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

// 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 , and Bernard Klein 1,2,5 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. Correspondence: Bernard Klein, email: // Keywords : Multiple Myeloma, Plasma cells, Minimal residual disease, Human Received : September 07, 2012, Accepted : October 23, 2012, Published : October 25, 2012 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.