Clinical Outcomes of Haploidentical Donor Compared with Unrelated and HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation for Hematologic Malignancies
Authors: Luo Yi , Tan Yamin , Lai Xiaoyu , Zheng Weiyan , Shi Jimin , Zheng Gaofeng , Huang He 
Published: October 2019

Abstract
Abstract 4159

Introduction:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic option for hematologic malignancies. In clinical trials, a HLA-matched donor can only be found for about 50% to 60% of patients referred for HSCT which greatly limit the application of this important procedure. Haploidentical HSCT would increase the availability of donors for nearly 100% of patients. However, haploidentical HSCT may be associated with high risks of complications, such as graft rejection, severe GVHD and infection etc. Although great progress have been achieved in haploidentical HSCT based on advanced technologies and novel drugs, no study has simultaneously compared the outcomes of haploidentical, unrelated and HLA-matched related donor HSCT.

Materials and Methods:
In this study, 225 patients with hematologic malignancies received allo-HSCT from diffent donor sources in our center (69 with haploidentical donors, 62 with HLA-matched related donors and 94 with unrelated donors). The clinical outcomes of haploidentical HSCT cohort, unrelated donor HSCT cohort and HLA-matched related donor HSCT cohort were compared. In HLA-matched sibling and unrelated donor transplantation cohorts, patients received a same conditioning regimen consisting of intravenous busulfan 3.2 mg/kg/d on days –7 to –4, intravenous cyclophosphamide 60 mg/kg/d on days –3 to –2, and 250 mg/m2 of Me-CCNU orally on day -1. For haploidentical HSCT, conditioning regimen consisted of Ara-C (4 g/m2/d) on day -10 and -9, Bu (9.6mg/kg) on day -8, -7 and -6, Cy (1.8 g/m2/d) on day -5 and -4, Me-CCNU (250 mg/kg) on day -3, and ATG (2.5 mg/kg/d) on day -5 to -2. GVHD prophylaxis consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate while ATG (1.5 mg/kg/d) for three or four days, were added in HLA-matched or mismatched unrelated HSCT.

Results:
The patients receiving haploidentical HSCT experienced grades III-IV aGVHD more frequently than those receiving unrelated donor HSCT and related matched donor HSCT (24.4% vs 12% vs 2.6% respectively, p<0.05). However the incidence of cGVHD was comparable (17.8% in the haploidentical cohort vs 37.3% in the unrelated donor cohort vs 25.6% in the related matched donor cohort, p>0.05). The transplantation-related mortality (TRM) at d100 were 17.4%, 8.5% and 1.6% in the haploidentical, unrelated and related matched transplantation cohorts respectively (p<0.05). The 3-year relapse incidence were 10.1%, 15.9%, 17.7% in the haploidentical, unrelated and relate matched transplantation cohorts respectively (p>0.05). The 3- year overall survival (OS) was comparable in three cohorts (64.2±6.4% in the haploidentical cohort vs 67.5±5.3% in the unrelated donor cohort vs 77.5±5.8% in the related matched cohort, p>0.05).

Conclusion:
Although a higher incidence of aGVHD and TRM was observed in the haploidentical transplantation cohort, the incidences of cGVHD and relapse were comparable in the haploidentical, unrelated and related matched transplantation cohorts. Ultimately the patients receiving haploidentical transplantation achieved comparable OS with those receiving unrelated donor transplantation. An HLA-matched HSCT is commonly the preferred transplantation and donors from HLA-matched related siblings are usually the first choice. Haploidentical stem cell transplantation is relatively safe and efficient for patients who do not have HLA matched donors.

Disclosures:
No relevant conflicts of interest to declare.