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Acute Leukemias

Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation

Leukemia volume 27, pages 836–842 (2013)Cite this article

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Abstract

The clinical features and outcomes of 148 patients with acute myeloid leukemia (AML) and 11q23 chromosomal abnormalities were compared with those of 2640 patients with non-11q23 AML. Patients with t(9;11) ), t(6;11) or other 11q23 balanced translocations (t(11;v)(q23;v)) presented at a younger age and with higher percentage of bone marrow blasts. Unbalanced 11q23 abnormalities were commonly associated with deletions of chromosomes 5q, 7q and/or complex karyotypes. In multivariate analysis, when compared with patients with non-11q23 AML and unfavorable-risk karyotype, there was a significant difference in overall survival (OS) for patients with t(9;11) (P=0.004), whereas there were no differences in OS for patients with t(6;11) (P=0.62), t(11;19) (P=0.20) and unbalanced 11q23 aberrations (P=0.85) or t(11;v)(q23;v) (P=0.59), indicating that t(9;11) has an independent intermediate prognostic significance, with all others being poor prognostic factors for OS; this was further confirmed by comparing them with patients with non-11q23 AML and intermediate-risk karyotype. Using intention-to treat analysis based on donor availability, we also noted that allogeneic stem cell transplant in first remission had a significant benefit toward improving OS (P<0.001) and relapse-free survival (P<0.001) in patients with AML and 11q23 abnormalities.

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References

  1. Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115: 453–474.

    Article  PubMed  Google Scholar 

  2. Lowenberg B . Diagnosis and prognosis in acute myeloid leukemia—the art of distinction. N Engl J Med 2008; 358: 1960–1962.

    Article  PubMed  Google Scholar 

  3. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.

    Article  CAS  PubMed  Google Scholar 

  4. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010; 116: 354–365.

    Article  CAS  PubMed  Google Scholar 

  5. Cox MC, Panetta P, Lo-Coco F, Del Poeta G, Venditti A, Maurillo L et al. Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: results in 378 adult patients. Am J Clin Pathol 2004; 122: 298–306.

    Article  CAS  PubMed  Google Scholar 

  6. Pui CH, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC et al. 11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia. J Clin Oncol 1994; 12: 909–915.

    Article  CAS  PubMed  Google Scholar 

  7. Satake N, Maseki N, Nishiyama M, Kobayashi H, Sakurai M, Inaba H et al. Chromosome abnormalities and MLL rearrangements in acute myeloid leukemia of infants. Leukemia 1999; 13: 1013–1017.

    Article  CAS  PubMed  Google Scholar 

  8. Muntean AG, Hess JL . The pathogenesis of mixed-lineage leukemia. Annu Rev Pathol 2012; 7: 283–301.

    Article  CAS  PubMed  Google Scholar 

  9. Krivtsov AV, Armstrong SA . MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 2007; 7: 823–833.

    Article  CAS  PubMed  Google Scholar 

  10. Balgobind BV, Zwaan CM, Pieters R, Van den Heuvel-Eibrink MM . The heterogeneity of pediatric MLL-rearranged acute myeloid leukemia. Leukemia 2011; 25: 1239–1248.

    Article  CAS  PubMed  Google Scholar 

  11. Tamai H, Inokuchi K . 11q23/MLL acute leukemia: update of clinical aspects. J Clin Exp Hematop 2010; 50: 91–98.

    Article  PubMed  Google Scholar 

  12. Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009; 114: 2489–2496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Coenen EA, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A et al. Prognostic significance of additional cytogenetic aberrations in 733 de novo pediatric 11q23/MLL-rearranged AML patients: results of an international study. Blood 2011; 117: 7102–7111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937–951.

    Article  CAS  PubMed  Google Scholar 

  15. Archimbaud E, Charrin C, Magaud JP, Campos L, Thomas X, Fiere D et al. Clinical and biological characteristics of adult de novo and secondary acute myeloid leukemia with balanced 11q23 chromosomal anomaly or MLL gene rearrangement compared to cases with unbalanced 11q23 anomaly: confirmation of the existence of different entities with 11q23 breakpoint. Leukemia 1998; 12: 25–33.

    Article  CAS  PubMed  Google Scholar 

  16. Blum W, Mrozek K, Ruppert AS, Carroll AJ, Rao KW, Pettenati MJ et al. Adult de novo acute myeloid leukemia with t(6;11)(q27;q23) - results from cancer and leukemia group B study 8461 and review of the literature. Cancer 2004; 101: 1420–1427.

    Article  PubMed  Google Scholar 

  17. Krauter J, Wagner K, Schafer I, Marschalek R, Meyer C, Heil G et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 2009; 27: 3000–3006.

    Article  PubMed  Google Scholar 

  18. Schoch C, Schnittger S, Klaus M, Kern W, Hiddemann W, Haferlach T . AML with 11q23/MLL abnormalities as defined by the WHO classification: incidence, partner chromosomes, FAB subtype, age distribution, and prognostic impact in an unselected series of 1897 cytogenetically analyzed AML cases. Blood 2003; 102: 2395–2402.

