Diagnosis

A diagnosis of CML (chronic myeloid leukaemia) is often suspected in patients with persistent unexplained leukocytosis and/or splenomegaly.


The work-up for these patients includes a complete blood count, with a cellular differential and platelet count. A bone marrow aspirate and biopsy are essential to quantify the percentage of blasts and basophils, to evaluate the degree of fibrosis, and to retrieve the appropriate diagnostic material for cytogenetic-molecular analyses.

Philadelphia (Ph) Chromosome

The leukocyte alkaline phosphatase (LAP) test mentioned in medical records or medical literature, has been largely supplanted in recent years by genetic testing techniques.


The diagnosis of CML is now confirmed by finding the Philadelphia (Ph) chromosome on genetic analysis.

Alternative Diagnoses

About 10% of patients with the haematological and clinical features of CML do not have the Ph chromosome on cytogenetic studies. One third to one half of these patients, nevertheless, test positive for the abnormal gene, or the abnormal protein associated with this chromosome, when more sensitive studies, such as FISH or PCR, are used. These patients have a similar prognosis and response to treatment as patients with classic Ph+ CML.

 

In the remaining patients, where the definitive studies are either negative or unavailable, there may be uncertainty about the diagnosis.

 

 

Alternative diagnoses to be considered in such situations are:
 

  • Other myeloproliferative disorders
    • Myelofibrosis
    • Polycythaemia vera
    • Essential thrombocythaemia

  • Atypical CML—a Ph- and Bcr-Abl-negative myeloproliferative disease (the following discussion will explain Bcr-Abl), which has a worse prognosis than classical Ph+ CML
  • Chronic neutrophilic leukaemia—a rare disease associated with a clonal abnormality confined to neutrophil precursors; the clinical course is hetero-geneous, but characterised by a more sustained, mature neutrophilic leukocytosis, thrombocytosis, and a more indolent behaviour, with less tendency to transform into the blast phase
  • Chronic myelomonocytic leukaemia—one of the myelodysplastic syndromes, which clinically may resemble CML, (chronic myeloid leukaemia), but is Ph-
  • Juvenile chronic myeloid leukaemia—a rare Ph- disease of children associated with WBC findings similar to CML, but with a clinical course more closely resembling AML

 

Leukaemoid reaction—a marked elevation in WBC count not due to a haematological malignancy; often due to an undiagnosed inflammatory process or toxic response, but occasionally due to an underlying solid malignancy.
Read about Treatment Options for CML, including risk group assessment, criteria, and goals of therapy.