Servicio de Farmacia, Área del Medicamento, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Servicio de Hematología y Hemoterapia, Hospital Universitari i Politècnic La Fe, Av. Fernando Abril Martorell, 106, 46026, Valencia, Spain.
Ann Hematol. 2018 Jul;97(7):1115-1153. doi: 10.1007/s00277-018-3304-y. Epub 2018 Apr 21.
Prognosis in relapsed and refractory acute myeloid leukemia (R/R AML) patients is dismal, with no satisfactory and standard salvage chemotherapy regimen. We performed a systematic review in order to analyze the clinical outcomes reported with conventional chemotherapy schemes in adult patients with R/R AML. To have a better understanding of the R/R ground, we included studies in R/R AML adult population at any disease stage (i.e., primary refractory as well as first relapse or beyond). Study selection included a total number of 157 out of 850 records, with a wide variety of schedules. Furthermore, only 24 studies were randomized clinical trials (RCTs), being the majority of the studies retrospective analyses in small cohorts. This review reveals that several intensive regimens (cytarabine + mitoxantrone + etoposide or gemtuzumab, and cytarabine + purine analogue ± antracycline) achieve relatively high complete remission (CR) rates (44 to 59.4%). However, most of these schemes did not obtain substantial CR duration (4.9 to 9.8 months) or overall survival (6.2 to 8.7 months). In unfit/vulnerable patients non-intensive approaches are recommended to control disease progression and minimize treatment-related mortality. A better knowledge of the prognostic factors, more effective and less toxic combinations using conventional and new therapies, as well as improvements in allo-HSCT procedure and timing, could play a role to improve the clinical outcomes in the future. Clinical trials should be the first treatment option in R/R AML, both in fit and unfit patients.
复发/难治性急性髓系白血病(R/R AML)患者的预后较差,尚无令人满意的标准挽救化疗方案。我们进行了系统评价,以分析常规化疗方案在 R/R AML 成年患者中的临床结果。为了更好地了解 R/R 基础,我们纳入了任何疾病阶段(即原发性耐药以及首次复发或复发后)的 R/R AML 成年人群的研究。研究选择包括从 850 条记录中筛选出的 157 项研究,方案种类繁多。此外,只有 24 项研究是随机临床试验(RCT),大多数研究是小队列的回顾性分析。本综述表明,几种强化方案(阿糖胞苷+米托蒽醌+依托泊苷或吉妥珠单抗和阿糖胞苷+嘌呤类似物±蒽环类药物)可实现相对较高的完全缓解(CR)率(44%至 59.4%)。然而,这些方案中的大多数并未获得实质性的 CR 持续时间(4.9 至 9.8 个月)或总生存时间(6.2 至 8.7 个月)。对于身体不适合/脆弱的患者,建议采用非强化方法来控制疾病进展并降低治疗相关死亡率。更好地了解预后因素、使用常规和新疗法的更有效且毒性更小的组合,以及改进同种异体 HSCT 程序和时机,可能在未来改善临床结果方面发挥作用。临床试验应成为 R/R AML 的首选治疗方法,无论是身体适合的还是不适合的患者。