Brethon Benoit, Yakouben Karima, Oudot Caroline, Boutard Patrick, Bruno Bénédicte, Jérome Cécile, Nelken Brigitte, de Lumley Lionel, Bertrand Yves, Dalle Jean-Hugues, Chevret Sylvie, Leblanc Thierry, Baruchel André
Hématologie Pédiatrique, Hôpital Saint-Louis, APHP, Paris, France.
Br J Haematol. 2008 Nov;143(4):541-7. doi: 10.1111/j.1365-2141.2008.07370.x. Epub 2008 Aug 28.
Gemtuzumab ozogamicin (GO) monotherapy is reported to yield a 20-30% response rate in advanced acute myeloid leukaemia (AML). This study examined the efficacy and tolerability of GO combined with cytarabine (GOCYT) in children with refractory/relapsed CD33(+) AML. Seventeen children received GO 3 mg/m(2) on days 1, 4 and 7 plus cytarabine 100 mg/m(2)/d for 7 d on a compassionate-use basis. Seven patients then received GO-based consolidation. At the outset of GOCYT, two patients were refractory; eight patients were in refractory first relapse; six patients had relapsed after stem cell transplantation (SCT); and one patient [del(5q) therapy-related AML (t-AML)] had not yet been treated. Mean follow-up was 17 months (8-33 months). Ten responses were obtained after GOCYT induction, including complete remission (CR) or CR without complete recovery of platelets (CRp) in six patients (35%). The responses improved in three children who received GOCYT consolidation, increasing the CR + CRp rate to 53%. SCT was subsequently performed in eight responders. Grade 3-4 adverse events consisted of haematological disorders (n = 17, 100%) and documented infections (n = 5, 29%). No cases of sinusoidal obstructive syndrome occurred. Three patients were alive at the cut-off date for this analysis, all of whom had responded to GOCYT. GOCYT combination therapy yielded a high response rate (53%) and showed acceptable toxicity in heavily pretreated children with refractory/relapsed AML. These results warrant a larger prospective study.
据报道,吉妥单抗奥佐米星(GO)单药治疗晚期急性髓系白血病(AML)的缓解率为20%-30%。本研究探讨了GO联合阿糖胞苷(GOCYT)治疗难治/复发CD33(+) AML儿童患者的疗效和耐受性。17例儿童在同情用药的基础上,于第1、4和7天接受3 mg/m²的GO治疗,同时接受100 mg/m²/d的阿糖胞苷治疗,持续7天。7例患者随后接受了基于GO的巩固治疗。在开始GOCYT治疗时,2例患者为难治性;8例患者处于难治性首次复发;6例患者在干细胞移植(SCT)后复发;1例患者[del(5q)治疗相关AML(t-AML)]尚未接受治疗。平均随访时间为17个月(8-33个月)。GOCYT诱导治疗后获得10例缓解,其中6例患者(35%)达到完全缓解(CR)或血小板未完全恢复的CR(CRp)。3例接受GOCYT巩固治疗的儿童缓解情况有所改善,CR + CRp率提高到53%。随后8例缓解者接受了SCT。3-4级不良事件包括血液系统疾病(n = 17,100%)和有记录的感染(n = 5,29%)。未发生肝窦阻塞综合征病例。在本次分析的截止日期时,3例患者存活,所有患者对GOCYT均有反应。GOCYT联合治疗在难治/复发AML的高度预处理儿童患者中产生了较高的缓解率(53%),且毒性可接受。这些结果值得进行更大规模的前瞻性研究。