COVID-19 and Stem Cell Graft Cryopreservation: What’s the Fuss About?

By Dr. Mehdi Hamadani, CIBMTR & Medical College of Wisconsin

The emergence of coronavirus disease 2019 (COVID-19) in Wuhan, China in December 2019 and its rapid evolution into a pandemic is a serious threat to the global social and economic order. This novel virus has caused a healthcare crisis, the likes of which, are not known to our generation. Many countries including the U.S. have imposed travel restrictions to curtail the spread of this infection. These restrictions unfortunately, have the unintended consequence of jeopardizing the reliable delivery of donor stem cell products to blood and marrow transplant centers. This combined with potentially reduced stem cell donor availability (due to infection, quarantine and constraints on travel to collection centers) directly impact a transplant center’s ability to infuse fresh donor-cells into intended hematopoietic cell transplant (HCT) recipients (on the scheduled day of transplantation).

Recognizing these challenges, the National Marrow Donor Program (NMDP) informed transplant centers that starting March 30, 2020, cryopreservation of unrelated donor grafts would be required prior to initiating conditioning on transplant recipients. Naturally, many transplant centers have instituted similar practices for HCT using cells from related donors. While a handful of published studies with small patient numbers, suggest no significant impact of graft cryopreservation on the outcomes of allogeneic HCT using conventional GVHD prophylaxis platforms (e.g. calcineurin inhibitor based), no data are available on whether this strategy is feasible for HCT using post-transplant cyclophosphamide (ptCY)-based GVHD prophylaxis.

Shortly after both the ASTCT & NMDP recommended cryopreservation of donor stem cells before starting transplant conditioning, CIBMTR was contacted by many transplant centers requesting data examining feasibility and safety of this approach in ptCY-based transplants. The CIBMTR leveraged its observational registry and statistical resources to prioritize an analysis evaluating the outcomes of patient undergoing ptCY-based allo-HCT, with either fresh or cryopreserved grafts, to inform clinical practice during the ongoing COVID-19 pandemic. This analysis (epublished in Biology of Blood and Marrow Transplantation) compared 274 patients undergoing allo-HCT from 2013-2018 with cryopreserved grafts and ptCY, with 1,080 propensity score matched controls receiving fresh grafts. The two cohorts (cryopreserved versus fresh) were similar in patient age, performance scores, diagnosis, DRI, HCT-CI, donor/graft source, and conditioning intensity. The data generated in this study were reassuring. Graft cryopreservation in ptCY-based allogeneic HCT was not associated with delayed hematopoietic recovery, increased risk of GVHD, transplant-related mortality, relapse, or overall mortality.

The study results, support using cryopreserved grafts for ptCY-based allogeneic HCT during the COVID-19 pandemic (and perhaps beyond). This effort, also underscores the importance of transplant registries like CIBMTR, for generating clinically relevant data to guide clinical practice (even during emergency situations, like the current pandemic).