Chronic Myeloid Leukemia (CML) is a blood and bone marrow cancer originating in blood-forming cells. It is genetically defined by the Philadelphia chromosome, an abnormal structure resulting from a swap between chromosomes 9 and 22. This swap creates the malfunctioning BCR::ABL1 gene, which produces a protein causing blood cells to grow and divide uncontrollably. The resulting overproduction of white blood cells drives the condition’s complications. Splenomegaly, an enlarged spleen, is a characteristic feature of CML and a common finding at diagnosis.
How CML Causes Spleen Enlargement
The BCR::ABL1 fusion gene causes a massive expansion of white blood cell precursors in the bone marrow. This overwhelming cellular production quickly fills the marrow space, forcing excess, immature blood cells to spill into the bloodstream. These circulating cancer cells then infiltrate and colonize other organs, most notably the spleen.
The primary mechanism of enlargement is extramedullary hematopoiesis, meaning blood cell production outside of the bone marrow. The spleen naturally produces blood cells during fetal development and reactivates this function under stress. In CML, the spleen attempts to assist the overwhelmed bone marrow by becoming a secondary factory for blood cell production. This intense cellular traffic causes the spleen to swell dramatically as it becomes densely packed with proliferating myeloid cells. The size of the spleen often correlates directly with the total number of circulating white blood cells, reflecting the overall burden of the leukemia.
Recognizing the Symptoms and Clinical Assessment
An enlarged spleen causes symptoms primarily due to its physical presence in the left upper quadrant of the abdomen. As it grows, the spleen pushes against neighboring organs, particularly the stomach. This pressure often causes abdominal fullness or discomfort.
A common complaint is early satiety, the sensation of feeling full quickly after eating only a small amount of food. This occurs because the enlarged spleen presses on the stomach, reducing its capacity. Patients may also experience pain in the left upper quadrant, ranging from a dull ache to a sharp, severe pain.
Severe, sudden pain may signal a splenic infarction, which occurs when a section of the enlarged spleen loses its blood supply. Clinically, assessment begins with a physical examination, where a physician often feels the enlarged organ extending below the left rib cage. The size is then confirmed and measured using imaging techniques, such as ultrasound or Computed Tomography (CT) scan.
Management and Treatment Strategies
Treating splenomegaly in CML focuses on addressing the underlying cancer, as the enlargement is a symptom of the proliferative disease. The standard of care involves targeted therapies called Tyrosine Kinase Inhibitors (TKIs). These drugs, such as imatinib, nilotinib, and dasatinib, specifically block the activity of the BCR::ABL1 protein driving the excessive cell growth.
By effectively controlling the leukemia cell count, TKIs lead to a significant and often rapid reduction in spleen size. This shrinkage alleviates pressure-related symptoms, such as abdominal discomfort and early satiety, and is a key measure of treatment success. A very large spleen at diagnosis indicates a higher disease burden, which may influence the choice of the initial TKI.
If splenomegaly is refractory to TKI therapy, or if the patient cannot tolerate the medication, secondary interventions may be considered. Splenic irradiation, a type of localized radiation therapy, can be used to shrink the spleen and provide palliative relief from pain and mass effect. This treatment is typically reserved for symptom control.
Splenectomy, the surgical removal of the spleen, is a less common option in the modern TKI era but remains a possibility for specific circumstances. Indications include life-threatening complications like splenic rupture or hemorrhage, or persistent, severe mechanical symptoms that fail to improve after switching to multiple TKIs. Although effective at immediately removing the enlarged organ, splenectomy carries risks, including higher rates of morbidity and mortality.