Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Myelodysplastic syndrome

Chronic myelomonocytic leukemia diagnosis and management

Abstract

Chronic myelomonocytic leukemia (CMML) is a rare, heterogeneous myeloid malignancy classified as a myelodysplastic syndromes/myeloproliferative neoplasm (MDS/MPN) overlap syndrome by the World Health Organization (WHO). Its initial presentation can be incidental or associated with myelodysplastic or myeloproliferative symptoms and up to 20% of patients harbor a concurrent inflammatory or autoimmune condition. Persistent monocytosis is the hallmark of CMML but diagnosis can be challenging. Increased understanding of human monocyte subsets, chromosomal abnormalities, and somatic gene mutations have led to more accurate diagnosis and improved prognostication. A number of risk stratification systems have been developed and validated but using those that incorporate molecular information such as CMML Prognostic Scoring System (CPSS)-Mol, Mayo Molecular, and Groupe Francophone des Myelodysplasies (GFM) are preferred. Symptom-directed approaches forms the basis of CMML management. Outcomes vary substantially depending on risk ranging from observation for a number of years to rapidly progressive disease and acute myeloid leukemia (AML) transformation. Patients who are low risk but with symptoms from cytopenias or proliferative features such as splenomegaly may be treated with hypomethylating agents (HMAs) or cytoreductive therapy, respectively, with the goal of durable symptoms control. Allogeneic hematopoietic cell transplantation should be considered for intermediate to high risk patients. The lack of effective pharmaceutical options has generated interest in novel therapeutics for this disease, and early phase clinical trial results are promising.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: The chronic myeloid neoplasms continuum.
Fig. 2: Recurrent gene mutations in CMML.
Fig. 3: CMML treatment algorithm.

References

  1. 1.

    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391–405.

    CAS  Article  Google Scholar 

  2. 2.

    Guru Murthy GS, Dhakal I, Mehta P. Incidence and survival outcomes of chronic myelomonocytic leukemia in the United States. Leuk Lymphoma. 2017;58:1648–54.

    PubMed  Article  Google Scholar 

  3. 3.

    Patnaik MM, Tefferi A. Chronic myelomonocytic leukemia: 2020 update on diagnosis, risk stratification and management. Am J Hematol. 2020;95:97–115.

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Solary E, Itzykson R. How I treat chronic myelomonocytic leukemia. Blood 2017;130:126–36.

    CAS  PubMed  Article  Google Scholar 

  5. 5.

    Zahid MF, Barraco D, Lasho TL, Finke C, Ketterling RP, Gangat N, et al. Spectrum of autoimmune diseases and systemic inflammatory syndromes in patients with chronic myelomonocytic leukemia. Leuk Lymphoma. 2017;58:1488–93.

    PubMed  Article  Google Scholar 

  6. 6.

    Grignano E, Mekinian A, Braun T, Liozon E, Hamidou M, Decaux O, et al. Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: a series of 26 cases and literature review. Leuk Res. 2016;47:136–41.

    PubMed  Article  Google Scholar 

  7. 7.

    Peker D, Padron E, Bennett JM, Zhang X, Horna P, Epling-Burnette PK, et al. A close association of autoimmune-mediated processes and autoimmune disorders with chronic myelomonocytic leukemia: observation from a single institution. Acta Haematol. 2015;133:249–56.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Ma WT, Gao F, Gu K, Chen DK. The role of monocytes and macrophages in autoimmune diseases: a comprehensive review. Front Immunol. 2019;10:1140.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  9. 9.

    Ambinder AJ, Miller J, DeZern AE. Autoimmune disease in CMML-the chicken or the egg? Best Pract Res Clin Haematol. 2020;33:101136.

    PubMed  Article  Google Scholar 

  10. 10.

    Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976;33:451–8.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292–302.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN, et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010;116:e74–80.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Guilliams M, Mildner A, Yona S. Developmental and functional heterogeneity of monocytes. Immunity 2018;49:595–613.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Selimoglu-Buet D, Wagner-Ballon O, Saada V, Bardet V, Itzykson R, Bencheikh L, et al. Characteristic repartition of monocyte subsets as a diagnostic signature of chronic myelomonocytic leukemia. Blood 2015;125:3618–26.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Talati C, Zhang L, Shaheen G, Kuykendall A, Ball M, Zhang Q, et al. Monocyte subset analysis accurately distinguishes CMML from MDS and is associated with a favorable MDS prognosis. Blood 2017;129:1881–3.

