Impact of Infused Peripheral Blood Stem Cell Parameters (Total Nucleated Cells, CD34+ Cells, CD3+ Cells and CFU-GM) on Transplant Outcome after Reduced Intensity Allogeneic HSCT.
Authors: Michallet Mauricette , Le Quoc-Hung , Thiebaut Anne , Ducastelle Sophie , Raus Nicole , Revesz Daniela , Troncy Jacques , Chelgoum Youcef , Bourgeot Jean-Paul , Dubost Philippe , Hequet Olivier , Nicolini Franck E. 
Published: October 2019

This study concerns the impact of infused PBSC parameters [total nucleated cells (TNC), CD34+ cells, CFU-GM and CD3+ cells] associated with the other pre-transplant variables on the transplant outcome after allogeneic reduced intensity conditioning hematopoietic stem cell transplantation (HSCT). There were 95 patients, 58 males and 37 females with a median age of 53 years (27–66.5). The diagnosis pre-transplant were 21 AML, 1 ALL, 8 CML or MPS, 10 CLL, 16 MDS, 9 NHL, 3 HD, 27 MM. The disease status pre-transplant were 29 CR, 38 PR, 10 stable disease (SD) and 18 progressive disease (PD) and we defined a low risk subgroup of 38 patients (40%) including all diseases in CR1 and MM in CR, PR1 or PR2. For conditioning, 31 patients received an association of Fludarabine and TBI, 54 Fludarabine, Busulfan and ATG (FBA) (ATG 2.5mg/kg:15, ATG 5mg/kg: 27, ATG 7.5–12.5mg/kg:12) and 10 received other associations. All patients received PBSC from 93 HLA identical sibling donors and 2 from 1 antigen HLA mismatched related donors with donor median age of 52 years (29–73). Fifty-eight patients were sex mismatched (F/M:36, M/F:22), for CMV status: 26 pairs were negative, 38 positive and 31 mismatched and 28 patients presented an incompatibility ABO Rhesus with their donors. The patients received a median number of TNC 9.41× 108/Kg (2.6–25), CD34+ cells 6×106/Kg (1.2–64), CD3+ cells 262 ×106/Kg (32.8–761) and CFU-GM of 127×104/Kg (12–470). After transplant, 41 patients developed an acute GVHD ≥ grade II (II: 16, III: 10 and IV: 15) and 39 patients a chronic GVHD (15 limited, 24 extensive). With a median follow-up of 24.5 months, 43 patients have relapsed and 37 are alive. The probability of OS and EFS at 3 years was 35.4% [26–48] and 23% [15–35] respectively and the TRM at 1 year 24%. The results of the multivariate analysis using a Cox proportional hazard model and a logistic regression stepwise procedure are shown in the table 1. In conclusion, this study shows a significant impact of recipient age, low risk disease, sex mismatching, FBA 2.5mg/kg, CMV status and TNC and demonstrates among the infused PBSC parameters the very important role of the CFU-GM number on transplant outcome after RICT.

Table 1: Multivariate analysis OS EFS TRM AGVHD cGVHD Disease status pre-transplant, type of donor, type of conditioning, HLA matching, ABO matching: NS Recipient Age HR:1.09 (1.01–1.16) HR:1.19 (1.03–1.38) HR:0.91 (0.84–0.99) HR:0.91 (0.84–0.99) p=0.01 p=0.02 p=0.04 p=0.04 Sex Matching HR:0.16 (0.03–0.89) p=0.04 CMV Status HR:0.11 (0.01–0.9) HR:0.11 (0.01–0.9) p=0.04 p=0.04 Low risk Disease HR:0.13 (0.02–0.77) HR:0.02 (0.001–0.04) HR:0.02 (0.001–0.04) p=0.02 p=0.01 p=0.01 FBA 2.5mg/kg HR:6.46 (1.50–27.71) p=0.01 TNC HR:1.19 (1.06–1.35) p=0.03 CFU-GM HR:1 (0.98–1.14) HR:1.006 (1.002–1.01) HR:1.01 (1.001–1.02) HR:0.99 (0.98–1) p=0.03 p=0.004 p=0.02 p=0.05