Shorter Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia: The Experience of the Prospective, Randomized Brazilian GBTLI ALL-93 Protocol

Abstract

AimMaintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate with daily 6-mercaptopurine (6MP) constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in limited-income countries (LIC).ObjectiveTo compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs. 24 months duration.Materials and methodsFrom October 1993 to September 1999, 867 consecutive untreated ALL patients <18 years of age were treated according to the Brazilian Cooperative Group for Childhood ALL Treatment (GBTLI) ALL-93 protocol. Risk classification was based exclusively on patient’s age and leukocyte count (NCI risk group) and clinical extra medullary involvement of the disease. Data were analyzed by the intention-to-treat approach.ResultsFourteen patients (1.6%) were excluded: wrong diagnosis (n = 7) and previous corticosteroid (n = 7). Of the 853 eligible patients, 421 were randomly allocated, at study enrollment, to receive 18-month (group 1) and 432 to receive 24-month (group 2) maintenance therapy. Complete remission rate was achieved in 96% of the patients (817/853). Twenty-eight patients (3.4%) died during the induction phase. Thirty-four patients (4.0%) were lost to follow-up. The overall EFS was 66.1 ± 1.7% at 15 years. No difference was seen according to maintenance: EFS15y was 65.8 ± 2.3% (group 1) and 66.3 ± 2.3% (group 2; p = 0.79). No difference between regimens was detected after stratifying the analyses according to factors associated with adverse prognosis in this study (age group <1 year or >10 years and high WBC at diagnosis). Overall death in remission rate was 6.85% (56 patients). Deaths during maintenance were 13 in group 1 and 12 in group 2, all due to infection. Over 15 years of follow-up, two patients both from group 2 presented a second malignancy (Hodgkin’s disease and thyroid carcinoma) after 8.3 and 11 years off therapy, respectively.ConclusionSix-month reduction of maintenance therapy in ALL children treated according to the GBTLI ALL-93 protocol provided the same overall outcome as 2-year duration regimen.

Low Bioavailability and High Immunogenicity of a New Brand of E. coli l-Asparaginase with Active Host Contaminating Proteins

“…According to the last Brazilian cancer incidence data, approximately 3000 children (up to 19 years of age) are diagnosed with ALL annually ( Estimativa 2018, 2017 ). Brazilian children enrolled in prospective cooperative clinical trials achieve survival rates comparable to those reported by centres in Western Europe and North America ( Ribeiro et al, 2007 ; Möricke et al, 2010 ; Silverman et al, 2010 ; Hunger et al, 2012 ; Brandalise et al, 2010 , Brandalise et al, 2016 ). ALL treatment is based fundamentally on combination chemotherapy.…”

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

“…The referring physicians provided information about the demographic and clinical follow up data for the patients. Patients were not formally enrolled in treatment protocols, but were treated according to either the Brazilian Group for Treatment of Childhood Leukemia (GBTLI-ALL99) or the Berlin-Frankfurt-Munster ALL (BFM–ALL) backbone protocols (14, 15).…”

Outcome of childhood acute lymphoblastic leukemia treatment in a single center in Brazil: A survival analysis study

“…Laks et al published in 2003 that a probability of 5‐year OS was 56.5% in a cohort from Rio Grande do Sul 22 . The GBTLI ALL‐93 study showed a probability of 15‐year EFS of 53.8% in HR patients 19 . Lustosa de Sousa et al in 2015 described the results of a cohort from 3 hospitals in Ceará.…”