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在新的靶向治疗时代,异基因干细胞移植治疗慢性粒细胞白血病仍是一个有前景的选择。

Allogeneic stem cell transplant for chronic myeloid leukemia as a still promising option in the era of the new target therapy.

作者信息

Stamatović Dragana, Balint Bela, Tukić Ljiljana, Elez Marija, Tarabar Olivera, Todorović Milena, Todorić-Zivanović Biljana, Ostojić Gordana, Tatomirović Zeljka, Marjanović Slobodan, Malesević Milomir

机构信息

Military Medical Academy, Clinic of Hematology, Belgrade, Serbia.

出版信息

Vojnosanit Pregl. 2012 Jan;69(1):37-42.

Abstract

BACKGROUND/AIM: Introducing tyrosine kinase inhibitors (TKIs) has essentially changed curative approach, to be precise, clearly improved treatment efficacy for chronic myeloid leukemia (CML). Thus, the place and usage of allogeneic stem cell transplant (SCT) in CML treatment--as a former "nearly monopolistic" therapeutic manner--is nowadays controversial. The objective of this retrospective study was to evaluate the results obtained in the treatment of CML patients, with a particular attempt to define parameters critical for clinical benefit and superior overall outcome following allogeneic SCT.

METHODS

A total of 32 CML patients (27 in chronic phase and 5 with advanced disease), with female/male ratio 11/21, aged from 9 to 54 (32 in average) years, underwent allogeneic SCTs (1993 to 2009). The initial treatment for 25 patients was interferon alpha (IFN-alpha) with or without ARA-C, and additional 7 patients with no response to imatinib mesylat (IM). The time from diagnosis to SCT was approximately 12 (range 3-37) months. The patient were categorized according to the risk for the disease, transplant-related mortality (TRM) scoring system, and stem cell (SC) source. The basic conditioning regimen was a combination of busulphan and cyclophosphamide (BuCy-2). Graft-versus-host disease (GvHD) was typically prevented with cyclosporine-A (CsA) and methotrexate (MTX).

RESULTS

Engraftment was observed in 26 (84.4%) patients, with polymorphonuclear (PMNs) and platelet (Plt) recovery on the 15th (range 10-22) and 19th (range 11-29) posttranspalnt days, respectively. Acute GvHD (aGvHD) had 13/26 (50%), and chronic GvHD (cGvHD) 10/21 (47.1%) patients. The incidence of overall TRM was 46.8% (15/32), while early death was noticed in 4 (12.5%) patients. A cause of death in 9 (28.1%) patients was cGvHD, in 2 (6.25%) patients infection, and in 3 (9.35%) cases disease-relapse was occurred. Fourteen (43.7%) of the patients are still alive, 9 from the low-risk group for TRM, with long-term survival from 1 to 16 years. Patients who received SCs from peripheral blood (PB) vs bone marrow (BM) had significantly faster engraftment (p < 0.05), lower oropharingeal mucositis rate (25% vs 70%; p < 0.05), but more frequent cGvHD (83.3% vs 30.3%; p < 0.05). A significantly improved (log-rank = 2.39; p < 0.01) overall survival (OS) was obtained in BM-setting.

CONCLUSION

The results obtained in this study are in accordance with data from analogous clinical trials. Exactly, in the era of the new target therapy (TKI application), allogeneic SCT can be still a convenient therapeutic approach for well-selected CML-patients, especially for those with initial high-risk disease and lower probability of TRM.

摘要

背景/目的:引入酪氨酸激酶抑制剂(TKIs)已从根本上改变了治疗方法,确切地说,显著提高了慢性髓性白血病(CML)的治疗效果。因此,异基因干细胞移植(SCT)作为一种曾经“几乎垄断”的治疗方式,在CML治疗中的地位和应用如今存在争议。这项回顾性研究的目的是评估CML患者的治疗结果,特别试图确定异基因SCT后对临床获益和更好总体结局至关重要的参数。

方法

共有32例CML患者(27例处于慢性期,5例患有晚期疾病),男女比例为11/21,年龄9至54岁(平均32岁),接受了异基因SCT(1993年至2009年)。25例患者的初始治疗为使用或不使用阿糖胞苷(ARA-C)的α干扰素(IFN-α),另外7例对甲磺酸伊马替尼(IM)无反应。从诊断到SCT的时间约为12(范围3 - 37)个月。患者根据疾病风险、移植相关死亡率(TRM)评分系统和干细胞(SC)来源进行分类。基本预处理方案为白消安和环磷酰胺联合使用(BuCy-2)。移植物抗宿主病(GvHD)通常用环孢素A(CsA)和甲氨蝶呤(MTX)预防。

结果

26例(84.4%)患者出现造血重建,中性多形核白细胞(PMNs)和血小板(Plt)分别在移植后第15天(范围10 - 22天)和第19天(范围11 - 29天)恢复。急性移植物抗宿主病(aGvHD)发生在13/26(50%)的患者中,慢性移植物抗宿主病(cGvHD)发生在10/21(47.1%)的患者中。总体TRM发生率为46.8%(15/32),4例(12.5%)患者出现早期死亡。9例(28.1%)患者的死亡原因是cGvHD,2例(6.25%)患者是感染,3例(9.35%)发生疾病复发。14例(43.7%)患者仍然存活,9例来自低TRM风险组,长期生存时间为1至16年。接受外周血(PB)来源干细胞与骨髓(BM)来源干细胞的患者造血重建明显更快(p < 0.05),口咽黏膜炎发生率更低(25%对70%;p < 0.05),但cGvHD更频繁(83.3%对30.3%;p < 0.05)。在BM情况下总体生存率(OS)显著提高(对数秩检验 = 2.39;p < 0.01)。

结论

本研究获得的结果与类似临床试验的数据一致。确切地说,在新的靶向治疗(TKI应用)时代,异基因SCT对于精心选择的CML患者仍然可以是一种合适的治疗方法,特别是对于那些初始患有高危疾病且TRM概率较低的患者。

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