title: High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants.
abstract: One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM-CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2-microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P < .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.
authors.affiliation: Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock 72205.
authors.forename: D H
authors.initials: DH
authors.lastname: Vesole
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
authors.forename: S
authors.initials: S
authors.lastname: Jagannath
authors.forename: B
authors.initials: B
authors.lastname: Cheson
authors.forename: G
authors.initials: G
authors.lastname: Tricot
authors.forename: R
authors.initials: R
authors.lastname: Alexanian
authors.forename: J
authors.initials: J
authors.lastname: Crowley
mesh_terms: D000367:Age Factors; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D011379:Prognosis; D016019:Survival Analysis; D013852:Thiotepa / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D013852:Thiotepa; D008558:Melphalan