As a result of the COVID-19 pandemic, most centers performing allogeneic hematopoietic cell transplant (allo-HCT) have switched to the use of cryopreserved grafts. Previous investigators have suggested that cryopreserved allografts may heighten risk of nonengraftment. To date, no study has investigated the effect of cryopreservation of CD34-selected hematopoietic progenitor cells (CD34+HPC) used as the sole graft source.
We sought to evaluate outcomes after unrelated donor or matched sibling allo-HCT with cryopreserved CD34+HPC.
This was a single center analysis of adult patients with hematologic malignancies who underwent allo-HCT with cryopreserved CD34 selected allo-HCT grafts from 1/2010 to 6/2017. All patients received ablative conditioning and antirejection prophylaxis with rabbit ATG. GCSF-mobilized leukapheresis products underwent CD34 selection using the CliniMACS Reagent System. Cells were then cryopreserved in DMSO (final concentration 7.5%) to -90°C using a controlled rate freezing system before transfer to vapor phase liquid nitrogen storage. In internal validation, this method has shown 92% mean CD34+ viability and 99.7% mean CD34+ recovery. Engraftment was defined as the first of 3 consecutive days of ANC ≥ 0.5. Platelet recovery was recorded as the first of 7 consecutive days with platelet count ≥ 20 K/mcL without transfusion. Kaplan-Meier methodology was used to estimate OS/RFS, and cumulative incidence functions were used to estimate relapse, NRM, and acute GvHD.
A total of 64 patients received a cryopreserved CD34 selected graft. Median CD34+ cell count before cryopreservation was 6.6 × 10^6/kg (range 1.4-16.1) and median CD3+ count 2.0 × 10^3/kg (range 0-21.1). All patients were engrafted, at a median of 11 days post-HCT (range 8-14). One patient had poor graft function in the setting of CMV viremia, requiring CD34 selected boost on day 57. Median time to platelet recovery was 16 days (range 13-99). Comparing cryopreserved versus fresh grafts, estimated 2-year OS was 70% (58-83%, 95% CI) vs 62% (57-67%, 95% CI) with fresh grafts (HR 0.86, 0.54-1.35 95% CI, p = 0.5). The estimated 2-year RFS was 59% (48-74%, 95% CI) versus 56% (51-61%, 95% CI; HR 1.01, 0.68-1.51 95% CI, p > 0.9). Cumulative incidence of relapse at 2 years was 29% (17-41%, 95% CI) versus 23% (19-27%, 95% CI; p = 0.16), while cumulative incidence of NRM at 2 years was 17% (9-28%, 95% CI) versus 23% (19-28%, 95% CI; p = 0.24). Grade II-IV acute GvHD by day 100 cumulative incidence was 16% in cryopreserved (8-26%, 95% CI), and 16% (13-20%, 95% CI; p = 0.97) after fresh graft infusion. Moderate to severe chronic GvHD by day 365 occurred in only one recipient of a cryopreserved graft (2%).
In patients with hematologic malignancies who received cryopreserved allogeneic CD34+HPC, engraftment, GvHD, and survival outcomes were consistent with that seen in fresh allogeneic CD34+HPC grafts at our center. Our laboratory validation and clinical experience demonstrate the safety of our cryopreservation procedure for CD34 selected allografts.

Copyright © 2021. Published by Elsevier Inc.