Lower middle-income countries face unique problems in the management of AML including delayed diagnosis and referral, severe socio-economic constraints(SSEC), and severe infections. We previously reported 10% induction-mortalities(IM) secondary to Multi-drug resistance organisms(MDRO) related sepsis or fungal pneumonia(FP) and 27% early treatment abandonment(ETA) from SSEC. With an aim to mitigate these adverse host-related factors(HFs), we offered oral metronomic chemotherapy(OMCT) as a bridge to intensive chemotherapy(IC).
Children ≤15-years of age with AML diagnosed between January-2014 and December-2017 were included. Baseline HFs screening included non-contrast Computerized-Tomography(NCCT) thorax and stool-surveillance culture. An assigned social-worker evaluated financial and supportive care needs. Patients with proven/probable FP and/or bacterial sepsis(Group-A), MDRO colonized(Group-B) or SSEC(Group-C), received group-specific interventions and initial OMCT [iOMCT: 4-weekly cycles of PrET (Prednisolone-40mg/m2, days 1-14(omitted for FP), Etoposide-50mg/m2qdand 6-TG-40mg/m2qd, days 1-21) till resolution and/or stabilization of HFs followed by IC-3+7(Anthracycline+Cytarabine) induction, 3-cycles of High-dose cytarabine(HIDAC), followed by maintenance-therapy(1year of OMCT). Response evaluation was by bone-marrow(BM) for morphology and minimal residual disease(MRD).
Of 180 AML patients in the study period, 95(53%)- Group-A=43, Group-B=24, Group-C=27, received a median of 1(Range:1-5)cycle of iOMCT. Eleven could not progress to IC, 9 from Group A(7-Deaths, 2-progression), and 2-ETAs from Group-C. By end of iOMCT, 19(20%) attained bone-marrow morphological remission(Blasts<5%) of whom 7(7%) were BM-MRD<0.01% after a median of 1(Range:1-3)cycle. Seventy-two(86%) of 84 patients proceeding to IC attained BM-MRD<0.01% after 2-cycles. No relapsed/refractory patients could be transplanted. At a median follow-up of 25(Range:1-60)months, the 2-year Event-Free Survival and Overall Survival of patients who received iOMCT followed by IC(46.3±3.9% and 47.2±3.9% respectively) and patients who received IC upfront(52±5.6% and 53.3±5.6% respectively) were comparable.
The use of initial OMCT provides an opportunity to deliver intensive chemotherapy in patients who are at high-risk for induction mortality and early treatment abandonment, and mitigates adverse host-factors allowing outcomes comparable to those receiving standard of care.