Late Gastrointestinal Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Gastrointestinal (GI) complications are common after allogeneic hematopoietic stem cell transplantation (HSCT) and contribute to significant morbidity and mortality. Although the first 100 days are typically considered the “acute” period after a transplant, many GI events occur after this time. These include “acute” GVHD (now reclassified as late acute GVHD), classic chronic GVHD, and overlap syndrome, as well as infections, ulcers, drug reactions, and more. In order to shed light on the problem of late GI complications after HSCT, we performed a single institution retrospective study of HSCT patients requiring endoscopy after Day 100.

Methods: We identified 397 patients who underwent allogeneic HSCT between 1/1/05-12/31/10. Of these, 176 (44%) had an endoscopic evaluation post-HSCT, including 79 with endoscopies performed after Day 100. Eight of these were performed for known conditions (e.g. follow up of previous GI bleed, screening colonoscopy at 3 years), leaving 71 patients (18%) who had endoscopies for late GI symptoms. In addition to reviewing these charts, biopsies were re-reviewed by two pathologists, blinded to clinical findings, to ensure uniform categorization in light of the NIH Consensus Criteria (Biol Blood Marrow Transp 2005;11:945-955). In addition to diagnosis, outcomes included overall survival (OS) and treatment-related mortality (TRM).

Results: Of 71 patients with late GI complications requiring endoscopy, 45 (63%) had GI GVHD [late acute: 39 (87%), classic chronic: 1 (2%), overlap: 5 (11%)].  Of the 26 without GVHD, the most common diagnoses were: infection (8: 6 CMV, 1 C diff, 1 unknown), gastritis/duodenitis (7), drugs (one each on mycophenolate and valgancyclovir), local disease relapse (2), delayed motility (1), and unknown (6). Baseline characteristics (Table 1) and signs and symptoms at endoscopy (Table 2) were generally similar in both groups with the exception of diarrhea which was more common in patients with GVHD (87% vs. 54%, p=0.01). While multivariate logistic regression analysis showed apoptosis score (1-4) was predictive of GVHD (OR=2.35, 95% CI 1.18-4.70), crypt destruction was predictive of need for TPN (OR=2.56, 95% CI 1.37-4.81). Patients with GVHD tended to shorter overall survival (e.g., 2-year OS of 31% vs, 50%) than those without (p=0.131) due to a higher incidence of treatment-related mortality (Figure 1, p=0.119).

Conclusion: Late GI complications are common after HSCT, with 18% of patients requiring endoscopy after Day 100. Few clinical characteristics distinguish GVHD from other etiologies and endoscopy is essential to establishing the diagnosis. Findings of crypt destruction may predict severe GVHD and need for TPN.