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)

A radiation-free, non-myeloablative, myelosuppressive protocol, containing dibromomannitol and cytosine arabinoside, that remarkably reduced the frequency of transplant-related complications, such as veno-occlusive liver disease (VOLD), severe mucositis, bacterial sepsis, hemorrhagic cystitis, interstitial pneumonitis, has been applied in 19 CML patients, allotransplanted from identical siblings. Five patients were in accelerated phase. Acute GVHD developed in two patients and chronic GVHD occurred in 66% of patients. Follow-up was 3 to 7 1/2 years. Although only eight patients were under 30 years of age, and only two patients had a history of less than 1 year, the leukemia-free survival was 82%. There were four hematological relapses. The reduction in post-BMT complications has greatly enhanced quality of life. The nurses reported significant reduction of work-load. Savings in eliminating the need for irradiation, parenteral nutrition, and several antibiotics are also remarkable. The remarkable reduction of certain transplant-related complications shows some advantage against busulphan-preconditioning.
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PMID:Reduction in the frequency of transplant-related complications in patients with chronic myeloid leukemia undergoing BMT preconditioned with a new, non-myeloablative drug combination. 960 96

We report the case of a 55-year-old female who despite having developed extensive chronic graft-versus-host disease (GVHD), relapsed 35 months after a T cell-replete sibling donor bone marrow transplant for Philadelphia-positive chronic myeloid leukaemia (Ph CML). She achieved complete cytogenetic remission after discontinuation of cyclosporin A and administration of two low-dose donor leucocyte infusions (DLI 1 x 10(6) and 5 x 10(6) CD3+ cells/kg). Eighteen months after the first infusion she remains well and in complete cytogenetic remission with a normocellular marrow and no exacerbation of GVHD.
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PMID:Achievement of complete cytogenetic remission after two very low-dose donor leucocyte infusions in a patient with extensive cGVHD relapsing in accelerated phase post allogeneic BMT for CML. 961 92

Mitoxantrone (Mito) is presently used in an increasing number of malignancies including leukemias, breast carcinomas and solid tumors. With it has come increased incidence of post remission cytopenias and delayed engraftment following autologous bone marrow transplantation (ABMT). We evaluated engraftment in 18 patients who underwent allogeneic BMT (allo-BMT) following a preparative regimen that included high dose Mito (60 mg m2). Sixteen patients with malignant disease (AML 10, ALL 3, CML 2, MDS 1) and two with non-malignant disease (SCID 1, osteopetrosis 1) underwent non-T cell depleted allo-BMT. Fourteen patients with malignancies were transplanted at an advanced stage of disease while only two patients were standard risk patients. Of the 18 patients, 12 were females and six males, with a median age of 30.5 (0.3-48) years. Nine patients, (breast cancer 3, malignant lymphoma 4 and AML 2), who underwent ABMT following preparative regimens with comparable doses of Mito, served as controls. Engraftment following allo-BMT was normal and not statistically different from engraftment following ABMT. Five patients, who underwent allo-BMT, developed >grade II acute graft versus host disease (GVHD) and two developed chronic GVHD. After a median follow up of 28 (6-42) months, five patients are alive (one with disease). In summary, engraftment following high dose Mito and allo-BMT is not statistically different from engraftment following ABMT. Controlled studies with a larger group of standard risk patients are needed to elucidate the role of Mito in conditioning regimens pre-BMT.
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PMID:Engraftment following mitoxantrone (Mito) based conditioning for allogeneic bone marrow transplantation (allo-BMT). 961 12

