TY - JOUR
T1 - Childhood acute lymphoblastic leukemia
T2 - Four years evaluation of protocols 2013 and 2016 in a single center in Indonesia, a lower-middle-income country
AU - Sutaryo, Sutaryo
AU - Widjajanto, Pudjo Hagung
AU - Mulatsih, Sri
AU - Ardianto, Bambang
AU - Pangarso, Alexandra Widita Swipratami
AU - Supriyadi, Eddy
AU - Purwanto, Ignatius
AU - Adelin, Claudia Priska
AU - Lestari, Rahmadani Puji
AU - Sagoro, Lintang
AU - Christian, Scholastika Dita
AU - Sabrina, Dea Sella
AU - Verena, Natasha
AU - Kors, Wijnanda Adriana
AU - Kaspers, Gertjan J. L.
AU - Veerman, Anjo J. P.
AU - Hagung, Widjajanto Pudjo
AU - Sri, Mulatsih
AU - Bambang, Ardianto
AU - Swipratami, Pangarso Alexandra Widita
AU - Eddy, Supriyadi
AU - Ignatius, Purwanto
AU - Priska, Adelin Claudia
AU - Puji, Lestari Rahmadani
AU - Lintang, Sagoro
AU - Sella, Sabrina Dea
AU - Natasha, Verena
AU - Adriana, Kors Wijnanda
AU - Gertjan, J. L. Kaspers
AU - Anjo, J. P. Veerman
N1 - Funding Information: The authors would like to express their special appreciation to the reviewers for their valuable comments and critics, the medical staff, the children, and the families who were willing to be involved in our study. Publisher Copyright: © 2022 Wiley Periodicals LLC.
PY - 2022/11/1
Y1 - 2022/11/1
N2 - 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.
AB - 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.
KW - acute lymphoblastic leukemia
KW - lower-middle-income country
KW - protocol development
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85134269763&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/pbc.29875
DO - https://doi.org/10.1002/pbc.29875
M3 - Article
C2 - 35856702
SN - 1545-5009
VL - 69
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 11
M1 - e29875
ER -