title: Minimal residual disease in cerebrospinal fluid at diagnosis: a more intensive treatment protocol was able to eliminate the adverse prognosis in children with acute lymphoblastic leukemia.
abstract: We analyzed cerebrospinal fluid (CSF) samples from 65 consecutive children with acute lymphoblastic leukemia (ALL) treated according to two different treatment protocols (GBTLI-ALL-93 and -99) with no puncture accident for minimal residual disease (MRD) in the central nervous system (CNS). Minimal residual disease was detected by polymerase chain reaction (PCR) with homo/heteroduplex analysis using consensus primers to IgH and TCR genes. MRD in the CSF at diagnosis was detected by PCR in 46.8% of children with no puncture accident or morphological involvement. In patients treated with GBTLI-ALL-93 a significantly lower 5-year event-free survival (EFS) was demonstrated for those with CSF involvement, in univariate (p = 0.01) and multivariate (p = 0.04) analysis. This observation was not true for patients treated with the more intensive protocol GBTLI-ALL-99 (p = 0.81). These findings suggest that MRD detection in the CSF is a common event in children with ALL. Treatment intensification provided by the GBTLI-ALL-99 apparently overcomes the detrimental effect of CNS minimal residual disease at diagnosis.
authors.affiliation: Department of Pediatrics, Ribeirão Preto Medicine School, University of Sao Paulo, Ribeirão Preto, Brazil.
authors.forename: Estefânia
authors.initials: E
authors.lastname: Biojone
authors.forename: Rosane De Paula
authors.initials: Rde P
authors.lastname: Queiróz
authors.forename: Elvis Terci
authors.initials: ET
authors.lastname: Valera
authors.forename: Newton Satoro
authors.initials: NS
authors.lastname: Odashima
authors.forename: Osvaldo Massaiti
authors.initials: OM
authors.lastname: Takayanagui
authors.forename: Marcos Borato
authors.initials: MB
authors.lastname: Viana
authors.forename: Luiz Gonzaga
authors.initials: LG
authors.lastname: Tone
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Scrideli
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007223:Infant; D018365:Neoplasm, Residual / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D016016:Proportional Hazards Models; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D012074:Remission Induction; D013997:Time Factors
chemical_list: D007143:Immunoglobulin Heavy Chains; D011948:Receptors, Antigen, T-Cell