Toxicity of fluadarabine versus antithymocyteglobulin in conditioning regimen of non-myeloablative allogeneic hematopoietic stem cell transplantation

doi:10.3969/j.issn.2095-4344.2013.06.015

Abstract

Abstract:

BACKGROUND: The highly-effective conditioning regimens of proper dose and low-toxicity are the key to the successful hematopoietic stem cell transplantation. Fludarabine and antithymocyteglobulin are intensive immunosuppressants, and are usually used in conditioning regimen of non-myeloablative hematopoietic stem cell transplantation.
OBJECTIVE: To compare the toxicity of fluadarabine versus antithymocyteglobulin in the conditioning regimen of non-myeloablative allogeneic hematopoietic stem cell transplantation.
METHODS: Thirty-two patients with malignant hematologic diseases were divided into fludarabine group and antithymocyteglobulin group according to the difference of immunosuppressants in conditioning regimen.Conditioning regimen consisted of fluadarabine or antithymocyteglobulin combined with the reduced-dose busulfan and cyclophosphamide or L-Sarcolysinum. The donor lymphocyte infusion was performed after the formation of mixed chimerism in antithymocyteglobulin group. The toxicity in the two groups was statistically analyzed, and the regimen-related toxicity was scored using the criteria of Bearman.
RESULTS AND CONCLUSION: No one died of regimen-related toxicity in two groups. There were no significant differences in the incidence of transaminase and diarrhea between fluadarabine and antithymocyteglobulin groups (P > 0.05); while the incidence of liver toxicity and mucositis in fluadarabine group was lower than that in the antithymocyteglobulin group (P < 0.05). About hemotologic toxicity, the time for white blood cell count reaching the lowest value and platelets ≥50×109/L, the volume of infused red cells and the volume of infused platelets in the fluadarabine group were lower than those in the antithymocyteglobulin group (P < 0.05).

Key words: stem cell, stem cell transplantation, fludarabine, antithymocyte globulin, nonmyeloablative hematopoietic stem cells transplantation, stem cells, cells transplantation, hematologic toxicity, conditioning, immunosuppressants, transfusion of blood components, organ toxicity, provincial grants-supported paper

CLC Number:

R394.2

Zhuang Xiao-yin, Li Qing-shan, Wang Shun-qing, Zhou Ming. Toxicity of fluadarabine versus antithymocyteglobulin in conditioning regimen of non-myeloablative allogeneic hematopoietic stem cell transplantation[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(6): 1037-1043.

Figures/Tables 5

肝脏毒性：氟达拉滨组出现肝脏毒性共7例(38.8%)，其中5例(27.7%)出现转氨酶升高，Ⅰ级3例，Ⅱ级2例；共有2例(11.1%)出现胆红素升高，Ⅰ级和2级各有1例；抗胸腺细胞球蛋白组出现肝脏毒性共10 例(70.9%)，其中3例(21.4%)出现转氨酶升高，其中Ⅰ级1例，Ⅱ级2例，共有7例(50%)出现胆红素升高，Ⅰ级2例，Ⅱ级5例。两组各出现1例轻度肝静脉阻塞病，所有的肝脏毒性均为可逆性，经护肝治疗后均可恢复正常。两组转氨酶升高发生率差异无显著性意义(P > 0.05)，两组胆红素升高发生率差异有显著性意义(P < 0.05)。胃肠道毒性：氟达拉滨组共有3例(16.6%)发生腹泻，均为Ⅰ级毒性(腹泻量500-2 000 mL/d)，持续2 d左右，未见血便或肠梗阻。抗胸腺细胞球蛋白组共有2例(14.2%)发生腹泻，均为Ⅰ级毒性，予止泻药物处理后可恢复正常。根据临床观察，几乎100%的患者预处理时有不同程度的恶心、呕吐、腹泻，严重的影响进食。两组差异无显著性意义(P > 0.05)。黏膜炎：氟达拉滨组有11例(61.1%)发生口腔黏膜炎，Ⅰ级8例，Ⅱ级1例，Ⅲ级1例，Ⅰ、Ⅱ级口腔溃疡和疼痛可以忍受，不需要静脉滴注止痛剂，予加强口腔护理及黏膜保护剂等处理后患者可于1周左右好转，Ⅲ级毒性患者，口腔溃疡及疼痛尚不能忍受，影响进食，需要持续静脉营养支持及外用止痛剂，但尚不需要留置胃管或行机械通气；抗胸腺细胞球蛋白组有3例(21.4%),Ⅰ级2例，Ⅱ级2例。两组差异有显著性意义(P < 0.05)。肾毒性：氟达拉滨组未见血肌酐升高。抗胸腺细胞球蛋白组有3例血肌酐升高，但未达基础水平的2倍以上，为Ⅰ级肾毒性。心脏毒性：氟达拉滨组无1例心脏毒性发生。抗胸腺细胞球蛋白组有4例患者发生了轻度的心律失常，2例表现为窦性心动过速，2例表现为房性早搏，予减慢输液速度及辅助药物治疗后，患者心率可恢复正常；抗胸腺细胞球蛋白组6例(42.8%)出现低血压。其他毒性：两组无神经系统毒性发生；两组无因预处理相关毒性而死亡。两组均未出现Ⅰ级毒性。两组Ⅱ、Ⅲ级毒性各有2例、1例，予水化、碱化尿液、利尿、膀胱冲洗后可好转，Ⅲ级毒性不需外科处理。血清病：抗胸腺细胞球蛋白组有3例血清病反应表现为皮疹、关节酸痛，予激素等对症治疗后症状可明显缓解"

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