RESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas , Anemia de Fanconi , Trasplante de Células Madre Hematopoyéticas , Neoplasias de la Boca , Humanos , Anemia de Fanconi/complicaciones , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Neoplasias de la Boca/diagnóstico , Mucosa BucalRESUMEN
Fanconi anemia (FA) has long been considered a severe inherited bone marrow failure (BMF) disorder of early childhood. Thus, management of this multisystem disorder has previously been unfamiliar to many hematologists specializing in the care of adolescents and young adults (AYA). The increased diagnosis of FA in AYA patients, facilitated by widely available germline genomic testing, improved long-term survival of children with FA following matched sibling and alternative donor hematopoietic stem cell transplantation (HSCT) performed for BMF, and expanding need in the near future for long-term monitoring in patients achieving hematologic stabilization following ex vivo gene therapy are all reasons why management of FA in AYA populations deserves specific consideration. In this review, we address the unique challenges and evidence-based practice recommendations for the management of AYA patients with FA. Specific topics addressed include hematologic monitoring in AYA patients yet to undergo HSCT, management of myeloid malignancies occurring in FA, diagnosis and management of nonhematologic malignances and organ dysfunction in AYA patients with FA, and evolving considerations for the long-term monitoring of patients with FA undergoing gene therapy.
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Anemia de Fanconi , Trasplante de Células Madre Hematopoyéticas , Adolescente , Humanos , Adulto Joven , Trastornos de Fallo de la Médula Ósea , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/genética , Anemia de Fanconi/terapia , Terapia GenéticaRESUMEN
OBJECTIVE: The aim of this study was to elaborate a specific protocol for the assessment and early identification of skin lesions in pediatric patients with Fanconi anemia undergoing hematopoietic stem cell transplantation. METHODS: This is a longitudinal, retrospective, and descriptive study. The medical records of 136 pediatric patients with Fanconi anemia who underwent hematopoietic stem cell transplantation between 2008 and 2018 at the Clinical Hospital of the Federal University of Paraná were reviewed. A specific protocol was created for data collection, which included age, sex, skin color, age at diagnosis of Fanconi anemia, transplantation data, family history of consanguinity, and pre- and post-transplant complications. In addition, the data included the presence of graft-versus-host disease of the skin and other organs, its classification, type of lesion, location, and also skin lesions not related to graft-versus-host disease. RESULTS: Among the skin manifestations in pre-transplant period, café-au-lait spots stood out (32.4%). At least one organ was affected by graft-versus-host disease in 55.1% of patients; the most common involvement being the mouth, followed by the skin. Rash and erythema were the most frequently observed cutaneous manifestations of graft-versus-host disease. CONCLUSION: A high prevalence of cutaneous manifestations of the disease was observed, as well as cutaneous manifestations of graft-versus-host disease. The protocol developed gathers relevant and standardized information for the follow-up of patients with Fanconi anemia undergoing hematopoietic stem cell transplantation, ensuring greater reliability of the information, and its implementation will allow the prospective evaluation of patients.
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Anemia de Fanconi , Enfermedad Injerto contra Huésped , Niño , Humanos , Anemia de Fanconi/terapia , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/patología , Estudios Retrospectivos , Reproducibilidad de los Resultados , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/patología , EritemaRESUMEN
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.
Asunto(s)
Anemia de Fanconi , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Niño , Ciclofosfamida/uso terapéutico , Anemia de Fanconi/complicaciones , Anemia de Fanconi/terapia , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Acondicionamiento Pretrasplante/efectos adversosRESUMEN
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.
Asunto(s)
Anemia de Fanconi , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Brasil/epidemiología , Anemia de Fanconi/complicaciones , Anemia de Fanconi/terapia , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Acondicionamiento Pretrasplante/efectos adversos , Donante no EmparentadoRESUMEN
Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for a variety of hematological diseases. Allogenic HSCT requires hematopoietic stem cells (HSCs) from matched donors and comes with cytotoxicity and mortality. Recent advances in genome modification of HSCs have demonstrated the possibility of using autologous HSCT-based gene therapy to alleviate hematologic symptoms in monogenic diseases, such as the inherited bone marrow failure (BMF) syndrome Fanconi anemia (FA). However, for FA and other BMF syndromes, insufficient HSC numbers with functional defects results in delayed hematopoietic recovery and increased risk of graft failure. We and others previously identified the adaptor protein LNK (SH2B3) as a critical negative regulator of murine HSC homeostasis. However, whether LNK controls human HSCs has not been studied. Here, we demonstrate that depletion of LNK via lentiviral expression of miR30-based short hairpin RNAs results in robust expansion of transplantable human HSCs that provided balanced multilineage reconstitution in primary and secondary mouse recipients. Importantly, LNK depletion enhances cytokine-mediated JAK/STAT activation in CD34+ hematopoietic stem and progenitor cells (HSPCs). Moreover, we demonstrate that LNK depletion expands primary HSPCs associated with FA. In xenotransplant, engraftment of FANCD2-depleted FA-like HSCs was markedly improved by LNK inhibition. Finally, targeting LNK in primary bone marrow HSPCs from FA patients enhanced their colony forming potential in vitro. Together, these results demonstrate the potential of targeting LNK to expand HSCs to improve HSCT and HSCT-based gene therapy.
