Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis

Hyunwoo Lee; Kunio Nakamura; Sridar Narayanan; Robert A. Brown; Richard A. Nash; Linda M. Griffith; Kaitlyn C. Steinmiller; Steven M. Devine; George J. Hutton; Uday Popat; Michael K. Racke; George E. Georges; James D. Bowen; Douglas L. Arnold

doi:10.1016/j.msard.2021.103149

Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis

Hyunwoo Lee^*, Kunio Nakamura, Sridar Narayanan, Robert A. Brown, Richard A. Nash, Linda M. Griffith, Kaitlyn C. Steinmiller, Steven M. Devine, George J. Hutton, Uday Popat, Michael K. Racke, George E. Georges, James D. Bowen, Douglas L. Arnold

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Background: Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT. Methods: We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up. Results: On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not. Conclusions: BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level.

Original language	English (US)
Article number	103149
Journal	Multiple Sclerosis and Related Disorders
Volume	54
DOIs	https://doi.org/10.1016/j.msard.2021.103149
State	Published - Sep 2021

Funding

Funding: The HALT-MS study was sponsored by the Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT, NIAID), National Institutes of Health; and conducted by the Immune Tolerance Network (ITN) (UM1 AI 109565) and DAIT-NIAID funded statistical and clinical coordinating centers (UM2 AI 117870). The funding organization and sponsor, DAIT, NIAID, NIH, participated in design and conduct of the study; data collection and management; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. The opinions expressed are those of the authors and do not represent the position of the National Institute of Allergy and Infectious Diseases, the NIH, or the US Government. Funding: The HALT-MS study was sponsored by the Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT, NIAID), National Institutes of Health; and conducted by the Immune Tolerance Network (ITN) (UM1 AI 109565) and DAIT-NIAID funded statistical and clinical coordinating centers (UM2 AI 117870). The funding organization and sponsor, DAIT, NIAID, NIH, participated in design and conduct of the study; data collection and management; preparation, review, and approval of the manuscript; and the decision to submit the manuscript for publication. The opinions expressed are those of the authors and do not represent the position of the National Institute of Allergy and Infectious Diseases, the NIH, or the US Government. Hyunwoo Lee was supported by a Doctoral Training Award from Fonds de Recherché du Quebec. Hyunwoo Lee was supported by a Doctoral Training Award from Fonds de Recherché du Quebec.

Keywords

Atrophy
Chemotherapy
Hematopoietic stem cell transplantation
Magnetic resonance imaging
Multiple sclerosis
Relapsing-remitting

ASJC Scopus subject areas

Clinical Neurology
Neurology

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Lee, H., Nakamura, K., Narayanan, S., Brown, R. A., Nash, R. A., Griffith, L. M., Steinmiller, K. C., Devine, S. M., Hutton, G. J., Popat, U., Racke, M. K., Georges, G. E., Bowen, J. D., & Arnold, D. L. (2021). Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis. Multiple Sclerosis and Related Disorders, 54, Article 103149. https://doi.org/10.1016/j.msard.2021.103149

@article{1c7c8abc883f4ed2904d65c4162c2453,

title = "Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis",

abstract = "Background: Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT. Methods: We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up. Results: On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not. Conclusions: BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level.",

keywords = "Atrophy, Chemotherapy, Hematopoietic stem cell transplantation, Magnetic resonance imaging, Multiple sclerosis, Relapsing-remitting",

author = "Hyunwoo Lee and Kunio Nakamura and Sridar Narayanan and Brown, {Robert A.} and Nash, {Richard A.} and Griffith, {Linda M.} and Steinmiller, {Kaitlyn C.} and Devine, {Steven M.} and Hutton, {George J.} and Uday Popat and Racke, {Michael K.} and Georges, {George E.} and Bowen, {James D.} and Arnold, {Douglas L.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = sep,

doi = "10.1016/j.msard.2021.103149",

language = "English (US)",

volume = "54",

journal = "Multiple Sclerosis and Related Disorders",

issn = "2211-0348",

publisher = "Elsevier B.V.",

}

Lee, H, Nakamura, K, Narayanan, S, Brown, RA, Nash, RA, Griffith, LM, Steinmiller, KC, Devine, SM, Hutton, GJ, Popat, U, Racke, MK, Georges, GE, Bowen, JD & Arnold, DL 2021, 'Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis', Multiple Sclerosis and Related Disorders, vol. 54, 103149. https://doi.org/10.1016/j.msard.2021.103149

