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 October 1984 to December 1994, 142 patients from six IGCI-BMT centers (78 acute myelogenous leukemia and 64 acute lymphoblastic leukemia) received allogeneic bone marrow from their HLA-identical sibling. The probability of LFS at 60 months is 41% for AML patients and 39% for ALL patients. A better LFS was documented in patients allografted in first CR compared to the patients treated in advanced stage of the disease. The overall relapse rate is 27% for AML patients and 45% for ALL patients. The relapse rate is higher for patients allografted in advanced stage of the disease (47 vs 26% at 60 months for AML and 55 vs 38% at 60 months for ALL). The incidence of moderate to severe acute GVHD is between 45-50% for both AML and ALL patients. Chronic GVHD was documented in 30% of AML patients and 38% of ALL patients. Transplant-related mortality for both AML and ALL is about 25%. Relapse and GVHD with or without infection are the main causes of death. These results confirmed that allogeneic BMT is very effective therapy for patients with acute leukemia, especially for patients transplanted in first CR.
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PMID:Allogeneic bone marrow transplantation for acute leukaemia--IGCI experience. International Group for Chemo-Immunotherapy. 880 7

Chronic graft-versus-host disease (GVHD) remains a difficult clinical problem to treat and manage. We have reviewed our treatment of 40 patients treated at a single institution with PUVA (ultraviolet irradiation and psoralen) over a 14 year period. Thirty-five patients were treated for refractory chronic GVHD and five patients were treated at presentation of high-risk chronic GVHD. Overall, 31 of 40 patients improved on PUVA treatment. Sixteen patients achieved a complete response to PUVA added to their GVHD regimen. Four of the 15 partial responders had complete resolution of cutaneous GVHD but persistence of other systemic manifestations. The remaining partial responders had at least a 50% improvement in GVHD. We have also used PUVA with a glass fiber extension to treat intra-oral GVHD. PUVA is well tolerated with a high rate of response in the skin and mild side effects except for three patients who had therapy discontinued after phototoxicity (burn).
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PMID:Treatment of chronic graft-versus-host disease with ultraviolet irradiation and psoralen (PUVA). 880 15

Allogeneic peripheral blood stem cell (PBSC) transplants from HLA-identical siblings were performed in 37 patients with advanced hematologic malignancies. Outcomes were compared to a historical group of 37 similar patients with advanced hematologic malignancies receiving bone marrow (BM) transplants from HLA-identical donors. The PBSC group and historical BM group were well matched for diagnosis, disease stage, age, and graft-versus-host disease (GVHD) prophylaxis. Patients received PBSC transplants between 1993 to 1995 while BM patients were treated between 1989 to 1994. Engraftment, measured by the time to reach a peripheral neutrophil count > 500/L and platelet count > 20,000/microL without transfusions, occurred on days 14 and 11 in the patients transplanted with PBSC compared to days 16 and 15 in the patients receiving BM (P = .00063, .00014). The PBSC group required a median of 8 U of red blood cells and 24 U of platelets compared to 17 U of red blood cells and 118 U of platelets for BM transplant recipients (P = .0005, .0001). The estimated risks of developing grades 2 to 4 acute GVHD were 37% for the PBSC group and 56% for the BM group (P = .18), while the estimated risks of grades 3 to 4 acute GVHD were 14% for the PBSC group and 33% for the BM group, P = .05). Chronic GVHD occurred in 7 of 18 evaluable patients receiving PBSC and 6 of 23 evaluable patients receiving BM, P = .5. The estimated risks of transplant-related mortality at 200 days were 27% versus 45% (P = .33) relapse were 70% versus 53% (P = .27) and of overall survival were 50% and 41% (P = .39) for patients transplanted with PBSC or BM, respectively. This retrospective comparison suggests that compared to marrow transplantation from HLA-identical donors, allogeneic PBSC transplantation from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of acute or chronic GVHD.
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PMID:Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation. 883 78

