Residual malignant and normal plasma cells shortly after high dose melphalan and stem cell transplantation. Highlight of a putative therapeutic window in Multiple Myeloma?
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Anouk Caraux1, Laure Vincent1,2, Salahedine Bouhya3, Philippe Quittet3, Jérôme Moreaux2, Guilhem Requirand2, Jean-Luc Veyrune4, Gaëlle Olivier3, Guillaume Cartron3, Jean-François Rossi3, and Bernard Klein1,2,5
1 INSERM, U1040, Montpellier, France
2 CHU Montpellier St Eloi, Institute of Research in Biotherapy, France
3 CHU Montpellier St Eloi, Service d’Hématologie et Oncologie Médicale, France
4 CHU Montpellier St Eloi, Cell Therapy Unit, France
5 Université Montpellier 1, France.
Bernard Klein, email:
Keywords: Multiple Myeloma, Plasma cells, Minimal residual disease, Human
Received: September 07, 2012, Accepted: October 23, 2012, Published: October 25, 2012
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.
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