Abstract
A 64-year-old man was diagnosed with limited cutaneous systemic sclerosis 5 years prior to this report. His sclerotic skin symptoms did not respond to oral low-dose prednisone (5–10 mg/day). Five years after the diagnosis, the patient presented with leukocytosis 3.8 × 109/L in a routine blood test, and was finally diagnosed with chronic-phase chronic myelogenous leukemia (CML). The leukemia responded optimally to initial dasatinib, and a complete cytogenetic response was achieved after 6 months of therapy. His skin symptoms dramatically improved in parallel with dasatinib therapy, as indicated by a decrease in the modified Rodnan skin score, from 12 points at diagnosis to 2 after 9 months. It has been reported that imatinib, a first-generation tyrosine kinase inhibitor, improves skin sclerosis in some patients with systemic sclerosis. To the best of our knowledge, this is the first report of simultaneous improvement of CML and limited cutaneous systemic sclerosis in response to dasatinib. Further study of the mechanism of action of dasatinib is crucial.
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Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM. The biology of chronic myeloid leukemia. N Engl J Med. 1999;341:164–72.
Lugo TG, Pendergast AM, Muller AJ, Witte ON. Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science. 1990;247:1079–82.
Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med. 2006;355:2408–17.
Kantarjian H, Shah NP, Hochhaus A, Cortes J, Shah S, Ayala M, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.
Saglio G, Kim D-W, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.
Usui N. Correction to: JSH guideline for tumors of hematopoietic and lymphoid tissues—lukemia: 4. Chronic myelogenous leukemia (CML)/myeloproliferative neoplasms (MPN). Int J Hematol. 2017;106:725–5.
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Arthritis Rheum. 2013;65:2737–47.
Sunderkötter C, Kuhn A, Hunzelmann N, Beissert S. Phototherapy. A promising treatment option for skin sclerosis in scleroderma? Rheumatology. 2006;45:iii52–4.
Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, et al. Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993;20:1892–6.
Quintás-Cardama A, Kantarjian H, O’brien S, Borthakur G, Bruzzi J, Munden R, et al. Pleural effusion in patients with chronic myelogenous leukemia treated with dasatinib after imatinib failure. J Clin Oncol. 2007;25:3908–14.
Schiffer CA, Cortes JE, Saglio G, Le Coutre P, Guilhot F, Bahceci E, et al. Lymphocytosis following first-line treatment for CML in chronic phase with dasatinib is associated with improved responses: a comparison with imatinib. Blood. 2010;116:358.
Watanabe N, Takaku T, Takeda K, Shirane S, Toyota T, Koike M, et al. Dasatinib-induced anti-leukemia cellular immunity through a novel subset of CD57 positive helper/cytotoxic CD4 T cells in chronic myelogenous leukemia patients. Int J Hematol. 2018;108:588–97.
Varga J, Abraham D. Systemic sclerosis: a prototypic multisystem fibrotic disorder. J Clin Invest. 2007;117:557–67.
Svegliati Baroni S, Santillo M, Bevilacqua F, Luchetti M, Spadoni T, Mancini M, et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N Engl J Med. 2006;354:2667–76.
Akhmetshina A, Dees C, Pileckyte M, Maurer B, Axmann R, Jungel A, et al. Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis. FASEB J. 2008;22:2214–22.
Spiera RF, Gordon JK, Mersten JN, Magro CM, Mehta M, Wildman HF, et al. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: Results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011;70:1003–9.
Khanna D, Saggar R, Mayes MD, Abtin F, Clements PJ, Maranian P, et al. A one-year, phase I/IIa, open-label pilot trial of imatinib mesylate in the treatment of systemic sclerosis-associated active interstitial lung disease. Arthritis Rheum. 2011;63:3540–6.
O’Hare T, Walters DK, Stoffregen EP, Jia T, Manley PW, Mestan J, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005;65:4500–5.
Kido M, Takeuchi S, Hayashida S, Urabe K, Sawada R, Furue M. Assessment of abnormal blood flow and efficacy of treatment in patients with systemic sclerosis using a newly developed microwireless laser Doppler flowmeter and arm-raising test. Br J Dermatol. 2007;157:690–7.
Martyanov V, Kim G-HJ, Hayes W, Du S, Ganguly BJ, Sy O, et al. Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease. PLoS One 2017: e0187580.
Milano A, Pendergrass SA, Sargent JL, George LK, McCalmont TH, Connolly MK, et al. Molecular subsets in the gene expression signatures of scleroderma skin. PLoS One. 2008;3:e2696.
Grockowiak E, Laperrousaz B, Jeanpierre S, Voeltzel T, Guyot B, Gobert S, et al. Immature CML cells implement a BMP autocrine loop to escape TKI treatment. Blood. 2017;130:2860–71.
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Arai, K., Yoshifuji, K., Motomura, Y. et al. Dasatinib for chronic myelogenous leukemia improves skin symptoms of systemic sclerosis. Int J Hematol 109, 718–722 (2019). https://doi.org/10.1007/s12185-019-02618-w
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DOI: https://doi.org/10.1007/s12185-019-02618-w