Which of the following is a known side effect of methotrexate?

• A. Bone marrow suppression
• B. Opportunistic infections
• C. Lymphomas
• D. All of the above

Answer: (D)

Methotrexate can cause toxicity in several body systems due to its effect on rapidly dividing cells and the immune system. Bone marrow suppression is a classic, dose-limiting toxicity because it disrupts DNA synthesis in hematopoietic cells, leading to lower counts of red cells, white cells, and platelets. With fewer white cells and impaired immune function, the risk of infections, including opportunistic infections, increases. Long-term or immunosuppressive use is also associated with lymphoproliferative disorders, including lymphomas, in some patients. Taken together, these effects reflect the broad toxicity profile of methotrexate, so all of the listed effects are known adverse outcomes. Clinically, this is why monitoring blood counts and liver enzymes, using folic acid supplementation to reduce some toxicities, and adjusting dosing are important.