title: Glomerular filtration rate prior to high-dose melphalan 200 mg/m(2) as a surrogate marker of outcome in patients with myeloma.
abstract: We correlated age and body surface area corrected glomerular filtration rate (GFR) at the time of high-dose melphalan (HDM) administration with treatment-related toxicity (TT), time to disease progression and survival. Between 8/85 and 6/98, 144 newly diagnosed myeloma patients with a median age of 53 years (range, 31-72) received infusional chemotherapy with vincristine, doxorubicin and methylprednisolone, with/without cyclophosphamide or verapamil, followed by HDM 200 mg/m(2)and stem cell rescue. An additional patient received HDM at diagnosis. GFR was below normal in 38 patients (26%). At presentation, patients with low GFR at the time of HDM had higher serum creatinine, beta(2)M, stage III disease, calcium and Bence-Jones proteinuria. Toxic deaths post-HDM were similar in both groups (2/38 (5%) vs. 4/107 (4%)), though patients with low GFR had more oral mucositis (P< 0.0001), diarrhoea (P = 0.005) and infections (P = 0.04). The response and relapse rates of the 2 groups were not substantially different, but the median overall survival (OS) was significantly shorter in patients with low GFR (5.1 vs 7.5 years, P = 0.015). Multivariate analysis showed that a normal GFR and being in CR at the time of HDM were predictive of longer OS. We conclude that in context of high-dose chemotherapy for myeloma, dose of melphalan should not be modified in patients with low GFR and that early intensive treatment at relapse may improve results in patients with abnormal renal function.
authors.affiliation: Leukaemia Unit, Royal Marsden NHS Trust, Surrey, UK.
authors.forename: B
authors.initials: B
authors.lastname: Sirohi
authors.forename: R
authors.initials: R
authors.lastname: Powles
authors.forename: S
authors.initials: S
authors.lastname: Kulkarni
authors.forename: C
authors.initials: C
authors.lastname: Rudin
authors.forename: R
authors.initials: R
authors.lastname: Saso
authors.forename: A
authors.initials: A
authors.lastname: Rigg
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; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D015415:Biomarkers; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000503:physiopathology*; D015999:Multivariate Analysis; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D015415:Biomarkers; D008558:Melphalan