Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy

Robert Chiesa; Jaap Jan Boelens; Christine N. Duncan; Jorn Sven Kuhl; Caroline Sevin; Neena Kapoor; Vinod K. Prasad; Caroline A. Lindemans; Simon A. Jones; Hernan M. Amartino; Mattia Algeri; Nancy Bunin; Cristina Diaz-De-Heredia; Daniel J. Loes; Esther Shamir; Alison Timm; Elizabeth McNeil; Andrew C. Dietz; Paul J. Orchard

doi:10.1182/bloodadvances.2021005294

Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy

Robert Chiesa, Jaap Jan Boelens, Christine N. Duncan, Jorn Sven Kuhl, Caroline Sevin, Neena Kapoor, Vinod K. Prasad, Caroline A. Lindemans, Simon A. Jones, Hernan M. Amartino, Mattia Algeri, Nancy Bunin, Cristina Diaz-De-Heredia, Daniel J. Loes, Esther Shamir, Alison Timm, Elizabeth McNeil, Andrew C. Dietz, Paul J. Orchard

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6 Scopus citations

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy can stabilize neurologic function and improve survival but has associated risks including transplant-related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n = 16) with Loes score >9 or neurological function score (NFS) >1 and 2 early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n = 24] and ED2 [Loes >4-9 and NFS ≤1; n = 13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n = 13), 0.5 and 0 in ED2 (n = 6), and 2.5 and 3.0 (n = 4) in AD cohort. TRM was lower in the ED (7%) compared with the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904.

Original language	English (US)
Pages (from-to)	1512-1524
Number of pages	13
Journal	Blood Advances
Volume	6
Issue number	5
DOIs	https://doi.org/10.1182/bloodadvances.2021005294
State	Published - Mar 8 2022

Bibliographical note

Funding Information:
This study was supported by bluebird bio, Inc. Medical writing and editing support for authors was provided by Iva Kronja of bluebird bio, Inc., and Patrice Ferriola of KZE PharmAssociates, who was funded by bluebird bio, Inc.

Publisher Copyright:
© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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Journal Article
Observational Study
Research Support, Non-U.S. Gov't

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Chiesa, R., Boelens, J. J., Duncan, C. N., Kuhl, J. S., Sevin, C., Kapoor, N., Prasad, V. K., Lindemans, C. A., Jones, S. A., Amartino, H. M., Algeri, M., Bunin, N., Diaz-De-Heredia, C., Loes, D. J., Shamir, E., Timm, A., McNeil, E., Dietz, A. C., & Orchard, P. J. (2022). Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy. Blood Advances, 6(5), 1512-1524. https://doi.org/10.1182/bloodadvances.2021005294

Chiesa, R, Boelens, JJ, Duncan, CN, Kuhl, JS, Sevin, C, Kapoor, N, Prasad, VK, Lindemans, CA, Jones, SA, Amartino, HM, Algeri, M, Bunin, N, Diaz-De-Heredia, C, Loes, DJ, Shamir, E, Timm, A, McNeil, E, Dietz, AC & Orchard, PJ 2022, 'Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy', Blood Advances, vol. 6, no. 5, pp. 1512-1524. https://doi.org/10.1182/bloodadvances.2021005294

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title = "Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy",

abstract = "Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy can stabilize neurologic function and improve survival but has associated risks including transplant-related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n = 16) with Loes score >9 or neurological function score (NFS) >1 and 2 early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n = 24] and ED2 [Loes >4-9 and NFS ≤1; n = 13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n = 13), 0.5 and 0 in ED2 (n = 6), and 2.5 and 3.0 (n = 4) in AD cohort. TRM was lower in the ED (7%) compared with the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904.",

author = "Robert Chiesa and Boelens, {Jaap Jan} and Duncan, {Christine N.} and Kuhl, {Jorn Sven} and Caroline Sevin and Neena Kapoor and Prasad, {Vinod K.} and Lindemans, {Caroline A.} and Jones, {Simon A.} and Amartino, {Hernan M.} and Mattia Algeri and Nancy Bunin and Cristina Diaz-De-Heredia and Loes, {Daniel J.} and Esther Shamir and Alison Timm and Elizabeth McNeil and Dietz, {Andrew C.} and Orchard, {Paul J.}",

note = "Funding Information: This study was supported by bluebird bio, Inc. Medical writing and editing support for authors was provided by Iva Kronja of bluebird bio, Inc., and Patrice Ferriola of KZE PharmAssociates, who was funded by bluebird bio, Inc. Publisher Copyright: {\textcopyright} 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.",

year = "2022",

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doi = "10.1182/bloodadvances.2021005294",

language = "English (US)",

volume = "6",

pages = "1512--1524",

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publisher = "American Society of Hematology",

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T1 - Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy

AU - Chiesa, Robert

AU - Boelens, Jaap Jan

AU - Duncan, Christine N.

AU - Kuhl, Jorn Sven

AU - Sevin, Caroline

AU - Kapoor, Neena

AU - Prasad, Vinod K.

AU - Lindemans, Caroline A.

AU - Jones, Simon A.

AU - Amartino, Hernan M.

AU - Algeri, Mattia

AU - Bunin, Nancy

AU - Diaz-De-Heredia, Cristina

AU - Loes, Daniel J.

AU - Shamir, Esther

AU - Timm, Alison

AU - McNeil, Elizabeth

AU - Dietz, Andrew C.

AU - Orchard, Paul J.

N1 - Funding Information: This study was supported by bluebird bio, Inc. Medical writing and editing support for authors was provided by Iva Kronja of bluebird bio, Inc., and Patrice Ferriola of KZE PharmAssociates, who was funded by bluebird bio, Inc. Publisher Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

PY - 2022/3/8

Y1 - 2022/3/8

N2 - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy can stabilize neurologic function and improve survival but has associated risks including transplant-related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n = 16) with Loes score >9 or neurological function score (NFS) >1 and 2 early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n = 24] and ED2 [Loes >4-9 and NFS ≤1; n = 13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n = 13), 0.5 and 0 in ED2 (n = 6), and 2.5 and 3.0 (n = 4) in AD cohort. TRM was lower in the ED (7%) compared with the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904.

AB - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy can stabilize neurologic function and improve survival but has associated risks including transplant-related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n = 16) with Loes score >9 or neurological function score (NFS) >1 and 2 early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n = 24] and ED2 [Loes >4-9 and NFS ≤1; n = 13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n = 13), 0.5 and 0 in ED2 (n = 6), and 2.5 and 3.0 (n = 4) in AD cohort. TRM was lower in the ED (7%) compared with the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904.

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ER -

Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy

Abstract

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