    CAS  PubMed  Article  Google Scholar 

  16. 16.

    Patnaik MM, Timm MM, Vallapureddy R, Lasho TL, Ketterling RP, Gangat N, et al. Flow cytometry based monocyte subset analysis accurately distinguishes chronic myelomonocytic leukemia from myeloproliferative neoplasms with associated monocytosis. Blood Cancer J. 2017;7:e584.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Tarfi S, Badaoui B, Freynet N, Morabito M, Lafosse J, Toma A, et al. Disappearance of slan-positive non-classical monocytes for diagnosis of chronic myelomonocytic leukemia with associated inflammatory state. Haematologica. 2019;105:e147–e152.

  18. 18.

    Solary E, Wagner-Ballon O, Selimoglu-Buet D. Incorporating flow cytometry and next-generation sequencing in the diagnosis of CMML. Are we ready for prime? Best Pract Res Clin Haematol. 2020;33:101134.

    PubMed  Article  Google Scholar 

  19. 19.

    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;99:840–9.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Such E, Cervera J, Costa D, Sole F, Vallespi T, Luno E, et al. Cytogenetic risk stratification in chronic myelomonocytic leukemia. Haematologica 2011;96:375–83.

    PubMed  Article  Google Scholar 

  21. 21.

    Tang G, Zhang L, Fu B, Hu J, Lu X, Hu S, et al. Cytogenetic risk stratification of 417 patients with chronic myelomonocytic leukemia from a single institution. Am J Hematol. 2014;89:813–8.

    PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    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;89:1111–5.

    CAS  PubMed  Article  Google Scholar 

  23. 23.

    Patel BJ, Przychodzen B, Thota S, Radivoyevitch T, Visconte V, Kuzmanovic T, et al. Genomic determinants of chronic myelomonocytic leukemia. Leukemia 2017;31:2815–23.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Itzykson R, Fenaux P, Bowen D, Cross NCP, Cortes J, De Witte T, et al. Diagnosis and treatment of chronic myelomonocytic leukemias in adults: recommendations from the European Hematology Association and the European LeukemiaNet. Hemasphere. 2018;2:e150.

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Chan O, Padron E. Moving towards a uniform risk stratification system in CMML—How far are we? Best Pract Res Clin Haematol. 2020;33:101131.

    PubMed  Article  Google Scholar 

  26. 26.

    Ball M, List AF, Padron E. When clinical heterogeneity exceeds genetic heterogeneity: thinking outside the genomic box in chronic myelomonocytic leukemia. Blood 2016;128:2381–7.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Elmariah H, DeZern AE. Chronic myelomonocytic leukemia: 2018 update to prognosis and treatment. Curr Hematol Malig Rep. 2019;14:154–63.

    PubMed  Article  Google Scholar 

  28. 28.

    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  PubMed  Article  Google Scholar 

  29. 29.

    Gelsi-Boyer V, Trouplin V, Roquain J, Adelaide 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;151:365–75.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Sallman DA, Komrokji R, Cluzeau T, Vaupel C, Al Ali NH, Lancet J, et al. ASXL1 frameshift mutations drive inferior outcomes in CMML without negative impact in MDS. Blood Cancer J. 2017;7:633.

    PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    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;5:e280.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Geyer JT, Tam W, Liu YC, Chen Z, Wang SA, Bueso-Ramos C, et al. Oligomonocytic chronic myelomonocytic leukemia (chronic myelomonocytic leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic myelomonocytic leukemia. Mod Pathol. 2017;30:1213–22.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Valent P, Orazi A, Savona MR, Patnaik MM, Onida F, van de Loosdrecht AA, et al. Proposed diagnostic criteria for classical chronic myelomonocytic leukemia (CMML), CMML variants and pre-CMML conditions. Haematologica 2019;104:1935–49.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Valent P. Oligo-monocytic CMML and other pre-CMML states: clinical impact, prognostication and management. Best Pract Res Clin Haematol. 2020;33:101137.

