Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome
Phase I/II study of gemtuzumab ozogamicin added to fludarabine, melphalan and allogeneic hematopoietic stem cell transplantation for high-risk CD33 positive myeloid leukemias and myelodysplastic syndrome
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DOI：
10.1038/sj.leu.2405014
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发表时间：
2008-02-01
期刊：
影响因子：
11.4
通讯作者：
Giralt, S.
中科院分区：
文献类型：
--
作者：
de Lima, M.;Champlin, R. E.;Giralt, S.
在一项I/II期试验中，我们研究了抗CD33免疫毒素getuzumab ozogamicin(GO)将改善氟达拉滨/马法兰作为异基因造血干细胞移植(HSCT)准备方案的疗效的假设。毒性定义为III-IV级器官损害、植入失败或在30天内死亡。“应答”是+30天的植入和缓解(CR)。我们试图确定在毒性和反应之间进行最佳权衡的GO剂量(2、4或6 mg m(-2))。所有患者都不是清髓方案的候选对象。治疗方案：GO(第12天)、氟达拉滨30 mg m(-2)(第5天至第2天)、马法兰140 mg m(-2)(第2天)、HSCT(第0天)。预防移植物抗宿主病的药物为他克莫司和甲氨蝶呤。诊断为急性髓系白血病47例，骨髓增生异常综合征4例，慢性粒细胞白血病1例。中位年龄53岁(范围13-72岁)。除3例患者外，其余患者均未进入CR。供者有血缘关系(n=33)或无血缘关系(n=19)。4 mg m(-2)的毒性和有效率分别为50%(n=4)和50%(n=4)。GO剂量降至2mgm(-2)：18%有毒性(n=8)，82%有反应(n=36)。100天TRM为15%，1例患者出现可逆性肝VOD。中位随访时间为37个月。中位无事件和总生存期分别为6个月和11个月。氟达拉滨/马法兰中加入GO 2 mg m(-2)是安全的，该方案值得进一步评价。
We investigated the hypothesis that gemtuzumab ozogamicin (GO), an anti-CD33 immunotoxin would improve the efficacy of fludarabine/melphalan as a preparative regimen for allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. Toxicity was defined as grades III-IV organ damage, engraftment failure or death within 30 days. 'Response' was engraftment and remission (CR) on day +30. We sought to determine the GO dose (2, 4 or 6 mg m(-2)) giving the best trade-off between toxicity and response. All patients were not candidates for myeloablative regimens. Treatment plan: GO (day - 12), fludarabine 30 mg m(-2) (days-5 to -2), melphalan 140 mg m(-2) (day - 2) and HSCT (day 0). GVHD prophylaxis was tacrolimus and mini-methotrexate. Diagnoses were AML (n = 47), MDS (n = 4) or CML (n = 1). Median age was 53 years (range, 13-72). All but three patients were not in CR. Donors were related (n = 33) or unrelated (n = 19). Toxicity and response rates at 4 mg m(-2) were 50% (n = 4) and 50% (n = 4). GO dose was de-escalated to 2 mg m(-2): 18% had toxicity (n = 8) and 82% responded (n = 36). 100-day TRM was 15%; one patient had reversible hepatic VOD. Median follow-up was 37 months. Median event-free and overall survival was 6 and 11 months. GO 2 mg m(-2) can be safely added to fludarabine/melphalan, and this regimen merits further evaluation.