Prognostic study of continuous variables (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age) in childhood acute lymphoblastic leukaemia. Analysis Of a population of 1545 children treated by the French Acute Lymphoblastic Leukaemia Group (FRALLE).
Many cutpoints have been proposed to categorize continuous variables in childhood acute lymphoblastic leukaemia (white blood cell count, peripheral blast cell count, haemoglobin level, platelet count and age), and have been used to define therapeutic subgroups. This variation in the choice of cutpoints leads to a bias called the 'Will Rogers phenomenon'. The aim of this study was to analyse variations in the relative risk of relapse or death as a function of continuous prognostic variables in childhood ALL and to discuss the choice of cutpoints. We studied a population of 1545 children with ALL enrolled in three consecutive protocols named FRALLE 83, FRALLE 87 and FRALLE 89. We estimated the risk of relapse or death associated with different values of each continuous prognostic variable by dividing the sample into quintiles of the distribution of the variables. As regards age, a category of children under 1 year of age was distinguished and the rest of the population was divided into quintiles. The floated variance method was used to calculate the confidence interval of each relative risk, including the reference category. The relation between the quantitative prognostic factors and the risk was monotonic for each variable, except for age. For the white blood cell count (WBC), the relation is log linear. The risk associated with WBC values in the upper quintile was 1.9 times higher than that in the lower quintile. The peripheral blast cell count correlated strongly with WBC (correlation coefficient: 0.99). The risk increased with the haemoglobin level, and the risk in the upper quintile was 1.3 times higher than that in the lower quintile. The risk decreased as the platelet count increased: the risk in the lower quintile was 1.2 times higher than that in the upper quintile. The risk increased gradually with increasing age above one year. The small subgroup of patients (2.5% of the population) under 1 year of age at diagnosis had a risk 2.6 times higher than the reference category of patients between 3 and 4.3 years of age. When the risk associated with a quantitative prognostic factor varies monotonously, the selection of a cutpoint is arbitrary and represents a loss of information. Despite this loss of information, such arbitrary categorization may be necessary to define therapeutic stratification. In that case, consensus cutpoints must be defined if one wants to avoid the Will Rogers phenomenon. The cutpoints proposed by the Rome workshop and the NCI are arbitrary, but may represent an acceptable convention.
Donadieu
J
J
Département de Biostatistique et d'épidémiologie, Institut Gustave Roussy, rue Camille Desmoulins, Villejuif, 94800, France.
Auclerc
M F
MF
Baruchel
A
A
Perel
Y
Y
Bordigoni
P
P
Landman-Parker
J
J
Leblanc
T
T
Cornu
G
G
Sommelet
D
D
Leverger
G
G
Schaison
G
G
Hill
C
C
D000293:Adolescent; D000367:Age Factors; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002452:Cell Count; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007958:Leukocyte Count; D010976:Platelet Count; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D013997:Time Factors
D000970:Antineoplastic Agents; D006454:Hemoglobins