Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome after High-Dose Chemotherapy
by
,
Malte Roerden
1,2,3,*
,
Stefan Wirths
1,
Martin Sökler
1,
Wolfgang A. Bethge
1,
Wichard Vogel
1,† and
Juliane S. Walz
1,2,3,4,5,† 1
Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, 72076 Tübingen, Germany
2
Institute for Cell Biology, Department of Immunology, University of Tübingen, 72076 Tübingen, Germany
3
Cluster of Excellence iFIT (EXC2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tübingen, 72076 Tübingen, Germany
4
Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany
5
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology (IKP) and Robert Bosch Center for Tumor Diseases (RBCT), Auerbachstr. 112, 70376 Stuttgart, Germany
*
Author to whom correspondence should be addressed.
†
These authors share senior authorship.
Cancers 2021, 13(11), 2558; https://doi.org/10.3390/cancers13112558
Submission received: 29 March 2021
/
Revised: 7 May 2021
/
Accepted: 18 May 2021
/
Published: 23 May 2021
(This article belongs to the Special Issue Hematologic Malignancy)
Simple Summary
High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (Auto-HSCT) is a standard frontline treatment for fit mantle cell lymphoma (MCL) patients. As there is a need for predictive factors to identify patients unlikely to benefit from this therapy, we investigated the prognostic impact of lymphoma cell contamination of autologous stem cell grafts. Analyzing a cohort of 36 MCL patients, we show that lymphoma cell contamination of stem cell grafts is associated with poor outcomes after Auto-HSCT. Its analysis might thus improve risk assessment and enable risk-stratified treatment strategies for MCL patients.
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.
