title: Residual malignant and normal plasma cells shortly after high dose melphalan and stem cell transplantation. Highlight of a putative therapeutic window in Multiple Myeloma?
abstract: Multiple Myeloma (MM) is an incurable malignant plasma cell disorder. We have evaluated the counts of Multiple Myeloma Cells (MMCs) and normal plasma cells (N-PCs), seven days after high-dose melphalan (HDM) and autologous stem transplantation (ASCT). Two third of patients had detectable minimal residual disease (MRD+) (71.7 MMCs/µL) after induction treatment with dexamethasone and proteasome inhibitor. MMC counts were reduced by 92% (P ≤ .05) but not eradicated 7 days after HDM+ASCT. Post-HDM+ASCT MMCs were viable and bathed in a burst of MMC growth factors, linked with post-HDM aplasia. In one third of patients (MRD- patients), MMCs were not detectable after induction treatment and remained undetectable after HDM+ASCT. Major difference between MRD- and MRD+ patients is that N-PC counts were increased 3 fold (P〈.05) by HDM+ASCT in MRD- patients, but were unaffected in MRD+ patients. Possible explanation could be that clearance of MMCs in MRD- patients makes more niches available for N-PCs. Thus, MMCs are not fully eradicated shortly after HDM, are bathed in high concentrations of MMC growth factors in an almost desert BM, are viable in short-term culture, which suggests providing additional therapies shortly after HDM to kill resistant MMCs before full repair of lesions.
authors.affiliation: INSERM, U1040, Montpellier, France.
authors.forename: Anouk
authors.initials: A
authors.lastname: Caraux
authors.forename: Laure
authors.initials: L
authors.lastname: Vincent
authors.forename: Salahedine
authors.initials: S
authors.lastname: Bouhya
authors.forename: Philippe
authors.initials: P
authors.lastname: Quittet
authors.forename: Jérôme
authors.initials: J
authors.lastname: Moreaux
authors.forename: Guilhem
authors.initials: G
authors.lastname: Requirand
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veyrune
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Olivier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Rossi
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D010950:Plasma Cells / Q000187:drug effects*; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008558:Melphalan