Chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia ( CMML ) is a malignant disease of the hematopoietic system. She was formerly counted among the myelodysplastic syndromes ( MDS), has in some respects but similar to a myeloproliferative neoplasm ( MPN ), eg chronic myeloid leukemia (CML ), so that they in of the WHO classification of hematologic neoplasms will be out in 2008 as " MDS / MPN ".

Incidence, clinical manifestations, symptoms

Exact incidence figures do not exist. However, CMML is certainly a rare disease with an estimated 1-3 new cases per year and 100,000 people. It occurs practically exclusively in old age and the median age at diagnosis is approximately 55-65 years. Approximately half of the patients demonstrate at the time of diagnosis to a normal or even decreased leukocyte count in the blood. In the other half of the leukocyte count is increased. However, is always an absolute increase of the monocytes ( > 1000/μl ) in peripheral blood detected ( diagnostic criterion, see below). Splenomegaly ( enlarged spleen ) and / or hepatomegaly ( enlarged liver ) are often (but not always) to find. The complaints of the patients are usually relatively uncharacteristic: unintended weight loss, general weakness ( fatigue ), fever, night sweats, may bleeding tendency ( at thrombocytopenia ). The diagnosis is ultimately made ​​on the basis of clinical manifestations, the (multiple custom built in larger time interval ) differential blood count and a bone marrow examination.

Disease Definition, Causes

The CMML is a clonal disease, which originates from a genetically modified bone marrow stem cell. The descendants of these degenerate malignant stem cell spread in the bone marrow, there displace the healthy blood formation and eventually appear in the peripheral blood. The causes and nature of the genetic changes in CMML are so far poorly understood. A number of genetic mutations have been identified, but these are only found in a subset of patients.

Diagnostic criteria of the WHO

An expert panel of the World Health Organization ( WHO) has formulated the following four criteria for the diagnosis of CMML:

  • Monocytosis in peripheral blood > 1 x 109 / l or> 1000/μl ( normal value < 800/μl )
  • Less than 20 % blasts ( = myeloblasts, mono blasts and promonocytes ) in the bone marrow
  • No evidence of the BCR -ABL oncogene or Philadelphia chromosome
  • Dysplasia in one or more rows of myelopoiesis ( erythropoiesis, granulopoiesis, megakaryopoiesis )

For the diagnosis, all 4 criteria must be met. If criteria are met only 3 of these 4, mostly found other diagnoses:

  • When a Philadelphia chromosome or BCR -ABL is detected, the diagnosis is not CMML, but CML
  • When the Monozytenanteil below 1000/μl, the other criteria are met, however, would be more likely to make the diagnosis of another myelodysplastic syndrome
  • If more than 20 % blasts present in the bone marrow, the diagnosis is " acute myeloid leukemia ".

The WHO, however, has admitted in its diagnostic criteria that the diagnosis CMML can also be made ​​if no dysplasia is detected, the other criteria are met, however, and especially the monocytosis is without an identifiable external cause for at least 3 months.

The WHO classification of 2001 and 2008 attempted an even finer division into two subgroups:

  • CMML 1: less than 5 % blasts in peripheral blood and less than 10% blast cells in the bone marrow
  • CMML -2: 5-19 % blasts in peripheral blood and 10-19 % blasts in the bone marrow.

It was also suggested at a eosinophil count in the peripheral blood of> 1500/μl the Annex " with eosinophilia " attach (ie CMML -1 or CMML -2 with eosinophilia).

In a retrospective evaluation of the Düsseldorf MDS Registry showed that the two groups CMML -1 and CMML -2 have a different prognosis in terms of overall survival and the risk of progression of the disease towards acute myeloid leukemia. However, the classification of CMML remains in flux and will certainly experience more changes in the future.

Therapy

In December 2008, the European Commission Vidaza ® ( azacitidine ) as an orphan drug approved for the treatment of myelodysplastic syndromes has. The indication includes treatment of high-risk MDS patients in the categories " Int -2 " and " high-risk " according to the International Prognostic Scoring System ( IPSS ). The approval of Vidaza was also for acute myeloid leukemia with 20-30 % blasts in the bone marrow, which have emerged from a myelodysplastic syndrome or CMML.

Literature and sources

  • Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW ( eds ): WHO classification of Tumours of Haemopoietic and Lymphoid Tissues of. IARC Press: Lyon 2008 ISBN 9789283224310 ( WHO classification of 2008).
  • Jaffe E, Harris NL, Stein H, Vardiman JW ( eds ): Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001 ( WHO classification of 2001)
International Classification of Diseases for Oncology Haematologica
188810
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