Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Alice Y. Chan; Jennifer W. Leiding; Xuerong Liu; Brent R. Logan; Lauri M. Burroughs; Eric J. Allenspach; Suzanne Skoda-Smith; Gulbu Uzel; Luigi D. Notarangelo; Mary Slatter; Andrew R. Gennery; Angela R. Smith; Sung Yun Pai; Michael B. Jordan; Rebecca A. Marsh; Morton J. Cowan; Christopher C. Dvorak; John A. Craddock; Susan E. Prockop; Shanmuganathan Chandrakasan; Neena Kapoor; Rebecca H. Buckley; Suhag Parikh; Deepak Chellapandian; Benjamin R. Oshrine; Jeffrey J. Bednarski; Megan A. Cooper; Shalini Shenoy; Blachy J. Davila Saldana; Lisa R. Forbes; Caridad Martinez; Elie Haddad; David C. Shyr; Karin Chen; Kathleen E. Sullivan; Jennifer Heimall; Nicola Wright; Monica Bhatia; Geoffrey D.E. Cuvelier; Frederick D. Goldman; Isabelle Meyts; Holly K. Miller; Markus G. Seidel; Mark T. Vander Lugt; Rosa Bacchetta; Katja G. Weinacht; Jeffrey R. Andolina; Emi Caywood; Hey Chong; Maria Teresa de la Morena; Victor M. Aquino; Evan Shereck; Jolan E. Walter; Morna J. Dorsey; Christine M. Seroogy; Linda M. Griffith; Donald B. Kohn; Jennifer M. Puck; Michael A. Pulsipher; Troy R. Torgerson

doi:10.3389/fimmu.2020.00239

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

Alice Y. Chan, Jennifer W. Leiding, Xuerong Liu, Brent R. Logan, Lauri M. Burroughs, Eric J. Allenspach, Suzanne Skoda-Smith, Gulbu Uzel, Luigi D. Notarangelo, Mary Slatter, Andrew R. Gennery, Angela R. Smith, Sung Yun Pai, Michael B. Jordan, Rebecca A. Marsh, Morton J. Cowan, Christopher C. Dvorak, John A. Craddock, Susan E. Prockop, Shanmuganathan ChandrakasanNeena Kapoor, Rebecca H. Buckley, Suhag Parikh, Deepak Chellapandian, Benjamin R. Oshrine, Jeffrey J. Bednarski, Megan A. Cooper, Shalini Shenoy, Blachy J. Davila Saldana, Lisa R. Forbes, Caridad Martinez, Elie Haddad, David C. Shyr, Karin Chen, Kathleen E. Sullivan, Jennifer Heimall, Nicola Wright, Monica Bhatia, Geoffrey D.E. Cuvelier, Frederick D. Goldman, Isabelle Meyts, Holly K. Miller, Markus G. Seidel, Mark T. Vander Lugt, Rosa Bacchetta, Katja G. Weinacht, Jeffrey R. Andolina, Emi Caywood, Hey Chong, Maria Teresa de la Morena, Victor M. Aquino, Evan Shereck, Jolan E. Walter, Morna J. Dorsey, Christine M. Seroogy, Linda M. Griffith, Donald B. Kohn, Jennifer M. Puck, Michael A. Pulsipher, Troy R. Torgerson

Pediatric Blood & Marrow Transplant & Cellular Therapy

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

65 Scopus citations

Abstract

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

Original language	English (US)
Article number	239
Journal	Frontiers in immunology
Volume	11
DOIs	https://doi.org/10.3389/fimmu.2020.00239
State	Published - Feb 21 2020

Bibliographical note

Funding Information:
We would like to thank all research study coordinators in the PIDTC. We would also like to thank Tara Bani, Catherine Chang, and Elizabeth Dunn in the PIDTC for their administrative help in contacting sites and organizing meetings. Funding. This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD; Public Health Service grant/cooperative agreements U54-AI082973 (PIs: MJC; September 2019 forward JP and DK); U54-NS064808 and U01-TR001263 (PI: JK) and R13-AI094943 (PIs: MJC; March 2018 forward JP); and the Division of Intramural Research, NIAID, NIH. LN was supported by the Division of Intramural Research, NIAID, NIH. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. Collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) was supported by the U54 grants above along with support of the PBMTC Operations Center by the St. Baldrick's Foundation and grant/cooperative agreement U10HL069254 (PI: MP) from the National Heart, Lung and Blood Institute (NHLBI), and the NIH. Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) was supported by grant/cooperative agreement U24-CA76518 (PI: MH) from the National Cancer Institute (NCI), NHLBI, and NIAID, NIH; and grant/cooperative agreement U01HL069294 from the NHLBI and NCI; contract HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. The content and opinions expressed are solely the responsibility of the authors and do not represent the official policy or position of the NIAID, ORDR, NCATS, NIH, HRSA, or any other agency of the US Government.

