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Myelodysplasias

Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes

A Corrigendum to this article was published on 09 October 2013

Abstract

We evaluated the prognostic relevance of several clinical and laboratory parameters in 226 Mayo Clinic patients with chronic myelomonocytic leukemia (CMML): 152 (67%) males and median age 71 years. At a median follow-up of 15 months, 166 (73%) deaths and 33 (14.5%) leukemic transformations were documented. In univariate analysis, significant risk factors for survival included anemia, thrombocytopenia, increased levels of white blood cells, absolute neutrophils, absolute monocyte count (AMC), absolute lymphocytes, peripheral blood and bone marrow blasts, and presence of circulating immature myeloid cells (IMCs). Spliceosome component (P=0.4) and ASXL1 mutations (P=0.37) had no impact survival. On multivariable analysis, increased AMC (>10 × 109/l, relative risk (RR) 2.5, 95% confidence interval (CI) 1.7–3.8), presence of circulating IMC (RR 2.0, 95% CI 1.4–2.7), decreased hemoglobin (<10 g/dl, RR 1.6, 99% CI 1.2–2.2) and decreased platelet count (<100 × 109/l, RR 1.4, 99% CI 1.0–1.9) remained significant. Using these four risk factors, a new prognostic model for overall (high risk, RR 4.4, 95% CI 2.9–6.7; intermediate risk, RR 2.0, 95% CI 1.4–2.9) and leukemia-free survival (high risk, RR 4.9, 95% CI 1.9–12.8; intermediate risk, RR 2.6, 95% CI 1.1–5.9) performed better than other conventional risk models and was validated in an independent cohort of 268 CMML patients.

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References

  1. Patnaik MM, Lasho TL, Finke CM, Hanson CA, Hodnefield JM, Knudson RA et al. Spliceosome mutations involving SRSF2, SF3B1, and U2AF35 in chronic myelomonocytic leukemia: prevalence, clinical correlates, and prognostic relevance. Am J Hematol 2012; 88: 201–206.

    Article  Google Scholar 

  2. Germing U, Kundgen A, Gattermann N . Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma 2004; 45: 1311–1318.

    CAS  Article  PubMed  Google Scholar 

  3. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D . Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1985; 59: 425–433.

    CAS  Article  PubMed  Google Scholar 

  4. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  5. Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia 1993; 7: 1315–1323.

    CAS  PubMed  Google Scholar 

  6. Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 2002; 99: 840–849.

    CAS  Article  PubMed  Google Scholar 

  7. Germing U, Strupp C, Aivado M, Gattermann N . New prognostic parameters for chronic myelomonocytic leukemia. Blood 2002; 100: 731–732,, author reply 732–733.

    CAS  Article  PubMed  Google Scholar 

  8. Such E, Cervera J, Costa D, Sole F, Vallespi T, Luno E et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica 2011; 96: 375–383.

    Article  PubMed  Google Scholar 

  9. Kantarjian H, O’Brien S, Ravandi F, Cortes J, Shan J, Bennett JM et al. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 2008; 113: 1351–1361.

    CAS  Article  PubMed  Google Scholar 

  10. Wilcox RA, Ristow K, Habermann TM, Inwards DJ, Micallef IN, Johnston PB et al. The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma. Leukemia 2011; 25: 1502–1509.

    CAS  Article  PubMed  Google Scholar 

  11. Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008; 26: 4791–4797.

    Article  PubMed  Google Scholar 

  12. Abdel-Wahab O, Kilpivaara O, Patel J, Busque L, Levine RL . The most commonly reported variant in ASXL1 (c.1934dupG;p.Gly646TrpfsX12) is not a somatic alteration. Leukemia 2010; 24: 1656–1657.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Boultwood J, Perry J, Pellagatti A, Fernandez-Mercado M, Fernandez-Santamaria C, Calasanz MJ et al. Frequent mutation of the polycomb-associated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia. Leukemia 2010; 24: 1062–1065.

    CAS  Article  PubMed  Google Scholar 

  14. Papaemmanuil E, Cazzola M, Boultwood J, Malcovati L, Vyas P, Bowen D et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011; 365: 1384–1395.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011; 478: 64–69.

    CAS  Article  PubMed  Google Scholar 

  16. Carbuccia N, Murati A, Trouplin V, Brecqueville M, Adelaide J, Rey J et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 2009; 23: 2183–2186.

    CAS  Article  PubMed  Google Scholar 

  17. Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009; 145: 788–800.

    CAS  Article  PubMed  Google Scholar 

  18. Patnaik MM, Lasho TL, Hodnefield JM, Knudson RA, Ketterling RP, Garcia-Manero G et al. SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood 2012; 119: 569–572.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Lasho TL, Jimma T, Finke CM, Patnaik M, Hanson CA, Ketterling RP et al. SRSF2 mutations in primary myelofibrosis: significant clustering with IDH mutations and independent association with inferior overall and leukemia-free survival. Blood 2012; 120: 4168–4171.

    CAS  Article  PubMed  Google Scholar 

  20. Abdel-Wahab O, Pardanani A, Patel J, Wadleigh M, Lasho T, Heguy A et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia 2011; 25: 1200–1202.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F et al. Revised International Prognostic Scoring System for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Porrata LF, Ristow K, Habermann TM, Ozsan N, Dogan A, Macon W et al. Absolute monocyte/lymphocyte count prognostic score is independent of immunohistochemically determined cell of origin in predicting survival in diffuse large B-cell lymphoma. Leuk Lymphoma 2012; 53: 2159–2165.

    Article  PubMed  Google Scholar 

  23. Patnaik MM, Hanson CA, Hodnefield JM, Knudson R, Van Dyke DL, Tefferi A . Monosomal karyotype in myelodysplastic syndromes, with or without monosomy 7 or 5, is prognostically worse than an otherwise complex karyotype. Leukemia 2011; 25: 266–270.

    CAS  Article  PubMed  Google Scholar 

  24. Tefferi A . Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010; 24: 1128–1138.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Gelsi-Boyer V, Brecqueville M, Devillier R, Murati A, Mozziconacci MJ, Birnbaum D . Mutations in ASXL1 are associated with poor prognosis across the spectrum of malignant myeloid diseases. J Hematol Oncol 2012; 5: 12.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Current study is supported in part by grants from the ‘Myeloproliferative Disorders Foundation, Chicago, IL, USA’ and ‘The Henry J. Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA’.

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Correspondence to A Tefferi.

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Patnaik, M., Padron, E., LaBorde, R. et al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia 27, 1504–1510 (2013). https://doi.org/10.1038/leu.2013.88

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  • DOI: https://doi.org/10.1038/leu.2013.88

Keywords

  • survival
  • prognosis
  • CMML
  • ASXL1

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