Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies
Pharmacokinetics of alemtuzumab after haploidentical HLA-mismatched hematopoietic stem cell transplantation using in vivo alemtuzumab with or without CD52-positive malignancies
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DOI：
10.1002/ajh.20694
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发表时间：
2006-11-01
影响因子：
12.8
通讯作者：
Kurokawa, Mineo
中科院分区：
文献类型：
--
作者：
Oshima, Kumi;Kanda, Yoshinobu;Kurokawa, Mineo
我们最近报道，在预处理方案中加入体内Alemtuzumab可实现2或3个位点不匹配的造血干细胞移植，而不会产生过度的移植物排斥或移植物抗宿主病风险。然而，在后来的一系列患者中，一名患者患有难治性慢性淋巴细胞白血病。移植时有较大残留肿瘤的患者出现移植物排斥反应。虽然先前无移植物排斥的患者中的alemtuzumab峰浓度高于5 μ g/ml，但该患者中的alemtuzumab峰浓度仅为1.44 μ g/ml。我们认为Alemtuzumab与较大的残留肿瘤结合，导致Alemtuzumab的血药浓度较低。因此，对于难治性CD 52阳性恶性血液病患者，在预处理方案前对肿瘤进行减容非常重要，或者当Alemtuzumab用于2或3位点不匹配移植中的体内T细胞清除时，应通过监测血药浓度来调整Alemtuzumab的剂量。
We recently reported that the addition of in vivo alemtuzumab to the conditioning regimen enables 2- or 3-locus-mismatched hematopoietic stem cell transplantation without an excessive risk of graft rejection or graft-versus-host disease. In a later series of patients, however, one patient with refractory chronic lymphocytic leukemia. with large residual tumors at transplantation developed graft rejection. While the peak alemtuzumab concentration in the previous patients without graft rejection was higher than 5 mu g/ml, the peak alemtuzumab concentration in this patient was only 1.44 mu g/ml. We considered that alemtuzumab was bound to the large residual tumors, which resulted in a low blood concentration of alemtuzumab. Therefore, it is important to debulk tumors before the conditioning regimen for patients with refractory CD52-positive hematological malignancies, or the dose of alemtuzumab should be adjusted by monitoring the blood concentration, when alemtuzumab is used for in vivo T-cell depletion in 2- or 3-locus-mismatched transplantation.