Residual malignant and normal plasma cells shortly after high dose melphalan and stem cell transplantation. Highlight of a putative therapeutic window in Multiple Myeloma?

Anouk Caraux 1 Laure Vincent 1, 2 Salahedine Bouhya 3 Philippe Quittet 3 Jérôme Moreaux 2 Guilhem Requirand 2 Jean-Luc Veyrune 4 Gaëlle Olivier 3 Guillaume Cartron 3 Jean-François Rossi 3 Bernard Klein 1, *
* Auteur correspondant
1 Cellules souches normales et cancéreuses
2 IRB - Institut de recherche en biothérapie
3 Service d'hématologie et oncologie médicale
4 Unité de Thérapie Cellulaire et Génétique
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.
keyword : minimal resigual disease human multiple myeloma plasma cells
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Oncotarget, Impact journals, 2012, 3 (11), pp.1335-47
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Anouk Caraux, Laure Vincent, Salahedine Bouhya, Philippe Quittet, Jérôme Moreaux, et al.. Residual malignant and normal plasma cells shortly after high dose melphalan and stem cell transplantation. Highlight of a putative therapeutic window in Multiple Myeloma?. Oncotarget, Impact journals, 2012, 3 (11), pp.1335-47. 〈inserm-00802665〉

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