy and marrow transplantation from an HLA-identical sibling. Four patients remain alive in complete remission from 153 to 784 days after transplant. The reason for failure in eight cases was persistence or relapse of lymphoma. In the other eight cases, death was due to a complication of the transplant procedure including interstitial pneumonia, veno-occlusive disease of the liver, graft-versus-host disease, or infection. These results appear similar to those previously observed in patients with acute leukemia in relapse in that a small but significant proportion of patients with otherwise end-stage disease may achieve prolonged complete remission after intensive chemoradiotherapy and allogeneic marrow transplantation.
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PMID:Treatment of non-Hodgkin's lymphoma with chemoradiotherapy and allogenic marrow transplantation. 637 14


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