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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)

Bone marrow transplantation is emerging as a viable therapeutic approach to a number of diseases that are usually or uniformly fatal. We review here recent experiences in bone marrow transplantation in man at UCLA and in various other institutions throughout the world. We examine marrow transplantation in immunodeficiency diseases, acute leukemia, and aplastic anemia and consider the problems of infection in the transplant recipients. The applications of tissue typing to marrow transplantation and immunologic manipulations, which may influence engraftment and graft-versus-host disease, are also reported.
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PMID:Bone marrow transplantation in man. 0 Sep 37

Seventy-six patients, aged 2 to 17 years, were treated with bone marrow transplantation for severe aplastic anaemia or acute leukaemia refractory to conventional therapy. 16 of the 22 patients (73%) who received marrow transplantations for aplastic anaemia are surviving, 12 of these for over one year. In acute leukaemia, using preparation with cyclophosphamide and total body irradiation, 8 of 33 patients (24%) receiving allogeneic and 5 of 8 (63%) receiving syngeneic transplantations are continuing in remission from 3 months to beyond 2 years. The longest continuing remission off therapy is now over 4 1/2 years after preparation with total body irradiation. The major causes of failure remain graft-versus-host disease, infection, graft rejection (aplastic anaemia), and leukaemic relapse.
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PMID:Marrow transplantation in treatment of children with aplastic anaemia or acute leukaemia. 0 16

Forty-nine patients with severe aplastic anemia, 33 due to unknown cause, 11 drug or chemical related, 2 associated with hepatitis, 1 with paroxysmal nocturnal hemoglobinuria, and 2 possibly associated with Fanconi syndrome did not show recovery after 0.5-96 (median 2) mo of conventional therapy. Twenty-two were infected and 21 were refractory to random platelet transfusions at the time of admission. All were given marrow grafts from HLA-identical siblings. Forty-five were conditioned for grafting by cyclophosphamide (CY), 50 mg/kg on each of 4 successive days, and four by 1000 rad total body irradiation. All were given intermittent methotrexate therapy within the first 100 days of grafting to modify graft-versus-host disease (GVHD). Three patients died from infection too early to evaluate (days 1-8). Forty-six had marrow engraftment. Of these, 20 are surviving with good peripheral blood counts between 186 and 999 days, and 18 have returned to normal activities. Chronic GCHD is a problem in five. Twelve patients died of infection following rejection of the marrow graft. Twelve patients died with bacterial or fungal infections or interstitial pneumonia and active GVHD or soon following resolution of GVHD. Two patients died with marrow engraftment and no GVHD, one with an interstitial, and the other with a bacterial pneumonia. Thirty-six patients who had received random donor blood transfusions were randomly assigned to receive either CY or procarbazine-antithymocyte globulin-CY as conditioning regimens to test whether the incidence of graft rejection could be decreased. There was no difference in the incidence of graft rejection between the two regimens. In 13 patients with rejection, second transplants were attempted either with the original marrow donor (9 patients) or another HLA-identical sibling (4 patients). Three of these transplants were not evaluable, seven were unsuccessful and three were successful with only one of the three surviving for more than 468 days. In conclusion, the long-term survival of 41% of the patients in the present study is similar to that achieved in our first 24 patients, and confirms the importance of marrow transplantation for the treatment of severe aplastic anemia. Marrow graft rejection, GVHD, and infections continue to be the major causes of failure.
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PMID:Aplastic anemia treated by allogeneic bone marrow transplantation: a report on 49 new cases from Seattle. 1 59

Marrow transplantation in aplastic anemia and leukemia has generally been limited to siblings who have been histocompatible at both the serological (A and B) and lymphocyte determined (D or MLC) loci of the HLA system. We studied three male patients, two with aplastic anemia and one with acute myelogenous leukemia, who received transplants from their histoincompatible mothers. MLC studies between donors and recipients showed varying degrees of stimulation. Definite engraftment occurred in one patient and transient engraftment in another. Engraftment in the third patient could not be evaluated. In the patient with sustained engraftment, there was clinical evidence of severe graft versus host disease (GVHD) however, this was not substantiated by histologic findings. This preliminary study suggests that MLC incompatibility may be more of an indicator of the risk of GVHD than of bone marrow rejection. If more effective control of GVHD can be accomplished, marrow transplantation between MLC-reactive individuals may become feasible.
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PMID:Experience with incompatible maternal donors for bone marrow transplantation. 1 47

