Updated on 23.04.2025

Introduction:

• It is a MPD characterized by sustained peripheral blood neutrophilia, bone marrow hypercellularity due to clonal neutrophilic granulocyte proliferation and hepatosplenomegaly.

Epidemiology:

• Around 150 cases reported
• Median age - 65 years

Pathogenesis:

• Mutation of gene encoding the receptor of colony stimulating factor 3 (CSF3R T618I)
• There is defective apoptosis leading to accumulation of segmented neutrophils in blood

Clinical Features:

• Fatigue, anorexia, weight loss, abdominal pain
• Splenomegaly
• Hepatomegaly
• Bleeding from mucocutaneous surface
• Gout and Pruritus
• Some progress to blast crisis

Investigations:

• Hemogram- Increased number of mature neutrophils
• Bone marrow:
  • Hypercellular with increased neutrophils and precursors
  • BM should be done in all cases, as some cases of myeloma can present like CNL.
• Cytochemistry
  • Neutrophil alkaline phosphatase – Increased
• Cytogenetics
  • No Ph Chromosome
  • 90%- Normal
  • 10%  show  +8, +9, del (20q), del (11q)
• PCR for BCR-ABL- CML with p230 has similar morphology to CNL, but it should be diagnosed as CML.
• CSF3R mutation testing
• S. Uric acid- Increased
• S. LDH- Increased
• S. Vitamin B12 and Vitamin B12 binding protein levels- Increased

Criteria for Diagnosis:

• Peripheral blood
  • White blood cell count>25,000/cmm
  • Segmented neutrophils plus banded neutrophils constitute >80% of the white blood cells
  • Neutrophil precursors (promyelocytes, myelocytes, and metamyelocytes) constitute < 10% of the white blood cells
  • Myeloblasts rarely observed
  • Monocyte count<1,000/cmm
• Bone marrow
  • Hypercellular
  • Neutrophil granulocytes increased in percentage and number
  • Neutrophil maturation appears normal
  • Myeloblasts constitute < 5% of the nucleated cells
• Not meeting WHO criteria for BCR-ABL1-positive chronic myeloid leukaemia, polycythaemia vera,essential thrombocythaemia, or primary myelofibrosis
• No rearrangement of PDGFRA, PDGFRB, or FGFR1, and no PCM1-JAK2 fusion
• CSF3R T6181 or another activating CSF3R mutation

or

Persistent neutrophilia (>3 months), splenomegaly, and no identifiable cause of reactiveneutrophilia including absence of a plasma cell neoplasm or, if a plasma cell neoplasm is present,demonstration of clonality of myeloid cells by cytogenetic or molecular studies

Prognosis:

• Mean survival – 6 months – 20 years
• Causes of death include- Intracranial bleed, severe infection, transformation to AML and toxic effects of intensive treatment

Treatment options:

• Ruxolitinib if there is CSF3R mutation
• Oral cytoreductive  agents- Hydroxyurea or Busulfan
• Interferon alpha
• Cytarabine
• HSCT in eligible patients- It is the only curative option.

Related Disorders:

• Chronic basophilic leukemia
  • Presents with general weakness, fatigue, fever, hepatosplenomegaly
  • Hyperhistaminemia leads to wheezing, urticaria, diarrhea, pruritus, peripheral edema
  • Peripheral smear
    • Leukocyte counts- normal / increased
    • Basophilia – 40-80%
    • Immature forms present
    • Basophils – Abnormal resembling tissue mast cells
  • LAP score- Normal
  • Serum & urine histamine levels: 10-15 times the normal.