TY - JOUR
T1 - Clinical significance of clonal hematopoiesis in the setting of autologous stem cell transplantation for lymphoma
AU - Lackraj, Tracy
AU - Ben Barouch, Sharon
AU - Medeiros, Jessie J.F.
AU - Pedersen, Stephanie
AU - Danesh, Arnavaz
AU - Bakhtiari, Mehran
AU - Hong, Michael
AU - Tong, Kit
AU - Joynt, Jesse
AU - Arruda, Andrea
AU - Minden, Mark D.
AU - Kuruvilla, John
AU - Bhella, Sita
AU - Kukreti, Vishal
AU - Crump, Michael
AU - Prica, Anca
AU - Chen, Christine
AU - Deng, Yangqing
AU - Xu, Wei
AU - Pugh, Trevor J.
AU - Keating, Armand
AU - Dick, John E.
AU - Abelson, Sagi
AU - Kridel, Robert
N1 - Funding Information:
Princess Margaret Cancer Foundation; Canadian Cancer Society Emerging Scholar, Grant/Award Number: 707152; Leukemia & Lymphoma Society Translational Research Program, Grant/Award Number: 6599‐20; Leukemia & Lymphoma Society of Canada, Grant/Award Number: 621322; the Ontario Research Fund, Grant/Award Number: 271LYM; Terry Fox New Frontiers Program, Grant/Award Number: 1047; Canadian Cancer Society, Grant/Award Number: 703212; International Development Research Center Ottawa Canada, Grant/Award Numbers: 109153, 108401; Canadian Institutes for Health Research, Grant/Award Numbers: 154293, 89932, 130412; Charles Best Canada Graduate Scholarships, Grant/Award Number: FBD‐170928 Funding information
Funding Information:
This study was supported by the Princess Margaret Cancer Foundation. Sharon Ben Barouch was supported by a Tannock Fellowship Award from the Princess Margaret Cancer Center. Jessie J. F. Medeiros is supported by the Canadian Institutes of Health Research Doctoral Award: Frederick Banting and Charles Best Canada Graduate Scholarships (FBD‐170928). Jesse Joynt was supported by the Dr. Edward Ketchum Graduate Student Scholarship. John E. Dick is supported by funds from the: Princess Margaret Cancer Center Foundation, Ontario Institute for Cancer Research through funding provided by the Government of Ontario, Canadian Institutes for Health Research grants 130412, 89932, and 154293, International Development Research Center Ottawa Canada grants 108401 and 109153, Canadian Cancer Society grant 703212, Terry Fox New Frontiers Program Project Grant 1047, University of Toronto's Medicine by Design initiative with funding from the Canada First Research Excellence Fund, and a Canada Research Chair. SA is supported by the Investigator Award received from the Ontario Institute for Cancer Research with funds from the province of Ontario. Robert Kridel is supported by the Princess Margaret Cancer Foundation, Genome Canada and the Ontario Research Fund project 271LYM, the Leukemia & Lymphoma Society of Canada grant 621322, the Leukemia & Lymphoma Society Translational Research Program 6599‐20, the Canadian Cancer Society Emerging Scholar Award grant 707152 and a Princess Margaret Division of Medical Oncology and Hematology Junior Faculty Grant.
Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/12/1
Y1 - 2022/12/1
N2 - Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p =.043) and from the time of ASCT (51.8% vs. 59.3%, p =.018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p =.445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13–2.67, p =.011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.
AB - Autologous stem cell transplantation (ASCT) remains a key therapeutic strategy for treating patients with relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Clonal hematopoiesis (CH) has been proposed as a major contributor not only to the development of therapy-related myeloid neoplasms but also to inferior overall survival (OS) in patients who had undergone ASCT. Herein, we aimed to investigate the prognostic implications of CH after ASCT in a cohort of 420 lymphoma patients using ultra-deep, highly sensitive error-correction sequencing. CH was identified in the stem cell product samples of 181 patients (43.1%) and was most common in those with T-cell lymphoma (72.2%). The presence of CH was associated with a longer time to neutrophil and platelet recovery. Moreover, patients with evidence of CH had inferior 5-year OS from the time of first relapse (39.4% vs. 45.8%, p =.043) and from the time of ASCT (51.8% vs. 59.3%, p =.018). The adverse prognostic impact of CH was not due to therapy-related myeloid neoplasms, the incidence of which was low in our cohort (10-year cumulative incidence of 3.3% vs. 3.0% in those with and without CH, p =.445). In terms of specific-gene mutations, adverse OS was mostly associated with PPM1D mutations (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.13–2.67, p =.011). In summary, we found that CH is associated with an increased risk of non-lymphoma-related death after ASCT, which suggests that lymphoma survivors with CH may need intensified surveillance strategies to prevent and treat late complications.
UR - http://www.scopus.com/inward/record.url?scp=85139033565&partnerID=8YFLogxK
U2 - 10.1002/ajh.26726
DO - 10.1002/ajh.26726
M3 - Article
C2 - 36087071
AN - SCOPUS:85139033565
SN - 0361-8609
VL - 97
SP - 1538
EP - 1547
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 12
ER -