Asunto(s)
Anemia de Fanconi , Trasplante de Células Madre Hematopoyéticas , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Antígenos CD34/metabolismo , Anemia de Fanconi/genética , Anemia de Fanconi/metabolismo , Anemia de Fanconi/terapia , Terapia Genética/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Células Madre Hematopoyéticas/metabolismo , Humanos , RatonesRESUMEN
Fanconi anemia (FA) is a rare disease characterized by progressive bone marrow failure, cancer predisposition, and multiple systemic malformations, including congenital abnormalities of the kidney and urinary tract (CAKUT). Hematopoietic cell transplantation (HCT), the only potentially curative treatment for the hematological complications of FA, may precipitate acute kidney injury (AKI) and hypertension. We retrospectively investigated 107 FA patients who underwent HCT between 2009 and 2017. We investigated the incidence and risk factors of AKI within 100 days after HCT in a cohort of FA patients, and kidney function and hypertension over 2-year follow-up.The incidence of AKI (mainly stage I) was 18.7%. Patients aged ≥ 11 years at transplantation showed a higher risk of AKI (OR 3.53). The eGFR was 60-90 mL/min/1.73 m2 in 53 (49.5%), 55 (51.4%), 50 (50.5%), 50 (51%), and 46 (59.7%) patients before HCT, at 100 days, 6 months, 1 year, and 2 years. Within the first 100 days after HCT, hypertension was observed in 72% of the patients and was associated with cyclosporine therapy. Most (62.3%) patients had stage 2 hypertension. CAKUT was observed in 33.7% of the patients and was associated with both hypertension (86%) and diminished kidney function but not with AKI.Conlusion: Although AKI, a commonly known HCT complication, was mild in this study, the prevalence of chronic kidney disease (CKD), as well as the high incidence of hypertension, specially associated with CAKUT point out the importance of kidney care in short and long-term follow up of FA patients. What is Known: ⢠Fanconi anemia (FA) is the most frequent inherited bone marrow failure in children, and 30% of cases have congenital anomalies of kidney (CAKUT). ⢠Acute kidney injury and hypertension after hematopoietic cell transplantation (HCT) may impact the outcomes.. What is New: ⢠Despite the presence of CAKUT and stage 2 CKD in 33.7% and 50% of the patients, respectively, AKI was mild and transitory after HCT in FA patients. ⢠CAKUT in FA patients was associated with lower kidney function and hypertension after HCT.
Asunto(s)
Lesión Renal Aguda , Anemia de Fanconi , Trasplante de Células Madre Hematopoyéticas , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Niño , Anemia de Fanconi/complicaciones , Anemia de Fanconi/epidemiología , Anemia de Fanconi/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Riñón , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Carcinoma de Células Escamosas , Anemia de Fanconi , Neoplasias de Cabeza y Cuello , Trasplante de Células Madre Hematopoyéticas , Neoplasias de la Boca , Carcinoma de Células Escamosas/terapia , Anemia de Fanconi/complicaciones , Anemia de Fanconi/terapia , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Neoplasias de la Boca/terapia , Factores de Riesgo , Carcinoma de Células Escamosas de Cabeza y Cuello/complicacionesRESUMEN
OBJECTIVES: To describe the prevalence of acquired ocular manifestations in patients with Fanconi anemia (FA) and to describe and correlate the congenital ocular malformations with the genetic subtypes of the disease. STUDY DESIGN: This is a cross-sectional observational study of 106 consecutive patients with confirmed diagnosis of FA who were followed at the Hematopoietic Stem Cell Transplantation (HSCT) Service at the Federal University of Paraná, Curitiba, Parana, Brazil. Participants underwent a complete ophthalmologic evaluation and 84 patients underwent ocular ultrasound examination. This study was conducted between November 2014 and August 2017. RESULTS: The patients ranged in age from 6 months to 43 years of age. Microphthalmia was the most common congenital ocular abnormality (95.2%). A decrease in anthropometric measurements was observed, including palpebral fissure length (78/103 patients [76.5%]), microcornea (48/103 patients [46.6%]), and ptosis (31/103 patients [30.1%]). We identified a new ophthalmic condition in 15 patients with FA, that is, epiretinal tissue on the optic disc. The genetic subtype was identified in 78 patients (79.6%), the FA-A subtype was most prevalent (50%). The most common acquired ocular manifestation (non-graft-versus-host disease [GVHD] related) in patients who did not undergo HSCT (n = 44) was limbal neovascularization (13.6%), whereas in patients who underwent HSCT (n = 62), the GVHD-related manifestation was ocular GVHD (51.6%). The most frequent symptom of ocular GVHD was keratoconjunctivitis sicca (29%). CONCLUSIONS: Several ocular manifestations were identified in patients with FA.
