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Tofacitinib as a novel salvage therapy for refractory T-cell large granular lymphocytic leukemia

Leukemia volume 29, pages 2427–2429 (2015)Cite this article

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T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disease characterized by clonal expansion of cytotoxic T lymphocytes.1 Association with a broad range of autoimmune disorders suggests that chronic antigen stimulation or an inability to eliminate or silence cells with autoimmune specificities may have a role in the clonal expansion of cytotoxic T lymphocytes. Among conditions associated with T-LGLL, rheumatoid arthritis (RA) is the most common, found at a much higher frequency in T-LGLL patients than the general population (11–36% vs 0.5–1%, respectively).2, 3, 4 Clinical observations suggest that there may be a pathophysiologic relationship between RA and T-LGLL, as indicated by the triad of splenomegaly, RA and neutropenia seen in Felty’s syndrome.4 In addition, aberrant signaling through both JAK/STAT and PI3K/AKT pathways has been implicated in T-LGLL5 with a proportion of patients demonstrating intrinsic STAT3 activation due to mutations.6

Various members of the JAK family are known to be involved in the differentiation and survival of hematopoietic cells, as well as in activation of immune cells.7 In particular, JAK3 has emerged as an important target for immunosuppression,7, 8 leading to development of JAK inhibitors such as tofacitinib citrate (CP690550), a JAK3-specific inhibitor9 currently FDA approved for refractory RA.10 The JAK/STAT pathway is a therapeutic target in other autoimmune disorders,11 raising the possibility that such a strategy may also be effective in T-LGLL.

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Author notes

  1. B Bilori and S Thota: These authors contributed equally to this work.

Authors and Affiliations

  1. Yale-Waterbury Internal Medicine Residency Program, Internal Medicine, Waterbury Hospital, Waterbury, CT, USA

    B Bilori

  2. Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH, USA

    S Thota, M J Clemente, B Patel, M Afable II & J P Maciejewski

  3. Department of Hematology and Medical Oncology, Hospital Universitario Morales Meseguer, Universidad de Murcia, IMIB-Arrixaca, Murcia, Spain

    A Jerez

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  1. B Bilori
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  6. M Afable II
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  7. J P Maciejewski
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Correspondence to J P Maciejewski.

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Bilori, B., Thota, S., Clemente, M. et al. Tofacitinib as a novel salvage therapy for refractory T-cell large granular lymphocytic leukemia. Leukemia 29, 2427–2429 (2015). https://doi.org/10.1038/leu.2015.280

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