目的:本研究的目的是研究沙利度胺在β-地中海贫血不同基因型表现中的治疗效果,以便于沙利度胺敏感型地中海贫血病例的早期筛查,并了解铁过载对沙利度胺的影响。
方法:从我们最初的52例患者样本中,在服用沙利度胺后,我们观察了48例β-地中海贫血患者2年。该队列包括34例输血依赖性地中海贫血(TDT)患者和14例非输血依赖性地中海贫血(NTDT)患者。我们记录了血红蛋白(Hb)的值,胎儿血红蛋白(HbF),和血清铁蛋白(SF)在基线期和1,3,6,12,18和24个月后,以及所有48例治疗前后的输血量。根据6个月观察期内Hb水平从基线的增加,对沙利度胺的反应分为四个水平:主反应(MaR),次要响应(MiR),慢响应(SLR),并且没有响应(NR)。与基线相比,血清铁蛋白水平降低被认为是铁超负荷的缓解。我们计算总反应率(ORR)如下:ORR=MaR+MiR+SLR/观察到的病例数。
结果:ORR为91.7%(44/48例),MAR占72.9%(35/48例)。在34例TDT患者中,21例(61.8%)无输血,剩下的13名患者仍然需要输血,但与基线相比,他们的总输血量减少了31.3%。我们共发现33例具有10种优势基因的组合,其中βCD41-42/βCD175例,βCD41-42/β-286例。根据观察组48例患者的治疗结果,MaR组33例,SLR/NR组15例。两组基线时的HbF差异有统计学意义(P=0.041)。两组在6个月和12个月时的Hb和HbF差异有统计学意义。分别(P<0.001)。与基线测量相比,在12个月和24个月时,SF水平显着下降(P<0.001)。
结论:在这项研究中,我们确定了10个对沙利度胺敏感的β-地中海贫血基因组合。这些基因组合可用于初步筛选和预测沙利度胺在临床实践中的治疗效果。我们检查了对沙利度胺的治疗反应,发现沙利度胺与标准化除铁联合给药更有利于减少铁过载。
OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of β-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide.
METHODS: From our initial sample of 52 patients, we observed 48 patients with β-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases.
RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with βCD41-42/βCD17 and 6 cases with βCD41-42/β-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001).
CONCLUSIONS: In this study, we identified 10 β-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.