Asunto(s)
Enfermedades de la Córnea , Anemia de Fanconi , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Estudios Transversales , Anemia de Fanconi/complicaciones , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/epidemiología , HumanosAsunto(s)
Enfermedades del Sistema Endocrino/etiología , Enfermedades del Sistema Endocrino/historia , Anemia de Fanconi/complicaciones , Anemia de Fanconi/historia , Niño , Enfermedades del Sistema Endocrino/diagnóstico , Enfermedades del Sistema Endocrino/terapia , Anemia de Fanconi/diagnóstico , Anemia de Fanconi/terapia , Historia del Siglo XX , Historia del Siglo XXI , HumanosRESUMEN
Systemic medications categorized as diphenylhydantoin, calcineurin inhibitor and calcium channel blocker may have effects on the oral cavity by modifying the inflammatory and immune response and causing undesired tissue proliferative reactions. Calcineurin inhibitors are medications commonly used for long periods in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) and solid organ transplantation. Medication-related fibrovascular hyperplasia (MRFH) is an extra gingival hyperplastic nodular growth associated with medications use. This study reports five cases of pediatric patients (6 to 12-years-old) diagnosed with Fanconi anemia (FA) after HSCT who presented similar oral mucosal lesions associated with the use of cyclosporine, phenobarbital and amlodipine. After excision of the lesions, histopathological analysis described them as pyogenic granuloma (PG). As the aetiology of the lesions manifested by the patients was associated with the use of medications, the final diagnosis was MRFH. Despite the clinical and histopathological similarity between PG and MRFH, it is fundamental to know the aetiological agent for achieving definitive diagnosis and correct management. Considering the etiologic agent (medication) and histopathological findings, it is suggested that the most appropriate term for this manifestation should be "medication-related fibrovascular hyperplasia". The correct nomenclature related to extra gingival hyperplastic lesions identified in patients on medications with potential to induce hyperplastic reactions should be adopted to facilitate scientific communication and improve the treatment.
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Bloqueadores de los Canales de Calcio/efectos adversos , Anemia de Fanconi/terapia , Granuloma Piogénico/inducido químicamente , Trasplante de Células Madre Hematopoyéticas , Inmunosupresores/efectos adversos , Enfermedades de la Boca/inducido químicamente , Amlodipino/efectos adversos , Niño , Ciclosporina/efectos adversos , Femenino , Humanos , Hiperplasia/inducido químicamente , Masculino , Fenobarbital/efectos adversosRESUMEN
Fanconi anemia (FA) is a rare genetic disease characterized by chromosomal instability and impaired DNA damage repair. FA patients develop oral squamous cell carcinoma (OSCC) earlier and more frequently than the general population, especially after hematopoietic stem cell transplantation (HSCT). Although evidence of an etiological role of the local microbiome and carcinogenesis has been mounting, no information exists regarding the oral microbiome of FA patients. The aim of this study was to explore the salivary microbiome of 61 FA patients regarding their oral health status and OSCC risk factors. After answering a questionnaire and receiving clinical examination, saliva samples were collected and analyzed using 16S rRNA sequencing of the V3-V4 hypervariable region. The microbial profiles associated with medical and clinical parameters were analyzed using general linear models. Patients were young (mean age, 22 y) and most had received HSCT ( n = 53). The most abundant phyla were Firmicutes [mean relative abundance (SD), 42.1% (10.1%)] and Bacteroidetes [(25.4% (11.4%)]. A history of graft-versus-host disease (GVHD) ( n = 27) was associated with higher proportions of Firmicutes (43.8% × 38.5%, P = 0.05). High levels of gingival bleeding were associated with the genera Prevotella (22.25% × 20%), Streptococcus (19.83% × 17.61%), Porphyromonas (3.63% × 1.42%, P = 0.03), Treponema (1.02% × 0.28%, P = 0.009), Parvimonas (0.28% × 0.07%, P = 0.02) and Dialister (0.27% × 0.10%, P = 0.04). Finally, participants transplanted over 11 y ago showed the highest levels of Streptococcus (18.4%), Haemophilus (12.7%) and Neisseria (6.8%). In conclusion, FA patients that showed poor oral hygiene harbored higher proportions of the genera of bacteria compatible with gingival disease. Specific microbial differences were associated with a history of oral GVHD and a history of oral mucositis.
