Squamous cell carcinoma development in Fanconi anemia patients who underwent hematopoietic stem cell transplantation

Abstract

We examined SCC development of 24 FA patients, who received HSCT from HLA‐matched relatives. In our BMT center, we applied low‐dose CY + LFI + ATG (n:13) as conditioning regimen for FA patients between 1992 and 1999, and CY + BU + ATG (n:11) between 1999 and 2002. The aim of this study was to investigate SCC development after HSCT and examine features of the follow‐up patients. The 10‐year overall survival (OS) of the group with LFI + regimen was 43%, whereas the group without LFI regimen was 60%. There was a statistically significant relationship between infections (viral/bacterial) and overall survival (Fisher's Exact test P < .001). Five out of 13 long‐term (>1 year) surviving patients developed SCC in the HNSCC (n:4) and esophagus (n:2) region (a patient with oral SCC developed a second primary esophageal SCC). The SCC rate in our FA patients was 38%, four of the SCC patients were transplanted with irradiation used conditioning regimens, three of them had acuteGvHD (Grade II‐III), only one developed chronic GvHD. The interval between HSCT and SCC diagnosis was median 13 (range 6‐18) years, the age for the development of cancer was median 21 (range 15‐32) years. Survival after SCC was low, median 6 months (range 6‐12), due to delayed SCC diagnosis, tumor progression under therapy and treatment‐related toxicities of the usually reduced RT and/or CT.

Oral Cancer in HSCT Pediatric Patients Arising on GVHD: A Comprehensive Review

“…In relation to the indication for HSCT, among the selected studies, 12 patients out of 33 were affected by Fanconi Anemia (FA), a genetically and phenotypically heterogeneous autosomal recessive, dominant or X-linked disorder, characterized by congenital abnormalities, bone marrow failure, and increased risk for cancer [ 32 ]. HSCT is considered the treatment of choice in FA patients who develop hematopoietic failure, but it may predispose to late cancer development by adding risk factors; among these, a strong association between GVHD and late malignancies has been demonstrated [ 20 , 27 ].…”

Fanconi anemia and hematopoietic stem cell transplant as risk factors for oral squamous cell carcinoma: A case report with a 12‐year follow‐up

“…conducted a study comparing diagnosis, treatment, and outcomes of OSCC in FA patients after HSCT, and found that the patients often ignore initial cancer symptoms. The delayed diagnosis contributed to the low survival rates 24 . Thus, despite a few studies reporting poor accuracy of oral self‐examination by FA patients and guardians, 23 educating the patients to perform proper self‐screening may be an effective auxiliary method combined with periodic professional evaluations.…”

“…The delayed diagnosis contributed to the low survival rates. 24 Thus, despite a few studies reporting poor accuracy of oral self-examination by FA patients and guardians, 23 educating the patients to perform proper self-screening may be an effective auxiliary method combined with periodic professional evaluations.…”

Importance of Population-Based Cancer Risk Information in the Care of Patients With Rare Genetic Disorders

“…Two recent reports of survivors of HSCT for FA demonstrated that 40%-70% (depending on the length of follow-up) of individuals developed squamous cell carcinoma of the head and neck region. 5,6 The situation with AT and adult-onset cancers is more complex as many patients with AT do not survive far into adulthood, given the combined risk of malignancy, immunodeficiency, and severe neurologic disability, resulting in tragic losses because of pulmonary failure during adolescence and young adulthood. 7,8 Dramatically different approaches for identifying every individual with a genetic condition in a geographic region have more recently involved genome-scale sequencing such as the study of individuals with DICER1 pathogenic variants in the Geisinger Health population 9 or conversely using highly specific and sensitive clinical features, for example, the astounding study where investigators systematically performed physical examinations on 152,819 six-year-old children in six German states using the neurofibromatosis type 1 diagnostic criteria to identify all individuals with neurofibromatosis type 1.…”

“…Two recent reports of survivors of HSCT for FA demonstrated that 40%-70% (depending on the length of follow-up) of individuals developed squamous cell carcinoma of the head and neck region. 5 , 6 The situation with AT and adult-onset cancers is more complex as many patients with AT do not survive far into adulthood, given the combined risk of malignancy, immunodeficiency, and severe neurologic disability, resulting in tragic losses because of pulmonary failure during adolescence and young adulthood. 7 , 8 …”