Oral Epithelial Dysplasia & Squamous Cell Carcinoma Following Allogeneic Hematopoietic Cell Transplantation

Abstract

Background: Improved survival after allogeneic hematopoietic stem cell transplantation (alloHCT) is associated with a greater incidence of secondary posttransplant malignancies, including oral squamous cell carcinoma (OSCC). Aim: Our study aimed to evaluate patient demographics, characteristic features, clinical outcomes, and prevalence of OSCC risk factors in patients diagnosed with OSCC and/or oral epithelial dysplasia (OED) post-alloHCT. Methods: A retrospective chart review was completed to examine patients treated with allogeneic hematopoietic cell transplantation (alloHCT) at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) between 1969 and 2018. Cases of oral squamous cell carcinoma (OSCC) and oral epithelial dysplasia (OED) were identified through the Gateway database. The clinical characteristics were reviewed via chart notes in Optic Web Library and electronic medical records via Epic Hyperspace. Descriptive statistics were used to summarize the general characteristics of the data variables. Overall survival was calculated from the date of diagnosis of OSCC to the date of death. The mortality risk was calculated after adjusting for covariates. Results: We identified 84 cases of OSCC and 10 cases of OED in 78 subjects treated with alloHCT. The median time from alloHCT to each diagnosis of OSCC/OED was 12.0 years (range 0.8-30.0 years). OSCC lesions were frequently observed on the ventrolateral surface of the tongue (N=23), followed by the buccal mucosa (N=10), the labial mucosa (N=8), and the gingiva (N=7). Same-site lesion recurrence was documented in 25.6% of cases (N=22). Thirty subjects (39.0%) had a smoking history of at least 100 cigarettes in their lifetime. Myeloablative conditioning with total body irradiation was the most common pretransplant conditioning regimen. Sixty-one patients (85.0%) had active oral chronic graft-versus-host disease (cGVHD) within 1 year of OSCC/OED diagnosis. Immunosuppressant therapy for cGVHD was used in over 85.0% of the study cohort. The mortality risk post-alloHCT was significantly increased among patients who developed OSCC compared to those who did not (Hazard Ratio = 3.11; 95% CI, 2.34 – 4.13, p<0.0001). The 5-year survival rate of our study cohort was 61.0% (95% CI: 49.0-71.0). We identified a co-occurrence of other posttransplant head and neck cancers, particularly SCCs and basal cell carcinomas of the head and neck. Conclusions: The median time from alloHCT to OSCC diagnosis was consistent with previously reported literature, though findings were notable for 12 cases diagnosed less than 4 years post-alloHCT. The ventrolateral tongue was the most common site of secondary OSCC; however, a relatively high number of cases were identified at anatomic locations less common in the general population. The present data highlight the need for ongoing long-term monitoring of alloHCT patients along with careful oral screening.