Lymphocyte transfusion from the marrow donor (DLT) is well established as an effective therapy for relapse of CML post allogeneic BMT. Reports thus far have been mostly limited to patients who received DLT from a matched sibling donor. We compared the efficacy and toxicity of DLT in 30 patients who were treated with cells from their HLA-identical sibling (n = 18) or from their phenotypically HLA-matched unrelated marrow donor (n = 12). The overall probability of obtaining a cytogenetic remission was 69% (95%CI: 51-83%) and was not significantly different between the two groups. The disease stage at the time of DLT was the only factor associated with cytogenetic remission by multivariate analysis; patients treated in cytogenetic or molecular relapse (n = 11) were seven times more likely (RR = 7.4, 95%CI: 2.4-22.4, P = 0.0005) to respond compared to patients treated for hematologic relapse (n = 19). There was a trend towards more acute GVHD II-IV in the unrelated donor group (58 vs 39%, P = 0.09), but the probability of developing extensive chronic GVHD was not significantly different (56 vs 39%, P = 0.4). We conclude that transfusion of donor cells from HLA-matched volunteer donors does not appreciably increase the risk of GVHD compared with transfusion of cells from HLA-identical siblings in patients with CML who relapse following allogeneic BMT. Conversely, there is no evidence for an increased graft-versus-leukemia effect after DLT from volunteer donors.
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PMID:Adoptive immunotherapy for relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: equal efficacy of lymphocytes from sibling and matched unrelated donors. 963 81

The risk of severe hepatic damage in patients with chronic hepatitis B virus (HBV) infection is well known; more effective treatments for this infection are needed. Lamivudine is being studied in immunocompetent and immunosuppressed HBV infected patients. We report a patient suffering from chronic replicative HBV infection after allogeneic BMT, who responded to lamivudine therapy. A 24-year-old woman with CML received an allogeneic BMT from her HLA-identical sister in June 1992. Before transplant, her HBV status demonstrated viral contact without active infection (HBsAb+, HBcAb+ IgG, HBeAb+). Four months after BMT mild chronic liver GVHD appeared, requiring immunosuppressive treatment. Antibodies to HBV completely disappeared post-transplant. Acute icteric hepatitis occurred 2 years later, with HBsAg+, high level of HBV-DNA, HBeAg+ and HBcAb IgM+. Lamivudine 100 mg/day rapidly reduced transaminase levels and effected HBV-DNA disappearance within 2 months. The treatment was well tolerated; no hematological side-effects occurred. This preliminary observation warrants further investigation of lamivudine treatment in bone marrow transplanted patients with active HBV infection.
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PMID:Lamivudine treatment for chronic replicative hepatitis B virus infection after allogeneic bone marrow transplantation. 967 62

The results of donor lymphocyte infusion (DLI) for treatment of relapse after bone marrow transplantation (BMT) are reviewed. Durable complete remission can be achieved at the molecular level for a majority (more than 70%) of patients with CML, when treated at early relapse. Results are less favourable for acute leukemias, although useful responses have been reported. Data are scarce though promising for myelodysplastic syndromes and multiple myeloma. Major treatment-associated toxicities are GVHD and bone marrow aplasia. The latter complication can be predicted by evaluating the level of residual donor-derived hematopoiesis. Modification of infused cells (CD8 negative selection or transduction with a suicide gene), addition of peripheral blood stem cells, and early implementation of escalating doses may counteract the complications and increase the response rate. Response rate is variably influenced by the presence of chronic GVHD after initial BMT, T-cell depleted BMT, underlying disease and stage at relapse, and the level of mixed chimerism. DLI is a direct demonstration of the graft-versus-leukemia effect (GVL). Because GVL after BMT is sometimes the predominant cause of cure, it may be advisable in such situations to redirect the conditioning regimens for BMT towards engraftment and less immediate cytotoxicity.
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PMID:Donor lymphocyte infusion for the treatment of relapse after allogeneic hematopoietic stem cell transplantation. 968 28

