255 - Steroid-Refractory Graft Versus Host Disease (SR-GVHD) of the Gastrointestinal (GI) Tract is Frequently Associated with Transplant Associated Thrombotic Microangiopathy (TA-TMA)

Abstract

Background: SR-GVHD is a major cause of non-relapse mortality (NRM) associated with significant hospital stays and medical costs. TA-TMA is also a well-described cause of NRM resulting in multi-organ system failure. We sought to evaluate the incidence of TA-TMA in patients with severe GI GVHD and to assess risk factors for its development. We hypothesized that patients with SR-GVHD would require more transfusions, a surrogate for TA-TMA, than those without. Methods: We performed a retrospective review of 124 patients with grade 3/4 GI GVHD who were admitted October 2008-October 2016. Patients who did not achieve a response by 7 days of 2 mg/kg steroids were defined as SR-GVHD and patients who had flare of GVHD symptoms requiring a second course of 2 mg/kg steroids were defined as steroid-dependent (SD) GVHD. We assigned patients to groups by likelihood of TA-TMA based on presence of at least 2 of 3 criteria: (1) > 2 transfusions after first GI biopsy, (2) evidence of hemolysis (schistocytes or nucleated RBCs) and (3) evidence of renal end-organ damage. Results: The median age at transplant was 54 years (range: 19-72) and 40.3% (n = 50) were female. Most transplants were done for malignant disease utilizing reduced intensity or non-myeloablative conditioning (66.1%). All but 10 patients received a GVHD prophylactic regimen containing tacrolimus. The median time to GVHD onset was 38 days (range: 12-273). TA-TMA occurred in 84 (68%) patients, typically following GVHD at a median of 142 days post-transplant and 78 days post-GVHD. Post-transplant infections included CMV reactivation (46.8%), viral infection other than CMV (60.5%), fungal infection (12.1%), and bacterial infection (65.3%). In multivariable analysis, the risk factors for developing TA-TMA from time of transplant included SD/SR-GVHD, viral infection other than CMV, and fungal infection (Table 1).Table 1Multivariable Model of Risk for Clinical TA-TMA from Time of Stem Cell Transplant Patients with SR-GVHD received more platelet and pRBC transfusions than those with steroid-responsive GVHD at 2 and 4 weeks post GVHD diagnosis (Figure 1). Regardless of GVHD steroid response and shorter follow-up of TA-TMA patients, patients with TA-TMA had longer hospitalization (median: 53 v. 25.5 days, P < .001). Patients with steroid-responsive GVHD and TA-TMA were hospitalized for a median of 71 days compared with 22.5 days for those with steroid responsive GVHD alone. Discussion: We show that SR/SD-GVHD is a risk factor for development of TA-TMA. Patients with SR-GVHD receive more transfusions and patients with both GVHD and TA-TMA have longer hospitalizations than those with GVHD alone. There are a number of causes of cytopenias in the post-transplant population and TA-TMA must be considered in the differential diagnosis. Conclusion: Further prospective study is warranted to understand the triggers of TA-TMA in patients with GVHD, particularly the role of viral and fungal infections.