High alpha‐1 antitrypsin clearance predicts severity of gut graft‐versus‐host disease (GVHD) in children
Authors: Hagen L. E. M. , Schechter T. , Luk Y. , Brodovitch A. , Gassas A. , Doyle J. J. 
Published: July 2011

Hagen LEM, Schechter T, Luk Y, Brodovitch A, Gassas A, Doyle JJ. High alpha‐1 antitrypsin clearance predicts severity of gut graft‐versus‐host disease (GVHD) in children. Pediatr Transplantation 2011: 15: 659–663. © 2011 John Wiley & Sons A/S.

Abstract:  The clinical evaluation and management of gut GVHD is a significant challenge in pediatric HSCT. It is often difficult to obtain pathological evidence to confirm diagnosis and/or to determine response to treatment. The severity of the disease itself may not be related to just the classic symptom of diarrhea. The objectives of this study were to prospectively evaluate patients with suspected gut GVHD for PLE as measured by AATC in stools at two different times for each patient and to compare the severity of the PLE with the severity of clinical acute gut GVHD. Thirteen patients were suspected of gut GVHD by clinical criteria (diarrhea > 10 mL/kg/24 h); one patient was excluded for being unable to complete the stool collection. Therefore, 12 patients, 10 boys and two girls, were studied. Median stool volume was 27.5 mL/kg/day (range 10.1–109.0).The median age at BMT was 11.1 yr (range 3.9–17.0 yr). All patients had negative stool electron microscopy for viruses and cultures for C. difficile on their first collection. Nine patients (75%) had two 24‐h stool collections performed at a median of eight days apart (range 7–14 days). At the time of the first collection, six patients had ≥stage 2 acute gut GVHD, and at second collection, four patients had ≥stage 2 gut GVHD and four collections were of non‐diarrheal stool (hence treatment response). Median AATC from all 21 collections was 19.0 mL/day (range 3.0–561.0), and levels >22 mL/day indicate the diagnosis of PLE. The four children initially suspected of GVHD but who had a negative biopsy completed a total of five collections with a median AATC of 5.0 mL/day (range 3.0–16.0) vs. a median of 33.5 for the remainder of the collections (range 3‐561). Stage of gut GVHD correlated with elevated AATC and with stool volume. AATC > 22 mL/day showed a sensitivity of 70% and specificity of 82% for significant gut GVHD (≥stage 2). Seven stool collections were taken at ≥stage 3 gut GVHD; six of those seven patients were positive for PLE. Larger stool volumes were more predictive, and five collections with stool volumes >30 mL/kg/day were positive for PLE. We conclude that a significant positive correlation exists between the severity of PLE and the stage of gut GVHD (p < 0.04), particularly obvious in patients with stages 2–4 GVHD (p = 0.03). Despite the small number of patients recruited, this study emphasizes the need to consider PLE as a useful aspect of the clinical picture. We suggest that in order to see a response to therapy and therefore a decrease in AATC, clinicians should wait at least 2 wk from the initiation of therapy before repeating AATC test. In light of the significant morbidity and mortality associated with ≥stage 2 gut GVHD, and as an important therapeutic decision for these patients, one may consider evaluating AATC if a biopsy is not an option.