Haploidentical Hematopoietic Stem Cell Transplantation of Sex-Matched Donor-Recipient Pair Has Survival Advantage: A Single-Center Study of 440 Cases

Abstract 228

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an important alternative option for patients with hematological malignancies who need urgent transplant but without HLA matched either sibling or unrelated donor (Dao-Pei Lu et al., Blood 2006; 107:3065). Each patient usually has several haploidentical family members who could be selected as a donor. To determine the principal of donor selection among all available related haploidentical candidates, the clinical outcomes of a large series of haplo-HSCT in our hospital are analyzed. From April 2002 to April 2010, consecutive 440 patients with hematological malignancies who underwent haplo-HSCT were included. The median age of patients was 23 (3-59) years old. The diagnosis included AML (39.8%), ALL (35.9%), MDS (3.6%), CML (16.1%), and others (4.6%). Transplants at CR1 or CML-CP1, ≥CR2 or CML-CP2/AP, and advanced disease (refractory/relapsed acute leukemia or CML-BC) were 33.4%, 40.9% and 25.7%. HLA mismatched at 1, 2, 3 loci was 13.2 %, 27.5%, 59.3%, respectively. Transplants in sex-matched donor-recipient pair, female donor to male recipient, and male donor to female recipient were 55.1%, 33.0% and 13.9%. Major clinical characteristics among these three arms were similar. All patients received unmanipulated combined marrow and peripheral blood stem cells for transplant after BUCy2/CyTBI plus ATG conditioning. Fludarabine was substituted for cyclophosphamide in some patients due to impaired organ function. Prophylaxis and treatment of GVHD were reported previously. Steady hematopoietic reconstitution was seen in 98.6% of recipients. The cumulative incidences of grade II to IV acute GVHD and chronic GVHD were 32.6%, 61.3%, respectively. 100-day mortality was 10.5%. With the median follow-up of 32 (3-99) months, 2-year and 5-year overall survival (OS) rates for patients who were in different disease status were 57.9% and 52.9%. Univariate and multivariate analysis all showed that disease status before transplant, CD34⁺ cell dosage infused and sex-matched or not between donor and recipient but not HLA disparity and age were pivotal impact factors on survival. Two-year OS of transplants in sex-matched donor-recipient pair, female donor to male recipient, male donor to female recipient were 65.5%, 55.3%, 37.6, respectively (p=0.000). No significant differences were found on OS of transplants among haploidentical donors from sibling or parent or offspring or other relatives. In conclusion, our clinical results from a large series of transplants demonstrate that haplo-HSCT in sex-matched donor-recipient pair has survival advantage. Therefore, in haplo-HSCT, sex-matched donor should be the first choice, if not available, then female donor to male recipient could be the second option.