This is a bit clinical, however as I am sending this site around looking for the best treatment, this diagnosis and this type of "double" leukemia is very rare, so I needed to put a  clinical description in here.  Basically it is both myeloprolific  (too many immature cells beong made that affect the spleen and liver and myelodysplastic What does the term "myelodysplastic" actually mean?Myelo = blood cells and Dysplastic = abnormal development or growth. So, when you have myelodysplastic syndrome, this means that your blood cells have an unusual shape and that they have abnormal growth.

Chronic myelomonocytic leukemia

Epidemiology

Pathophysiology

CMML was initially characterized as a myelodysplastic syndrome because of the associated dysplasia and cytopenia observed in some patients; however, some patients display myeloproliferative features (increased myelopoiesis).⁵ High peripheral monocyte counts are often associated with pericardial, pleural, synovial, and ascitic effusions, as well as hepatomegaly and splenomegaly secondary to tissue infiltration by monocytes.

Signs and Symptoms

Patients with the dysplastic or proliferative form of CMML may have shortness of breath, fatigue, bleeding or bruising, or they might have infections as the blood counts decrease secondary to splenic sequestration, dysplasia, crowding out of normal hematopoietic cells by myeloproliferation, or a combination of these factors. As noted earlier, patients with the myeloproliferative form can develop splenomegaly (enlarged spleen) hepatomegaly (enlarged liver) skin lesions, and effusions and can present with abdominal pain or swelling, shortness of breath, or joint swelling.¹⁶

Diagnosis

The diagnosis requires evaluation of peripheral blood monocyte counts, in addition to bone marrow aspirate and biopsy (Fig. 8). Cytogenetics as well as molecular methods including fluorescence in situ hybridization (FISH) or RT-PCR forBCR/ABL1 fusion should be performed to rule out CML.

Figure 8: Click to Enlarge

Treatment

Supportive care for CMML includes transfusions and growth factor therapy. The active treatment of CMML has been disappointing. Younger patients with a human leukocyte antigen (HLA)–identical sibling should be evaluated for allogeneic bone marrow transplantation.¹⁶ However, most patients with CMML are older and are not candidates for bone marrow transplantation. Low-dose chemotherapy (cytosine arabinoside) has low response rates, and intensive chemotherapy has been less active than in MDS.¹⁶Hydroxyurea may be used for patients with splenomegaly (enlarged spleen) or high leukocyte counts; however, the responses are often partial, and blood counts can decrease during treatment. Investigators have examined other agents such as etoposide (VP-16). In a randomized trial, hydroxyurea yielded higher response rates and better survival than etoposide in patients with advanced CMML.¹⁶ Other agents, such as topotecan, a topoisomerase I inhibitor, have also been studied. However, their long-term impact, and the result of combining them with other agents, is unknown. Hypomethylating agents and farnesyltransferase inhibitors have also been evaluated.

A subset of patients who have CMML with eosinophilia have a t(5;12)(q33;p13) translocation, encoding a TEL/PDGFRβfusion protein. This group of patients might benefit from treatment with imatinib, which inhibits PDGFR as well as the BCR/ABL1 kinase.

Outcomes

The prognosis in CMML is highly dependent on the number of blasts in the bone marrow.⁵ The life expectancy can vary from several months to several years. A study of 213 patients with CMML was used to define a prognostic scoring system.¹⁵In a multivariate analysis, hemoglobin lower than 12 g/dL, the presence of circulating immature myeloid cells, an absolute lymphocyte count higher than 2.5 × 10⁹/L, and 10% or more marrow blasts were associated with a shorter survival.¹⁵ Based on the number of adverse factors (0 to 4), four subgroups of patients could be defined (low, intermediate 1, intermediate 2, and high risk), with respective median survivals of 24, 15, 8, and 5 months. This scoring system has subsequently been validated in a separate set of patients.

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Jak2 and myeloproliferative disorders

Janus kinase 2 is a tyrosine kinase. Constitutive activation of tyrosine kinases can lead to uncontrolled cell growth. Recently, the V617F mutation in JAK2 was found in a significant proportion of myeloproliferative disorders (60%-90% of PV and 50%-60% of ET and CIMF).¹⁷ Other JAK2 mutations have now been identified (i.e., exon 12). The presence of this mutation is determined by PCR assays and may be helpful in differentiating a myeloproliferative disorder from a reactive cause for elevated counts. JAK2 allele burden might also be important in identifying high-risk patients with PV or ET (i.e. those at risk for requiring treatment with chemotherapy or those at risk for developing major cardiovascular complications).¹⁸ Incorporation of this information may lead to a risk-adapted treatment approach in the future. Clinical trials with small molecule inhibitors of JAK2 are currently enrolling patients, and these drugs will likely become an important part of the therapeutic armamentarium.

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Summary

• The myeloproliferative disorders include polycythemia vera, chronic idiopathic myelofibrosis, essential thrombocythemia, and chronic myelogenous leukemia. Chronic myelomonocytic leukemia has features that overlap traditional myelodysplastic and myeloproliferative disorders.
• Myeloproliferative disorders are characterized by the clonal proliferation of one or more hematopoietic cell lineages.
• Review of the peripheral blood film and a bone marrow aspirate or biopsy is needed to make a definitive diagnosis.
• Reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in-situ hybridization (FISH) for theBCR/ABL1gene fusion should be performed to rule out chronic myelogenous leukemia.
• Janus kinase 2, a tyrosine kinase, is mutated in a significant proportion of myeloproliferative disorders, and may represent a therapeutic target.

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