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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Chronic myelomonocytic leukaemia and its relatives are bone-marrow cancers that behave partly like myelodysplasia (poorly made blood cells) and partly like a proliferative disease (an excess of monocytes or platelets). Hypomethylating agents produce responses in a minority and stabilise counts in more, transplant can cure the fit, and RAS-pathway and JAK inhibitors are in trials.
The myelodysplastic/myeloproliferative neoplasms combine dysplasia and cytopenias with proliferation. Chronic myelomonocytic leukaemia (CMML) is the prototype: persistent monocytosis (above 0.5 x 10^9/L and at least 10 percent of leukocytes under WHO 2022) with dysplasia, absence of BCR-ABL1 and of PDGFRA/B, FGFR1 or JAK2 rearrangements, and a characteristic mutational profile: TET2 and SRSF2 co-mutation in around half, with ASXL1, RUNX1, SETBP1 and RAS-pathway (NRAS, KRAS, CBL) mutations driving the proliferative phenotype and worse outcome. The other members are atypical CML (SETBP1, ETNK1; dysplastic neutrophilia), MDS/MPN with SF3B1 mutation and thrombocytosis (ring sideroblasts, often with JAK2 V617F), MDS/MPN not otherwise specified, and in children juvenile myelomonocytic leukaemia (JMML; RAS-pathway, neurofibromatosis type 1 and Noonan syndrome). Risk is scored by CPSS and the molecular CPSS-Mol, which incorporate blast count, white count, transfusion need, cytogenetics and ASXL1, NRAS, RUNX1 and SETBP1 mutations.
Allogeneic transplant is the only curative therapy and is offered to fit patients with higher-risk disease. Hypomethylating agents are the drug standard: azacitidine and decitabine are approved for CMML (the oral decitabine-cedazuridine label also includes CMML), producing responses in a minority and stabilising counts in more, without clear evidence that they change the mutational clone. Hydroxyurea controls proliferative disease and splenomegaly and was as good as etoposide in the only randomised trial. JMML is treated with azacitidine as a bridge to transplant, the only cure. For MDS/MPN with ring sideroblasts, luspatercept and JAK inhibitors are used by extension from MDS and MPN. Trials are testing RAS-pathway inhibition (MEK inhibitors), JAK inhibition (ruxolitinib in proliferative CMML), the anti-GM-CSF antibody lenzilumab, venetoclax combinations for accelerated disease, and hypomethylating-agent combinations.
| Setting | Approach | Guideline |
|---|---|---|
| Higher-risk CMML, fit with a donor | Allogeneic haematopoietic stem cell transplant, often after hypomethylating-agent cytoreduction; the only curative option. | NCCN Category 2A |
| Higher-risk or symptomatic CMML, not transplant candidate | Azacitidine or decitabine (or oral decitabine-cedazuridine) until progression; supportive care with transfusion and growth factors. | NCCN Category 2A |
| Proliferative CMML with symptomatic leucocytosis or splenomegaly | Hydroxyurea (superior to etoposide in the randomised GFM trial); ruxolitinib in trials for symptomatic proliferative disease. | not mapped |
| Juvenile myelomonocytic leukaemia | Allogeneic transplant; azacitidine as bridging therapy (EMA approval 2019 for JMML); watchful waiting for some CBL- or Noonan-associated cases that regress spontaneously. | not mapped |