Phase I trial of parathyroid hormone to facilitate stem cell mobilization
Phase I trial of parathyroid hormone to facilitate stem cell mobilization
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DOI：
10.1016/j.bbmt.2007.03.007
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发表时间：
2007-07-01
影响因子：
4.3
通讯作者：
Spitzer, Thomas R.
中科院分区：
文献类型：
--
作者：
Ballen, Karen K.;Shpall, Elizabeth J.;Spitzer, Thomas R.
自体造血干细胞移植是治疗许多淋巴瘤患者的一种方法，并已被证明可以提高多发性骨髓瘤患者的生存率。大约20%的患者无法动员足够的造血干细胞来安全地进行自体干细胞移植。甲状旁腺激素（PTH）影响成骨细胞和干细胞生态位，并已被证明在小鼠竞争性移植模型中移植后给予可提高存活率。在这项I期研究中，20名有1次或2次不成功的干细胞动员尝试的受试者接受PTH，剂量递增为40 μ g、60 μ g、80 μ g和100 μ g，持续14天。在治疗的第10-14天，受试者接受非格司亭10 μ g/kg。PTH耐受性良好，无剂量限制性毒性。47%的既往动员失败的受试者符合外周血中> 5个CD 34（+）细胞/μ L的动员标准。在2次既往动员尝试中未能达到足够CD 34（+）细胞计数的受试者中，40%符合动员标准。在人类癌症患者中，PTH在高达100 μ g的剂量下耐受良好。甲状旁腺素动员造血干细胞的疗效需要在更大规模的II期研究中进行测试。(c)2007年美国血液和骨髓移植学会。
Autologous stem cell transplantation is a curative procedure for many patients with lymphomas, and has been shown to improve survival in patients with multiple myeloma. Approximately 20% of patients are unable to mobilize sufficient hematopoietic stem cells to proceed safely to autologous stem cell transplantation. Parathyroid hormone (PTH) affects osteoblasts and the stem cell niche, and has been shown to improve survival when given posttransplant in a mouse competitive transplant model. In this Phase I study, 20 subjects who had I or 2 unsuccessful stem cell mobilization attempts, received PTH in escalating doses of 40 jig, 60 mu g, 80 jig, and 100 mu g for 14 days. On days 10-14 of treatment, subjects received filgrastim 10 mu g/kg. The PTH was tolerated well and there was no dose-limiting toxicity. Forty-seven percent of subjects who had failed I prior mobilization attempt met the mobilization criteria of > 5 CD 34(+) cells/mu L in the peripheral blood. Forty percent of subjects who failed to reach adequate CD34(+) cell counts in 2 prior mobilization attempts met the mobilization criteria. PTH was well tolerated at doses up to 100 jig in human cancer patients. The efficacy of PTH for mobilization of hematopoietic stem cells will need to be tested in a larger Phase II study. (c) 2007 American Society for Blood and Marrow Transplantation.