Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study

Hesham Eissa; Monica S. Thakar; Ami J. Shah; Brent R. Logan; Linda M. Griffith; Huaying Dong; Roberta E. Parrott; Richard J. O'Reilly; Jasmeen Dara; Neena Kapoor; Lisa Forbes Satter; Sharat Chandra; Malika Kapadia; Shanmuganathan Chandrakasan; Alan Knutsen; Soma C. Jyonouchi; Lyndsay Molinari; Ahmad Rayes; Christen L. Ebens; Pierre Teira; Blachy J. Dávila Saldaña; Lauri M. Burroughs; Sonali Chaudhury; Deepak Chellapandian; Alfred P. Gillio; Fredrick Goldman; Harry L. Malech; Kenneth DeSantes; Geoff D.E. Cuvelier; Jacob Rozmus; Ralph Quinones; Lolie C. Yu; Larisa Broglie; Victor Aquino; Evan Shereck; Theodore B. Moore; Mark T. Vander Lugt; Talal I. Mousallem; Joeseph H. Oved; Morna Dorsey; Hisham Abdel-Azim; Caridad Martinez; Jacob H. Bleesing; Susan Prockop; Donald B. Kohn; Jeffrey J. Bednarski; Jennifer Leiding; Rebecca A. Marsh; Troy Torgerson; Luigi D. Notarangelo; Sung Yun Pai; Michael A. Pulsipher; Jennifer M. Puck; Christopher C. Dvorak; Elie Haddad; Rebecca H. Buckley; Morton J. Cowan; Jennifer Heimall

doi:10.1016/j.jaci.2023.09.027

Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study

Hesham Eissa^*, Monica S. Thakar, Ami J. Shah, Brent R. Logan, Linda M. Griffith, Huaying Dong, Roberta E. Parrott, Richard J. O'Reilly, Jasmeen Dara, Neena Kapoor, Lisa Forbes Satter, Sharat Chandra, Malika Kapadia, Shanmuganathan Chandrakasan, Alan Knutsen, Soma C. Jyonouchi, Lyndsay Molinari, Ahmad Rayes, Christen L. Ebens, Pierre TeiraBlachy J. Dávila Saldaña, Lauri M. Burroughs, Sonali Chaudhury, Deepak Chellapandian, Alfred P. Gillio, Fredrick Goldman, Harry L. Malech, Kenneth DeSantes, Geoff D.E. Cuvelier, Jacob Rozmus, Ralph Quinones, Lolie C. Yu, Larisa Broglie, Victor Aquino, Evan Shereck, Theodore B. Moore, Mark T. Vander Lugt, Talal I. Mousallem, Joeseph H. Oved, Morna Dorsey, Hisham Abdel-Azim, Caridad Martinez, Jacob H. Bleesing, Susan Prockop, Donald B. Kohn, Jeffrey J. Bednarski, Jennifer Leiding, Rebecca A. Marsh, Troy Torgerson, Luigi D. Notarangelo, Sung Yun Pai, Michael A. Pulsipher, Jennifer M. Puck, Christopher C. Dvorak, Elie Haddad, Rebecca H. Buckley, Morton J. Cowan, Jennifer Heimall

^*Corresponding author for this work

Pediatrics

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

7 Scopus citations

Abstract

Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT). Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID). Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001). Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.

Original language	English (US)
Pages (from-to)	287-296
Number of pages	10
Journal	Journal of Allergy and Clinical Immunology
Volume	153
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2023.09.027
State	Published - Jan 2024

Funding

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), grant U54AI082973 (MPI: J. M. Puck, C. C. Dvorak, E. Haddad) and grants U54NS064808 and U01TR001263 (PI: J. Krischer). The Primary Immune Deficiency Treatment Consortium (PIDTC) is a part of the Rare Diseases Clinical Research Network of ORDR, NCATS. The collaborative work of the PIDTC with the Pediatric Transplantation and Cellular Therapy Consortium is supported by the U54 grants listed, along with support of the Pediatric Blood and Marrow Transplant Consortium Operations Center by the St Baldrick’s Foundation and U10HL069254 (PI: M. M. Horowitz). C.L.E. is supported by funding from NIH’s National Center for Advancing Translational Sciences , grants KL2TR002492 and UL1TR002494. L.D.N. is supported by the Division of Intramural Research, NIAID, NIH grant 1 ZIA AI001222-02 (PI: L. D. Notarangelo). S.-Y.P. is supported by funding from the Intramural Research Program, NIH, National Cancer Institute, Center for Cancer 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, Health Resources and Services Administration , or any other agency of the US government. M.A.P. is supported by 1U01AI126612-01A1, P30CA040214, and 2UG1HL069254. 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), grant U54AI082973 (MPI: J. M. Puck, C. C. Dvorak, E. Haddad) and grants U54NS064808 and U01TR001263 (PI: J. Krischer). The Primary Immune Deficiency Treatment Consortium (PIDTC) is a part of the Rare Diseases Clinical Research Network of ORDR, NCATS. The collaborative work of the PIDTC with the Pediatric Transplantation and Cellular Therapy Consortium is supported by the U54 grants listed, along with support of the Pediatric Blood and Marrow Transplant Consortium Operations Center by the St Baldrick's Foundation and U10HL069254 (PI: M. M. Horowitz). C.L.E. is supported by funding from NIH's National Center for Advancing Translational Sciences, grants KL2TR002492 and UL1TR002494. L.D.N. is supported by the Division of Intramural Research, NIAID, NIH grant 1 ZIA AI001222-02 (PI: L. D. Notarangelo). S.-Y.P. is supported by funding from the Intramural Research Program, NIH, National Cancer Institute, Center for Cancer 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, Health Resources and Services Administration, or any other agency of the US government. M.A.P. is supported by 1U01AI126612-01A1, P30CA040214, and 2UG1HL069254.

