588 results on '"Fanconi Anemia complications"'
Search Results
2. Transplant outcome in pediatric Fanconi anemia.
- Subjects
- Humans, Child, Child, Preschool, Male, Female, Adolescent, Hematopoietic Stem Cell Transplantation, Infant, Treatment Outcome, Fanconi Anemia therapy, Fanconi Anemia complications
- Published
- 2024
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- View/download PDF
3. Fanconi anemia: realizing hematopoietic cure.
- Author
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Satty AM
- Subjects
- Humans, Fanconi Anemia therapy, Fanconi Anemia pathology, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation
- Published
- 2024
- Full Text
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4. Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia.
- Author
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Lum SH, Eikema DJ, Piepenbroek B, Wynn RF, Samarasinghe S, Dalissier A, Kalwak K, Ayas M, Hamladji RM, Yesilipek A, Dalle JH, Uckan-Cetinkaya D, Bierings M, Kupesiz A, Halahleh K, Skorobogatova E, Öztürk G, Faraci M, Renard C, Evans P, Corbacioglu S, Locatelli F, Dufour C, Risitano A, and Peffault de Latour R
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- Humans, Child, Female, Male, Adolescent, Retrospective Studies, Child, Preschool, Transplantation Conditioning methods, Treatment Outcome, Infant, Leukemia, Myeloid, Acute therapy, Leukemia, Myeloid, Acute mortality, Unrelated Donors, Survival Rate, Follow-Up Studies, Disease-Free Survival, Fanconi Anemia therapy, Fanconi Anemia mortality, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology, Graft vs Host Disease mortality
- Abstract
Abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only established curative option for Fanconi anemia (FA)-associated bone marrow failure (BMF)/aplastic anemia (AA) and acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS). We performed a retrospective multicenter study on 813 children with FA undergoing first HSCT between 2010 and 2018. Median duration of follow-up was 3.7 years. Median age at transplant was 8.8 years (IQR, 6.5-18.1). Five-year overall survival (OS), event-free survival (EFS), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) were 83% (95% confidence interval [CI], 80-86), 78% (95% CI, 75-81), and 70% (95% CI, 67-74), respectively. OS was comparable between matched family donor (MFD; n = 441, 88%) and matched unrelated donor (MUD; n = 162, 86%) and was superior to that of mismatched family donor (MMFD) or mismatched unrelated donor (MMUD; n = 144, 72%) and haploidentical donor (HID; n = 66, 70%; P < .001). In multivariable analysis, a transplant indication of AML/MDS (vs AA/BMF), use of MMFD/MMUD and HID (vs MFD), and fludarabine-cyclophosphamide (FluCy) plus other conditioning (vs FluCy) independently predicted inferior OS, whereas alemtuzumab vs antithymocyte globulin was associated with better OS. Age ≥10 years was associated with worse EFS and GRFS. Cumulative incidences (CINs) of primary and secondary graft failure were 2% and 3% respectively. CINs of grade 3 to 4 acute GVHD and chronic GVHD were 12% and 8% respectively. The 5-year CIN of secondary malignancy was 2%. These data suggest that HSCT should be offered to patients with FA with AA/BMF at a younger age in the presence of a well-matched donor., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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5. Clinical and genetic features of Fanconi anemia associated with a variant of FANCA gene: Case report and literature review.
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Zhong L, Zhang W, Zhang K, Li C, Mu X, Chu Y, Gai Z, and Wei H
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- Humans, Male, Child, Preschool, Mutation, Hematopoietic Stem Cell Transplantation, Fanconi Anemia genetics, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia Complementation Group A Protein genetics
- Abstract
Rationale: Fanconi anemia (FA) is a hereditary disease caused by mutations in the genes involved in the DNA damage repair pathway. The FANCA gene is the most commonly pathogenic gene, accounting for more than 60% of all causative genes., Patient Concerns: The clinical case is a 3-year-old boy showed mild anemia and scattered bleeding spots the size of a needle tip all over his body., Diagnoses: Compound heterozygous mutation was identified in the FANCA gene in the FA case: c.1A > T from the father in exon 1; the deletion of chr16: 89857810-89858476 (exon13-14 del) from the mother; finally, the patient was diagnosed as Fanconi anemia., Intervention: After diagnosis, the child received chemotherapy (Ara-C + Flu + Cy + ATG). Then, the hematopoietic stem cell transplantation and unrelated umbilical cord blood transfusion were performed., Outcomes: The child is recovering well and is in regular follow-up., Conclusion and Lessons: The discovery of new mutations in the FANCA gene enriches the genetic profile of FA and helps clinicians to further understand this disease and guide genetic counseling and prenatal diagnosis. Whole-exome sequencing is a powerful tool for diagnosing FA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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6. Small pituitary volume and central nervous system anomalies in Fanconi Anemia.
- Author
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Corredor B, Solís I, Zubicaray J, Sevilla J, and Argente J
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- Humans, Male, Female, Cross-Sectional Studies, Child, Adolescent, Child, Preschool, Adult, Young Adult, Central Nervous System abnormalities, Central Nervous System pathology, Central Nervous System diagnostic imaging, Organ Size, Pituitary Gland diagnostic imaging, Pituitary Gland pathology, Pituitary Gland abnormalities, Fanconi Anemia pathology, Fanconi Anemia complications, Magnetic Resonance Imaging
- Abstract
Introduction: Fanconi anemia (FA) is a genomic instability disorder associated with congenital abnormalities, including short stature and the presence of central nervous system anomalies, especially in the hypothalamic-pituitary area. Thus, differences in pituitary size could associate with the short stature observed in these patients. Our aim was to evaluate whether central nervous system abnormalities and pituitary gland volume correlate with height and hormone deficiencies in these patients., Methods: In this cross-sectional exploratory study 21 patients diagnosed with FA between 2017 and 2022 in a Spanish Reference Center were investigated. Magnetic resonance imaging (MRI) was performed and pituitary volume calculated and corelated with height and other endocrine parameters., Results: The percentage of abnormalities in our series was 81%, with a small pituitary (pituitary volume less than 1 SD) being the most frequent, followed by Chiari malformation type 1. The median value of pituitary volume was -1.03 SD ( IQR : -1.56, -0.36). Short stature was found in 66.7% [CI95% 43-85.4]. Total volume (mm
3) increases significantly with age and in pubertal stages. There were no differences between volume SD and pubertal stage, or the presence of endocrine deficiencies. No correlations were found between pituitary volume and the presence of short stature. The intraclass correlation index (ICC) average for volume was 0.85 [CI95% 0.61-0.94] indicating a good-to-excellent correlation of measurements., Discussion: Central nervous system anomalies are part of the FA phenotype, the most frequent after pituitary hypoplasia being posterior fossa abnormalities, which may have clinical repercussions in the patient. It is therefore necessary to identify those who could be candidates for neurosurgical intervention. The size of the pituitary gland is smaller in these patients, but this does not seem to be related to hormone deficiency and short stature or exposure to a low dose of total body irradiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Corredor, Solís, Zubicaray, Sevilla and Argente.)- Published
- 2024
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7. Fanconi Anaemia associated with café au lait spots: A rare case report.
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Qazi M, Khan BA, Kumar V, Amin M, and Ateeque K
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- Humans, Female, Chromosome Breakage, Epoxy Compounds, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics, Cafe-au-Lait Spots genetics
- Abstract
Fanconi Anaemia is an autosomal recessive disorder, which is characterised by progressive pancytopenia, café au lait spots (>50%), bruising, petechie, recurrent infections, short height (50%), and thumb and radial bone anomalies (40%). Herein, is presented a case of a lean emaciated female child, who presented with the chief complaints of fever, loose stools and decreased appetite for one month reported at Sindh Government General Hospital, Karachi, on February, 1, 2023. She had cutaneous findings of hyperpigmentation and café au lait spots and a tri-phalangeal thumb. On investigation, pancytopenia and a low reticulocyte count of 0.7% was also observed. Karyotype and chromosomal breakage test induced by Diepoxybutane confirmed her as a case of Fanconi Anaemia.
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- 2024
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8. Transformation of an abnormal karyotype to acute erythroid leukemia in a pediatric patient with Fanconi anemia: A case report.
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Hernandez L, Galeotti J, Gold S, and Alexander TB
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- Humans, Abnormal Karyotype, Male, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic pathology, Child, Child, Preschool, Fanconi Anemia genetics, Fanconi Anemia complications, Fanconi Anemia diagnosis, Leukemia, Erythroblastic, Acute genetics, Leukemia, Erythroblastic, Acute pathology, Leukemia, Erythroblastic, Acute diagnosis
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- 2024
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9. Pediatric acute promyelocytic leukemia and Fanconi anemia: Case report and literature review.
