Prediction Model to Evaluate Engraftment Kinetics Following Stem Cell Transplantation

Introduction: Early engraftment following allogeneic or autologous stem cell transplant (AlloSCT or AutoSCT) reduces the risk of morbidity, hospital stay and infection related mortality. Engraftment kinetics are determined by CD34 cell dose and dose of 2x106/kg is considered as minimum to safely perform AutoSCT. Higher doses of CD34 in AlloSCT may be associated with better outcome but increases the risk of cGVHD. There is limited information about safety to use CD34 dose below 4x106/kg in AlloSCT

Methods: Engraftment kinetics were analysed in 1056 patients (AlloSCT: 405, AutoSCT: 540, CART: 111) receiving cellular therapy from January 2017 to June 2024 to identify yearly trends in infused CD34 dose, time to engraftment, rate of delayed/failed engraftment and predictors of engraftment kinetics. Data were collected from apheresis data base, transplant database clinical records and hospital information system. Aim was

Results: Patient received AlloSCT [n=405, M/F:64%/36%, median age: 53 yr.]; AutoSCT [n=540, M/F: 64%/36%, median age: 59 yr.]; CART [n=111, M/F: 60%/40%, median age: 59 yr.]. Indication for AlloSCT was Ac. leukaemia (n= 223), Chr. Leukaemia (n=11), Lymphoma (n=65), MDS/MPN (n=89) and other (n=17). Indication for AutoSCT was myeloma (n=317), Lymphoma (n=190) and solid tumours (n=32). CART therapy was done for lymphoma (n=90, ALL/CLL (n=7/1) and solid tumours (n=11). Cell source for AlloSCT was PBSC (n=364), BM (n=6), cord blood (n=26) and CD34 top-up (n=9); for AutoSCT, PB (538) or CD34 top-up (n=2). For AlloSCT, conditioning was reduced intensity in 73%, Alemtuzumab/ATG was used in 64% and TBI was used in 22% (dose >6Gy in 54%). Median PBSC CD34 dose was 5.1 (range: 0.3-20.5) for AlloSCT and 3.3 (range: 1.95-26.7) for AutoSCT. For AutoSCT, CD34 dose was <2 (n=2), 2-4 (n= 337), 4-6 (n=116) or >6 (n=85) and for AlloSCT it was <2 (n=10), 2-4 (n=70), 4-6 (n=254) or >6 (n=38). 48 received cryopreserved AlloPBSC. Infused CD34 dose was similar over seven years. Time to neutrophil engraftment was 12d (4-84) for AutoSCT, 16d (0-132) for MUD, 18d (10-30) for haploSCT and 16d (10-129) for siblings. Time to platelet engraftment was 14d (0-389) for AutoSCT, 13d (0-321) for MUD, 25d (11-60) for haploSCT and 13d (0-129) for siblings. In CART, neutrophils and platelets recovered at a median of 12d and 27 days (neutrophils never below 0.5: 23; Platelets never below 50: 81). CD34 dose<2 showed trend towards longer time to neutrophil engraftment (23 d. vs. 16 d., p=0.07) for AlloSCT but not AutoSCT. There was no difference with increasing CD34 doses above 2. Time to platelet recovery in AlloSCT was longer with CD34 dose<2 (14 d. vs. 27d, p=0.034) but there was no difference with dose above or below 4. For AutoSCT increasing CD34 dose reduced time to platelet engraftment (2-4: 14d, 4-6: 13d, >6: 12d; p=0.0002). Cryopreserved AlloPBSC delayed neutrophil engraftment (18d vs. 16d, p=0.01). Incidence of delayed or failed engraftment was 2.0% for AutSCT and 9.9% for AlloSCT (Sibling: 11.9%, MUD: 9.7%, Haplo: 7.4%; p=0.77). Multivariate analysis identified four independent factors predictive of faster neutrophil engraftment in AlloSCT, reduced intensity conditioning (HR: 1.3, 95% CI: 1-1.8, p=0.04), use of Campath/ATG (HR:0.62, 95% CI: 0.44-0.84, p=0.003), CD34 dose>4 (HR: 0.8, 95% CI: 0.6-0.9, p=0.05) and non-cryopreserved cells (HR: 0.61, 95% CI: 0.46-0.82, p=0.001). Combining each risk factor identified three risk categories for neutrophil engraftment [0 RF: 15d. (4-89); 1-3 RF: 17d (0-132); 4 RF: 23d (15-46); HR:0.83, 95% CI: 0.75-0.91, p<0.001] and incidence of delayed engraftment (0 RF: 5.2%, 1-3 RF: 13.4%, 4 RF: 27.3%, p=0.006).

Conclusions: Risk of delayed engraftment is low in AutoSCT . CD34 dose above 2 seems to be optimum for safe AutoSCT . Neutrophil engraftment is not quicker in AlloSCT with CD34 doses higher than 2 but platelet engraftment is faster with CD34 dose of 4. Hence CD34 dose of 4 can be considered optimum for AlloSCT. The risk factors and the risk factor score identified in this analysis can be used to predict and avoid the risk of delayed engraftment.

Castleton:Pfizer: Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Kite/Gilead: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Abdulgawad:Kite/Gilead: Honoraria. Somervaille:CellCentric Ltd: Research Funding; Novartis: Consultancy; BMS: Consultancy; GSK: Consultancy; MSD: Consultancy. Searle:Shattuck Labs, Sanofi, BMS, DarkBlue Therapeutics: Consultancy; Janssen, Abbvie, Beigene, BMS, Nurix: Honoraria; Pfizer, Janssen, Jazz, Abbvie: Speakers Bureau.