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Models of Prognostication in Chronic Myelomonocytic Leukemia

  • Myelodysplastic Syndromes (M Savona, Section Editor)
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Abstract

Purpose of Review

Within the group of the myelodysplastic/myeloproliferative overlap neoplasms of the adult age, chronic myelomonocytic leukemia (CMML) is characterized by an extremely variable clinical course. This review aims to cover over the years main advancements in the identification of CMML clinical and biological features associated to survival outcomes and the consequent development of prognostic tools for individual patient treatment decision making.

Recent Findings

According to the last WHO classification of myeloid neoplasms, three subgroups of patients may be recognized on the base of percentage of blasts in marrow and in peripheral blood (CMML-0, CMML-1, and CMML-2), with corresponding decreasing life-expectations. Nonetheless, in each of the subgroups, prominent disparateness of biological characteristics associates to a large heterogeneity of clinical presentation, with very different prognostic implications. Recent findings indicate that the integration of clinical and molecular data appears to provide the most helpful prognostic information.

Summary

Together with an orderly enlightenment for the increasing conception of specific disease characteristics, this review offers a comprehensive and thoughtful summary of the prognostic models developed over the last three decades for CMML.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood. 2008;112(1):45–52.

    Article  CAS  PubMed  Google Scholar 

  2. •• Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):blood-2016-03-643544. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27069254. This article includes the very last WHO diagnostic and subclassification criteria for CMML.

  3. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick H, et al. The chronic myeloid leukaemias: guidelines for distinguishing chronic granulocytic, atypical chronic myeloid, and chronic myelomonocytic leukaemia. Proposals by the French-American-British Cooperative Leukaemia Group. Br J Haematol. 1994;87(4):746–54. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7986717

    Article  CAS  PubMed  Google Scholar 

  4. Onida F, Beran M. Diagnosis and management of chronic myelomonocytic leukemia. 3, Current Hematologic Malignancy Reports. 2008. p. 31–6.

  5. Onida F, Barosi G, Leone G, Malcovati L, Morra E, Santini V, et al. Management recommendations for chronic myelomonocytic leukemia: consensus statements from the SIE, SIES, GITMO groups. Haematologica. 2013;98(9):1344–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51(2):189–99.

    Article  CAS  PubMed  Google Scholar 

  7. Solal-Celigny P, Desaint B, Herrera A, Chastang C, Amar M, Vroclans M, et al. Chronic myelomonocytic leukemia according to FAB classification: analysis of 35 cases. Blood. 1984;63(3):634–8. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6582939

    CAS  PubMed  Google Scholar 

  8. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol. 1985;59(3):425–33.

    Article  CAS  PubMed  Google Scholar 

  9. Alessandrino EP, Orlandi E, Brusamolino E, Lazzarino M, Morra E, Castagnola C, et al. Chronic myelomonocytic leukemia: clinical features, cytogenetics, and prognosis in 30 consecutive cases. Hematol Oncol. 1985;3(2):147–55.

    Article  CAS  PubMed  Google Scholar 

  10. Fenaux P, Jouet JP, Zandecki M, Lai JL, Simon M, Pollet JP, et al. Chronic and subacute myelomonocytic leukaemia in the adult: a report of 60 cases with special reference to prognostic factors. Br J Haematol. 1987;65(1):101–6.

    Article  CAS  PubMed  Google Scholar 

  11. Stark J, Head C, Roberts BE, Scott CS. AN. T. Prognostic factors and survival in chronic myelomonocytic leukaemia (CMML). Br J Cancer. 1987;56(1):59–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. van der Weide M, Sizoo W, Nauta JJ, Krefft J, Langenhuijsen MM. Myelodysplastic syndromes: analysis of clinical and prognostic features in 96 patients. Eur J Haematol. 1988;41(2):115–22. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3165865

    Article  PubMed  Google Scholar 

  13. García S, Sanz MA, Amigo V, Colomina P, Carrera MD, Lorenzo JI, et al. Prognostic factors in chronic myelodysplastic syndromes: a multivariate analysis in 107 cases. Am J Hematol. 1988;27(3):163–8.

    Article  PubMed  Google Scholar 

  14. Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F. Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases. J Clin Oncol. 1988;6(9):1417–24.

    Article  CAS  PubMed  Google Scholar 

  15. Worsley A, Oscier DG, Stevens J, Darlow S, Figes A, Mufti GJ, et al. Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol. 1988;68(1):17–21.

