Authors
1. Vinh Ton (Role: Presenting Author) 2. Dr. Akshay Pulavarty (Role: Author) 3. Dr. Taiye Odedosu (Role: Author) New York University Grossman School of Medicine, New York, NY.
Introduction
Individuals with Fanconi anemia (FA) have a significantly higher risk for developing Head and Neck Squamous Cell Carcinomas (HNSCC). Due to impaired DNA-crosslink-damage-repair mechanisms in individuals with FA, they have significant toxicity to platinum chemotherapy.
Case Presentation
A 34-year-old Hispanic male with recently diagnosed Stage IVB SCC of the right palate presented to the hospital for induction chemotherapy with docetaxel, cisplatin, 5-fluorouracil. The patient was younger than the average HNSCC patient and reported no tobacco or alcohol use, but his tumor stained for p16: a surrogate marker for tumors driven by HPV infection. On admission, his pre-chemotherapy labs revealed a normocytic anemia with Hgb 9.6 g/dL. By the final day of chemotherapy, the patient developed profound pancytopenia and neutropenia, and he soon developed abdominal pain, diarrhea, and vomiting. Days later, he developed a fever, tachycardia, and hypotension, with critical thrombocytopenia (Plt 1x103/mcL). He was transferred to the MICU for septic shock secondary to Pseudomonas bacteremia, where he remained for 11 days, requiring vasopressors and multiple blood, platelet, and plasma transfusions to support his hypotension, severe pancytopenia, and hematochezia. He was stabilized and transferred to the medicine floor for further management of electrolyte abnormalities, but within two days went into hemorrhagic shock secondary to hematochezia. Massive transfusion protocol was initiated, and he was transferred back to the MICU for stabilization. After 6 days he returned to the medicine floor. Over time, his pancytopenia improved, and doses of filgrastim and prophylactic broad-spectrum antibiotics were discontinued four weeks after he completed his chemotherapy regimen. He was discharged for outpatient follow-up.
Discussion
The patient's unusually toxic response to his chemotherapy raised suspicion for an unidentified genetic disease. Characteristics suspicious for undiagnosed Fanconi anemia became more salient upon review: the patient's short stature (significantly shorter than his family), his congenital hypoplastic right thumb, and his anemia present at admission. Follow up peripheral blood smear was notable for neutrophils with Dohle bodies and dysplastic neutrophils with pseudo Pelger-Huet anomaly, indicative of likely myelodysplastic syndrome and consistent with FA. Genetic testing confirmed the diagnosis. Individuals with FA have a 500-700-fold higher incidence of HNSCC than the general population (1–4), and tend to be diagnosed much younger than the typical age of 50 (5). Furthermore, FA is associated with congenital abnormalities such as the short stature and hypoplastic thumbs of this patient (6). FA patients have mutations in DNA-damage-repair proteins, leaving their cells particularly vulnerable to platinum chemotherapy (6). Such toxicity was readily apparent in this patient who received cisplatin; during his hospital course, his WBC counts fell below 1x103/mcL (nadir 0.03 x103/mcL) for 23 days despite daily injections of filgrastim. His platelet count nadired at 1x103/mcL was supported with infusions every 1-2 days. His hemoglobin nadired at 3.6 g/dL and fluctuated between 5-12 g/dL, supported by transfusions. This patient had several unique characteristics indicative of Fanconi anemia, but they were overlooked as noncontributory. Had FA been suspected and identified prior to chemotherapy, the patient could have received a less toxic treatment regimen that could have prevented his extended hospital course.
References
- Alter BP. Cancer in Fanconi anemia, 1927-2001. Cancer. 2003;97:425-440. [PMID: 12518367] doi:10.1002/cncr.11046
- Alter BP, Greene MH, Velazquez I, et al. Cancer in Fanconi anemia [Letter]. Blood. 2003;101:2072. [PMID: 12584146] doi:10.1182/blood-2002-11-3597
- Kutler DI, Auerbach AD, Satagopan J, et al. High incidence of head and neck squamous cell carcinoma in patients with Fanconi anemia. Arch Otolaryngol Head Neck Surg. 2003;129:106-112. [PMID: 12525204] doi:10.1001/archotol.129.1.106
- Rosenberg PS, Greene MH, Alter BP. Cancer incidence in persons with Fanconi anemia. Blood. 2003;101:822-826. [PMID: 12393424] doi:10.1182/blood-2002-05-1498
- Kutler DI, Patel KR, Auerbach AD, et al. Natural history and management of Fanconi anemia patients with head and neck cancer: a 10-year follow-up. Laryngoscope. 2016;126:870-879. [PMID: 26484938] doi:10.1002/lary.25726
- Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 2010;24:101-122. [PMID: 20417588] doi:10.1016/j.blre.2010.03.002
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