    PubMed  Article  Google Scholar 

  35. 35.

    Germing U, Strupp C, Aivado M, Gattermann N. New prognostic parameters for chronic myelomonocytic leukemia. Blood 2002;100:731–2.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    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;121:3005–15.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Schuler E, Schroeder M, Neukirchen J, Strupp C, Xicoy B, Kundgen A, et al. Refined medullary blast and white blood cell count based classification of chronic myelomonocytic leukemias. Leuk Res. 2014;38:1413–9.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Loghavi S, Sui D, Wei P, Garcia-Manero G, Pierce S, Routbort MJ, et al. Validation of the 2017 revision of the WHO chronic myelomonocytic leukemia categories. Blood Adv 2018;2:1807–16.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Elena C, Galli 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;128:1408–17.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  40. 40.

    Patnaik MM, Itzykson R, Lasho TL, Kosmider O, Finke CM, Hanson CA, et al. ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia 2014;28:2206–12.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    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;31:2428–36.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Patnaik MM, Barraco D, Lasho TL, Finke CM, Hanson CA, Ketterling RP, et al. DNMT3A mutations are associated with inferior overall and leukemia-free survival in chronic myelomonocytic leukemia. Am J Hematol. 2017;92:56–61.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    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:e333.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  44. 44.

    Grossmann V, Kohlmann A, Eder C, Haferlach C, Kern W, Cross NC, et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia 2011;25:877–9.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Patnaik MM, Vallapureddy R, Lasho TL, Hoversten KP, Finke CM, Ketterling R, et al. EZH2 mutations in chronic myelomonocytic leukemia cluster with ASXL1 mutations and their co-occurrence is prognostically detrimental. Blood Cancer J. 2018;8:12.

    PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Damm F, Itzykson R, Kosmider O, Droin N, Renneville A, Chesnais V, et al. SETBP1 mutations in 658 patients with myelodysplastic syndromes, chronic myelomonocytic leukemia and secondary acute myeloid leukemias. Leukemia 2013;27:1401–3.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Savona MR, Malcovati L, Komrokji R, Tiu RV, Mughal TI, Orazi A, et al. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults. Blood 2015;125:1857–65.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Hunter AM, Zhang L, Padron E. Current management and recent advances in the treatment of chronic myelomonocytic leukemia. Curr Treat Options Oncol. 2018;19:67.

    PubMed  Article  Google Scholar 

  49. 49.

    Merlevede J, Droin N, Qin T, Meldi K, Yoshida K, Morabito M, et al. Mutation allele burden remains unchanged in chronic myelomonocytic leukaemia responding to hypomethylating agents. Nat Commun. 2016;7:10767.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Hunter A, Al Ali N, Mai A, Talati C, Kuykendall A, Sweet KL, et al. Leukocytosis is associated with end organ damage in chronic myelomonocytic leukemia (CMML) and can be mitigated with cytoreductive therapy. Blood 2018;132:3109.

    Article  Google Scholar 

  51. 51.

    Wattel E, Guerci A, Hecquet B, Economopoulos T, Copplestone A, Mahe B, et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood 1996;88:2480–7.

    CAS  PubMed  Article  Google Scholar 

  52. 52.

    Xicoy B, Germing U, Jimenez MJ, Garcia O, Garcia R, Schemenau J, et al. Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia. Eur J Haematol. 2016;97:33–8.

    CAS  PubMed  Article  Google Scholar 

  53. 53.

    Moyo V, Lefebvre P, Duh MS, Yektashenas B, Mundle S. Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol. 2008;87:527–36.

    CAS  PubMed  Article  Google Scholar 

  54. 54.

    Hunter AM, Al Ali N, Sallman DA, Sweet KL, Kuykendall AT, Talati C, et al. WHO-defined Chronic Myelomonocytic Leukemia-2 (CMML-2) patients rapidly progress to AML suggesting this entity represents a transitory clinical state. Blood 2019;134:1717.

    Article  Google Scholar 

  55. 55.

