ABSTRACT
We analyzed the outcome of 25 consecutive patients with chronic hematological malignancy who underwent allogeneic stem-cell transplantation conditioned with fludarabine (30 mg/m2/day, thrice) and total body irradiation (2 Gy). All patients received peripheral blood stem cells from an HLA-identical sibling donor. With a median follow-up of 769 days (range, 244 - 1231), the estimated 2-year overall survival (OS), event-free survival (EFS), transplantation-related mortality and relapse rates were 53%, 45%, 27%, and 39%, respectively. All patients had initial engraftment. Acute Grade II - IV graft-versus-host disease (GVHD) was recorded in 14 patients (56%), including 7 (28%) with Grade III - IV GVHD. Sixteen of the 23 patients (70%) who survived more than 100 days developed chronic GVHD. OS and EFS were adversely influenced by acute Grade III - IV GVHD (p < 0.001 and p = 0.033, respectively), but chronic GVHD seemed to favorably influence these two parameters (p = 0.03 and p < 0.001, respectively). Patients with full-donor chimerism at day 30 had lower relapse rates, as did those who received high-dose allogeneic CD8+ lymphocytes with their graft (p = 0.026). Collectively, these results provide a framework for refining nonmyeloablative conditioning, to improve outcome with an acceptable risk of GVHD.
Subject(s)
Antineoplastic Agents/therapeutic use , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Transplantation Conditioning , Vidarabine/analogs & derivatives , Whole-Body Irradiation , Adult , Combined Modality Therapy , DNA (Cytosine-5-)-Methyltransferases/antagonists & inhibitors , Female , Graft vs Host Disease/therapy , Hematopoietic Stem Cells/drug effects , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Survival Rate , Transplantation Chimera , Transplantation, Homologous , Vidarabine/therapeutic useABSTRACT
Improvements in HLA-typing by DNA-based methods now allow accurate genotyping of unrelated bone marrow (UBM) donors and recipients and also definition of haplotypes. In this regard, B*5002 has been predicted in linkage disequilibrium with Cw*0602, DRB1*0406 and DQB1*0402 based on the frequency of allele coexistence. Here, we confirm this assumption by HLA genotyping of four informative families and three unrelated individuals. In the four families, the extended haplotype HLA-B*5002, -Cw*0602, -DRB1*0406, DQB1*0402 can be definitely assigned by the mode of heritance. Furthermore, this association of alleles was also found in the three B*5002 unrelated individuals. Knowledge of the frequent linkage disequilibrium of these rare alleles can improve UBM donor search strategies.
Subject(s)
Bone Marrow Transplantation/immunology , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DR Antigens/genetics , Family Health , Female , HLA-B Antigens/immunology , HLA-C Antigens/immunology , HLA-DQ Antigens/immunology , HLA-DQ beta-Chains , HLA-DR Antigens/immunology , HLA-DRB1 Chains , Haplotypes , Humans , Linkage Disequilibrium , Male , Tissue Donors , White People/geneticsSubject(s)
Alleles , HLA-DR Antigens/genetics , Base Sequence , HLA-DRB1 Chains , Humans , Molecular Sequence Data , Polymerase Chain ReactionABSTRACT
Using sequence-specific amplifications, a practical and fast technique for DRB and DQB typing has been developed. The primers are chosen in order to amplify groups of alleles corresponding to the same serological specificity. In a second step, precise allelic determination is obtained by studying the restriction fragment length polymorphism of the PCR products. The experience of three laboratories using this technique in the context of organ or bone marrow transplantation is reported.
