Cord Blood Transplants Supported By Unrelated Donor CD34 Progenitor Cells
Authors: Gomez-Arteaga Alexandra , Guarneri Danielle , Gergis Usama , Hsu Jingmei , Mayer Sebastian A. , Phillips Adrienne A. , Shore Tsiporah B. , Van Besien Koen 
Published: October 2019

Abstract
Introduction: Umbilical cord blood (UCB) transplant supported by third party CD34-selected cells results in rapid count recovery, UCB mediated GVL effects and low rates of chronic GvHD. For patients lacking haplo-identical relatives, other sources of CD34 progenitors are needed.
Methods: We identified partially matched unrelated donors for patients lacking suitable haplo-identical donors -including second-degree relatives - and who otherwise were candidates for haplo-cord transplant. Most were treated on prospective studies (clinicaltrials.gov 00943800 and 01810588). For 5 patients, UCB were obtained through NCT01351545.
Results: Between 12/2014 to 7/2018 of 126 candidates for haplo-cord transplant, 26 (21%) had no suitable related donor. Most common reasons were: no first or second degree partially matched donors, ill or unavailable relative, high titers of HLA-antibodies against all relatives, or evidence of hematological familial hereditary syndrome. Diagnoses were: 16 AML/MDS, 5 ALL, 2 MPN, 1 NHL, 1 plasma cell leukemia and 1 SAA. Median age was 57 (24-75). 50% were women. 42% non-Hispanic white (NHW), 19% non-Hispanic blacks (NHB), 19% Hispanic, 8% other minorities. CIBMTR Disease Risk Index (DRI): 46% intermediate, 38% high and 8% very high. Median HCT-CI was 3.5 (25%-75% IQR 2-6). Conditioning: 16 Flu/Mel/TBI (94% 400cGray), 8 Flu/Mel,1 Flu/Cy, 1 Etoposide/TBI. All except 1 received ATG 4.5 mg/kg and all received post-transplant Tacrolimus and MMF. UCB matching was 4/8, 5/8, 6/8 or 7/8 HLA in 12%, 27%, 23%, and 38%, respectively. HLA matching for unrelated haplos was 5-6/12, 7-8/12, >9/ 12 HLA in 15%, 54% and 19%, respectively. For UCB, median cells collected were 2.1 (range1.1-4.0) ×107 TNC/kg. CD34 cell dose of unrelated donor graft was 3-5 ×106 CD34/kg. Median time to ANC engraftment was 11 days (range 9-35) and platelet engraftment was 18 days (range11-124). Chimerism on day 56 are shown in figure 1. There were three patients with graft failures: Pt #5 with complete graft rejection, autologous reconstitution, but ongoing clinical remission that persists to date (Day+ 1223); Pt #13 with graft failure and subsequent relapse, rescued with second UCB HSCT but died of progression of disease; and pt #18 who died from infectious complications after graft failure. Acute GvHD occurred in 35% of patients (4 Grade I-II, 4 Grade III, and 1 Grade IV). cGvHD was rare: One patient with mild severity and a second with severe lung involvement. After a median follow up of 209 days, 6 months cumulative incidence of relapse (CIR) was 16% and non-relapse mortality (NRM) was 20%. Median OS was 14 months (95%CI 7-27).
Conclusion: 20% of adults without matched related or unrelated donors, also lack suitable first or second degree haplo-identical donors. UCB transplant with partially matched unrelated donor accessory cells provides an alternative for transplantation. Engraftment is rapid, rates of acute GVHD are acceptable and incidence of chronic GVHD is very low. Prolonged survival is encouraging in this patient cohort with adverse characteristics and who would not be candidate for haplo-identical HSCT.

Disclosures
No relevant conflicts of interest to declare.