title: High-Dose Melphalan Plus Thiotepa as Conditioning Regimen before Second Autologous Stem Cell Transplantation for "De Novo" Multiple Myeloma Patients: A Phase II Study.
abstract: High-dose melphalan (MEL) is the standard therapy for autologous stem cell transplantation (ASCT) in multiple myeloma (MM), although the optimal conditioning regimen remains yet to be identified. Thiotepa (THIO) appears to be a potentially effective option, with broad-spectrum antitumor efficacy that can be added to myeloablative multiagent regimens for ASCT in hematopoietic tumors. We conducted a phase II trial, adding THIO (275 mg/m(2)) to high-dose MEL (140 mg/m(2)) before a second ASCT, in a tandem ASCT strategy, in 64 patients with "de novo" MM. Overall, there was no transplant-related mortality. The incidence of neutropenic fever and mucositis (grades 3 to 4) was 39% and 9%, respectively. Median number of days to neutrophil and platelet engraftment were 11 and 12, respectively. After the second transplantation, the complete response improved to 43.8%. Overall response rate was 86%. After a median follow-up of 18.1 months, 13 patients had progressed and 3 died from MM. Median progression-free survival was not reached, and actuarial 2-year rates of progression-free and overall survival were 71% and 88.9%, respectively. Our results suggest that THIO/MEL is a feasible and safe conditioning regimen for ASCT in MM and should be explored for efficacy in a phase III study.
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Oncology Department, "La Maddalena" Hospital, Palermo, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Musso
authors.affiliation: Hematology and Stem Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera BMM, Reggio Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Messina
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Hematology Department, Fondazione "G. Pascale", Istituto di Ricovero e Cura a Carattere Scientifico, Napoli, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Marcacci
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Oncology Department, "La Maddalena" Hospital, Palermo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Crescimanno
authors.affiliation: Hematology and Stem Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera BMM, Reggio Calabria, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Console
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Hematology Department, Fondazione "G. Pascale", Istituto di Ricovero e Cura a Carattere Scientifico, Napoli, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Donnarumma
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Oncology Department, "La Maddalena" Hospital, Palermo, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Scalone
authors.affiliation: Onco-Hematology and Stem Cell Transplantation Unit, Hematology Department, Fondazione "G. Pascale", Istituto di Ricovero e Cura a Carattere Scientifico, Napoli, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Hematology and Stem Transplantation Unit, Onco-Hematology Department, Azienda Ospedaliera BMM, Reggio Calabria, Italy. Electronic address: dr.massimomartino@gmail.com.
authors.forename: Massimo
authors.initials: M
authors.lastname: Martino
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology; D005260:Female; D005334:Fever / Q000209:etiology / Q000473:pathology; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D052016:Mucositis / Q000209:etiology / Q000473:pathology; D009101:Multiple Myeloma / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011446:Prospective Studies; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage* / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D013852:Thiotepa; D008558:Melphalan
keywords: Autologous transplantation; Conditioning regiment; High-dose melphalan; Multiple myeloma; Thiotepa