细胞因子
少量研究表明,干扰素可以在有限程度上诱导ALL患者缓解。 初步数据表明,IL-2可有效治疗复发的急性髓系白血病,但对ALL患者无效。 评估干扰素及IL-2在ALL治疗中的作用需要进一步研究。[70]Lamanna N, Weiss M. Treatment options for newly diagnosed patients with adult acute lymphoblastic leukemia. Curr Hematol Rep. 2004 Jan;3(1):40-6.http://www.ncbi.nlm.nih.gov/pubmed/14695849?tool=bestpractice.com[77]Ravandi F. Role of cytokines in the treatment of acute leukemias: a review. Leukemia. 2006 Apr;20(4):563-71.http://www.ncbi.nlm.nih.gov/pubmed/16498390?tool=bestpractice.com
单克隆抗体
依帕珠单抗 (epratuzumab) 是一种抗 CD22 单克隆抗体,对其用于复发性 ALL 患者的治疗正在研究中。[129]Raetz EA, Cairo MS, Borowitz MJ, et al; Children's Oncology Group Pilot Study. Chemoimmunotherapy reinduction with epratuzumab in children with acute lymphoblastic leukemia in marrow relapse: a Children's Oncology Group Pilot Study. J Clin Oncol. 2008 Aug 1;26(22):3756-62.http://jco.ascopubs.org/content/26/22/3756.longhttp://www.ncbi.nlm.nih.gov/pubmed/18669463?tool=bestpractice.com[130]Raetz EA, Cairo MS, Borowitz MJ, et al. Re-induction chemoimmunotherapy with epratuzumab in relapsed acute lymphoblastic leukemia (ALL): phase II results from Children's Oncology Group (COG) study ADVL04P2. Pediatr Blood Cancer. 2015 Jul;62(7):1171-5.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4701208/http://www.ncbi.nlm.nih.gov/pubmed/25732247?tool=bestpractice.com BiTE 单抗已通过美国食品药品监督管理局 (FDA) 的快速审批,可用于在完全血液学缓解阶段出现微小残留病的 B 细胞 ALL 患者。[131]Gökbuget N, Dombret H, Bonifacio M, et al. Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia. Blood. 2018 Apr 5;131(14):1522-31.http://www.bloodjournal.org/content/131/14/1522.long?sso-checked=truehttp://www.ncbi.nlm.nih.gov/pubmed/29358182?tool=bestpractice.com BiTE 单抗已获批准用于复发性或难治性 B 细胞 ALL。
培门冬酶(聚乙二醇化左旋天冬酰胺酶)
左旋天冬酰胺酶常用于治疗儿童急性淋巴细胞白血病,通常通过肌内注射给药。与原生大肠杆菌左旋天冬酰胺酶相比,培门冬酶(聚乙二醇化大肠杆菌左旋天冬酰胺酶)的半衰期更长,免疫原性可能更低,并可静脉使用。在新确诊的急性淋巴细胞白血病患儿中,与注射用原生大肠杆菌左旋天冬酰胺酶相比,培门冬酶的毒性不会更高,效果与其相近,并能减轻焦虑。[132]Place AE, Stevenson KE, Vrooman LM, et al. Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. Lancet Oncol. 2015 Dec;16(16):1677-90.http://www.ncbi.nlm.nih.gov/pubmed/26549586?tool=bestpractice.com
其他新的治疗方法
正在研究的重要分子靶点包括 FLT3 受体激酶通路、凋亡通路 JAK-STAT、MEK、SRC、ABL、PDGFR、KIT 激酶、端粒酶和蛋白酶体。[65]Gokbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2006 Jan;(1):133-41.http://www.ncbi.nlm.nih.gov/pubmed/17124052?tool=bestpractice.com[133]Chalandon Y, Schwaller J. Targeting mutated protein tyrosine kinases and their signaling pathways in hematologic malignancies. Haematologica. 2005 Jul;90(7):949-68.http://www.ncbi.nlm.nih.gov/pubmed/15996933?tool=bestpractice.com 氯法拉滨[134]Advani AS, Gundacker HM, Sala-Torra O, et al. Southwest Oncology Group Study S0530: a phase 2 trial of clofarabine and cytarabine for relapsed or refractory acute lymphocytic leukaemia. Br J Haematol. 