Background
Chronic myelomonocytic leukemia (CMML) is a rare de novo clonal hematopoietic stem cell disorder with overlapping features of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN). The diagnosis is challenging and carrying risk for leukemic transformation. The median age at CMML diagnosis is ~71-73 years, with a male preponderance. According to the 2016 World Health Organization (WHO) classification of myeloid neoplasms, CMML is characterized by the presence of sustained (>3 months) peripheral blood (PB) monocytosis (≥1 × 109/L; monocytes ≥10% of white blood cell count) along with dysplastic features in the bone marrow (BM). < 20% blasts/blasts equivalent in the PB and BM. It has recommended categorization of CMML into "proliferative" (MPN-CMML) and "dysplastic" (MDS-CMML) sub-types; based on a total leukocytic count (TLC) (of ≥13 × 109/L for MPN-CMML). Also, based on PB and BM blast %, CMML can be sub-classified into three categories; (a) CMML-0 (<2% PB blasts including promonocytes and <5% BM blasts), (b) CMML-1 (2-4% PB blasts including promonocytes and 5%-9% BM blasts), and (c) CMML-2 (>5% PB blasts including promonocytes and 10%-19% BM blasts and/or when any Auer rods are present.
Objective: To retrospectively analyze the cases of CMML diagnosed in the Hematology Department, National Center for Cancer Care and Research (NCCCR), Doha, Qatar from January 2013 to July 2020 with the assessment of risk and prognosis.
Materials and methods: The results from flow cytometry, cytology, PB, and BM morphology, cytogenetics and molecular genetics were re-estimated. The CMML-specific prognostic scoring system (CPSS) was used for the risk stratification.
Results:12 patients diagnosed as CMML were detected and included in the study, 10 males and 2 females, with a median age of 64 years. 3 Arabs and 9 non-Arabs. 10 patients were transfusion dependent. 6 patients had splenomegaly and 2 of them had massive splenomegaly (>20 cm in craniocaudal length).
According to the TLC, 8 were myeloproliferative (CMML/MP) and 4 were myelodysplastic CMML. 4 of our patients were below 40 years (classified as young adults as per WHO) and all were of the proliferative type.
The flow cytometry of PB and/or BM was done to 11 patients. The monocytic cells were characterized by co-expressing CD14 and CD64 and showed aberrant expression of CD56 on 5 patients. According to the morphology of the BM, one case was described as MDS/MPN or MPN, and the rest of the cases were diagnosed as MDS/MPN. According to WHO 2016 diagnostic criteria of CMML: one case was diagnosed as CMML0, one case was diagnosed as CMML1, 9 cases were diagnosed as CMML2 and one case was diagnosed as MPN/MDS -CMML2 or as MPN. The cytogenetic risk was high in 4 patients, intermediate in one patient, and low in 7 patients. According to CPSS, one patient was an intermediate risk I, 4 was intermediate-risk II, and 7 were high risk. Molecular analysis and NGS were done for 4 patients that were most recently diagnosed. One case showed NRAS in 30%, one case showed KRAS in 57%, one case showed DNMT3A and NPM1 each 42% and one case showed WT1 (36%), FLT3 (33%) and NPM1 (15%).
Regarding management and supportive care, 10 out of 12 patients required transfusion support. 4 patients (3 Proliferative and one Dysplastic) were not eligible for active management and received only symptomatic treatment. 5 patients of the proliferative type were started on hydroxyurea. The other 3 patients were of dysplastic subtype who received hypomethylating agent +/- allogenic bone marrow transplant.
6 patients traveled back to their home country and lost follow up, 5 expired, and one patient still alive.
Conclusion: CMML is a unique and rare hematopoietic neoplasm with complex biology and pathology. It is an aggressive rare disease that carries a dismal prognosis, with poor survival and a high risk of transformation. The therapeutic options are limited. In our clinic, for the 7 years period, CMML was confirmed only in 12 patients. The great majority of them were old males of the non-Arab nationality, transfusion-dependent, presented with TLC (> 13x10^3/ul Proliferative) of CMML2 subtype and high CPSS risk score. 33% of our patients were young adults (less than 40 years old) and were of the proliferative type. The combination of clinical, morphological, immunophenotyping, cytogenetic and molecular information is required to improve the accuracy of CMML prognostication.
Disclosures
No relevant conflicts of interest to declare.
Immunophenotypes of Chronic Myelomonocytic Leukemia (CMML) Subtypes by Flow Cytometry
