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)

Among 42 consecutive recipients of unrelated marrow were 39 HLA-A, -B, -DR identical, matched unrelated donors (MUD) and three with one HLA antigen mismatch. The majority were genomically typed for DRB, DQA, DQB and DPB. The recipients of MUD marrow were compared with 39 recipients of marrow from HLA-identical siblings with similar diagnoses, disease status and age. Each group included 24 patients with hematological malignancies, 6 with severe aplastic anemia and 9 inherited disorders. Immunosuppression consisted of anti-thymocyte globulin (ATG; pre-BMT mainly to recipients of unrelated marrow), CsA and four doses of MTX. Grade I acute GVHD was treated with prednisolone 2 mg/kg. In a comparison of MUD marrow recipients and HLA-identical siblings 34 of 39 and 36 of 39 of the patients engrafted, respectively. Recipients of MUD marrow and HLA-identical siblings achieved 0.2 x 10(9) WBC/l on day 16 (median) and 14, respectively (P = 0.03). Furthermore, the recipients of MUD marrow needed more platelet transfusions (P = 0.04). The incidence of acute GVHD grade II-III was 15% in the MUD marrow recipients compared with 11% among the HLA-identical siblings. The 2-4 year cumulative incidence of chronic GVHD was 29% and 22% in the two groups, respectively. The overall 2-year survival was 59 and 78%, respectively. Among patients with CML in chronic phase or accelerated phase (n = 26), 2-year relapse-free survival was 79% in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings. 765 90

A 23-year-old woman had a normal full-term delivery 78 months after BMT for ALL. Conditioning therapy was Ara C 1.4 g/m2 x 4, CY 60 mg/kg x 2 and TBI 2.5 Gy x 5 at a dose rate of 3.5 cGy/min. Despite GVHD prophylaxis with short-term MTX and CsA, she developed grade I acute GVHD, but showed no evidence of chronic GVHD. Following amenorrhea for 4 years, menstruation recommenced spontaneously. She had a normal pregnancy 6 years after BMT resulting in a healthy infant with simple hypospadias. This and previous reports indicate that normal pregnancy is possible after BMT with TBI in excess of 10 Gy.
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PMID:Successful pregnancy after allogeneic bone marrow transplantation following conditioning with total body irradiation. 870 12

Between November 1978 and September 1988, 184 patients with acute myeloid leukemia in first remission received marrow transplants from HLA-identical siblings after conditioning with 120 mg/kg of cyclophosphamide and 12.0 Gy fractionated total body irradiation. Patients received either cyclosporine (CYA, n = 59), methotrexate (MTX, n = 82), or MTX + CYA (n = 43 as graft-versus-host disease (GVHD) prophylaxis. The probabilities of grades II-IV acute GVHD after CYA, MTX or MTX+CYA were 0.43, 0.48 and 0.28, respectively (p = 0.06). The probability of non-relapse mortality was 0.53, 0.50 and 0.42 at 4 years in patients treated with CYA, MTX, or MTX + CYA, respectively. The probability of relapse was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX and 0.44 in patients receiving MTX + CYA (p = 0.02). The probability of survival at 4 years was 0.54 with CYA, 0.51 with MTX and 0.45 with MTX + CYA. A multivariate analysis of risk factors for relapse examined age, WBC at diagnosis, blast count at diagnosis, percentage of marrow blasts, FAB subtype, the number of remission induction courses to achieve a remission, maintenance therapy, consolidation therapy, marrow cell dose, donor-recipient sex, GVHD prophylaxis regimen and isolation and decontamination in laminar airflow rooms. GVHD prophylaxis with MTX + CYA was independently significantly associated with an increased risk of relapse (relative risk 2.25, p = 0.01). Acute GVHD was associated with increased non-relapse mortality (RR = 3.58, p < 0.0001). The administration of MTX + CYA did not adversely affect survival because patients receiving this regimen experienced less mortality from causes other than relapse when compared with patients receiving either CYA or MTX alone.
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PMID:Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia. 771 67

