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老年复发性急性髓系白血病患者的当前治疗结果及治疗选择

Current Therapeutic Results and Treatment Options for Older Patients with Relapsed Acute Myeloid Leukemia.

作者信息

Ferrara Felicetto, Lessi Federica, Vitagliano Orsola, Birkenghi Erika, Rossi Giuseppe

机构信息

Division of Hematology, Cardarelli Hospital, 80128 Napoli, Italy.

Department of Medicine, Hematology and Clinical Immunology Unit, University of Padua, 35153 Padua, Italy.

出版信息

Cancers (Basel). 2019 Feb 14;11(2):224. doi: 10.3390/cancers11020224.

Abstract

Considerable progress has been made in the treatment of acute myeloid leukemia (AML). However, current therapeutic results are still unsatisfactory in untreated high-risk patients and poorer in those with primary refractory or relapsed disease. In older patients, reluctance by clinicians to treat unfit patients, higher AML cell resistance related to more frequent adverse karyotype and/or precedent myelodysplastic syndrome, and preferential involvement of chemorefractory early hemopoietic precursors in the pathogenesis of the disease further account for poor prognosis, with median survival lower than six months. A general agreement exists concerning the administration of aggressive salvage therapy in young adults followed by allogeneic stem cell transplantation; on the contrary, different therapeutic approaches varying in intensity, from conventional salvage chemotherapy based on intermediate⁻high-dose cytarabine to best supportive care, are currently considered in the relapsed, older AML patient population. Either patients' characteristics or physicians' attitudes count toward the process of clinical decision making. In addition, several new drugs with clinical activity described as "promising" in uncontrolled single-arm studies failed to improve long-term outcomes when tested in larger randomized clinical trials. Recently, new agents have been approved and are expected to consistently improve the clinical outcome for selected genomic subgroups, and research is in progress in other molecular settings. While relapsed AML remains a tremendous challenge to both patients and clinicians, knowledge of the molecular pathogenesis of the disease is fast in progress, potentially leading to personalized therapy in most patients.

摘要

急性髓系白血病(AML)的治疗已取得显著进展。然而,对于未经治疗的高危患者,目前的治疗效果仍不尽人意,而对于原发性难治或复发疾病患者,治疗效果更差。在老年患者中,临床医生不愿治疗身体状况不佳的患者、与更频繁的不良核型和/或先前的骨髓增生异常综合征相关的较高AML细胞耐药性,以及化疗难治性早期造血前体细胞在疾病发病机制中的优先参与,进一步导致预后不良,中位生存期低于6个月。对于年轻成人,先进行积极的挽救性治疗然后进行异基因干细胞移植,这一点已达成普遍共识;相反,对于复发的老年AML患者群体,目前考虑采用从基于中高剂量阿糖胞苷的传统挽救性化疗到最佳支持治疗等强度不同的不同治疗方法。患者的特征或医生的态度在临床决策过程中都很重要。此外,在非对照单臂研究中被描述为“有前景”的几种具有临床活性的新药,在大型随机临床试验中进行测试时未能改善长期疗效。最近,新药物已获批准,预计将持续改善特定基因组亚组的临床结局,并且在其他分子背景下的研究也在进行中。虽然复发AML对患者和临床医生来说仍然是一个巨大的挑战,但对该疾病分子发病机制的了解正在迅速进展,有望在大多数患者中实现个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd2a/6406399/31fdbe553858/cancers-11-00224-g001.jpg

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