Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant.
Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant.
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DOI：
10.1002/ajh.21449
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发表时间：
2009-08
影响因子：
12.8
通讯作者：
Remick, Scot C.
中科院分区：
文献类型：
--
作者：
Barr, Paul M.;Lazarus, Hillard M.;Cooper, Brenda W.;Schluchter, Mark D.;Panneerselvam, Ashok;Jacobberger, James W.;Hsu, Jack W.;Janakiraman, Nalini;Simic, Aleksandra;Dowlati, Afshin;Remick, Scot C.
苔藓抑素1，从海洋苔藓虫中分离，通过调节蛋白激酶C途径增强细胞毒性药物的疗效，并与长春新碱联合治疗弥漫性大B细胞淋巴瘤。此外，通过流式细胞术测定的外周血T淋巴细胞的凋亡频率可以预测哪些患者会对这种组合产生反应。我们检测了自体干细胞移植后复发的侵袭性B细胞非霍奇金淋巴瘤患者，苔藓抑素1 50μg/m2，24小时内给药，长春新碱1.4 mg/m2，第1天和第15天，每28天一次。终点包括肿瘤反应、毒性和生存期。通过使用膜联蛋白V染色的流式细胞术，反应与CD 5+细胞凋亡频率的增加相关。入组了14例患者，其中13例可评价缓解。总缓解率为31%，2例患者达到完全缓解。最常见的毒性为3级淋巴细胞减少症（7例患者）、3 - 4级中性粒细胞减少症（2例患者）和3级低磷血症（2例患者）。所有患者的中位无进展生存期和总生存期分别为5.7和21.4个月。1例患者表现出T细胞凋亡频率增加，也实现了完全缓解。苔藓抑素1和长春新碱对侵袭性非霍奇金淋巴瘤患者有效。未来研究靶向蛋白激酶C通路的药物可能受益于使用流式细胞术评估T细胞凋亡的早期反应评估。
Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50μg/m2 given over 24 hours and vincristine 1.4 mg/m2 on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma relapsing after autologous stem cell transplantation. End points included tumor response, toxicity and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with 2 patients achieving a complete response. The most common toxicities were grade 3 lymphopenia (7 patients), grade 3 to 4 neutropenia (2 patients), and grade 3 hypophosphatemia (2 patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine has efficacy in select patients with aggressive non-Hodgkin lymphoma. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis.
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影响因子：
11.5
作者：
Roberts, John D.;Smith, Mitchell R.;Grant, Steven
通讯作者：
Grant, Steven
DOI：
10.1093/jnci/85.22.1812
发表时间：
1993-11-17
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
PHILIP, PA;REA, D;HARRIS, AL
通讯作者：
HARRIS, AL
影响因子：
45.3
作者：
Schouten, HC;Qian, W;Kvalheim, G
通讯作者：
Kvalheim, G
影响因子：
3.7
作者：
KAPLAN, EL;MEIER, P
通讯作者：
MEIER, P
DOI：
10.1016/0167-4889(87)90239-4
发表时间：
1987-06-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
TALLANT, EA;SMITH, JB;WALLACE, RW
通讯作者：
WALLACE, RW