Over a 5-year period we evaluated 65 myeloma patients aged < or = 55 years as potential candidates for intensive therapy and allogeneic BMT. Twenty six (40%) patients were transplanted; the median duration of disease was 4 months (range 2-58 months) and median number of prior regimens was 1 (range 1-5); all but five patients had chemosensitive disease. Conditioning regimens included combinations of BU+CY+MEL in 14 patients, BUCY2 in eight and CY+TBI in four. Donors were HLA-matched siblings in 19 cases, one antigen mismatched siblings in three and unrelated donors in four. All patients received CsA, plus either methylprednisolone (n = 5) or MTX with or without other agents (n = 19). Grade III or IV regimen-related toxicity (RRT) was relatively infrequent (3 patients) and was not seen in nine patients conditioned with BU (total dose 12 mg/kg) + MEL (100 mg/m2) + CY (90 mg/m2). Grade II-IV acute GVHD occurred in 20 patients, and was the cause of death in three. Chronic GVHD also caused three deaths. Thirteen of 21 evaluable patients (62%) achieved a CR and six achieved a PR. Actuarial progression-free survival (PFS) was 40% (95% confidence interval (CI) 19-61%) at a median follow-up of 14 months (range 3-56 months); the PFS was 52% (95% CI 24-74%) in chemoresponsive patients, compared with 0% in chemoresistant patients (P = 0.0066).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Treatment of myeloma using intensive therapy and allogeneic bone marrow transplantation. 774 43

Comprehensive programmes for BMT started in Hong Kong in 1990. As of September 1993, there are a total of 13 BMT beds in Government-funded University Hospitals performing about 110 transplants per year or 18 transplants per million population per year. So far, 194 transplants were performed: allogeneic BMT (72.2%), autologous BMT (11.8%), matched unrelated donor BMT (8.8%), identical twin BMT (1.5%), mismatched BMT (2.1%) and second BMT (3.6%). The major indication was haematological malignancy (84%). About 40% of the patients were prepared by chemotherapy alone. A combination of CsA and short MTX was the commonest GVHD prophylaxis. The incidence of GVHD was the same as in the Caucasians. Results of transplant outcome were comparable to those reported by the International Bone Marrow Transplant Registry.
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PMID:Bone marrow transplantation in Hong Kong. 792 Mar

Seventy-three leukemic HLA-identical siblings undergoing BMT received individualized prophylaxis against GVHD based on estimated risk of GVHD development. Patients with an estimated low risk of GVHD were given MTX. MTX + CsA were given to patients having a high risk of GVHD. CsA treatment was discontinued as early as possible after engraftment followed by weekly MTX until 3 months after BMT. Conditioning was busulfan + CY (BuCY, n = 35) or CY/TBI (n = 38). CY/TBI patients given MTX combined with CsA for 1 year served as retrospective controls (n = 39). The incidence of acute GVHD was similar in the three groups. The incidence of chronic GVHD was 59% in the BuCY group and 40% in the CY/TBI group compared with 25% in the controls (p = 0.002 vs BuCY). The incidence of relapse at 2 years was 6% in the BuCY group and 35% in the CY/TBI group (p = 0.01) vs 36% in the control group (p = 0.01 vs BuCY). Actuarial 2-year relapse-free survival was 76, 58 and 51% in the three groups, respectively (p = 0.06, BuCY vs controls). In multivariate analysis individualized prophylaxis was associated with chronic GVHD. Poor survival correlated with high risk leukemia and absence of chronic GVHD. Poor relapse-free survival was associated with high risk leukemia and TBI.
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PMID:Individualized prophylaxis against graft-versus-host disease in leukemic marrow transplant recipients. 795 Nov 24

Graft rejection has been a problem after marrow grafts for patients with aplastic anemia who were conditioned with cyclophosphamide (CY). Rejection lessened when patients were given the marrow donor's peripheral blood buffy-coat cells in addition to the marrow, but this result was achieved at the price of more chronic graft-versus-host disease (GVHD). Results with second transplants suggested that CY alternating with antithymocyte globulin (ATG) was more immunosuppressive than CY alone. Therefore, the current study explored CY and ATG without buffy-coat cell transfusions in 39 patients with aplastic anemia given marrow transplants from HLA-identical family members (siblings in 38 cases, father in 1 case). We hoped both to minimize the risks of graft rejection and of chronic GVHD and to improve survival. Patients were 2 to 52 years of age (median, 24.5); 87% had received previous transfusions, and 41% had therapy with immunosuppressive agents before transplant. They were administered four daily doses of CY (total, 200 mg/kg) alternating with three doses of ATG (total, 90 mg/kg) followed by an HLA-identical marrow graft. Methotrexate and cyclosporine were administered to prevent GVHD. Two patients rejected their grafts (5%), and both were successfully retransplanted. Acute (grade 2 or 3) GVHD occurred in 15% and chronic GVHD in 34% of patients. The actuarial survival rate at 3 years was 92%, which compares favorably to the 72% survival rate in 39 historical patients who were matched with current patients for age and risk factors for rejection and GVHD. CY/ATG is a well-tolerated and effective conditioning program for marrow grafting in aplastic anemia that, when combined with GVHD prevention by methotrexate/cyclosporine, results in excellent survival.
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PMID:Cyclophosphamide combined with antithymocyte globulin in preparation for allogeneic marrow transplants in patients with aplastic anemia. 804 76

