Cytokine release syndrome in haploidentical stem cell transplant may impact T-cell recovery and relapse.

Cytokine release syndrome (CRS) following haploidentical hematopoietic cell transplantation (HCT) resembles the CRS after chimeric antigen receptor (CAR)-T therapy. We conducted this single-center retrospective study evaluating the association of post-haploidentical HCT CRS with clinical outcomes and immune reconstitution. One hundred sixty-nine patients who underwent haploidentical HCT between 2011 and 2020 were identified. Of these, 98 patients (58%) developed CRS after HCT. CRS was diagnosed based on the presence of fever within the first 5 days after HCT without evidence of infection or infusion reaction, and graded according to established criteria. The development of post-haploidentical HCT CRS was associated with a lower incidence of disease relapse (p=0.024) but with an increased risk of chronic GVHD (p=0.01). The association of CRS with a lower incidence of relapse was not confounded by graft source or disease diagnosis. Neither CD34 nor TNC dose was associated with CRS independently of graft type. In patients developing CRS, CD4+ Treg (p<0.0005), CD4+ Tcon (p<0.005) and CD8+ T-cells (p<0.005) were increased at 1 month following HCT compared to those who did not develop CRS, but not at later time points. The increase in CD4+ regulatory T cells at 1 month post HCT was most notable among patients with CRS who received a bone marrow graft (p<0.005). The development of post haploidentical HCT CRS is associated with a reduced incidence of disease relapse and with a transient effect on post HCT immune reconstitution of T cells and their subsets. Validation of these observations in a multicenter cohort is required.