Cytokine release syndrome: implications for transplant outcomes in haploidentical and HLA-matched HSCT using PTCy

This study assessed 552 allogeneic hematopoietic cell transplantation (HCT) recipients with posttransplant cyclophosphamide (PTCy) to evaluate the incidence, characteristics, risk factors, and impact of early posttransplant cytokine release syndrome (CRS) on outcomes. The cohort included 36% matched sibling donors (MSD), 34% matched unrelated donors (MUD), 27% haploidentical donors, and 4% mismatched unrelated donors (MMUD). CRS was observed in 182 patients, with the highest incidence in haploidentical transplants (80%) compared to MMUD (32%), MUD (23%), and MSD (8%). Most CRS cases were mild, with 93% classified as grade 1 and 6% as grade 2, with only one severe case of grade 3. In haploidentical transplants, CRS was linked to a lower risk of severe chronic graft-versus-host disease (GVHD) and non-relapse mortality (NRM), leading to improved overall survival. In contrast, among HLA-matched recipients (MSD and MUD), there were no significant differences in outcomes between those with or without CRS. However, subgroup analysis revealed that CRS in patients with myeloid malignancies, including acute myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms, was associated with a reduced relapse rate, improving survival outcomes. In conclusion, while CRS is typically mild and short-lived, it significantly impacts survival, particularly in haploidentical transplants and HLA-matched patients with myeloid malignancies.