Effect of Stem Cell Cryopreservation on Day 60 Donor Chimerism in Unrelated Donor Allogeneic Stem Cell Transplantation using Reduced Intensity Conditioning and ATG-based GVHD Prophylaxis.

Background

Cryopreservation of hematopoietic stem cell grafts has become more widely adopted. The impact of cryopreservation on clinical outcomes remains ambiguous with existing studies limited by retrospective designs, and heterogeneity in transplant protocol. The implications of cryopreservation of grafts on donor chimerism is also not well researched.

Methods

We retrospectively analysed 154 adults undergoing unrelated donor allogeneic HCT with reduced-intensity conditioning and ATG-based GVHD prophylaxis. Patients received either cryopreserved (n=85) or fresh (n=69) peripheral blood stem cell grafts. Day +60 chimerism was performed in 83.5% (n=71) patients in the cryopreserved arm and 82.6% (n=57) patients in the non-cryopreserved arm). Primary endpoint was day +60 lineage-specific donor chimerism comparison between the two groups. Secondary endpoints included comparison of engraftment kinetics, GVHD, relapse, overall survival (OS), progression-free survival (PFS), and graft-versus-host disease-free relapse-free survival (GRFS).

Results

Cryopreserved grafts were associated with lower median day +60 CD3+ donor chimerism (89% vs 95.5%; p=0.03) while CD33+ chimerism was unaffected. Neutrophil (Median 18 vs 16 days; P<0.01) and platelet (Median 19 vs 17 days; P<0.01) engraftment were modestly delayed, and hospital stay was longer (Median 36 vs 31 days; P=0.01) for cryopreserved grafts. Rates of acute and chronic GVHD, relapse and non-relapse mortality were not different between the two groups. Survival outcomes, namely OS, PFS, and GRFS were also similar between groups. Multivariate analysis showed cryopreservation of stem cells was independently associated (OR - 2.39; 95% CI 1.08-5.30) with reduced likelihood of D+60 full (>95% on both lineages) donor chimerism (33.8% vs 54.4%; p=0.03).

Conclusions

Cryopreservation was associated with modestly lower early donor CD3+ chimerism and delayed engraftment but did not appear to affect relapse or survival in unrelated donor HCT with reduced-intensity conditioning and ATG-based GVHD prophylaxis. While larger studies looking specifically at impact of cryopreservation on donor chimerism are needed, our data supports the safe use of cryopreserved grafts in this setting.