- Author
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Freycon C, Sepulchre E, Lavallée VP, Mitchell D, MacMillan ML, Vezina C, and Goudie C
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- Humans, Male, Child, Preschool, BRCA2 Protein genetics, Genetic Predisposition to Disease, Fanconi Anemia genetics, Fanconi Anemia diagnosis, Fanconi Anemia therapy, Fanconi Anemia complications, Leukemia, Promyelocytic, Acute genetics, Leukemia, Promyelocytic, Acute diagnosis
- Abstract
Acute promyelocytic leukemia (APL) represents 5%-10% of childhood acute myeloid leukemia (AML) and is the most curable subtype of AML. Fanconi anemia (FA) is one of the most common inherited bone marrow failure syndromes caused by biallelic pathogenic variants (PV) in specific DNA-repair genes. Biallelic PVs in FANCD1/BRCA2 (FA-D1) account for 3% of FA and are associated with early-onset leukemia and a high risk of solid tumors. We report a 4 year-old boy from non-consanguineous parents diagnosed with standard risk APL. This child had café-au-lait spots and an extra thumb remnant. Genomic sequencing revealed two PV in FANCD1/BRCA2 confirming a diagnosis of FA-D1. Chromosomal breakage studies were compatible with FA. Each parent carried one variant and had no personal history of cancer. Morphological then molecular remissions were achieved with all-trans retinoic acid and Arsenic trioxide. This patient underwent haploidentical stem cell transplant. In addition to our patient, a literature search revealed four additional patients with APL/FA, with a total of three patients with FA-D1. This raises the possibility of an association between such rare disorders. Practical management of APL in the setting of FA-D1 is discussed with an overview of current evidence and knowledge gaps., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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- 2024
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10. Fanconi Anemia in a 31-Year-Old Patient with Multiple Malignant Tumor Foci, Including Appendiceal Cancer, and Multiple Coexisting Pathologies.
- Author
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Dyaczyński M, Sannikova L, and Worek D
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- Humans, Male, Adult, Neoplasms, Multiple Primary, Bone Marrow Transplantation, Fanconi Anemia complications, Appendiceal Neoplasms complications
- Abstract
BACKGROUND Fanconi anemia (FA) is a genetic disorder that impairs the function of the bone marrow and predisposes individuals to aplastic anemia. The condition is caused by mutations in genes responsible for DNA repair. People with FA have an increased risk of developing tumors due to DNA damage. Flat-cell carcinomas of the head, neck, esophagus, and genital organs are often observed in individuals with FA. CASE REPORT A 31-year-old man with Fanconi anemia and a history of bone marrow transplantation was admitted to the General Surgery Department due to elevated levels of the CEA marker. Before the transplantation, chromosomal anomalies, bone marrow hypoplasia, kidney agenesis, and bone defects were noted. After the transplantation, he developed a skin rash. He was also diagnosed with squamous cell carcinoma of the lip and chronic conditions, including cholestatic liver damage, hypertension, and hypothyroidism. During the diagnostic process, computed tomography showed signs of Barrett's esophagus, numerous polyps in the stomach and intestines, and a nodular formation measuring 4.5×5×5.5 cm in the right iliac region. Laparoscopy revealed a neoplasm of the appendix with numerous metastases on the inner abdominal wall and omentum. Histological analysis confirmed mucinous appendiceal cancer. The patient was discharged for palliative treatment at the Oncology Center with a final diagnosis of appendiceal cancer, mucinous type, grade G3. This case underscores the importance of early and comprehensive cancer screening in individuals with FA, particularly those with a history of bone marrow transplantation. CONCLUSIONS This clinical case underscores the critical importance of thorough and timely cancer diagnosis in individuals with this genetic pathology.
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- 2024
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11. Fanconi Anemia Complicated by Cervical Precancer, Vulvar, and Oral Squamous Cell Cancer.
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Day T, Stuart L, Ius Y, Haqshenas G, Garland SM, and Scurry J
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- Humans, Female, Vulvar Neoplasms complications, Vulvar Neoplasms pathology, Vulvar Neoplasms diagnosis, Uterine Cervical Neoplasms complications, Uterine Cervical Neoplasms diagnosis, Uterine Cervical Neoplasms pathology, Precancerous Conditions pathology, Precancerous Conditions complications, Histocytochemistry, Adult, Microscopy, Mouth Neoplasms complications, Mouth Neoplasms pathology, Mouth Neoplasms diagnosis, Carcinoma, Squamous Cell complications, Carcinoma, Squamous Cell pathology, Fanconi Anemia complications, Fanconi Anemia diagnosis
- Abstract
Competing Interests: SMG is supported by National Health and Medical Research Council (NHMRC) Leadership Investigator grant number 1197951. The authors have declared they have no conflicts of interest.
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- 2024
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12. Two siblings with Fanconi anemia (FANCQ, ERCC4/XPF) presenting with tumor-mimicking lesions in the brain and acute neurological deterioration.
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Özdemir ZC, Yarar C, Öztunalı Ç, Töret E, Çarman KB, and Bör Ö
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- Humans, Male, Child, Adolescent, Brain Neoplasms genetics, Brain Neoplasms pathology, Brain Neoplasms complications, Female, Magnetic Resonance Imaging, Mutation, Diagnosis, Differential, Fanconi Anemia complications, Fanconi Anemia genetics, Fanconi Anemia pathology, Siblings, DNA-Binding Proteins genetics
- Abstract
The complementation Q group (FANCQ) subtype of Fanconi anemia (FA) caused by the ERCC4/XPF mutation is very rare. Two siblings, aged 13 and 10 with Fanconi phenotypic features, presented with right hemiparesis and focal-onset seizures. In both cases, cranial magnetic resonance imaging (MRI) showed mass-like lesions accompanied by peripheral edema and calcification. In one case, oral steroid treatment and surgical excision were performed, while in the other case, the cranial lesion regressed just with steroid treatment and without surgery. Both siblings remained wheelchair-bound due to neurological dysfunction. One case died due to hepatocellular carcinoma. ERCC4/XPF gene mutation was detected in both siblings., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)
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- 2024
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13. Fanconi anemia neuroinflammatory syndrome: brain lesions and neurologic injury in Fanconi anemia.
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Bartlett AL, Wagner JE, Jones B, Wells S, Sabulski A, Fuller C, and Davies SM
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- Humans, Male, Female, Child, Adolescent, Young Adult, Adult, Child, Preschool, Magnetic Resonance Imaging, Fanconi Anemia complications, Fanconi Anemia pathology, Fanconi Anemia diagnosis, Neuroinflammatory Diseases etiology, Neuroinflammatory Diseases pathology, Brain pathology, Brain diagnostic imaging
- Abstract
Abstract: Fanconi anemia (FA) is a complex inherited bone marrow failure syndrome characterized by chromosomal instability and defective DNA repair, causing sensitivity to DNA interstrand crosslinking agents. Our understanding of the full adult phenotype of the disease continues to evolve, because most patients with FA died of marrow failure in the first decade of life before more recent advances in allogeneic hematopoietic cell transplantation. Herein, we report a previously undescribed, clinically concerning, progressive neurologic syndrome in patients with FA. Nine nonimmunosuppressed pediatric patients and young adults with FA presented with acute and chronic neurological signs and symptoms associated with distinct neuroradiological findings. Symptoms included, but were not limited to, limb weakness, papilledema, gait abnormalities, headaches, dysphagia, visual changes, and seizures. Brain imaging demonstrated a characteristic radiographic appearance of numerous cerebral and cerebellar lesions with associated calcifications and often a dominant ring-enhancing lesion. Tissue from the dominant brain lesions in 4 patients showed nonspecific atypical glial proliferation, and a small number of polyomavirus-infected microglial cells were identified by immunohistochemistry in 2 patients. Numerous interventions were pursued across this cohort, in general with no improvement. Overall, these patients demonstrated significant progressive neurologic decline. This cohort highlights the importance of recognizing FA neuroinflammatory syndrome, which is distinct from malignancy, and warrants careful ongoing evaluation by clinicians., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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14. Umbilical Cord Blood Transplantation for Fanconi Anemia With a Special Focus on Late Complications: a Study on Behalf of Eurocord and SAAWP-EBMT.
