Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: investigation of dose level with clinical correlates
Interleukin-2-activated hematopoietic stem cell transplantation for breast cancer: investigation of dose level with clinical correlates
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DOI：
10.1038/sj.bmt.1700954
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发表时间：
1997-10-01
影响因子：
4.8
通讯作者：
Mazumder, A
中科院分区：
文献类型：
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作者：
Meehan, KR;Verma, UN;Mazumder, A
在体外用IL-2孵育造血干细胞24小时产生细胞毒性T细胞。当输注到患者体内时，这些细胞可能会刺激移植物抗肿瘤（GVT）效应。本临床试验旨在评估IL-2激活的外周血干细胞（PBSC）重建造血的能力，研究IL-2的剂量水平和剂量限制性毒性，并评估移植后IL-2激活的自体PBSC联合IL-2的临床结果和初步实验室效应。61例II-IV期乳腺癌患者接受卡铂（200 mg/m2/d，连用3天）和环磷酰胺（2 g/m2/d，连用3天）治疗后，接受自体外周血干细胞，在IL-2中培养24 h，然后从移植当天开始给予IL-2。评估了三种递增剂量的IL-2，持续时间增加至4周。在移植后接受IL-2治疗的57例患者中，19例患者（33.3%）由于持续发热（n = 9）、腹泻（n = 2）、肺毛细血管渗漏综合征（n = 3）、皮疹（n = 1）、房颤（n = 1）或患者要求（n = 3）而无法完成计划的IL-2治疗疗程。1例死亡发生在住院期间。中性粒细胞植入发生在第11.5天（平均值;范围8-21天），血小板植入发生在第11.7天（平均值;范围7-33天）。IL-2的最大耐受剂量为6 × 105 IU/m2/天，持续4周。所有阶段的无病生存率与文献中的当前报告相当。初步实验室评价包括IL-2活化的PBSC的FACScan分析，表明CD 3（+）、CD 25（+）、HLA-DR+ T细胞的百分比增加。移植后15天检测时，患者外周血样本中存在表型相似的细胞。本研究证实了II-IV期乳腺癌患者接受大剂量化疗后，IL-2激活的PBSC可成功植入。该方案是可行的，尽管毒性是常见的，但它们是可管理的，并且与IL-2的剂量增加和持续时间相关。
Incubating hematopoietic stem cells with IL-2 in vitro for 24 h generates cytotoxic T cells. When infused into patients, these cells may stimulate a graft-versus-tumor (GVT) effect. This clinical trial was designed to assess the ability of IL-2 activated peripheral blood stem cells (PBSC) to reconstitute hematopoiesis, to investigate dose levels and dose-limiting toxicities of IL-2, and to evaluate clinical results and preliminary laboratory effects using a combination of IL-2-activated autologous PBSC followed by IL-2 after transplantation. Sixty-one women with stage II-IV breast cancer were treated, After the administration of carboplatin (200 mg/m(2)/day for 3 days) and cyclophosphamide (2 g/m(2)/day for 3 days), patients received autologous PBSC that were cultured in IL-2 for 24 h followed by parenteral administration of IL-2 beginning the day of transplantation. Three escalating doses of IL-2 were evaluated with increasing duration up to 4 weeks. Of the 57 patients receiving IL-2 after tranplantation, 19 patients (33.3%) were unable to complete the planned course of IL-2 therapy due to persistent fevers (n = 9), diarrhea (n = 2), pulmonary capillary leak syndrome (n = 3), development of a rash (n = 1), atrial fibrillation (n = 1), or patient's request (n = 3). One death occurred during hospitalization. Engraftment of neutrophils occurred on day 11.5 (mean; range 8-21 days) and platelets on day 11.7 (mean; range 7-33 days). The maximal tolerated dose of IL-2 was 6 x 10(5) IU/m(2)/day for 4 weeks. Disease-free survival rates for all stages were comparable to current reports in the literature, Preliminary laboratory evaluations include FACScan analysis of the IL-2 activated PBSC demonstrating an increased percentage of CD3(+), CD25(+), HLA-DR+ T cells. Phenotypically similar cells were present in peripheral blood samples of patients when tested 15 days after transplantation. This study demonstrates successful engraftment with IL-2-activated PBSC after high-dose chemotherapy for women with stage II-IV breast cancer. The regimen is feasible and, although toxicities are common, they are manageable and correlate with increasing dose and duration of IL-2.