HLA Allele Matched Unrelated Donor Stem Cell Transplant As First Line Therapy for Children with Acquired Severe Aplastic Anemia

From August 2000 to November 2011, 127 children under the age of 18 years with acquired severe aplastic anemia (SAA) received hematopoietic stem cell transplantation (HSCT) in one of the 10 Asia Pacific institutions of the VABMT Consortium, including 53 with matched sibling donor (MSD) and 74 with alternative donor (AD). Among these 74 AD, 22 were matched unrelated donor (MUD), 32 were mismatched unrelated donor (MMUD) and 20 were mismatched related donor (MMRD). Although the MSD group developed less grade II-IV acute GVHD compared to the AD group (14.3% vs 32.8%, P=0.029), there was no significant difference in grade III-IV GVHD (10.2% vs 12.5%, p=0.774) or chronic GVHD (19.6% vs 35.0%, p= 0.088). After a median follow-up of 33.5 months, the incidence of graft failure and 3-year overall survival were similar between the MSD and AD groups (15.1% vs 15.5%, P=0.658; 90.2% vs 82.1%, p=0.201; respectively). With an excellent outcome in MUD HSCT (95.5% 3-year survival), the survival rate of the matched donor group (MSD+MUD) collectively was much better than that of the mismatched group (MMRD+MMUD) (91.6% vs 76.1%, p=0.019). In univariate analysis, conditioning without radiation was the only risk factor for graft failure (p=0.045). Grades II-IV acute GVHD (p=0.013) and graft failure (p©‚0.001) were risk factors for poor survival. In multivariate analysis, only graft failure was significantly associated with survival probability (p= 0.012). Collectively, these data suggest that conditioning with radiation is important for engraftment and successful HSCT. MUD HSCTs are highly successful and may be considered a first line therapy in the absence of MSD.