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Rafii H, Volt F, Bierings M, Dalle JH, Ayas M, Rihani R, Faraci M, de Simone G, Sengeloev H, Passweg J, Cavazzana M, Costello R, Maertens J, Biffi A, Johansson JE, Montoro J, Guepin GR, Diaz MA, Sirvent A, Kenzey C, Rivera Franco MM, Cappelli B, Scigliuolo GM, Rocha V, Ruggeri A, Risitano A, De Latour RP, and Gluckman E
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- Humans, Female, Male, Adult, Child, Child, Preschool, Adolescent, Retrospective Studies, Infant, Young Adult, Fanconi Anemia therapy, Fanconi Anemia complications, Cord Blood Stem Cell Transplantation, Transplantation Conditioning methods, Graft vs Host Disease epidemiology
- Abstract
Hematopoietic cell transplantation (HCT) remains the sole available curative treatment for Fanconi anemia (FA), with particularly favorable outcomes reported after matched sibling donor (MSD) HCT. This study aimed to describe outcomes, with a special focus on late complications, of FA patients who underwent umbilical cord blood transplantation (UCBT). In this retrospective analysis of allogeneic UCBT for FA performed between 1988 and 2021 in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers, a total of 205 FA patients underwent UCBT (55 related and 150 unrelated) across 77 transplant centers. Indications for UCBT were bone marrow failure in 190 patients and acute leukemia/myelodysplasia in 15 patients. The median age at transplantation was 9 years (range, 1.2 to 43 years), with only 20 patients aged >18 years. Among the donor-recipient pairs, 56% (n = 116) had a 0 to 1/6 HLA mismatch. Limited-field radiotherapy was administered to 28% (n = 58) and 78% (n = 160) received a fludarabine (Flu)-based conditioning regimen. Serotherapy consisted of antithymocyte globulin (n = 159; 78%) or alemtuzumab (n = 12; 6%). The median follow-up was 10 years for related UCBT and 7 years for unrelated UCBT. Excellent outcomes were observed in the setting of related UCBT, including a 60-day cumulative incidence (CuI) of neutrophil recovery of 98.1% (95% confidence interval [CI], 93.9% to 100%), a 100-day CuI of grade II-IV acute graft-versus-host disease (GVHD) of 17.3% (95% CI, 9.5% to 31.6%), and a 5-year CuI of chronic GVHD (cGVHD) of 22.7% (95% CI, 13.3% to 38.7%; 13% extensive). Five-year overall survival (OS) was 88%. In multivariate analysis, none of the factors included in the model predicted a better OS. In unrelated UCBT, the 60-day CuI of neutrophil recovery was 78.7% (95% CI, 71.9% to 86.3%), the 100-day CuI of grade II-IV aGVHD was 31.4% (95% CI, 24.6% to 40.2%), and the 5-year CuI of cGVHD was 24.3% (95% CI, 17.8% to 32.2%; 12% extensive). Five-year OS was 44%. In multivariate analysis, negative recipient cytomegalovirus serology, Flu-based conditioning, age <9 years at UCBT, and 0 to 1/6 HLA mismatch were associated with improved OS. A total of 106 patients, including 5 with acute leukemia/myelodysplasia, survived for >2 years after UCBT. Nine of these patients developed subsequent neoplasms (SNs), including 1 donor-derived acute myelogenous leukemia and 8 solid tumors, at a median of 9.7 years (range, 2.3 to 21.8 years) post-UCBT (1 related and 8 unrelated UCBT). In a subset of 49 patients with available data, late nonmalignant complications affecting various organ systems were observed at a median of 8.7 years (range, 2.7 to 28.8 years) post-UCBT. UCB is a valid source of stem cells for transplantation in patients with FA, with the best results observed after related UCBT. After unrelated UCBT, improved survival was observed in patients who underwent transplantation at a younger age, with Flu-based conditioning, and with better HLA parity. The incidence of organ-specific complications and SNs was relatively low. The incidence of SNs, mostly squamous cell carcinoma, increases with time. Rigorous follow-up and lifelong screening are crucial in survivors of UCBT for FA., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
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- 2024
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15. Liver abnormalities are frequent and persistent in patients with Fanconi anemia.
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Snyder AJ, Campbell KM, Lane A, Mehta PA, Myers K, Davies SM, and Koo J
- Subjects
- Child, Humans, Young Adult, Adult, Androgens adverse effects, Phenotype, Fanconi Anemia complications, Fanconi Anemia therapy, Liver Diseases
- Abstract
Abstract: Liver disease has not been well described in patients with Fanconi anemia (FA). Improvements in outcomes of transplant mean that more individuals with FA are reaching adulthood and new features of the FA phenotype are being discovered. We performed a retrospective review of liver function in a cohort of 97 patients with FA followed-up for at least 10 years at a single center. We identified a high frequency of transaminitis (n = 31, 32%) without elevation of bilirubin and with no evidence of structural hepatic abnormality in patients with FA. Transaminitis was persistent in many cases, sometimes lasting more than a decade without clinical manifestation, although 2 patients with prolonged transaminitis are deceased from liver failure, indicating important long-term clinical consequences. Transaminitis was found in patients who had and had not received transplant but was more frequent in recipients of transplant. Exposure to total body irradiation increased risk (odds ratio, 15.5 [95% confidence interval, 2.44-304.54]; P = .01), whereas treatment with androgens did not. Review of limited numbers of liver biopsies and autopsy material showed a cholestatic pattern of liver injury, with progressive fibrosis, in the majority of patients. Occurrence in cases without transplant as well as cases with transplant argues against a potential diagnosis of atypical liver graft-versus-host disease. Limited data regarding therapy suggest no benefit from treatment with steroids or other immune suppressive medications or ursodeoxycholic acid. Our data show that liver disease is common in patients with FA, and because most children with FA now reach adulthood, end-stage liver disease in young adulthood means systematic testing of potential therapies is urgently needed., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
- Published
- 2024
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16. HLA-haploidentical T-cell receptor αβT/B-cell-depleted stem cell transplantation for Fanconi anemia.
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Iguchi A, Uchiyama T, Fujimori K, Gocho Y, Sakaguchi H, Deguchi T, Tomizawa D, Imadome KI, Onodera M, and Matsumoto K
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- Male, Humans, Child, Cyclophosphamide, Receptors, Antigen, T-Cell, Transplantation Conditioning adverse effects, Fanconi Anemia therapy, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation adverse effects, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Graft vs Host Disease drug therapy
- Abstract
HLA-haploidentical stem cell transplantation (haplo-SCT) using post-transplant high-dose cyclophosphamide (PT-CY) is an alternative choice when a suitable donors is unavailable. However, PT-CY is difficult in patients with Fanconi anemia (FA) due to their high vulnerability to alkylating agents. For FA, we prefer haplo-SCT by T-cell receptor αβT-cell and B-cell depletion (αβT/B-depleted haplo-SCT), which can reduce the risks of PT-CY-related complications and graft-versus-host disease (GVHD). An 11-year-old boy with diagnosed FA (FANCG mutation) and bone marrow failure was to receive αβT/B-depleted haplo-SCT from his father (HLA 4/8 allele matched) due to absence of an HLA-matched donors. αβT/B-depleted peripheral blood stem cells (CD34 + cell count, 1.17 × 10
7 /kg; αβ + T-cell count, 1.3 × 105 /kg) were infused following conditioning consisting of fludarabine (150 mg/m2 ), cyclophosphamide (40 mg/kg), anti-thymocyte globulin (5 mg/kg), rituximab (375 mg/m2 ), and thoraco-abdominal irradiation (3 Gy). Tacrolimus was used for GVHD prophylaxis until day + 30. Neutrophil engraftment was achieved on day + 9, and complete chimerism was confirmed on days + 28 and + 96. At 12-month post-SCT, the patient was well without GVHD or any other complications. αβT/B-depleted haplo-SCT is a good choice not only for patients unsuitable for PT-CY, but also for all pediatric recipients to reduce SCT-related complications., (© 2024. Japanese Society of Hematology.)- Published
- 2024
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17. Oral cancer and oral potentially malignant disorders in patients with Fanconi anemia - A systematic review.
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Santana NCM, de Sena ACVP, Rocha PADS, de Arruda JAA, Torres-Pereira CC, Abreu LG, Fournier BPJ, Warnakulasuriya S, and Silva TA
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- Female, Humans, Fanconi Anemia complications, Mouth Diseases, Mouth Neoplasms pathology, Precancerous Conditions, Squamous Cell Carcinoma of Head and Neck pathology
- Abstract
The purpose of the present study was to perform a systematic review focusing on oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) in Fanconi anemia (FA) individuals. Electronic searches were undertaken in five databases supplemented by manual scrutiny and gray literature. Case reports and/or cases series were included. The searches yielded 55 studies describing 112 cases of OSCC (n = 107) and/or OPMD (n = 5) in FA individuals. The mean age at diagnosis of OSCC/OPMD was 27.1 (±9.6) years, and females (51.8 %) were slightly more affected. Ulcer (n = 37) or mass (n = 25) were described as clinical presentations for OSCC and OPMD. White lesions (n = 4) were the most common manifestation in OPMD. Tongue (47.2 %) was the most frequent location. Sixty-one (54.5 %) individuals underwent HSCT. Surgical resection (n = 75) was the main treatment adopted. The estimated rate of OPMD malignant transformation was 1.8 % and recurrences following OSCC excision occurred in 26.8 % of individuals. Overall, at 60 months of follow-up, the probability of survival fell to 25.5 % and at 64 months the probability of recurrence increased to 63.2 %. The present data support the need for strict surveillance of patients with FA, even in the absence of OPMD, for early OSCC detection and reduction of mortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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18. Cancer in buccal mucosa in patients with Fanconi anemia: Report of six cases.
