Unmanipulated Haploidentical Transplant Followed By Post-Transplant Cyclophosphamide and Selective Ex Vivo T-Cell Depleted Haploidentical Transplant Results in Comparable Outcome As Unrelated Cord Blood Transplant for Adults with Haematological Malignancies- a Multicenter Study in Singapore

Background: Outcomes after haploidentical (Haplo) haematopoietic cell transplantation (HCT) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk haematological malignancies without human leukocyte antigen (HLA) matched related or unrelated donor. There is paucity of data comparing the outcome of UCBT and haplo HCT. We retrospectively analyse and compare the outcome of adult patients with haematological malignancies receiving UCBT and haplo HCT using two different platform for graft-versus-host disease (GVHD) prophylaxis: selective ex-vivo T cell (TCRαβ and CD45RA+) depleted haplo HCT (Koh LP et al. Blood 2018; 132: 2093a) vs unmanipulated T cell replete haplo HCT with high dose posttransplant cyclophosphamide (PTCy).

Methods: We studied 169 adults patients receiving allogeneic HCT using 4-6/6 HLA matched UCB (n=100) graft or Haplo (n=69) for various haematologic malignancies between Aug 2006 and July 2019, following myeloablative (MAC, n=76) or reduced intensity conditioning (RIC, N=93) regimen. 37 Haplo patients received unmanipulated non ex-vivo, T cell depleted graft followed by PT Cy for graft-versus-host disease (GVHD) prophylaxis (Haplo PTCy), whereas 32 patients received haplo-HCT with selective ex vivo T cell (TCRαβ and CD45RA+) depleted grafts for GVHD prophylaxis (Haplo-TCD).

Results: Two year overall survival (OS) for patients undergoing UCB, Haplo PTCy and Haplo-TCD transplant were 46%, 54% and 55% (p=0.379), and event free survival (EFS) were 41%, 50% and 45% (p=0.573), respectively; these were not significantly different among the 3 groups. Two year cumulative incidence (C.I.) of non-relapse mortality (UCB 32% vs Haplo PT Cy 20% vs 31%; p=0.514), relapse-related mortality (RRM) (UCB 24% vs Haplo PT Cy 21% vs 16%; p=0.596) and grades 3 - 4 acute GVHD at 6 months (UCB 9% vs Haplo PT Cy 6% vs 10%; p=0.758) were not significantly different among the 3 groups. However, C.I. of chronic GVHD at 2 years was higher in PTCy as compared with others (Haplo PT Cy 28% vs UCB 4% and Haplo TCD 5%, respectively, P<0.001). Multivariable analysis showed a significant association with OS and EFS for disease risk index (DRI) (p<0.001) and HCT comorbidity index (p<0.001), with no statistically significant impact from the type of stem cell graft used. In patients with low/intermediate risk DRI, the 2 year OS for TCD, PTCy and UCB were 71%, 55% and 56%, respectively (p=0.729), and the corresponding 2 year LFS were 59%, 54% and 48%, respectively (p=0.994). In patients with high/very high risk DRI, the 2 year OS for TCD, PTCy and UCB were 19 %, 51% and 18%, respectively (p=0.177), and the corresponding 2 year LFS were 0 %, 18% and 18%, respectively (p=0.774).

Conclusions: Haploidentical HCT using either unmanipulated graft and PTCy or selective Ex Vivo TCRαβ and CD45RA+ depleted graft results in equivalent outcome to those HCT performed using UCB. It provides additional alternative for patients lacking HLA matched donors.