Graft-versus-host disease (GVHD) remains a major obstacle to allogeneic bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjusted the dose to maintain a constant whole blood level. Forty-five patients, ranging in age from 16 to 56, mean 39.5 years, undergoing allogeneic transplantation for various hematological malignancies received CsA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m2 i.v. was given on day +1, followed by 10 mg/m2 on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The mean rise in creatinine was 0.89 mg/dl. There was an association between the concomitant administration of amphotericin B and CsA and the development of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 patients. None of the patients developed serious neurological side effects. Greater than grade-I acute GVHD developed in only 13% of the patients. We conclude that administering CsA as an adjusted dose by continuous intravenous infusion is well tolerated and effective in preventing acute GVHD in patients undergoing allogeneic bone marrow transplantation.
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PMID:Adjusted-dose continuous-infusion cyclosporin A to prevent graft-versus-host disease following allogeneic bone marrow transplantation. 811 Aug 73

Transplant related mortality and relapse after bmt have a negative influence on the outcome of patients transplanted for acute leukaemia in first remission. Transplant related mortality includes graft-versus-host disease, infections and graft failure. To prevent gvhd and associated infections without increased graft rejection, a protocol of combined in vivo/ex vivo T-cell depletion (Campath IgG 20 mg i.v. for 5 days and Campath IgM T-cell depleted graft) with no further immunosuppression was initiated. Up to now 22 adult patients (median age 39 years, range 21 to 51) have been transplanted. One graft failure most probably due to persistent leukaemia, three acute gvhd (grade I) and no chronic gvhd occurred. Two patients relapsed after bmt and died. Two further patients died due to idiopathic interstitial pneumonitis and acute liver failure, respectively. Eighteen patients are alive in complete remission. With a median follow up of 13 months (1-30) the probability of survival is 78%, disease free survival is 80% and transplant related mortality is 10%. We compared these results with 3 historical control groups with different regimens of gvhd prophylaxis. 1. MTX group (n = 15): With a median follow up of 135 (115-147) months after bmt the probability of survival is 40%, disease free survival is 40% and transplant related mortality is 60% (mainly gvhd and infection). 2. Campath group (only ex vivo T-cell depletion n = 25): With a median follow up of 86 (62-102) months probability of survival is 52%, disease free survival is 43% and transplant related mortality is 36% (mainly rejection and infection).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro and in vivo depletion of T cells. 812 50

The risks for the development of idiopathic pneumonia after allogeneic BMT were assessed in a case-series review at a single marrow transplantation center. All allogeneic marrow recipients (n = 299) (age range 1-60 years) with severe aplastic anemia (SAA) transplanted from family member donors after conditioning with CY were evaluated. Post-grafting immunosuppression consisted of MTX alone in 205 patients (69%), CY alone in 16 (5%) and a combination of the two in 78 (26%). The incidence estimate for any pneumonia within the first 200 days after transplant was 18% (95% confidence interval = 14-24%). Of 48 cases of pneumonia, CMV infection was documented in 44%, 21% were idiopathic and the remainder were either due to other infections or were not evaluated. The effect of acute GVHD on the incidence of pneumonia was examined using multivariate Cox proportional hazards models which included covariates for potential confounding factors. Consistent with previous reports, acute GVHD was associated with an increased incidence of any pneumonia (relative risk (RR) = 3.5, 95% Cl = 1.9-6.9; p < 0.001). Specifically, acute GVHD also was associated with the largest risk of idiopathic pneumonia (RR = 5.0, 95% Cl = 1.1-22; p = 0.04). In conclusion, recognition of acute GVHD as a risk factor for idiopathic pneumonia suggests that mechanisms in addition to chemoradiation damage are responsible for non-infectious lung injury after BMT.
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PMID:Acute graft-versus-host disease and the risks for idiopathic pneumonia after marrow transplantation for severe aplastic anemia. 824 81


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