Chronic myelomonocytic leukemia
Chronic myelomonocytic leukemia | |
---|---|
Blood film, genetic testing | |
Frequency | Less than 1 per 100,000 per year |
Chronic myelomonocytic leukemia (CMML) is a type of
CMML shows characteristics of a
Signs and symptoms
One of the most common signs of CMML is
Cause
Although the cause of CMML is unknown, environmental
Pathogenesis
With a high rate of
Genetic mutations
Clonal genetic abnormalities are common in CMML but they are not specific for diagnosis of the disease. The most common found are the 8+, −7/del (7q) and structural 12p abnormalities.
Diagnosis
The phenotypical characteristics of CMML are;
Classification
Leukemia subtypes are categorised into single clinical entities so that they can be diagnosed and treated appropriately. Leukaemias are subdivided into
FAB classification
The
WHO classification
In 2001, the WHO Classification of Myeloid Neoplasms was published, classifying CMML into a new group of diseases, the myelodysplastic/myeloproliferative neoplasms (MDS/MPN), reflecting the disease's neoplastic nature. Other diseases in this category are
Diagnostic criteria
FAB criteria
The FAB criteria for diagnosis are as follows:[21]
- Monocyte count >1x109/L
- 0–19% blasts in bone marrow
- <5% blasts in peripheral blood
The FAB also arbitrarily categorises CMML into myelodysplastic-like and myeloproliferative-like groups. A white blood count of 13x109 is used as a cut-off to differentiate the two.[12]
WHO criteria
The WHO criteria for diagnosis are as follows:[3]
- Persistent peripheral blood monocytosis with counts >1x109/L
- No Philadelphia chromosome or BCR-ABL1 fusion gene
- No rearrangement of PDGFRA or PDGFRB gene
- <20% myeloblasts, monoblasts and promonocytes in peripheral blood or bone marrow
- Dysplasia in one or more of the myeloid lineages; if myelodysplasia is absent or minimal then a diagnosis of CMML can be made if other requirements are met and:
- A molecular genetic abnormality is present in haematopoietic cells, or
- Monocytosis present for ≥3 months and other causes of monocytosis have been ruled out
WHO defined CMML has two main subsets, CMML-1 and CMML-2. CMML-1 is diagnosed if
- Myeloblasts, monoblasts or promonocytes are 5-19% in blood, or
- Myeloblasts, monoblasts or promonocytes are 10-19% in bone marrow, or
- Auer rods are present
CMML-1 and CMML-2 can be additionally grouped as CMML-1 or CMML-2 with eosinophilia. These are diagnosed if the above criteria are met and the blood eosinophil count is >1.5x109/L.[8]
Presence of two or more phenotypic abnormalities can aid a diagnosis of CMML in the absence of identifying cytogenetic or dysplastic features. These can include the expression of CD56 and/or CD2, or under-expression of HLA-DR.[3]
Prognosis
Factors affecting prognosis
CMML-2 has a reduced overall survival as compared with CMML-1, with median survivals of 15 and 20 months, respectively. Myeloproliferative CMML (>13x109 monocytes/L) has a reduced survival compared with myelodysplastic CMML. A platelet count of <100 x109/L reduces overall survival. A haemoglobin level of <10g/dL has a reduced overall survival. Some cytogenetic abnormalities have implications on the prognosis of CMML. Normal karyotypes or the single loss of the Y chromosome have low risk prognoses. Trisomy 8, chromosome 7 abnormalities and complex karyotypes comprise a high risk group. Other cytogenetic abnormalities have intermediate prognoses. Somatic mutations in genes such as ASXL1 and EZH2 are associated with a poor prognosis.[12]
CMML has a 20–30% chance of transformation to AML, a lower rate than other similar diseases. The CMML-2 subtype is associated with increased risk of transformation and ASXL1 and RUNX1 mutations also increase the risk of transition to AML.[12][22][23]
Scoring systems
IPSS
The International Prognostic Scoring System (IPSS) was developed in the mid-1990s to assess the prognosis of MDS patients. This system stratifies cases into 2 groups; a lower-risk group (sub divided into low and intermediate-1) and a higher risk (subdivided into intermediate-2 and high). It uses the blast percentage, number of cytopenias and bone marrow cytogenetics data to place cases of CMML into these groups. Due to the scoring system being developed for MDS, the more myeloproliferative cases of CMML (WBC >13x109) are excluded from the scoring system. Although the IPSS scoring system is used clinically, there is a high variability in each group. For this reason, new modalities for assessing prognosis in MDS (and CMML) are being developed.[12][24]
MD Anderson Prognostic Scoring System
A new method developed using data from the
The Düsseldorf score
The Düsseldorf score stratifies cases using four categories, giving one point for each; bone marrow blasts ≥5%, LDH >200U/L, haemoglobin ≤9g/dL and a platelet count ≤100,000/uL. A score of 0 indicates a low risk group' 1-2 indicates an intermediate risk group and 3-4 indicates a high risk group. The cumulative 2 year survival of scores 0, 1-2 and 3-4 is 91%, 52% and 9%; and risk of AML transformation is 0%, 19% and 54% respectively.[10]
Treatment
The treatment of CMML remains challenging due to the lack of clinical trials investigating the disease as its own clinical entity. It is often grouped with MDS in clinical trials, and for this reason the treatment of CMML is very similar to that of MDS. Most cases are dealt with as supportive rather than curative because most therapies do not effectively increase survival. Indications for treatment include the presence of B symptoms, symptomatic organ involvement, increasing blood counts, hyperleukocytosis, leukostasis and/or worsening cytopenias.[6][10]
Blood transfusions and erythropoietin administration are used to raise haemoglobin levels in cases with anemia.[6]
Hematopoietic stem cell transplantation remains the only curative treatment for CMML. However, due to the late age of onset and presence of other illnesses, this form of treatment is often not possible.[5][28]
Epidemiology
There have been few individual epidemiological studies of CMML, due to the difficulty in the disease classification. CMML has an estimated incidence of less than 1 per 100,000 persons per year.[12] The median age of diagnosis is 65–75. CMML has a propensity for males rather than females, at a ratio of 1.5–3:1.[8]
References
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- ^ "FDA Approves New Therapy for Myelodysplastic Syndromes (MDS) That Can Be Taken at Home". U.S. Food and Drug Administration (FDA) (Press release). 7 July 2020. Retrieved 7 July 2020. This article incorporates text from this source, which is in the public domain.
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