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Mattos da Silva PQ, Ballardin BS, and Torres-Pereira CC
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- Humans, Mouth Mucosa, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia therapy, Mouth Neoplasms diagnosis, Carcinoma, Squamous Cell, Hematopoietic Stem Cell Transplantation
- Abstract
Introduction: Fanconi anemia (FA) is a recessive hereditary disease characterized by bone marrow failure, and the treatment is hematopoietic stem cell transplantation (HSCT). Patients diagnosed with FA are more predisposed to develop oral squamous cell carcinoma (SCC), and this risk increases in transplant patients. The clinical characteristics of the oral manifestations of SCC in this group of patients do not differ from the lesions present in patients without the disease; however, they can be diagnosed in young patients and less common locations, such as, for example, in the buccal mucosa., Objective: To report a case series of patients diagnosed with FA with oral SCC., Method: Included in this case series are six patients diagnosed with SCC in the buccal mucosa with similar clinical characteristics., Final Considerations: There are still difficulties in establishing the natural history of oral lesions in patients with FA. Thus, disclosing a series of cases with similar changes may be relevant to improving and refining the multidisciplinary team's clinical view of suspected SCC or oral potentially malignant disorders (OPMD), providing surveillance and timely management., (© 2023 Special Care Dentistry Association and Wiley Periodicals LLC.)
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- 2024
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19. Optimization of radiotherapy in Fanconi anemia-related medulloblastoma.
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Rumley S and Pater L
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- Humans, Antineoplastic Combined Chemotherapy Protocols, Fanconi Anemia complications, Fanconi Anemia radiotherapy, Medulloblastoma radiotherapy, Medulloblastoma drug therapy, Cerebellar Neoplasms radiotherapy, Cerebellar Neoplasms drug therapy, Radiation Oncology
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- 2024
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20. T-cell depleted allogeneic hematopoietic stem cell transplant for the treatment of Fanconi anemia and MDS/AML.
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Satty AM, Klein E, Mauguen A, Kunvarjee B, Boelens JJ, Cancio M, Curran KJ, Kernan NA, Prockop SE, Scaradavou A, Spitzer B, Tamari R, Ruggiero J, Torok-Castanza J, Mehta PA, O'Reilly RJ, and Boulad F
- Subjects
- Humans, Young Adult, Adult, Retrospective Studies, Transplantation, Homologous adverse effects, Transplantation Conditioning methods, T-Lymphocytes, Fanconi Anemia therapy, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute, Graft vs Host Disease etiology
- Abstract
The only curative approach for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) arising in patients with Fanconi anemia (FA) is allogeneic hematopoietic stem cell transplantation (HCT); however, HCT approaches are inconsistent and limited data on outcomes exist. We retrospectively evaluated outcomes of thirty patients with FA and MDS/AML who underwent first allogeneic HCT with a T-cell depleted (TCD) graft at our institution. Patients were transplanted on successive protocols with stepwise changes in cytoreduction and GVHD prophylaxis. All but two patients (93%) experienced durable hematopoietic engraftment. With median follow-up of 8.7 years, 5-year OS was 66.8% and DFS 53.8%. No significant differences in survival were found in patients with high-risk prognostic features (age ≥20 years, AML diagnosis, alternative donor graft) or when stratified by conditioning regimen. The 5-year cumulative incidences of relapse and NRM were 24.3% and 21.9%, respectively. NRM was higher in patients ≥20 years at HCT but did not otherwise differ. We herein demonstrate promising outcomes following allogeneic HCT for patients with FA and MDS/AML using TCD grafts, particularly in a cohort of high-risk patients with 50% ≥20 years and a majority receiving mismatched grafts. Future prospective studies are needed to compare this approach with other HCT platforms., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
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21. Autosomal recessive systemic microangiopathy associated with FANCL Fanconi anaemia.
- Author
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Cousyn L, Demeret S, Philippi A, Bergametti F, Villa C, Morbini P, Riant F, Soulier J, Tournier-Lasserve E, and Denier C
- Subjects
- Humans, Fanconi Anemia Complementation Group L Protein, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2023
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22. Research progress of the Fanconi anemia pathway and premature ovarian insufficiency†.
- Author
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Zhao J, Zhang Y, Li W, Yao M, Liu C, Zhang Z, Wang C, Wang X, and Meng K
- Subjects
- Humans, Female, Adult, DNA Repair genetics, DNA Replication, Ubiquitination, Mutation, DNA Damage, Fanconi Anemia complications, Fanconi Anemia genetics, Fanconi Anemia metabolism
- Abstract
The Fanconi anemia pathway is a key pathway involved in the repair of deoxyribonucleic acidinterstrand crosslinking damage, which chiefly includes the following four modules: lesion recognition, Fanconi anemia core complex recruitment, FANCD2-FANCI complex monoubiquitination, and downstream events (nucleolytic incision, translesion synthesis, and homologous recombination). Mutations or deletions of multiple Fanconi anemia genes in this pathway can damage the interstrand crosslinking repair pathway and disrupt primordial germ cell development and oocyte meiosis, thereby leading to abnormal follicular development. Premature ovarian insufficiency is a gynecological clinical syndrome characterized by amenorrhea and decreased fertility due to decreased oocyte pool, accelerated follicle atresia, and loss of ovarian function in women <40 years old. Furthermore, in recent years, several studies have detected mutations in the Fanconi anemia gene in patients with premature ovarian insufficiency. In addition, some patients with Fanconi anemia exhibit symptoms of premature ovarian insufficiency and infertility. The Fanconi anemia pathway and premature ovarian insufficiency are closely associated., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2023
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23. Gonadal function in pediatric Fanconi anemia patients treated with hematopoietic stem cell transplant.
- Author
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Koo J, Grom-Mansencal I, Howell JC, Rios JM, Mehta PA, Davies SM, and Myers KC
- Subjects
- Humans, Child, Male, Female, Retrospective Studies, Follicle Stimulating Hormone, Fanconi Anemia complications, Fanconi Anemia therapy, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Primary Ovarian Insufficiency etiology, Primary Ovarian Insufficiency diagnosis
- Abstract
Gonadal dysfunction and reduced fertility are clinical manifestations well described in patients with Fanconi anemia (FA) and following hematopoietic stem cell transplantation (HSCT). It is difficult to differentiate gonadal dysfunction from the primary disease itself or from HSCT procedures. Therefore, it is important to manage expectations about gonadal failure and infertility for all patients with FA, regardless of the HSCT status. We performed a retrospective analysis of 98 pediatric patients with FA who were transplanted between July 1990 and June 2020 to evaluate the incidence of gonadal dysfunction in female and male patients with FA. New-onset premature ovarian insufficiency (POI) was diagnosed in a total of 30 (52.6%) patients. Follicle-stimulating hormone and luteinizing hormone levels were increased in patients diagnosed with POI. Anti- Mullerian hormone levels declined in POI patients after HSCT (r2=0.21; P=0.001). Twenty (48.8%) male patients were diagnosed with testicular failure. Follicle-stimulating hormone levels increased after HSCT even in patients without testicular failure (r2=0.17; P=0.005). Inhibin B levels decreased over time after HSCT in patients with testicular failure (r2=0.14; P=0.001). These data indicate brisk decline in already impaired gonadal function in transplanted children with FA.
- Published
- 2023
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24. Exceptional Response to Olaparib: A Case Report of Metastatic Esophageal Squamous Cell Carcinoma in a Patient With Fanconi Anemia, Germline FANCA Mutation, and Somatic BRCA2 Mutations.
- Author
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Haggstrom LR, Tucker K, Williams R, Nelson A, Walsh R, Brungs D, and Aghmesheh M
- Subjects
- Humans, Germ Cells, Mutation, Fanconi Anemia Complementation Group A Protein, BRCA2 Protein genetics, Esophageal Squamous Cell Carcinoma drug therapy, Esophageal Squamous Cell Carcinoma genetics, Fanconi Anemia complications, Fanconi Anemia drug therapy, Fanconi Anemia genetics, Esophageal Neoplasms drug therapy, Esophageal Neoplasms genetics
- Published
- 2023
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- View/download PDF
25. Recurrent Tumefactive Central Nervous System Lesions Due to BRIP1 -Related Fanconi Anemia.
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Nathoo N, Gavrilova RH, Trejo-Lopez JA, McGarrah PW, Go RS, Alqallaf A, and Tobin WO
- Subjects
- Humans, Mutation genetics, Central Nervous System pathology, Fanconi Anemia complications, Fanconi Anemia genetics, Fanconi Anemia pathology
- Abstract
Introduction: Fanconi anemia (FA) is an inherited condition associated with genetic mutations that affect DNA repair proteins. More than 20 genes involved in the FA/BRCA pathway have been implicated in FA, including BRIP1 . Tumefactive brain lesions are rare in FA., Case Report: We describe a patient with FA and recurrent tumefactive brain lesions preceded by calcifications on head computed tomography. A biopsy revealed white-matter gliosis with severe vasculopathy. Whole-genome sequencing demonstrated a BRIP1 homozygous variant with a final diagnosis of recurrent tumefactive brain lesions due to BRIP1 -associated CNS vasculopathy. Immunosuppressive treatment was ineffective in the present case., Conclusions: Mechanistically, the specific role of BRIP1 mutation in CNS inflammation and vasculopathy is unclear. However, immunodeficiency disorders can lead to autoimmunity and/or immune dysregulation due to the possible loss or gain of function of components of the immune system., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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26. Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia.
