Acute myeloid leukemia in a patient receiving phase iii clinical trial of tofacitinib (xeljanz) therapy for ulcerative colitis: a case study with literature review

Author: 
Ming Xie and Hongwei Ma

A 53 year old male with ulcerative colitis (UC) in phase III clinical trial of Tofacitinib therapy for 2 years was admitted for pancytopenia and circulating blasts in peripheral blood. Subsequent bone marrow biopsy demonstrated diffuse leukemic infiltrate with nearly absent normal hematopoiesis. Leukemic cells showed minimal morphological differentiation. Flow cytometry study revealed acute myeloid leukemia (AML), with co-expression of CD5 (dim), CD7 (heterogeneous) and CD10 (h). The leukemic cells were negative for intracellular myeloperoxidase(MPO), CD3, Tdt and CD79a, which were confirmed by immunohistochemical studies. AML cells showed a complex karyotype 41-43, -1,dup(1)(p32p36.3),add(4)(q22),del(5)(q31q35),add(7)(q36),+8,add(8)(q24),-13,add(14)(p10),-15,-17,+19,-22[cp20]. FISH study was negative for RPN1, MECOM, RUNX1T1, MLL, PML, CBF-beta, RARA, and RUNX1 gene mutations. Patient showed no response to cytarabine based “7+3” chemotherapy regimen, with persistent AML in the bone marrow biopsy on day 14 post introduction chemotherapy. Unresponsive to further treatment, the patient died 23 days after the initial AML diagnosis due to multiple complications including metabolic encephalopathy, neutropenic fever, sepsis, acute kidney injury and acute diarrhea. This is the first case report on the clinicopathological features of AML in patients receiving Tofacitinib therapy for UC in a phase III clinical trial. Further clinical studies are needed for the evaluation of long term safety of Tofacitinib therapy in these patients.

Page: 
185-187
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