Cytokine release syndrome in adults with acute leukemia after allo-HCT with posttransplant cyclophosphamide prophylaxis.

Cytokine release syndrome (CRS) is a common complication following allogeneic hematopoietic cell transplantation (allo-HCT) with posttransplant cyclophosphamide (PTCy). However, its incidence, risk factors, and clinical significance remain incompletely characterized. We retrospectively analyzed 362 adult patients with acute leukemia in complete remission who underwent PTCy-based allo-HCT at a single center between 2020 and 2025. CRS was observed in 69 patients (19.1%); all cases were grade 1-2 by the 2019 ASTCT criteria. Incidence differed significantly by donor type: 39.5% in haploidentical, 15.4% in mismatched unrelated (MMUD), 8.0% in matched unrelated, and 1.4% in matched related donor recipients (p < 0.001). On multivariable analysis, CRS risk increased with HLA disparity versus matched donors (MMUD OR 2.92, p = 0.026; haploidentical OR 12.2, p < 0.001), and was higher with peripheral blood than bone marrow grafts (OR 3.59, p = 0.025). CRS was associated with higher incidence of grade II-IV acute graft-versus-host disease (aGVHD) (35 vs 18%, p = 0.002), while survival, non-relapse mortality, and relapse incidence did not differ significantly. Histological examination of CRS-associated cutaneous lesions demonstrated perivascular lymphocytic dermatitis without features of aGVHD. Ruxolitinib administration for extensive cutaneous involvement was associated with resolution of skin manifestations. HLA mismatch and peripheral blood grafts are associated with CRS, which may precede subsequent aGVHD.