16th CONGRESS OF EHA_EUROPEAN HEMATOLOGY ASSOCIATION, June 9-12, 2011
SIDE EFFECTS OF HYDROXYUREA IN CLASSIC CHRONIC MYELOPROLIFERATIVE NEOPLASMS. A RETROSPECTIVE STUDY OF 3,411 PATIENTS
E Antonioli 1, P Guglielmelli 2, L Pieri 2, MC Finazzi 3, E Rumi 4, V Martinelli 5, N Vianelli 6, ML Randi 7, I Bertozzi7 , V De Stefano 8, T Za 8,M Ruggeri 9, F Rodeghiero 9, E Elli 10, E Pogliani 10, R Cacciola 11, E Cacciola 11, G Leone 8, M Baccarani6 , F Passamonti 4, G Finazzi 3, A Rambaldi 3, A Bosi2, T Barbui 3, A Vannucchi 2
1- AOU Careggi, Firenze, Italy 2- University of Florence, Firenze, Italy 3- Ospedali Riuniti, Bergamo, Italy 4- IRCCS, Pavia, Italy 5- Haematology, University of Napoli, Napoli, Italy 6- Haematology Unit, Bologna, Italy 7- Internal medicine, Padova, Italy 8- Hematology, Univ Cattolica, Roma, Italy 9- Haematology, Vicenza, Italy 10- Elli, E, Haematology unit, San Gerardo, Monza, Italy 11- Haematology, Catania, Italy Backgroud. Hydroxyurea (HU) is the drug of choice for the treatment of patients with high risk myeloproliferative neoplasms (MPN). Its more frequent side effects are represented by gastrointestinal toxicity, cutaneous and mucosal toxicity, pulmonary toxicity and fever. A number of anecdotal cases have been reported in the literature, but epidemiological information on large series of patients are not yet available. Aims. To collect information on the rate and characteristics of HU-related side effects, we examined data from a retrospective survey of ten hematological centers in Italy. To ensure consistency of data, we only included clinically relevant HU-related manifestations such cutaneous and mucosal lesions, fever and pneumonitis. Methods. This study was performed within the GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto) MPN Working Party, under the auspices of AGIMM (AIRC-
Gruppo Italiano Malattie Mileoproliferative). Centers were asked to identify, in their own data base, all subjects with a diagnosis of MPN who had received hydroxyurea and developed one of the side effects considered above. Diagnosis of PV, ET or PMF was made according to either the WHO2008 or PVSG/WHO2001 criteria, while diagnosis of post-PV or post-ET MF was made according to the IWG-MRT plus the histological WHO criteria. Furthermore, for comparison populations, each participating centre provided information on the total number of referring patients with matched diagnosis who had been in treatment with HU and had not developed side effects in the same period of time. Results. The whole study population was comprised of 3,411 MPN patients, of whom 963 were PV, 1912 ET, 357 PMF, 93 PPV and 86 PET. A total of 184 patients (5%) who developed HU-related side effects were identified: 16 of them developed fever, 167 muco-cutaneous lesions and 1 pneumonitis. Pulmonary toxicity attributed to HU was diagnosed in a 68-year-old male with JAK2V617F negative PMF who was being treated since ten years with 1 g/ daily. High degree (>39.°C) fever developed in 16 patients: 4 PV, 11 ET and 1 MF. Eight males and 8 females, median age 64 yrs (range 50-79 yrs), 86% were JAK2V617F mutated. Fever was reported after a median period of 31 days (range, 1-109) of treatment at median dosage of 0.5 g daily (range, 0.15-1 g), for a total HU median dose of 15 g (range, 0.5-52.5 g) for patient. Muco-cutaneous lesions were referred by 167 patients; 28 patients developed mucosal lesions, 118 patients presented cutaneous ulcers, while other cutaneous lesions including keratosis, dyschromia, basalioma and dermatitis developed in 21 patients, as detailed in the table. Two patients reported both mucosal and cutaneous lesions. Conclusions. With the intrinsic limitations of the retrospective design, this study provides, for the first time, an estimate of the rate of HU-related side effects (5%) overall strenghtening the good tolerability of the drug.
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