AUTHOR=Brandalise Silvia R. , Viana Marcos B. , Pinheiro Vitória R. P. , Mendonça Núbia , Lopes Luiz F. , Pereira Waldir V. , Lee Maria L. M. , Pontes Elitânia M. , Zouain-Figueiredo Gláucia P. , Azevedo Alita C. A. C. , Pimentel Nilma , Fernandes Maria Z. , Oliveira Hilda M. , Vianna Sônia R. , Scrideli Carlos A. , Werneck Fernando A. , Álvares Maria N. , Boldrini Érica , Loggetto Sandra R. , Bruniera Paula , Mastellaro Maria J. , Souza Eni M. , Araújo Rogério A. , Bandeira Flávia , Tan Doralice M. , Carvalho Nelson A. , Salgado Maria A. S. TITLE=Shorter Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia: The Experience of the Prospective, Randomized Brazilian GBTLI ALL-93 Protocol JOURNAL=Frontiers in Pediatrics VOLUME=4 YEAR=2016 URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2016.00110 DOI=10.3389/fped.2016.00110 ISSN=2296-2360 ABSTRACT=Aim

Maintenance 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).

Objective

To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs. 24 months duration.

Materials and methods

From 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.

Results

Fourteen 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.

Conclusion

Six-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.