reduced Cytokine Release Syndrome and improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplant

The optimal timing of immunosuppression and post-transplant cyclophosphamide (PTCy) in haploidentical stem cell transplant (haplo-HSCT) is not known. However, cytokine release syndrome (CRS) following haplo-HSCT is associated with worse transplant outcomes and the incidence of CRS may be affected by the timing of immunosuppression and PTCy. In this study, we compared CRS and other outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. In this study, we compared CRS and transplant outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. This is a retrospective cohort study of 91 patients who received haplo-HSCT at Intermountain Health Blood and Marrow Transplant Program. The original or standard haplo-HSCT GVHD prophylaxis regimen schedule included PTCy on days +3 and +4, with MMF and tacrolimus starting on day +5. The modified regimen adopted in November 2020, changed PTCy to days +3 and +5, with an earlier introduction of tacrolimus and MMF, starting on day -1 and 0 respectively. Grade ≥ 1 CRS occurred in 32% of patients in the modified regimen, 82% in standard regimen (P < 0.0001), and 65% overall. Likewise, grade ≥ 2 CRS was lower with the modified regimen, 16% vs 57% (P = 0.0002). Mean duration of CRS symptoms lasted longer with the standard regimen, 3.14 days vs 1.44 days (P = 0.0003). Incidence of acute graft-versus-host disease (aGVHD) grades III-IV or extensive chronic GVHD (cGVHD) at 1 year was lower in the modified regimen 6% vs 32% (P = 0.0068). No differences were found in overall survival, relapse, or GVHD-free relapse-free survival (GRFS), although there appeared to be a trend towards improved GRFS in the modified regimen. Post-hoc analysis comparing GRFS in patients with and without CRS found that CRS was associated with lower GRFS at 1 year, 36% vs 63% (P = 0.0138). Days of broad-spectrum antibiotic therapy decreased by 7.5 days (P = 0.0017) and days to hospital discharge was reduced by 7.1 days (P = 0.0241) with the modified regimen. This is the first analysis to evaluate and find a difference in CRS with early initiation of immunosuppressive therapy in haplo-HSCT. Our results suggest that this modified GVHD regimen benefits patients by reducing CRS and high grade GVHD compared to the standard PTCy-based GVHD prophylaxis regimen in haplo-HSCT. Additionally, this novel regimen did not appear to negatively impact outcomes.