Büchner T, Hiddemann W, Berdel W, Wörmann B, Löffler H, Schoch C, Haferlach T, Ludwig W D, Maschmeyer G, Staib P, Andreesen R, Balleisen L, Haase D, Eimermacher H, Aul C, Rasche H, Uhlig J, Grüneisen A, Reis H E, Hartlapp J, Hirschmann W D, Weh H J, Pielken H J, Gassmann W, Sauerland M C, Heinecke A
Department of Medicine, Hematology/Oncology, University of Münster, Germany.
Cancer Chemother Pharmacol. 2001 Aug;48 Suppl 1:S41-4. doi: 10.1007/s002800100305.
Intensive induction therapy in acute myeloid leukemia (AML) as in some other systemic malignancies is a strategy fundamentally different from post-remission strategies. Approaches such as consolidation treatment, prolonged maintenance, and autologous or allogeneic transplantation in first remission are directed against the minimal residual disease in which a malignant cell population has survived induction treatment and shows resistance due to special genetic or kinetic features. In contrast, induction therapy deals with naive tumor cells possibly different from their counterparts in remission in terms of their kinetic status and sensitivity. Therefore, in AML the introduction of intensification strategies into the induction phase of treatment has been suggested as a new step in addition to intensification in the postremission phase. As expected from the dose effects observed in post-remission treatment with high-dose cytarabine (AraC) or longer treatment, similar dose effects have been found in induction treatment both from the incorporation of high-dose AraC and from the double-induction strategy used in patients up to 60 years of age. As a particular effect, patients with poor-risk AML according to an unfavorable karyotype, high LDH in serum, or a delayed response show longer survival following double induction containing high-dose AraC as compared to standard-dose AraC. A corresponding dose effect in the induction treatment of patients aged 60 years and older has been found with daunorubicin 60 vs 30 mg/m2 as part of the thioguanine/ AraC/daunorubicin (TAD) regimen with the higher dosage significantly increasing the response rate and survival in these older patients who represent a poor-risk group as a whole. Thus we have been able to demonstrate both in younger and older patients that a poor prognosis can be improved by a more intensive induction therapy. High-dose AraC in induction, however, exhibits cumulative toxicity in that repeated courses containing high-dose AraC in the post-remission period lead to long-lasting aplasias of about 6 weeks. Thus after intensive induction treatment, high-dose chemotherapy in remission may be practicable using stem-cell rescue and may contribute to a further improvement in the outcome in poor-risk as well as average-risk patients with AML. These approaches are currently under investigation by the German AML Cooperative Group (AMLCG). "The more intensive the better" is certainly not the way to go in the management of AML and other systemic malignancies but some increase in intensity may be possible and better.
急性髓系白血病（AML）的强化诱导治疗与其他一些全身性恶性肿瘤的强化诱导治疗一样，是一种与缓解后治疗策略截然不同的策略。巩固治疗、延长维持治疗以及首次缓解时的自体或异基因移植等方法，针对的是微小残留病，即恶性细胞群体在诱导治疗后存活下来，并因其特殊的基因或动力学特征而表现出耐药性。相比之下，诱导治疗针对的是原始肿瘤细胞，其动力学状态和敏感性可能与缓解期的肿瘤细胞不同。因此，在AML中，除了缓解期强化治疗外，有人建议在治疗的诱导阶段引入强化策略作为新的一步。正如在高剂量阿糖胞苷（AraC）缓解后治疗或更长疗程治疗中观察到的剂量效应所预期的那样，在诱导治疗中也发现了类似的剂量效应，这既来自高剂量AraC的加入，也来自60岁及以下患者使用的双诱导策略。作为一个特殊的效应，根据核型不良、血清乳酸脱氢酶（LDH）水平高或反应延迟判断为高危AML的患者，与标准剂量AraC相比，接受含高剂量AraC的双诱导治疗后生存期更长。在60岁及以上患者的诱导治疗中，发现柔红霉素剂量为60mg/m²与30mg/m²相比有相应的剂量效应，作为硫鸟嘌呤/阿糖胞苷/柔红霉素（TAD）方案的一部分，较高剂量显著提高了这些整体上属于高危组的老年患者的缓解率和生存率。因此，我们已经能够证明，无论是年轻患者还是老年患者，强化诱导治疗都可以改善不良预后。然而，诱导治疗中的高剂量AraC具有累积毒性，因为缓解期重复使用含高剂量AraC的疗程会导致约6周的长期造血功能抑制。因此，在强化诱导治疗后，使用干细胞救援进行缓解期高剂量化疗可能是可行的，并且可能有助于进一步改善高危以及中危AML患者的治疗结果。德国AML协作组（AMLCG）目前正在对这些方法进行研究。“强度越高越好”肯定不是AML和其他全身性恶性肿瘤治疗的正确方法，但强度可能可以适当提高且这样做可能更好。