Keywords

HCT
SCID
bone marrow transplantation
late effects
survivorship

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/j.jaci.2023.09.027

Cite this

Eissa, H., Thakar, M. S., Shah, A. J., Logan, B. R., Griffith, L. M., Dong, H., Parrott, R. E., O'Reilly, R. J., Dara, J., Kapoor, N., Forbes Satter, L., Chandra, S., Kapadia, M., Chandrakasan, S., Knutsen, A., Jyonouchi, S. C., Molinari, L., Rayes, A., Ebens, C. L., ... Heimall, J. (2024). Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study. Journal of Allergy and Clinical Immunology, 153(1), 287-296. https://doi.org/10.1016/j.jaci.2023.09.027

@article{c85604d6ba0344af994cc9b4a79ca8e2,

title = "Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study",

abstract = "Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT). Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID). Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001). Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.",

keywords = "HCT, SCID, bone marrow transplantation, late effects, survivorship",

author = "Hesham Eissa and Thakar, {Monica S.} and Shah, {Ami J.} and Logan, {Brent R.} and Griffith, {Linda M.} and Huaying Dong and Parrott, {Roberta E.} and O'Reilly, {Richard J.} and Jasmeen Dara and Neena Kapoor and {Forbes Satter}, Lisa and Sharat Chandra and Malika Kapadia and Shanmuganathan Chandrakasan and Alan Knutsen and Jyonouchi, {Soma C.} and Lyndsay Molinari and Ahmad Rayes and Ebens, {Christen L.} and Pierre Teira and {D{\'a}vila Salda{\~n}a}, {Blachy J.} and Burroughs, {Lauri M.} and Sonali Chaudhury and Deepak Chellapandian and Gillio, {Alfred P.} and Fredrick Goldman and Malech, {Harry L.} and Kenneth DeSantes and Cuvelier, {Geoff D.E.} and Jacob Rozmus and Ralph Quinones and Yu, {Lolie C.} and Larisa Broglie and Victor Aquino and Evan Shereck and Moore, {Theodore B.} and {Vander Lugt}, {Mark T.} and Mousallem, {Talal I.} and Oved, {Joeseph H.} and Morna Dorsey and Hisham Abdel-Azim and Caridad Martinez and Bleesing, {Jacob H.} and Susan Prockop and Kohn, {Donald B.} and Bednarski, {Jeffrey J.} and Jennifer Leiding and Marsh, {Rebecca A.} and Troy Torgerson and Notarangelo, {Luigi D.} and Pai, {Sung Yun} and Pulsipher, {Michael A.} and Puck, {Jennifer M.} and Dvorak, {Christopher C.} and Elie Haddad and Buckley, {Rebecca H.} and Cowan, {Morton J.} and Jennifer Heimall",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2024",

month = jan,

doi = "10.1016/j.jaci.2023.09.027",

language = "English (US)",

volume = "153",

pages = "287--296",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

number = "1",

}

Eissa, H, Thakar, MS, Shah, AJ, Logan, BR, Griffith, LM, Dong, H, Parrott, RE, O'Reilly, RJ, Dara, J, Kapoor, N, Forbes Satter, L, Chandra, S, Kapadia, M, Chandrakasan, S, Knutsen, A, Jyonouchi, SC, Molinari, L, Rayes, A, Ebens, CL, Teira, P, Dávila Saldaña, BJ, Burroughs, LM, Chaudhury, S, Chellapandian, D, Gillio, AP, Goldman, F, Malech, HL, DeSantes, K, Cuvelier, GDE, Rozmus, J, Quinones, R, Yu, LC, Broglie, L, Aquino, V, Shereck, E, Moore, TB, Vander Lugt, MT, Mousallem, TI, Oved, JH, Dorsey, M, Abdel-Azim, H, Martinez, C, Bleesing, JH, Prockop, S, Kohn, DB, Bednarski, JJ, Leiding, J, Marsh, RA, Torgerson, T, Notarangelo, LD, Pai, SY, Pulsipher, MA, Puck, JM, Dvorak, CC, Haddad, E, Buckley, RH, Cowan, MJ & Heimall, J 2024, 'Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study', Journal of Allergy and Clinical Immunology, vol. 153, no. 1, pp. 287-296. https://doi.org/10.1016/j.jaci.2023.09.027

TY - JOUR

T1 - Posttransplantation late complications increase over time for patients with SCID

T2 - A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study

AU - Eissa, Hesham

AU - Thakar, Monica S.

