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

Lea Amalia Lind Elkjær; Oriane Cédile; Marcus Høy Hansen; Christian Nielsen; Michael Boe Møller; Niels Abildgaard; Jacob Haaber; Charlotte Guldborg Nyvold

doi:10.1016/j.lrr.2022.100341

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

Lea Amalia Lind Elkjær, Oriane Cédile, Marcus Høy Hansen, Christian Nielsen, Michael Boe Møller, Niels Abildgaard, Jacob Haaber, Charlotte Guldborg Nyvold^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival. Using next-generation sequencing, we explore whether the diagnostic MCL clonotype is present within the infused SCP. MRD was detected in 4/17 of the SCPs, ranging 4–568 clonal cells/100,000 cells. With a median survival of 17 months, 3/4 of patients with MRD+ graft succumbed from MCL relapse versus 2/13 in the MRD– fraction. Patients receiving MRD+ grafts had increased risk of mortality, and thus screening of SCPs may be important for clinical decision-making.

Originalsprog	Engelsk
Artikelnummer	100341
Tidsskrift	Leukemia Research Reports
Vol/bind	18
Antal sider	5
ISSN	2213-0489
DOI	https://doi.org/10.1016/j.lrr.2022.100341
Status	Udgivet - jan. 2022

Bibliografisk note

Funding Information:
The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation. We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance.

Funding Information:
The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation . We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance.

Publisher Copyright:
© 2022

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10.1016/j.lrr.2022.100341Licens: CC BY-NC-ND

1-s2.0-S221304892200053X-mainForlagets udgivne version, 981 KBLicens: CC BY-NC-ND

Citationsformater

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abstract = "High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival. Using next-generation sequencing, we explore whether the diagnostic MCL clonotype is present within the infused SCP. MRD was detected in 4/17 of the SCPs, ranging 4–568 clonal cells/100,000 cells. With a median survival of 17 months, 3/4 of patients with MRD+ graft succumbed from MCL relapse versus 2/13 in the MRD– fraction. Patients receiving MRD+ grafts had increased risk of mortality, and thus screening of SCPs may be important for clinical decision-making.",

keywords = "Autologous stem cell transplantation, Mantle cell lymphoma, Measurable residual disease, Minimal residual disease, Relapse",

author = "Elkj{\ae}r, {Lea Amalia Lind} and Oriane C{\'e}dile and Hansen, {Marcus H{\o}y} and Christian Nielsen and M{\o}ller, {Michael Boe} and Niels Abildgaard and Jacob Haaber and Nyvold, {Charlotte Guldborg}",

note = "Funding Information: The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation. We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance. Funding Information: The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation . We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance. Publisher Copyright: {\textcopyright} 2022",

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doi = "10.1016/j.lrr.2022.100341",

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AU - Elkjær, Lea Amalia Lind

AU - Cédile, Oriane

AU - Hansen, Marcus Høy

AU - Nielsen, Christian

AU - Møller, Michael Boe

AU - Abildgaard, Niels

AU - Haaber, Jacob

AU - Nyvold, Charlotte Guldborg

N1 - Funding Information: The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation. We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance. Funding Information: The project received funding from the Danish Medical Association, the Danish Cancer Society, the Harboe Foundation, the OUH Free Research Fund, the Danish Lymphoma Group and the Torben and Alice Frimodt's foundation . We thank Dennis Lund Hansen for his expertise in survival analysis (Department of Haematology, OUH), Vickie Svane Kristensen (Research Unit for Haematology, OUH) for language assistance and Nina Friis Jensen (Department of Pathology, OUH) for excellent technical assistance. Publisher Copyright: © 2022

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N2 - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival. Using next-generation sequencing, we explore whether the diagnostic MCL clonotype is present within the infused SCP. MRD was detected in 4/17 of the SCPs, ranging 4–568 clonal cells/100,000 cells. With a median survival of 17 months, 3/4 of patients with MRD+ graft succumbed from MCL relapse versus 2/13 in the MRD– fraction. Patients receiving MRD+ grafts had increased risk of mortality, and thus screening of SCPs may be important for clinical decision-making.

AB - High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has become a treatment option for fit patients with mantle cell lymphoma (MCL). However, these patients often relapse within few years, potentially caused by contaminating lymphoma cells within the reinfused stem cell product (SCP). Studies have shown that measurable residual disease, also termed minimal residual disease (MRD), following ASCT predicts shorter survival. Using next-generation sequencing, we explore whether the diagnostic MCL clonotype is present within the infused SCP. MRD was detected in 4/17 of the SCPs, ranging 4–568 clonal cells/100,000 cells. With a median survival of 17 months, 3/4 of patients with MRD+ graft succumbed from MCL relapse versus 2/13 in the MRD– fraction. Patients receiving MRD+ grafts had increased risk of mortality, and thus screening of SCPs may be important for clinical decision-making.

KW - Autologous stem cell transplantation

KW - Mantle cell lymphoma

KW - Measurable residual disease

KW - Minimal residual disease

KW - Relapse

U2 - 10.1016/j.lrr.2022.100341

DO - 10.1016/j.lrr.2022.100341

M3 - Journal article

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AN - SCOPUS:85135926197

SN - 2213-0489

VL - 18

JO - Leukemia Research Reports

JF - Leukemia Research Reports

M1 - 100341

ER -

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

Abstract

Bibliografisk note

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