Reduced Cytokine Release Syndrome and Improved Outcomes with Earlier Immunosuppressive Therapy in Haploidentical Stem Cell Transplantation.

The optimal timing of immunosuppression and post-transplantation cyclophosphamide (PTCy) in haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is unknown. However, cytokine release syndrome (CRS) following haplo-HSCT is associated with worse transplantation outcomes, and the incidence of CRS may be affected by the timing of immunosuppression and PTCy. In this study, we compared CRS and other transplantation outcomes in 2 cohorts receiving different immunosuppression and PTCy schedules following haplo-HSCT. This was a retrospective cohort study of 91 patients who underwent haplo-HSCT at the Intermountain Health Blood and Marrow Transplant Program. The original or standard haplo-HSCT GVHD prophylaxis regimen included PTCy on days +3 and +4, with mycophenolate mofetil (MMF) and tacrolimus starting on day +5. The modified regimen adopted in November 2020 changed PTCy to days +3 and +5, with earlier introduction of tacrolimus and MMF, on day -1 and day 0, respectively. Grade ≥1 CRS occurred in 32% of patients in the modified regimen, in 82% of patients in the standard regimen (P <.0001), and 65% overall. Likewise, grade ≥2 CRS was lower with the modified regimen (16% versus 57%; P = .0002). The mean duration of CRS symptoms was longer with the standard regimen (3.14 days versus 1.44 days; P = .0003). The incidence of acute graft-versus-host disease grade III-IV or extensive chronic GVHD (cGVHD) at 1 year was lower in the modified regimen (6% versus 32%; P = .0068). No differences between the standard and modified regimens were seen in overall survival, relapse, or GVHD-free relapse-free survival (GRFS), although there appeared to be a trend toward improved GRFS with the modified regimen. Post hoc analysis comparing GRFS in patients with CRS and those without CRS found that CRS was associated with lower GRFS at 1 year (36% versus 63%; P = .0138). The duration of broad-spectrum antibiotic therapy was decreased by 7.5 days (P = .0017) and the time to hospital discharge was reduced by 7.1 days (P = .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.

Standardized Titration Protocol Reduces the Incidence of Paclitaxel Infusion-Related Hypersensitivity Reactions.

PURPOSE: Infusion-related hypersensitivity reactions with paclitaxel are common despite the use of dexamethasone and diphenhydramine premedications. Paclitaxel titration protocols that may reduce reactions are empirically derived from clinical observations, and there are no phase III trials that confirm superiority of any management recommendations. The purpose of this study was to compare the frequency and severity of hypersensitivity reactions associated with a recently initiated standardized paclitaxel titration protocol verses standard-of-care (SOC) infusion protocols. MATERIALS AND METHODS: This was a retrospective review of hypersensitivity reactions in patients receiving paclitaxel infusions at five ambulatory infusion centers using a standardized titration protocol (February 2021 to April 2021) versus SOC paclitaxel (November 2018 to December 2019). Patients were age 18 years or older and presented for their first or second infusions. The primary study measure was the rate of hypersensitivity reactions. Secondary evaluations included the timing of the reaction after the start of the infusion, use of premedications, and severity of reactions. RESULTS: A total of 451 patients were included in this study. Eighty-four (18.6%) patients were identified in the titration protocol group and 367 (81.4%) patients in the SOC group. Hypersensitivity reactions occurred in 4.8% of the titration group and 18.3% of the SOC group (odds ratio [OR], 0.224; 95% CI, 0.09 to 0.74; P = .002). Grade 3 or greater infusion reactions were 0% in the titration group versus 18% in the SOC group (OR, 0.28; P < .008). Reactions occurred later with the titration protocol, compared with the SOC paclitaxel infusion. Finally, no differences were observed in the use of appropriate premedications. CONCLUSION: A standardized paclitaxel titration protocol was associated with a significant reduction in the rate of infusion-related hypersensitivity reactions in patients receiving their first and second infusions. A prospective randomized trial is needed to validate these observations.