title: BeEAM (bendamustine, etoposide, cytarabine, melphalan) before autologous stem cell transplantation is safe and effective for resistant/relapsed lymphoma patients.
abstract: We designed a phase 1-2 study to evaluate the safety and the efficacy of increasing doses of bendamustine (160 mg/m², 180 mg/m², and 200 mg/m² given on days -7 and -6) coupled with fixed doses of etoposide, cytarabine, and melphalan (BeEAM regimen) as the conditioning regimen to autologous stem cell transplantation for resistant/relapsed lymphoma patients. Forty-three patients (median age, 47 years) with non-Hodgkin (n = 28) or Hodgkin (n = 15) lymphoma were consecutively treated. Nine patients entered the phase 1 study; no patients experienced a dose-limiting toxicity. Thirty-four additional patients were then treated in the phase 2. A median number of 6 × 10⁶ CD34(+) cells/kg (range, 2.4-15.5) were reinfused. All patients engrafted, with a median time to absolute neutrophil count > 0.5 × 10⁹/L of 10 days. The 100-day transplantation-related mortality was 0%. After a median follow-up of 18 months, 35 of 43 patients (81%) are in complete remission, whereas 6 of 43 relapsed and 2 of 43 did not respond. Disease type (non-Hodgkin lymphomas vs Hodgkin disease) and disease status at transplantation (chemosensitive vs chemoresistant) significantly influenced DFS (P = .01; P = .007). Remarkably, 4 of 43 (9%) patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell transplantation. In conclusion, the new BeEAM regimen is safe and effective for heavily pretreated lymphoma patients. The study was registered at European Medicines Agency (EudraCT number 2008-002736-15).
authors.affiliation: Hematology and Stem Cell Transplant Center, Marche Nord Hospital, Pesaro, Italy. g.visani@ospedalesansalvatore.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Visani
authors.forename: Lara
authors.initials: L
authors.lastname: Malerba
authors.forename: Pietro Maria
authors.initials: PM
authors.lastname: Stefani
authors.forename: Saveria
authors.initials: S
authors.lastname: Capria
authors.forename: Piero
authors.initials: P
authors.lastname: Galieni
authors.forename: Francesco
authors.initials: F
authors.lastname: Gaudio
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Meloni
authors.forename: Filippo
authors.initials: F
authors.lastname: Gherlinzoni
authors.forename: Claudio
authors.initials: C
authors.lastname: Giardini
authors.forename: Sadia
authors.initials: S
authors.lastname: Falcioni
authors.forename: Francesca
authors.initials: F
authors.lastname: Cuberli
authors.forename: Marco
authors.initials: M
authors.lastname: Gobbi
authors.forename: Barbara
authors.initials: B
authors.lastname: Sarina
authors.forename: Armando
authors.initials: A
authors.lastname: Santoro
authors.forename: Felicetto
authors.initials: F
authors.lastname: Ferrara
authors.forename: Marco
authors.initials: M
authors.lastname: Rocchi
authors.forename: Enrique M
authors.initials: EM
authors.lastname: Ocio
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Caballero
authors.forename: Alessandro
authors.initials: A
authors.lastname: Isidori
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D000069461:Bendamustine Hydrochloride; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy / Q000379:methods*; D019172:Transplantation Conditioning / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D009588:Nitrogen Mustard Compounds; D003561:Cytarabine; D005047:Etoposide; D000069461:Bendamustine Hydrochloride; D008558:Melphalan