Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2000 Dec;83(12):1617–1622. doi: 10.1054/bjoc.2000.1504

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)

J Donadieu 1,2, M-F Auclerc 3, A Baruchel 3, Y Perel 4, P Bordigoni 5, J Landman-Parker 2, T Leblanc 3, G Cornu 6, D Sommelet 5, G Leverger 2, G Schaison 3, C Hill 1, for the FRALLE group
PMCID: PMC2363446  PMID: 11104555

Abstract

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. © 2000 Cancer Research Campaign http://www.bjcancer.com

Keywords: acute lymphoblastic leukaemia, childhood, prognostic factors, continuous variable, cutpoint

Full Text

The Full Text of this article is available as a PDF (69.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman D. G., Lausen B., Sauerbrei W., Schumacher M. Dangers of using "optimal" cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst. 1994 Jun 1;86(11):829–835. doi: 10.1093/jnci/86.11.829. [DOI] [PubMed] [Google Scholar]
  2. Bleyer W. A. Remaining problems in the staging and treatment of childhood lymphoblastic leukemia. Am J Pediatr Hematol Oncol. 1989 Winter;11(4):371–379. [PubMed] [Google Scholar]
  3. Bleyer W. A., Sather H., Coccia P., Lukens J., Siegel S., Hammond G. D. The staging of childhood acute lymphoblastic leukemia: strategies of the Childrens Cancer Study Group and a three-dimensional technic of multivariate analysis. Med Pediatr Oncol. 1986;14(5):271–280. doi: 10.1002/mpo.2950140506. [DOI] [PubMed] [Google Scholar]
  4. Bucsky P., Reiter A., Ritter J., Dopfer R., Riehm H. Die akute lymphoblastische Leukämie im Säuglingsalter: Ergebnisse aus fünf multizentrischen Therapiestudien ALL-BFM 1970-1986. Klin Padiatr. 1988 May-Jun;200(3):177–183. doi: 10.1055/s-2008-1033706. [DOI] [PubMed] [Google Scholar]
  5. Chessells J. M., Bailey C., Richards S. M. Intensification of treatment and survival in all children with lymphoblastic leukaemia: results of UK Medical Research Council trial UKALL X. Medical Research Council Working Party on Childhood Leukaemia. Lancet. 1995 Jan 21;345(8943):143–148. doi: 10.1016/s0140-6736(95)90164-7. [DOI] [PubMed] [Google Scholar]
  6. Donadieu J., Auclerc M. F., Baruchel A., Leblanc T., Landman-Parker J., Perel Y., Michel G., Cornu G., Bordigoni P., Sommelet D. Critical study of prognostic factors in childhood acute lymphoblastic leukaemia: differences in outcome are poorly explained by the most significant prognostic variables. Fralle group. French Acute Lymphoblastic Leukaemia study group. Br J Haematol. 1998 Aug;102(3):729–739. doi: 10.1046/j.1365-2141.1998.00818.x. [DOI] [PubMed] [Google Scholar]
  7. Easton D. F., Peto J., Babiker A. G. Floating absolute risk: an alternative to relative risk in survival and case-control analysis avoiding an arbitrary reference group. Stat Med. 1991 Jul;10(7):1025–1035. doi: 10.1002/sim.4780100703. [DOI] [PubMed] [Google Scholar]
  8. Feinstein A. R., Sosin D. M., Wells C. K. The Will Rogers phenomenon. Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med. 1985 Jun 20;312(25):1604–1608. doi: 10.1056/NEJM198506203122504. [DOI] [PubMed] [Google Scholar]
  9. Gustafsson G., Kreuger A., Clausen N., Garwicz S., Kristinsson J., Lie S. O., Moe P. J., Perkkiö M., Yssing M., Saarinen-Pihkala U. M. Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO) Acta Paediatr. 1998 Nov;87(11):1151–1161. doi: 10.1080/080352598750031149. [DOI] [PubMed] [Google Scholar]
  10. Hill C. Valeur pronostique d'une variable continue et point de césure optimal. Bull Cancer. 1993 Aug;80(8):649–652. [PubMed] [Google Scholar]
