A clinical case report illustrates the complex treatment landscape for chronic myelomonocytic leukemia (CMML), a heterogeneous hematopoietic disorder with overlapping features of myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS), collectively referred to as MDS/MPN.

A 76-year-old male with a history of medical issues, including nicotine and alcohol dependence, presented with worsening bilateral lower extremity swelling and shortness of breath over 3 months. His initial evaluation revealed severe anemia, bilateral lower extremity edema, and elevated B-type natriuretic peptide. Laboratory results showed high white blood cell count, markedly low hemoglobin, and decreased platelets.

Further examination of a peripheral blood smear demonstrated dysgranulopoiesis, anisocytosis, and abnormal nuclear forms. Bone marrow analysis indicated myeloid hyperplasia, increased blast cells, and dysplasia in multiple cell lineages.

Molecular studies revealed mutations in ASXL1, ETV6, EZH2, and SMC1A, leading to a diagnosis of CMML within the MDS/MPN category.

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Due to the patient’s age and risk factors, hospice care was initially considered, but the family declined and opted for nonchemotherapy treatments. Hydroxyurea, prednisone, and epoetin were administered, with limited success. Subsequent lenalidomide treatment did not significantly impact blood transfusion requirements.

“Unlike some typical MDS cases in which a combination of lenalidomide, steroid and erythropoietin have proven effective in reducing or even eliminating the need for repeated blood transfusion, our patient failed to show any response to such therapy. The case presented here may be unique in that the patient was diagnosed correctly as CMML but failed to respond to any conventional therapy,” the author wrote in Clinical Case Reports.

A switch to azacitidine resulted in a dramatic and concerning increase in white blood cell count, leading to treatment discontinuation. Despite various interventions, including high-dose hydroxyurea, the patient’s condition continued to deteriorate. He eventually passed away under hospice care.


Islam A. An unusual response to 5-azacitidine by a patient with chronic myelomonocytic leukemia. Clin Case Rep. Published online August 2, 2023. doi:10.1002/ccr3.7748