TY - JOUR

T1 - Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis

AU - Lee, Hyunwoo

AU - Nakamura, Kunio

AU - Narayanan, Sridar

AU - Brown, Robert A.

AU - Nash, Richard A.

AU - Griffith, Linda M.

AU - Steinmiller, Kaitlyn C.

AU - Devine, Steven M.

AU - Hutton, George J.

AU - Popat, Uday

AU - Racke, Michael K.

AU - Georges, George E.

AU - Bowen, James D.

AU - Arnold, Douglas L.

PY - 2021/9

Y1 - 2021/9

N2 - Background: Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT. Methods: We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up. Results: On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not. Conclusions: BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level.

AB - Background: Brain volume loss (BVL) is commonly observed after high-dose immunosuppression and autologous hematopoietic cell transplantation (HDIT/HCT) for treatment of multiple sclerosis (MS). To better understand the mechanisms of underlying BVL associated with this treatment, we characterized the time courses of whole-brain (WB), grey-matter (GM) and white-matter (WM) volume loss in relapsing-remitting MS (RRMS) patients who received BEAM-based HDIT/HCT. Methods: We used Jacobian integration to measure MRI-based WB, GM and WM volume changes up to 5 years after transplant in twenty-four RRMS participants who underwent BEAM-based HDIT/HCT. Using a two-piecewise mixed-effects model, we estimated the short-term (baseline to 1 year) and long-term (beyond 1 year) rates of BVL after HDIT/HCT. We also compared the rates based on the presence of gadolinium-enhancing lesions at baseline, and the maintenance of event-free survival during follow-up. Results: On average, accelerated short-term BVL of -1.37% (SE: 0.21), -0.86% (SE: 0.28) and -2.18% (SE: 0.26) occurred in WB, GM and WM, respectively. Baseline T1-weighted MRI WM lesion volume was a significant predictor in the WB (short-term) and the WM (short-term and long-term). The average rates of BVL after the initial acceleration were -0.22%/y (SE: 0.10), -0.13%/y (SE: 0.11) and -0.36%/y (SE: 0.11) in the WB, GM and WM, respectively. Participants with gadolinium-enhancing lesions at baseline had significantly higher short-term rates of GM (-1.56% vs. -0.27%, p = 0.01) and WB volume loss (-1.94% vs. -0.81%, p = 0.006) at 1 year follow-up as compared to those without gadolinium-enhancing lesions. WM volume loss was not significantly different (-2.59% vs. -1.66%, p = 0.16). Participants who maintained event-free survival had similar rates of BVL compared to those who did not. Conclusions: BVL may accelerate for months after HDIT/HCT. However, over the long-term, adequate HDIT/HCT may reduce BVL rates to those similar to normal aging at the WB level.

KW - Atrophy

KW - Chemotherapy

KW - Hematopoietic stem cell transplantation

KW - Magnetic resonance imaging

KW - Multiple sclerosis

KW - Relapsing-remitting

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UR - http://www.scopus.com/inward/citedby.url?scp=85110392254&partnerID=8YFLogxK

U2 - 10.1016/j.msard.2021.103149

DO - 10.1016/j.msard.2021.103149

M3 - Article

C2 - 34284316

AN - SCOPUS:85110392254

SN - 2211-0348

VL - 54

JO - Multiple Sclerosis and Related Disorders

JF - Multiple Sclerosis and Related Disorders

M1 - 103149

ER -

Brain volume change after high-dose immunosuppression and autologous hematopoietic cell transplantation for relapsing-remitting multiple sclerosis

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