Chronic myelogenous leukemia diagnostic study of choice

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2]

Overview

Chronic myelogenous leukemia is diagnosed clinically, based on history and symptoms and is confirmed with karyotyping or FISH. There is no single diagnostic study of choice, different techniques are applied so far to detect philadelphia chromosome, BCR-ABL oncogene,

Diagnostic Study of Choice

Study of choice

• There is no single diagnostic study of choice for the diagnosis of chronic myelogenous leukemia.

• Chronic myelogenous leukemia is primarily diagnosed based on the clinical presentation, supported by the typical findings in the blood and bone marrow, and then confirmed by using one of the following:
  • Conventional cytogenetics
  • Fluorescence in situ hybridization (FISH) analysis
  • Reverse transcription polymerase chain reaction (RT-PCR)

Diagnostic results

• 

  Philadelphia chromosomes

  

  Philadelphia chromosome

  The following findings on performing PCR is confirmatory for Chronic myelogenous leukemia:
  • The Philadelphia chromosome
  • The BCR-ABL1 fusion gene
  • The BCR-ABL1 fusion mRNA

Sequence of Diagnostic Studies

• The peripheral blood studies must be performed as a first step when:

• The patient presented with signs of:
  • Anemia
  • Lecopenia
  • Thrombocytopenia

• Peripheral blood studies may show:
  • Absolute leukocytosis (median of 100,000/µL) with a left shift and classic myelocyte bulge (more myelocytes than the more mature metamyelocytes seen on the blood smear)
  • Blasts usually number <2%;
  • Absolute basophilia, in 90% of cases
  • Monocytosis is often seen, but generally not an increased monocyte percentage
  • Absolute monocytosis is more prominent in the unusual cases with a p190 BCR-ABL
  • Platelet count is usually normal or elevated
  • Thrombocytopenia suggests an alternative diagnosis or the presence of advanced stage, rather than chronic phase, disease.

• The various investigations must be performed in the following order:
  • Peripheral blood studies
  • Bone marrow biopsy

Name of Diagnostic Criteria:

• WHO criteria of diagnosing different phases of chronic myeloid leukemia is following:

WHO Criteria of diagnosing different phases of CML

CML chronic phase	CML accelerated phase	CML blast phase
Granulocytosis in the presence of ph chromosome and/or BCR/ABL	Increasing spleen size and WBC unresponsive to therapy	Blasts ≥ 20% in perpheral blood and bone marrow
NO sign of CML accelerated phase	Cytogenetic evidence of clonal evolution of Blasts 10–19% in peripheral blood and/or bone marrow	Extramedullary blast proliferation
	Peripheral blood basophils ≥ 20%	Large foci or clusters of blasts in the bone marrow biopsy
	Persistent thrombocytopenia (< 100 x 109/L) unrelated to therapy or Persistent thrombocytosis (> 1000 x 109/L) unresponsive to therapy