Clinical Follow-up of Patients with Myeloproliferative Neoplasms Presenting Skin Ulcers During Treatment with Hydroxyurea
Authors: Latagliata Roberto , Cedrone Michele , Villivà Nicoletta , De Gregoris Cinzia , Breccia Massimo , Spadea Antonio , De Muro Marianna , Tafuri Agostino , Anaclerico Barbara , Felici Stefano , D'Andrea Mariella , Montefusco Enrico , Abruzzese Elisabetta , Spirito Francesca , Leonetti Crescenzi Sabrina , Recine Umberto , Mazzucconi Maria Gabriella , Annino Luciana , Cimino Giuseppe , Avvisati Giuseppe , Petti Maria Concetta , Alimena Giuliana , Montanaro Marco , Andriani Alessandro 
Published: October 2019

Abstract
Abstract 5157
Hydroxyurea (HU) is widely employed in the treatment of Myeloproliferative Neoplasms (MPN); however, painful skin ulcers are a limiting toxicity during HU treatment in >5% of patients. To evaluate the clinical impact of such complication on the outcome of these patients, we retrospectively revised 1001 cases (M/F 437/564, median age 65.6 years, IR 55.6 – 73.7) with MPN consecutively diagnosed at 6 Centers in Rome who received HU treatment during the course of disease. There were 537 patients with Essential Thrombocythemia (ET), 336 with Polycythemia Vera (PV), 102 with Primary Myelofibrosis (PMF) and 26 with unclassifiable Chronic Myeloproliferative Disorders (CMPD-u); 863 patients (86.2%) received HU as 1st line treatment while 138 (13.8%) as 2nd or 3rd line treatment. On the whole, 71 patients (7.1%) developed painful skin ulcers after a median period of 54.1 months (IR 27.7 – 97.6) from HU start; as concerns the site, in 56/71 patients (78.8%) skin ulcers were located in the perimalleolar area while in the remaining 15 patients in other skin areas (localized to the head or to the extremities in 8 and 7 patients, respectively). When the skin ulcers occurred, HU treatment was continued at the same dosage in 11 patients (15.4%), was reduced in 13 patients (18.4%) and temporarily interrupted in 11 patients (15.4%): the remaining 36 patients (50.8%) needed a permanent drug discontinuation. Among these latter patients, pipobroman was started in 20 patients, anagrelide in 5, alpha-interferon in 3, melphalan in 3; in addition, no further treatment was given in 1 patient and 4 patients were lost to follow-up. As to ulcer resolution, 11/71 patients were not evaluable (2 too early, 9 lost to follow-up). Among the 60 evaluable patients, after a median period of 6.3 months (IR 3.6 – 11.3) from the onset of the skin ulcers, 43 patients (71.6%) had a complete resolution and 17 patients (28.4%) had an improvement without complete resolution. The incidence of 2nd neoplasia [3/71 (4.2%) patients with skin ulcers vs 73/930 (7.8%) patients without skin ulcers] and blastic phase evolution [2/71 (2.8%) patients with skin ulcers vs 41/930 (4.4%) patients without skin ulcers] were not increased after the skin ulcer occurrence. After a median period from skin toxicity of 30.7 months (IR 14.3 – 63.6), 9 patients were lost to follow-up, 11 patients died and 51 patients are still alive. In conclusion, painful skin ulcers during HU treatment are a relatively common complication in MPN patients, require HU discontinuation in > 50% of cases and in a sizable rate of patients there is only a partial healing of skin lesion: however, this complication and the requested treatment changes do not seem to impact on the subsequent clinical follow-up of MPN patients.

Disclosures:
No relevant conflicts of interest to declare.