Asunto(s)
Carcinoma de Células Escamosas/microbiología , Anemia de Fanconi/complicaciones , Microbiota , Neoplasias de la Boca/microbiología , Saliva/microbiología , Factores de Edad , Anemia de Fanconi/terapia , Femenino , Hemorragia Gingival/microbiología , Enfermedad Injerto contra Huésped/microbiología , Trasplante de Células Madre Hematopoyéticas , Humanos , Masculino , Mucositis/microbiología , Higiene Bucal , Factores de Riesgo , Adulto JovenRESUMEN
Fanconi Anemia patients are a high risk group for solid and hematologic malignancies. The risk seems to be influenced by age, chronic graft versus host disease and immunosuppressive drug regimens. Reports of oral malignant transformation in Fanconi Anemia after hematopoietic stem cell transplantation (HSCT) are increasing probably because of longer survival rates. This is the report of an 18- and her 28-year old sister who developed a post-HSCT oral squamous cell carcinoma. There were significant differences regarding time to malignant transformation, marrow donor characteristics and graft versus host disease evolution and treatment. The report reinforce the need for a routine head and neck screening for cancer in this particular syndrome and suggest that familial history should also be considered in Fanconi anemia patients at risk for oral malignancy after HSCT.
Asunto(s)
Trasplante de Médula Ósea , Carcinoma de Células Escamosas/diagnóstico , Anemia de Fanconi/terapia , Neoplasias de la Boca/diagnóstico , Hermanos , Adolescente , Adulto , Carcinoma de Células Escamosas/complicaciones , Anemia de Fanconi/complicaciones , Femenino , Humanos , Neoplasias de la Boca/complicacionesRESUMEN
In total, 17 pediatric patients with hematologic malignancies (n=14) and Fanconi anemia (FA) (n=3) underwent haploidentical SCT with T-cell depletion. The patients were conditioned with reduced-intensity regimens, and CYA was used for GVHD prophylaxis. Successful engraftment occurred in 16 patients (94%). One patient failed to achieve a primary engraftment. Another patient rejected the first SCT after 10 weeks and had a successful second transplant. Of all engrafted patients, only one developed severe acute GVHD. Ten patients were alive at a median follow-up of 18 months (range, 5-62 months). The 5-years' OS was 53.8%. The three patients with FA are currently well with full-donor chimerism at 16, 6 and 5 months post transplant, respectively. The OS of 14 patients with high-risk hematologic malignancies was 47.6%. Three patients died as a result of post transplant leukemia relapse. CMV infection, GVHD and organ injury were other causes of mortality. Haploidentical SCT was found to be an alternative feasible treatment in Uruguay for patients who need allogenic transplantation but lack an HLA-identical family donor. It should be considered as an early option in FA patients before transformation or significant exposure to blood products.
Asunto(s)
Anemia de Fanconi/terapia , Neoplasias Hematológicas/terapia , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anemia Aplásica/terapia , Niño , Preescolar , Infecciones por Citomegalovirus/etiología , Anemia de Fanconi/complicaciones , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/prevención & control , Antígenos HLA/inmunología , Neoplasias Hematológicas/mortalidad , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Quimera por Trasplante , Acondicionamiento Pretrasplante/efectos adversos , Trasplante Homólogo , Resultado del Tratamiento , Uruguay/epidemiologíaRESUMEN
A 14-year-old girl with Fanconi anemia was submitted to allogeneic hematopoietic stem cell transplantation. After 17 days she developed hemorrhagic cystitis due to polyoma BK virus (BKV), confirmed by PCR (polymerase chain reaction). Two weeks after the appearance of the urinary symptoms the patient presented numerous papules and vesicles on both hands and feet. PCR of the skin lesions and plasma was positive for BKV. The relationship of BKV with frequent infections in immunocompromised patients is well established. The positive PCR of vesicular fluid suggests that this was the causative agent of the skin lesion in this case. There are no reports of skin lesions with positive PCR for BKV.
