Chronic neutrophilic leukemia

The chronic Neutrophilenleukämie ( CNL ) is a rare disease of the hematopoietic system and is counted among the chronic myeloproliferative disorders ( within the meaning of the WHO classification 2001) and to the myeloproliferative neoplasms (as defined in the WHO classification 2008).

Epidemiology

The disease is very rare and the exact incidence is unknown ( in the literature have been less than 100 cases described ). Men and women seem to be equally affected. The disease usually occurs in adulthood.

Clinical features

The CNL is characterized by a proliferation of neutrophils in the blood and bone marrow. There is an enlargement of the liver and spleen ( hepatosplenomegaly ). The etiology of the disease is unknown.

Immunophenotype and genetics

Immunzytologisch shows the CNL are not specific. Cytogenetically usually shows a normal karyotype. In 2013, several scientific papers have been published that in patients with somatic CNL (ie acquired, not inherited ) mutations in the gene CSF3R ( colony stimulating factor 3 receptor ) have been reported on chromosome 1. These mutations seem to occur with high prevalence and specificity of CNL, so that they are suitable as a diagnostic marker.

Diagnostic criteria

The diagnosis can be made on certain criteria, due to the presence of:

  • > 80% of the leukocytes are granulocytes with segmented nuclei
  • <10 % of the leukocytes are granulocytic precursors ( metamyelocytes, myelocytes, promyelocytes )
  • <1% of the leukocytes are myeloblasts
  • Hyper -cellular bone marrow:
  • Proliferation of neutrophil granulocytes
  • <5% myeloblasts
  • No maturation disorders in neutrophils
  • Hepatosplenomegaly
  • No other reason for a Neutrophilenvermehrung:
  • No chronic infection or inflammatory disease
  • No tumor disease underlying
  • No Philadelphia chromosome or BCR -ABL oncogene
  • No other myeloproliferative disorder ( polycythemia vera, Essential thrombocythemia myelofibrosis )
  • No myelodysplastic syndrome, no chronic myelomonocytic leukemia

From the criteria it is clear that the diagnosis of CNL is usually provided as a diagnosis of exclusion. That is, until other, much more common diseases must be ruled out before a diagnosis of CNL can be provided. The main differences for CML are: 1, no evidence of BCR -ABL or Philadelphia chromosome, second only predominantly proliferation of mature neutrophils, hardly the immature precursors.

Therapy

There is no therapy studies due to the rarity of the disease. The disease can be treated with mild cytoreductive drugs as Hydroyurea. If there is a CSF3R mutation, a therapeutic trial with dasatinib should be done.

Literature and sources

  • Jaffe E, Harris NL, Stein H, Vardiman JW (eds): Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001
  • Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (eds): WHO Classification of Tumours of haematopoietic and lymphoid tissues, Fourth Edition. IARC Press: Lyon 2008, ISBN 92-832-2431-0
International Classification of Diseases for Oncology World Health Organization Leukocytosis Digital Object Identifier
189005
de