- Author
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Farkas G, Székely G, Goda V, Kállay KM, Kocsis ZS, Szakszon K, Benyó G, Erdélyi D, Liptai Z, Csordás K, Kertész G, Szegedi I, Kriván G, Takácsi-Nagy Z, Polgár C, and Jurányi Z
- Subjects
- Humans, Chromosome Breakage, Diagnosis, Differential, Mitomycin, Bleomycin, Anemia, Aplastic etiology, Anemia, Aplastic genetics, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics
- Abstract
Background: FA patients are hypersensitive to preconditioning of bone marrow transplantation., Objective: Assessment of the power of mitomycin C (MMC) test to assign FA patients., Methods: We analysed 195 patients with hematological disorders using spontaneous and two types of chromosomal breakage tests (MMC and bleomycin). In case of presumed Ataxia telangiectasia (AT), patients' blood was irradiated in vitro to determine the radiosensitivity of the patients., Results: Seven patients were diagnosed as having FA. The number of spontaneous chromosomal aberrations was significantly higher in FA patients than in aplastic anemia (AA) patients including chromatid breaks, exchanges, total aberrations, aberrant cells. MMC-induced ≥10 break/cell was 83.9 ± 11.4% in FA patients and 1.94 ± 0.41% in AA patients (p < .0001). The difference in bleomycin-induced breaks/cell was also significant: 2.01 ± 0.25 (FA) versus 1.30 ± 0.10 (AA) (p = .019). Seven patients showed increased radiation sensitivity. Both dicentric + ring, and total aberrations were significantly higher at 3 and 6 Gy compared to controls., Conclusions: MMC and Bleomycin tests together proved to be more informative than MMC test alone for the diagnostic classification of AA patients, while in vitro irradiation tests could help detect radiosensitive-as such, individuals with AT., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2023
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27. Successful sequential liver and hematopoietic stem cell transplantation in a patient with Fanconi anemia.
- Author
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Di Stasio F, Bravi M, Bonanomi S, Balduzzi A, Prunotto G, Migliorino GM, Dufour C, D'Antiga L, and Vendemini F
- Subjects
- Child, Infant, Newborn, Humans, Bone Marrow Failure Disorders, Liver, Fanconi Anemia complications, Fanconi Anemia therapy, Hematopoietic Stem Cell Transplantation, Liver Transplantation, Pancytopenia
- Abstract
Background: In Fanconi anemia bone marrow failure is the major cause of morbidity and mortality and hematopoietic stem cell transplantation represents the only curative treatment. Liver disease, in terms of elevated liver function tests, as well as benign and malignant liver tumors, occurs especially in case of androgen treatment. We report a unique case of a child with Fanconi anemia with FANCD2 mutation who developed neonatal cryptogenic liver cirrhosis and bone marrow failure. The child successfully underwent sequential liver transplantation and hematopoietic stem cell transplantation in the first 2 years of life. Nineteen months after hematopoietic stem cell transplantation and 30 months after liver transplantation, the patient is clinically well with normal hematopoietic function and excellent liver function., Conclusion: This is the first FA patient who successfully received sequential LT and HSCT highlighting that successful sequential transplantation is feasible in Fanconi anemia patients., (© 2023 Wiley Periodicals LLC.)
- Published
- 2023
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28. Fanconi Syndrome Associated with Long-term Treatment with Zoledronate.
- Author
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Katsunuma R, Mitsumoto K, Mizumoto A, Hirai Y, Nakauchi C, and Uzu T
- Subjects
- Female, Humans, Aged, 80 and over, Zoledronic Acid adverse effects, Diphosphonates adverse effects, Fanconi Syndrome chemically induced, Fanconi Syndrome diagnosis, Fanconi Syndrome complications, Osteomalacia etiology, Fanconi Anemia complications, Hypophosphatemia diagnosis
- Abstract
Intravenous bisphosphonate therapy is used to prevent fractures in the management of bone metastasis. However, it may induce renal damage. We herein report an 81-year-old woman with Fanconi syndrome and osteomalacia who had been diagnosed with metastatic breast cancer and received treatment with zolendronate for over 5 years. Her bone markers normalized after switching zolendronate to denosmab and starting vitamin D and mineral supplementation. This case shows that chronic renal damage induced by zolendronate can cause osteomalacia. In patients with intravenous zolendronate therapy, close monitoring of renal and bone markers is needed, even under long-term therapy.
- Published
- 2023
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29. Oral Premalignant and Malignant Lesions in Fanconi Anemia Patients.
- Author
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Archibald H, Kalland K, Kuehne A, Ondrey F, Roby B, and Jakubowski L
- Subjects
- Humans, Male, Female, Child, Hematopoietic Stem Cell Transplantation adverse effects, Precancerous Conditions, Retrospective Studies, Cohort Studies, Minnesota epidemiology, Fanconi Anemia complications, Fanconi Anemia epidemiology, Fanconi Anemia surgery, Head and Neck Neoplasms complications, Head and Neck Neoplasms epidemiology
- Abstract
Objective: There is a lack of data supporting cancer surveillance in pediatric Fanconi Anemia patients. We sought to describe the rates of upper aerodigestive lesions and malignancy in this population to augment current management guidelines., Methods: A retrospective cohort study of patients with Fanconi Anemia from a quaternary referral center between 2007-2021 was completed for head and neck cancer risk., Results: One hundred and five FA patients were reviewed. Average age at presentation was 11.3 years old and 90.5% of patients underwent hematopoietic stem cell transplant (HSCT). A total of 8.6% of patients had leukoplakia or erythroplakia and 3.8% developed malignancy. The standardized incidence ratio of head and neck malignancy was 483.8. Patients presented with leukoplakia and malignancy at an average age of 14.6 and 25.1 years old, respectively. Malignancies were aggressive and marked by recurrence. There were no premalignant or malignant lesions found on flexible laryngoscopy. This series represents the largest longitudinal series of pediatric FA head and neck lesions., Conclusions: Fanconi Anemia patients should begin screening for head and neck cancer at age 10 or after HSCT., Level of Evidence: Level 4 Laryngoscope, 133:1745-1748, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)
- Published
- 2023
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30. Fanconi anemia-isogenic head and neck cancer cell line pairs: A basic and translational science resource.
- Author
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Nguyen HT, Tang W, Webster ALH, Whiteaker JR, Chandler CM, Errazquin R, Roohollahi K, Fritzke M, Hoskins EE, Jonlin E, Wakefield L, Sullivan LB, Chen EY, Dorsman J, Brakenhoff R, Paulovich AG, Grompe M, Garcia-Escudero R, Wells SI, Smogorzewska A, and Monnat RJ Jr
- Subjects
- Female, Humans, Squamous Cell Carcinoma of Head and Neck, Translational Science, Biomedical, Cell Line, Tumor, Fanconi Anemia genetics, Fanconi Anemia complications, Fanconi Anemia pathology, Head and Neck Neoplasms genetics, Carcinoma, Squamous Cell genetics
- Abstract
Fanconi anemia (FA) is a heritable malformation, bone marrow failure and cancer predisposition syndrome that confers an exceptionally high risk of squamous carcinomas. These carcinomas originate in epithelia lining the mouth, proximal esophagus, vulva and anus: their origins are not understood, and no effective ways have been identified to prevent or delay their appearance. Many FA-associated carcinomas are also therapeutically challenging: they may be multi-focal and stage-advanced at diagnosis, and most individuals with FA cannot tolerate standard-of-care systemic therapies such as DNA cross-linking drugs or ionizing radiation due to constitutional DNA damage hypersensitivity. We developed the Fanconi Anemia Cancer Cell Line Resource (FA-CCLR) to foster new work on the origins, treatment and prevention of FA-associated carcinomas. The FA-CCLR consists of Fanconi-isogenic head and neck squamous cell carcinoma (HNSCC) cell line pairs generated from five individuals with FA-associated HNSCC, and five individuals with sporadic HNSCC. Sporadic, isogenic HNSCC cell line pairs were generated in parallel with FA patient-derived isogenic cell line pairs to provide comparable experimental material to use to identify cell and molecular phenotypes driven by germline or somatic loss of Fanconi pathway function, and the subset of these FA-dependent phenotypes that can be modified, complemented or suppressed. All 10 FANC-isogenic cell line pairs are available to academic, non-profit and industry investigators via the "Fanconi Anemia Research Materials" Resource and Repository at Oregon Health & Sciences University, Portland OR., (© 2023 UICC.)
- Published
- 2023
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31. Phenotypes of adults with Fanconi anaemia.