We have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLA-matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl-prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+ cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14 (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg had significantly accelerated neutrophil and platelet engraftment and this number of CD34+ cells would appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out of 36 evaluable patients, there was no significant difference between the standard- and poor-risk groups in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further evidence supporting the potential of PBSC to replace bone marrow as the major source of haemopoietic cells for allogeneic transplantation.
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PMID:Allogeneic peripheral blood stem cell transplantation for haematological malignancies--an analysis of kinetics of engraftment and GVHD risk. 901 25

Chronic graft-versus-host disease (GVHD) is thought to result from abnormalities of several cytokine regulations in vivo. We analyzed interleukin-5 (IL-5) production by peripheral lymphocytes in a patient showing hypereosinophilia associated with chronic GVHD after allogeneic bone marrow transplantation. IL-5 production by activated T-lymphocytes which are known to play a major role in chronic GVHD was upregulated when stimulated by PMA + ionomycin. Therefore, hypereosinophilia observed in our patient may be correlated with IL-5 production in donor T-lymphocytes.
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PMID:[Hypereosinophilia after allogeneic bone marrow transplantation. A possible role of IL-5 overproduction by donor T-cells chronic GVHD]. 909 65

The appropriate timing of bone marrow transplantation (BMT) for adults with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) is controversial. Although allogeneic transplantation results in a lower risk of disease recurrence than intensive chemotherapy alone, overall outcome following BMT may not be improved due to the higher incidence of therapy-related fatal complications, frequently as a result of the development of graft-versus-host disease (GVHD). Selective T-cell depletion of donor marrow can reduce the incidence of GVHD and thereby limit transplant-related toxicity. Herein we report the risk of GVHD, incidence of transplant related mortality (TRM), likelihood of disease relapse, and overall survival in adult patients undergoing BMT with CD6 depleted allogeneic marrow for acute leukemia in first remission. Forty-one consecutive allogeneic transplants were performed on patients with acute leukemia and high-risk features (28 AML, 13 ALL) using T12 monoclonal antibody and complement to remove CD6+ T cells from donor marrow. No pre- or posttransplant immune suppressive medications for GVHD prophylaxis were administered. The actuarial estimated risk of grade 2 to 4 acute GVHD was 15% in patients receiving HLA identical grafts. Chronic GVHD developed in five patients. The estimated risk of TRM for patients in first complete remission was 5% at Day +100 and 16% at 2 years. Fatalities attributable to infection with cytomegalovirus or Epstein-Barr virus occurred in only three patients. Estimated probabilities of relapse, overall survival, and event-free survival at 4 years were 25%, 71%, and 63%, respectively. No significant differences in GVHD, TRM, relapse rate, or survival was observed for patients with AML compared with those with ALL. Allogeneic transplantation with CD6 depleted bone marrow is effective in consolidating remissions of high-risk patients with acute leukemia in first remission without excessive toxicity.
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PMID:CD6-depleted allogeneic bone marrow transplantation for acute leukemia in first complete remission. 910 25

Chronic graft-versus-host disease (cGVHD) is a disease of immune dysregulation that resembles an autoimmune disease. It usually involves the skin, mucosal and serosal surfaces and, less commonly, the hematopoietic system. We report hemolytic anemia (HA) as the primary manifestation of de novo cGVHD in recipients of partially mismatched related donor transplants. Five of 40 eligible patients developed HA at a median of 168 days post-transplant. Recipients were mismatched for one to three major HLA antigens. Conditioning therapy consisted of total body irradiation, etoposide, Ara-C, cycle-phosphamide and steroids. GVHD prophylaxis included partial T cell depletion, using anti alpha/beta CD3 antibody (T10B9) and complement, in addition to post-transplant immunosuppression. At presentation, all patients were receiving cyclosporine with or without low-dose steroids. Along with a mean Hb of 7.1 g%, patients had an increased reticulocyte count, a mild raised lactic dehydrogenase and a positive Coombs' test (in 2/5 patients). Four patients had also demonstrated a decrease in platelet count. Treatment was initiated with high-dose steroids and intravenous gamma globulin and response was observed within 1 week. Awareness of this presentation of cGVHD and early therapeutic intervention can result in successful reversal of presumed immune-mediated red cell and platelet destruction.
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PMID:De novo chronic graft-versus-host disease presenting as hemolytic anemia following partially mismatched related donor bone marrow transplant . 913 74

