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. 2001 Oct;85(4):321–325. doi: 10.1136/adc.85.4.321

Down's syndrome and acute lymphoblastic leukaemia: clinical features and response to treatment

J Chessells 1, G Harrison 1, S Richards 1, C Bailey 1, F Hill 1, B Gibson 1, I Hann 1
PMCID: PMC1718934  PMID: 11567943

Abstract

AIMS—To examine the clinical and biological features of acute lymphoblastic leukaemia in children with Down's syndrome (DS), to compare their survival with other children, and to determine if entry to trials and survival has improved.
METHODS—Examination of presenting features and response to treatment in patients treated in two consecutive national trials, MRC UKALL X and XI.
RESULTS—The proportion of children with DS was significantly higher in UKALL XI (1.9%) than UKALL X (0.9%). Children with DS tended to be under 10 years and to have the common ALL subtype. Cytogenetic analysis showed that favourable features, such as high hyperdiploidy and t(12;21) were less frequent but also that there was a lack of translocations associated with a poor prognosis. Children with DS showed no increase in risk of relapse at any site but their survival and event free survival were inferior to other children. These results were caused by an increased number of infective deaths during remission (11% compared to 2%). At five years overall survival was 73% in DS children compared with 82% in other children; event free survival was 53% compared to 63% in non-DS children.
CONCLUSIONS—Entry of children with DS to national trials has increased and survival has improved. However they remain at risk of relapse and also of treatment related mortality. These findings emphasise the need for both intensive chemotherapy and optimal supportive care.



