Marsh RA¹, Leiding JW², Logan BR³, Griffith LM⁴, Arnold DE⁵, Haddad E⁶, Falcone EL⁷, Yin Z³, Patel K³, Arbuckle E⁸, Bleesing JJ¹, Sullivan KE⁵, Heimall J⁵, Burroughs LM⁹, Skoda-Smith S¹⁰, Chandrakasan S¹¹, Yu LC¹², Oshrine BR¹³, Cuvelier GDE¹⁴, Thakar MS⁹, Chen K¹⁵, Teira P¹⁶, Shenoy S¹⁷, Phelan R¹⁸, Forbes LR¹⁹, Chellapandian D²⁰, Dávila Saldaña BJ²¹, Shah AJ²², Weinacht KG²³, Joshi A²⁴, Boulad F²⁵, Quigg TC²⁶, Dvorak CC²⁷, Grossman D²⁸, Torgerson T²⁹, Graham P²⁸, Prasad V³⁰, Knutsen A³¹, Chong H³², Miller H³³, de la Morena MT³⁴, DeSantes K³⁵, Cowan MJ²⁷, Notarangelo LD³⁶, Kohn DB³⁷, Stenger E³⁸, Pai SY³⁹, Routes JM⁴⁰, Puck JM²⁷, Kapoor N⁴¹, Pulsipher MA⁴¹, Malech HL²⁸, Parikh S⁴², Kang EM⁴³; submitted on behalf of the Primary Immune Deficiency Treatment Consortium. Author informationJ Clin Immunol. 2019 Aug 2. doi: 10.1007/s10875-019-00659-8. [Epub ahead of print]

Author information

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.

6Immunology-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.

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.