Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity.
Complete Remissions of Adult T-cell Leukemia with Anti-CD25 Recombinant Immunotoxin LMB-2 and Chemotherapy to Block Immunogenicity.
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DOI：
10.1158/1078-0432.ccr-15-1412
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发表时间：
2016-01-15
期刊：
影响因子：
--
通讯作者：
Pastan I
中科院分区：
文献类型：
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作者：
Kreitman RJ;Stetler-Stevenson M;Jaffe ES;Conlon KC;Steinberg SM;Wilson W;Waldmann TA;Pastan I
成人T细胞白血病（ATL）通常是CD 25+，并迅速致命。抗CD 25重组免疫毒素LMB-2的I相活性受到免疫原性和快速生长的限制。为了防止周期之间的抗药抗体和白血病进展，在环磷酰胺和氟达拉滨之后用LMB-2进行II期试验。ATL患者在第1至3天接受环磷酰胺和氟达拉滨，2周后开始以3周的间隔在第1至3天接受环磷酰胺和氟达拉滨，然后在第3、5和7天静脉注射LMB-2 30-40 μg/kg，最多6个周期。使用三种不同剂量水平的环磷酰胺和氟达拉滨，20+200（n = 3）、25+250（n = 12）和30+300 mg/m2（n = 2）。在17例入组并接受氟达拉滨和环磷酰胺治疗的第1周期患者中，15例接受了含LMB-2的后续周期，因此可评价缓解。缺乏抗体形成允许在大多数患者中重新治疗。在接受25+250或30+300 mg/m2氟达拉滨和环磷酰胺治疗的10例可评价白血病患者中，6例（60%）达到完全缓解（CR），2例（20%）达到部分缓解（PR），5例白血病细胞>25%的患者均达到CR。5例淋巴瘤性ATL或较低剂量的氟达拉滨和环磷酰胺均未获得缓解。6例CR的中位CR持续时间为40周。一个是在47个月时没有检测到ATL。毒性主要归因于氟达拉滨和环磷酰胺。LMB-2的毛细血管泄漏是非剂量限制性的。1例CR患者死于既存感染。LMB-2与氟达拉滨和环磷酰胺联合给药以预防抗药抗体和快速周期间进展，在白血病ATL中实现CR方面非常有效。氟达拉滨和环磷酰胺剂量/方案对于该高危人群的安全性和疗效很重要。
Adult T-cell leukemia (ATL) is usually CD25+ and rapidly fatal. Anti-CD25 recombinant immunotoxin LMB-2 had phase I activity limited by immunogenicity and rapid growth. To prevent antidrug antibodies and leukemic progression between cycles, a phase II trial was performed with LMB-2 after cyclophosphamide and fludarabine. ATL patients received cyclophosphamide and fludarabine days 1 to 3 and 2 weeks later began up to 6 cycles at 3-week intervals of cyclophosphamide and fludarabine days 1 to 3 followed by LMB-2 30–40 μg/kg i.v. days 3, 5, and 7. Three different dose levels of cyclophosphamide and fludarabine were used, 20+200 (n = 3), 25+250 (n = 12), and 30+300 mg/m2 (n = 2). Of 17 patients enrolled and treated with fludarabine and cyclophosphamide for cycle-1, 15 received subsequent cycle (s) containing LMB-2 and were therefore evaluable for response. Lack of antibody formation permitted retreatment in most patients. Of 10 evaluable leukemic patients receiving 25+250 or 30+300 mg/m2 of fludarabine and cyclophosphamide, 6 (60%) achieved complete remission (CR) and 2 (20%) partial remission (PR), and all 5 with >25% leukemic cells achieved CR. No responses were achieved in 5 with lymphomatous ATL or lower fludarabine and cyclophosphamide doses. Median CR duration for the 6 CRs was 40 weeks. One is without detectable ATL at 47 months. Toxicity was mostly attributable to fludarabine and cyclophosphamide. Capillary leak from LMB-2 was non-dose limiting. One patient in CR died of a preexisting infection. LMB-2, administered with fludarabine and cyclophosphamide to prevent antidrug antibodies and rapid intercycle progression, is highly effective in achieving CR in leukemia ATL. Fludarabine and cyclophosphamide dose/schedule is important for safety and efficacy in this high-risk population.
DOI：
10.1111/j.1349-7006.1990.tb02665.x
发表时间：
1990-09
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Kodaka T;Uchiyama T;Ishikawa T;Kamio M;Onishi R;Itoh K;Hori T;Uchino H;Tsudo M;Araki K
通讯作者：
Araki K