    Symeonidis A, van Biezen A, de Wreede L, Piciocchi A, Finke J, Beelen D, et al. Achievement of complete remission predicts outcome of allogeneic haematopoietic stem cell transplantation in patients with chronic myelomonocytic leukaemia. A study of the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation. Br J Haematol. 2015;171:239–46.

    PubMed  Article  Google Scholar 

  56. 56.

    Damaj G, Duhamel A, Robin M, Beguin Y, Michallet M, Mohty M, et al. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Societe Francaise de Greffe de Moelle et de Therapie-Cellulaire and the Groupe-Francophone des Myelodysplasies. J Clin Oncol. 2012;30:4533–40.

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Kongtim P, Popat U, Jimenez A, Gaballa S, El Fakih R, Rondon G, et al. Treatment with hypomethylating agents before allogeneic stem cell transplant improves progression-free survival for patients with chronic myelomonocytic leukemia. Biol Blood Marrow Transpl. 2016;22:47–53.

    CAS  Article  Google Scholar 

  58. 58.

    Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20:2429–40.

    CAS  PubMed  Article  Google Scholar 

  59. 59.

    Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794–803.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Costa R, Abdulhaq H, Haq B, Shadduck RK, Latsko J, Zenati M, et al. Activity of azacitidine in chronic myelomonocytic leukemia. Cancer 2011;117:2690–6.

    CAS  PubMed  Article  Google Scholar 

  61. 61.

    Wijermans PW, Ruter B, Baer MR, Slack JL, Saba HI, Lubbert M. Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res. 2008;32:587–91.

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Fianchi L, Criscuolo M, Breccia M, Maurillo L, Salvi F, Musto P, et al. High rate of remissions in chronic myelomonocytic leukemia treated with 5-azacytidine: results of an Italian retrospective study. Leuk Lymphoma. 2013;54:658–61.

    CAS  PubMed  Article  Google Scholar 

  63. 63.

    Coston T, Pophali P, Vallapureddy R, Lasho TL, Finke CM, Ketterling RP, et al. Suboptimal response rates to hypomethylating agent therapy in chronic myelomonocytic leukemia; a single institutional study of 121 patients. Am J Hematol. 2019;94:767–79.

    CAS  PubMed  Google Scholar 

  64. 64.

    Santini V, Allione B, Zini G, Gioia D, Lunghi M, Poloni A, et al. A phase II, multicentre trial of decitabine in higher-risk chronic myelomonocytic leukemia. Leukemia 2018;32:413–8.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Meldi K, Qin T, Buchi F, Droin N, Sotzen J, Micol JB, et al. Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia. J Clin Invest. 2015;125:1857–72.

    PubMed  PubMed Central  Article  Google Scholar 

  66. 66.

    Duchmann M, Yalniz FF, Sanna A, Sallman D, Coombs CC, Renneville A, et al. Prognostic role of gene mutations in chronic myelomonocytic leukemia patients treated with hypomethylating agents. EBioMedicine 2018;31:174–81.

    PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Ebrahem Q, Mahfouz RZ, Ng KP, Saunthararajah Y. High cytidine deaminase expression in the liver provides sanctuary for cancer cells from decitabine treatment effects. Oncotarget 2012;3:1137–45.

    PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019;6:e194–e203.

    PubMed  Article  Google Scholar 

  69. 69.

    Garcia-Manero G, Griffiths EA, Steensma DP, Roboz GJ, Wells R, McCloskey J, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood 2020;136:674–83.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  70. 70.

    Garcia-Manero G, McCloskey J, Griffiths EA, Yee KWL, Zeidan AM, Al-Kali A, et al. Pharmacokinetic exposure equivalence and preliminary efficacy and safety from a randomized cross over phase 3 study (ASCERTAIN study) of an oral hypomethylating agent ASTX727 (cedazuridine/decitabine) compared to IV decitabine. Blood 2019;134:846.

    Article  Google Scholar 

  71. 71.

    Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-beta superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014;20:408–14.

    CAS  PubMed  Article  Google Scholar 

  72. 72.

    Platzbecker U, Germing U, Gotze KS, Kiewe P, Mayer K, Chromik J, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose-finding study with long-term extension study. Lancet Oncol. 2017;18:1338–47.

    CAS  PubMed  Article  Google Scholar 

  73. 73.

