Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation Using the Donors with the HLA-B*5801-TNFα -308A Haplotype Produced Higher Frequency of Untoward Effects in Acute Lymphocytic Leukemia Patients

Abstract 2002

In this study, we investigated the clinical characteristics of acute lymphoblastic leukemia (ALL) patients using sibling donors with HLA-B*5801-TNFα-308A haplotype (B5801-TNF2) for haploidentical or identical hematopoietic stem cell transplantation (HSCT). A total of 136 B-ALL cases and 29 T/NK-ALL cases were recruited. DNA samples from the patients and their siblings were assayed for genotyping of HLA and TNFα at -308 (rs1800629). B5801-TNF2 haplotype in donors was determined by analyzing TNFα -308 and HLA-B genotypes in patients and their family members. Outcomes within 2 years including overall mortality and non-relapse mortality, disease course and complications within 100 days were compared among patients using related donors with HLA-B*5801-TNFα-308A haplotype for haploidentical HSCT (B5801-TNF2+HID group), those using related donor without HLA-B*5801-TNFα-308A haplotype for haploidentical HSCT (B5801-TNF2-HID group), and those using related sibling either B5801-TNF2+ or B5801-TNF2- haplotype for identical HSCT (SID group). In the 165 sibling donors after HSCT, 35 were found to carry HLA-B*5801-TNFα-308A haplotype. There were 21 cases in B5801-TNF2+HID group, 100 cases in B5801-TNF2-HID group, and 44 cases in SID group. Compared patients in B5801-TNF2-HID and SID groups, patients in B5801-TNF2+HID group had higher overall mortality (adjusted P=0.039) and non-relapse mortality within 2 years (adjusted P=0.001), delayed platelet engraftment (adjusted P<0.0001), higher incidences of severe acute graft-versus-host disease (P=0.007), severe late onset hemorrhagic cystitis (P=0.002), blood stream infection (P=0.017), and invasive fungal disease (P=0.004) within 100 days. Therefore, sibling donors carrying HLA-B*5801-TNFα-308A haplotype for haploidentical HSCT caused higher mortality rate and higher frequency of severe complications in ALL recipients.