Unmanipulated bone marrow transplantation from one-HLA locus mismatched siblings carries high transplant-related mortality in Chinese patients

Abstract

BACKGROUND AND OBJECTIVES. We compared the outcome of bone marrow transplantation (BMT) from HLA-identical siblings (MSD) and one HLA-locus mismatched siblings (PMSD) in Chinese patients with hematologic malignancies in terms of transplant-related mortality (TRM) and disease relapse to see whether PMSD can feasibly increase the availability of donors in our population. DESIGN AND METHODS. Medical records of patients who had received a BMT from sibling donors in the Queen Mary Hospital, Hong Kong, from March 1990 to February 2000 were reviewed (MSD 326, PMSD 20). Patients and their donors were matched for HLA-A, -B and DRB1 loci using standard serologic methods as well as polymerase chain reaction-sequence specific primers. All patients received standard anti-microbials and graft -versus host disease (GVHD) prophylaxis including cyclosporin A and a short course of methotrexate. RESULTS. A total of 346 BMT patients were analyzed of whom 326 and 20 patients had received transplants from matched and one locus mismatched siblings, respectively. Patients receiving BMT from PMSD had a significantly higher TRM than those receiving their BMT from MSD (p=0.0016). Six patients received BMT from HLA-DR PMSD: one died 2 months post-BMT as a result of post-transplantation-related lymphoproliferative disease. Fourteen patients received BMT from HLA-A or -B PMSD: 11 of these patients died after a median of 5.6 months (range 0.6-13.7 months) due to severe GVHD (n=5), graft failure (n=2), bleeding (n=1), leukemic relapse (n=2) and thrombotic thrombocytopenic purpura (n=1). Two out of the three survivors had primary graft failure: one of these two required infusion of back-up marrow and the other had autologous regeneration. Patients in the PMSD group were at greater risk of developing severe GVHD than their MSD-recipient counterparts (p<0.001). There was no significant difference in the probability of disease relapse between patients who received BMT from MSD or PMSD. INTERPRETATION AND CONCLUSIONS. BMT from PMSD (especially those with mismatches at HLA class I loci) carried a higher risk of TRM and morbidity than BMT from MSD in our population.