1527. Beware Unintended Consequences: An Epidemiologic Investigation of Colonic Catastrophes in a Lung Transplant (LTx) Program Following a Change in Induction Immunosuppression
Session: Poster Abstract Session: Infections and Transplantation
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Background:   In response to high rates of CMV disease (28%) among D+/R- LTx recipients (pts), we changed from alemtuzumab (Amab) to basiliximab (Bmab) induction in mid-2010.  Within 9 months, we encountered 7 cases of colonic disease that required colectomy.

Methods:
In this epidemiologic investigation, the case definition was disease requiring colectomy within 100 days post-LTx from 1/1/10-5/31/11.  Controls underwent LTx during the same period and did not have colonic disease.

Results:
Yearly colectomy rates (2009-11) were 3%, 4% and 13%.  During the study, 73% (133/181) of LTx pts received Amab and 27% (48/181) Bmab (D+/R-, 32; cancer, 16).  7 cases were identified after 9/20/10.  4 had acute abdomen, 2 shock and 1 BRBPR. CT showed pneumatosis intestinalis (5) and toxic megacolon (2). Cases involved ascending and proximal transverse colon.  Etiologies were unknown; histopathology reported “ischemia”. There were no differences in demographics, underlying diseases, pre-LTx risk factors, surgical techniques, time to extubation or infections.  Cases had longer bypass time (median 351 vs 215 min, p=0.02), occurred in 10% (5/48) of pts receiving Bmab vs 1.5% (2/132) Amab (p=0.015), and involved higher median doses of steroid (20 vs 5 mg) and mycophenolate mofetil (MMF) (2.9±0.9 vs 1.3g±0.4; p<0.0001). Multivariate analysis identified Bmab induction, higher dose steroid and MMF as risk factors (p<0.0001). Re-review of histopathology revealed punched-out ischemic foci adjacent to dilated crypts and increased apoptotic cells.  Differential diagnoses included ischemia and drug injury, but the robust blood supply of the right colon and focal lesions favored the latter.  Dilated crypts and apoptotic cells have been linked to MMF toxicity. We decreased MMF dose from 3 to 2g in 7/11; no further cases have been observed. 

Conclusion:
  As part of a change from Amab to Bmab induction, maintenance doses of steroid and MMF were increased.  The change in immunosuppression achieved its objective of reducing CMV infection, but the rare entity of catastrophic MMF colon toxicity was an unintended consequence. The new regimen also worsened rejection rates and wound healing, highlighting how strategies to combat infections post-Tx may come at costs in non-ID outcomes.
Cornelius Clancy, MD, Infectious Disease, University of Pittsburgh Medical Center, Pittsburgh, PA; Infectious Disease, University of Pittsburgh and VA Pittsburgh, Pittsburgh, PA and M. Hong Nguyen, MD, University of Pittsburgh, Pittsburgh, PA

Disclosures:

C. Clancy, None

M. H. Nguyen, None

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