Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab.
Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab.
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DOI：
10.1002/pbc.24188
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发表时间：
2013-01
影响因子：
3.2
通讯作者：
Jordan, Michael B.
中科院分区：
文献类型：
--
作者：
Marsh, Rebecca A.;Allen, Carl E.;McClain, Kenneth L.;Weinstein, Joanna L.;Kanter, Julie;Skiles, Jodi;Lee, Nadine D.;Khan, Shakila P.;Lawrence, Julia;Mo, Jun Q.;Bleesing, Jack J.;Filipovich, Alexandra H.;Jordan, Michael B.
噬血细胞淋巴组织细胞增多症(HLH)是一种威胁生命的高炎症综合征，目前仍难以治疗。即使采用目前的标准促黄体生成素治疗，只有大约一半的患者会经历疾病的完全缓解，早期死亡仍然是一个重要的问题。抢救疗法只在有限的病例报告中被描述，而且没有关于二线疗法的大型研究。我们回顾了22名儿童和成人患者的图表，这些患者在我们的中心或与我们的小组协商后接受了阿伦图珠单抗治疗难治性HLH。患者在阿伦图珠单抗之前接受常规治疗的中位数为8周(范围2-70)，而在阿伦图珠单抗之前的治疗包括地塞米松(100%)、依托泊苷(77%)、环孢菌素(36%)、鞘内氢化可的松+/−甲氨蝶呤(23%)、甲基强的松龙(9%)和利妥昔单抗(14%)。患者接受中位剂量为1 mg/kg的阿伦珠单抗(范围为0.1-8.9 mg/kg)，中位剂量为4天(范围2-10天)。14名患者经历了总体部分缓解，定义为在阿仑珠单抗治疗2周后，HLH2个或更多可量化症状或实验室标志物至少改善25%(%)。另有5名患者在单一可量化症状或实验室标志物HLH方面有25%或更大的改善(23%)。77%的患者存活下来接受了异基因造血细胞移植。患者经历了一系列可接受的并发症，包括巨细胞病毒和腺病毒血症。Alemtuzumab似乎是难治性HLH的一种有效的抢救剂，在许多患者中导致HCT的改善和生存。需要进行前瞻性试验，以确定最佳的剂量水平、计划和反应。
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that remains difficult to treat. Even with current standard HLH therapy, only approximately half of patients will experience complete resolution of disease, and early mortality remains a significant problem. Salvage therapies have been described only in limited case reports, and there are no large studies of second-line therapies. We reviewed the charts of 22 pediatric and adult patients who received alemtuzumab for the treatment of refractory HLH at our center or in consultation with our group. Patients had received conventional therapies for a median of 8 weeks (range 2–70) prior to alemtuzumab, and treatment immediately prior to alemtuzumab included dexamethasone (100%), etoposide (77%), cyclosporine (36%), intrathecal hydrocortisone +/− methotrexate (23%), methylprednisolone (9%), and rituximab (14%). Patients received a median dose of 1mg/kg alemtuzumab (range 0.1–8.9mg/kg) divided over a median of 4 days (range 2–10). Fourteen patients experienced an overall partial response, defined as at least a 25% improvement in 2 or more quantifiable symptoms or laboratory markers of HLH 2 weeks following alemtuzumab (64%). Five additional patients had a 25% or greater improvement in a single quantifiable symptom or laboratory marker of HLH (23%). Seventy-seven percent of patients survived to undergo allogeneic hematopoietic cell transplantation. Patients experienced an acceptable spectrum of complications, including CMV and adenovirus viremia. Alemtuzumab appears to be an effective salvage agent for refractory HLH, leading to improvement and survival to HCT in many patients. Prospective trials to define optimal dosing levels, schedules, and responses are needed.
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影响因子：
12.8
作者：
Olin, Rebecca L.;Nichols, Kim E.;Naghashpour, Mojdeh;Wasik, Mariusz;Shelly, Brenda;Stadtmauer, Edward A.;Vogl, Dan T.
通讯作者：
Vogl, Dan T.
影响因子：
20.3
作者：
Lundin, J;Kimby, E;Österborg, A
通讯作者：
Österborg, A
影响因子：
--
作者：
HALE G;XIA M-Q;WALDMANN H
通讯作者：
WALDMANN H
影响因子：
6.5
作者：
Horne, A;Janka, G;Henter, JI
通讯作者：
Henter, JI
影响因子：
8
作者：
Ouachée-Chardin, M;Elie, C;Fischer, A
通讯作者：
Fischer, A