title: Risk-adjusted manipulation of melphalan dose before stem cell transplantation in patients with amyloidosis is associated with a lower response rate.
abstract: High-dose chemotherapy and autologous stem cell transplantation are used increasingly to treat patients with light-chain-related amyloidosis (AL). Treatment-related mortality is approximately 15%. To enable more patients to undergo stem cell transplantation, a risk-adapted strategy has been developed to treat with lower chemotherapy doses those patients who are at excessive risk. It is unclear whether reducing the chemotherapy dose in patients at excessive risk of treatment toxicity reduces the overall response. We retrospectively reviewed 171 AL patients who underwent conditioning chemotherapy with stem cell transplantation. The patients comprised two groups: those receiving standard high-dose melphalan and those receiving intermediate-dose melphalan. Responses were categorized as hematologic response, which used criteria for myeloma response. The two groups showed statistically significant differences; the overall response rates were 75% in the high-dose group and 53% in the intermediate-dose group although treatment-related mortality was the same in both groups. Reducing the melphalan dose appeared to render more AL patients eligible for stem cell transplantation but sacrificed an element of response. Methods are needed to reduce treatment-related toxicity so that more patients can receive full-dose conditioning chemotherapy.
authors.affiliation: Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. gertz.morie@mayo.edu
authors.forename: M A
authors.initials: MA
authors.lastname: Gertz
authors.forename: M Q
authors.initials: MQ
authors.lastname: Lacy
authors.forename: A
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: S M
authors.initials: SM
authors.lastname: Ansell
authors.forename: M A
authors.initials: MA
authors.lastname: Elliott
authors.forename: D A
authors.initials: DA
authors.lastname: Gastineau
authors.forename: D J
authors.initials: DJ
authors.lastname: Inwards
authors.forename: I N M
authors.initials: IN
authors.lastname: Micallef
authors.forename: L F
authors.initials: LF
authors.lastname: Porrata
authors.forename: A
authors.initials: A
authors.lastname: Tefferi
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
mesh_terms: D000328:Adult; D000368:Aged; D000686:Amyloidosis / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality / Q000592:standards; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage* / Q000633:toxicity; D008875:Middle Aged; D012189:Retrospective Studies; D020379:Risk Adjustment; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D008558:Melphalan