Asunto(s)
Virus BK/aislamiento & purificación , Cistitis/virología , Anemia de Fanconi/virología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Infecciones Tumorales por Virus/diagnóstico , Adolescente , Antivirales/uso terapéutico , Virus BK/efectos de los fármacos , Cidofovir , Cistitis/tratamiento farmacológico , Citosina/análogos & derivados , Citosina/uso terapéutico , Anemia de Fanconi/terapia , Femenino , Hemorragia/virología , Humanos , Organofosfonatos/uso terapéutico , Reacción en Cadena de la Polimerasa , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/tratamiento farmacológico , Resultado del Tratamiento , Infecciones Tumorales por Virus/sangre , Infecciones Tumorales por Virus/tratamiento farmacológicoRESUMEN
BACKGROUND: Fanconi's anemia (FA) is a rare recessive genetic disorder characterized by bone marrow failure, developmental and congenital abnormalities, which frequently evolves to aplastic anemia and neoplasias, primarily acute leukemia and head-neck carcinomas. Risk of malignancies increases after hematopoietic stem cell transplantation (HSCT), and the role of human papillomavirus (HPV) in FA carcinogenesis have been proposed. OBJECTIVE: To investigate prevalence of oral HPV in FA patients without oral malignant lesions. MATERIALS AND METHODS: After oral examination, 76 subjects without detectable oral malignant lesions were included and classified in four groups: 20 FA submitted to HSCT (I), 22 FA not submitted to HSCT (II), 18 severe aplastic anemia (SAA) submitted to HSCT (III) and 16 healthy subjects (IV). Liquid-based cytology sampling, HPV screening by polymerase chain reaction and genotyping by reverse hybridization were performed. RESULTS: The HPV detection rates were: group I 35%, group II 27.3%, group III 38% and group IV 6.25%. Prevalence of high risk HPV types, mainly HPV16, was detected. Compared with control group, suggestions for increased likelihood of being HPV infected in SAA (OR = 9.55, 95% CI: 1.01-125.41) and FA patients submitted to HSCT (OR = 8.08, 0.83-72.29) emerged. CONCLUSION: Patients without oral malignant lesions submitted to HSCT, have high prevalence of oral HPV. HPV screening and close follow up should be considered in these patients.
Asunto(s)
Alphapapillomavirus/clasificación , Anemia de Fanconi/complicaciones , Enfermedades de la Boca/virología , Infecciones por Papillomavirus/complicaciones , Adolescente , Adulto , Anemia Aplásica/terapia , Niño , Preescolar , ADN Viral/análisis , Anemia de Fanconi/terapia , Femenino , Estudios de Seguimiento , Técnicas de Genotipaje , Trasplante de Células Madre Hematopoyéticas , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/aislamiento & purificación , Papillomavirus Humano 6/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
A 38-year-old female of African-Caribbean origin presented with symptomatic anemia and was found to have hypoplastic thumbs and patchy hypopigmentation. Peripheral blood examination revealed pancytopenia and the bone marrow biopsy confirmed marrow hypoplasia. Fanconi anemia was later confirmed by flow cytometry and diepoxybutane testing. Treatment was limited to transfusions after development of toxicity with cyclosporine and androgen therapy. She manifested classical features of transfusion-related hemosiderosis and died 12 years after initial presentation.
Asunto(s)
Anemia de Fanconi/diagnóstico , Adulto , Edad de Inicio , Transfusión Sanguínea , Anemia de Fanconi/epidemiología , Anemia de Fanconi/terapia , Femenino , Humanos , Quelantes del Hierro/uso terapéutico , Jamaica , Pulgar/anomalíasRESUMEN
Related to the underlying DNA repair defect that is the hallmark of Fanconi anemia (FA), preparatory regimen-related toxicities have been obstacles to hematopoietic cell transplantation (HCT). In an attempt to decrease the risk and severity of regimen-related toxicities, nonirradiation regimens have been explored. The aim of this study is to compare outcomes after irradiation and nonirradiation regimens in 148 FA patients and identify risk factors impacting upon HCT outcomes. Hematopoietic recovery, acute and chronic graft-versus-host disease (aGVHD, GVHD), and mortality were similar after irradiation and nonirradiation regimens. In both groups of recipients aged >10 years, prior use of androgens and cytomegalovirus seropositivity in either the donor or recipient were associated with higher mortality. With median follow-ups >5 years, the 5-year probability of overall survival, adjusted for factors impacting overall mortality was 78% and 81% after irradiation and nonirradiation regimens, P = .61. In view of the high risk of cancer and other radiation-related effects on growth and development, these results support the use of nonirradiation preparatory regimens. As the peak time for developing solid tumors after HCT is 8 to 9 years, longer follow-up is required before definitive statements can be made regarding the impact of nonirradiation regimens on cancer risk.