Childhood acute lymphoblastic leukemia: Four years evaluation of protocols 2013 and 2016 in a single center in Indonesia, a lower‐middle‐income country

Abstract

Background The prognosis of childhood acute lymphoblastic leukemia (ALL) in Indonesia, a lower‐middle‐income country (LMIC), is lower than in high income countries (HICs). The Indonesian ALL2013 protocol resulted in too many toxic deaths (21%) and abandonments (11%). Therefore, we drafted an adapted protocol, ALL2016. Main changes: no anthracyclines in standard risk (SR), prednisone replaced dexamethasone at induction in high risk (HR), and anthracyclines and cyclophosphamide were rescheduled in HR. Procedure Patients (aged: 1–18 years) were stratified into SR and HR. HR was defined as age over 10 years, leucocyte count over 50 × 109/L, central nervous system (CNS) involvement, mediastinal mass, T‐cell phenotype, testicular involvement, or poor prednisone response. Results ALL2013 included 174 patients (106 SR and 68 HR) and ALL2016 188 (91 SR and 97 HR). Although the number of HR patients was significantly higher in ALL2016 (51.6% vs. 39.1%; p = .017), the outcome of ALL2016 improved over ALL2013 (4‐year‐probable overall survival (pOS) 60.1% vs. 50.0%; p = .042 and 4‐year‐probable event‐free survival (pEFS) 49.5% vs. 36.8%; p = .018). ALL2016 showed a nonsignificant advantage for SR patients (4‐year‐pEFS 56.0% vs. 47.2%; p = .220 and 4‐year‐pOS 70.3% vs. 61.3%; p = .166), but less toxic deaths (7% vs. 20%; p = .011). In HR group, the outcomes were significantly better in ALL2016 (4‐year‐pEFS 43.3% vs. 20.6%; p = .004; 4‐year‐pOS 50.5% vs. 32.4%; p = .014) especially due to less relapses (31% vs. 62%; p = .001). Isolated CNS relapses went down from 18 to 8% in HR (p = .010) and 11 to 5% in SR (p = .474). Both SR and HR showed lower numbers of abandonment in ALL2016 (6% vs. 14%; p = .039). Conclusions Overall ALL2016 results improved over ALL2013. Modest changes in protocol resulted in less initial toxicity and abandonments.

Survival and Treatment Outcomes of Childhood Acute Lymphoblastic Leukemia in a Low-Middle Income Country: A Single-Center Experience in West Java, Indonesia

“…High- risk patients had lower OS and EFS as mentioned in many previous studies due to poorer prognosis and more intensive therapy. 18,23 Most of the patients were in the high-risk stratification group. In addition to the high rate of relapse, the delay in patients getting diagnosed and receiving treatment may lead to further progressivity of leukemic cells requiring the administration of more intensive therapy.…”