Chronic Myeloid Leukemia (CML) is a cancer of the blood and bone marrow that causes an overproduction of white blood cells. A common consequence is splenomegaly, or an enlarged spleen, which occurs when the organ becomes overwhelmed trying to filter the excess abnormal cells from the blood. This enlargement is often one of the first noticeable signs of the underlying leukemia.
The Pathophysiology of CML-Induced Splenomegaly
CML originates from a genetic mutation in bone marrow stem cells, creating the BCR-ABL1 fusion gene. This gene drives the overproduction of abnormal white blood cells, particularly granulocytes. These leukemic cells are released from the bone marrow and circulate in the blood, accumulating in other organs.
In individuals with CML, the spleen attempts to filter the massive number of abnormal white blood cells from circulation. This excessive workload causes the spleen to become a site for extramedullary hematopoiesis, where blood cell production occurs outside the bone marrow.
This infiltration by leukemic cells and subsequent extramedullary hematopoiesis causes the spleen to expand significantly. The organ becomes a reservoir for the proliferating CML cells, disrupting its normal structure and function.
Symptoms and Physical Manifestations
A primary symptom of an enlarged spleen is fullness or discomfort in the upper left abdomen, caused by the spleen pressing against the stomach and other nearby organs. Some individuals experience pain in this area that can radiate to the left shoulder. This pain may become sharp if a part of the spleen loses its blood supply, a condition known as splenic infarction.
Early satiety, the feeling of being full after eating a small amount, is also common. The enlarged spleen reduces the stomach’s capacity, which can lead to unintentional weight loss. The body’s increased metabolic rate from the cancer can also cause fatigue and excessive sweating.
Symptom severity correlates with the degree of spleen enlargement. In the early, chronic phase of CML, symptoms may be mild or absent, with the condition sometimes discovered during a routine physical exam. As the disease progresses, the spleen can become massively enlarged, leading to more pronounced symptoms.
The Diagnostic Process
The diagnostic process often begins with a physical examination where a physician palpates the abdomen to detect an enlarged spleen. The doctor assesses how far the spleen extends below the left rib cage for an initial estimate of its size. However, a physical exam is not always definitive, as a palpable spleen can be found in healthy individuals and not all enlarged spleens are easily felt.
Imaging tests are used to confirm splenomegaly and obtain precise measurements. An abdominal ultrasound is a common first step, as it is non-invasive and effective at visualizing the spleen and its dimensions. A spleen length over 13 centimeters is considered enlarged.
A computed tomography (CT) scan of the abdomen can also provide detailed images and is useful for measuring splenic volume. These imaging results, combined with blood and bone marrow tests to confirm CML, allow doctors to use spleen size as a clinical marker. Spleen size helps stage the disease and monitor a patient’s response to treatment.
Management and Treatment Strategies
The primary approach to managing CML-induced splenomegaly is treating the underlying leukemia. Controlling the cancer cells relieves the burden on the spleen, allowing its size to return to normal or near-normal. The standard of care for CML is a class of targeted drugs known as tyrosine kinase inhibitors (TKIs), which are oral medications that target the BCR-ABL1 protein driving the cancer.
TKIs like imatinib, nilotinib, and dasatinib block the signaling pathways that allow leukemic cells to multiply. This leads to a rapid reduction of abnormal cells, alleviating the burden on the spleen. Response to TKI therapy is monitored with blood tests, and a decrease in spleen size indicates a complete hematologic response. Most patients remain on TKI therapy long-term to keep the leukemia in remission.
If TKI therapy is not effective enough or if symptoms from an extremely enlarged spleen require immediate relief, other treatments are considered. Low-dose radiation therapy can be directed at the spleen to shrink it and alleviate pain. However, radiation is for symptom control and does not treat the underlying CML.
A splenectomy, or the surgical removal of the spleen, is another option for severe cases. This procedure is less common due to effective TKIs but may be used if the spleen causes significant pain, is at risk of rupturing, or is contributing to dangerously low blood counts. Allogeneic stem cell transplantation is a curative option reserved for patients resistant to TKI therapy or who have progressed to advanced disease phases.