2010 Dec;151(5):430-4.http://www.ncbi.nlm.nih.gov/pubmed/21113977?tool=bestpractice.com[135]Ghanem H, Jabbour E, Faderl S, et al. Clofarabine in leukemia. Expert Rev Hematol. 2010 Feb;3(1):15-22.http://www.ncbi.nlm.nih.gov/pubmed/21082931?tool=bestpractice.com[136]Grigoleit GU, Kapp M, Tan SM, et al. Clofarabine-based salvage chemotherapy for relapsed or refractory acute leukemia before allogeneic stem cell transplantation: results from a case series. Leuk Lymphoma. 2009 Dec;50(12):2071-4.http://www.ncbi.nlm.nih.gov/pubmed/19886845?tool=bestpractice.com 呋咯地辛和奈拉滨[137]Sigalas P, Tourvas AD, Moulakakis A, et al. Nelarabine induced complete remission in an adult with refractory T-lineage acute lymphoblastic leukemia: A case report and review of the literature. Leuk Res. 2009 Jul;33(7):e61-3.http://www.ncbi.nlm.nih.gov/pubmed/19157550?tool=bestpractice.com 与传统治疗一起正在研究中。[138]Buie L, Epstein SS, Lindley CM. Nelarabine: a novel purine antimetabolite antineoplastic agent. Clin Therap. 2007 Sep;29(9):1887-99.http://www.ncbi.nlm.nih.gov/pubmed/18035189?tool=bestpractice.com 可以尝试使用脂质体包裹的长春新碱、柔红霉素和阿糖胞苷降低细胞毒性的不良反应,[139]Thomas DA, Kantarjian HM, Stock W, et al. Phase 1 multicenter study of vincristine sulfate liposomes injection and dexamethasone in adults with relapsed or refractory acute lymphoblastic leukemia. Cancer. 2009 Dec 1;115(23):5490-8.http://www.ncbi.nlm.nih.gov/pubmed/19708032?tool=bestpractice.com 同时可以作为存在 NOTCH1 突变的 T-ALL 的 γ-分泌酶抑制剂和存在 FLT-3 突变的 MLL 重排 B-ALL 的 FLT-3 抑制剂。[140]Ferrando A. The role of NOTCH1 signaling in T-ALL. Hem Am Soc Hematol Educ Program. 2009 Jan:(1);353-61.http://asheducationbook.hematologylibrary.org/content/2009/1/353.longhttp://www.ncbi.nlm.nih.gov/pubmed/20008221?tool=bestpractice.com[141]Weisberg E, Barret R, Liu Q, et al. FLT3 inhibition and mechanisms of drug resistance in mutant FLT3 positive AML. Drug Resist Updat. 2009 Jun;12(3):81-9.http://www.ncbi.nlm.nih.gov/pubmed/19467916?tool=bestpractice.com 使用硼替佐米的蛋白酶体抑制剂是ALL治疗的潜在靶点。[142]Szczepanek J, Pogorzala M, Konatkowska B, et al. Differential ex vivo activity of bortezomib in newly diagnosed paediatric acute lymphoblastic and myeloblastic leukaemia. Anticancer Res. 2010 Jun;30(6):2119-24.http://www.ncbi.nlm.nih.gov/pubmed/20651360?tool=bestpractice.com[143]Messinger Y, Gaynon P, Raetz E, et al. Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): a report from the therapeutic advances in childhood leukemia (TACL) consortium. Pediatr Blood Cancer. 2010 Aug;55(2):254-9.http://www.ncbi.nlm.nih.gov/pubmed/20582937?tool=bestpractice.com