Haploidentical Peripheral Blood Stem Cell Transplantation Using Non-Myeloablative Conditioning With Post-Transplant Cyclophosphamide Regimen Is Safe and Is Associated With Very Encouraging Post-Transplant Outcomes
Authors: Bhamidipati Pavan Kumar , DiPersio John F. , Stokerl-Goldstein Keith , Uy Geoffrey L. , Westervelt Peter , Gao Feng , Vij Ravi , Schroeder Mark A. , Abboud Camille N. , Pusic Iskra , Manjappa Shivaprasad , Romee Rizwan 
Published: October 2019

Introduction
The availability of HLA matched donors remains a major obstacle for successful allogeneic hematotopoietic cell transplantation. The use of HLA-mismatched alternate donors such as cord blood and haploidentical donor stem cell sources have allowed for greater access for those patients who need an allo-HSCT but lack a suitable matched sibling or unrelated donor. Introduction of high dose cytoxan in the early post-transplant period has significantly improved the outcomes of patients undergoing haploidentical transplantation and has eliminated the need for expensive and labor-intensive ex-vivo T cell depletion. Encouraging results have been reported using this platform with bone marrow as the source of stem cells. However, there have been only limited reports using this transplant platform with G-CSF mobilized peripheral blood stem cells (PBSC) as a source of stem cells for haloidentical transplantation. Here we report the outcomes of 18 patients who underwent haploidentical transplant for hematological malignancies from single institution treated on the Hopkins non-meloablative conditioning regimen but with G-CSF mobilized PBSC as a source of stem cells from a haplo-identical family donor.

Patients and Methods
A total of 18 patients (median age 41 years, range 22-73 years, 11 males and 7 females) between July 2009 and June 2013 underwent haploidentical transplant at Washington University School of Medicine in St Louis using the Hopkins non-myeloablative conditioning regimen with post transplant cytoxan (fludarabine (30 mg/m2/day on days -6 to -2), cytoxan (14.5 mg/kg/day on days -6 and -5) and TBI (single dose at 200cGy on day -1) and all these patients received two doses of post-transplant cytoxan (50mg/kg on D+3 and D+4). G-CSF mobilized PBSC from parents (n=9) or siblings (9) were used as a graft source with median CD34+ cell dose of 5.0 x 106/kg and median CD3+ T cell dose of 19.7 x 107/kg. GVHD prophylaxis regimen included MMF plus tacrolimus (16/18 patients) or MTX plus tacrolimus (2/18 patients). Median follow-up of all patients was 251 (range 17-1174) days. Diagnoses included AML (n=12), ALL (n=2), NHL (n=2), CLL (n=1) and aplastic anemia (n=1). 7 out of 12 AML patients underwent transplant with active disease (not in remission) and 4/18 of these patients had prior history of allogeneic HCT.

Results
16 patients (89%) engrafted (> 95% donor chimerism), median time to neutrophil engraftment was 15 days (range: 12-28 days) and median time to platelet engraftment was 18 days (range: 11-40 days). None of these patients had secondary graft failure. 1-year overall survival (OS) for all patients was 62% and 100-day and 1-year non-relapse mortality (NRM) rates were 11% and 17% respectively. Both 1-year and 2-year relapse free survival (RFS) rates were 53%. Despite very high CD3+ T cell doses, cumulative incidence of grade II-IV aGVHD was 40.7% while grade III-IV aGvHD occurred in only 3 patients (17%). Cumulative incidence of cGVHD at 1 and 2 years were both at 8% (extensive in only 1 patient). CMV reactivation occurred in 11 patients (61%) but did not significantly impact their survival or relapse rates and none of these patients developed CMV disease.

Conclusions
Here we report the outcomes of 18 patients with hematologic malignancies or marrow failure states undergoing haploidentical transplant using the published Hopkins NMA conditioning platform with post-transplant high dose cytoxan and with G-CSF mobilized PBSC as a source of donor stem cells. In spite of the limited numbers of patients transplanted, our results suggest that this approach is both safe and effective and associated with rapid multilineage engraftment, low rates of both aGvHD and cGvHD and encouraging overall and disease-free survival rates and low rates of NRM. Based on these results, 1) G-CSF mobilized PBSC from haploidentical donors should be considered as an alternative source of haploidentical stem cells to BM and 2) future randomized trials using this platform to test the role of haploidential G-CSF mobilized PBSC with other unrelated donor stem cell sources (cord blood and matched unrelated could also be considered in the future.

Disclosures:
Abboud: Alexion: Honoraria; Ariad: Honoraria; Novartis: Honoraria; Teva: Speakers Bureau.