title: High-dose melphalan with autotransplantation for refractory multiple myeloma: results of a Southwest Oncology Group phase II trial.
abstract: OBJECTIVE
  To evaluate high-dose melphalan followed by autologous stem-cell transplantation in patients with refractory multiple myeloma.
  
  
  METHODS
  Multiple myeloma patients with alkylating agent or vincristine/doxorubicin/dexamethasone-refractory disease were eligible for the phase II multi-institutional Southwest Oncology Group trial S8993. Patients up to age 70 years were enrolled between April 15, 1991, and May 1, 1996. Patients without prior stem-cell collection were primed with high-dose cyclophosphamide (HD-CTX; 6 g/m(2)) and granulocyte-macrophage colony-stimulating factor. After stem-cell procurement, patients received melphalan 200 mg/m(2) with autologous transplantation. Upon recovery from melphalan, patients were to receive interferon alfa-2b until relapse.
  
  
  RESULTS
  Seventy-two patients were enrolled onto S8993; five were ineligible and one received no therapy. Of the 66 assessable patients, 56 patients underwent the transplant procedure; 54 were assessable for response and 56 for toxicity. The response to HD-CTX (n = 37) included three complete remissions (CRs; 8%) and five partial remissions (PR; 14%); response to melphalan (n = 54) included 16 CRs (30%) and 19 PRs (35%), for an overall CR and >/= PR (n = 66; intent-to-treat) of 27% and 58%, respectively. Toxicities included six treatment-related deaths: two during HD-CTX and four during transplantation. The median progression-free survival (PFS) and overall survival (OS) durations on an intent-to-treat basis from transplant registration was 11 months and 19 months (95% confidence interval, 14 to 29 months), respectively. The 3-year actuarial PFS and OS rates were 25% and 31%, respectively.
  
  
  CONCLUSIONS
  High-dose therapy with melphalan 200 mg/m(2) is feasible with high response rates (58% overall) and an OS of 19 months in patients with refractory multiple myeloma.
authors.affiliation: University of Arkansas for Medical Science, Little Rock, AR, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Vesole
authors.forename: J J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: R
authors.initials: R
authors.lastname: Catchatourian
authors.forename: P J
authors.initials: PJ
authors.lastname: Stiff
authors.forename: D B
authors.initials: DB
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Cromer
authors.forename: S E
authors.initials: SE
authors.lastname: Salmon
authors.forename: B
authors.initials: B
authors.lastname: Barlogie
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000506:poisoning; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011994:Recombinant Proteins; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D008558:Melphalan