Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study
Bortezomib with chemotherapy is highly active in advanced B-precursor acute lymphoblastic leukemia: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Study
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DOI：
10.1182/blood-2012-04-418640
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发表时间：
2012-07-12
期刊：
影响因子：
20.3
通讯作者：
Bostrom, Bruce C.
中科院分区：
文献类型：
--
作者：
Messinger, Yoav H.;Gaynon, Paul S.;Bostrom, Bruce C.
复发性小儿急性淋巴细胞白血病（ALL）的治疗受到低缓解率和高毒性的阻碍，特别是在第二次和随后的复发中。我们的I期研究T2005-003显示硼替佐米与长春新碱、地塞米松、聚乙二醇化天冬酰胺酶和多柔比星的组合具有可接受的毒性。我们报告了该联合治疗在2-3个既往治疗方案失败的复发ALL患者中的2期扩展。22例复发性ALL患者接受硼替佐米联合该方案治疗;他们的年龄范围为1至22岁，他们患有B前体ALL（n = 20）或T细胞ALL（n = 2）。2例（9%）患者发生3级周围神经病变。在3例患者死于细菌感染后，最后6例患者接受万古霉素、左氧氟沙星和伏立康唑预防性治疗，未导致进一步的感染性死亡。14例患者达到完全缓解（CR），2例患者达到CR，但血小板未恢复，总体缓解率为73%，符合允许早期关闭的预定标准。B细胞前体患者情况最好，20例CR + CR中有16例（80%）血小板未恢复，而2例T细胞ALL患者无应答。因此，硼替佐米与化疗的这种组合在B前体ALL中是有效的，预防性抗生素可能有助于降低死亡率。硼替佐米在儿童前体B细胞ALL的联合治疗中值得进一步评价。本研究在http://www.clinicaltrials.gov注册为NCT 00440726。（血。2012;120（2）：285-290）
Therapy of relapsed pediatric acute lymphoblastic leukemia (ALL) is hampered by low remission rates and high toxicity, especially in second and subsequent relapses. Our phase 1 study, T2005-003, showed that the combination of bortezomib with vincristine, dexamethasone, pegylated asparaginase, and doxorubicin had acceptable toxicity. We report the phase 2 expansion of this combination in patients with relapsed ALL who failed 2-3 previous regimens. Twenty-two patients with relapsed ALL were treated with bortezomib combined with this regimen; their ages ranged from 1 to 22 years, and they had either B-precursor ALL (n = 20) or T-cell ALL (n = 2). Grade 3 peripheral neuropathy developed in 2 (9%) patients. After 3 patients died from bacterial infections, treatment with vancomycin, levofloxacin, and voriconazole prophylaxis resulted in no further infectious mortality in the last 6 patients. Fourteen patients achieved complete remission (CR), and 2 achieved CR without platelet recovery, for an overall 73% response rate, meeting predefined criteria allowing for early closure. B-precursor patients faired best, with 16 of 20 (80%) CR + CR without platelet recovery, whereas the 2 patients with T-cell ALL did not respond. Thus, this combination of bortezomib with chemotherapy is active in B-precursor ALL, and prophylactic antibiotics may be useful in reducing mortality. Bortezomib merits further evaluation in combination therapy in pediatric B-precursor ALL. This study is registered at http://www.clinicaltrials.gov as NCT00440726. (Blood. 2012;120(2):285-290)