Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome after High-Dose Chemotherapy

Abstract

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation

“… 9 , 12 To date, no studies have examined the prognostic value of HTS-based minimal residual disease (MRD) assessment in patients with DLBCL undergoing ASCT. Older studies have shown that patients with DLBCL undergoing ASCT who received a minimally contaminated stem cell product (based on cell culture, Southern analysis, or polymerase chain reaction) had significantly worse survival outcomes 13 , 14 , 15 similar observations have been made for patients with mantle cell 16 , 17 , 18 and follicular lymphoma. 19 , 20 Novel MRD assays may provide a more sensitive marker of contaminated graft before ASCT, and therefore could guide more selective use of ASCT.…”

Exploration of residual disease in stem cell products from mantle cell lymphoma using next-generation sequencing

“…In line with this observation, Roerden et al. [10] demonstrated that 4/36 (11%) patients with MRD positive grafts were identified by multi-parameter flow cytometry. Here, the progression-free and overall survival were significantly inferior for graft-positive patients.…”

“… [9] , where longitudinal NGS-based MRD surveillance helped to identify patients bound for relapse following autologous stem cell transplantation and extends the association between graft-MRD detected by flow cytometry and decrease in progression-free and overall survival made by Roerden et al. [10] . Although studies have proven that MRD status following treatment is of paramount prognostic importance, little is still known concerning residual disease in SCPs used for ASCT and its potential role in disease relapse.…”