. 2019 Oct;39(7):653-667.

doi: 10.1007/s10875-019-00659-8. Epub 2019 Aug 2.

Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

Rebecca A Marsh¹, Jennifer W Leiding², Brent R Logan³, Linda M Griffith⁴, Danielle E Arnold⁵, Elie Haddad⁶, E Liana Falcone⁷, Ziyan Yin³, Kadam Patel³, Erin Arbuckle⁸, Jack J Bleesing¹, Kathleen E Sullivan⁵, Jennifer Heimall⁵, Lauri M Burroughs⁹, Suzanne Skoda-Smith¹⁰, Shanmuganathan Chandrakasan¹¹, Lolie C Yu¹², Benjamin R Oshrine¹³, Geoffrey D E Cuvelier¹⁴, Monica S Thakar⁹, Karin Chen¹⁵, Pierre Teira¹⁶, Shalini Shenoy¹⁷, Rachel Phelan¹⁸, Lisa R Forbes¹⁹, Deepak Chellapandian²⁰, Blachy J Dávila Saldaña²¹, Ami J Shah²², Katja G Weinacht²³, Avni Joshi²⁴, Farid Boulad²⁵, Troy C Quigg²⁶, Christopher C Dvorak²⁷, Debi Grossman²⁸, Troy Torgerson²⁹, Pamela Graham²⁸, Vinod Prasad³⁰, Alan Knutsen³¹, Hey Chong³², Holly Miller³³, M Teresa de la Morena³⁴, Kenneth DeSantes³⁵, Morton J Cowan²⁷, Luigi D Notarangelo³⁶, Donald B Kohn³⁷, Elizabeth Stenger³⁸, Sung-Yun Pai³⁹, John M Routes⁴⁰, Jennifer M Puck²⁷, Neena Kapoor⁴¹, Michael A Pulsipher⁴¹, Harry L Malech²⁸, Suhag Parikh⁴², Elizabeth M Kang⁴³; submitted on behalf of the Primary Immune Deficiency Treatment Consortium

Affiliations

¹ Department of Pediatrics, University of Cincinnati, and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
² Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins-All Children's Hospital, University of South Florida, St. Petersburg, FL, USA.
³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Immunology-Rheumatology Division, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
⁷ Division of Immunity and Viral Infections, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada; and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
⁸ Department of Pediatrics, Duke University, Durham, NC, USA.
⁹ Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, The University of Washington School of Medicine, Seattle, WA, USA.
¹⁰ Seattle Children's Hospital, Seattle, WA, USA.
¹¹ Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
¹² Division of Hematology/Oncology and Hematopoietic Stem Cell Transplantation, The Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, LA, USA.
¹³ Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
¹⁴ Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
¹⁵ Division of Allergy and Immunology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹⁶ CHU Sainte-Justine, Hematology-Oncology Division, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
¹⁷ Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA.
¹⁸ Pediatric Blood and Marrow Transplant Program, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁹ Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA, and Section of Allergy, Immunology and Retrovirology, Texas Children's Hospital William T. Shearer Center for Human Immunobiology, Houston, TX, USA.
²⁰ Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
²¹ Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC, USA, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
²² Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Lucille Packard Children's Hospital, Palo Alto, CA, USA.
²³ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
²⁴ Division of Pediatric Allergy and Immunology, Mayo Clinic, Rochester, MN, USA.
²⁵ Department of Pediatrics, BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX, USA.
²⁷ Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco Benioff Children's Hospital, San Francisco, CA, USA.
²⁸ Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁹ Department of Pediatrics, Divisions of Immunology/Rheumatology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
³⁰ Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC, USA.
³¹ Pediatric Allergy and Immunology, Cardinal Glennon Children's Medical Center, Saint Louis University, St. Louis, MO, USA.
³² UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
³³ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
³⁴ Department of Pediatrics/Immunology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
³⁵ American Family Children's Hospital, University of Wisconsin, Madison, WI, USA.
³⁶ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
³⁷ David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
³⁸ Aflac Center and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, USA.
³⁹ Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA.
⁴⁰ Division of Allergy and Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴¹ Blood and Marrow Transplant Program, Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴² Division of Pediatric Blood and Marrow Transplant, Duke University, Durham, NC, USA.
⁴³ Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ekang@niaid.nih.gov.

