What Causes Splenomegaly in Chronic Myeloid Leukemia?

An enlarged spleen is the most common sign of chronic myeloid leukemia (CML), and it grows so slowly that many people don’t notice it until it is very large.1Jaypee Journals (J Med Sci). Histopathological Spectrum of Splenic Lesions in Morbid and Autopsy Specimens The cause is the leukemia itself spilling into the spleen, not a separate disease of the organ. An abnormal gene drives the bone marrow to make huge numbers of leukemia cells, and many of them move into the spleen, where the spleen becomes a second home in which they grow and shelter.2PubMed Central. Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance

How the CML Gene Floods the Body With White Cells

CML begins when two genes break and fuse, forming an abnormal gene called BCR-ABL.3PubMed. The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia It makes a protein that acts like a growth switch stuck in the on position.4PubMed. The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia The normal version is regulated, but the fused version resists the body’s signals to turn off.5PubMed. The impact of the BCR-ABL oncogene in the pathology and treatment of chronic myeloid leukemia Normal blood-forming cells divide when the body signals a need, such as bleeding or infection, and then settle back down. As a result, blood-forming stem cells in the marrow keep dividing far beyond what the body needs.6PubMed. Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis The outcome is a very high white blood cell count, which is often how CML is first found.7PubMed. Chronic myeloid leukemia: a historical perspective

In CML, the extra cells still mature into working white cells, which is why CML often develops slowly over years rather than suddenly. And because the problem starts in a single stem cell, every cell descended from it carries the same fused gene, so the leukemia keeps growing from one original mistake. That change happens in blood cells during life. It isn’t passed down from parents, and in most cases it isn’t caused by anything the person did.

Most CML drugs, such as imatinib, block the stuck switch directly, which slows cell production at the source. Fewer leukemia cells means less material to fill the spleen, so it often shrinks once treatment starts.

For context, the spleen is normally about fist-sized and can’t be felt. It sits under the left ribs, filters blood, removes old or damaged blood cells, and helps fight infection.

Why the Leukemia Cells Move Into the Spleen

An enlarged spleen in CML comes from two things: leukemia cells filling the organ, and the spleen starting to make blood cells itself.8PubMed Central. Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance The first happens because leukemia stem cells hold on to the bone marrow less well and drift out toward the spleen.9PubMed Central. Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia A chemical “come here” signal drops in the marrow and rises in the spleen, pulling cells there.10PubMed Central. Chemokines as a Conductor of Bone Marrow Microenvironment in Chronic Myeloid Leukemia In animal studies, the CML gene alone caused blood-making in the spleen and liver within weeks.11Blood. Efficient and Rapid Induction of a Chronic Myelogenous Leukemia-Like Myeloproliferative Disease in Mice Receiving P210 bcr/abl-Transduced Bone Marrow

The spleen is an easy place to settle. It already receives a large flow of blood every minute, so circulating leukemia cells pass through it constantly.

“Infiltration” means leukemia cells physically move into the spleen’s tissue and crowd in among the normal cells. The spleen itself isn’t becoming cancerous. It is built like a sponge full of blood-filled channels, which gives arriving cells plenty of room to lodge. As more cells arrive and multiply, the organ stretches and gains weight, which is why it can be felt below the ribs.

Blood-making in the spleen adds to this. Before birth, the spleen and liver make blood, and in CML that ability switches back on. The spleen then holds both arriving cells and newly made ones, which adds bulk on top of infiltration.

Once there, the cells are fed and protected. Cells in the spleen release growth signals that help leukemia cells survive and multiply.12Open Journal of Hematology. CML cell trafficking: Influence of the stromal microenvironment Certain spleen cells also give leukemia stem cells a protected resting place, and resting stem cells can be harder for drugs to reach and kill.13PubMed Central. Splenic red pulp macrophages provide a niche for CML stem cells and induce therapy resistance

This comes largely from laboratory and animal work. It helps explain why drugs shrink the bulk of the disease faster than they clear every last stem cell, though for most people the disease still comes under control.

A shrunken spleen doesn’t mean all leukemia stem cells are gone. Sheltered cells are one reason doctors track blood gene tests long term, and stopping treatment on your own can let those cells regrow.

How a Big Spleen Traps Normal Blood Cells

A larger spleen holds more of the blood flowing through it, so it can trap 5.5 to 20 times more blood cells than normal.14Experimental and Therapeutic Medicine. Hypersplenism: History and current status (Review) More red cells, white cells and platelets get destroyed, which lowers counts in the blood, though in CML the white count usually stays high overall.15Experimental and Therapeutic Medicine. Hypersplenism: History and current status (Review) In one case, removing a huge spleen made white cells and platelets jump, revealing hidden CML.16PubMed Central. Chronic Myeloid Leukemia Masked by Massive Splenomegaly: Splenectomy as a Strategy in a Resource-Limited Setting

The spleen normally screens blood by slowing it down so worn-out cells can be removed. When the organ is enlarged, blood moves through even more slowly and spends longer in contact with those removal cells. Healthy cells that would usually pass through get held up and removed along with the damaged ones. That is why a person with CML can have a very high white count yet still be short of red cells or platelets. An enlarged spleen can also simply hold a large share of the body’s blood cells inside it at any moment, so fewer circulate and show up on a blood test. Low red cells cause tiredness and breathlessness, and low platelets can cause easy bruising.

