title: Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma - a phase I/II feasibility and tolerance study of 17 patients.
abstract: Aiming to target the minimal residual disease in patients with multiple myeloma, a phase I/II single centre study was undertaken for feasibility and tolerance of intensive acute lymphoblastic leukaemia consolidation chemotherapy (ALL-IC) as part of a strategy for post-transplant consolidation targeted at pre-B cells. Seventeen newly diagnosed patients with myeloma (median age 55 years; 30-65) were initially treated with courses of infused cyclophosphamide, vincristine, adriamycin and methylprednisolone (C-VAMP) followed by melphalan 200 mg/m2(HDM) and peripheral blood stem cell rescue (PBSC). Forty-seven percent were in CR and the rest in PR after HDM. ALL-IC consisted of vincristine, daunorubicin, etoposide, cytarabine, 6-thioguanine and prednisolone given over 5 days. All patients became neutropenic (<0.5 x 109/l) at a median of 10 days (4-18) and one of the 17 patients (5.8%) died 15 days post ALL-IC of sepsis. A further four have died of relapse with an overall survival (OS) of 67% at 4 years. Two of nine patients in PR at the time of ALL-IC achieved CR. Matched-pair analysis of 34 control patients shows no difference for OS and event-free survival between ALL-IC and controls. We conclude that ALL-IC given to myeloma patients after HDM/PBSC is as safe as when used in ALL and warrants further assessment in randomised trials for myeloma.
authors.affiliation: Leukaemia and Myeloma Units, Royal Marsden NHS Trust and Institute of Cancer Research, Sutton, UK.
authors.forename: R
authors.initials: R
authors.lastname: Powles
authors.forename: B
authors.initials: B
authors.lastname: Sirohi
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
authors.forename: N
authors.initials: N
authors.lastname: Bhagwati
authors.forename: R
authors.initials: R
authors.lastname: Saso
authors.forename: N
authors.initials: N
authors.lastname: Raje
authors.forename: C
authors.initials: C
authors.lastname: Horton
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: J
authors.initials: J
authors.lastname: Mehta
authors.forename: J
authors.initials: J
authors.lastname: Treleaven
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D018365:Neoplasm, Residual; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D008558:Melphalan