Chronic myelomonocytic leukemia (CMML) is a rare hematologic malignancy classified as a myelodysplastic/myeloproliferative neoplasm (MDS/MPN). The packet definition characterizes CMML by persistent monocytosis, absence of the Philadelphia chromosome and BCR/ABL fusion gene, fewer than 20% blasts in bone marrow and blood, myelodysplasia, and absence of PDGFRA or PDGFRB rearrangements. CMML is an acquired myeloid malignancy; no Mendelian inheritance pattern and no germline causative genes are recorded in this packet. Juvenile myelomonocytic leukemia (JMML, MONDO:0011908) is listed as a related subtype within the MONDO classification.

Individual HPO-coded phenotype records are not present in this packet. CMML is an acquired myeloid malignancy arising in adults, with bone marrow pathology producing cytopenias and persistent monocytosis as definitional features. Clinical trial enrollment criteria across active studies in this packet specify adult patient populations with confirmed CMML.

CMML is an acquired hematologic malignancy. No germline causative genes and no Mendelian inheritance patterns are documented in this packet. Somatic mutations in hematopoietic progenitors drive disease development. The packet definition distinguishes CMML from chronic myelogenous leukemia by the absence of the Philadelphia chromosome and BCR/ABL, and from other MDS/MPN entities by the absence of PDGFRA or PDGFRB rearrangements.

Diagnosis requires confirmation of persistent monocytosis, bone marrow and blood blast counts below 20%, myelodysplastic features, and laboratory exclusion of both Philadelphia chromosome/BCR/ABL and PDGFRA/PDGFRB rearrangements, as specified in the packet definition. Active clinical trials use these diagnostic criteria as eligibility requirements.

No FDA-approved treatments are listed in this packet's approved_treatments field. Three active orphan designations are recorded: a co-packaged azacitidine/cedazuridine combination (Taiho Oncology), a recombinant SIRPalpha-Fc fusion protein (ImmuneOnco), and a humanized anti-LILRB4 monoclonal antibody (Immune-Onc Therapeutics). A fourth compound holds WITHDRAWN designation status and is not a current option. Orphan designation does not constitute FDA approval. Phase 1 and Phase 2 trials (NCT04655755, MD Anderson; NCT05600894, NCI) evaluate venetoclax combined with ASTX727 in CMML.

Population-level survival statistics are not provided in this packet. The research landscape encompasses 277 classified publications, with case reports as the dominant study type alongside 50 reviews and active biomarker-focused publications. The absence of approved therapies and the active orphan drug pipeline reflect an area of ongoing unmet therapeutic need.

Active investigations include NCT04655755 (Phase 1, MD Anderson) and NCT05600894 (Phase 2, NCI) evaluating venetoclax with ASTX727 for CMML; NCT07046078 (Phase 2, Fred Hutchinson) examining FLAG-Ida chemotherapy followed by hematopoietic cell transplant in high-grade myeloid malignancies; NCT05233618 (Phase 1) evaluating tagraxofusp for post-transplant CMML maintenance; and NCT04603001 (Phase 1, Eli Lilly) examining LY3410738 in IDH1/IDH2-mutant hematologic malignancies. The 277-article publication base documents biomarker and investigational therapeutic activity.