- Author
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Wang YM, Loveless M, Miller E, Nelson AS, Mehta PA, Davies SM, and Myers KC
- Subjects
- Male, Female, Humans, Retrospective Studies, Phenotype, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia therapy, Hematopoietic Stem Cell Transplantation methods, Myelodysplastic Syndromes complications
- Abstract
The long-term outcomes of adults with Fanconi anaemia (FA) have improved with advances in haematopoietic stem cell transplantation (HSCT) and more detailed follow-up and screening guidelines. The phenotype of those who survive to adulthood may differ from the typical presentation of FA. We collected retrospective clinical data on adults with FA who received their care at the Cincinnati Children's Hospital Medical Center. In our final cohort of 52 patients, there were 29 females and 23 males, with median (range) age of 21 (18-37) years. Overall, 42 patients (81%) were alive at last follow-up. In all, 36 adults (69%) had undergone HSCT, including eight who had developed myelodysplasia or acute myeloid leukaemia. Eight (15%) developed squamous cell carcinoma. Endocrine complications were common, including hypothyroidism (42%), diabetes (10%), low body mass index (31%) and low bone mineral density (51%). The majority of adults with FA were employed (52%) or full-time students (13%). A significant subset of patients with FA are surviving into adulthood without requiring HSCT. Endocrine abnormalities and the development of solid tumours complicate adulthood. With improved survival outcomes following HSCT and more aggressive malignancy screening protocols, ongoing longitudinal analysis will be important to further characterise this cohort and the phenotype of untransplanted adults with FA., (© 2022 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2023
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32. The First Case of Acute Myeloid Leukemia With Underlying Fanconi Anemia due to FANCF Variants in Korea.
- Author
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Suh E, Shin S, Ju HY, Yoo KH, Kim HY, Cho D, Kim SH, and Kim HJ
- Subjects
- Humans, Republic of Korea, Fanconi Anemia Complementation Group F Protein, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics, Leukemia, Myeloid, Acute complications, Leukemia, Myeloid, Acute diagnosis
- Published
- 2023
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33. Multiple synchronous malignancies in an infant with concomitant homozygous BRCA2 and PMS2 mutations with Fanconi anemia phenotype.
- Author
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Alghanim HM, Eltawel M, Alhaidari AI, Alobaid MM, Moghairi AM, Sufiani F, and Ahmad N
- Subjects
- Humans, BRCA2 Protein genetics, Genetic Predisposition to Disease, Mismatch Repair Endonuclease PMS2 genetics, Mutation, Phenotype, Fanconi Anemia complications, Fanconi Anemia genetics, Kidney Neoplasms genetics, Neoplasms, Multiple Primary genetics, Wilms Tumor complications
- Abstract
Hereditary cancer predisposition accounts for more than 10% of all cancers in pediatric age group and this is increasingly recognized as an important entity because of modern sequencing techniques. We report a rare association of two concurrent cancer predisposition syndromes, BRCA2 and PMS2, in a young child who presented with concurrent malignancies including Wilms tumor, myelodysplastic syndrome and an indeterminate brain lesion who succumbed to his disease. Multiple synchronous malignancies present difficult clinical and psycho-social challenges which need to be carefully addressed in the setting of a multi-disciplinary team approach.
- Published
- 2023
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34. Fanconi anemia-associated signature in cancer.
- Author
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Danovi S
- Subjects
- Humans, Nuclear Proteins, Fanconi Anemia complications, Fanconi Anemia genetics, Neoplasms genetics
- Published
- 2023
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- View/download PDF
35. Two decades of stem cell transplantation in patients with Fanconi anemia: Analysis of factors affecting transplant outcomes.
- Author
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Fink O, Even-Or E, Avni B, Grisariu S, Zaidman I, Schejter YD, NaserEddin A, Najajreh M, and Stepensky P
- Subjects
- Humans, Transplantation, Homologous methods, Tissue Donors, Transplantation Conditioning methods, Fanconi Anemia therapy, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease epidemiology, Bronchiolitis Obliterans Syndrome
- Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for the hematological complications of patients with Fanconi anemia (FA). Over the last two decades, HSCT outcomes have improved dramatically following the development of regimens tailored for FA patients. In this study, we analyzed genetic, clinical, and transplant data of 41 patients with FA who underwent HSCT at Hadassah Medical Center between November 1996 and September 2020. Overall survival (OS) was 82.9% with a median follow-up time of 2.11-years (95% CI, .48-16.56). Thirteen patients (31.7%) developed acute graft-versus-host disease (GVHD), three of them with grades 3-4. Nine patients developed chronic GVHD, five had extensive disease. Twelve patients (29.3%) developed stable mixed-chimerism with complete resolution of bone marrow failure (BMF); none of them had acute nor chronic GVHD. Significantly higher GVHD rates were observed in transplants from peripheral blood stem cell grafts as compared to other stem cell sources (p = .002 for acute and p = .004 for chronic GVHD). Outcome parameters were comparable between HSCT from matched-sibling (n = 20) to other donors (n = 21), including survival rates (p = .1), time to engraftment (p = .69 and p = .14 for neutrophil and platelet engraftment time, respectively), chimerism status (p = .36 and p = .83 for full-donor and mixed chimerism, respectively), and GVHD prevalence (p = 1). Our results demonstrate the vast improvements in HSCT outcomes of patients with FA, narrowing the gap between matched-sibling versus alternative donor transplantations. Our data identifies factors that may significantly affect transplant outcomes such as graft source and chimerism status., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)
- Published
- 2023
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36. Fanconi anemia and haploidentical stem cell transplantation.
- Author
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Medina-Valencia D, Aristizabal AM, Beltran E, and Franco AA
- Subjects
- Child, Cyclophosphamide therapeutic use, Humans, Transplantation Conditioning adverse effects, Fanconi Anemia complications, Fanconi Anemia therapy, Graft vs Host Disease drug therapy, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Background: Fanconi anemia is a congenital disorder belonging to bone marrow syndromes, with a risk of developing malignancy. Hematopoietic stem cell transplantation is the only curative treatment in these cases. Here, we aimed to report our clinical experience in pediatric patients with Fanconi anemia treated with haploidentical stem cell transplantation and post-transplant cyclophosphamide, an alternative strategy., Methods: We performed a case report based on clinical records of two patients who signed the informed consent form and were treated at Fundación Valle del Lili., Result: Two pediatric patients, both with reduced-intensity conditioning, prophylaxis for acute graft-versus-host disease with post-transplant cyclophosphamide. They achieved primary neutrophil/platelets engraftment, and 100% chimerism. Had grade I or II graft-versus-host disease resolved? Currently are alive and in complete remission., Conclusions: The use of mismatched related donors for haploidentical stem cell transplantation and post-transplant cyclophosphamide might be a promising option, and well-tolerated in pediatric patients. Serial chimerism can be useful during follow-up., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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37. Development of a mouse model for spontaneous oral squamous cell carcinoma in Fanconi anemia.
- Author
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Errazquin R, Page A, Suñol A, Segrelles C, Carrasco E, Peral J, Garrido-Aranda A, Del Marro S, Ortiz J, Lorz C, Minguillon J, Surralles J, Belendez C, Alvarez M, Balmaña J, Bravo A, Ramirez A, and Garcia-Escudero R
- Subjects
- Animals, Disease Models, Animal, Keratins, Mice, Mice, Knockout, Squamous Cell Carcinoma of Head and Neck, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell pathology, Fanconi Anemia complications, Fanconi Anemia genetics, Fanconi Anemia pathology, Head and Neck Neoplasms, Mouth Neoplasms genetics
- Abstract
Fanconi anemia (FA) patients frequently develop oral squamous cell carcinoma (OSCC). This cancer in FA patients is diagnosed within the first 3-4 decades of life, very often preceded by lesions that suffer a malignant transformation. In addition, they respond poorly to current treatments due to toxicity or multiple recurrences. Translational research on new chemopreventive agents and therapeutic strategies has been unsuccessful partly due to scarcity of disease models or failure to fully reproduce the disease. Here we report that Fanca gene knockout mice (Fanca
- / - ) frequently display pre-malignant lesions in the oral cavity. Moreover, when these animals were crossed with animals having conditional deletion of Trp53 gene in oral mucosa (K14cre;Trp53F2-10/F2-10 ), they spontaneously developed OSCC with high penetrance and a median latency of less than ten months. Tumors were well differentiated and expressed markers of squamous differentiation, such as keratins K5 and K10. In conclusion, Fanca and Trp53 genes cooperate to suppress oral cancer in mice, and Fanca-/- ;K14cre;Trp53F2-10/F2-10 mice constitute the first animal model of spontaneous OSCC in FA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)- Published
- 2022
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38. Unmanipulated haploidentical haematopoietic cell transplantation with radiation-free conditioning in Fanconi anaemia: A retrospective analysis from the Chinese Blood and Marrow Transplantation Registry Group.
