Management of Philadelphia chromosome-positive acute lymphoblastic leukemia.
Management of Philadelphia chromosome-positive acute lymphoblastic leukemia.
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DOI：
10.1038/leusup.2012.7
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发表时间：
2012-08
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影响因子：
--
通讯作者：
OG Ottmann
中科院分区：
文献类型：
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作者：
OG Ottmann
针对ABL激酶的酪氨酸激酶抑制剂（TKI）目前在费城染色体阳性急性淋巴细胞白血病（Ph+ ALL）的一线治疗中常规使用，导致血液学缓解率超过90%。当TKI与化疗联合使用而不是作为单药治疗时，最小残留疾病水平通常较低。虽然与历史对照相比，基于TKI的方案的结局已大幅改善，但首次缓解时的异基因干细胞移植（SCT）为大多数符合SCT条件的患者提供了最佳治愈机会。SCT后给予伊马替尼可进一步降低分子复发，并与无复发生存率和总生存率的显著改善相关。非移植患者的高复发率主要归因于BCR-ABL酪氨酸激酶结构域突变的白血病克隆的出现。正在进行的新TKI研究将确定这些更有效的药物是否能够在不进行SCT的情况下维持缓解。微小残留病评估已成为Ph+ ALL管理的一个组成部分，因为它具有预后重要性，并用于指导治疗干预。目前正在临床试验中研究新型免疫干预和TKI联合治疗，可能进一步改善Ph+ ALL患者的预后。
Tyrosine kinase inhibitors (TKIs) directed against the ABL kinase are now used routinely during frontline therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and result in hematologic remission rates exceeding 90%. Minimal residual disease levels are generally lower when TKIs are used in combination with chemotherapy rather than as monotherapy. Although outcome has improved substantially with TKI-based regimens compared with historic controls, allogeneic stem cell transplantation (SCT) in first remission provides the best chance of cure for the majority of patients eligible for SCT. Administration of imatinib after SCT further reduces molecular recurrence and is associated with greatly improved relapse-free and overall survival. The high relapse rate in non-transplanted patients is largely attributable to the emergence of leukemic clones with mutations in the tyrosine kinase domain of BCR-ABL. Ongoing studies with newer TKIs will determine whether these more potent agents are able to sustain remissions without SCT. Assessment of minimal residual disease has become an integral part of the management of Ph+ ALL, as it has prognostic importance and is used to guide therapeutic intervention. Novel immunotherapeutic interventions and combinations of TKIs are currently being investigated in clinical trials and may further improve the prognosis of patients with Ph+ ALL.