Oral Mucositis Incidence and Severity after Methotrexate and Non-Methotrexate Containing GVHD Prophylaxis Regimens.

Oral mucositis (OM) occurs in up to 75% of recipients of high-dose chemoradiotherapy conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (HSCT). OM affects patient quality of life by causing oropharyngeal pain, and by impairing communication and swallowing. As a result, narcotic analgesia and total parenteral nutrition (TPN) are commonly required in the recovery period after HSCT. Methotrexate (MTX), an antiproliferative agent used as GVHD prophylaxis, impairs mucosal regeneration after conditioning-related injury, and worsens and prolongs OM. We assessed the impact of sirolimus, a novel immunosuppressive agent used in lieu of MTX for GVHD prophylaxis, on outcomes associated with OM. Methods: Two cohorts of patients were prospectively analyzed for OM severity, and chart reviews were performed to assess correlative outcomes. All patients underwent HLA-matched sibling PBSC transplantation after Cy-TBI conditioning. GVHD prophylaxis consisted of sirolimus/tacrolimus (ST) in the study group and tacrolimus/methotrexate (TM) in the control group. OM was assessed 3x/week using a prospectively validated 6-point assessment tool, by members of the Oral Medicine Service. At each assessment, the evaluators systematically evaluated for the presence of erythema and ulceration of the oral mucosa at nine pre-defined locations within the oral cavity. The use of narcotics and TPN was recorded from the time of transplantation to hospital discharge. Results: 30 patients received ST and 24 patients received TM as GVHD prophylaxis after HLA-matched PBSCT between 10/2000 and 5/2003. The two groups were balanced for demographic variables, including age, sex, and disease status at transplant. OM severity was reduced in the ST group. Mild, moderate and severe OM was noted in 37, 57 and 7% of the ST group and 8, 42 and 50% of the TM group (p=0.0002). As a result, TPN use was reduced in the ST group (17 vs. 43% of hospital days, p=0.02), and a higher proportion of subjects required no TPN in the ST group (47 vs. 21%, p=0.08). The total number of hospital days where narcotics were required for pain control was lower in the ST group in comparison with the TM group (14 vs. 16 days median, p = NS). The time from transplant to first hospital discharge was shorter in the ST group compared with the TM group (18 vs. 22 days median, p= 0.07) Conclusions: The use of ST for GVHD prophylaxis is associated with less severe oropharyngeal mucositis than TM, despite equivalent conditioning regimen intensity. As a result, TPN use was reduced, narcotic use was reduced and the duration of hospitalization was shortened. The use of less toxic GVHD regimens without MTX may have significant impact on patient quality of life, patient outcomes and economic outcomes associated with allogeneic stem cell transplantation.