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Cytogenetics and Molecular Genetics

High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome

Leukemia volume 28, pages 1511–1518 (2014)Cite this article

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Abstract

High hyperdiploidy (HeH, 51–65 chromosomes) is an established genetic subtype of acute lymphoblastic leukaemia (ALL). The clinical and cytogenetic features as well as outcome of HeH among adolescents and adults have not been thoroughly investigated. Among 1232 B-cell precursor ALL patients (15–65 years) treated in the UKALLXII/ECOG2993 trial, 160 (13%) had a HeH karyotype, including 80 patients aged >24 years. The frequency of HeH was the same in Philadelphia chromosome (Ph)-positive and -negative cases, but Ph-positive patients were older. The cytogenetic profiles of Ph-positive and Ph-negative HeH cases were similar, although trisomy 2 was strongly associated with Ph-positive HeH. Overall, Ph-positive HeH patients did not have an inferior overall survival compared with Ph-negative patients (P=0.2: 50 vs 57% at 5 years). Trisomy of chromosome 4 was associated with a superior outcome in Ph-negative patients, whereas +5 and +20 were associated with an inferior outcome in Ph-positive and Ph-negative patients, respectively. All three markers retained significance in multivariate analysis adjusting for age and white cell count: hazard ratio for risk of death 0.47 (95% CI: 0.27–0.84) (P=0.01), 3.73 (1.51–9.21) (P=0.004) and 2.63 (1.25–5.54) (P=0.01), respectively. In conclusion, HeH is an important subtype of ALL at all ages and displays outcome heterogeneity according to chromosomal gain.

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References

  1. Moorman AV . The clinical relevance of chromosomal and genomic abnormalities in B-cell precursor acute lymphoblastic leukaemia. Blood Rev 2012; 26: 123–135.

    Article  CAS  Google Scholar 

  2. Maia AT, Tussiwand R, Cazzaniga G, Rebulla P, Colman S, Biondi A et al. Identification of preleukemic precursors of hyperdiploid acute lymphoblastic leukemia in cord blood. Genes Chromosomes Cancer 2004; 40: 38–43.

    Article  Google Scholar 

  3. Davidsson J, Paulsson K, Lindgren D, Lilljebjorn H, Chaplin T, Forestier E et al. Relapsed childhood high hyperdiploid acute lymphoblastic leukemia: presence of preleukemic ancestral clones and the secondary nature of microdeletions and RTK-RAS mutations. Leukemia 2010; 24: 924–931.

    Article  CAS  Google Scholar 

  4. Paulsson K, Forestier E, Lilljebjorn H, Heldrup J, Behrendtz M, Young BD et al. Genetic landscape of high hyperdiploid childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2010; 107: 21719–21724.

    Article  CAS  Google Scholar 

  5. Paulsson K, Johansson B . High hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 2009; 48: 637–660.

    Article  CAS  Google Scholar 

  6. Sutcliffe MJ, Shuster JJ, Sather HN, Camitta BM, Pullen J, Schultz KR et al. 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. Leukemia 2005; 19: 734–740.

    Article  CAS  Google Scholar 

  7. Moorman AV, Richards SM, Martineau M, Cheung KL, Robinson HM, Jalali GR et al. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Blood 2003; 102: 2756–2762.

    Article  CAS  Google Scholar 

  8. Dastugue N, Suciu S, Plat G, Speleman F, Cave H, Girard S et al. Hyperdiploidy with 58-66 chromosomes in childhood B-acute lymphoblastic leukemia is highly curable: 58951 CLG-EORTC results. Blood 2013; 121: 2415–2423.

    Article  CAS  Google Scholar 

  9. Paulsson K, Forestier E, Andersen MK, Autio K, Barbany G, Borgstrom G et al. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols. Haematologica 2013; 98: 1424–1432.

