Chronic Myeloid Leukemia (CML)

Snapshot

A 62-year-old man presents to his primary care provider for an urgent care visit. He reports feeling very fatigued recently. He denies any change in bowel movements or any blood in his stool. On physical exam, he has mild splenomegaly. Blood tests come back with increased leukocytosis with neutrophilic dominance and increased basophils. Concerned, his primary care provider refers him to hematology-oncology. His peripheral smear shows myeloid cells.

Introduction

Also known as chronic myelogenous leukemia
Clonal hematopoietic stem cell disorder
Pathogenesis
- Philadelphia chromosome
- translocation t(9;22)
- BCR-ABL fusion gene
  - hyperactive tyrosine kinase
Epidemiology
- median disease onset 67 years of age
- 15% of all adult leukemias
May transform into blast crisis
AML or ALL

Presentation

Symptoms
- B symptoms (fever, weight loss, fatigue)
- splenomegaly
  - LUQ discomfort
  - early satiety
Physical exam
splenomegaly common

Evaluation

Complete blood count with differential
- ↑ WBC
- ↑ neutrophils
- ↑ basophils
- ↑ metamyelocytes
↓ leukocyte alkaline phosphatase
- low activity in mature granulocytes
Bone marrow aspirate and biopsy
Cytogenetic analysis or FISH showing Philadelphia chromosome (most accurate)

Differential Diagnosis

Treatment

Medical management
- tyrosine kinase inhibitors are first-line
  - imatinib (Gleevec)
  - nilotinib
  - dasatinib
Surgical management
- hematopoietic stem cell transplant
  - never first-line
the only curative therapy

Prognosis, Prevention, and Complications

Prognosis
- worse prognosis with older age at diagnosis
- increased overall survival with tyrosine kinase inhibitor therapy
Complications
- transformation to acute leukemia (blast crisis)
- infection
- bleeding
- bone pain
- splenic infarcts due to splenomegaly