- Author
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Xu L, Lu Y, Hu S, Li C, Tang Y, Wang H, Yan J, Chen J, Liu S, Sun Y, Wu X, Lin F, Lu P, and Huang X
- Subjects
- Humans, Busulfan therapeutic use, Retrospective Studies, Transplantation Conditioning adverse effects, Transplantation Conditioning methods, Bone Marrow, Neoplasm Recurrence, Local drug therapy, Cyclophosphamide therapeutic use, Registries, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Fanconi Anemia therapy, Fanconi Anemia complications, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods
- Abstract
Haematopoietic cell transplantation (HCT) is the only curative treatment for haematological complications in patients with Fanconi anaemia (FA). Haploidentical (haplo-) HCT is a promising alternative for FA. We aimed to analyse the outcomes of unmanipulated haplo-HCT in patients with FA with radiation-free conditioning. A total of 56 patients from 11 centres between 2013 and 2021 in China were retrospectively analysed. The mean (SD) cumulative incidence was 96.4% (0.08%) for 30-day neutrophil engraftment and 85.5% (0.24%) for 100-day platelet engraftment. With a median (range) follow-up of 2.4 (0.2-5.8) years, favourable mean (SD) overall survival of 80.9% (5.5%) and event-free survival of 79.3% (5.6%) were achieved. The mean (SD) incidences of acute graft-versus-host disease (aGvHD) Grade II-IV and Grade III-IV were 55.4% (0.45%) and 42.9 (0.45%) respectively. The mean (SD) cumulative incidence of 3-year chronic graft-versus-host disease (cGvHD) was 34.7% (0.86%) and that of moderate-to-severe cGvHD was 9.0% (0.19%). Our data demonstrate that in unmanipulated haplo-HCT for patients with FA, radiation-free regimens based on fludarabine and low-dose cyclophosphamide ± busulfan achieved favourable engraftment and survival with relatively high incidences of aGvHD and cGvHD. These results prompt the use of low-intensity conditioning without radiation and intensive GvHD prophylaxis when considering unmanipulated haplo-HCT in patients with FA., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)
- Published
- 2022
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39. Cancer in children with biallelic BRCA1 variants and Fanconi anemia-like features: Report of a malignant brain tumor in a young child.
- Author
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Borlin PR, Brazzola P, Frontzek K, Zanoni P, Morscher RJ, Hench J, Frank S, Kottke R, Rushing EJ, Goeggel Simonetti B, Steindl K, and Guerreiro Stucklin AS
- Subjects
- BRCA1 Protein genetics, Child, Genetic Predisposition to Disease, Humans, Mutation, Brain Neoplasms genetics, Fanconi Anemia complications, Fanconi Anemia genetics
- Published
- 2022
- Full Text
- View/download PDF
40. Tongue cancer following hematopoietic cell transplantation for Fanconi anemia.
- Author
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Di Bartolomeo M, Anesi A, Pellacani A, Negrello S, Natale A, Figurelli S, Vaddinelli D, Angelini S, Chiarini L, Nocini R, and Di Bartolomeo P
- Subjects
- Adult, Humans, Retrospective Studies, Fanconi Anemia complications, Fanconi Anemia therapy, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects, Tongue Neoplasms therapy
- Abstract
Objectives: The aim of this retrospective study was to determine the incidence and the clinical outcome of tongue cancer (TC) in patients affected by Fanconi anemia (FA) who received an allogeneic hematopoietic cell transplantation (HCT)., Materials and Methods: The patient database from the Bone Marrow Transplant Center of Pescara was reviewed to enroll FA patients. Patients', donors', HCT's, and screening's data were collected as well to look for the incidence and the treatment of TC., Results: Twelve patients affected by FA were identified. Three patients died for transplant-related causes. Five of nine surviving patients were diagnosed with TC at a median of 21.7 years since transplantation and at a median age of 32.10 years. Interestingly, no patient manifested graft-versus-host-disease (GvHD). The 28-year cumulative incidence function of TC was 46.9% (95% CI, 36.9-56.9%). Two patients were treated with chemotherapy alone, two patients were treated with surgery alone, and one with surgery followed by chemotherapy. Overall, 4 patients with TC showed a clinical course characterized by a marked aggressiveness of the tumor disease which led to death due to cancer progression between 2 and 13 months. One patient is surviving 8 months after diagnosis of TC., Conclusions: Our study confirms the high incidence of tumors and in particular tongue tumors in allotransplanted FA patients. A careful screening has to be life-long maintained., Clinical Relevance: Considering the rarity of FA and the frailty of FA patients, this study may add important information for the cancer management of these patients., (© 2022. The Author(s).)
- Published
- 2022
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41. Characterization of Fanconi Anemia Patients with Head and Neck Squamous Cell Carcinoma: Israel Fanconi Registry.
- Author
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Tsur N, Frig O, Steinberg-Shemer O, Tamary H, Kurman N, Mizrachi A, and Popovtzer A
- Subjects
- Humans, Israel epidemiology, Registries, Squamous Cell Carcinoma of Head and Neck epidemiology, Squamous Cell Carcinoma of Head and Neck therapy, Fanconi Anemia complications, Fanconi Anemia epidemiology, Fanconi Anemia therapy, Head and Neck Neoplasms epidemiology, Head and Neck Neoplasms therapy
- Abstract
Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response., Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry., Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts., Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5-57) months., Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.
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- 2022
42. The incidence and spectrum of congenital hand differences in patients with Fanconi anaemia: analysis of 48 patients.
- Author
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Bourke G, Wilks D, Kinsey S, Feltbower RG, Giri N, and Alter BP
- Subjects
- Humans, Incidence, Thumb abnormalities, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia epidemiology, Hand Deformities
- Abstract
We analysed the spectrum of congenital hand differences in a cohort of patients with Fanconi anaemia (FA). Data of 48 FA patients at the National Cancer Institute were reviewed focusing on age at diagnosis, type and severity of limb difference and any potential association with other known clinical anomalies that are part of the FA phenotype, specifically VACTERL-H and PHENOS. Twenty-eight patients had an upper limb difference, which always included thumb hypoplasia. Twenty-three patients had bilateral upper limb differences, including varying combinations and severities of thumb hypoplasia, radial dysplasia and thumb duplication. Patients with a limb difference were diagnosed at a younger age (<2 years: 15/28 with limb anomaly versus 4/20 without a limb anomaly). However, 7/28 with limb anomalies, usually thumb hypoplasia, were not diagnosed until after 6 years of age. This study demonstrates the broad spectrum of radial ray anomalies within the FA phenotype along with the possibility of either unilateral or bilateral upper limb differences and adds further merit to consideration of screening for FA in all cases of radial ray anomaly. Level of evidence: II.
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- 2022
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43. Microsurgical Head and Neck Reconstruction in Patients With Fanconi Anemia.
- Author
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Wright MA, Kutler DI, Reeve GS, and Spector JA
- Subjects
- Humans, Neck surgery, Neoplasm Recurrence, Local surgery, Retrospective Studies, Fanconi Anemia complications, Fanconi Anemia surgery, Free Tissue Flaps surgery, Head and Neck Neoplasms surgery, Plastic Surgery Procedures adverse effects
- Abstract
Abstract: Patients with Fanconi anemia (FA) are at increased risk for head and neck cancers that often necessitate extensive reconstructions. Such patients have multiple comorbidities including anemia and thrombocytopenia frequently requiring bone marrow transplant, and they are at an increased risk of cancer recurrence and need for further extirpation. in the present study, charts from 3 patients with FA who underwent microvascular free tissue transfer by the senior author were retrospectively reviewed for pertinent pre- and peri-operative details in addition to functional and cosmetic outcomes. Two of these patients ultimately required metachronous free flap reconstructions for recurrence. All patients had acceptable functional and cosmetic outcomes following each instance of free flap reconstruction, thereby demonstrating the utility of microvas- cular free tissue transfer in patients with FA. The authors herein present each patient's clinical history in addition to a discussion of the current literature and an outline of our approach to these challenging cases., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)
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- 2022
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44. [Progress in pathogenesis of bone marrow failure in Fanconi anemia].
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Zhang GG, Zhang R, and Wang TY
- Subjects
- Bone Marrow Failure Disorders, Humans, Fanconi Anemia complications
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- 2022
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45. Fanconi anemia and hematopoietic stem cell transplant as risk factors for oral squamous cell carcinoma: A case report with a 12-year follow-up.
- Author
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Macedo LFDSL, Domaneschi C, Miguita Luiz L, Peres MPSM, and Franco JB
- Subjects
- Follow-Up Studies, Humans, Risk Factors, Squamous Cell Carcinoma of Head and Neck complications, Carcinoma, Squamous Cell therapy, Fanconi Anemia complications, Fanconi Anemia therapy, Head and Neck Neoplasms, Hematopoietic Stem Cell Transplantation adverse effects, Mouth Neoplasms therapy
- Abstract
Fanconi anemia is a rare disorder resulting from defects in genes responsible for DNA damage responses. It is characterized by congenital anomalies, aplastic anemia, and a predisposition to cancer. Currently, hematopoietic stem cell transplant (HSCT) is the only curative treatment available for bone marrow failure; however, HSCT increases oral squamous cell carcinoma (OSCC) risk. Here we report the case of a patient diagnosed with Fanconi anemia in childhood who was treated with HSCT and later diagnosed with multiple OSCCs during a 12-year follow-up. Despite multiple surgical interventions and radiotherapy regimens, the patient`s health deteriorated. Management of individuals with Fanconi anemia is challenging and must be provided by a multidisciplinary healthcare team to ensure better staging, treatment planning, and coordination., (© 2021 Special Care Dentistry Association and Wiley Periodicals LLC.)
