Definition, Etiology, Pathogenesis Top
Chronic myelomonocytic leukemia (CMML) is a rare (0.3 cases/100,000 people/year) clonal hematologic disorder characterized by persistent monocytosis in peripheral blood, the absence of the Ph chromosome and BCR-ABL1 gene, and ≤20% blasts in bone marrow.
Clinical Features And Natural History Top
General symptoms are weakness (anemia), weight loss (anorexia), low-grade or high-grade fever, and night sweats.
Signs and symptoms of cytopenia include features of anemia (easy fatigability, tachycardia, pale skin), neutropenia (increased susceptibility to infections), and thrombocytopenia (bleeding).
Signs and symptoms caused by extramedullary leukemic infiltrates: Hepatosplenomegaly, lymphadenopathy, cutaneous lesions; pleural, pericardial, and peritoneal effusions in patients with high monocyte counts.
Natural history depends on the stage of the disease (CMML-1 or CMML-2). The risk of transformation to acute myelogenous leukemia (AML) is 15% to 30%. The median survival is between 20 and 40 months.
1. Complete blood count: Monocytosis >1000/microL, white blood cell (WBC) counts normal or slightly decreased (neutropenia) in ~50% of patients, otherwise slightly increased; mild basophilia and eosinophilia; moderate thrombocytopenia is frequent, and in some patients atypical giant platelets may be observed; normocytic (rarely macrocytic) anemia.
2. Bone marrow examination: In 75% of patients, bone marrow aspiration reveals increased bone marrow cellularity, usually with dominant neutrophil or erythroid lineage and evident monocytic proliferation; >50% of patients have dysplastic changes, and in >80% of patients, megakaryocytes with abnormal nuclear segmentation are observed. In ~30% of cases, trephine biopsy also reveals bone marrow fibrosis.
3. Cytogenetic and molecular studies, immunophenotyping: Nonspecific clonal cytogenetic abnormalities are observed in 20% to 40% of patients. About 20% of patients with CMML have the JAK2 mutation.
4. Imaging studies: Abdominal ultrasonography may reveal hepatosplenomegaly, lymphadenopathy, and ascites. Chest radiographs may show pleural effusions. Echocardiography may reveal pericardial effusion.
1. The World Health Organization diagnostic criteria:
1) Persistent peripheral blood monocytosis >1000/microL.
2) Absence of the Ph chromosome and BCR-ABL1 gene.
3) Absence of PDGFRA and PDGFRB gene rearrangements.
4) Peripheral and bone marrow blasts (myeloblasts, monoblasts, promonocytes) <20% (patients with >20% blasts are diagnosed with AML).
5) Dysplasia of ≥1 hematopoietic lineages (in patients with minimal or no dysplasia, the following additional criteria must be fulfilled: presence of acquired clonal cytogenetic abnormalities in bone marrow cells, monocytosis lasting ≥3 months, exclusion of other causes of monocytosis).
2. CMML subtypes:
1) Myelodysplastic CMML (MD-CMML): WBC count ≤13,000/microL.
2) Myeloproliferative CMML (MP-CMML): WBC count >13,000/microL.
1. Infection: Bacterial infections (tuberculosis, syphilis, endocarditis), viral infections (cytomegalovirus, varicella/zoster, herpes simplex), fungal infections (acute and chronic).
2. Diseases of the gastrointestinal system: Inflammatory bowel disease (Crohn disease, ulcerative colitis), alcoholic liver disease, celiac disease.
3. Systemic connective tissue diseases, for instance, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis syndromes, polymyositis.
4. Granulomatous diseases, such as sarcoidosis.
5. Hematopoietic disorders: Acute monocytic and myelomonocytic leukemias, chronic myelogenous leukemia, myeloid neoplasms with the PDGFRB gene rearrangement, non-Hodgkin lymphoma, chronic lymphocytic leukemia, Hodgkin lymphoma, multiple myeloma, Waldenström macroglobulinemia, hemolytic anemia, Langerhans cell histiocytosis, immune thrombocytopenic purpura.
6. Other: Glucocorticoid therapy, splenectomy, tetrachloroethane poisoning, convalescence phase of acute infections, bone marrow regeneration after radiotherapy or chemotherapy, use of granulocyte colony-stimulating factor or granulocyte and macrophage colony-stimulating factor.
1. Supportive treatment as in myelodysplastic syndromes.
2. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment; it may be considered in younger patients for whom a human leukocyte antigen-matched donor is available. The results of HSCT are similar to those achieved in patients with myelodysplastic syndrome.
3. Cytoreductive treatment: Usually with hydroxyurea (INN hydroxycarbamide); this is used mainly in MP-CMML.
4. Hypomethylating agents: Azacitidine is used in patients with MD-CMML and ≥10% blasts in bone marrow.
Chemotherapy rarely achieves complete remissions. The average survival is longer in MD-CMML (16-31 months) than in MP-CMML (11-17 months).