RESUMO
Hematopoietic cell transplantation (HCT) can cure bone marrow failure in patients with Fanconi Anemia (FA), and it is generally accepted that these patients should receive low-intensity conditioning because of the underlying DNA repair defect in their cells. Outcomes for recipients of matched related HCT have generally been favorable, but only a few studies have scrutinized the factors that may affect the eventual outcome of these patients. This retrospective analysis of 94 pediatric patients with FA who underwent related HCT at King Faisal Specialist Hospital & Research Center was carried out to attempt to identify factors that may affect outcome. Results showed overall survival (OS) probabilities of 92.5%, 89%, and 86% at 1, 5, and 10 years, respectively. In univariate analysis, use of higher dose cyclophosphamide (CY) (60 mg/kg) conditioning was associated with a better 10-year OS than lower dose CY (20 mg/kg) conditioning (91% versus 82%, respectively; P = .035), and use of radiation-containing regimens was associated with a significantly lower 10-year OS than nonradiation regimens (76% versus 91%, respectively; P = .005). Of the 4 regimens used in this study, the fludarabine-based regimen was associated with the highest survival (95.2%; P = .034). The use of the higher dose CY (60 mg/kg) was associated with a significantly increased incidence of hemorrhagic cystitis (HC) (20% versus 5.6% respectively; P = .049). Three patients (3%) developed squamous cell carcinoma (2 oropharyngeal and 1 genitourinary), at 9.4, 5.4, and 13.3 years after HCT; 2 of them had radiation-containing conditioning. In conclusion, our data suggest that although using a higher dose CY (60 mg/kg) conditioning regimen may be associated with better survival, it is also associated with a significantly increased risk of HC. The addition of fludarabine to the low-dose CY (20 mg/kg) is associated with the best survival. On the other hand, radiation-containing regimens are associated with significantly lower survival.
Assuntos
Carcinoma de Células Escamosas/patologia , Cistite/patologia , Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas , Hemorragia/patologia , Neoplasias Orofaríngeas/patologia , Condicionamento Pré-Transplante/métodos , Adolescente , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Criança , Pré-Escolar , Ciclofosfamida/efeitos adversos , Cistite/induzido quimicamente , Cistite/imunologia , Cistite/mortalidade , Anemia de Fanconi/imunologia , Anemia de Fanconi/mortalidade , Anemia de Fanconi/patologia , Feminino , Raios gama/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/imunologia , Hemorragia/mortalidade , Teste de Histocompatibilidade , Humanos , Lactente , Masculino , Agonistas Mieloablativos/efeitos adversos , Neoplasias Orofaríngeas/induzido quimicamente , Neoplasias Orofaríngeas/imunologia , Neoplasias Orofaríngeas/mortalidade , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Transplante Homólogo , Doadores não Relacionados , Vidarabina/efeitos adversos , Vidarabina/análogos & derivadosRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children occurring most commonly in the head and neck region. The treatment involves using a multimodality approach including chemotherapy, surgery, and radiation therapy. Survival for patients with localized disease has improved markedly, but the treatment of advanced disease remains a challenge. We report the clinical characteristics and outcome for patients treated at a tertiary care center in Saudi Arabia. METHODS: Patients aged 0-14 years diagnosed with RMS between 2005 and 2018 were included. Statistical analysis was performed using SPSS software. Kaplan-Meier method was used to calculate overall and event free survival. Cox proportional hazards model was used for multivariate analysis. RESULTS: One hundred and twenty-four patients were analyzed. The median age was 5.7 years with male predominance (2.4:1). The most common primary sites were head/neck (30%) and the genitourinary tract (25%). Embryonal RMS was present in 81%; alveolar in 19%. Most patients had intermediate risk disease (60%). The 5-year overall and event free survivals were 64.3% and 53.3%, respectively. Survival was influenced by primary tumor site, histology, and clinical risk group. Unfavorable primary site, high risk stratification, and poor initial response to therapy predicted a poor outcome. CONCLUSION: This study provides an insight on the current management outcomes for our patients with RMS. Cytogenetics and molecular diagnostics need to be incorporated as standard of care in the therapeutic approach of our patients. In addition, there is a need for national collaborative efforts to improve the outcome of RMS in children and adolescents.
Assuntos
Rabdomiossarcoma , Sarcoma , Adolescente , Humanos , Criança , Masculino , Pré-Escolar , Feminino , Estudos Retrospectivos , Centros de Atenção Terciária , Arábia Saudita/epidemiologia , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/terapia , Rabdomiossarcoma/patologiaRESUMO
Low-dose cyclophosphamide (CY) is now considered the backbone of many of the conditioning regimens used in patients with Fanconi anemia undergoing allogeneic stem cell transplantation (SCT). To reduce the risk of rejection and improve results, CY is usually used in combination with other agents/modalities, such as antithymocyte globulin (ATG), busulfan, radiation, and, more recently, fludarabine (Flu). In this study, we used a uniform Flu-based conditioning regimen (ie, CY, Flu, ATG) in 26 pediatric patients with Fanconi anemia undergoing SCT. The median patient age at the time of SCT was 7.8 years, and the stem cell source was an HLA-matched related donor in 19 patients and partially HLA-matched unrelated cord blood in 7 patients. The CY, Flu, ATG regimen was well tolerated overall, with a remarkably low incidence of graft-versus-host disease and hemorrhagic cystitis. All 19 patients in the matched related donor group engrafted and were alive and transfusion-independent at a median follow-up time of 19 months, compared with only 2 of 7 patients in the unrelated cord blood group. We conclude that the combination of CY, Flu, and ATG in the doses used in this study is well tolerated, and that the proclaimed positive effect of adding Flu to the conditioning regimens of patients with Fanconi anemia undergoing SCT is most pronounced in recipients of HLA-matched related transplants. Its value in unrelated cord blood transplantation probably depends on other factors, such as the degree of HLA matching and the cell dose.