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Multicenter Study
. 2024 Jan;153(1):287-296.
doi: 10.1016/j.jaci.2023.09.027. Epub 2023 Oct 2.

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

Hesham Eissa  1 , Monica S Thakar  2 , Ami J Shah  3 , Brent R Logan  4 , Linda M Griffith  5 , Huaying Dong  4 , Roberta E Parrott  6 , Richard J O'Reilly  7 , Jasmeen Dara  8 , Neena Kapoor  9 , Lisa Forbes Satter  10 , Sharat Chandra  11 , Malika Kapadia  12 , Shanmuganathan Chandrakasan  13 , Alan Knutsen  14 , Soma C Jyonouchi  15 , Lyndsay Molinari  16 , Ahmad Rayes  17 , Christen L Ebens  18 , Pierre Teira  19 , Blachy J Dávila Saldaña  20 , Lauri M Burroughs  2 , Sonali Chaudhury  21 , Deepak Chellapandian  22 , Alfred P Gillio  23 , Fredrick Goldman  24 , Harry L Malech  25 , Kenneth DeSantes  26 , Geoff D E Cuvelier  27 , Jacob Rozmus  28 , Ralph Quinones  29 , Lolie C Yu  30 , Larisa Broglie  31 , Victor Aquino  32 , Evan Shereck  33 , Theodore B Moore  34 , Mark T Vander Lugt  35 , Talal I Mousallem  6 , Joeseph H Oved  7 , Morna Dorsey  8 , Hisham Abdel-Azim  36 , Caridad Martinez  37 , Jacob H Bleesing  11 , Susan Prockop  12 , Donald B Kohn  38 , Jeffrey J Bednarski  39 , Jennifer Leiding  40 , Rebecca A Marsh  11 , Troy Torgerson  41 , Luigi D Notarangelo  42 , Sung-Yun Pai  43 , Michael A Pulsipher  17 , Jennifer M Puck  8 , Christopher C Dvorak  8 , Elie Haddad  44 , Rebecca H Buckley  6 , Morton J Cowan  8 , Jennifer Heimall  15
Affiliations
Multicenter Study

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

Hesham Eissa et al. J Allergy Clin Immunol. 2024 Jan.

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.

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Conflict of interest statement

JJB - Advisory Board for Sobi; Advisory Board for Prime Medicine; Advisory Board for Horizon Therapeutics. BJDS - Consultancy for Sobi. JRH - Author Royalties from UpToDate; Grant/Research Support from CSL Behring, Regeneron, Enzyvant, ADMA; DSMB Jasper Therapeutics. JMP – Royalties from UpToDate. MT- Advisory Board for Proteios Technology, Inc; Advisory Board for ImmunoVec, Inc. MJC – Royalties from UpToDate; DSMB for bluebird bio, Rocket Pharma, and Chiesi, Inc; SAB for Homology Medicines, Inc.

Figures

Figure 1
Figure 1. Study Population
The 6902 study population included SCID patients treated between 1982–2012 at 32 PIDTC centers. HCT - Hematopoietic cell transplantation
Figure 2
Figure 2. Cumulative incidence of CLE
The incidence of CLE increased over time post- 1st HCT from 25% at 2 years to 41% at 15 years. CLE – Chronic and late effects defined as either conditions present prior to 2 years from HCT and remaining unresolved, or new conditions that developed at or beyond 2 years after HCT. HCT - Hematopoietic cell transplantation
Figure 3
Figure 3. Landmark analysis of deaths beyond 2 years post-HCT
Among the 399 patients who survived to 2 years after 1st HCT, without need for 2nd HCT or being lost to follow-up, 15-year overall survival was 90%. HCT - Hematopoietic cell transplantation; OS - overall survival.
See this image and copyright information in PMC

References

    1. Thakar M, Logan BR, Puck JM, Dunn EA, Buckley RH Cowan MJ et al. Measuring the impact of newborn screening on survival after hematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium. Lancet 2023, In Press. - PMC - PubMed
    1. Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM, et al. Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: a PIDTC natural history study. Blood. 2017;130(25):2718–27 - PMC - PubMed
    1. Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371(5):434–46. - PMC - PubMed
    1. Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res. 2011;49(1–3):25–43. - PMC - PubMed
    1. Hardin O, Lokhnygina Y, Buckley RH. Long-Term Clinical Outcomes of Severe Combined Immunodeficiency Patients Given Nonablative Marrow Transplants. J Allergy Clin Immunol Pract. 2022;10(4):1077–83. - PubMed

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