    Article  Google Scholar 

  10. Paulsson K, Harrison CJ, Andersen MK, Chilton L, Nordgren A, Moorman AV et al. Distinct patterns of gained chromosomes in high hyperdiploid acute lymphoblastic leukemia with t(1;19)(q23;p13), t(9;22)(q34;q22) or MLL rearrangements. Leukemia 2013; 27: 974–977.

    Article  CAS  Google Scholar 

  11. Goldstone AH, Richards SM, Lazarus HM, Tallman MS, Buck G, Fielding AK et al. In adults with standard-risk acute lymphoblastic leukemia, the greatest benefit is achieved from a matched sibling allogeneic transplantation in first complete remission, and an autologous transplantation is less effective than conventional consolidation/maintenance chemotherapy in all patients: final results of the International ALL Trial (MRC UKALL XII/ECOG E2993). Blood 2008; 111: 1827–1833.

    Article  CAS  Google Scholar 

  12. Fielding AK, Rowe JM, Richards SM, Buck G, Moorman AV, Durrant IJ et al. Prospective outcome data on 267 unselected patients with Philadelphia-chromosome positive adult acute lymphoblastic leukaemia confirms superiority of allogeneic transplant over chemotherapy the pre-imatinib era Results from the international ALL trial MRC UKALLXII/ECOG2993. Blood 2009; 113: 4489–4496.

    Article  CAS  Google Scholar 

  13. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): Analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII / Eastern Cooperative Oncology Group (ECOG) 2993 Trial. Blood 2007; 109: 3189–3197.

    Article  CAS  Google Scholar 

  14. Fielding AK, Rowe JM, Buck G, Foroni L, Gerrard G, Litzow MR et al. UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia. Blood 2013; e-pub ahead of print 25 November 2013 doi:10.1182/blood-2013-09-529008.

    Article  Google Scholar 

  15. Harrison CJ, Moorman AV, Barber KE, Broadfield ZJ, Cheung KL, Harris RL et al. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukaemia: a UK Cancer Cytogenetics Group Study. Br J Haematol 2005; 129: 520–530.

    Article  Google Scholar 

  16. Storring JM, Minden MD, Kao S, Gupta V, Schuh AC, Schimmer AD et al. Treatment of adults with BCR-ABL negative acute lymphoblastic leukaemia with a modified paediatric regimen. Br J Haematol 2009; 146: 76–85.

    Article  Google Scholar 

  17. Huguet F, Leguay T, Raffoux E, Thomas X, Beldjord K, Delabesse E et al. Pediatric-inspired therapy in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia: the GRAALL-2003 study. J Clin Oncol 2009; 27: 911–918.

    Article  CAS  Google Scholar 

  18. Ramanujachar R, Richards S, Hann I, Goldstone A, Mitchell C, Vora A et al. Adolescents with acute lymphoblastic leukaemia: outcome on UK national paediatric (ALL97) and adult (UKALLXII/E2993) trials. Pediatr Blood Cancer 2007; 48: 254–261.

    Article  Google Scholar 

  19. GFCH. Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings and outcome. A Collaborative Study of the Groupe Francais De Cytogenetique Hematologique. Blood 1996; 87: 3135–3142.

    Google Scholar 

  20. Martin Ramos ML, Lahuerta Palacios JJ, Martinez LJ, Gomez Rodriguez MJ, Moreno IA, Barreiro ME . Karyotype and prognosis in adult Spanish acute lymphoblastic leukemia. Haematologica 2001; 86: 438–439.

    CAS  PubMed  Google Scholar 

  21. Mi JQ, Wang X, Yao Y, Lu HJ, Jiang XX, Zhou JF et al. Newly diagnosed acute lymphoblastic leukemia in China (II): prognosis related to genetic abnormalities in a series of 1091 cases. Leukemia 2012; 26: 1507–1516.

    Article  CAS  Google Scholar 

  22. Gomez-Segui I, Cervera J, Such E, Martinez-Cuadron D, Luna I, Ibanez M et al. Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia. Ann Hematol 2012; 91: 19–25.

