Büchner Thomas, Berdel Wolfgang E, Haferlach Claudia, Haferlach Torsten, Schnittger Susanne, Müller-Tidow Carsten, Braess Jan, Spiekermann Karsten, Kienast Joachim, Staib Peter, Grüneisen Andreas, Kern Wolfgang, Reichle Albrecht, Maschmeyer Georg, Aul Carlo, Lengfelder Eva, Sauerland Maria-Cristina, Heinecke Achim, Wörmann Bernhard, Hiddemann Wolfgang
University of Münster, Department of Hematology/Oncology, Münster, Germany.
J Clin Oncol. 2009 Jan 1;27(1):61-9. doi: 10.1200/JCO.2007.15.4245. Epub 2008 Dec 1.
The purpose of the study was to assess the contribution of age and disease variables to the outcome of untreated patients with acute myeloid leukemia (AML) receiving varying intensive induction chemotherapy.
Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.
In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.
Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.
本研究旨在评估年龄和疾病变量对接受不同强度诱导化疗的急性髓系白血病（AML）未治疗患者结局的影响。
年龄在16至85岁之间、患有原发性AML、已知核型且缓解后化疗方案统一的患者被纳入两项连续试验，符合条件并被随机分配接受标准剂量（阿糖胞苷、柔红霉素和6-硫鸟嘌呤）与高剂量（阿糖胞苷和米托蒽醌）联合诱导化疗，或接受两个疗程的高剂量联合化疗。根据核型、核磷蛋白和FLT3突变、白细胞计数、血清乳酸脱氢酶以及残留原始细胞定义亚组。
在1284例患者中，60岁及以下和60岁以上患者的4年总生存率分别为37%和16%（P < .001），持续缓解持续时间分别为46%和22%（P < .001）。在所有定义的亚组中均发现了类似的与年龄相关的结局差异。在任何年龄组或预后亚组中，未观察到根据随机分配的治疗方案在结局上存在差异。关于预后亚组，也考虑了分子因素。
在统一条件下，老年和年轻AML患者的风险特征存在适度差异，且对强化化疗均无剂量反应。在所有亚组中观察到的他们在结局上的根本差异仍无法解释。进一步的分子研究可能阐明AML中的年龄效应并确定新的靶点。
