The Assessment Of Stem Cell Graft Contamination Via Next-Generation Flow Cytometry Serves As A Negative Predictor For Deep Remissions Post-Autologous Stem Cell Transplantation In Multiple Myeloma

Context High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is the standard option for eligible multiple myeloma (MM) patients. Though beneficial, there is clinical heterogeneity post-ASCT, which necessitates the identification of strong predictors for early relapse. Contamination of stem cell grafts by aberrant plasma cells (APCs) has been considered as a possible predictive marker, though there are limited reported series with no clear conclusions. Objective The evaluation of graft contamination as a predictive biomarker and its impact in bone marrow (BM) reconstitution. Design We prospectively evaluated graft contamination utilizing a highly sensitive next-generation flow approach (NGF). Clinical endpoints considered were response improvement, time to achieve CR, and/or MRD negativity post-ASCT. The median follow-up period was 22 months. Patients and Methods The study included 199 transplant-eligible MM patients. The median LOD for APC detection was 2.9x10–6. MRD was examined at the first evidence of CR achievement and every three months since then. BM profiling was examined on day 100 post-ASCT with NGF. Results Contamination was present in 79/199 (39.7%) patients with a median level of 2x10–5. The presence and levels of contamination were correlated with response to induction treatment with 94%, 71%, and 43% of those achieving CR, VGPR, and PR, respectively, showing no APCs in their grafts (con-). Contaminating grafts (con+) conferred worse response improvement post-ASCT and prolonged periods for subsequent CR and MRD negativity achievement. The median time to achieve CR was 4 and 11 months for con- and con+ patients (HR: 2.01, 95% CI:1.44–2.81; p Conclusions These data, together with the absence of significant intercorrelations with baseline clinical features, highlight graft contamination (of even marginal residual disease) as an early independent predictive biomarker that could be utilized for patient stratification post-ASCT.