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Risk‐adapted therapy for the management of cytokine release syndrome in children undergoing unmanipulated haploidentical stem cell transplantation
Author(s) -
Jayakumar Indira,
Uppuluri Ramya,
Lakshmanan Chidhambharam,
Kumar Gowdhaman Anand,
Vellaichamy Swaminathan Venkateswaran,
Raj Revathi
Publication year - 2021
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/petr.13964
Subject(s) - medicine , tocilizumab , cytokine release syndrome , transplantation , hematopoietic stem cell transplantation , nasal cannula , sepsis , prospective cohort study , ferritin , surgery , gastroenterology , cannula , covid-19 , disease , infectious disease (medical specialty)
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.