Improved outcome of haploidentical transplantation in severe aplastic anemia using reduced-intensity fludarabine-based conditioning

// Wu Yamei 1, * , Luo Rongmu 2, * , Cao Yongbin 1 , Si Yingjian 2 , Li Xiaohong 1 , Zhang Xiaomei 2 , Yan Pei 1 , Du Zhenlan 2 , Wang Haitao 1 , Wang Jing 1 , Wang Bojing 1 , Wu Xiaoxiong 1 and Da Wanming 1, 2, 3 1 Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing 100048, China 2 Department of Hematology, Affiliated BaYi Children’s Hospital, PLA Army General Hospital, Beijing 100700, China 3 Department of Hematology, Chinese PLA General Hospital, Beijing 100853, China * These authors have contributed equally to this work and should be considered as co-first authors Correspondence to: Da Wanming, email: Dwanming@medmail.com.cn Wu Xiaoxiong, email: xiongwuxiao@sohu.com Keywords: haploidentical, hematopoietic stem cell transplantation, severe aplastic anemia, graft-versus-host disease, graft failure Received: March 13, 2017      Accepted: June 19, 2017      Published: July 31, 2017 ABSTRACT Significant improvements in hematopoietic stem cell transplantation (HSCT) with haploidentical family donors (HFD) have confirmed its therapeutic role in severe aplastic anemia (SAA) and led to the evolution of treatment algorithms. However, the optimal conditioning regimen for HFD-HSCT remains undefined, especially the dosage of cyclophosphamide (Cy). A total of 77 patients with SAA from two research centers, who received HFD-HSCT with reduced-intensity fludarabine + cyclophosphamide + thymoglobulin ± busulfan conditioning regimen plus third-party cells infusion were included in this study, of which 67 pairs had 4-5 loci mismatched. We were particularly interested in whether the dosage of Cy significantly impacted graft failure (GF) and overall survival (OS). All patients showed sustained hematopoietic engraftment without any increase in severe aGVHD and transplantation-related mortality (TRM). The incidences of grade II-IV aGVHD, grade III-IV aGVHD and extensive cGVHD were 18%, 10% and 7%, respectively. The probabilities of 1-year and 5-year OS were 93.1% and 87.9%, respectively. Furthermore, patient age 8×10 8 /kg and donor age <45 years were associated with better survival ( P =0.043, P =0.023, and P =0.037, respectively) and engraftment ( P =0.019, P =0.008, and P =0.001, respectively). Our findings indicated that SAA patients lack MSD benefited the most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen. Improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.