Diagnosis and Treatment of Chronic Myelomonocytic Leukemias in Adults: Recommendations From the European Hematology Association and the European LeukemiaNet

Abstract

Chronic myelomonocytic leukemia (CMML) is a disease of the elderly, and by far the most frequent overlap myelodysplastic/myeloproliferative neoplasm in adults. Aside from the chronic monocytosis that remains the cornerstone of its diagnosis, the clinical presentation of CMML includes dysplastic features, cytopenias, excess of blasts, or myeloproliferative features including high white blood cell count or splenomegaly. Prognosis is variable, with several prognostic scoring systems reported in recent years, and treatment is poorly defined, with options ranging from watchful waiting to allogeneic stem cell transplantation, which remains the only curative therapy for CMML. Here, we present on behalf of the European Hematology Association and the European LeukemiaNet, evidence- and consensus-based guidelines, established by an international group of experts, from Europe and the United States, for standardized diagnostic and prognostic procedures and for an appropriate choice of therapeutic interventions in adult patients with CMML.

Figure 1

Flow cytometry panel of CD14 and CD16 expression on gated monocytes in (A) an aged healthy donor, a patient with reactive monocytosis, and a CMML case, showing in the latter a proportion of CD14+/CD16− monocytes >94% (reproduced with permission from Selimoglu-Buet et al) and (B) in a CMML patient before, during, and after occurrence of a chondritis inflammatory episode (reproduced with permission from Selimoglu-Buet et al). CMML = chronic myelomonocytic leukemia.

Figure 2

Therapeutic algorithm for lower-risk CMML patients. ∗According to proposed CMML prognostic scores.^,,,,@ Indicates nonfit (patients with multiple comorbidities and/or poor performance) or fit (patients with no comorbidities and good performance status). ^† Indicates failure of nontransplant strategies. Nontransplant interventions may include >1 line of nontransplant intervention. ∗∗ Indicates poor-risk features (defined as poor-risk cytogenetics, persistent blast increase [>50% or with >15% BM blasts], life-threatening cytopenias [neutrophil counts, <0.3 × 10⁹/L; platelet counts, <30 × 10⁹/L], high red blood cell transfusion intensity ≥2 units per months for 6 months; poor-risk molecular features). ^# Indicates transplant strategies (all forms of hematopoietic stem cell transplantation, see text). BM = bone marrow, CMML = chronic myelomonocytic leukemia.

Figure 3

Therapeutic algorithm for higher-risk CMML patients. ∗According to proposed CMML prognostic scores. ^,,,,@ Indicates nonfit (patients with multiple comorbidities and/or poor performance) or fit (patients with no comorbidities and good performance status). ^† Indicates failure of nontransplant strategies. Nontransplant interventions may include >1 line of nontransplant intervention. ∗∗ Indicates poor-risk features (defined as poor-risk cytogenetics, persistent blast increase [>50% or with >15% BM blasts], life-threatening cytopenias [neutrophil counts, <0.3 × 10⁹/L; platelet counts, <30 × 10⁹/L], high red blood cell transfusion intensity ≥2 units per months for 6 months; poor-risk molecular features). ^# Indicates transplant strategies (all forms of hematopoietic stem cell transplantation, see text). BM = bone marrow, CMML = chronic myelomonocytic leukemia.

Figure 4

Treatment strategies in patients not candidates for transplant.