Search

Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL), especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58) and to the placebo arm (n = 52). Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8%) achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884) versus 270 (range: 14–25,480) × 109 cells/L (P > 0.01), greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07), clinical sepsis (50.0% versus 38.5%, P = 0.22), and death (18.9% versus 5.8%, P = 0.05).Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

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 × 10 9 /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., (© 2022 Wiley Periodicals LLC.)