In this retrospective study, 23 recipients of peripheral blood progenitor cells (PBPC) were compared to 23 recipients of bone marrow (BM). The donors were 12 HLA-A-B-DR identical siblings and 11 HLA-A-B-DR identical unrelated donors in the PBPC and BM groups, respectively. Diagnoses in the PBPC group were CML seven, AML, nine, ALL three, lymphoma one, myeloma two and aspartylglucosaminuria (AGU) one. The median age was 40 (5-55) years. The BM group was matched for diagnosis, age, conditioning therapy, GVHD prophylaxis and G-CSF treatment after BMT. A higher number of MNC (P<0.001), CD34+ (P = 0.05), CD3+ (P<0.001) and CD56+ (P<0.001) cells in the graft, a reduced number of platelet transfusions (P = 0.03) and a significant hastening of neutrophil and platelet recovery were seen in the PBPC group compared to the BM group. In logistic regression analysis, the following factors were important for engraftment of ANC >0.5 x 10(9)/l: peripheral blood progenitor cell transplantation (PBPCT) (P = 0.003) and mononuclear cells (MNC) > or =2.5 x 10(8)/kg recipient in the graft (above median) (P = 0.009) in univariate analysis. For recovery of platelets >30 x 10(9)/l: PBPCT (P = 0.03) and HLA-identical sibling donors (P = 0.05) were significant in multivariate analysis. A trend towards a lower incidence of bacteremia was seen in the PBPC group, ie 22 vs 48% (P = 0.06) in the BM group. GVHD, TRM and survival did not differ between the two groups.
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PMID:Faster neutrophil and platelet engraftment, but no differences in acute GVHD or survival, using peripheral blood stem cells from related and unrelated donors, compared to bone marrow. 970 19

Marrow transplantation from unrelated donors has been linked with an increased risk of graft-versus-host disease (GVHD). In an attempt to lower the risk of acute GVHD we used CD34 marrow cell selection for T cell depletion. Since T cell depletion has been linked to an increased risk of relapse and an increased risk of marrow failure, we used PCR amplification of minisatellite sequences to investigate donor cell engraftment and RT-PCR amplification of recurrent chromosomal translocations to investigate the residual disease post-transplant. Twenty-three patients who underwent BMT after positive selection of the CD34-positive cell population were studied. Results were then compared with those of 37 patients who underwent transplantation with unmanipulated marrow graft. Among the 23 patients who received CD34+ selected cell grafts, seven (30%) had evidence of full donor engraftment, 14 had evidence of residual recipient cells (61%), one had a non-take, and one autologous bone marrow recovery. Analysis of the chimaerism status post-transplant in 36 patients who received unmanipulated marrow grafts showed that 31 patients (86%) had evidence of full donor engraftment. The difference in the incidence of mixed chimaerism profile between patients who received unmanipulated marrow graft and those receiving CD34+ selected cell grafts was statistically significant (P< 0.01). Nine patients who received CD34+ selected cell grafts could be analysed for the presence of minimal residual disease post-transplant (one with t(9;22) acute lymphoblastic leukaemia and eight with CML). In the patient transplanted for a Ph-positive acute leukaemia, and in two out of the eight patients with CML, the search fora fusion transcript was consistently negative after transplantation. Among the six patients with evidence of residual disease, three patients also had a mixed chimaerism profile and were given donor lymphocyte infusions. Minimal residual disease study was performed post-transplant in 16 patients who received unmanipulated marrow grafts. In 10 of 14 patients with CML, and in two patients with acute leukaemia the search for a fusion transcript was consistently negative after transplantation. The difference in the incidence of minimal residual disease between patients who received an unmanipulated marrow graft and those receiving CD34+ selected cell grafts was not statistically significantly significant, but numbers of patients included in this analysis are still few. In conclusion, our study highlights the strong influence of graft manipulation on the incidence of mixed chimaerism after transplantation from an unrelated donor.
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PMID:Influence of CD34 cell selection on the incidence of mixed chimaerism and minimal residual disease after allogeneic unrelated donor transplantation. 973 94