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Selected References

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  1. 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]
  2. Chessels J. M., Swansbury G. J., Reeves B., Bailey C. C., Richards S. M. Cytogenetics and prognosis in childhood lymphoblastic leukaemia: results of MRC UKALL X. Medical Research Council Working Party in Childhood Leukaemia. Br J Haematol. 1997 Oct;99(1):93–100. doi: 10.1046/j.1365-2141.1997.3493163.x. [DOI] [PubMed] [Google Scholar]
  3. Craze J. L., Harrison G., Wheatley K., Hann I. M., Chessells J. M. Improved outcome of acute myeloid leukaemia in Down's syndrome. Arch Dis Child. 1999 Jul;81(1):32–37. doi: 10.1136/adc.81.1.32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dördelmann M., Schrappe M., Reiter A., Zimmermann M., Graf N., Schott G., Lampert F., Harbott J., Niemeyer C., Ritter J. Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics and treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Münster Group. Leukemia. 1998 May;12(5):645–651. doi: 10.1038/sj.leu.2400989. [DOI] [PubMed] [Google Scholar]
  5. Garré M. L., Relling M. V., Kalwinsky D., Dodge R., Crom W. R., Abromowitch M., Pui C. H., Evans W. E. Pharmacokinetics and toxicity of methotrexate in children with Down syndrome and acute lymphocytic leukemia. J Pediatr. 1987 Oct;111(4):606–612. doi: 10.1016/s0022-3476(87)80131-2. [DOI] [PubMed] [Google Scholar]
  6. Hann I. M., Richards S. M., Eden O. B., Hill F. G. Analysis of the immunophenotype of children treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia Trial XI (MRC UKALLXI). Medical Research Council Childhood Leukaemia Working Party. Leukemia. 1998 Aug;12(8):1249–1255. doi: 10.1038/sj.leu.2401093. [DOI] [PubMed] [Google Scholar]
  7. Hann I., Vora A., Harrison G., Harrison C., Eden O., Hill F., Gibson B., Richards S., UK Medical Research Council's Working Party on Childhood Leukaemia Determinants of outcome after intensified therapy of childhood lymphoblastic leukaemia: results from Medical Research Council United Kingdom acute lymphoblastic leukaemia XI protocol. Br J Haematol. 2001 Apr;113(1):103–114. doi: 10.1046/j.1365-2141.2001.02668.x. [DOI] [PubMed] [Google Scholar]
  8. Hann I., Vora A., Richards S., Hill F., Gibson B., Lilleyman J., Kinsey S., Mitchell C., Eden O. B. Benefit of intensified treatment for all children with acute lymphoblastic leukaemia: results from MRC UKALL XI and MRC ALL97 randomised trials. UK Medical Research Council's Working Party on Childhood Leukaemia. Leukemia. 2000 Mar;14(3):356–363. doi: 10.1038/sj.leu.2401704. [DOI] [PubMed] [Google Scholar]
  9. Hargrave D. R., Hann I. I., Richards S. M., Hill F. G., Lilleyman J. S., Kinsey S., Bailey C. C., Chessells J. M., Mitchell C., Eden O. B. Progressive reduction in treatment-related deaths in Medical Research Council childhood lymphoblastic leukaemia trials from 1980 to 1997 (UKALL VIII, X and XI). Br J Haematol. 2001 Feb;112(2):293–299. doi: 10.1046/j.1365-2141.2001.02543.x. [DOI] [PubMed] [Google Scholar]
  10. Hasle H., Clemmensen I. H., Mikkelsen M. Risks of leukaemia and solid tumours in individuals with Down's syndrome. Lancet. 2000 Jan 15;355(9199):165–169. doi: 10.1016/S0140-6736(99)05264-2. [DOI] [PubMed] [Google Scholar]
  11. Lange B. The management of neoplastic disorders of haematopoiesis in children with Down's syndrome. Br J Haematol. 2000 Sep;110(3):512–524. doi: 10.1046/j.1365-2141.2000.02027.x. [DOI] [PubMed] [Google Scholar]
  12. Lanza C., Volpe G., Basso G., Gottardi E., Perfetto F., Cilli V., Spinelli M., Ricotti E., Guerrasio A., Madon E. The common TEL/AML1 rearrangement does not represent a frequent event in acute lymphoblastic leukaemia occuring in children with Down syndrome. Leukemia. 1997 Jun;11(6):820–821. doi: 10.1038/sj.leu.2400651. [DOI] [PubMed] [Google Scholar]
  13. Legare R. D., Lu D., Gallagher M., Ho C., Tan X., Barker G., Shimizu K., Ohki M., Lenny N., Hiebert S. CBFA2, frequently rearranged in leukemia, is not responsible for a familial leukemia syndrome. Leukemia. 1997 Dec;11(12):2111–2119. doi: 10.1038/sj.leu.2400852. [DOI] [PubMed] [Google Scholar]
  14. Levitt G. A., Stiller C. A., Chessells J. M. Prognosis of Down's syndrome with acute leukaemia. Arch Dis Child. 1990 Feb;65(2):212–216. doi: 10.1136/adc.65.2.212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Peto R., Pike M. C., Armitage P., Breslow N. E., Cox D. R., Howard S. V., Mantel N., McPherson K., Peto J., Smith P. G. Design and analysis of randomized clinical trials requiring prolonged observation of each patient. II. analysis and examples. Br J Cancer. 1977 Jan;35(1):1–39. doi: 10.1038/bjc.1977.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pui C. H., Raimondi S. C., Borowitz M. J., Land V. J., Behm F. G., Pullen D. J., Hancock M. L., Shuster J. J., Steuber C. P., Crist W. M. Immunophenotypes and karyotypes of leukemic cells in children with Down syndrome and acute lymphoblastic leukemia. J Clin Oncol. 1993 Jul;11(7):1361–1367. doi: 10.1200/JCO.1993.11.7.1361. [DOI] [PubMed] [Google Scholar]
  17. Ragab A. H., Abdel-Mageed A., Shuster J. J., Frankel L. S., Pullen J., van Eys J., Sullivan M. P., Boyett J., Borowitz M., Crist W. M. Clinical characteristics and treatment outcome of children with acute lymphocytic leukemia and Down's syndrome. A Pediatric Oncology Group study. Cancer. 1991 Feb 15;67(4):1057–1063. doi: 10.1002/1097-0142(19910215)67:4<1057::aid-cncr2820670432>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  18. Robison L. L., Nesbit M. E., Jr, Sather H. N., Level C., Shahidi N., Kennedy A., Hammond D. Down syndrome and acute leukemia in children: a 10-year retrospective survey from Childrens Cancer Study Group. J Pediatr. 1984 Aug;105(2):235–242. doi: 10.1016/s0022-3476(84)80119-5. [DOI] [PubMed] [Google Scholar]
  19. Rubnitz J. E., Pui C. H., Downing J. R. The role of TEL fusion genes in pediatric leukemias. Leukemia. 1999 Jan;13(1):6–13. doi: 10.1038/sj.leu.2401258. [DOI] [PubMed] [Google Scholar]
  20. Wheeler K., Chessells J. M., Bailey C. C., Richards S. M. Treatment related deaths during induction and in first remission in acute lymphoblastic leukaemia: MRC UKALL X. Arch Dis Child. 1996 Feb;74(2):101–107. doi: 10.1136/adc.74.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]

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