title: Shorter Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia: The Experience of the Prospective, Randomized Brazilian GBTLI ALL-93 Protocol.
abstract: OBJECTIVE
  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.
  
  
  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: EFS15ywas 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.
  
  
  CONCLUSIONS
  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.
authors: Boldrini Children's Center , Campinas , Brazil.
authors: Silvia R
authors: SR
authors: Brandalise
authors: Federal University of Minas Gerais , Belo Horizonte , Brazil.
authors: Marcos B
authors: MB
authors: Viana
authors: Boldrini Children's Center , Campinas , Brazil.
authors: Vitória R P
authors: VR
authors: Pinheiro
authors: Onco Bahia Hospital , Salvador , Brazil.
authors: Núbia
authors: N
authors: Mendonça
authors: A. C. Camargo Hospital , São Paulo , Brazil.
authors: Luiz F
authors: LF
authors: Lopes
authors: Santa Maria University , Santa Maria , Brazil.
authors: Waldir V
authors: WV
authors: Pereira
authors: GRAACC , São Paulo , Brazil.
authors: Maria L M
authors: ML
authors: Lee
authors: GRUPO Hospital , São José , Brazil.
authors: Elitânia M
authors: EM
authors: Pontes
authors: Nossa Senhora da Glória Hospital , Rio de Janeiro , Brazil.
authors: Gláucia P
authors: GP
authors: Zouain-Figueiredo
authors: Varela Santiago Children's Hospital , Natal , Brazil.
authors: Alita C A C
authors: AC
authors: Azevedo
authors: Erick Loeff Hospital , Salvador , Brazil.
authors: Nilma
authors: N
authors: Pimentel
authors: Varela Santiago Children's Hospital , Natal , Brazil.
authors: Maria Z
authors: MZ
authors: Fernandes
authors: Felicio Rocho Hospital , Belo Horizonte , Brazil.
authors: Hilda M
authors: HM
authors: Oliveira
authors: State Public Hospital , São Paulo , Brazil.
authors: Sônia R
authors: SR
authors: Vianna
authors: Clinic Hospital , Ribeirão Preto , Brazil.
authors: Carlos A
authors: CA
authors: Scrideli
authors: State Public Hospital , Rio de Janeiro , Brazil.
authors: Fernando A
authors: FA
authors: Werneck
authors: Center Chemotherapy LTD. , Belo Horizonte , Brazil.
authors: Maria N
authors: MN
authors: Álvares
authors: São Judas Tadeu Hospital , Barretos , Brazil.
authors: Érica
authors: É
authors: Boldrini
authors: Hematology Center , São Paulo , Brazil.
authors: Sandra R
authors: SR
authors: Loggetto
authors: Santa Casa , São Paulo , Brazil.
authors: Paula
authors: P
authors: Bruniera
authors: CLEMED Clinic , Jundiai , Brazil.
authors: Maria J
authors: MJ
authors: Mastellaro
authors: Ana Costa Hospital , Santos , Brazil.
authors: Eni M
authors: EM
authors: Souza
authors: Cancer Hospital , Uberlândia , Brazil.
authors: Rogério A
authors: RA
authors: Araújo
authors: Hematology and Hemotherapy Foundation (HEMOPE) , Recife , Brazil.
authors: Flávia
authors: F
authors: Bandeira
authors: Onco Bahia Hospital , Salvador , Brazil.
authors: Doralice M
authors: DM
authors: Tan
authors: St. Joachim's Portuguese Charity Hospital , São Paulo , Brazil.
authors: Nelson A
authors: NA
authors: Carvalho
authors: Boldrini Children's Center , Campinas , Brazil.
authors: Maria A S
authors: MA
authors: Salgado
keywords: childhood acute lymphoblastic leukemia; maintenance ALL chemotherapy; pediatric ALL survival in middle-low-income countries