Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster I
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, Acute Myeloid Malignancies, AML, Diseases, Lymphoid Malignancies, Adverse Events, Myeloid Malignancies
Currently there is variability among donation and transplant centers around the practice of cryopreservation prior to allo-HSCT. With ongoing surges of COVID-19 and evolution of new variants, the risk of donors or recipients contracting COVID-19 leading to delays or disruptions in planned allo-HSCT remains high. In January 2022 with the rise of the Omicron variant of COVID-19, the NMDP reinstated the cryopreservation recommendation. Anecdotal reports indicate multiple recent instances of a planned URD testing positive for COVID-19 after conditioning chemotherapy had started but before stem cell harvest, raising the potential for severe deleterious outcomes in the intended transplant recipient.
Given the unremitting COVID-19 surges three years into the pandemic and continued uncertainty around longer-term survival and relapse rates of allo-HSCT using cryopreserved stem cells, we reanalyzed our prior cohort and added 116 additional patients (40 cryopreserved, 76 fresh) with at least 1-year follow up for a total of 141 and 279 patients receiving cryopreserved versus fresh (respectively) URD PBSCs between January 1, 2019, and July 31, 2021. The cohorts had similar baseline characteristics including donor/recipient age/sex, disease, and conditioning regimen/intensity. Patients receiving cryopreserved cells were more likely to receive post-transplant cyclophosphamide as part of the graft versus host disease (GVHD) prophylaxis regimen (24% vs 15%, p=0.015). Median follow-up time among survivors in this cohort was 22 months (range, 4-41 months). Two-year OS was not different in patients receiving fresh versus cryopreserved stem cells (63% vs 63%, p=0.73) (Figure 1A). Two-year PFS was also similar (57% for fresh, 52% for cryopreserved, p=0.27) (Figure 1A). Relapse (36% vs 30%, p=0.17) and NRM (12% vs 13%, p=0.79) at two years were comparable between patients receiving fresh versus cryopreserved stem cells (Figure 1B). In total, 8 patients died of COVID-19 in this cohort (4 fresh, 3 cryopreserved). Cumulative incidence of moderate/severe chronic GVHD (cGVHD) was higher in patients receiving fresh stem cells versus cryopreserved (24% vs 9%, p=0.0003). Whereas cryopreservation was associated with lower T-cell chimerism early after transplant, by 1-year post-transplant, T-cell chimerism was not different (2% vs 5% of fresh vs cryopreserved patients with T-cell chimerism <75% at 1 year, p=0.14). However, Day 30 T-cell chimerism <75% was associated with a reduction in OS and PFS regardless of cryopreservation of stem cells (data not shown).
As the COVID-19 pandemic continues with frequent surges in case numbers and rapid viral evolution, the risk for interruptions in life-saving allo-HSCT therapies remains high. Our data show that allo-HSCT with cryopreserved URD PBSCs results in similar OS, PFS, relapse rates, and NRM at 2 years post-transplantation. We found that cryopreservation is associated with lower 1-year cumulative incidence of moderate/severe cGVHD without compromise in OS. While this is an intriguing finding, larger multicenter analyses are needed to confirm these observations.
Disclosures: Cutler: Janssen: Consultancy; Incyte: Consultancy; Sanofi: Consultancy; Jazz: Consultancy; Deciphera: Consultancy; Editas: Consultancy; Pfizer: Consultancy; CareDx: Consultancy; Mallinckrodt: Consultancy; BMS: Consultancy; CTI BioPharma: Consultancy; Equilium: Consultancy; Cimeio: Current equity holder in private company; Omeros: Consultancy. Ritz: Equillium: Research Funding; Gadeta: Research Funding; Kite/Gilead: Research Funding; Oncternal: Research Funding; Novartis: Research Funding; Akron Biotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvroBio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Clade Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Draper: Consultancy, Membership on an entity's Board of Directors or advisory committees; Garuda Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; LifeVault Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Smart Immune: Consultancy, Membership on an entity's Board of Directors or advisory committees; Talaris Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; TScan Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shapiro: Miltenyi: Honoraria. Romee: Glycostem Therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; Skyline Therapeutics: Research Funding; Crispr Therapeutics: Research Funding; xNK therapeutics: Membership on an entity's Board of Directors or advisory committees, Other: Scientific Advisory Board; InnDura Therapeutics: Current equity holder in publicly-traded company. Wu: BioNTech: Current equity holder in publicly-traded company; Pharmacyclics: Research Funding. Nikiforow: Kite, a Gilead Compnay: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Soiffer: Be The Match/National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees; Juno: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy; VOR Biopharma: Consultancy; Jazz: Consultancy; Rheos Therapeutics: Consultancy; Alexion: Consultancy; Kiadis: Membership on an entity's Board of Directors or advisory committees.