Detection of Minimal Residual Disease by Flow Cytometry for Patients with Multiple Myeloma Submitted to Autologous Hematopoietic Stem Cell Transplantation

Abstract

The treatment strategy in multiple myeloma (MM) is to get complete remission followed by high-dose chemotherapy and autologous Hematopoietic Stem Cell Transplantation (HSCT). Neoplastic Plasma Cells (NPCs) are CD45−/dim, CD38+high, CD138+, CD19−, and CD56+high in most cases. The description of this immunophenotype is of major importance as it leads to the correct identification of minimal residual disease (MRD). Samples from 44 Patients were analyzed prospectively in this study. We analyzed if the presence of MRD at three months after HSCT was predictive of relapse or death. There were 40 evaluable patients of whom 16/40 patients had MRD at three moths after HSCT and there were none in cytological relapse. The mean overall survival (OS) was 34 months and disease-free survival (RFS) was 28 months after HSCT. There was no significant difference in the log rank analysis comparing OS and the presence of MRD (P = 0,611) and RFS (P = 0,3106). Here, we demonstrate that three color flow cytometry (FCM) is more sensitive for MDR evaluation than cytological analyzes. However, based in our data we can not affirm that MRD is a good predictor of MM relapse or death. In conclusion, our results could be attributed to a short followup, small sample size, and over most to the inability of a three-color FCM to detect the NPC population.

Comparison of Minimal Residual Disease Detection by Multiparameter Flow Cytometry, ASO-qPCR, Droplet Digital PCR, and Deep Sequencing in Patients with Multiple Myeloma Who Underwent Autologous Stem Cell Transplantation

“…Multiparameter flow cytometry (MFC) (four or more colors) is frequently applied in clinical practice for the detection of MRD [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and although its sensitivity (approximately 10 −4 ) is inferior to that of the allele-specific oligonucleotide-PCR (ASO-PCR) assay, there is little difference between the clinical values of these methods [ 15 ]. Previous IMWG criteria define immunophenotypic CR (iCR) as stringent CR (sCR), in which MRD is not detected by MFC [ 23 ].…”

Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma

“…8,12–14,16–18,24,25,28–31 The impact of MRD status on OS was assessed in 12 studies involving 1,100 patients (599 MRD-negative, 501 MRD-positive). 6,8,13,14,16–19,24,25,28,31 Compared with MRD positivity, MRD negativity was associated with better PFS (HR 0.41; 95% CI 0.36–0.48; P < .0001) (Figure 2A) and OS (HR 0.57; 95% CI 0.46–0.71; P < .0001) (Figure 2B). Median PFS was 54 months for MRD-negative patients and 26 months for MRD-positive patients (Figure 2C); median OS was 98 and 82 months, respectively (Figure 2D).…”

“…12–14,16–18,29,30 One study found no significant difference in outcomes between patients with or without detectable MRD. 14 Others noted that MRD status did not correlate with standard response criteria.…”

“…12–14,16–18,29,30 One study found no significant difference in outcomes between patients with or without detectable MRD. 14 Others noted that MRD status did not correlate with standard response criteria. 17,18 In the study conducted by Rawstron et al, 6 it was noted that 34 of 246 (26%) MRD-negative patients did not achieve conventional CR, including 29 (12%) who had less than very good partial response (VGPR).…”

“…After applying eligibility criteria 21 studies were included in the qualitative assessments (Figure 1). Of the 21 articles identified, 13 involved patients with NDMM and in 9 articles it was not reported whether the population was limited to NDMM patients. Sixteen articles involved ASCT-eligible patients and 1 involved ASCT-ineligible patients; the remaining 4 studies included both ASCT-eligible and ASCT-ineligible patients.…”