  11. Hilsenbeck S. G., Clark G. M., McGuire W. L. Why do so many prognostic factors fail to pan out? Breast Cancer Res Treat. 1992;22(3):197–206. doi: 10.1007/BF01840833. [DOI] [PubMed] [Google Scholar]
  12. Hiyoshi Y., Fujimoto T., Kuriya N., Otani Y., Mibu K., Yanai M., Sasaki K., Shingaki Y., Yokoyama T., Kadoya S. Prognostic factors in children with acute lymphoblastic leukemia. Part II: Multivariate analysis. Children's Cancer and Leukemia Study Group. Jpn J Clin Oncol. 1985 Mar;15(1):13–23. [PubMed] [Google Scholar]
  13. Jacquillat C., Weil M., Auclerc M. F., Chastang C., Flandrin G., Izrael V., Schaison G., Degos L., Boiron M., Bernard J. Prognosis and treatment of acute lymphoblastic leukemia. Study of 650 patients. Cancer Chemother Pharmacol. 1978;1(2):113–122. doi: 10.1007/BF00254045. [DOI] [PubMed] [Google Scholar]
  14. Mastrangelo R., Poplack D., Bleyer A., Riccardi R., Sather H., D'Angio G. Report and recommendations of the Rome workshop concerning poor-prognosis acute lymphoblastic leukemia in children: biologic bases for staging, stratification, and treatment. Med Pediatr Oncol. 1986;14(3):191–194. doi: 10.1002/mpo.2950140317. [DOI] [PubMed] [Google Scholar]
  15. Mastrangelo R. The problem of "staging" in childhood acute lymphoblastic leukemia: a review. Med Pediatr Oncol. 1986;14(3):121–123. doi: 10.1002/mpo.2950140304. [DOI] [PubMed] [Google Scholar]
  16. Reiter A., Schrappe M., Ludwig W. D., Hiddemann W., Sauter S., Henze G., Zimmermann M., Lampert F., Havers W., Niethammer D. Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86. Blood. 1994 Nov 1;84(9):3122–3133. [PubMed] [Google Scholar]
  17. Schaison G., Olive D., Leverger G., Vannier J. P., de Lumley L., Bancillon A., Cornu G. Treatment of acute lymphoblastic leukemia: protocol Fralle 83-85. Haematol Blood Transfus. 1990;33:467–472. [PubMed] [Google Scholar]
  18. Schemper M., Smith T. L. A note on quantifying follow-up in studies of failure time. Control Clin Trials. 1996 Aug;17(4):343–346. doi: 10.1016/0197-2456(96)00075-x. [DOI] [PubMed] [Google Scholar]
  19. Schorin M. A., Blattner S., Gelber R. D., Tarbell N. J., Donnelly M., Dalton V., Cohen H. J., Sallan S. E. Treatment of childhood acute lymphoblastic leukemia: results of Dana-Farber Cancer Institute/Children's Hospital Acute Lymphoblastic Leukemia Consortium Protocol 85-01. J Clin Oncol. 1994 Apr;12(4):740–747. doi: 10.1200/JCO.1994.12.4.740. [DOI] [PubMed] [Google Scholar]
  20. Schrappe M., Beck J., Brandeis W. E., Feickert H. J., Gadner H., Graf N., Havers W., Henze G., Jobke A., Kornhuber B. Die Behandlung der akuten lymphoblastischen Leukämie im Kindes- und Jugendalter: Ergebnisse der multizentrischen Therapiestudie ALL-BFM 81. Klin Padiatr. 1987 May-Jun;199(3):133–150. doi: 10.1055/s-2008-1026780. [DOI] [PubMed] [Google Scholar]
  21. Smith M., Arthur D., Camitta B., Carroll A. J., Crist W., Gaynon P., Gelber R., Heerema N., Korn E. L., Link M. Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia. J Clin Oncol. 1996 Jan;14(1):18–24. doi: 10.1200/JCO.1996.14.1.18. [DOI] [PubMed] [Google Scholar]
  22. TIVEY H. Prognosis for survival in the leukemias of childhood; review of the literature and the proposal of a simple method of reporting survival data for these diseases. Pediatrics. 1952 Jul;10(1):48–59. [PubMed] [Google Scholar]
  23. ZUELZER W. W. IMPLICATIONS OF LONG-TERM SURVIVAL IN ACUTE STEM CELL LEUKEMIA OF CHILDHOOD TREATED WITH COMPOSITE CYCLIC THERAPY. Blood. 1964 Nov;24:477–494. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES