Showing papers by "Juri Alessandro Giannotta published in 2017"

Reactive follicular hyperplasia on dasatinib treatment for chronic myeloid leukemia

Abstract: Dear Editor, Dasatinib (DAS) is an oral dual Abl and Src tyrosine kinase inhibitor licensed in the treatment of chronic myeloid leukemia (CML) [1, 2] and is well known to exert an immunomodulatory effect both in vivo and in vitro [3]. DAS shows a distinct toxicity profile among which a previously unrecognized adverse event (AE) is represented by persistent lymphadenopathy with reactive follicular hyperplasia (FLH). Recently, lymphadenopathy with morphologic features of reactive FLH has been described in two small series of longtermDAS-treated CML patients [4, 5], which globally encompass twelve patients, even though only three in the first-line setting. In addition, only in a few patients complete FLHmorphologic and immunophenotypic features were reported. Herein, we describe two cases of patients with chronic phase (CP)-CML, intermediate risk according to Sokal score, and e14a2 transcript type, who presented with unexplained lymphadenopathy during front-line DAS therapy. Case 1: in October 2012, a 30-year-old man was diagnosed with CP-CML and he was front-line treated with DAS 100 mg QD, rapidly obtaining a major and subsequently a deep molecular response. DAS was well tolerated but approximately after 48months, bilateral cervical lymphadenopathy appeared. At a subsequent ultrasound examination, multiple enlarged lymph nodes were detected both in the cervical and submandibular area. Case 2: in April 2016, a 49-year-old man was diagnosed with CP-CML and he was front-line treated with DAS 100 mg QD. The drug was well tolerated and after 12 months of therapy he obtained a major molecular response. Nevertheless, in April 2017 a swelling at the angle of the left mandible and concomitant bilateral cervical, preauricular, and sovraclavear lymphadenopathy appeared. At a subsequent ultrasound examination, multiple enlarged lymph nodes were detected both in the cervical and left submandibular area. For both patients, no generalized lymphadenopathy was noted and no constitutional symptoms were reported. As screening for active viral infection was negative and no signs of local or systemic infectious disease were detected, an excisional biopsy was performed, showing in both cases enlarged lymph nodes with overall preserved architecture, marked follicular hyperplasia with evident reactive germinal centers (CD10+, BCL6+, BCL2and very high Ki-67 immunoreactivity), and moderate expansion of the paracortical T-zone in which a predominance of small CD3+, CD5+ T lymphocytes was identifiable together with scattered enlarged CD45+, CD30−/+, CD15−, and CD20+/− immunoblasts (Fig. 1). In situ hybridization for EBV-encoded RNA was negative. A diagnosis of FLH was made, ruling out an extramedullary blastic transformation of CML. Then, both patients definitely discontinued DAS and started ponatinib at a daily dose of 15 mg, achieving complete clinical resolution of lymphadenopathy. For what concerns FLH pathogenesis, it should be underlined that Lyn, a Src family protein, is expressed in B lymphocytes and regulates their activity via Akt/PKB signaling pathway. Thus, DAS inhibitory impact on Src kinases and the consequent upregulation of Akt/PKB pathway could contribute to the B lymphocytes proliferation and FLH development. * Alessandra Iurlo aiurlo@policlinico.mi.it