PMID: 31376032
PMCID: PMC6754755
DOI: 10.1007/s10875-019-00659-8

Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

Rebecca A Marsh et al. J Clin Immunol. 2019 Oct.

. 2019 Oct;39(7):653-667.

doi: 10.1007/s10875-019-00659-8. Epub 2019 Aug 2.

Authors

Affiliations

¹ Department of Pediatrics, University of Cincinnati, and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
² Division of Allergy and Immunology, Department of Pediatrics, Johns Hopkins-All Children's Hospital, University of South Florida, St. Petersburg, FL, USA.
³ Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴ Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
⁵ Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
⁶ Immunology-Rheumatology Division, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
⁷ Division of Immunity and Viral Infections, Institut de Recherches Cliniques de Montréal, Montréal, QC, Canada; and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
⁸ Department of Pediatrics, Duke University, Durham, NC, USA.
⁹ Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, The University of Washington School of Medicine, Seattle, WA, USA.
¹⁰ Seattle Children's Hospital, Seattle, WA, USA.
¹¹ Division of Bone Marrow Transplant, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
¹² Division of Hematology/Oncology and Hematopoietic Stem Cell Transplantation, The Center for Cancer and Blood Disorders, Children's Hospital/Louisiana State University Medical Center, New Orleans, LA, USA.
¹³ Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
¹⁴ Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.
¹⁵ Division of Allergy and Immunology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
¹⁶ CHU Sainte-Justine, Hematology-Oncology Division, Department of Pediatrics, University of Montreal, Montreal, QC, Canada.
¹⁷ Division of Pediatric Hematology/Oncology/Bone Marrow Transplantation, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO, USA.
¹⁸ Pediatric Blood and Marrow Transplant Program, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁹ Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA, and Section of Allergy, Immunology and Retrovirology, Texas Children's Hospital William T. Shearer Center for Human Immunobiology, Houston, TX, USA.
²⁰ Blood and Marrow Transplant Program, Johns Hopkins All Children's Hospital, St. Petersburg, FL, USA.
²¹ Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC, USA, and Department of Pediatrics, The George Washington University, Washington, DC, USA.
²² Division of Stem Cell Transplantation and Regenerative Medicine, Stanford School of Medicine, Lucille Packard Children's Hospital, Palo Alto, CA, USA.
²³ Division of Stem Cell Transplantation and Regenerative Medicine, Department of Pediatrics, Stanford School of Medicine, Stanford, CA, USA.
²⁴ Division of Pediatric Allergy and Immunology, Mayo Clinic, Rochester, MN, USA.
²⁵ Department of Pediatrics, BMT Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
²⁶ Texas Transplant Institute, Methodist Children's Hospital, San Antonio, TX, USA.
²⁷ Pediatric Allergy, Immunology, and Blood and Marrow Transplant Division, San Francisco Benioff Children's Hospital, San Francisco, CA, USA.
²⁸ Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
²⁹ Department of Pediatrics, Divisions of Immunology/Rheumatology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
³⁰ Division of Pediatric Blood and Marrow Transplant, Duke University Medical Center, Durham, NC, USA.
³¹ Pediatric Allergy and Immunology, Cardinal Glennon Children's Medical Center, Saint Louis University, St. Louis, MO, USA.
³² UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.
³³ Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, AZ, USA.
³⁴ Department of Pediatrics/Immunology, University of Washington and Seattle Children's Hospital, Seattle, WA, USA.
³⁵ American Family Children's Hospital, University of Wisconsin, Madison, WI, USA.
³⁶ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
³⁷ David Geffen School of Medicine at University of California, Los Angeles, CA, USA.
³⁸ Aflac Center and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, GA, USA.
³⁹ Hematology-Oncology, Boston Children's Hospital, Boston, MA, USA.
⁴⁰ Division of Allergy and Immunology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
⁴¹ Blood and Marrow Transplant Program, Division of Hematology, Oncology and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴² Division of Pediatric Blood and Marrow Transplant, Duke University, Durham, NC, USA.
⁴³ Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. ekang@niaid.nih.gov.

