Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results
Ruxolitinib treatment for steroid refractory acute and chronic graft vs host disease in children: Clinical and immunological results
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DOI：
10.1002/ajh.25376
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发表时间：
2019-03-01
影响因子：
12.8
通讯作者：
Angel Diaz, Miguel
中科院分区：
文献类型：
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作者：
Gonzalez Vicent, Martay;Molina, Blanca;Angel Diaz, Miguel
Ruxolitinib是一种很有前途的治疗类固醇难治性移植物抗宿主病（GvHD）。然而，有关对T细胞影响的数据可能与机会性感染风险增加有关。我们分析了GvHD患儿服用鲁索利替尼后的临床和免疫学变化。纳入了22名接受移植并接受ruxolitinib的儿童。鲁索利替尼适应症分别为13例和9例患者的急性和慢性GvHD。急性GvHD和慢性GvHD的总体缓解率（ORR）较高，分别为77%和89%。Ruxolitinib与CD 4效应记忆（EM）增加和CD 4中枢记忆百分比降低相关。CD 4调节性T细胞百分比显著降低。对ruxolitinib达到完全反应的患者在ruxolitinib之前具有更高的自然杀伤（NK）细胞，而患者没有反应。与无应答者相比，应答者的CD 4淋巴细胞百分比增加，CD 8和NK细胞百分比降低。病毒感染占54%，细菌感染占18%，真菌感染占13%。复发和非复发死亡的累积发生率分别为19 +/-9%和28 +/-10%。2年总生存率和无病生存率分别为62 +/- 11%和58 +/-11%。Ruxolitinib是治疗急性和慢性GvHD的一种有希望的治疗方法，ORR分别为77%和89%。它在免疫系统中产生重要的变化，如CD 4 EM细胞增加，NK细胞和调节性T细胞减少。现在，我们需要药代动力学研究来确定ruxolitinib在儿童中的剂量，并进行密切监测和抗菌预防。
Ruxolitinib is a promising treatment for steroid refractory graft-vs-host disease (GvHD). However, data concerning effects on T cells are probably involved in increased risk of opportunistic infections. We analyzed clinical and immunological changes in children with GvHD taking ruxolitinib. Twenty-two children that underwent transplantation and received ruxolitinib were included. Ruxolitinib indication was acute and chronic GvHD in 13 and 9 patients, respectively. Overall response rate (ORR) in acute GvHD and chronic GvHD was high, of 77% and 89%, respectively. Ruxolitinib was associated with an increase in CD4 effector memory (EM), and decrease of CD4 central memory percentage. CD4 regulatory T cells percentage decreased significantly. Patients who achieved complete response to ruxolitinib had higher natural killer (NK) cells before ruxolitinib that patients who did not respond. Also there was an increase of CD4 lymphocytes percentage, with decrease of CD8 and NK cells percentage in responders against non-responders. There were 54%, 18% and 13% of infections caused by virus, bacteria and fungi, respectively. Cumulative incidence of relapse and non-relapse mortality was 19 +/- 9%and 28 +/- 10%, respectively. Overall survival and disease-free survival rate at 2 years were 62 +/- 11% and 58 +/- 11%, respectively. Ruxolitinib is a promising treatment for acute and chronic GvHD with a high ORR of 77% and 89%, respectively. It produces important changes in immune system, such as increase of CD4 EM cells and decrease in NK and regulatory T cells. Now, we need pharmacokinetic studies to determine ruxolitinib dose in children and close surveillance and antimicrobial prophylaxis.