ABL tyrosine kinase inhibitor-induced pulmonary alveolar proteinosis in chronic myeloid leukemia

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of eosinophilic periodic acid Schiff-positive material in the intra-alveolar and bronchiolar spaces. Tyrosine kinase inhibitors, including imatinib, nilotinib, and dasatinib, have shown excellent efficacy in the treatment of chronic myeloid leukemia (CML). We report a case of acquired PAP in a patient with CML receiving tyrosine kinase inhibitors. A 67-year-old man with CML presented with progressive back pain 5 months after starting imatinib treatment. Acquired PAP was diagnosed based on physical, radiographic, and histopathological findings. The presence of granulocyte-macrophage colony-stimulating autoantibodies suggested that autoimmune mechanisms were involved in the pathogenesis. Interestingly, PAP developed in association with imatinib and dasatinib administration, but not with nilotinib treatment. The patient died of refractory leukemia in lymphoid blast crisis with a newly emerged T315I mutation. Although the incidence is very rare, imatinib and dasatinib associated with PAP development has been reported. Meanwhile, PAP in nilotinib-treated patients has not been reported. Our observation in one patient receiving multiple TKIs suggests that nilotinib may be safer than imatinib or dasatinib in avoiding the development or exacerbation of PAP.