Grade III-IV cytokine release syndrome is associated with inferior survival in patients undergoing haploidentical donor stem cell transplants.

Abstract

7546 Background: Haploidentical transplant (HIDT) with post-transplant cyclophosphamide (pCY) is being increasingly used because of the universal availability of donor and rapid graft acquisition time. Cytokine release syndrome (CRS) is one of the commonly occurring complications in this population. The information on the impact of CRS on the post-HIDT outcomes is limited. Methods: We retrospectively evaluated 91 patients who underwent HIDT between June 2012 and June 2019 for the onset and severity of CRS. CRS was graded per ASTCT guidelines. The primary objective was to compare RFS (relapse-free survival), NRM (non-relapse mortality), OS (overall survival) and GVHD in patients with no CRS, CRS grade 1-2 and 3-4. Results: All received peripheral blood stem cells and pCY/tacrolimus/mycophenolate as GVHD prophylaxis. Fifty-six (62%) received reduced intensity and 35 (38%) received full intensity conditioning regimen. Ten (10.9%) had no CRS, 74 (81.3%) developed grade 1-2 CRS and seven (7.7%) experienced grade 3-4 CRS. Median time to onset of CRS was one day post-transplant. The most common symptoms were fever (87%), fatigue (30%), nausea/vomiting (24%), rigors (24%), diarrhea (20%) and rash (11%). Fifteen (20%) with grade 1-2 and six (85%) with grade 3-4 CRS received tocilizumab. Day +100 cumulative incidence of grade III-IV acute GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 0%, 2.7%, and 14.3%, respectively (P = 0.36). One-year cumulative incidence of chronic GVHD for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 31.9% and 14.3%, respectively (P = 0.70). One-year NRM for no CRS, grade 1-2 and grade 3-4 CRS was 30%, 16.5%, and 57.1%, respectively (P = 0.002). One-year RFS for no CRS, grade 1-2 and grade 3-4 CRS was 48%, 63.4% and 28.6%, respectively (p = 0.03). OS at 1-year for no CRS, grade 1-2 and grade 3-4 CRS was 60%, 73.9%, and 28.6%, respectively (P = 0.008). Multivariable analysis revealed that grade 3-4 CRS was associated with significantly higher NRM (HR 5.54, P = 0.002), worse RFS (HR 3.41, P = 0.011) and worse OS (HR 4.91, P = 0.001). Conditioning regimen, degree of HLA match and disease risk index did not affect post-transplant outcomes and were not predictors for developing CRS. Conclusions: Our study showed that grade 3-4 CRS was associated with inferior post-transplant outcomes. However, no impact on acute or chronic GVHD was noted. Therefore, early recognition and prompt management of CRS may help improve outcomes.