Publisher Copyright:
© Copyright © 2020 Chan, Leiding, Liu, Logan, Burroughs, Allenspach, Skoda-Smith, Uzel, Notarangelo, Slatter, Gennery, Smith, Pai, Jordan, Marsh, Cowan, Dvorak, Craddock, Prockop, Chandrakasan, Kapoor, Buckley, Parikh, Chellapandian, Oshrine, Bednarski, Cooper, Shenoy, Davila Saldana, Forbes, Martinez, Haddad, Shyr, Chen, Sullivan, Heimall, Wright, Bhatia, Cuvelier, Goldman, Meyts, Miller, Seidel, Vander Lugt, Bacchetta, Weinacht, Andolina, Caywood, Chong, de la Morena, Aquino, Shereck, Walter, Dorsey, Seroogy, Griffith, Kohn, Puck, Pulsipher and Torgerson.

Keywords

autoimmunity
genetics
hematopoietic cell transplant
immune dysregulation
primary immune deficiencies

Publisher link

10.3389/fimmu.2020.00239

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Chan, A. Y., Leiding, J. W., Liu, X., Logan, B. R., Burroughs, L. M., Allenspach, E. J., Skoda-Smith, S., Uzel, G., Notarangelo, L. D., Slatter, M., Gennery, A. R., Smith, A. R., Pai, S. Y., Jordan, M. B., Marsh, R. A., Cowan, M. J., Dvorak, C. C., Craddock, J. A., Prockop, S. E., ... Torgerson, T. R. (2020). Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey. Frontiers in immunology, 11, Article 239. https://doi.org/10.3389/fimmu.2020.00239

Chan, AY, Leiding, JW, Liu, X, Logan, BR, Burroughs, LM, Allenspach, EJ, Skoda-Smith, S, Uzel, G, Notarangelo, LD, Slatter, M, Gennery, AR, Smith, AR, Pai, SY, Jordan, MB, Marsh, RA, Cowan, MJ, Dvorak, CC, Craddock, JA, Prockop, SE, Chandrakasan, S, Kapoor, N, Buckley, RH, Parikh, S, Chellapandian, D, Oshrine, BR, Bednarski, JJ, Cooper, MA, Shenoy, S, Davila Saldana, BJ, Forbes, LR, Martinez, C, Haddad, E, Shyr, DC, Chen, K, Sullivan, KE, Heimall, J, Wright, N, Bhatia, M, Cuvelier, GDE, Goldman, FD, Meyts, I, Miller, HK, Seidel, MG, Vander Lugt, MT, Bacchetta, R, Weinacht, KG, Andolina, JR, Caywood, E, Chong, H, de la Morena, MT, Aquino, VM, Shereck, E, Walter, JE, Dorsey, MJ, Seroogy, CM, Griffith, LM, Kohn, DB, Puck, JM, Pulsipher, MA & Torgerson, TR 2020, 'Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey', Frontiers in immunology, vol. 11, 239. https://doi.org/10.3389/fimmu.2020.00239

@article{3987c43146dc4635b232e8490a024745,

title = "Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey",

abstract = "Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.",

keywords = "autoimmunity, genetics, hematopoietic cell transplant, immune dysregulation, primary immune deficiencies",