Ninety-five patients undergoing an allogeneic bone marrow transplant (BMT) and developing acute graft-versus-host disease (aGvHD) were randomized to receive low-dose intravenous 6-methylprednisolone (6MPred; 2 mg/kg /d; n = 47) or high-dose 6MPred (10 mg/kg/d; n = 48) for 5 days, with subsequent tapering doses. On day 5 patients not responding or progressing on low-dose 6MPred could be switched to high-dose 6MPred. All patients, aged 1 to 55 years, were recipients of unmanipulated BMT from HLA identical sibling donors. Patients were stratified at randomization for age (</>/= 20 years), disease (acute leukemia, chronic myeloid leukemia [CML], nonneoplastic disease), disease status (early/advanced), and GvHD prophylaxis (cyclosporin/cyclosporin + methotrexate). Primary endpoints were response to treatment and evolution of aGvHD to grade III-IV. Secondary endpoints were cytomegalovirus (CMV) infections, transplant-related mortality (TRM), and relapse. The median interval between BMT and treatment was 12 days (6 to 43). Results in the two groups (2 v 10 mg/kg) were as follows: response of aGvHD 68% versus 71% (P = .9), evolution to aGvHD grade III-IV 17% versus 20% (P = . 6), CMV infections 55% versus 60% (P = .7), 3-year actuarial TRM 28% versus 32% (P = .7), relapse 17% versus 7% (P = .1). The actuarial survival at 3 years was 63% versus 62% (P = .9) with a median follow up of 580 and 778 days. On day 5 of therapy, 26 patients assigned to low-dose (2 mg/kg) 6MPred were switched to a higher dose of 6MPred because of no response or progression. Their actuarial TRM was 46%, which is significantly higher than TRM of patients who responded on 2 mg/kg and continued with tapering doses (TRM = 16%, P = .007). In conclusion, early treatment of acute GvHD with 6MPred 10 mg/kg/d does not improve the response rate as compared with 2 mg/kg/d, nor does it prevent evolution to aGvHD grade III-IV. CMV infections, TRM, and survival were also comparable. A group of patients at high risk of TRM can be identified after 5 days of treatment with 6MPred 2 mg/kg and could be eligible for alternative forms of therapy.
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PMID:Early treatment of acute graft-versus-host disease with high- or low-dose 6-methylprednisolone: a multicenter randomized trial from the Italian Group for Bone Marrow Transplantation. 974 66

Donor lymphocyte infusions (DLI) are an effective treatment of leukemia relapse after allogeneic bone marrow transplantation. Undesired side-effects are the development of graft-versus-host disease (GVHD) and the occurrence of pancytopenia in some patients. In a pilot study, we investigated if unmanipulated G-CSF-mobilized peripheral blood stem cells which naturally contain large numbers of T lymphocytes (D-PBSC/LI) would be equally effective or even superior than DLI in generating a graft-versus-leukemia reaction (GVL) but could mitigate or prevent the development of pancytopenia. We treated 12 patients with CML chronic phase (n = 5), CML blast crisis (n = 2), AML (n = 2), ALL (n = 1), CLL (n = 1) and multiple myeloma (n = 1). In five patients with acute leukemia or CML blast crisis D-PBSC/LI followed intensive chemotherapy (group A), in seven patients D-PBSC/LI were given without any prior chemotherapy (group B). In group A two patients were evaluable for hematologic toxicity. Leukopenia <1000/microl lasted for 10 and 19 days, and thrombocytopenia <20,000/microl for 11 and 13 days, respectively. In group B leukopenia <1000/microl and thrombocytopenia <20,000/microl was observed in only one patient. Moderate cytopenia developed in four of five evaluable patients. A complete remission could be achieved in all seven patients with CML who all developed acute and/or chronic GVHD. None of the remaining five patients achieved a complete remission despite acute and/or chronic GVHD in two of them. Four patients died from disease progression, one patient from a secondary lymphoma, and one patient as a result of uncontrolled GVHD. In conclusion, D-PBSC/LI is effective in inducing GVL reaction but it does not prevent pancytopenia in each case. It remains unclear if it mitigates the incidence and severity of pancytopenia.
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PMID:Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. 975 47


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