PMID: 31376032
PMCID: PMC6754755
DOI: 10.1007/s10875-019-00659-8

Erratum in

Correction: Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT.
Marsh RA, Leiding JW, Logan BR, Griffith LM, Arnold DE, Haddad E, Falcone EL, Yin Z, Patel K, Arbuckle E, Bleesing JJ, Sullivan KE, Heimall J, Burroughs LM, Skoda-Smith S, Chandrakasan S, Yu LC, Oshrine BR, Cuvelier GDE, Thakar MS, Chen K, Teira P, Shenoy S, Phelan R, Forbes LR, Martinez C, Chellapandian D, Dávila Saldaña BJ, Shah AJ, Weinacht KG, Joshi A, Boulad F, Quigg TC, Dvorak CC, Grossman D, Torgerson T, Graham P, Prasad V, Knutsen A, Chong H, Miller H, de la Morena MT, DeSantes K, Cowan MJ, Notarangelo LD, Kohn DB, Stenger E, Pai SY, Routes JM, Puck JM, Kapoor N, Pulsipher MA, Malech HL, Parikh S, Kang EM; submitted on behalf of the Primary Immune Deficiency Treatment Consortium. Marsh RA, et al. J Clin Immunol. 2020 Nov;40(8):1211-1213. doi: 10.1007/s10875-020-00852-0. J Clin Immunol. 2020. PMID: 32860171 Free PMC article.

Abstract

Introduction: Inflammatory bowel disease (IBD) affects approximately 1/3 of patients with chronic granulomatous disease (CGD). Comprehensive investigation of the effect of allogeneic hematopoietic cell transplantation (HCT) on CGD IBD and the impact of IBD on transplant outcomes is lacking.

Methods: We collected data retrospectively from 145 patients with CGD who had received allogeneic HCT at 26 Primary Immune Deficiency Treatment Consortium (PIDTC) centers between January 1, 2005 and June 30, 2016.

Results: Forty-nine CGD patients with IBD and 96 patients without IBD underwent allogeneic HCT. Eighty-nine percent of patients with IBD and 93% of patients without IBD engrafted (p = 0.476). Upper gastrointestinal acute GVHD occurred in 8.5% of patients with IBD and 3.5% of patients without IBD (p = 0.246). Lower gastrointestinal acute GVHD occurred in 10.6% of patients with IBD and 11.8% of patients without IBD (p = 0.845). The cumulative incidence of acute GVHD grades II-IV was 30% (CI 17-43%) in patients with IBD and 20% (CI 12-29%) in patients without IBD (p = 0.09). Five-year overall survival was equivalent for patients with and without IBD: 80% [CI 66-89%] and 83% [CI 72-90%], respectively (p = 0.689). All 33 surviving evaluable patients with a history of IBD experienced resolution of IBD by 2 years following allogeneic HCT.

Conclusions: In this cohort, allogeneic HCT was curative for CGD-associated IBD. IBD should not contraindicate HCT, as it does not lead to an increased risk of mortality. This study is registered at clinicaltrials.gov NCT02082353.

Keywords: Allogeneic hematopoietic cell transplantation; allogeneic bone marrow transplantation; allogeneic hematopoietic stem cell transplantation; chronic granulomatous disease; inflammatory bowel disease; primary immunodeficiency.

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Conflict of interest statement

Conflict-of-interest disclosure

The authors declare no competing financial interests.

Figures

**Figure 1.**
Myeloid (A) and T-cell (B) donor chimerism in patients with and without IBD. *Indicates p<0.05.

**Figure 2.**
Cumulative incidence of acute GVHD grades I-IV (A), grades II-IV (B), and grades III-IV (C) in patients with and without IBD prior to allogeneic HCT.

**Figure 3.**
Cumulative incidence of acute GVHD grades I-IV (A), grades II-IV (B), and grades III-IV (C) in patients without IBD, in patients with IBD that was reported to be controlled, and patients with IBD that was reported to be uncontrolled prior to allogeneic HCT.

**Figure 4.**
Five-year overall survival in patients with and without IBD (A), further divided into controlled or uncontrolled IBD (B), in patients who received myeloablative versus reduced intensity/reduced toxicity conditioning regimens (C), and in patients stratified by donor HLA match (D).

**Figure 5.**
Height z score (A) and weight z score (B) in patients with and without IBD. *Indicates p<0.05.

See this image and copyright information in PMC

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Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

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Chronic Granulomatous Disease-Associated IBD Resolves and Does Not Adversely Impact Survival Following Allogeneic HCT

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