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

Rebecca A Marsh, Jennifer W Leiding, Brent R Logan, Linda M Griffith, Danielle E Arnold, Elie Haddad, E Liana Falcone, Ziyan Yin, Kadam Patel, Erin Arbuckle, Jack J Bleesing, Kathleen E Sullivan, Jennifer Heimall, Lauri M Burroughs, Suzanne Skoda-Smith, Shanmuganathan Chandrakasan, Lolie C Yu, Benjamin R Oshrine, Geoffrey D E Cuvelier, Monica S Thakar, Karin Chen, Pierre Teira, Shalini Shenoy, Rachel Phelan, Lisa R Forbes, Deepak Chellapandian, Blachy J Dávila Saldaña, Ami J Shah, Katja G Weinacht, Avni Joshi, Farid Boulad, Troy C Quigg, Christopher C Dvorak, Debi Grossman, Troy Torgerson, Pamela Graham, Vinod Prasad, Alan Knutsen, Hey Chong, Holly Miller, M Teresa de la Morena, Kenneth DeSantes, Morton J Cowan, Luigi D Notarangelo, Donald B Kohn, Elizabeth Stenger, Sung-Yun Pai, John M Routes, Jennifer M Puck, Neena Kapoor, Michael A Pulsipher, Harry L Malech, Suhag Parikh, Elizabeth M Kang, submitted on behalf of the Primary Immune Deficiency Treatment Consortium, Rebecca A Marsh, Jennifer W Leiding, Brent R Logan, Linda M Griffith, Danielle E Arnold, Elie Haddad, E Liana Falcone, Ziyan Yin, Kadam Patel, Erin Arbuckle, Jack J Bleesing, Kathleen E Sullivan, Jennifer Heimall, Lauri M Burroughs, Suzanne Skoda-Smith, Shanmuganathan Chandrakasan, Lolie C Yu, Benjamin R Oshrine, Geoffrey D E Cuvelier, Monica S Thakar, Karin Chen, Pierre Teira, Shalini Shenoy, Rachel Phelan, Lisa R Forbes, Deepak Chellapandian, Blachy J Dávila Saldaña, Ami J Shah, Katja G Weinacht, Avni Joshi, Farid Boulad, Troy C Quigg, Christopher C Dvorak, Debi Grossman, Troy Torgerson, Pamela Graham, Vinod Prasad, Alan Knutsen, Hey Chong, Holly Miller, M Teresa de la Morena, Kenneth DeSantes, Morton J Cowan, Luigi D Notarangelo, Donald B Kohn, Elizabeth Stenger, Sung-Yun Pai, John M Routes, Jennifer M Puck, Neena Kapoor, Michael A Pulsipher, Harry L Malech, Suhag Parikh, Elizabeth M Kang, submitted on behalf of the Primary Immune Deficiency Treatment Consortium

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.