Graft-versus-host disease (GVHD) occurs in a number of clinical settings. It is well recognized after bone marrow transplantation, an increasingly used therapeutic option for haematological disorders. Chronic GVHD, occurring at an interval greater than 100 days post-transplant, has many systemic manifestations, but it is the cutaneous manifestations which are most frequent and often most troubling to the patients. In this review article, the wide spectrum of cutaneous chronic GVHD (including involvement of hair, nails and mucosae), and its complications and associations are discussed. The clinical and histological features and management guidelines are presented to assist the dermatologist with diagnosis and treatment of this condition.
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PMID:Cutaneous manifestations of chronic graft-versus-host disease. 915 58

The PML (for 'ProMyelocytic Leukemia') gene product is a nuclear zinc finger protein, identified when the chromosomal translocation fusing this gene to the retinoic acid receptor was found in acute promyelocytic leukemia. Recently, a frequent occurrence of autoantibodies against the PML protein was detected in primary biliary cirrhosis (PBC) sera, suggesting that this protein could represent an autoantigenic trigger in PBC. Chronic GVHD features are close to those of PBC and in addition, antinuclear and antinucleolar antibodies are frequently detected in patients' sera. In order to determine if an abnormal expression of PML, followed by the development of anti-PML antibodies, can be implicated in chronic GVHD pathogenesis, we studied the expression of PML in the skin of seven patients with chronic GVHD as well as the presence of circulating anti-PML antibodies. PML was highly expressed by the lesional skin keratinocytes, but circulating antibodies were never detected. PML is induced by interferon (IFN) gamma. The expression of PML by GVHD epidermis is likely secondary to the IFN gamma produced by infiltrating lymphocytes. Since PML display growth suppressor properties, the role of this protein in tissue lesions is discussed.
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PMID:PML is expressed in chronic graft-versus-host disease lesions. 919 56

We studied the outcome of BMT in 38 consecutive CML patients in CP1 who received transplants depleted of lymphocytes using counterflow centrifugation. In all patients the conditioning regimen was intensified by the addition of anthracyclines. Donors were HLA, MLC-identical siblings. Six patients (16%) died within 6 months. All 37 patients with a follow-up of more than 0.5 months engrafted and only one (3%) suffered from acute GVHD > or = grade 3. Chronic GVHD was evaluable in 33 patients and was extensive in six (18%). The projected 5-year probabilities of hematologic, cytogenetic and molecular relapse were 30% (95% confidence interval (CI), 10-49%), 35% (95% CI, 14-56%), and 34% (95% CI, 13-55%), respectively. The projected 5-year probability of survival was 68% (95% CI, 50-86%). Projected at 5 years, probabilities of leukemia-free survival (LFS) in hematologic, cytogenetic and molecular remission were 55% (95% CI, 37-73%), 51% (95% CI, 32-69%), and 51% (95% CI, 32-70%), respectively. All patients with relapse but one who relapsed in blastic phase were treated with retransplantation (n = 1) or with the infusion of lymphocytes (n = 6). Six patients regained second hematologic remission and five entered second cytogenetic and molecular remission. Including these patients, the probability of survival in first or second hematologic remission at the end of follow-up was 68% (95% CI, 50-86%). The probabilities of survival in first or second cytogenetic and molecular remission at the end of follow-up were both 61% (95% CI, 42-80%). We advocate revaluation of T cell depletion of donor marrow for patients with CML-CP1, especially for those at high risk of developing GVHD.
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PMID:Survival in first or second remission after lymphocyte-depleted transplantation for Philadelphia chromosome-positive CML in first chronic phase. 920 14


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