RESUMO
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important therapeutic option for patients with hematologic malignancies. However, the development of graft-versus-host disease (GVHD) after allo-HSCT remains a challenge. Although systemic steroid therapy is the established first-line therapy for acute GVHD (aGVHD) and chronic GVHD (cGVHD), many patients are unresponsive or resistant to corticosteroid therapy, and the response is insufficient. This study aimed to evaluate the clinical characteristics of patients who developed aGVHD and cGVHD after allo-HSCT. This noninterventional, retrospective study used large national registry data from the Transplant Registry Unified Management Program. The study included 29,690 patients with a hematologic disease who underwent their first allo-HSCT between January 2010 and December 2019. The primary study endpoints were the cumulative incidence of aGVHD and cGVHD. The secondary endpoints were overall survival (OS) and nonrelapse mortality (NRM) of patients with aGVHD and cGVHD and OS and NRM of patients who received second-line therapy for aGVHD. Of 29,690 patients who underwent allo-HSCT, the graft source was related bone marrow (RBM) in 2807, related peripheral blood (RPB) in 6167, unrelated bone marrow in 10,556, unrelated peripheral blood (UPB) in 774, and unrelated cord blood in 9339. The cumulative incidence of grade II-IV aGVHD at 100 days was high after the related and unrelated mismatched transplantation. The response rates for first- and second-line therapy for aGVHD were low in the RBM/RPB-mismatched (59.6%/61.6%) and UPB-mismatched subgroups (45.5%), respectively. The 3-year NRM in patients with aGVHD was high in the RPB and UPB mismatched subgroups (37.9% and 31.2%, respectively). Developing a novel treatment for steroid-refractory aGVHD is necessary to improve transplantation outcomes, particularly for patients undergoing HLA-mismatched allo-HSCT.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Sistema de Registros , Transplante Homólogo , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Japão/epidemiologia , Adolescente , Transplante Homólogo/efeitos adversos , Adulto Jovem , Criança , Idoso , Pré-Escolar , Resultado do Tratamento , LactenteRESUMO
In this retrospective, real-world study, we used medical claims data to evaluate the incidence of thromboembolic events (TEs), time to TE, associated risk factors, and health-care resource utilization (HRU) in Japanese patients with polycythemia vera (PV; N = 606) from April 1, 2008, to August 31, 2015. Baseline characteristics of interest included median age, 67.0 years; previous TEs, 11.6%; cardiovascular conditions (CVCs), 45.7%; and ≥ 3 risk factors, 17.8%. Overall, 100 patients experienced TEs (118 events) at a rate of 8.15/100 person-years [TE-free survival rate, 69.3% (2008-2015)]. The annual total health-care costs [mean (per person)] were significantly impacted by the presence of TEs (yes vs. no: ¥993,000 vs ¥459,000; P < 0.001). These results confirm that the presence of CVCs increases the risk of TEs in Japanese patients with PV; occurrence of TEs was associated with a higher HRU in these patients.
Assuntos
Recursos em Saúde/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Policitemia Vera/complicações , Policitemia Vera/terapia , Tromboembolia/epidemiologia , Tromboembolia/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Doenças Cardiovasculares/epidemiologia , Comorbidade , Análise de Dados , Feminino , Custos de Cuidados de Saúde , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Policitemia Vera/economia , Policitemia Vera/epidemiologia , Estudos Retrospectivos , Risco , Fatores de Risco , Tromboembolia/economia , Adulto JovemRESUMO
We performed the quantitative analysis of chondroitin sulfate (CS) obtained from raw materials and various pharmaceutical preparations. To quantify CS content in raw materials and in an ophthalmic solution, each test sample and the authentic CS were first digested by chondroitinase ABC. The CS disaccharides produced were analyzed by strong anion-exchange high-performance liquid chromatography (SAX-HPLC) and CS content was quantified by calculating the total peak areas of the disaccharides derived from a CS calibration curve. In the case of soft capsules, CS was first extracted with hexane followed by phenol-chloroform to remove oil and protein ingredients. The extracted CS samples were depolymerized by chondroitinase ABC and CS content was determined. Quantitative analysis of the disaccharides derived from raw materials and an ophthalmic solution showed the CS contents (%) were 39.5+/-0.1 to 105.6+/-0.1 and 103.3+/-1.2, respectively. In case of CS analysis in soft capsules and liquid preparations, the overall recovery (%) of the spiked CS was 96.79+/-0.53-103.54+/-1.78 and 97.10+/-1.82 to 103.17+/-2.34, respectively. In conclusion, the quantitative analysis of the disaccharides produced by enzymatic digestion can be used in the direct quantitation of CS containing pharmaceutical formulations.