Publication Date:
2020-11-05
Description:
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. Results 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 (p1%) 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). Conclusions 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.
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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