Complete Donor T-Cell Chimerism Predicts Lower Relapse Incidence after Standard Double Umbilical Cord Blood Reduced Intensity Conditioning Regimen Allogeneic Transplantation in Adults
Authors: Peterlin Pierre , Delaunay Jacques , Guillaume Thierry , Gastinne Thomas , Mahe Beatrice , Dubruille Viviane , Blin Nicolas , Le Bourgeois Amandine , Brissot Eolia , Lode Laurence , Le Gouill Steven , Moreau Philippe , Mohty Mohamad , Chevallier Patrice 
Published: November 2019

Double umbilical cord blood (dUCB) allogeneic transplantation following low dose TBI, cyclophosphamide and Fludarabine (TCF regimen)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there is little data regarding the impact on long-term outcome of CD3+ T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases and who receieved dUCB conditioned with TCF were included in this retrospective study. Peripheral blood CD3+ TCC was considered until day +100 post-tranplant in order to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3+ TCC, respectively, within the first 100 days post-transplant. With a median follow-up of 36 months, 3 year-OS, DFS, and relapse incidence were 61%, (95% CI 43-75); 50% (95% CI 32.5-66) and 28% (95% CI 16-44), respectively. In univariate analysis, a full CD3+ TCC was associated with a better 3-year DFS : 59% (95% CI 39-75.5) versus 14% (95% CI 7-46), (HR=0.24 [0.09-0.65], p=0.005) and a lower cumulative incidence of relapse : 24% (95% CI 21.5-57) versus 78% (95% CI 52-99), (HR=0.18 [0.05-0.5], p=0.004). In multivariate analysis, a full CD3+ TCC remained associated with a lower incidence or relapse (HR=0.17, 95% CI 0.028-0.99, p=0.049). CD3+ TCC has no impact on GVHD and NRM in this study. In conclusion, in our study, full CD3+ TCC was independently associated with a lower risk of relapse after dUCB TCF RIC allogeneic transplant in adults, highlighting the need to develop immunotherapy approaches allowing for early conversion to full chimerism after dUCB.

Abstract 2479. Table 1 Patients, sustained cord blood and transplantation characteristics. Patients, sustained cord blood and transplantation characteristics Full TCC (n=29) Mixed TCC (n=7) p No.of patients % No.of patients % Patients characteristic Age at transplant, years, median (range) 57 (22-69) 47 (17-64) NS Sex female 14 48 3 43 NS Hematological malignancy : Lymphoid / myeloid 14 / 15 48 / 52 3 / 4 43 / 57 NS Statut at transplant : RC / RP 23 / 6 79 / 21 6 / 1 86 / 14 NS Time to transplant, days, median (range) 395 (137-5645) 216 (92-604) NS Cord blood characteristics Age of cord blood, months, median (range) 31 (9-165) 116 (23-140) NS Matching cordon with patient NS 4/6 10 35 3 43 5/6 19 65 3 43 6/6 0 0 1 14 Number of total nucleated cell 10^8/kg before and after thawing, respectively, median (range) 0,28 (0,16-0,455) ; 0,248 (0,157-0,406) 0,222 (0,135-0,492) ; 0,22 (0,11-0,392) NS Number of CD34+ cell 10^6/kg before and after thawing, respectively, median (range) 0,066 (0,022-0,215) ; 0,043 (0,02-0,2) 0,078 (0,031-0,427) ; 0,041 (0,019-0,259) NS Mismatch between cord blood and patient Sex 14 48 3 43 NS Serology CMV 13 45 3 43 NS ABO 16 55 2 28 NS Rhesus 22 76 6 86 NS Graft Neutrophil count recovery >0.5 G/L, days, median (range) 17 (6-32) 11 (7-20) NS Platellet recovery >20G/L, days, median (range) 41 (0-164) 31 (0-67) NS Acute GVHD (grade II-IV / grade III-IV) 19 (12 / 6) 65 (41 / 21) 4 (3 / 1) 57 (43 / 14) NS Chronic GVHD (Limited / Extensive) 11 (8 / 3) 38 (28 / 10) 3 (2 / 1) 43 (28 / 14) NS Chimerism Rate, %, median (range) 100 (96-100) 82 (14-94) <0,001

Table 2 Multivariate analysis for DFS, OS and CIR. Multivariate analysis Hazard Ratio 95% CI P values DFS Age (continuos variable) 0.97 0.93 to 1.01 0.174 Sex 0.37 0.10 to 1.26 0.111 TCC full versus mixed 0.28 0.074 to 1.04 0.058 Chronic GVHD : noversus yes 4.68 1.12 to 19.53 0.034 OS Age (continuous variable) 0.95 0.91 to 0.99 0.022 myeloid vs lymphoid 9.13 1.7 to 49.05 0.010 Acute GVHD : none vs grade 3-4 0.24 0.06 to 0.93 0.038 TCC full versus mixed 0.62 0.15 to 2.46 0.495 CIR Age (continuos variable) 0.95 0.91 to 1.00 0.057 Sex 0.88 0.15 to 5.26 0.892 TCC full versus mixed 0.17 0.028 to .99 0.049 Chronic GVHD : no versus yes 8.19 0.46 to 146.41 0.153

Disclosures

No relevant conflicts of interest to declare.