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Upper GI acute GvHD adds minimal prognostic value
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Figure 3. Overall survival for patients with aGvHD with or without UGI symptoms. Kaplan-Meier probabilities of overall survival from time of aGvHD onset for patients with various grades of aGvHD with or without any UGI symptoms. A. Transplantation from a matched-related donor. B. Transplantation from a well-matched or par- tially-matched unrelated donor. UGI: upper gastrointestinal. aGvHD: acute graft-versus-host disease.
Grade II aGvHD (non-UGI) symptoms tended to have inferior OS and DFS and higher TRM compared to those with Grade I aGvHD, particularly after URD HSCT (data not shown).
Prognostic impact of upper GI acute GvHD with additional GvHD involvement
Populations Analyzed. To investigate the prognostic impact of UGI aGvHD symptoms when present in addi- tion to other manifestations, we performed pairwise com- parisons between patients with aGvHD involving various organs without UGI involvement and those with similar organ involvement plus UGI symptoms. Significant dif- ferences in demographics between those who did and did not experience UGI symptoms at a given aGvHD grade, such as year of transplantation, were addressed in the sta- tistical models (Online Supplementary Table S3).
Overall survival, disease-free survival, and relapse. There was no significant difference in OS, DFS or relapse between patients with aGvHD either with or without UGI symptoms within each aGvHD grade (Table 4, Figure 3). Inferior OS and DFS were seen after MRD HSCT when UGI symptoms were noted in addition to Grades III/IV disease, but this did not attain statistical significance (HR 1.39, P=0.027; HR 1.38, P=0.027, respectively). Of note, patients with Grade I skin-only aGvHD had similar outcomes to those with Stage 1-2 skin aGvHD plus UGI involvement (currently Grade II).
Treatment-related mortality and chronic GvHD. There was no difference in TRM between patients with aGvHD with or without UGI symptoms, with the exception that more severe TRM was seen for MRD recipients when UGI symptoms occurred in addition to Grades III/IV manifes- tations (HR 1.78, P=0.0028). Unlike what was observed during the initial description of UGI aGvHD, there was no consistent effect of additional symptoms of UGI aGvHD on the subsequent development of cGvHD, including in
patients with otherwise skin-only Grade I aGvHD (MRD HR 1.00, P=1.00; URD HR 1.15, P=0.32) (Figure 4).
Prognosis of isolated UGI acute GvHD compared to Other Grade II organ involvement
In a secondary subset analysis, we analyzed patients who had Grade II manifestations other than UGI involve- ment, namely those who had skin-only Stage 3 disease (n=505), those who had liver involvement +/- any other non-UGI Grade II involvement (n=185), and those who had only LGI +/- skin disease (n=185). Those with liver disease tended to have been transplanted earlier, between 2000-2004; otherwise, the demographics were similar.
Compared to patients with iUGI aGvHD, only URD recipients with Grade II liver involvement had inferior OS (HR 1.68, P=0.0027) and TRM (HR 2.08, P=0.011) (Online Supplementary Table S4). No differences were seen between iUGI and other Grade II subgroups for any out- comes after MRD transplant. However, URD recipients from the groups with liver, LGI or skin involvement all showed increased rates of cGvHD over those with iUGI (all P-values <0.004).
Discussion
We embarked upon this analysis to expand on the observations of Weisdorf et al. derived from a single insti- tution in 1990 regarding the incidence and prognostic impact of UGI aGvHD on clinical outcomes. Our popula- tion included adult recipients of MRD and well- or partial- ly-matched URD T-cell replete HSCTs following mye- loablative conditioning for AML, ALL, CML and MDS from the CIBMTR database. Rates of Grades II-IV aGvHD seen were 44.3%, consistent with historical expe- rience.30-32 Of the entire cohort, 2.7% experienced iUGI aGvHD (n=229) and 12.1% had UGI involvement. This
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