title: Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma.
abstract: Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out-patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone successful transplantation. Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long-term repopulating capacity.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: H M
authors.initials: HM
authors.lastname: Lokhorst
authors.forename: P
authors.initials: P
authors.lastname: Sonneveld
authors.forename: P W
authors.initials: PW
authors.lastname: Wijermans
authors.forename: M
authors.initials: M
authors.lastname: van Marwijk Kooy
authors.forename: O J
authors.initials: OJ
authors.lastname: Meuwissen
authors.forename: R H
authors.initials: RH
authors.lastname: van Oers
authors.forename: R
authors.initials: R
authors.lastname: van der Griend
authors.forename: A W
authors.initials: AW
authors.lastname: Dekker
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000628:therapy; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D018906:Antineoplastic Agents, Alkylating; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim; D008558:Melphalan