    Article  CAS  PubMed  Google Scholar 

  16. Sanz GF, Sanz MA, Vallespí T, Cañizo MC, Torrabadella M, García S, et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood. 1989;74(1):395–408. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2752119

    CAS  PubMed  Google Scholar 

  17. del Cañizo MC, Sanz G, San Miguel JF, Vallespi T, Irriguible D, Torrabadella M, et al. Chronic myelomonocytic leukemia—clinicobiological characteristics: a multivariate analysis in a series of 70 cases. Eur J Haematol. 1989;42(5):466–73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2731594

    Article  PubMed  Google Scholar 

  18. Tefferi A, Hoagland HC, Therneau TM, Pierre RV. Chronic myelomonocytic leukemia: natural history and prognostic determinants. Mayo Clin Proc. 1989;64(10):1246–54. Available from: http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L20005760%5Cnhttp://sfx.ub.rug.nl:9003/sfx_local?sid=EMBASE&issn=00256196&id=doi:&atitle=Chronic+myelomonocytic+leukemia:+Natural+history+and+prognostic+determinants&stitle=MAYO+CLIN

    Article  CAS  PubMed  Google Scholar 

  19. Storniolo AM, Moloney WC, Rosenthal DS, Cox C, Bennett JM. Chronic myelomonocytic leukemia. Leukemia. 1990;4(11):766–70.

    CAS  PubMed  Google Scholar 

  20. Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia. 1992;6(1):52–9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1736014

    CAS  PubMed  Google Scholar 

  21. Catalano L, Improta S, de Laurentiis M, Molica S, Majolino I, Musto P, et al. Prognosis of chronic myelomonocytic leukemia. Haematologica. 1996;81(4):324–9.

    CAS  PubMed  Google Scholar 

  22. 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(9):1315–23. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8371581

    CAS  PubMed  Google Scholar 

  23. Germing U, Kündgen A, Gattermann N. Risk assessment in chronic myelomonocytic leukemia (CMML). Leuk Lymphoma. 2004;45(7):1311–8.

    Article  CAS  PubMed  Google Scholar 

  24. 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(6):2079–88. Available from: http://www.bloodjournal.org/content/89/6/2079.abstract

    CAS  PubMed  Google Scholar 

  25. 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(6):1351–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Schanz J, Tüchler H, Solé F, Mallo M, Luño E, Cervera J, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820–9.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Malcovati L, Della Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23(30):7594–603.

    Article  PubMed  Google Scholar 

  28. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.

    Article  PubMed  Google Scholar 

  29. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring system (IPSS-R) for myelodysplastic syndromes. Blood [Internet]. 2012;2454–65. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22740453 .

  30. Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH, Glassman AB, Albitar M, Kwari MI, Beran M. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients Prognostic factors and scoring systems in chronic myelomonocytic leukemia : a retrospective analysis of 213 patients. Blood. 2002;99(3):840–9.

  31. Germing U, Strupp C, Aivado M, Gattermann N. New prognostic parameters for chronic myelomonocytic leukemia? Blood. 2002;100:731–3.

    Article  CAS  PubMed  Google Scholar 

  32. Beran M, Wen S, Shen Y, Onida F, Jelinek J, Cortes J, et al. Prognostic factors and risk assessment in chronic myelomonocytic leukemia: validation study of the M.D. Anderson Prognostic Scoring System. Leuk Lymphoma. 2007;48(6):1150–60.

    Article  PubMed  Google Scholar 

  33. Parikh SA, Tefferi A. Chronic myelomonocytic leukemia: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. 2013;88(11):967–74.

    Article  CAS  PubMed  Google Scholar 

  34. Itzykson R, Kosmider O, Renneville A, Morabito M, Preudhomme C, Berthon C, et al. Clonal architecture of chronic myelomonocytic leukemias. Blood. 2013;121(12):2186–98.

    Article  CAS  PubMed  Google Scholar 

  35. Itzykson R, Solary E. An evolutionary perspective on chronic myelomonocytic leukemia. Leukemia. 2013;27(7):1441–50. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23558522

    Article  CAS  PubMed  Google Scholar 

  36. Such E, Cervera J, Costa D, Solé F, Vallespí T, Luño E, et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica. 2011;96(3):375–83.

    Article  PubMed  Google Scholar 

  37. Such E, Germing U, Malcovati L, Cervera J, Kuendgen A, Della Porta MG, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood. 2013;121(15):3005–15.

    Article  CAS  PubMed  Google Scholar 

  38. Patnaik MM, Padron E, LaBorde RR, Lasho TL, Finke CM, Hanson CA, et al. Mayo prognostic model for WHO-defined chronic myelomonocytic leukemia: ASXL1 and spliceosome component mutations and outcomes. Leukemia. 2013;27(7):1504–10. Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=23531518&retmode=ref&cmd=prlinks%5Cnpapers2://publication/doi/10.1038/leu.2013.88

    Article  CAS  PubMed  Google Scholar 

  39. Itzykson R, Kosmider O, Renneville A, Gelsi-Boyer V, Meggendorfer M, Morabito M, et al. Prognostic score including gene mutations in chronic myelomonocytic leukemia. J Clin Oncol. 2013;31(19):2428–36.

