Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
Treatment of Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia.
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DOI：
10.1007/s11864-019-0603-z
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发表时间：
2019-01-24
影响因子：
4.3
通讯作者：
Ravandi, Farhad
中科院分区：
文献类型：
--
作者：
Abou Dalle, Iman;Jabbour, Elias;Short, Nicholas J.;Ravandi, Farhad
关键词：
随着酪氨酸激酶抑制剂(TKIs)在治疗Ph+ALL中的应用，患者的预后有了显著的改善。目前，在前线环境下的标准护理是TKI结合化疗。年龄调整的化疗或皮质类固醇单独用于合并TKI的老年患者，长期受益不大。治疗的主要目标是实现早期深分子缓解，因为在3个月达到完全分子缓解已被证明预示着较高的长期存活率。通过更有效的TKI如Dasatinib或Ponatinib实现这一目标的概率更高，因此我们建议使用第二代或第三代TKI而不是伊马替尼。临床医生应该意识到可能发生的致命心血管事件，主要与波纳替尼有关。首次缓解时仍应考虑异基因造血干细胞移植，尤其是接受伊马替尼联合治疗的年轻患者。在3个月内达到完全分子缓解的患者子集可能能够继续巩固和维持化疗和TKI，而不需要异基因HSCT。鞘内化学预防对所有患者都是强制性的，一些研究表明有必要进行12种鞘内治疗。纳入新药物的新策略，如抗体-药物结合物、双特异性单抗、有效的TKI和CAR T细胞正在研究中。
With the introduction of tyrosine kinase inhibitors (TKIs) in the management of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), the prognosis of patients has improved dramatically. Currently, the standard of care in the frontline setting is TKI in combination with chemotherapy. Age-adjusted chemotherapy or corticosteroids alone have been used with TKIs in elderly patients with comorbidities with modest long-term benefit. The primary goal of treatment is the achievement of early deep molecular remission as achievement of complete molecular remission at 3 months has been demonstrated to be predictive of higher long-term survival. The probability of attaining this goal by a more potent TKIs like dasatinib or ponatinib is higher, thus we recommend the use of second or third generation TKI over imatinib. Clinicians should be aware of possible fatal cardiovascular events mainly related to ponatinib. Allogeneic hematopoietic stem cell transplantation (alloHSCT) should still be considered in first remission, especially for younger patients treated with imatinib combination therapy. A subset of patients achieving complete molecular remission at 3 months may be able to continue consolidation and maintenance with chemotherapy and TKI without the need for alloHSCT. Intrathecal chemoprophylaxis is mandatory for all patients and some studies have suggested the need for 12 intrathecal therapies. New strategies incorporating novel agents, such as antibody-drug conjugates, bispecific monoclonal antibodies, potent TKIs, and CAR T cells are under investigation.
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DOI：
10.1056/nejmoa1609783
发表时间：
2017-03-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kantarjian H;Stein A;Gökbuget N;Fielding AK;Schuh AC;Ribera JM;Wei A;Dombret H;Foà R;Bassan R;Arslan Ö;Sanz MA;Bergeron J;Demirkan F;Lech-Maranda E;Rambaldi A;Thomas X;Horst HA;Brüggemann M;Klapper W;Wood BL;Fleishman A;Nagorsen D;Holland C;Zimmerman Z;Topp MS
通讯作者：
Topp MS
影响因子：
2.7
作者：
Assi, Rita;Kantarjian, Hagop;Jabbour, Elias
通讯作者：
Jabbour, Elias
DOI：
10.1056/nejmoa1306494
发表时间：
2013-11-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cortes JE;Kim DW;Pinilla-Ibarz J;le Coutre P;Paquette R;Chuah C;Nicolini FE;Apperley JF;Khoury HJ;Talpaz M;DiPersio J;DeAngelo DJ;Abruzzese E;Rea D;Baccarani M;Müller MC;Gambacorti-Passerini C;Wong S;Lustgarten S;Rivera VM;Clackson T;Turner CD;Haluska FG;Guilhot F;Deininger MW;Hochhaus A;Hughes T;Goldman JM;Shah NP;Kantarjian H;PACE Investigators
通讯作者：
PACE Investigators
影响因子：
45.3
作者：
Martinelli, Giovanni;Boissel, Nicolas;Stein, Anthony
通讯作者：
Stein, Anthony
影响因子：
45.3
作者：
Bassan, Renato;Rossi, Giuseppe;Rambaldi, Alessandro
通讯作者：
Rambaldi, Alessandro