Single Institution Experience with Haploidentical HSCT Using Ptcy for Pediatric Hematological Malignancies

Background: Haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) using post-transplant Cytoxan (PTCy) for graft vs host disease (GVHD) prophylaxis is a growing subtype amongst all HSCTs for high-risk acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), myelodysplastic syndromes (MDS), mixed phenotypic leukemias (MPAL) and lymphomas. We present here a single institution experience over ten years comparing three groups, namely Haplo-HSCT, matched related donor (MRD-HSCT) and unrelated donor (MUD-HSCT) transplants. Historically Haplo-HSCT was not preferred over MUD-HSCT due to concerns of GVHD and other treatment related complications including viral reactivations.

Objective: Our goal was to compare all three transplant cohorts with respect to overall survival (OS) outcomes, incidence of graft vs host disease (GVHD); treatment complications such as veno-occlusive disease and CMV reactivation.

Method: After IRB approval for a retrospective study, we reviewed patient charts for all transplants between July 2010 and June 2020. Total 105 patients who received allogeneic HSCT for various hematological malignancies were included in the review, ALL (n = 58); AML/MDS/CML (n = 40), MPAL (n =2) and lymphomas (n=5). The median age at the time of transplant was 13 years (0.7- 23.3 yrs.). Of these 42 patients had haploidentical donors, 34 patients had matched related and 29 had unrelated donors. Amongst the Haplo-HSCT cohort stem cell source was bone marrow (BM) (n = 31) and peripheral blood (PBSC) (n = 11) while the MRD-HSCT cohort had BM (n = 24) and PBSC (n = 10) and for the MUD-HSCT BM (n = 10), PBSC (n = 10) and cord blood (UCB) (n = 9).

Results: One-year overall survival was for the groups Haplo-HSCT, MRD-HSCT, MUD-HSCT, was 78.6%, 73.5% and 62% and respectively. Incidences of Acute GVHD (grades 1 and 2) were 42.9%, 5.9%, and 41.4%, respectively and Acute GVHD (grades 3 and 4) were 9.5%, 8.8% and 10.3% respectively. Chronic GVHD limited were 4.8%, 0% and 0% and respectively. Chronic GVHD extensive were 11.9%, 8.8% and 24.1% respectively. Veno-occlusive disease was diagnosed in 16.7%, 11.8% and 34.5% respectively. CMV reactivation was 28.6%, 17.6% and 44.8% respectively.

Conclusion: This single institution retrospective study suggests the potential of Haplo-HSCT as a curative treatment for high-risk hematological malignancies with comparable results to MRD-HSCT and potentially better outcomes than MUD-HSCT. It also highlights the

role of PTCy as a financially viable option for GVHD prophylaxis.

Chavan:CARE DX: Membership on an entity's Board of Directors or advisory committees. Huynh:Servier Pharmaceuticals: Research Funding.