The 17-gene stemness score associates with relapse risk and long-term outcomes following allogeneic haematopoietic cell transplantation in acute myeloid leukaemia

Dennis D H Kim; Igor Novitzky Basso; Taehyung Simon Kim; Seong Yoon Yi; Kyoung Ha Kim; Tracy Murphy; Steven Chan; Mark Minden; Ivan Pasic; Wilson Lam; Arjun Law; Fotios V Michelis; Armin Gerbitz; Auro Viswabandya; Jeffrey Lipton; Rajat Kumar; Stanley W K Ng; Tracy Stockley; Tong Zhang; Ian King; Jonas Mattsson; Jean C Y Wang

doi:10.1002/jha2.466

The 17-gene stemness score associates with relapse risk and long-term outcomes following allogeneic haematopoietic cell transplantation in acute myeloid leukaemia

EJHaem. 2022 May 23;3(3):873-884. doi: 10.1002/jha2.466. eCollection 2022 Aug.

Authors

Dennis D H Kim^{1

2}, Igor Novitzky Basso¹, Taehyung Simon Kim^{1

3

4}, Seong Yoon Yi^{1

5}, Kyoung Ha Kim^{1

6}, Tracy Murphy^{1

2}, Steven Chan^{1

2}, Mark Minden^{1

2}, Ivan Pasic^{1

2}, Wilson Lam^{1

2}, Arjun Law^{1

2}, Fotios V Michelis^{1

2}, Armin Gerbitz^{1

2}, Auro Viswabandya^{1

2}, Jeffrey Lipton^{1

2}, Rajat Kumar^{1

2}, Stanley W K Ng⁷, Tracy Stockley^{8

9

10}, Tong Zhang⁸, Ian King⁸, Jonas Mattsson^{1

2

11}, Jean C Y Wang^{2

1}

Affiliations

¹ Department of Medical Oncology and Hematology Princess Margaret Cancer Centre University of Toronto Toronto Canada.
² Faculty of Medicine University of Toronto Toronto Canada.
³ Department of Computer Science University of Toronto Toronto Canada.
⁴ The Donnelly Centre for Cellular and Biomolecular Research University of Toronto Toronto Canada.
⁵ Department of Internal Medicine Inje University Ilsan Paik Hospital Goyang Korea.
⁶ Department of Internal Medicine College of Medicine Seoul Hospital Soonchunhyang University Seoul Korea.
⁷ Cancer Genome Project Wellcome Sanger Institute Hinxton UK.
⁸ The Advanced Molecular Diagnostics Lab Princess Margaret Cancer Centre Toronto Canada.
⁹ Clinical Laboratory Genetics Laboratory Medicine Program University Health Network Toronto Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada.
¹¹ Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation Princess Margaret Cancer Centre Toronto Canada.

Abstract

A 17-gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia-free survival (LFS), relapse incidence (RI) and non-relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub-groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft-versus-host-disease was associated with more favourable outcomes in both groups. The 17-gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Keywords: AML; Acute leukaemia; Gene expression; LSC 17 score; Stem cell transplantation.