Risk-adapted therapy for the management of cytokine release syndrome in children undergoing unmanipulated haploidentical stem cell transplantation.

Background: We aimed to describe an algorithm for the management of cytokine release syndrome (CRS) associated with haploidentical hematopoietic stem cell transplantation (haploSCT).
Patients and Methods: We performed a prospective study where children up to 18 years of age undergoing haploSCT with post-transplant cyclophosphamide from September 2014 to March 2020 were included. Supportive care included low-dose adrenaline, high-flow nasal cannula, and N-acetylcysteine (NAC). Methylprednisolone and tocilizumab were administered in the peri-engraftment phase for grade 2 CRS or one-log increase and grade 3 CRS or a two-log increase in ferritin, respectively.
Results: Data were analyzed in 135/148 children as 13 children died before engraftment due to sepsis. CRS was noted in 97% transplants (grade 1-74.1%, grade 2-15.6%, grade 3-6.7%, grade 4-1.4%). Grade 2 and above CRS was higher in non-malignant conditions (33% vs 13%, P-value .009). The percentage median rise in ferritin was 129%-grade 1, 171%-grade 2, and 344%-grade 3. Seven children received tocilizumab, and two of whom had ferritin values greater than 100 000 ng/mL with no mortality in this group. Low-dose adrenaline, high-flow nasal cannula, and ventilator support were needed in 13%, 10%, and 4%, respectively. Mortality in our cohort was 3/135 (2.2%), with two deaths due to sepsis and one due to grade 4 CRS.
Conclusions: A risk-stratified approach using steroids in grade 2 and tocilizumab in grade 3/4 in the setting of haploSCT with NAC infusion and early use of low-dose adrenaline and HFNC can help provide adequate control of CRS, thereby ensuring optimal outcomes and survival.
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