    Fenaux P, Platzbecker U, Mufti GJ, Garcia-Manero G, Buckstein R, Santini V, et al. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020;382:140–51.

    CAS  PubMed  Article  Google Scholar 

  74. 74.

    Geissler K, Ohler L, Fodinger M, Virgolini I, Leimer M, Kabrna E, et al. Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells. J Exp Med. 1996;184:1377–84.

    CAS  PubMed  Article  Google Scholar 

  75. 75.

    Geissler K, Jager E, Barna A, Alendar T, Ljubuncic E, Sliwa T, et al. Chronic myelomonocytic leukemia patients with RAS pathway mutations show high in vitro myeloid colony formation in the absence of exogenous growth factors. Leukemia 2016;30:2280–1.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  76. 76.

    Padron E, Painter JS, Kunigal S, Mailloux AW, McGraw K, McDaniel JM, et al. GM-CSF-dependent pSTAT5 sensitivity is a feature with therapeutic potential in chronic myelomonocytic leukemia. Blood 2013;121:5068–77.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  77. 77.

    Patnaik MM, Sallman DA, Mangaonkar AA, Heuer R, Hirvela J, Zblewski D, et al. Phase 1 study of lenzilumab, a recombinant anti-human GM-CSF antibody, for chronic myelomonocytic leukemia. Blood 2020;136:909–13.

    PubMed  Article  Google Scholar 

  78. 78.

    Padron E, DeZern AE, Niyongere S, Ball MC, Balasis M, Ramadan H, et al. Promising results of a phase 1/2 clinical trial of ruxolitinib in patients with chronic myelomonocytic leukemia. Blood 2017;130:162.

    Google Scholar 

  79. 79.

    Pemmaraju N, Lane AA, Sweet KL, Stein AS, Vasu S, Blum W, et al. Tagraxofusp in blastic plasmacytoid dendritic-cell neoplasm. N Engl J Med. 2019;380:1628–37.

    CAS  PubMed  Article  Google Scholar 

  80. 80.

    Patnaik MM, Ali H, Gupta V, Schiller GJ, Lee S, Yacoub A, et al. Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with relapsed/refractory chronic myelomonocytic leukemia (CMML). J Clin Oncol. 2019;37:7059.

    Article  Google Scholar 

  81. 81.

    Savona MR, Kantarjian HM, Roboz GJ, O’Connell CL, Walsh KJ, Tibes R, et al. Landmark response and survival analyses from 102 MDS and CMML patients treated with guadecitabine in a phase 2 study showing that maximum response and survival is best achieved with adequate treatment duration. Blood 2019;134:2957.

    Article  Google Scholar 

  82. 82.

    Assi R, Kantarjian HM, Garcia-Manero G, Cortes JE, Pemmaraju N, Wang X, et al. A phase II trial of ruxolitinib in combination with azacytidine in myelodysplastic syndrome/myeloproliferative neoplasms. Am J Hematol. 2018;93:277–85.

    CAS  PubMed  Article  Google Scholar 

  83. 83.

    Itzykson R, Santini V, Chaffaut C, Lionel A, Thepot S, Giagounidis A, et al. Decitabine versus hydroxyurea for advanced proliferative CMML: results of the Emsco randomized phase 3 dacota trial. Blood 2020;136:53–4.

    Article  Google Scholar 

  84. 84.

    Ades L, Watts JM, Radinoff A, Arnan M, Cerrano M, Lopez PF, et al. Phase II study of pevonedistat (P) + azacitidine (A) versus A in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML), or low-blast acute myelogenous leukemia (LB AML) (NCT02610777). J Clin Oncol. 2020;38:7506.

    Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

O.C. wrote the original draft and made some of the figures. A.R. revised the manuscript and made some of the figures. E.P. revised the manuscript and supervised the work.

Corresponding authors

Correspondence to Aline Renneville or Eric Padron.

Ethics declarations

Conflict of interest

EP: research funding from Incyte, Kura Oncology and BMS, honoraria from Novartis. The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chan, O., Renneville, A. & Padron, E. Chronic myelomonocytic leukemia diagnosis and management. Leukemia (2021). https://doi.org/10.1038/s41375-021-01207-3

Download citation

Search

Quick links