author = "Chan, {Alice Y.} and Leiding, {Jennifer W.} and Xuerong Liu and Logan, {Brent R.} and Burroughs, {Lauri M.} and Allenspach, {Eric J.} and Suzanne Skoda-Smith and Gulbu Uzel and Notarangelo, {Luigi D.} and Mary Slatter and Gennery, {Andrew R.} and Smith, {Angela R.} and Pai, {Sung Yun} and Jordan, {Michael B.} and Marsh, {Rebecca A.} and Cowan, {Morton J.} and Dvorak, {Christopher C.} and Craddock, {John A.} and Prockop, {Susan E.} and Shanmuganathan Chandrakasan and Neena Kapoor and Buckley, {Rebecca H.} and Suhag Parikh and Deepak Chellapandian and Oshrine, {Benjamin R.} and Bednarski, {Jeffrey J.} and Cooper, {Megan A.} and Shalini Shenoy and {Davila Saldana}, {Blachy J.} and Forbes, {Lisa R.} and Caridad Martinez and Elie Haddad and Shyr, {David C.} and Karin Chen and Sullivan, {Kathleen E.} and Jennifer Heimall and Nicola Wright and Monica Bhatia and Cuvelier, {Geoffrey D.E.} and Goldman, {Frederick D.} and Isabelle Meyts and Miller, {Holly K.} and Seidel, {Markus G.} and {Vander Lugt}, {Mark T.} and Rosa Bacchetta and Weinacht, {Katja G.} and Andolina, {Jeffrey R.} and Emi Caywood and Hey Chong and {de la Morena}, {Maria Teresa} and Aquino, {Victor M.} and Evan Shereck and Walter, {Jolan E.} and Dorsey, {Morna J.} and Seroogy, {Christine M.} and Griffith, {Linda M.} and Kohn, {Donald B.} and Puck, {Jennifer M.} and Pulsipher, {Michael A.} and Torgerson, {Troy R.}",

note = "Funding Information: We would like to thank all research study coordinators in the PIDTC. We would also like to thank Tara Bani, Catherine Chang, and Elizabeth Dunn in the PIDTC for their administrative help in contacting sites and organizing meetings. Funding. This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD; Public Health Service grant/cooperative agreements U54-AI082973 (PIs: MJC; September 2019 forward JP and DK); U54-NS064808 and U01-TR001263 (PI: JK) and R13-AI094943 (PIs: MJC; March 2018 forward JP); and the Division of Intramural Research, NIAID, NIH. LN was supported by the Division of Intramural Research, NIAID, NIH. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. Collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) was supported by the U54 grants above along with support of the PBMTC Operations Center by the St. Baldrick's Foundation and grant/cooperative agreement U10HL069254 (PI: MP) from the National Heart, Lung and Blood Institute (NHLBI), and the NIH. Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) was supported by grant/cooperative agreement U24-CA76518 (PI: MH) from the National Cancer Institute (NCI), NHLBI, and NIAID, NIH; and grant/cooperative agreement U01HL069294 from the NHLBI and NCI; contract HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. The content and opinions expressed are solely the responsibility of the authors and do not represent the official policy or position of the NIAID, ORDR, NCATS, NIH, HRSA, or any other agency of the US Government. Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2020 Chan, Leiding, Liu, Logan, Burroughs, Allenspach, Skoda-Smith, Uzel, Notarangelo, Slatter, Gennery, Smith, Pai, Jordan, Marsh, Cowan, Dvorak, Craddock, Prockop, Chandrakasan, Kapoor, Buckley, Parikh, Chellapandian, Oshrine, Bednarski, Cooper, Shenoy, Davila Saldana, Forbes, Martinez, Haddad, Shyr, Chen, Sullivan, Heimall, Wright, Bhatia, Cuvelier, Goldman, Meyts, Miller, Seidel, Vander Lugt, Bacchetta, Weinacht, Andolina, Caywood, Chong, de la Morena, Aquino, Shereck, Walter, Dorsey, Seroogy, Griffith, Kohn, Puck, Pulsipher and Torgerson.",

year = "2020",

month = feb,

day = "21",

doi = "10.3389/fimmu.2020.00239",

language = "English (US)",

volume = "11",

journal = "Frontiers in immunology",

issn = "1664-3224",

publisher = "Frontiers Media SA",

}

TY - JOUR

T1 - Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD)

T2 - A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

AU - Chan, Alice Y.

AU - Leiding, Jennifer W.

AU - Liu, Xuerong

AU - Logan, Brent R.

AU - Burroughs, Lauri M.

AU - Allenspach, Eric J.

AU - Skoda-Smith, Suzanne

AU - Uzel, Gulbu

AU - Notarangelo, Luigi D.

AU - Slatter, Mary

AU - Gennery, Andrew R.

AU - Smith, Angela R.

AU - Pai, Sung Yun

AU - Jordan, Michael B.

AU - Marsh, Rebecca A.

AU - Cowan, Morton J.

AU - Dvorak, Christopher C.

AU - Craddock, John A.

AU - Prockop, Susan E.

AU - Chandrakasan, Shanmuganathan

AU - Kapoor, Neena

AU - Buckley, Rebecca H.

AU - Parikh, Suhag

AU - Chellapandian, Deepak

AU - Oshrine, Benjamin R.

AU - Bednarski, Jeffrey J.

