Abstract

Abstract 3057

We conducted a study to examine potential associations between the maximum severity of oral mucositis (OM) and subsequent peak severity of acute graft-versus-host disease (GVHD) within 100 days after hematopoietic cell transplantation (HCT).

Patients and Methods:

The study cohort included 1689 consecutive patients who received high-intensity conditioning for treatment of hematological disease between 1995 and 2011 and had at least 2 oral medicine evaluations between days 5 and 15 after HCT with related or unrelated allogeneic bone marrow or growth factor-mobilized blood cells. Severity of OM was assessed prospectively according to the Oral Mucositis Index (OMI) (Schubert, et al, 1984). This index scores oral mucosal changes (atrophy, erythema, and pseudomembranous ulcerations) in 13 areas of the oral cavity. Acute GVHD was graded according to previously described criteria (Leisenring, et al, 2006). The maximum OMI scores between days 5 and 15 were divided into quartiles (0–17, 18–25, 26–39, and 40–89). Maximum OMI total score, and clinical features of erythema and ulceration were considered as a risk factor in the analysis. Survival was estimated by the Kaplan-Meier method. Cumulative incidences (CI) of overall and acute gut GVHD were estimated by standard methods, treating death as a competing risk. Cox regression was used to estimate hazard ratios for events occurring with the first 100 days after HCT, adjusting for other risk factors.

Results:

The cohort median age was 40 (range, 0–67) years. Of the 1689 patients, 426 (25%) were males recipients with female donors, 971 (57%) had low risk disease (i.e., CML in chronic phase, MDS/RA or MDS/RARS, or acute leukemia in remission) and 718 (43%) had high risk (all others diagnoses). 1011 patients (60%), received TBI-containing conditioning regimens, 1473 (90%) received methotrexate with a calcineurin inhibitor for GVHD prophylaxis, 866 (51%) received bone marrow, and 786 (47%) received mobilized blood cells. 651 patients (39%) had HLA-matched related donors, 552 (33%) had HLA-matched unrelated donors, and 479 (28%) had HLA-mismatched related or unrelated donors. The maximum OMI was 0–17 in 429 (25%) patients, 18–25 in 418 (25%), 26–39 in 434 (26%) and 40–89 in 408 (24%). 946 patients (56%) had grades II-IV acute GVHD, and 383 (23%) had grades III-IV GVHD. 906 patients (54%) had stage 1 gut GVHD, and 224 (13%) had stage 2–4 gut GVHD. The incidence rates of overall and gut acute GVHD according to OMI quartiles are shown in Table 1. Erythema was the clinical feature that most correlated with both acute overall and gut acute GVHD (p<0.0001). Table 2 displays the adjusted* hazard ratios (HR) for acute overall and gut GVHD according to maximum OMI. Higher maximum OMI was associated with increased mortality (p<0.0001).

Conclusion:

We propose that oropharyngeal injury caused by the pretransplant conditioning regimen reflects tissue injury throughout the gastrointestinal tract. Our results support the hypothesis that tissue injury caused by the conditioning regimen increases the risk of acute GVHD.

Table 1:

Incidence of acute overall and gut GVHD according to OMI quartile

Acute GVHD Maximum Oral Mucositis Index Quartiles P 
0–17 18–25 26–39 40–89 
Overall grade II-IV 74% 76% 82% 83% <0.0001 
Overall grade III-IV 15% 19% 24% 32% <0.0001 
Gut stage I-IV 62% 65% 70% 70% <0.0001 
Gut stage II-IV 9% 12% 14% 19% <0.0001 
Acute GVHD Maximum Oral Mucositis Index Quartiles P 
0–17 18–25 26–39 40–89 
Overall grade II-IV 74% 76% 82% 83% <0.0001 
Overall grade III-IV 15% 19% 24% 32% <0.0001 
Gut stage I-IV 62% 65% 70% 70% <0.0001 
Gut stage II-IV 9% 12% 14% 19% <0.0001 
Table 2:

Adjusted* hazard ratios (HR) for acute overall and gut GVHD according to OMI quartile

 Maximum Oral Mucositis Index Quartiles 
 0–17 18–25 26–39 40–89 
 (Reference) HR (95% CI) HR (95% CI) HR (95% CI) 
Overall grade II-IV 1.0 1.04 (0.9–1.2) 1.06 (0.9–1.2) 1.19 (1.0–1.4) 
Overall grade III-IV 1.0 1.23 (0.9–1.7) 1.32 (1.0–1.8) 1.73 (1.3–2.4) 
Gut stage I 1.0 1.07 (0.9–1.3) 1.15 (1.0–1.4) 1.22 (1.0–1.5) 
Gut stage II-IV 1.0 1.37 (0.9–2.1) 1.39 (0.9–2.1) 1.88 (1.2–2.9) 
 Maximum Oral Mucositis Index Quartiles 
 0–17 18–25 26–39 40–89 
 (Reference) HR (95% CI) HR (95% CI) HR (95% CI) 
Overall grade II-IV 1.0 1.04 (0.9–1.2) 1.06 (0.9–1.2) 1.19 (1.0–1.4) 
Overall grade III-IV 1.0 1.23 (0.9–1.7) 1.32 (1.0–1.8) 1.73 (1.3–2.4) 
Gut stage I 1.0 1.07 (0.9–1.3) 1.15 (1.0–1.4) 1.22 (1.0–1.5) 
Gut stage II-IV 1.0 1.37 (0.9–2.1) 1.39 (0.9–2.1) 1.88 (1.2–2.9) 
*

Adjusted for donor/patient gender, conditioning, graft source, donor relation, HLA match, and year of transplant.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.