Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone

Martinelli, V;COCCO, ELEONORA;Capra, R.;Salemi, G.;GALLO, PASQUALE;CAPOBIANCO, MARTINA;Pesci, I.;Ghezzi, A.;Pozzilli, C.;Lugaresi, A.;Bellantonio, P.;Amato, M. P.;Grimaldi, L. M.;Trojano, M.;Mancardi, G. L.;Bergamaschi, R.;Gasperini, C.;Rodegher, M.;Straffi, L.;Ponzio, M.;Comi, G.;Radaelli, M.;Esposito, F.;Moiola, L.;Colombo, B.;Rossi, P.;Marrosu, M. G.;Frau, J.;LOREFICE, LORENA;Coghe, G.;Savettieri, G.;Ragonese, P.;Cusimano, V.;Perini, P.;Rinaldi, F.;Vidali, A.;Bertolotto, A.;Malucchi, S.;Di Sapio, A.;Montanari, E.;Guareschi, A.;Rizzo, A.;Zaffaroni, M.;Baldini, S.;De Rossi, N.;Cordioli, C.;Rasia, S.;Salvetti, M.;Buttinelli, C.;Ausili Cefaro, L.;De Luca, Giovanna;Tommaso, D.;Farina, D.;Fantozzi, R.;Ruggieri, S.;Hakiki, B.;Zipoli, V.;Portaccio, E.;Bartolozzi, M. L.;Scandellari, C.;Stecchi, S.;Marchello, L. P.;Palmeri, B.;Vitello, G.;Iaffaldano, P.;Lucchese, G.;Dattola, V.;Buccafusca, M.;Sola, P.;Simone, A. M.;Barreca, F.;Patti, F.;Laisa, P.;Cavalla, P.;Masera, S.;Tavazzi, E.;Galgani, S.;Tedeschi, G.;Sacco, R.;Provinciali, L.;Maura, D.;Lus, G.;Alfieri, G.;Ticca, A.;Piras, M. L.;Maimone, D.;Bianca, M.;Iudice, A.;Giro, M. E.;Galeotti, M.;Florio, C.;Spitalieri, P.;La Mantia, L.;Motti, L.;Rottoli, M. R.;Granella, F.;Solaro, C.;Scarpini, E.;Servillo, G.;Cavaletti, G.

2011-01-01

---

Abstract

Objectives: To evaluate the incidence and dose-dependency of mitoxantrone (MTX)-associated acute myelocytic leukemia (AML) in the network of Italian multiple sclerosis (MS) clinics. Methods: We performed a multicenter retrospective cohort study of patients treated with MTX in MS centers under the Italian national health care system between 1998 and 2008. Demographic, disease, treatment, and follow-up information were collected using hospital records. Results: Data were available for 3,220 patients (63% women) from 40 Italian centers. Follow-up (mean±SD) was 49±29 months (range 12-140 months).Weobserved 30 cases of AML (incidence 0.93% [95% confidence interval 0.60%-1.26%]). The mean cumulative dose was higher in patients with AML (78 vs 65 mg/m2, p=0.028). The median interval from the start of therapy to AML diagnosis was longer than expected at 33 months (range 13-84 months); 8 patients (27%) developed AML 4 years or more after the first MTX infusion. The rate of mortality associated with AML was 37%. Conclusions: This higher than expected risk of AML and related mortality requires that treatment decisions must be made jointly between clinicians and patients who understand their prognosis, treatment options, and treatment-related risks. The now large exposed MS population must be monitored for hematologic abnormalities for at least 6 years from the end of therapy, to ensure the rapid actions needed for early diagnosis and treatment of AML.