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- 2022
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46. Recurrent Sweet syndrome presenting in a figurate pattern in a patient with Fanconi anemia.
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Cerejeira A, Amoedo P, Coelho AR, Silva R, Pedrosa A, Nogueira A, and Azevedo F
- Subjects
- Humans, Fanconi Anemia complications, Fanconi Anemia diagnosis, Sweet Syndrome complications, Sweet Syndrome diagnosis
- Published
- 2022
- Full Text
- View/download PDF
47. Fanconi Anemia Gene Variants in Patients with Gonadal Dysfunction.
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Daum H and Zlotogora J
- Subjects
- DNA Helicases genetics, DNA-Binding Proteins genetics, Humans, Mutation, Phenotype, Azoospermia genetics, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics
- Abstract
Fanconi anemia (FA) is a multisystem disease, characterized by the triad of physical abnormalities, bone marrow failure, and increased risk for malignancy. In the past few years, data has accumulated regarding fertility issues in FA patients, mostly due to gonadal dysfunction, which is prevalent in FA patients reaching puberty. It seems that attenuated FA phenotype lacking the classical manifestations often is presented with POI or azoospermia. Searching the literature, we summarized data regarding FA patients presenting as suffering from sub/infertility due to gonadal dysfunction, with or without other FA symptoms. We present a summary of the patients having biallelic pathogenic variants in FA genes FANCA, FANCM, BRCA2, and XRCC2 that presented with gonadal dysfunction with or without other phenotypic features of FA. Some were in mosaic, while some are considered hypomorphic, enabling residual protein function. There are also a few descriptions of POI associated with monoallelic pathogenic variants in FANCA, BRCA2, and FANCL. We conclude that the diagnosis of FA in gonadal dysfunction patients is of utmost importance due to its actionability. Follow-up strategies in FA patients are designed to discover early stages of leukemias and solid tumors and thus save lives. The feasibility of next-generation sequencing (NGS) can now ease this diagnostic procedure. An open question is the justification of performing NGS for all isolated azoospermia/POI patients., (© 2021. Society for Reproductive Investigation.)
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- 2022
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48. Fanconi anaemia: A syndrome with distinct subgroups.
- Author
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Alter BP, Giri N, McReynolds LJ, and Altintas B
- Subjects
- Adult, Bone Marrow Failure Disorders, Child, Congenital Bone Marrow Failure Syndromes, Female, Humans, Squamous Cell Carcinoma of Head and Neck, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia genetics, Head and Neck Neoplasms, Hematopoietic Stem Cell Transplantation, Leukemia
- Abstract
Fanconi anaemia (FA) is an inherited bone marrow failure syndrome (IBMFS) with a high cancer predisposition rate. Traditional diagnoses are made before age 10 years due to bone marrow failure (BMF) and characteristic birth defects. Up to 10% of published cases were adults at diagnosis. We hypothesized that FA subgroups diagnosed in childhood are distinct from those diagnosed as adults. We classified patients by age at diagnosis of FA as FA-PED (<18 years) or FA-ADULT (≥18 years). The National Cancer Institute IBMFS cohort included 178 FA-PED and 26 FA-ADULT cases. We compared various features; the cumulative incidences of first adverse events (severe BMF leading to haematopoietic cell transplant or death, leukaemia, or solid tumours) were compared using competing-risk analyses. FA-ADULT lacked the 'typical' FA features (birth defects and early-onset BMF or leukaemia), were mainly female, had more patients with FANCA genotype, and had or developed more head and neck squamous-cell carcinoma (HNSCC) and/or gynaecological cancers compared with FA-PED, albeit at similar ages in both subgroups. FA-ADULT is a distinct subgroup that remained unrecognized during childhood. Centres for adult haematology-oncology should consider FA diagnosis in patients with early-onset HNSCC or gynaecological cancer with or without haematologic problems., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2022
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49. Etiologies of hearing loss in Fanconi Anemia.
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Karempelis P, Greenlund L, Gruhl R, Dorrity J, Wagner J, and Roby B
- Subjects
- Audiometry, Pure-Tone, Child, Hearing Loss, Conductive complications, Hearing Loss, Conductive etiology, Humans, Retrospective Studies, Fanconi Anemia complications, Fanconi Anemia diagnosis, Fanconi Anemia therapy, Hearing Loss complications, Hearing Loss etiology, Hearing Loss, Sensorineural etiology
- Abstract
Objectives: We aim to describe types of hearing loss associated with Fanconi anemia patients who underwent a bone marrow transplant (BMT) to identify possible etiologies of hearing loss. Additionally, we hope to investigate hearing loss early in life as a potential predictor of needing a BMT surgery. Fanconi anemia is a rare autosomal recessive disease that is the most common inherited bone marrow failure syndrome, characterized by bone marrow failure and multiple congenital anomalies, including hearing loss. This is the largest study to date reviewing types of hearing loss in patients with Fanconi anemia, specifically in those who have undergone BMTs., Methods: A retrospective chart review of patients diagnosed with Fanconi anemia at a single institution, tertiary, referral-based children's hospital with a bone marrow transplant team specializing in Fanconi anemia was conducted from 4/19/1976 to 10/19/2015. History, physical examination, audiometry, and imaging findings were reviewed in patients with and without history of bone marrow transplant. Patient hearing levels, as measured by pure tone audiometry at 500 Hz, 1, 2, and 4 kHz, were evaluated. Patients were grouped by transplant status and results and were assessed to determine type and degree of hearing loss. Statistical analysis was performed to compare the likelihood of bone marrow transplant procedures in Fanconi anemia patients with normal and abnormal hearing., Results: There were 252 patients with Fanconi anemia identified via diagnosis search in institutional electronic medical records using CPT codes and cross referencing with the Fanconi Anemia database, 58 of whom had available audiometric data. Of the 58 Fanconi anemia patients with available audiograms, 21 (36%) had abnormal audiograms; 37 patients had normal audiograms. Twenty out of 21 (95%) patients who had abnormal audiograms had undergone bone marrow transplants. Thirty-one of 37 (84%) patients with normal audiograms had received bone marrow transplants. Statistical analysis showed that patients with hearing loss were more likely to require a BMT in the future (OR = 3.87, p = 0.05). Of the patients with abnormal audiograms and a bone marrow transplant (n = 20), 14 (70%) had conductive hearing loss, 5 (25%) had mixed hearing loss, and 1 patient (5%) had sensorineural hearing loss. 13 of 20 patients (65%) had bilateral hearing loss and eight of 20 (40%) had unilateral hearing loss. Of those patients with conductive hearing loss (n = 15), the most common etiologies were Eustachian tube dysfunction (47%), external auditory canal stenosis (33%), and abnormal middle ear anatomy (13%)., Conclusions: Hearing loss is a common finding in Fanconi anemia patients who have undergone BMTs with conductive hearing loss being the most common audiologic manifestation in our cohort of patients. This demonstrates the necessity of frequent hearing screenings in this population and close collaboration with audiology throughout patient care. Our study indicates that hearing status early in life may be a predictor of needing a bone marrow transplant in the future. Further studies should explore the long-term impact of BMT surgery on hearing status., (Copyright © 2022 Elsevier B.V. All rights reserved.)
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- 2022
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50. Transplantation for Fanconi anaemia: lessons learned from Brazil.
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Bonfim C, Nichele S, Loth G, Funke VAM, Nabhan SK, Pillonetto DV, Lima ACM, and Pasquini R
- Subjects
- Brazil epidemiology, Humans, Transplantation Conditioning adverse effects, Unrelated Donors, Fanconi Anemia complications, Fanconi Anemia therapy, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Hematopoietic Stem Cell Transplantation adverse effects
- Abstract
Fanconi anaemia is a challenging disease to manage, and haematopoietic stem-cell transplantation (HSCT) is the treatment of choice for the haematological complications related to this disease. Over these past two decades, we have observed a substantial improvement in survival outcomes after matched related and unrelated donor HSCT, even for patients living in low-income and middle-income countries. Long-term overall survival is still suboptimal because of the risk of malignancies and other disease-related complications. For patients without well matched donors, alternative donor transplantation using mismatched related donors is an option but is historically associated with a high incidence of graft failure and graft-versus-host disease (GVHD). Herein we discuss the development of a HSCT programme for Fanconi anaemia in our centre in Curitiba, Brazil. Because ex vivo, T-cell depletion is unavailable in our country, we adapted the haploidentical donor transplantation platform using post-HSCT cyclophosphamide to overcome graft failure and GVHD associated with HLA-mismatched donor transplantation. The withdrawal of pre-HSCT cyclophosphamide reduced the severity of mucositis and did not interfere with engraftment. The addition of serotherapy improved overall survival by decreasing the incidence of severe acute and chronic GVHD. Although we have improved overall survival and expanded access to HSCT for Fanconi anaemia, our patients face many challenges, especially viral reactivation and GVHD disease, that merit attention. We acknowledge that there is a learning curve to adopt the haploidentical approach for Fanconi anaemia to low-resourced settings, and this Brazilian experience might require further modifications along with national and international collaborations to be implemented in other countries., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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