title: Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen.
abstract: High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.
authors.affiliation: Dipartimento Oncologico "La Maddalena", UOC di Oncoematologia e TMO, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Musso
authors.affiliation: Azienda Ospedaliera 'Bianchi Melacrino Morelli', C.T.M.O. Centro Unico Regionale Trapianti di Cellule Staminali e Terapie Cellulari, Reggio Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Messina
authors.affiliation: UOC di Ematologia e Trapianto di Cellule Staminali, P.O. "Vito Fazzi", Lecce, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Di Renzo
authors.affiliation: Unità Terapia Intensiva Ematologica per il Trapianto Emopoietico, Ospedale Civile, Pescara, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Carlo
authors.affiliation: Dipartimento di Oncologia ed Ematologia, A.O. U.Città della Salute e della Scienza di Torino San Giovanni Battista, S.C. Ematologia, Torino, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Vitolo
authors.affiliation: Dipartimento Oncologico "La Maddalena", UOC di Oncoematologia e TMO, Palermo, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Scalone
authors.affiliation: Dipartimento di Ematologia, Istituto Nazionale Tumori, Fondazione 'G. Pascale', IRCCS, UOC di Ematologia Oncologica e Trapianto di Cellule Staminali, Napoli, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Marcacci
authors.affiliation: Divisione di Ematologia, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Potito R
authors.initials: PR
authors.lastname: Scalzulli
authors.affiliation: Azienda Ospedaliera 'Bianchi Melacrino Morelli', C.T.M.O. Centro Unico Regionale Trapianti di Cellule Staminali e Terapie Cellulari, Reggio Calabria, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Moscato
authors.affiliation: UOC di Ematologia e Trapianto di Cellule Staminali, P.O. "Vito Fazzi", Lecce, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Matera
authors.affiliation: Dipartimento Oncologico "La Maddalena", UOC di Oncoematologia e TMO, Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Crescimanno
authors.affiliation: Unità Terapia Intensiva Ematologica per il Trapianto Emopoietico, Ospedale Civile, Pescara, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Santarone
authors.affiliation: Dipartimento di Oncologia, Trapianti e Tecnologie Avanzate, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Orciuolo
authors.affiliation: ARNAS Ospedale Civico Benfratelli, U.O. di Ematologia, Palermo, Italy.
authors.forename: Anxur
authors.initials: A
authors.lastname: Merenda
authors.affiliation: Ospedale Generale Provinciale "Cardinale G. Panico", S.C. di Ematologia e Trapianto di Cellule Staminali, Tricase, Lecce, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.affiliation: Dipartimento di Ematologia, Università di Bari, Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Pastore
authors.affiliation: Dipartimento di Ematologia, Istituto Nazionale Tumori, Fondazione 'G. Pascale', IRCCS, UOC di Ematologia Oncologica e Trapianto di Cellule Staminali, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Donnarumma
authors.affiliation: U.O. Complessa di Ematologia, IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Genova, Italy.
authors.forename: Angelo M
authors.initials: AM
authors.lastname: Carella
authors.affiliation: Dipartimento di Oncologia ed Ematologia, A.O. U.Città della Salute e della Scienza di Torino San Giovanni Battista, S.C. Ematologia, Torino, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciochetto
authors.affiliation: Divisione di Ematologia, IRCSS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Cascavilla
authors.affiliation: Ospedale Generale Provinciale "Cardinale G. Panico", S.C. di Ematologia e Trapianto di Cellule Staminali, Tricase, Lecce, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Mele
authors.affiliation: Unità Operativa di Ematologia, Istituti Ospitalieri di Cremona, Cremona, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Lanza
authors.affiliation: Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Nicola
authors.affiliation: Sezione di Statistica Medica e Biometria 'GA Maccaro', Dipartimento di Scienze Cliniche e di Comunità, Università di Milano, Milano, Italy.
authors.forename: Erminio
authors.initials: E
authors.lastname: Bonizzoni
authors.affiliation: Dipartimento di Ematologia, Istituto Nazionale Tumori, Fondazione 'G. Pascale', IRCCS, UOC di Ematologia Oncologica e Trapianto di Cellule Staminali, Napoli, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D004341:Drug Evaluation / Q000379:methods; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006689:Hodgkin Disease / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000628:therapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D012042:Registries; D016879:Salvage Therapy / Q000009:adverse effects / Q000379:methods; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003561:Cytarabine; D005047:Etoposide; C054368:fotemustine; D008558:Melphalan
keywords: Hodgkin lymphoma; autologous stem cell transplantation; fotemustine; high-dose chemotherapy