High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease

Asaf D. Yanir, Imelda C. Hanson, William T. Shearer, Lenora M. Noroski, Lisa R. Forbes, Feliz O. Seeborg, Sarah Nicholas, Ivan Chinn, Jordan S. Orange, Nicholas L. Rider, Kathryn S. Leung, Swati Naik, George Carrum, Ghadir Sasa, Meenakshi Hegde, Bilal A. Omer, Nabil Ahmed, Carl E. Allen, Yassine Khaled, Meng Fen WuHao Liu, Stephen M. Gottschalk, Helen E. Heslop, Malcolm K. Brenner, Robert A. Krance, Caridad A. Martinez

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.

Original languageEnglish (US)
Pages (from-to)1643-1650
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

Fingerprint

Chronic Granulomatous Disease
Hematopoietic Stem Cell Transplantation
Autoimmune Diseases
Incidence
Tissue Donors
Unrelated Donors
Graft vs Host Disease
Chimerism
Respiratory Burst
Thyroid Diseases
Autoimmunity
Brain Injuries

Keywords

  • Autoimmune disease
  • Chimerism
  • Chronic granulomatous disease
  • Hematopoietic stem cell transplantation
  • Immune reconstitution
  • Myeloablative conditioning
  • Unrelated donors

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Yanir, A. D., Hanson, I. C., Shearer, W. T., Noroski, L. M., Forbes, L. R., Seeborg, F. O., ... Martinez, C. A. (2018). High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. Biology of Blood and Marrow Transplantation, 24(8), 1643-1650. https://doi.org/10.1016/j.bbmt.2018.03.029

High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. / Yanir, Asaf D.; Hanson, Imelda C.; Shearer, William T.; Noroski, Lenora M.; Forbes, Lisa R.; Seeborg, Feliz O.; Nicholas, Sarah; Chinn, Ivan; Orange, Jordan S.; Rider, Nicholas L.; Leung, Kathryn S.; Naik, Swati; Carrum, George; Sasa, Ghadir; Hegde, Meenakshi; Omer, Bilal A.; Ahmed, Nabil; Allen, Carl E.; Khaled, Yassine; Wu, Meng Fen; Liu, Hao; Gottschalk, Stephen M.; Heslop, Helen E.; Brenner, Malcolm K.; Krance, Robert A.; Martinez, Caridad A.

In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 8, 01.08.2018, p. 1643-1650.

Research output: Contribution to journalArticle

Yanir, AD, Hanson, IC, Shearer, WT, Noroski, LM, Forbes, LR, Seeborg, FO, Nicholas, S, Chinn, I, Orange, JS, Rider, NL, Leung, KS, Naik, S, Carrum, G, Sasa, G, Hegde, M, Omer, BA, Ahmed, N, Allen, CE, Khaled, Y, Wu, MF, Liu, H, Gottschalk, SM, Heslop, HE, Brenner, MK, Krance, RA & Martinez, CA 2018, 'High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease', Biology of Blood and Marrow Transplantation, vol. 24, no. 8, pp. 1643-1650. https://doi.org/10.1016/j.bbmt.2018.03.029
Yanir, Asaf D. ; Hanson, Imelda C. ; Shearer, William T. ; Noroski, Lenora M. ; Forbes, Lisa R. ; Seeborg, Feliz O. ; Nicholas, Sarah ; Chinn, Ivan ; Orange, Jordan S. ; Rider, Nicholas L. ; Leung, Kathryn S. ; Naik, Swati ; Carrum, George ; Sasa, Ghadir ; Hegde, Meenakshi ; Omer, Bilal A. ; Ahmed, Nabil ; Allen, Carl E. ; Khaled, Yassine ; Wu, Meng Fen ; Liu, Hao ; Gottschalk, Stephen M. ; Heslop, Helen E. ; Brenner, Malcolm K. ; Krance, Robert A. ; Martinez, Caridad A. / High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease. In: Biology of Blood and Marrow Transplantation. 2018 ; Vol. 24, No. 8. pp. 1643-1650.
@article{29fa48a6e03f4d62afa7f09b0720ee56,
title = "High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease",
abstract = "There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.",
keywords = "Autoimmune disease, Chimerism, Chronic granulomatous disease, Hematopoietic stem cell transplantation, Immune reconstitution, Myeloablative conditioning, Unrelated donors",
author = "Yanir, {Asaf D.} and Hanson, {Imelda C.} and Shearer, {William T.} and Noroski, {Lenora M.} and Forbes, {Lisa R.} and Seeborg, {Feliz O.} and Sarah Nicholas and Ivan Chinn and Orange, {Jordan S.} and Rider, {Nicholas L.} and Leung, {Kathryn S.} and Swati Naik and George Carrum and Ghadir Sasa and Meenakshi Hegde and Omer, {Bilal A.} and Nabil Ahmed and Allen, {Carl E.} and Yassine Khaled and Wu, {Meng Fen} and Hao Liu and Gottschalk, {Stephen M.} and Heslop, {Helen E.} and Brenner, {Malcolm K.} and Krance, {Robert A.} and Martinez, {Caridad A.}",
year = "2018",
month = "8",
day = "1",
doi = "10.1016/j.bbmt.2018.03.029",
language = "English (US)",
volume = "24",
pages = "1643--1650",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - High Incidence of Autoimmune Disease after Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease

AU - Yanir, Asaf D.

AU - Hanson, Imelda C.

AU - Shearer, William T.

AU - Noroski, Lenora M.

AU - Forbes, Lisa R.

AU - Seeborg, Feliz O.

AU - Nicholas, Sarah

AU - Chinn, Ivan

AU - Orange, Jordan S.

AU - Rider, Nicholas L.

AU - Leung, Kathryn S.

AU - Naik, Swati

AU - Carrum, George

AU - Sasa, Ghadir

AU - Hegde, Meenakshi

AU - Omer, Bilal A.

AU - Ahmed, Nabil

AU - Allen, Carl E.

AU - Khaled, Yassine

AU - Wu, Meng Fen

AU - Liu, Hao

AU - Gottschalk, Stephen M.

AU - Heslop, Helen E.

AU - Brenner, Malcolm K.

AU - Krance, Robert A.

AU - Martinez, Caridad A.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.

AB - There is a lack of consensus regarding the role and method of hematopoietic stem cell transplantation (HSCT) on patients with chronic granulomatous disease (CGD). Long-term follow-up after HSCT in these patient population is essential to know its potential complications and decide who will benefit the most from HSCT. We report the outcome of HSCT and long-term follow-up in 24 patients with CGD, transplanted in our center from either related (n = 6) or unrelated (n = 18) donors, over a 12-year period (2003 to 2015), using high-dose alemtuzumab in the preparative regimen. We evaluated the incidence and timing of adverse events and potential risk factors. We described in detailed the novel finding of increased autoimmunity after HSCT in patients with CGD. At a median follow-up of 1460 days, 22 patients were full donor chimeras, and 2 patients had stable mixed chimerism. All assessable patients showed normalization of their neutrophil oxidative burst test. None of the patients developed grades II to IV acute graft-versus-host disease, and no patient had chronic graft-versus-host disease. Twelve of 24 patients developed 17 autoimmune diseases (ADs). Severe ADs (cytopenia and neuropathy) occurred exclusively in the unrelated donor setting and mainly in the first year after HSCT, whereas thyroid AD occurred in the related donor setting as well and more than 3 years after HSCT. Two patients died due to infectious complications after developing autoimmune cytopenias. One additional patient suffered severe brain injury. The remaining 21 patients have long-term Lansky scores ≥ 80. The outcome of HSCT from unrelated donors is comparable with related donors but might carry an increased risk of developing severe AD. A lower dose of alemtuzumab may reduce this risk and should be tested in further studies.

KW - Autoimmune disease

KW - Chimerism

KW - Chronic granulomatous disease

KW - Hematopoietic stem cell transplantation

KW - Immune reconstitution

KW - Myeloablative conditioning

KW - Unrelated donors

UR - http://www.scopus.com/inward/record.url?scp=85047370228&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047370228&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2018.03.029

DO - 10.1016/j.bbmt.2018.03.029

M3 - Article

C2 - 29630926

AN - SCOPUS:85047370228

VL - 24

SP - 1643

EP - 1650

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

SN - 1083-8791

IS - 8

ER -