The role of bone marrow transplantation in patients with Fanconi anemia and head and neck squamous cell carcinoma receiving radiotherapy: An examination of the International Fanconi Anemia (IFAR) Registry

Introduction: Fanconi anemia (FA) patients have a high predilection for developing aggressive head and neck squamous cell carcinoma (HNSCC) at an early age. Because of their aggressive HNSCC, these patients frequently require multiple modality treatment, including radiation therapy. However, their underlying chromosomal instability makes giving radiation to these patients difficult because of increased radiation-induced complications. In order to better understand this problem, we evaluated a large population of FA patients with HNSCC who received radiation therapy for HNSCC. Hypothesis: FA patients who have undergone prior bone marrow transplant (BMT) and present with head and neck squamous cell carcinoma (HNSCC) demonstrate decreased relative risk of radiation-induced complications compared to FA patients who have not received BMT. Study Design: Retrospective Cohort Study Methods: Demographic information, genotypic data, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry (IFAR) who developed HNSCC from 1981-2017 were analyzed. Results: Data were collected from the IFAR registry for n=50 patients. The mean age at time of HNSCC diagnosis was 30.5 + 9.0 years, and 36% of total patients were male. 42% of the patients received adjuvant or neoadjuvant radiotherapy for HNSCC, with the most common subsites involving the oral tongue (n=8), followed by alveolus (n=3) and supraglottis (n=2). The average dose given was 48.8 + 16.9 Gy over a 28- to 70-day period. Among patients receiving radiotherapy, 24% had received a bone marrow transplant. No patients who had a prior BMT were noted to develop pancytopenia as a radiation-related complication, while 68% of those without prior BMT developed pancytopenia from radiation. 6/16 patients who did not undergo transplant completed the full course of radiation, while 4/5 BMT patients were able to complete treatment. Both mucositis and sepsis were secondary complications more common in the non-BMT group (56% vs. 40%, and 12% vs. 0%, respectively). The relative risk of pancytopenia among patients receiving BMT and adjuvant radiation was 0.15 (95% CI 0.01-2.2); however, this was not statistically significant given the small BMT-group sample size (p=0.17). Interestingly, 80% of patients in the BMT group exhibited genetic mutations of the Fanconi complementation group C. Among patients who received a BMT and adjuvant radiotherapy, 5 patients died of XRT-related complications, while only 1 patient died from these complications in the BMT group. Conclusion: While it is well known that FA patients have a high predilection for developing aggressive HNSCC at an early age, among the patients who received preradiation bone marrow transplant the incidence of radiation-induced pancytopenia was reduced. This reduction suggests that FA patients undergoing radiotherapy for HNSCC may exhibit less adverse side effects of radiation treatment if they received a prior BMT. Citation Format: Ade Obayemi, K.R. Patel, O. Rosti, A. Smogorzewska, D. Kutler. The role of bone marrow transplantation in patients with Fanconi anemia and head and neck squamous cell carcinoma receiving radiotherapy: An examination of the International Fanconi Anemia (IFAR) Registry [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; 2019 Apr 29-30; Austin, TX. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_2):Abstract nr B23.