Tyrosine Kinase Inhibitor-Associated Aplastic Anemia- A Lethal Adverse Effect and its Management Difficulties

In the pre-tyrosine kinase inhibitors era, allogenic bone marrow transplant was the treatment of choice for chronic myeloid leukemia-chronic phase (CML-CP). In the tyrosine kinase inhibitor (TKI) era life expectancy of CML-CP patients has matched the general population making it the treatment of choice. TKI is associated with hematological and non-hematological side effects. TKI-associated bone marrow hypoplasia is a rare complication and can be lethal if the patient presents with severe sepsis. Here we describe two fatal cases of TKI-associated bone marrow hypoplasia. The first patient was a 50-year-old newly diagnosed CML-CP patient who had a complete hematological response with BCR ABL quantitative 10.6% at 3 months of Dasatinib therapy. After four and half month’s patient presented with severe sepsis, grade-4 pancytopenia, and hypoplastic marrow and succumbed despite the best supportive care, growth factors, and stoppage of TKI. The second patient was a 50-year-old case of CML-CP refractory to 3 lines of TKI therapy. After 2 months of 4th-line Bosutinib therapy, the patient presented with sepsis, grade 4 pancytopenia, and hypoplastic marrow. This patient also succumbed despite the best supportive care, growth factors, and stoppage of TKI therapy. So TKI-associated bone marrow hypoplasia is a fatal side effect. It should be suspected in patients presenting with grade-4 pancytopenia either after 3 months of 1st line TKI therapy or before 3 months of TKI therapy in patients on 2 nd or more lines of TKI therapy due to refractory disease.