    Article  CAS  PubMed  Google Scholar 

  19. Mrozek K, Heinonen K, Lawrence D, Carroll AJ, Koduru PR, Rao KW et al. Adult patients with de novo acute myeloid leukemia and t(9; 11)(p22; q23) have a superior outcome to patients with other translocations involving band 11q23: a cancer and leukemia group B study. Blood 1997; 90: 4532–4538.

    CAS  PubMed  Google Scholar 

  20. Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642–4649.

    Article  PubMed  Google Scholar 

  21. Cortes J, O'Brien S, Kantarjian H, Cork A, Stass S, Freireich EJ et al. Abnormalities in the long arm of chromosome 11 (11q) in patients with de novo and secondary acute myelogenous leukemias and myelodysplastic syndromes. Leukemia 1994; 8: 2174–2178.

    CAS  PubMed  Google Scholar 

  22. Balgobind BV, Van Vlierberghe P, van den Ouweland AM, Beverloo HB, Terlouw-Kromosoeto JN, van Wering ER et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. Blood 2008; 111: 4322–4328.

    Article  CAS  PubMed  Google Scholar 

  23. Goemans BF, Zwaan CM, Miller M, Zimmermann M, Harlow A, Meshinchi S et al. Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia. Leukemia 2005; 19: 1536–1542.

    Article  CAS  PubMed  Google Scholar 

  24. Hollink IH, Zwaan CM, Zimmermann M, Arentsen-Peters TC, Pieters R, Cloos J et al. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML. Leukemia 2009; 23: 262–270.

    Article  CAS  PubMed  Google Scholar 

  25. Ostgard LS, Kjeldsen E, Holm MS, Brown Pde N, Pedersen BB, Bendix K et al. Reasons for treating secondary AML as de novo AML. Eur J Haematol 2010; 85: 217–226.

    Article  PubMed  Google Scholar 

  26. Tamai H, Yamaguchi H, Hamaguchi H, Yagasaki F, Bessho M, Kobayashi T et al. Clinical features of adult acute leukemia with 11q23 abnormalities in Japan: a co-operative multicenter study. Int J Hematol 2008; 87: 195–202.

    Article  PubMed  Google Scholar 

  27. Meyer C, Burmeister T, Strehl S, Schneider B, Hubert D, Zach O et al. Spliced MLL fusions: a novel mechanism to generate functional chimeric MLL-MLLT1 transcripts in t(11;19)(23; p13.3) leukemia. Leukemia 2007; 21: 588–590.

    Article  CAS  PubMed  Google Scholar 

  28. Meyer C, Kowarz E, Hofmann J, Renneville A, Zuna J, Trka J et al. New insights to the MLL recombinome of acute leukemias. Leukemia 2009; 23: 1490–1499.

    Article  CAS  PubMed  Google Scholar 

  29. Meyer C, Schneider B, Reichel M, Angermueller S, Strehl S, Schnittger S et al. Diagnostic tool for the identification of MLL rearrangements including unknown partner genes. Proc Natl Acad Sci USA 2005; 102: 449–454.

    Article  CAS  PubMed  Google Scholar 

  30. Wechsler DS, Engstrom LD, Alexander BM, Motto DG, Roulston D . A novel chromosomal inversion at 11q23 in infant acute myeloid leukemia fuses MLL to CALM, a gene that encodes a clathrin assembly protein. Genes Chromosomes Cancer 2003; 36: 26–36.

    Article  CAS  PubMed  Google Scholar 

  31. Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS et al. Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: Evidence for its fusion with MLL in acute myeloid leukemia. Proc Natl Acad Sci USA 2000; 97: 2145–2150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gupta V, Tallman MS, Weisdorf DJ . Allogeneic hematopoietic cell transplantation for adults with acute myeloid leukemia: myths, controversies, and unknowns. Blood 2011; 117: 2307–2318.

    Article  CAS  PubMed  Google Scholar 

  33. Koreth J, Schlenk R, Kopecky KJ, Honda S, Sierra J, Djulbegovic BJ et al. Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials. JAMA 2009; 301: 2349–2361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Basara N, Schulze A, Wedding U, Mohren M, Gerhardt A, Junghanss C et al. Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission. Leukemia 2009; 23: 635–640.

    Article  CAS  PubMed  Google Scholar 

  35. Gupta V, Tallman MS, He W, Logan BR, Copelan E, Gale RP et al. Comparable survival after HLA-well-matched unrelated or matched sibling donor transplantation for acute myeloid leukemia in first remission with unfavorable cytogenetics at diagnosis. Blood 2010; 116: 1839–1848.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Y Chen, H Kantarjian, S Pierce, S Faderl, S O'Brien, E Jabbour, N Daver, T Kadia, Z Estrov, G Garcia-Manero, J Cortes & F Ravandi

  2. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    W Qiao

  3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    L Abruzzo

  4. Department of Cellular Therapy and Stem Cell Transplantation The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M de Lima & P Kebriaei

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Correspondence to F Ravandi.

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Chen, Y., Kantarjian, H., Pierce, S. et al. Prognostic significance of 11q23 aberrations in adult acute myeloid leukemia and the role of allogeneic stem cell transplantation. Leukemia 27, 836–842 (2013). https://doi.org/10.1038/leu.2012.319

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