Head and neck squamous cell carcinoma following allogeneic bone marrow transplantation: Clinical features, genomic Alterations, and limited efficacy of palliative chemotherapy.
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BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is an uncommon but serious late complication after allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated clinical features, molecular alterations, and outcomes of post-HSCT HNSCC, with emphasis on recurrent disease. METHODS: Thirty-four patients diagnosed with HNSCC after allogeneic HSCT between January 2009 and May 2025 were retrospectively analyzed. Clinical characteristics, transplantation history, tumor location, HPV status, treatment, PD-L1 expression, and survival were assessed. Whole-exome sequencing (WES) was performed. RESULTS: Median age at HNSCC diagnosis was 53 years (range, 6-75), with 73.5 % male. Leukemia was the most common primary malignancy (70.5 %). The oral tongue was the most frequent site (55.9 %), followed by buccal mucosa (23.5 %). Median interval from HSCT to HNSCC was 86.8 months (95 % CI, 72.4-104.7), and median follow-up was 54.8 months (95 % CI, 24.1-85.4). Chronic GVHD was associated with inferior disease-free survival (44.4 months vs. not reached; HR 3.98; 95 % CI, 1.05-15.04; P = 0.044). Among four patients with recurrent HNSCC receiving palliative chemotherapy, median progression-free survival was only 0.7 months (95 % CI, 0.669-0.865). One patient with high PD-L1 expression received pembrolizumab but derived limited benefit. WES identified recurrent TP53 mutations and alterations in PIK3R2, KIT, EGFR, and PIK3CA. All tumors were microsatellite stable with low tumor mutational burden. CONCLUSIONS: HNSCC after HSCT typically develops after prolonged latency and shows favorable outcomes with curative therapy. However, recurrence is marked by rapid progression and poor systemic treatment response, underscoring the prognostic relevance of chronic GVHD and the need for novel therapeutic strategies.