Identifying causes of variability in outcomes in children with acute lymphoblastic leukemia treated in a resource‐rich developing country

Abstract

Background The outcome of children with acute lymphoblastic leukemia (ALL) in developing countries is less favorable than in developed countries, primarily due to resource constraints. However, it is unknown whether the therapeutic results differ. Thus, we hypothesized that outcomes in resource‐rich developing countries would be similar to those in industrialized regions. Procedure We performed a retrospective analysis of 224 consecutive children with ALL, who were treated according to the Children's Cancer Group (CCG) protocols between January 2001 and December 2007. High‐risk (HR) and standard‐risk (SR) patients were treated with modified CCG‐1961 and CCG‐1991 protocols, respectively. Modifications included substitution of dexamethasone for prednisone in HR patients and addition of two intrathecal methotrexate treatments for CNS2 patients during induction. All patients received double delayed intensification with two interim maintenance phases. Results Five‐year overall survival (OS), event‐free survival (EFS) and disease‐free survival (DFS) were 84.7 ± 2.4%, 77.0 ± 2.9%, and 81.4 ± 2.7%, respectively. Remission was achieved in 98.1% of the patients. Induction failure and relapse rates were 1.9% and 15.1%, respectively. Death as the first event occurred in 6.4% of cases, of which 2.7% and 3.7% involved deaths in induction and remission, respectively. Interestingly, a significant reduction in induction deaths was observed over time. Conclusions Despite the encouraging results observed in the present study, our patients displayed significantly lower survival outcomes compared to subjects treated in major clinical trials conducted by leading leukemia cooperative groups. Furthermore, this work underscores the need for targeted interventions to reduce death as the first event in developing regions. Pediatr Blood Cancer 2015;62:945–950. © 2014 Wiley Periodicals, Inc.

Cytogenetic Profile and FLT3 Gene Mutations of Childhood Acute Lymphoblastic Leukemia

“…Although the overall frequency of prognostically relevant, common genetic lesions (RUNX1-ETV6, E2A-PBX1, BCR-ABL1, MLL rearrangements, and hyperdiploidy) in our study is different from international, regional, and national studies, it has been found to be similar to those reported from most Western, regional, and local studies 17,22,30,31 regarding its impact on patient outcome. This is evident by a significantly worse survival outcome for the HR patients (71.3%) compared with (92.4%) for SR patients at 5 years ( P  < .001).…”

High-dose methotrexate vs. Capizzi methotrexate for the treatment of childhood T-cell acute lymphoblastic leukemia

“…Patients were treated using modified regimens based on the Children's Oncology Group (COG) experience ( Table 1 ) [3] , [9] , [10] . Modifications included the use of dexamethasone instead of prednisone, and extended intensification using double delayed intensification (DI-1 and DI-2) and double interim maintenance (IM) phases.…”

“…We evaluated children with T-ALL treated before and after the substitution of high dose methotrexate (HDMTX) for standard escalating Capizzi methotrexate (C-MTX) in the first interim maintenance phase (IM1). We hypothesized that the outcomes of patients with T-ALL treated with a modified Children's Oncology Group (COG) backbone protocol [3] , [9] , [10] that included double delayed intensification and interim-maintenance (IM1 and IM2) phases while incorporating HDMTX would have superior outcomes compared to C-MTX. The effect of patient gender, age, white blood cell count (WBC), CNS involvement, testicular involvement, slow early response and treatment type on patient outcome was evaluated.…”

Comparison of clinical trial versus non-clinical trial treatment outcomes of childhood acute lymphoblastic leukemia using comparable regimens

“…3 In the present study, SR patients were treated with CCG-1991 (regimen OD). 5 In contrast, 650 HR patients were treated on the increased intensity regimen (IPII) of the original CCG-1961 and received vincristine, prednisone, asparaginase, daunorubicin, and intrathecal methotrexate during induction and one (regimen C) or two (regimen D) delayed intensification phases. 4 In the present study, HR patients were treated on adapted CCG-1961 (regimen D) in which prednisone was replaced with dexamethasone.…”

“…4 In the present study, HR patients were treated on adapted CCG-1961 (regimen D) in which prednisone was replaced with dexamethasone. 5…”