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Comparison Of Clinical Outcome Between HLA Allele Matched And 1-2 Alleles Disparity Unrelated Donor Bone Marrow Transplantation

Posted on:2003-11-21Degree:MasterType:Thesis
Country:ChinaCandidate:B LiangFull Text:PDF
GTID:2144360092490659Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of choice for a range of malignant and non-malignant hematologic diseases. Unfortunately, fewer than 30% of patients have a human leukocyte antigen (HLA)-matched sibling. Advances in our understanding of the HLA system and the development of large international donor registries are supporting the increasing use of unrelated donors as an alternative source of stem cells. Compared with genotypically HLA-identical bone marrow transplantation (BMT), grafting with unrelated donor (URD) is associated with higher mortality rate. Severe acute graft-versus-host disease (aGVHD) and graft failure are the main causes of transplant-related mortality (TRM) in this setting, and might be related to the degree of HLA incompatibility.Before 1998, HLA typing have included serological methods for HLA-A and -B locus and DNA-based typing for HLA-DRB1. However, the risk of aGVHD, graft failure and death remain higher among patients transplanted with HLA-identical URD-BMT than among those transplanted with HLA-identical siblings. The higher incidence of these complications in recipients of URD-BMT may be the result ofHLA allele and minor histocompatibility antigens (mHAgs) disparity. More recently, studies have been conducted in which HLA-A, -B, and -DR have been analysed at the allele level using DNA-based typing methods. With advances in the understanding of the HLA system, the outcome of URD-BMT have been improved. The clinical significance of HLA class I and II allele compatibility in patients receciving URD-BMT is not clear until now. To determine the impact of HLA class I and II allele disparities on patient outcome after URD-BMT, We compare the clinical outcome of HLA allele matched with 1-2 alleles disparity URD-BMT.ObjectiveTo compare the clinical outcome of HLA allele matched with 1-2 alleles disparity unrelated donor bone marrow transplantation (URD-BMT) and explore the impact of HLA class I and II allele disparities on patient outcome after URD-BMT.Materials and MethodsPatients39 patients received HLA allele matched URD-BMT and 21 patients received HLA 1-2 alleles disparity URD-BMT for acute leukemia , chronic myeloid leukemia and MDS in our hospital between November 1998 and December 2002. The patients with CML were in first chronic phase and the patients with acute leukemia were in fist or second remission.MethodsConditioning regimens were Bu16mg/kg plus CTX 120mg/kg, mycophenolatemofetil (MMF), CsA and MTX were given to prevent graft-versus-host-disease(aGVHD) . Continue intravenous drip of low dose heparin and prostaglandin Elwere given to prevent hepatic veno-occlusive disease (VOD), Ganciclovir was used toprevent CMV infection until the antigenemia turn to negative. The date of engraftment was defined as the first of 3 consecutive days when the absolute neutrophil count (ANC) was more than or equal to 0.5×109/L, Analysis of DNA short series repeated sequence polymorphism as the evidence of donor marrow engraftment . Acute GVHD was graded as I to IV according to Glucksberg's criteria. Patients who had evidence of engraftment were evaluable for acute GVHD. Transpant-related mortality (TRM) was defined as death resulting from any cause other than relapse. Relapse was defined by morphologic evidence of disease in the peripheral blood, marrow or extramedullary sites.StatisticsContinuous variables were compared by the Independent-Samples T Test. Differnces in distribution were compared by the Chi-square test or Fisher's exact test if appropriate. Kaplan-Meier methods were used to describe survival.ResultsPatients characteristicsThere are no significant differences between two groups in terms of patient age, donor age, diagnosis-transplant interval, number of courses of induction therapy of acute leukemia. There were more male patients in HLA allele matched group than 1 -2 alleles disparity group (P=0.038).Engraftment38 (97.4%) of HLA allele matched group and 18 (85.7%) of HLA 1-2 alle...
Keywords/Search Tags:bone marrow transplantation, Human leucocyte antigen, Acute graft versus host disease, Graft failure
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