Clinical Impact of Graft Cryopreservation on Allogeneic Stem Cell Transplantation: An Italian, Registry-Based Study on Behalf of the "Gruppo Italiano Per Il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare" (GITMO)

Abstract

The coronavirus disease 2019 (COVID-19) pandemic created major challenges for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Scientific societies and authorities recommended cryopreserving grafts before starting conditioning regimens, despite limited data on the clinical impact. The Italian Group for Bone Marrow Transplantation (GITMO) conducted a registry-based study involving 3492 patients who underwent allo-HSCT between March 2018 and September 2021. The cryopreserved cohort (n = 976) included patients who received cryopreserved grafts during the pandemic and was compared to the historical cohort (n = 2516). Graft cryopreservation was associated with a lower day 30 incidence of neutrophil and platelet engraftment (adjusted sHR = 0.8 and 0.7, p = 0.031 and p < 0.001, respectively) and delayed hematopoietic recovery. However, primary graft failure rates at day +30 were similar in the cryo and historical cohort (4% vs. 5%, respectively; p = 0.337), also after adjustment (RR = 1.19, p = 0.518). Day 100 incidence of grade II-IV acute GVHD was comparable between the two groups (adjusted sHR = 1.2, p = 0.194). Regarding chronic GVHD incidence, we found that it was higher in patients aged < 18 years in the cryo group (adjusted sHR = 3.9, p = 0.002), but lower in those aged 18-55 years (adjusted sHR = 0.7, p = 0.008). Cumulative incidence of relapse did not differ between historical and cryo cohort (adjusted sHR 1.0. p = 0.943), as well as non-relapse mortality (adjusted sHR 1.1, p = 0.196) and relapse-free survival (adjusted sHR = 1.1, p = 0.197). However, a shorter overall survival was observed in the cryopreserved group (adjusted HR = 1.2, p = 0.038). Transplant centers should carefully balance the benefits and drawbacks of cryopreservation in allo-HSCT.

Keywords: COVID‐19; cryopreservation; engraftment; graft versus host disease; hematopoietic stem cell transplantation.

FIGURE 1

Acute and chronic GVHD incidence in the two cohorts. (A) Cumulative incidence of grade 2–4 aGVHD: 30‐day cumulative incidence (CI) 9.6% (95% CI: 7.4–11.1) in cryo cohort versus 9.2% (95% CI: 8.1–10.4) in historical cohort, 100‐day CI 23.1% (20.5%–25.9%) and 20.3% (95% CI: 18.7–21.9), respectively; (B) Cumulative incidence of cGVHD: 1‐year CI 17.3% (95% CI: 14.9–19.7) in cryo cohort versus 19.5% (95% CI: 18–21.1) in historical cohort, 2‐year CI 22.2% (95% CI: 19.5–25) and 23.3% (95% CI: 21.6–24.9), respectively; (C) Cumulative incidence of cGVHD in patients aged < 18 years: 1‐year CI 30% (95% CI: 18.7%–42.1%) in cryo cohort versus 7.2% (95% CI: 4.5%–10.7%) in historical cohort and 2‐year CI 33.6% (95% CI: 20.9%–46.8%) in cryo cohort versus 9.1% (95% CI: 6%–13%) in historical cohort; (D) Cumulative incidence of cGVHD in patients aged 18–55 years: 1‐year CI 15% (95% CI: 11.8%–18.5%) in cryo cohort versus 21.3% (95% CI: 19%–23.8%) in historical cohort and 2‐year CI 20.5% (95% CI: 16.6%–24.6%) in cryo cohort versus 25.3% (95% CI: 22.8%–27.8%) in historical cohort; (E) Cumulative incidence of cGVHD patients aged > 55 years: 1‐year CI: 17.9% (95% CI: 14.5%–21.5%) in cryo cohort versus 20.7% (95% CI: 18.4%–23.2%) in historical cohort and 2‐year CI 22.4% (95% CI: 18.6%–26.4%) in cryo cohort versus 24.7% (95% CI: 22.1%–27.3%) in historical cohort. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2

Post‐transplant outcomes incidence in the two cohorts. (A) Cumulative incidence of relapse: 1‐year CI 19.5% (95% CI: 17.0%–22.1%) in cryo cohort and 19.5% (17.9%–21.0%) in historical cohort; 2‐year CI 24.8% (95% CI: 21.9%–27.7%) in cryo cohort and 24.6% (95% CI: 22.9%–26.3%) in historical cohort; (B) Non‐relapse mortality: 1‐year CI 18.9% (95% CI: 16.5–21.5) in cryo cohort versus 16.3% (95% CI: 14.8–17.8) in historical cohort, 2‐year CI 22.9% (95% CI: 20.225.8) versus 19% (95% CI: 17.5–20‐6), respectively; (C) Relapse‐free survival: At 1 year 61.9% (95% CI: 58.7–64.9) in cryo cohort versus 64% (95% CI: 62.1 65.8) in historical cohort; at 2 years 53.2% (95% CI: 49.8–56.5) versus 56.7% (95% CI: 54.7–58.6), respectively; (D) Overall survival: At 1 year 72% (95% CI: 69–74.8) in the cryo versus 73.3% (71.5–74.9) in the historical cohort; at 2 years 60% (95% CI: 57–63.7) versus 65% (95% CI: 63–66.8), respectively. [Color figure can be viewed at wileyonlinelibrary.com]