Skin Toxicity of Hydroxyurea In Ph- Myeloproliferative Neoplasms: Incidence and Clinical Features
Authors: Latagliata Roberto , Cedrone Michele , Villivà Nicoletta , Breccia Massimo , Anaclerico Barbara , Volpicelli Paola , Ferretti Antonella , Felici Stefano , Montefusco Enrico , Abruzzese Elisabetta , Spadea Antonio , Spirito Francesca , Cotroneo Ettore , De Muro Marianna , Annino Luciana , Cimino Giuseppe , Alimena Giuliana , Montanaro Marco , Andriani Alessandro 
Published: October 2019

Abstract
Abstract 3077
Hydroxyurea (HU) is still the cornerstone in the cytoreductive treatment of Myeloproliferative Neoplasms (MPN); however, skin toxicity has been reported as a limiting toxicity during HU treatment in many case reports. To evaluate the real incidence and the clinical features of such complication, among 942 patients with MPN consecutively diagnosed at 3 Centers in Rome, we revised 587 patients (M/F 263/324, median age 64.2 years, IR 53.7 – 72.7) who received HU treatment during the course of disease. There were 304 patients with Essential Thrombocythemia (ET), 202 with Polycythemia Vera (PV), 68 with Primary Myelofibrosis (PMF) and 13 with unclassifiable Chronic Myeloproliferative Disorders (CMPD-u); 496 patients (84.5%) received HU as 1st line treatment while 91 (15.5%) as 2nd or 3rd line treatment. On the whole, 50 patients (8.5%) had a skin toxicity during HU treatment, after a median period from HU start of 32.1 months (IR 10.5 – 74.6) and a mean HU dosage of 1085 mg (+/&− 390 mg); as to the different types of toxicity, 31 patients (62%) had a painful ulcerative skin toxicity (UST) that in 25/31 was located in the perimalleolar area, 9 patients (18%) had oral aphthous ulcers and 10 patients (20%) a non ulcerative skin toxicity (NUST) with erythema and skin infiltration (diffuse in 2 patients, localized to the head or to the extremities in 5 and 3 patients, respectively). Among these different types of skin toxicity there was no difference as to mean HU dosage; however, oral aphthous ulcers were an early toxicity (median time from HU start 1.9 months, IR 1.6 – 2.7) while UST and NUST were late complications (median time from HU start 35.1 months, IR 22.9 – 81.7, and 36.1 months, IR 17.0 – 64.5, respectively). When the skin toxicity occurred, HU treatment was continued at the same dosage in 5 patients (10%), was reduced in 12 patients (24%) and temporarily interrupted in 7 patients (14%); the remaining 26 patients (52%) needed a permanent drug discontinuation. After a median period of 4.3 months (IR 2.4 – 9.0) from the onset of the skin toxicity, 38 patients (76%) had a complete resolution and 8 patients (24%) an improvement without complete resolution; oral aphthous ulcers and NUST had a shorter median time of resolution compared to UST (1.8 months, IR 0.7 – 6.6, and 3.1 months, IR 3.0 – 8.4, versus 6.0 months, IR 3.1 – 16.5, respectively). In conclusion, skin toxicity during HU treatment is more common than expected, with about 9% of incidence and can have different clinical features; moreover, it often need a permanent drug discontinuation and in about 25% of patients there is only a partial resolution. Thus, further studies are warranted to highlight pathogenesis, which could be different in the various types of toxicity, and individual predisposing factors.

Disclosures:
No relevant conflicts of interest to declare.