The long-term efficacy in blood transfusions,hematologic parameter changes,and complications after splenectomy in patients with transfusion-dependent thalassemia

BackgroundA splenectomy can reduce transfusion requirements in patients with thalassemia. However, the role of a splenectomy remains controversial because its efficacy has not yet been fully determined and there are concerns over potential complications. The purpose of this study was to assess the efficacy, potential changes in hematologic parameters, and any complications associated with splenectomy.MethodsMedical records of 50 patients with transfusion-dependent thalassemia (TDT) who had undergone a splenectomy, along with those of 20 control subjects with intact spleens, were retrospectively reviewed.ResultsThe primary outcomes indicate the efficacy of a splenectomy in reducing red cell transfusions. Fifty TDT post-splenectomy patients were included in this study, of which 28 (56%) were female. The median age of all patients was 20.5 (18–28 years of age). Twenty-seven patients (54%) transformed from TDT to non-transfusion-dependent thalassemia (NTDT) after the splenectomy; 100% with Hb H disease, 58.3% with beta-thalassemia/Hb E disease, and 23.5% with homozygous beta-thalassemia. According to multivariable logistic regression analysis, Hb H disease (adjusted OR 55.23, 95% CI 1.35–22.8.10) and receiving a splenectomy at > ten years of age (adjusted OR 25.36, 95% CI 1.62–396.47) were associated with higher responses. The prevalence of pulmonary hypertension and thromboembolic events were similar between the splenectomy patients and non-splenectomy patients.ConclusionSplenectomy reduced transfusion requirements in TDT patients. The predictive factors as a response to a splenectomy included Hb H disease amongthose receiving a splenectomy at > ten years of age.     

输血依赖型 β地中海贫血小儿铁代谢与心肾功能的关系分析

目的 分析输血依赖型β地中海贫血小儿铁代谢与心肾功能的关系.方法 选取2014年2月至2019年2月海口市第三人民医院收治的108例输血依赖型β地中海贫血病儿,并于同时间段向社会招募96例健康小儿,分别记为研究组和正常组.检测并对比两组铁代谢指标、心功能指标及肾功能指标,采用Pearson相关性分析法分析研究组小儿铁代谢分别与心功能及肾功能的关系.结果 两组血清铁(SI)、血清铁蛋白(SF)、总铁结合力(TIBC)指标均差异有统计学意义(P<0.05),且研究组各指标均明显高于正常组[(18.36±3.59)μmol/L比(12.44±2.17)μmol/L、(271.41±57.35)μg/L比(112.24±18.36)μg/L、(94.62±15.63)μmol/L比(62.18±9.74)μmol/L];研究组左心室射血分数(LVEF)指标显著低于正常组(P<0.05)[(47.32±5.56)％比(54.28±6.89)％]、研究组左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)指标均显著高于正常组(P<0.05)[(52.64±5.91)mm比(47.42±4.36)mm、(38.28±4.69)mm比(33.45±4.13)mm];两组尿微量白蛋白(mAlb)、β2-微球蛋白(β2-MG)、N-乙酰-β-D-氨基葡萄糖苷酶(UN?AG)均差异有统计学意义(P<0.05),且研究组均明显高于正常组[(21.31±3.93)mg/d比(16.47±3.27)mg/d、(181.31±27.62)μg/L比(173.44±25.13)μg/L、(11.58±2.42)U/L比(8.84±1.23)U/L];研究组中铁代谢指标SI、SF、TIBC与LVEF指标呈负相关,与LVEDD、LVESD、mAlb、β2-MG、UNAG均呈正相关.结论 输血依赖型β地中海贫血小儿铁代谢指标SI、SF、TIBC、心功能指标LVEF、LVEDD、LVESD及肾功能指标mAlb、β2-MG、UNAG均存在异常.铁代谢与心功能、肾功能均存在相关性.     

