Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia
Kim-Hien T Dao, Magdolna B Solti, Julia E Maxson, Elliott F Winton, Richard D Press, Brian J Druker, Jeffrey W Tyner, Kim-Hien T Dao, Magdolna B Solti, Julia E Maxson, Elliott F Winton, Richard D Press, Brian J Druker, Jeffrey W Tyner
Abstract
Mutations in CSF3R (colony-stimulating factor 3 receptor) are frequent oncogenic drivers in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). Here we describe a 75 year old man who was diagnosed with CSF3R-T618I-positive atypical CML. He presented with leukocytosis, anemia, and thrombocytopenia and developed massive splenomegaly and severe constitutional symptoms. Hydroxyurea was given over a 6 month period but failed to provide any measureable clinical benefit. Eventually, he was treated with ruxolitinib, an FDA-approved JAK1/2 inhibitor, which resulted in dramatic improvement of his blood counts. He also had significant reduction of spleen volume and constitutional symptoms. This case highlights the need for a clinical trial to interrogate JAK1/2 as a potential molecular target in CNL and aCML in patients with or without CSF3R mutation. A clinical trial evaluating the safety and efficacy of ruxolitinib for this patient population is registered at ClinicalTrials.gov (NCT02092324).
Keywords: Atypical chronic myeloid leukemia; Chronic neutrophilic leukemia; Colony-stimulating factor 3 receptor; Ruxolitinib.
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References
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Source: PubMed