title: Dose escalation therapy in previously untreated patients with multiple myeloma following Z-Dex induction treatment.
abstract: A phase I-II study of high-dose (HD) alkylating agents in newly diagnosed patients with multiple myeloma after maximum response to Z-Dex (idarubicin, dexamethasone) therapy and DHAP (cisplatin, HD cytosine arabinoside, dexamethasone), stem cell mobilization is reported. Twenty-six patients, median age 56 years (range 42-66), completed Z-Dex chemotherapy and peripheral blood stem cells (PBSC) were mobilized with DHAP. Patients then preceded to cyclophosphamide (HD Cy: 6 g/m(2)) with granulocyte colony-stimulating factor followed by busulphan-melphalan-conditioned PBSC autograft. Interferon alpha was introduced at 3 months post transplant as maintenance therapy. Six patients failed to complete the full protocol. Median time from diagnosis to transplantation was 8 months (range 6-12). Mean CD34+ cell dose collected was 15.8 x 10(6)/kg (CI 11.8, 19.8). Median time from DHAP to HD-Cy was 6 weeks (range 4-12) and from HD-Cy to transplant was 8 weeks (range 6-12). The median follow-up was 36 months (range 6-63). On an intent-to-treat basis, the response rates were three complete response (CR, 12%), 21 partial response (PR, 80%) and two stable disease (SD, 8%) post Z-Dex, five CR (19%) and 21 PR (81%) post HD-Cy, and 14 CR (54%) and 12 PR (46%) post transplant. The treatment-related mortality (TRM) was 4% (1 patient). Median overall survival (OS) and progression-free survival (PFS) have not been reached; estimated values were 60 and 48 months respectively. The 3-year OS and PFS were 72% and 62%. Actuarial 5-year OS and event-free survival were 49% and 32%. DHAP produces effective PBSC mobilization and sequential HD therapy, including autologous PBSCT, in patients who received Z-Dex; this offers significant durable disease response rates with acceptable TRM.
authors.affiliation: Academic Transfusion Medicine Unit, Department of Medicine, University of Glasgow, Glasgow, Scotland, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Clark
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Douglas
authors.forename: Lyndsay D
authors.initials: LD
authors.lastname: Mitchell
authors.forename: I Grant
authors.initials: IG
authors.lastname: McQuaker
authors.forename: Anne N
authors.initials: AN
authors.lastname: Parker
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Tansey
authors.forename: Ian M
authors.initials: IM
authors.lastname: Franklin
authors.forename: Gordon
authors.initials: G
authors.lastname: Cook
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002066:Busulfan / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D003907:Dexamethasone; D003520:Cyclophosphamide; D002066:Busulfan; D002945:Cisplatin; D008558:Melphalan; D015255:Idarubicin