    Article  CAS  PubMed  Google Scholar 

  40. Gelsi-Boyer V, Trouplin V, Roquain J, Adélaïde J, Carbuccia N, Esterni B, et al. ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia. Br J Haematol. 2010;151(4):365–75.

    Article  CAS  PubMed  Google Scholar 

  41. Xavier Calvo, Meritxell Nomdedeu, Rodrigo Santacruz, Núria Martínez, Dolors Costa, Arturo Pereira, Natalia Estrada, Blanca Xicoy, Jordi Esteve, Benet Nomdedeu. Comparison of three prognostic scoring systems in a series of 146 cases of chronic myelomonocytic leukemia (CMML): MD Anderson Prognostic Score (MDAPS), CMML-Specific Prognostic Scoring System (CPSS) and mayo prognostic model. In: Blood. 2014. p. 4660.

  42. Calvo X, Nomdedeu M, Santacruz R, Martínez N, Costa D, Pereira A, et al. Comparison of three prognostic scoring systems in a series of 146 cases of chronic myelomonocytic leukemia (CMML): MD Anderson prognostic score (MDAPS), CMML-specific prognostic scoring system (CPSS) and Mayo prognostic model. A detailed review of prognos. Leuk Res. 2015;39(11):1146–53.

    Article  Google Scholar 

  43. • Patnaik M, Itzykson R, Lasho T, Kosmider O, Finke C, Hanson C, et al. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia. 2014;28(11):2206–12. https://doi.org/10.1038/leu.2014.125. This article illustrates the Molecular Mayo Model of prognostication in CMML, developed by an important cooperative study of the Mayo Clinic with GFM.

    Article  CAS  PubMed  Google Scholar 

  44. • Wassie EA, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study. Am J Hematol. 2014;89(12):1111–5. The Mayo-French cytogenetic classification was the first to identify the negative prognostic significance of monosomal karyotype in CMML.

    Article  CAS  PubMed  Google Scholar 

  45. Alsahlawi A, Alkhateeb H, Patnaik M, Begna K, Elliott M, Hogan WJ, et al. Monosomal karyotype predicts adverse prognosis in patients diagnosed with chronic myelomonocytic leukemia: a single-institution experience. Clin Lymphoma Myeloma Leuk. 2015;15(2):39–41.

    Article  Google Scholar 

  46. •• Padron E, Garcia-Manero G, Patnaik MM, Itzykson R, Lasho T, Nazha A, et al. An international data set for CMML validates prognostic scoring systems and demonstrates a need for novel prognostication strategies. Blood Cancer J. 2015;5(7):e333. https://doi.org/10.1038/bcj.2015.53. This study reports on the comparison between the most important prognostic models in a joint dataset from a very large series of patients from eight tertiary cancer centers in three different countries.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. • Patnaik MM, Wassie EA, Padron E, Onida F, Itzykson R, Lasho TL, et al. Chronic myelomonocytic leukemia in younger patients: molecular and cytogenetic predictors of survival and treatment outcome. Blood Cancer J. 2015;4(1):e270. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25555161 . This was the first study to investigate on prognostic factors in young patients (age < 65 years) with CMML.

    Article  Google Scholar 

  48. •• Elena C, Gall A, Such E, Meggendorfer M, Germing U, Rizzo E, et al. Integrating clinical features and genetic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408–17. The CPSS-mol is the first model to incorporate multiple genes mutations together with clinical characteristics to assess prognosis of CMML patients.

  49. Francesco Onida, Simona Iacobelli, Guillermo Garcia-Manero, Mrinal M Patnaik, Raphaël Itzykson, Terra L. Lasho, Aziz Nazha, Raajit K. Rampal, Matias Eugenio Sanchez, Elias J. Jabbour, Najla H Al Ali, Zachary Thompson, Simona Colla, Pierre Fenaux, Hagop M. Kantarjian, Eric Solary and Eric Padron. A new clinically-based subclassification proposal in cmml with significant prognostic implications to overcome the MDS/MPN categorizing dilemma. Vol. 128, Blood. 2016.

  50. C. Rautenberg, E. Schuler, K. Nachtkamp, T. Schroeder, S. Blum, C. Aul, R. Haas, U. Germing. Validation of a new clinically based classification system for stratification of prognosis in patients with CMML. Vol. 55, Leukemia Research. 2017.

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  1. University of Milan - Dept. of Oncology and Hemato-Oncology Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico - Hematology/BMT Unit, Via Francesco Sforza no.35, 20122, Milan, Italy

    Francesco Onida

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Onida, F. Models of Prognostication in Chronic Myelomonocytic Leukemia. Curr Hematol Malig Rep 12, 513–521 (2017). https://doi.org/10.1007/s11899-017-0416-8

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