# Influence of white blood cell count trajectories on the risk of differentiation syndrome during induction therapy with all-trans-retinoic acid and arsenic trioxide in pediatric acute promyelocytic leukemia

## TL;DR

This study shows that changes in white blood cell counts during treatment can predict the risk of a serious complication in children with a type of leukemia.

## Contribution

The study identifies specific white blood cell trajectory patterns linked to increased risk of differentiation syndrome in pediatric APL patients.

## Key findings

- Four distinct white blood cell count trajectory classes were identified in pediatric APL patients.
- Patients with high-level increasing or low-level increasing WBC trajectories had significantly higher DS risk.
- Class 1 patients required more frequent transfusions during induction therapy.

## Abstract

This study aims to investigate the association between early dynamic trajectories of white blood cell (WBC) count and the risk of differentiation syndrome (DS) during induction therapy with All-trans-retinoic Acid (ATRA) combined with arsenic trioxide (ATO) in pediatric patients with acute promyelocytic leukemia (APL).

A retrospective cohort of pediatric APL patients treated with ATRA and ATO induction therapy between January 2016 and December 2024 is analyzed. Latent growth mixture modeling (LGMM) is employed to identify distinct WBC count trajectories over the first seven days of induction therapy. DS is diagnosed according to Frankel's criteria. Logistic regression analyses are performed to evaluate associations between WBC trajectory classes and the occurrence of DS, treatment-related complications, and transfusion requirements.

A total of 93 patients are included, with an overall incidence of DS of 40.9% during induction therapy. Four distinct WBC trajectory classes are identified: Class 1 (high-level increasing group), Class 2 (high-level decreasing group), Class 3 (persistently low-level group), and Class 4 (low-level increasing group). After adjustment for potential confounders, patients in Class 1 (OR: 11.37, 95% CI: 1.17–124.71) and Class 4 (OR: 8.34, 95% CI: 1.94–35.92) remain at significantly increased risk of DS compared to those in Class 3, while no significant difference in DS risk is observed between Class 2 and Class 3. Furthermore, patients in Class 1 require more frequent transfusion support, including red blood cells, platelets, and plasma (p < 0.001) during induction therapy.

The trajectory of WBC count during ATRA and ATO induction therapy may serve as an indicator for predicting the risk of DS in pediatric APL patients.