Chronic myeloid leukaemia is a malignant clonal disorder of haematopoietic stem cells.
At presentation, one-third of patients may be asymptomatic; if present, symptoms typically include malaise, fever, weight loss, abdominal discomfort, and night sweats.
Splenomegaly is the most common physical finding; nearly all patients will have elevated WBC count.
Presence of Philadelphia chromosome and /or molecular demonstration of the BCR-ABL transcript confirms diagnosis.
Treatment with a BCR-ABL tyrosine kinase inhibitor (TKI) gives long-term remission without significant adverse events in most patients.
Treatment-free remission may be attempted for select patients, and thus functional cure after TKI therapy is feasible.
Chronic myeloid leukaemia (CML) is a malignant clonal disorder of the haematopoietic stem cell that results in marked myeloid hyperplasia of the bone marrow. Dysregulation of haematopoiesis arises due to a BCR-ABL fusion gene that causes an abnormal expansion of myeloid cells in the bone marrow and peripheral blood. The 'chronic phase' of the disease may transform to an 'accelerated' or 'blast' phase in 5% to 10% of patients despite treatment with a tyrosine kinase inhibitor, the latter resulting in acute myeloid or acute lymphoblastic leukaemia (ALL).
History and exam
Key diagnostic factors
- presence of risk factors
- shortness of breath
- left upper quadrant discomfort or fullness
- sternal tenderness
Other diagnostic factors
- weight loss
- excessive sweating
- retinal haemorrhages
- age 65 to 74 years
- ionising radiation exposure
- male sex
1st investigations to order
- complete metabolic profile
- peripheral blood smear
- bone marrow biopsy
- cytogenetic studies
- quantitative reverse transcription PCR (qRT-PCR) including breakpoint analysis
- fluorescent in situ hybridisation (FISH)
relapse after allogeneic HSCT or allogeneic HSCT contraindicated
Michael J. Mauro, MD
Leader, Myeloproliferative Neoplasms Program, Leukemia Service
Attending Physician and Member
Memorial Sloan Kettering Cancer Center
Professor, Weill Cornell Medicine
MJM has received institutional research support for clinical trials from Novartis, Bristol Myers Squibb, Takeda, and Sun Pharma/Sparc, and honoraria for consulting/advisory boards from Novartis, Bristol Myers Squibb, Takeda, and Pfizer.
Dr Michael Mauro would like to gratefully acknowledge Dr Tim Somervaille, Dr Han Myint, and Dr Robert Chen, the previous contributors to this topic.
TS has received travel support and speaker expenses from Novartis, and has served as a consultant to Novartis for development of drugs for indications other than CML. HM sits on the advisory board of Novartis and Bristol-Myers Squibb, and also does speaking engagements on their behalf. RC declares that he has no competing interests.
Rebecca Connor, MD
Section of Hematology and Oncology
Department of Internal Medicine
Wake Forest University Baptist Medical Center
RC declares that she has no competing interests.
Richard E. Clark, MA, MD, FRCP, FRCPath
Professor of Haematology
Royal Liverpool University Hospital
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