Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables

Abstract

Summary.We determined the proportion of survival variability explained by the usual prognostic factors in childhood acute lymphoblastic leukaemia (ALL) during a prognostic study of 1552 patients enrolled in three consecutive Fralle group protocols (Fralle 83, Fralle 87 and Fralle 89). The event-free survival rates at 5 years were 54·8% (SD 1·9), 43·1% (SD 2·7) and 55·6% (SD 2·2), respectively. In the univariate analysis the following variables were predictive of poor outcome: male gender, elevated leucocytosis (> 50 × 10 9 /l), circulating blastosis, haemoglobin >12 g/dl, platelet count <100 × 10 9 /l, age under 1 year or over 9 years, enlarged mediastinum, nodes, spleen and liver, T phenotype, absence of CD10 þ cells; testicular and meningeal involvement, poor response to induction therapy (CCSG M3), and LDH >400 U/l. Among the cytogenetic features, hyperdiploidy had a protective effect, whereas hypodiploidy, translocation and other structural abnormalities had a negative influence, particularly in cases of t(9;22) or t(4;11). Multivariate analysis summarized the prognostic information in terms of four variables: age, gender, leucocytosis and cytogenetic features. Missing data had little influence on the results. However, despite their significance in the multivariate analysis, these four variables each had very low predictive power (1·1% for gender, 2·0% for age, 3·5% for leucocytosis, and 1·6% for cytogenetic features). Thus, the most significant prognostic factors in childhood ALL each explain no more than 4% of the variability in prognosis. This may explain the disappointing practical value of these factors and underlines the need for prognostic tools in childhood ALL.

High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative

“…20,31 The Dutch and Swedish Childhood Leukemia Groups found the diagnostic karyotype to be only of borderline significance as a predictor of outcome. 31,32 Donadieu et al, 3 presented data from 1552 pediatric ALL patients registered in the FRALLE protocols. Using univariate and multivariate analyses, they concluded that the predictive power of chromosome analysis was only 1.6.…”

“…1,2 Although many other clinical and biological factors have been identified and assessed for prognostic value, 3 few remain significant when subjected to multivariate analysis. 4,5 One factor that consistently appeared favorable, even in the context of other risk factors, was chromosome number and further analyses suggested the presence of specific chromosomes could be more important than a simple increase in ploidy.…”

Age-related patterns of immunoglobulin and T-cell receptor gene rearrangements in precursor-B-ALL: implications for detection of minimal residual disease

“…53 In addition to infants, children 410 years also showed a more immature Ig/TCR gene rearrangement pattern, comparable to that seen in adult ALL patients. 30 Interestingly, patients with precursor-B-ALL aged o1 y or 49 years, have a less favorable prognosis, 55,56 comparable to the prognosis of adult patients. So, childhood ALL in patients 410 years is more comparable to adult ALL than to childhood ALL in patients between 1 and 9 years, not only with respect to prognosis but also with respect to the Ig/TCR gene rearrangement pattern.…”

Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study

“…Patients were treated in accordance with current protocol at the time of leukemia diagnosis, depending on AL type (AML or ALL; that is, FRench group for childhood ALL (FRALLE), European Organisation for Research and Treatment of Cancer (EORTC), Leucémie Aiguë Myéloblastique Enfant (LAME) or ELAM). [19][20][21][22][23] Overall, 16 patients underwent central nervous system irradiation.…”