Early response to chemotherapy as a prognostic factor in childhood acute lymphoblastic leukaemia: a methodological review


J. Donadieu, Biostatistics and Epidemiology Unit, Institut Gustave Roussy, Villejuif, F-94805 cedex, France. E-mail: jean.donadieu@trs.ap-hop-paris.fr


Published studies of the prognostic value of the early response to induction treatment in childhood acute lymphoblastic leukaemia (ALL) were analysed. Three criteria were used to judge the early treatment response: persistence of peripheral blasts (PPB) or of bone marrow blasts (PBMB) during induction therapy and minimal residual disease (MRD) after completion of induction therapy. Studies with more than 50 patients, published between 1980 and 2000, were reviewed. Among 13 659 distinct articles published on ALL, we identified only 43 applicable studies. Within- and between-laboratory variations were evaluated in only one study. Treatment modalities differed among, and sometimes within, studies. The cut-off points used in the statistical analyses were never discussed, and in many studies appeared to be selected after multiple tests. The proportion of missing data was > 30% in almost all studies of MRD, as a result of technical difficulties and not missing samples. PPB and PBMB were associated with shorter survival in, respectively, 13 out of 14 and 15 out of 16 studies. Detection of MRD was associated with poor outcome in 12 of the 13 studies. Because none of the parameters used to measure the early response to induction therapy for childhood ALL have been properly assessed as prognostic factors, we conclude that they should be considered only as candidate prognostic indicators pending more thorough studies.