73 consecutive patients with severe aplastic anemia were treated by marrow transplantation from hematologically normal HLA identical siblings. 68 patients lived long enough to document marrow engraftment. 21 rejected the graft and 19 of these died. 47 sustained engraftment and 18 of these died. In 16 patients, death was associated with graft versus host disease. 29 patients with sustained engraftment are alive with complete hematologic restoration between 8 mo and 5 yr. This analysis, by using a proportional hazards regression model, was directed at identifying factors that predicted survival (and absence of graft versus host disease). Of the 24 factors entered into the analysis only two strongly correlated with survival: (a) sex match of donor and recipient (P less than 0.01), and (b) absence of refractoriness to random donor platelets at the time of transplantation (P less than 0.05). Refractoriness adversely influenced the survival of the sex mismatched patients, These data suggest that X and Y-associated transplantation antigen systems are important determinants of the outcome of marrow grafts between HLA identical siblings for the treatment of aplastic anemia. The machanism by which refractoriness to random donor platelets influences survival is currently unclear.
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PMID:Treatment of aplastic anemia by marrow transplantation from HLA identical siblings. Prognostic factors associated with graft versus host disease and survival. 1 72

The neutrophil function of seven patients receiving allogeneic bone marrow transplantion was studied. Five of the patients had been transplanted for aplastic anaemia and two for acute leukaemia. Determinations were made of neutrophil phagocytosis, chemotaxis, random migration, and microbicidal activity for Candida albicans and Staphylococcus aureus. One patient showed a decreased ability to kill C. albicans at a time when she had active pneumonia due to Pneumocystis carinii. The remainder of the studies showed normal neutrophil functions. No differences were observed in the patients who had graft versus host disease [GvH] from those without GvH. These studies suggest that defects in phagocytic neutrophil function do not contribute significantly to the impaired host defenses in recipients of bone marrow transplantation.
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PMID:Neutrophil function in bone marrow transplant recipients. 1 82

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.
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PMID:Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor. 2 51

Pre- and post-transplant bone marrow samples from 20 patients with aplastic anemia were studied. Morphologic evidence of marrow reconstitution was noted in 18 patients one to three weeks following transplantation. In most instances the engrafted marrow elements in early weeks appeared as small clusters of erythroid or myeloid precursors. Bone marrow biopsy or clot sections obtained four to eight weeks after transplantation were more cellular with larger clusters of hematopoietic cells, which were most often composed of mixed cellular elements, including megakaryocytes. Two patients with morphologic evidence of engraftment died shortly after transplantation and were excluded from further analysis. In four of the remaining 16 patients grafts were "rejected" three to eight weeks after transplant. A fifth patient who received a marrow graft from his identical twin showed a transient increase in marrow cellularity without clinical improvement. However, the second marrow transplantation in this patient using the same donor after conditioning with cyclophosphamide resulted in moderate clinical improvement. In four of the five patients developing graft "rejection" or failure there was an increase in marrow mast cells in pre- and post-transplant marrow samples. In contrast, only two of 11 patients with successful engraftment had an increase in mast cells. Although the pathophysiologic role of mast cells in marrow transplantation is unclear, the present study suggests a possible inverse correlation between the numbers of marrow mast cells and the likelihood of successful engraftment. Bone marrow samples in patients with graft versus host disease displayed a slight increase in the number of eosinophils, lymphocytes, and plasma cells.
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PMID:Morphologic aspects of bone marrow transplantation in patients with aplastic anemia. 2 34

Seventeen patients with aplastic anemia or acute leukemia received transplants from donors who had major ABO incompatibilities. Antibody titers were decreased by plasma and whole blood exchanges prior to marrow infusion. All 17 patients were successfully engrafted, and there was one possible rejection in the patient with the highest pretransplant anti-A IgG titer. Nine of 17 patients are currently alive. A review was carried out of transplants performed in Seattle between HLA-matched siblings with aplastic anemia and leukemia. Two hundred forty-six evaluable patients with ABO-compatible donors were compared with 46 with minor ABO-incompatible donors. There was no effect of minor ABO incompatibility on graft rejection, incidence and severity of graft-versus-host disease, or survival.
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PMID:ABO-incompatible marrow transplants. 3 Jan 94

Forty-one patients, suffering from severe aplastic anaemia were treated either with ALG alone (27 patients) or ALG followed by infusion of allogeneic bone marrow (14 patients). Eighteen patients (67 per cent) are presently alive after ALG alone at over 100 to over 550 days. Fourteen (52 per cent) showed sustained improvement of haematopoiesis, two are alive without change, one recovered autologous haematopoiesis after cyclophosphamide conditioning and transfusion of HLA identical marrow and one is lost to follow-up. Eight patients (57 per cent) are currently alive after ALG and transfusion of haplotype identical marrow with self-sustaining autologous haematopoiesis at over 200 days to over four and a half years. No lethal complications occurred and none of the bone marrow infusions led to permanent engraftment or graft-versus-host disease. The mechanism of action is not known, but our results support the hypothesis that unspecified autoimmune reactions block the normal outgrowth of haematopoietic precursor cells in a substantial number of patients with aplastic anaemia. This therapeutic approach seems to offer good chances of survival, especially for those patients who do not have an HLA identical sibling. Its value should be further investigated.
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PMID:Treatment of aplastic anaemia by antilymphocyte globulin with or without marrow infusion. 3 Dec 56


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