USMLE preparation and Medical PG Entrance- Chronic Myeloid Leukemia

Chronic Myeloid Leukemia:

  • Myeloproliferative stem-cell disorder
  • Proliferation of all haematopoietic lineages -predominantly in the granulocytic series
  • Characteristic genetic change – Reciprocal translocation between chromosomes 9 and 22 (Philadelphia (Ph) chromosome) 
  • List of Myeloproliferative disorders:
  • CML
  • Chronic Neutrophilic leukemia
  • Mastocytosis
  • Polycythemia Vera
  • Primary myelofibrosis
  • Chronic Eosinophilic leukemia ( NOS)
  • Essential Thrombocytosis
  • CML – 20 % of all cases of Leukemia
  • The disease is found in all races
  • Male predominance (1.4:1)
  • Average age at presentation – 50 yrs

Pathophysiology:

  • Cytogenetic aberration – Reciprocal translocation between the long arms of chromosomes 22 and 9 [t(9;22)]
  • The translocation results in a shortened chromosome 22
  • First described by Nowell and Hungerford
  • Relocation of an oncogene called ABLfrom the long arm of chromosome 9 to a specific breakpoint cluster region (BCR) in the long arm of chromosome 22
  • TheABLoncogene encodes a tyrosine protein kinase

Clinical Features:

–Easy fatigability

–Loss of sense of well-being

–Decreased tolerance to exertion

–Anorexia

–Abdominal discomfort

–Early satiety

–Weight loss

–Excessive sweating

  • Tiredness- M symptom- 37% cases
  • Weight loss-26%
  • Breathlessness

Laboratory studies

Blood counts and blood smear

  • Hemoglobin concentration is decreased
  • The leukocyte count raised
  • Immature WBs- Myelocytes, Promyelocytes, Metamyelocytes, Neutrophils, Blast ells
  • The basophil and eosinophil counts are increased (Absolute)
  • The platelet count is normal or increased

Biochemistry:

–Neutrophil Alkaline Phosphatase reduced ( Seen in around 90% cases)- Differentiate between Leukemoid reaction and myelofibrosis)

–Serum  transcobalamin increased

–Serum uric acid increased

–Increased Serum Alkaline Phosphatase level

–Lactate dehydrogenase increased

–Mean histamine levels increased

Bone Marrow studies

  • Hypercellular ( Fat-50%, cells-50% normally)
  • Mitotic figures are increased
  • Myeloid hyperplasia
  • M:E ratio increased
  • Macrophages that mimic Gaucher cells
  • Macrophages – engorged with lipids – yield ceroid pigment – imparting a granular and bluish cast – sea-blue histiocytes
  • Increased reticulin fibrosis (Collagen type III)
  • Angiogenesis
  • Increase in basophils, eosinophils

Course of the disease:

I. Chronic Phase

Most patients are asymptomatic

Incidental leukocytosis/splenomegaly

Bleeding and infectious complications are uncommon in the chronic phase 

2-5% blast cells seen

Accelerated phase:

  • Anemia progresses and cause fatigue, loss of sense of well-being
  • Aggressive phase
  • Splenomegaly
  • Ranges from 4-5 years
  • Blasts 10-19%
  • Basophilia > 20%

Blast crisis:

  • ≥20% blasts in blood or bone marrow
  • Resembles acute leukemia
  • Anemia worsens, Thrombocytopenia ous
  • Extramedullary Chloroma seen

–2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase

–Infection and bleeding common

–Abdominal pain, bone pain

Survival is 6-12 months (worse for myeloid phenotype)

Juvenile CML :

  • Common in children
  • Increase in Fetal Hemoglobin
  • Variant of CML
  • Philadelphia chromosome –e, BR-ABL negative
  • Monocytosis , Blast cells in BM < 20%
  • Thrombocytopenia
  • May be associated with Neurofibromatosis 1 and Noonan syndrome
  • Bad prognosis

Chronic Myelomonocytic Leukemia:

  • Clonal hematopoietic stem cell disorder
  • Myelodysplastic/myeloproliferative neoplasm by the 2008 WHO classification
  • Absolute monocytosis (>1 × 10(9) L(-1) ) in the peripheral blood > 3 months
  • Blast Cells are < 20% in blood or bone marrow
  • Philadelphia Chromosome is negative
  • Minimal dysplasia in myeloid lineages

Prognosis:

Sokal Index calculated

  • 1. Age
  • 2. Cytogenetics
  • Percentage of circulating blasts
  • Platelet count
  • Spleen size

Treatment:

Imatinib Mesylate

  • Hematological remission was seen in 95%
  • Now the treatment of choice for CML
  • Dose- 400mg/day

Be the first to comment

Leave a Reply

Your email address will not be published.


*