TEMPORARY REMOVAL: Improving outcomes in Pediatric acute lymphoblastic leukemia with a uniform multicentric protocol (ICiCLe): experience from an Indian center

Although five-year survival of pediatric acute lymphoblastic leukemia (ALL) exceeds 90 % in high-income countries, outcomes in lower- and middle-income countries (LMICs), including India, remain sub-optimal due to treatment abandonment, undernutrition, and therapy-related toxicity. To address some of these disparities, the Indian Collaborative Childhood Leukemia (ICiCLe) group developed a multicentric, risk-adapted protocol. This retrospective, observational study from a single center evaluated outcomes of pediatric ALL patients treated before and after adopting the ICiCLe protocol. Patients were divided into two groups: those treated with various protocols (Group 1: 2013–2014), before initiation of ICiCLe protocol, and those treated with the ICiCLe protocol (Group 2: 2015–2022). Additional changes made during the implementation of the protocol included: outpatient management of febrile neutropenia, active patient-tracking during treatment, teleconsultation, and socio-economic support. Outcome parameters included disease-free survival (DFS), overall survival (OS), minimal residual disease (MRD) at end of induction, and predictors of survival. In this study, out of 471 patients, Group 2 (n = 356) had more high-risk patients than Group 1 (n = 115) i.e. 44.1 % vs 35.6 %; which is reflected in MRD positivity (21.1 % vs 9.1 %). Except for T-ALL patients, the remaining baseline characteristics were comparable for both groups. Three-year DFS and OS increased from 62.3 (51.4–71.4)% and 62.8 (53–71.2)% in Group 1 to 72.5 (66.3–77.8)% and 74.5 (68.6–79.5)% in Group 2, respectively. Predictors of improved survival included MRD response [HR = 2.16 (1.37–3.4), p = 0.001] and adherence to use of uniform protocol [HR = 0.64 (0.43–0.96), p = 0.033]. This study highlights the potential for standardized, resource-adapted protocols in LMICs to improve survival rates for pediatric ALL. Conclusions are limited by the retrospective observational nature of the study, and ongoing challenges remain ensuring equitable access, adherence, and affordability of care.