-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2421 Next-Generation Sequencing Minimal Residual Disease of Mantle Cell Lymphoma in Autologous Stem Cell Grafts and Its Implication on Tumor Recurrence

Program: Oral and Poster Abstracts
Session: 731. Clinical Autologous Transplantation: Results: Poster II
Hematology Disease Topics & Pathways:
Biological, Adult, survivorship, Diseases, Mantle Cell Lymphoma, Therapies, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Biological Processes, Technology and Procedures, Lymphoid Malignancies, Study Population, Clinically relevant, Quality Improvement , transplantation, stem cells, NGS
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Yu-Hung Wang, MD1*, Yi-Kuang Chuang2*, Yu-Hsuan Yang2*, Shan-Chi Yu3*, Yi-Tsung Yang4*, Bor-Sheng Ko, MD, PhD5*, Ming Yao, MD6*, Tai-Chung Huang, MD, PhD6* and Jih-Luh Tang, M.D., Ph.D.5

1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
2Tai Cheng Stem Cell Therapy Center, National Taiwan University Cancer Center, Taipei, Taiwan
3National Taiwan University Hospital, Taipei City, TWN
4Division of Hematology-Oncology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Taipei City, Taiwan
5Department of Hematological Oncology, National Taiwan University Cancer Center, Taipei, Taiwan
6Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Background & Purpose

The clinical course of mantle cell lymphoma (MCL) is often inflicted with tumor recurrence even though front-line autologous stem cell transplantation (ASCT) is the current standard of care. To elucidate the mechanism of post-transplant recurrence, this study aimed to interrogate the minimal residual disease (MRD) of MCL in the autologous grafts.

Materials & Methods

Paired samples of 17 MCL patients’ lymphoma diagnostic FFPE specimens were analyzed in parallel with their harvested autologous stem cell grafts. Extracted genomic DNA was subjected to LymphoTrack Dx IGH/IGK assay coupled with Illumina MiSeq sequencer to characterize the post-recombination immunoglobulin VDJ sequences. Positivity of MRD was defined for any identical sequences identified both in the diagnostic FFPE and in the autologous graft DNA. As the control for recombined VDJ protein motif analysis, diagnostic FFPE samples from 23 patients with diffuse large B cell lymphoma (DLBCL) were analyzed with the same platform.


Of the 17 patients undertaking autologous stem cell harvest, 11 patients achieved complete response and 6 were in partial response before stem cell harvest. Sixteen of these actually underwent transplantation while one died of disease before transplantation. MRD was detected via next-generation sequencing (NGS) in 5 patients’ autologous grafts with variable MRD loads and recombined VDJ stereotypes (Table 1). VH3-21 was the most prominent stereotype (41%), followed by VH4-59 (14%). The median somatic hypermutation rate was 0.88% (range 0 - 5.17%). Interestingly, a 46-amino-acid domain in recombined VDJ sequences, which was hydroxyl and amine group-rich, differed between MCL and DLBCL: hydrophilic amino acids were enriched in 6 positions of this domain in MCL (p<0.05). Among the five patients who had MRD in autologous grafts, the median MRD read number was 12,764 reads (range 89 - 33,554) with the median read depth of 195,865 reads (range 94,820 - 396,894). The MRD loads in the autologous grafts were inversely correlated with post-harvest PFS (Figure 1a and 1b). As for post-ASCT outcomes, patients with MRD had a trend toward worse PFS and OS than those without MRD (medians, 10 months vs 27 months, and 25 months vs 66.8 months, respectively). In subgroup analysis, a higher load of NGS-MRD (>1%) correlated with shorter post-ASCT PFS and OS than those without MRD (medians, 1.9 months vs 27 months (p=0.024) in Figure 1c, and 11.9 months vs 66.8 months (p=0.001) in Figure 1d, respectively).


Identification of MRD in autologous grafts by deep-sequencing VDJ recombination helped stratify MCL patients’ post-ASCT outcomes. Higher MRD loads correlated with inferior post-ASCT PFS and OS. The implication of recombined VDJ stereotypes and their impact on ASCT outcomes warrants further investigation.

Disclosures: Ko: Roche: Honoraria.

*signifies non-member of ASH