    Article  Google Scholar 

  23. Heerema NA, Raimondi SC, Anderson JR, Biegel J, Camitta BM, Cooley LD et al. Specific extra chromosomes occur in a modal number dependent pattern in pediatric acute lymphoblastic leukemia. Genes Chromosomes Cancer 2007; 46: 684–693.

    Article  CAS  Google Scholar 

  24. Heerema NA, Sather HN, Sensel MG, Zhang T, Hutchinson RJ, Nachman JB et al. Prognostic impact of trisomies of chromosomes 10, 17 and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (>50 chromosomes). J Clin Oncol 2000; 18: 1876–1887.

    Article  CAS  Google Scholar 

  25. Raimondi SC, Pui CH, Hancock ML, Behm FG, Filatov L, Rivera GK . Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia. Leukemia 1996; 10: 213–224.

    CAS  PubMed  Google Scholar 

  26. Whitehead VM, Vuchich MJ, Lauer SJ, Mahoney D, Carroll AJ, Shuster JJ et al. Accumulation of high levels of methotrexate polyglutamates in lymphoblasts from children with hyperdiploid (>50 chromosomes) B-lineage acute lymphoblastic leukemia: a Pediatric Oncology Group study. Blood 1992; 80: 1316–1323.

    CAS  PubMed  Google Scholar 

  27. Chauvenet AR, Martin PL, Devidas M, Linda SB, Bell BA, Kurtzberg J et al. Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of childhood: a report from Children's Oncology Group Study P9201. Blood 2007; 110: 1105–1111.

    Article  CAS  Google Scholar 

  28. Gruszka-Westwood AM, Horsley SW, Martinez-Ramirez A, Harrison CJ, Kempski H, Moorman AV et al. Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia. Genes Chromosomes Cancer 2004; 41: 191–202.

    Article  CAS  Google Scholar 

  29. Roberts P, Burchill SA, Brownhill S, Cullinane CJ, Johnston C, Griffiths MJ et al. Ploidy and karyotype complexity are powerful prognostic indicators in the Ewing's sarcoma family of tumors: a study by the United Kingdom Cancer Cytogenetics and the Children's Cancer and Leukaemia Group. Genes Chromosomes Cancer 2008; 47: 207–220.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank the following: (1) the UK Cancer Cytogenetics Group (UKCCG) and the Eastern Co-operative Oncology Group (ECOG) cytogenetic laboratories for providing data; (2) Gordon Dewald and past and present members of the Leukaemia Research Cytogenetics Group for collecting and reviewing the cytogenetic data; and (3) the doctors who participated in the UKALLXII/ECOG2993 trial. AVM and CJH also thank Leukaemia & Lymphoma Research (LLR) for financial support. We also thank Dr Sue Richards (Clinical Trial Service Unit, University of Oxford) for data management and statistical input.

Author contributions

AVM and LC designed the study, performed statistical analyses and wrote the manuscript; GB provided trial data and statistical advice; AVM, CJH and RPK classified the cytogenetic abnormalities and managed the UK and ECOG cytogenetic databases; JMR, MST, AHG and AKF co-ordinated the clinical trial; and all authors approved the final version of the manuscript.

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Authors and Affiliations

  1. Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

    L Chilton, C J Harrison & A V Moorman

  2. Clinical Trial Service Unit, University of Oxford, Oxford, UK

    G Buck

  3. Department of Cytogenetics, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

  4. Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel

    J M Rowe

  5. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA

    M S Tallman

  6. Department of Haematology, University College Hospital London, London, UK

    A H Goldstone

  7. Department of Haematology, Royal Free and University College of London Medical School, London, UK

    A K Fielding

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Correspondence to A V Moorman.

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Chilton, L., Buck, G., Harrison, C. et al. High hyperdiploidy among adolescents and adults with acute lymphoblastic leukaemia (ALL): cytogenetic features, clinical characteristics and outcome. Leukemia 28, 1511–1518 (2014). https://doi.org/10.1038/leu.2013.379

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