Page 150 - 2018_10-Haematologica-web

S. Nikiforow et al.
AB
Figure 4. Cumulative incidence of cGvHD according to aGvHD grades and UGI symptoms. Cumulative incidence curves for cGvHD from time of aGvHD onset for patients with various grades of aGvHD with or without any UGI symptoms, as labeled. A. Transplantation from a matched-related donor. B. Transplantation from a well-matched or partially-matched unrelated donor. UGI: upper gastrointestinal. aGvHD: acute graft-versus-host disease.
incidence was similar to the 13% described after myeloab- lative MRD HSCT in 1990.1 Among those who developed aGvHD, 20% had UGI involvement similar to the rates of 24-39% observed by others. The rate of isolated UGI symptoms among those with aGvHD was 4.4% com- pared with 6.7%, historically.2,3,19,20,33
Using this CIBMTR cohort, we sought to address two major questions. First, we sought to determine the correct placement of iUGI aGvHD, currently defined as Stage 1 GI and overall Grade II aGvHD. We found no differences in OS, DFS, relapse, TRM or cGvHD incidence between patients with iUGI and those with Grade I or Grade II aGvHD without UGI symptoms, and noted a reduced incidence of cGvHD after iUGI among URD recipients. Furthermore, in a limited secondary analysis, we noted no difference in outcomes comparing patients with iUGI aGvHD to those without aGvHD. Thus, we did not repro- duce the initial findings by Weisdorf et al. that rates of cGvHD after iUGI were above those in Grades 0 and I aGvHD but similar to those after Grade II non-UGI GvHD.1
Next, we asked whether the presence of UGI when found in conjunction with other aGvHD manifestations impacted outcomes, specifically focusing on whether UGI symptoms in addition to Grade I skin-only disease yielded outcomes similar to Stage II disease (i.e., Skin Stage 3, Liver Stage 1, and LGI Stage 1). We found no impact on outcomes in early Grades I or II aGvHD, whereas documentation of UGI symptoms in addition to Grades III/IV aGvHD correlated with worse outcomes, particularly TRM, after MRD HSCT. Whether UGI symptoms severe enough to be diagnosed in the setting of Grade III/IV manifestations comprise the same entity and share the same pathology as iUGI cannot be ascer- tained, and the biologic rationale for this finding is unclear. However, these findings are unlikely to change the management of this patient group. Based on these
analyses, our study does not show a significant prognos- tic impact of UGI aGvHD, in isolation or combination, on transplant-related outcomes and suggests that the classifying of UGI as a Grade II entity as it is currently diagnosed and reported might be incorrect.
The major limitations of this analysis, and any investi- gation of UGI aGvHD, are the difficulties surrounding diagnosis, lack of specificity of symptoms, unclear time of onset, and a seeming reluctance among transplant physi- cians to pursue or document biopsy confirmation of UGI involvement.34 Anecdotally, individual transplant centers vary in UGI biopsy performance and reporting, especially when LGI symptoms are present.35,36 In the study herein, only 61 of 251 participating centers reported a case of iUGI aGvHD. Among the 8567 patients included, only 1737 biopsies (20.3%) were documented. In patients with iUGI aGvHD specifically, 69% did not have a biopsy recorded. Therefore, the incidence may be under-reported in our database or confused with non-specific GI inflam- mation.
Perhaps most importantly, the above results are in the context of systemic steroid administration to 90% of patients with UGI aGvHD, with dose, duration of, and response to therapy not specified in this data set. It is highly possible that widespread use of systemic steroids is impacting outcomes in this group, especially as many have demonstrated that UGI aGvHD has higher response rates than other Grade II manifestations.1,2,33 Therefore, we can only state that UGI aGvHD, when diagnosed, report- ed to the CIBMTR, and treated according to current stan- dards of care across multiple institutions, does not impact prognosis. This is in contrast to all other manifestations of aGvHD, particularly Grades II-IV for which, despite treat- ment with systemic corticosteroids, occurrence is histori- cally associated with worse outcomes.10-12,33,37
In our primary analyses, utilizing a multivariate model including all patient groups and starting from the time of
1716
haematologica | 2018; 103(10)