RESUMEN
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.
RESUMEN
Cinqüenta e dois pacientes estudados entre novembro de 1987 e agosto de 1992 tendo sido submetidos a um ou mais ciclos de quimioterapia com VMCP (vincristina 2mg IV dl; melphalan 4 mg/m² VO d2-5; ciclofosfamida 100 mg/m² VO d2-5 e prednisona 100 mg VO d2-5 - repetidos a cada 28 dias, ou conforme a toxicidade hematológica). Vinte e seis pacientes foram submetidos a radioterapia concomitante. Foi utilziado o estadiamento proposto pelo SWOG (Durie e Salmon, 1975), onde 15 (28,8 por cento) pacientes foram estadiados como IIIA e 32 (61,5 por cento) como IIIB, quatro (7,4 por cento como II e um (2,2 por cento como I. Os critérios de resposta foram os mesmos adotados pelo SWOG; porém, consideramos também como Resposta Parcial (RP) a melhora do PS em um ponto ou mais. Sete pacientes entraram em Remissäo Completa, 12 em Remissäo Parcial e 20 foram considerados com Doença Estável e 13 näo responderam ao tratamento. A Sobrevida Mediana para todos os pacientes, calculada pelo método de Kaplan-Meier, foi de 41 meses. A toxicidade foi tolerável na maioria dos pacientes, sendo grau 3-4 em 16 (30,8 por cento) pacientes em pelo menos um episódio. A principal toxicidade dose limitante foi hematológica. Três pacientes morreram por leucopenia e infecçäo e um por toxicidade gastrointestinal (7,6 por cento). Oito pacientes estäo perdidos do follow-up. Os autores consideram o esquema eficaz e com resultados compatíveis com os da literatura,com toxicidade dentro das expectativas