Cryopreservation of Peripheral Blood Stem Cells From Matched Related and Unrelated Donors Is Associated with Delayed Neutrophil and Platelet Engraftment but Does Not Influence Relapse-Free Survival
Authors: Medd Patrick G , Nagra Sandeep , Hollyman Daniel , Craddock Charles F. , Malladi Ram 
Published: October 2019

Abstract
Abstract 2998
Cryopreservation of peripheral blood stem cells (PBSC) for allogeneic transplantation (allo-SCT) has potential advantages including ensuring an adequate stem cell dose is available prior to commencing transplant conditioning and allowing more flexible transplant scheduling. Concerns that cryopreservation may impair engraftment have, however, limited its use. In addition, no published series have examined cryopreservation of matched unrelated donor (MUD) PBSC. In this study, we assessed engraftment and survival following allo-SCT using cryopreserved PBSC. Seventy-six allo-SCT using cryopreserved PBSC were assessed: 57 from HLA matched family donors and 19 from MUD where HLA allelic match was 10/10 (n=14) or 9/10 (n=5). Transplants were performed between 2004 and 2010. Indications for allo-SCT were myeloid malignancy (n=50) or lymphoid malignancy (n=26). Disease was early phase in 51 (67.1%) and late phase in 25 (32.9%) patients. Conditioning was myeloablative (MAC) in 27 and reduced intensity (RIC) in 49 patients, 49 patients received in vivo T cell depletion with alemtuzumab or anti-thymocyte globulin. Median follow-up (FU) of survivors was 41 months. Comparison was made against a broadly matched control group comprising 79 allo-SCT using fresh PBSC.
Cumulative incidence of neutrophil engraftment to >0.5 × 109/L at day 14 was (95% confidence interval (CI)) 73.3% (61.–82) vs 92.3% (83.4–96.5) for cryopreserved vs fresh PBSC respectively. Neutrophil engraftment was significantly delayed (P=0.00031, Log-rank test) in the cryopreserved group but neutrophil engraftment at day 30 was identical at 99% in both groups. Platelet (plt) engraftment to >50 × 109/L at day 14 was 27.6% (18.8–38.1) vs 58.9% (47.1–69) for cryopreserved vs fresh PBSC respectively, P<0.0001. Cumulative incidence of plt engraftment at day 30 was 72.3% (60.3–81.2) vs 96.2% (87.4–98.9) for cyropreserved and fresh PBSC respectively. In multivariate analysis delayed neutrophil engraftment was associated with cryopreservation (hazard ratio (HR)=1.59, 95% CI 1.2–2.13, P=0.0014), MAC (HR=1.67, 95%CI 1.22–2.3, P=0.0015) and lymphoid malignancy (HR=1.49, 95% CI 1.11–2, P=0.0077). Delayed plt engraftment was associated with cryopreservation (HR=2.17, 95% CI 1.49–3.13, P<0.0001) and related donor transplant (HR=1.46, 95% CI 1.05–2, P=0.025). Eight patients, 6 in the cryopreserved and 2 in the fresh PBSC group required CD34 selected PBSC ‘top-up’ for primary engraftment failure, 5 of whom (4 cryopreserved, 1 fresh) were alive at last follow-up. One patient in the fresh and none in the cryopreserved PBSC group experienced late secondary graft failure. Relapse-free survival at 2 years was 40.7% (30.4–54.4) vs 50.2% (39.6–63.6) P=0.42 for cryopreserved vs fresh PBSC respectively. There were no significant differences in relapse incidence, transplant-related mortality, incidence of grades II-IV acute graft-vs-host disease or extensive chronic GvHD between cryopreserved and fresh PBSC.
Whilst cryopreservation of PBSC for allo-SCT in both matched related and MUD allo-SCT is associated with significantly delayed neutrophil and platelet engraftment, only delayed platelet engraftment is likely to be of clinical significance. Survival was comparable to allo-SCT using fresh PBSC. In lieu of evidence from prospective trials, PBSC cryopreservation should be considered as an option in selected patients for whom its benefits outweigh the risks of delayed engraftment.

Disclosures:
Craddock: Celgene: Honoraria, Research Funding.