Survival of Thalassemic Patients Referred to the Boo Ali Sina Teaching Hospital,Sari, Iran

β-Thalassemia major (TM) is the most prevalent genetic disease in Mazandaran Province. Currently, about 2,700 TM patients have been registered and are under treatment in the province. This study was undertaken to evaluate the survival of patients attending a dedicated clinic at the Boo Ali Sina Teaching Hospital, Sari, Iran, which was established in 1986. This survival analysis was conducted from July 2004 to September 2006. New deaths were updated in September 2006. A total of 1,010 medical records were reviewed. Place of residence, date of birth, first transfusion, initiation date of chelation, diagnosis of cardiac complications, diabetes and death were recorded. Compliance to treatment assessed by calculating the percentage of actual usage to prescribed iron chelator medicine and also by asking the attending nurse who was constantly present throughout the last 15 years. Validity of the opinion of the nurse was ascertained in a previous study. Kaplan-Meier statistics were used for analysis. The odds ratio (OR) and its 95% confidence interval (CI) for some risk factors of death were calculated. The survival rate of patients born before and after 1986 was also compared. Survival of both genders for birth cohort before and after 1986 was not statistically significant although the cohort of patients born after 1986 was better at 30 years old (68 vs. 80%). The survival of TM patients is improving but the prevalence of complications is high.     

成人重型和输血依赖的非重型再生障碍性贫血中西医结合诊疗专家共识

通过组织全国中医血液病重点学科与重点专科建设单位部分专家讨论,就成人重型和输血依赖的非重型再生障碍性贫血的中西医结合诊疗方案达成一致意见并形成了较为完善的诊治规范体系。在再生障碍性贫血(简称"再障")诊断明确的前提下,对于成人重型再障(急髓劳病),有相合供者且条件适合者优先选择异基因骨髓移植,无相合供者首选强烈免疫抑制治疗与中医药的联合应用以截断细胞因子风暴;对于成人输血依赖的非重型再障(慢髓劳病)首选中医药与雄激素的联合应用以促进骨髓造血功能恢复。文章就再障的诊断与鉴别诊断、中医辨证论治、西医基础治疗等给予具体的诊治建议,以期为中西医结合诊疗再障提供指导和帮助。     

A Phase II,Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with β-Thalassemia Major

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with β-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000?µg/L; cardiac MRI T2*?<20?ms, or liver iron concentration [LIC; by MRI R2]? ≥5?mg/g). Patients received deferasirox at an initial dose of 10?mg/kg/day, with up-titration to a maximum of 20?mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1?±?3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n?=?20; 74.1%) were able to achieve the intended dose of 20?mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n?=?4; urinary tract infection, n?=?1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0?IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0?IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0?µg/L at baseline to 845.3?µg/L following 52 weeks of therapy (P?<?.001); 9 patients (33.3%) achieved a level of <500?µg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1?mg/g; P?<?.001) and an increase in median cardiac T2* (from 26.0 to 28.0?ms; P?=?.520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20?mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile.     

Lenalidomide in the context of complex karyotype or interrupted treatment: case reviews of del(5q)MDS patients with unexpected responses

Lenalidomide has particular activity in patients with transfusion-dependent del(5q) myelodysplastic syndromes (MDS), but mechanistic information is limited regarding the relationship between erythroid and cytogenetic responses. We reviewed medical records from three distinct subgroups of del(5q) MDS patients who had unexpected effects with lenalidomide treatment: 1. two patients with complex karyotypes who achieved both cytogenetic remissions and transfusion independence; 2. two patients with 5q- syndrome who took lenalidomide for less than 12 weeks but remained transfusion independent for 15+ months still displaying del(5q) metaphases after 6 and 12 months; and 3. one patient who was a non-responder on lenalidomide during treatment but became transfusion independent for 13+ months after discontinuation. All but the latter patient in this series had reduction of affected metaphases, suggesting that erythroid responses might be mediated by result from partial or complete suppression of the malignant clone, either directly or indirectly through modulation of the bone marrow microenvironment. These clinical observations illustrate the heterogeneity of del(5q)MDS pathogenesis and the diversity of lenalidomide responses within this patient subset.