In Chronic Myeloid Leukemia (CML), what symptoms justify splenectomy in the Tyrosine Kinase Inhibitor (TKI) era?

Splenectomy Indications in CML in the TKI Era

In the TKI era, splenectomy in CML should be limited to patients with persistent symptoms and complications such as hemorrhage, splenic abscesses, pseudocyst formation, and emergency organ-threatening conditions such as splenic rupture, as cytoreductive therapy with TKIs can lead to successful regression of splenomegaly without surgical intervention in most cases. 1

Symptom Targets That Justify Splenectomy

• Persistent or increasing splenomegaly unresponsive to TKI therapy - According to WHO and ELN criteria, this is considered a sign of accelerated phase disease 1
• Splenic infarction with complications - While cytoreductive therapy can resolve uncomplicated splenic infarction, surgical intervention is warranted when complications develop 1
• Hemorrhagic complications - Subcapsular hemorrhage or splenic rupture causing hemoperitoneum requires emergency splenectomy 1
• Mechanical symptoms - Severe pain and discomfort from massive splenomegaly that significantly impacts quality of life despite adequate TKI therapy 1
• Splenic abscesses or pseudocyst formation - These complications may necessitate surgical intervention 1

Why Splenectomy Doesn't Modify Disease Biology

• BCR-ABL1 oncogene persistence - Splenectomy does not address the fundamental molecular abnormality (Philadelphia chromosome) that drives CML pathogenesis 1, 2
• Bone marrow involvement - The primary disease site in CML is the bone marrow, not the spleen, which is merely a site of extramedullary hematopoiesis 1
• Limited benefit in disease course - Historical data shows splenectomy has been found to be of little benefit in modifying the natural history of CML 3
• TKIs target the molecular driver - Modern therapy with TKIs directly inhibits the BCR-ABL1 tyrosine kinase activity that drives the disease, providing molecular control that splenectomy cannot achieve 2, 4

Risks of Splenectomy in CML

• Significant perioperative mortality - Reported mortality rates of approximately 9% make this a high-risk procedure 3
• Postoperative complications - Including infections, bleeding, and thrombotic events 3
• Risk of extreme thrombocytosis - Can occur post-splenectomy and may increase thrombotic risk 3
• Hepatomegaly - May develop or worsen after splenectomy due to compensatory extramedullary hematopoiesis 3

Modern Management Approach

• First-line therapy - TKIs (imatinib, dasatinib, nilotinib, bosutinib, or asciminib) are the standard of care for CML-CP and effectively reduce splenomegaly in most patients 1, 2
• Monitoring response - Regular assessment of hematologic, cytogenetic, and molecular responses guides therapy adjustments 1
• TKI switching - For patients with inadequate response or intolerance to first-line TKI, switching to an alternative TKI often resolves persistent symptoms including splenomegaly 5, 4
• Cytoreductive therapy - Short-term use of hydroxyurea may be considered for rapid cytoreduction in cases of marked splenomegaly before TKI therapy takes effect 1

Algorithm for Management of Splenomegaly in CML

1. Initial presentation with splenomegaly: Start appropriate TKI based on risk assessment and comorbidities 1
2. Persistent splenomegaly despite TKI therapy:
   • Evaluate for treatment compliance 2
   • Assess for BCR-ABL1 mutations that may confer resistance 1
   • Consider switching to alternative TKI 4
3. Refractory splenomegaly with complications:
   • For splenic infarction: Continue TKI therapy unless complications develop 1
   • For mechanical symptoms: Consider splenectomy only after failure of multiple TKIs 1
   • For emergency conditions (rupture, hemorrhage): Immediate surgical intervention 1

In conclusion, while splenectomy was more commonly performed in the pre-TKI era, its role in modern CML management is limited to specific symptomatic indications where TKI therapy has failed to provide adequate control of spleen-related complications.