As the spleen shrinks, fewer cells get trapped, so counts can shift. Doctors watch them closely early in treatment, and the changes are expected and help guide dosing.

Symptoms of an Enlarged Spleen in CML

A very large spleen can swell the abdomen and cause anemia even in the early stable stage of the disease.22PubMed Central. Surgical management of giant splenomegaly in chronic myeloid leukemia: a challenging splenectomy case Early symptoms are vague, so many people put them down to stress or diet, and someone may only notice a lump when dressing or lying on their left side. Many people are diagnosed from a routine blood test before any symptoms bother them. Doctors check size by feeling below the left ribs, often giving it in centimetres below the rib edge; ultrasound can measure it more precisely.

What Spleen Size Says About Your Outlook

Spleen size at diagnosis goes into risk scores23Journal of Islamabad Medical & Dental College. Prognostic Scoring in Patients of Chronic Myeloid Leukemia: Correlation between Sokal and Hasford Scoring Systems24PubMed Central. Prognostic scoring systems in chronic myeloid leukaemia The EUTOS score uses only spleen size and the share of basophils, a type of white cell.25PubMed Central. Prognostic scoring systems in chronic myeloid leukaemia A larger spleen moves you toward a higher risk group.26PubMed Central. Risk Stratification of Chronic Myeloid Leukemia According to Different Prognostic Scores But scores also weigh age, platelets and immature cells, so size alone doesn’t decide outlook.27PubMed Central. Prognostic scoring systems in chronic myeloid leukaemia Children with CML tend to have larger spleens and more disease at diagnosis than adults.28Blood. Spleen Size at Diagnosis and Genomic BCR-ABL1 Breakpoint Distribution Differ Age-Dependently in Pediatric Patients with Chronic Myeloid Leukemia (CML)

Spleen size is a snapshot of how much leukemia was present at diagnosis. It can’t tell how well your leukemia will respond to a drug, and two people with the same spleen size can have quite different results.

A risk score estimates, in groups of people, how likely the disease is to behave aggressively. It doesn’t predict what will happen to one person. Doctors use the group to decide how closely to monitor you and sometimes which drug to start with. High risk doesn’t mean treatment won’t work, and your response to treatment matters more over time than the starting score.

A spleen that keeps growing despite proper treatment is linked to a higher chance of moving to the aggressive blast phase.29PubMed. An assessment of the clinicohematological criteria for the accelerated phase of chronic myeloid leukemia If that happens while you are taking the drug as prescribed, doctors typically repeat blood and marrow or gene tests to see what has changed. They also check that the drug is being taken correctly and consider whether the leukemia has become resistant to it.

Shrinking the Spleen and Rare Complications

Most people take daily tablets that block the CML gene. The spleen often becomes impossible to feel within weeks to months, and fullness and appetite usually improve as it shrinks. Drugs come first because they address the cause of the enlargement, the overproduction of leukemia cells. Radiation and surgery only deal with the organ, leaving the overproduction unchanged, so they are kept for cases where drugs haven’t worked well enough or aren’t available.

Once effective drugs arrived, spleen radiation became reserved for advanced or drug-resistant cases.30PubMed. Clinical indications and biological mechanisms of splenic irradiation in chronic leukaemias and myeloproliferative disorders In one group, radiation relieved spleen pain in about 7 in 10 courses and halved spleen size in about two-thirds of courses.31PubMed. Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea32PubMed. Splenic irradiation in the treatment of patients with chronic myelogenous leukemia or myelofibrosis with myeloid metaplasia. Results of daily and intermittent fractionation with and without concomitant hydroxyurea It is given as a series of low-dose sessions. It can lower blood counts, so doctors monitor the blood closely during and after the course. The benefit is usually temporary, since without effective drug control the spleen can enlarge again.

Surgery to remove a huge spleen is sometimes done, especially where drugs are hard to get.33PubMed Central. Chronic Myeloid Leukemia Masked by Massive Splenomegaly: Splenectomy as a Strategy in a Resource-Limited Setting It is a major operation, and a very large spleen makes it harder, so surgeons weigh the risks carefully. Without a spleen, the body is somewhat more prone to serious infections, so vaccinations and infection precautions are usually advised.

Complications are rare. A very large spleen can rupture on its own, mainly from congestion and cell infiltration.34PubMed Central. Spontaneous splenic rupture in a patient with chronic myeloid leukemia: A case report Parts of the spleen can lose blood supply, and clotting problems may add bleeding.35PubMed Central. Spontaneous splenic rupture in a patient with chronic myeloid leukemia: A case report Massive splenic infarction with a clot in the liver’s main vein is extremely rare.36PubMed. Massive splenic infarction and portal vein thrombosis in children with chronic myeloid leukemia

While the spleen is big, avoid contact sports until it shrinks. Seek urgent care for sudden sharp left belly pain or pain spreading to the left shoulder, and treat dizziness with that pain as a possible sign of internal bleeding. Tell your care team about new swelling despite treatment.