AU - Cooper, Megan A.

AU - Shenoy, Shalini

AU - Davila Saldana, Blachy J.

AU - Forbes, Lisa R.

AU - Martinez, Caridad

AU - Haddad, Elie

AU - Shyr, David C.

AU - Chen, Karin

AU - Sullivan, Kathleen E.

AU - Heimall, Jennifer

AU - Wright, Nicola

AU - Bhatia, Monica

AU - Cuvelier, Geoffrey D.E.

AU - Goldman, Frederick D.

AU - Meyts, Isabelle

AU - Miller, Holly K.

AU - Seidel, Markus G.

AU - Vander Lugt, Mark T.

AU - Bacchetta, Rosa

AU - Weinacht, Katja G.

AU - Andolina, Jeffrey R.

AU - Caywood, Emi

AU - Chong, Hey

AU - de la Morena, Maria Teresa

AU - Aquino, Victor M.

AU - Shereck, Evan

AU - Walter, Jolan E.

AU - Dorsey, Morna J.

AU - Seroogy, Christine M.

AU - Griffith, Linda M.

AU - Kohn, Donald B.

AU - Puck, Jennifer M.

AU - Pulsipher, Michael A.

AU - Torgerson, Troy R.

N1 - Funding Information: We would like to thank all research study coordinators in the PIDTC. We would also like to thank Tara Bani, Catherine Chang, and Elizabeth Dunn in the PIDTC for their administrative help in contacting sites and organizing meetings. Funding. This work was supported by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases (NIAID); and the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Bethesda, MD; Public Health Service grant/cooperative agreements U54-AI082973 (PIs: MJC; September 2019 forward JP and DK); U54-NS064808 and U01-TR001263 (PI: JK) and R13-AI094943 (PIs: MJC; March 2018 forward JP); and the Division of Intramural Research, NIAID, NIH. LN was supported by the Division of Intramural Research, NIAID, NIH. The PIDTC is a part of the Rare Diseases Clinical Research Network (RDCRN) of ORDR, NCATS. Collaborative work of the PIDTC with the Pediatric Blood and Marrow Transplant Consortium (PBMTC) was supported by the U54 grants above along with support of the PBMTC Operations Center by the St. Baldrick's Foundation and grant/cooperative agreement U10HL069254 (PI: MP) from the National Heart, Lung and Blood Institute (NHLBI), and the NIH. Collaborative work of the PIDTC with the Center for International Blood and Marrow Transplant Research (CIBMTR) was supported by grant/cooperative agreement U24-CA76518 (PI: MH) from the National Cancer Institute (NCI), NHLBI, and NIAID, NIH; and grant/cooperative agreement U01HL069294 from the NHLBI and NCI; contract HHSH250201200016C and HHSH234200637015C with the Health Resources and Services Administration (HRSA/DHHS); and grants N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research. The content and opinions expressed are solely the responsibility of the authors and do not represent the official policy or position of the NIAID, ORDR, NCATS, NIH, HRSA, or any other agency of the US Government. Publisher Copyright: © Copyright © 2020 Chan, Leiding, Liu, Logan, Burroughs, Allenspach, Skoda-Smith, Uzel, Notarangelo, Slatter, Gennery, Smith, Pai, Jordan, Marsh, Cowan, Dvorak, Craddock, Prockop, Chandrakasan, Kapoor, Buckley, Parikh, Chellapandian, Oshrine, Bednarski, Cooper, Shenoy, Davila Saldana, Forbes, Martinez, Haddad, Shyr, Chen, Sullivan, Heimall, Wright, Bhatia, Cuvelier, Goldman, Meyts, Miller, Seidel, Vander Lugt, Bacchetta, Weinacht, Andolina, Caywood, Chong, de la Morena, Aquino, Shereck, Walter, Dorsey, Seroogy, Griffith, Kohn, Puck, Pulsipher and Torgerson.

PY - 2020/2/21

Y1 - 2020/2/21

N2 - Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

AB - Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

KW - autoimmunity

KW - genetics

KW - hematopoietic cell transplant

KW - immune dysregulation

KW - primary immune deficiencies

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UR - http://www.scopus.com/inward/citedby.url?scp=85081208356&partnerID=8YFLogxK

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DO - 10.3389/fimmu.2020.00239

M3 - Article

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AN - SCOPUS:85081208356

SN - 1664-3224

VL - 11

JO - Frontiers in immunology

JF - Frontiers in immunology

M1 - 239

ER -

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey

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