AU - Shah, Ami J.

AU - Logan, Brent R.

AU - Griffith, Linda M.

AU - Dong, Huaying

AU - Parrott, Roberta E.

AU - O'Reilly, Richard J.

AU - Dara, Jasmeen

AU - Kapoor, Neena

AU - Forbes Satter, Lisa

AU - Chandra, Sharat

AU - Kapadia, Malika

AU - Chandrakasan, Shanmuganathan

AU - Knutsen, Alan

AU - Jyonouchi, Soma C.

AU - Molinari, Lyndsay

AU - Rayes, Ahmad

AU - Ebens, Christen L.

AU - Teira, Pierre

AU - Dávila Saldaña, Blachy J.

AU - Burroughs, Lauri M.

AU - Chaudhury, Sonali

AU - Chellapandian, Deepak

AU - Gillio, Alfred P.

AU - Goldman, Fredrick

AU - Malech, Harry L.

AU - DeSantes, Kenneth

AU - Cuvelier, Geoff D.E.

AU - Rozmus, Jacob

AU - Quinones, Ralph

AU - Yu, Lolie C.

AU - Broglie, Larisa

AU - Aquino, Victor

AU - Shereck, Evan

AU - Moore, Theodore B.

AU - Vander Lugt, Mark T.

AU - Mousallem, Talal I.

AU - Oved, Joeseph H.

AU - Dorsey, Morna

AU - Abdel-Azim, Hisham

AU - Martinez, Caridad

AU - Bleesing, Jacob H.

AU - Prockop, Susan

AU - Kohn, Donald B.

AU - Bednarski, Jeffrey J.

AU - Leiding, Jennifer

AU - Marsh, Rebecca A.

AU - Torgerson, Troy

AU - Notarangelo, Luigi D.

AU - Pai, Sung Yun

AU - Pulsipher, Michael A.

AU - Puck, Jennifer M.

AU - Dvorak, Christopher C.

AU - Haddad, Elie

AU - Buckley, Rebecca H.

AU - Cowan, Morton J.

AU - Heimall, Jennifer

PY - 2024/1

Y1 - 2024/1

N2 - Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT). Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID). Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001). Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.

AB - Background: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children in the United States and Canada onto a retrospective multicenter natural history study of hematopoietic cell transplantation (HCT). Objective: We investigated outcomes of HCT for severe combined immunodeficiency (SCID). Methods: We evaluated the chronic and late effects (CLE) after HCT for SCID in 399 patients transplanted from 1982 to 2012 at 32 PIDTC centers. Eligibility criteria included survival to at least 2 years after HCT without need for subsequent cellular therapy. CLE were defined as either conditions present at any time before 2 years from HCT that remained unresolved (chronic), or new conditions that developed beyond 2 years after HCT (late). Results: The cumulative incidence of CLE was 25% in those alive at 2 years, increasing to 41% at 15 years after HCT. CLE were most prevalent in the neurologic (9%), neurodevelopmental (8%), and dental (8%) categories. Chemotherapy-based conditioning was associated with decreased-height z score at 2 to 5 years after HCT (P < .001), and with endocrine (P < .001) and dental (P = .05) CLE. CD4 count of ≤500 cells/μL and/or continued need for immunoglobulin replacement therapy >2 years after transplantation were associated with lower-height z scores. Continued survival from 2 to 15 years after HCT was 90%. The presence of any CLE was associated with increased risk of late death (hazard ratio, 7.21; 95% confidence interval, 2.71-19.18; P < .001). Conclusion: Late morbidity after HCT for SCID was substantial, with an adverse impact on overall survival. This study provides evidence for development of survivorship guidelines based on disease characteristics and treatment exposure for patients after HCT for SCID.

KW - HCT

KW - SCID

KW - bone marrow transplantation

KW - late effects

KW - survivorship

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UR - http://www.scopus.com/inward/citedby.url?scp=85176234805&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2023.09.027

DO - 10.1016/j.jaci.2023.09.027

M3 - Article

C2 - 37793572

AN - SCOPUS:85176234805

SN - 0091-6749

VL - 153

SP - 287

EP - 296

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 1

ER -

Posttransplantation late complications increase over time for patients with SCID: A Primary Immune Deficiency Treatment Consortium (PIDTC) landmark study

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