In vivo cell growth and pharmacologic determinants of clinical response in acute myelogenous leukemia.
In vivo cell growth and pharmacologic determinants of clinical response in acute myelogenous leukemia.
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DOI：
10.1182/blood.v73.1.24.24
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发表时间：
1989
期刊：
影响因子：
20.3
通讯作者：
J. Karp;R. Donehower;J. Enterline;G. Dole;M. Fox;P. Burke
中科院分区：
文献类型：
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作者：
J. Karp;R. Donehower;J. Enterline;G. Dole;M. Fox;P. Burke
体内初始细胞减灭后残留的恶性细胞增殖率可预测的增加，为成人急性髓系白血病（AML）使用1 - B - D - 阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara - C）进行定时序贯治疗（TST）提供了理论基础。通过比较治疗前（第0天）和体内药物残留肿瘤增殖预测峰值（第8天）所获得的AML骨髓细胞生长动力学和生化药理学决定因素，评估了体内白血病细胞生长、细胞内阿糖胞苷代谢以及对含阿糖胞苷的TST的临床反应之间的关系。对DNA合成和细胞内阿糖胞苷净代谢的连续测量表明，与初诊并达到完全缓解的成人的治疗前细胞相比，第8天残留肿瘤中的这两个决定因素均显著增加，但对于TST难治性患者则不然。AML细胞增殖和生化药理学之间的相互关系共同量化了通过缓解的实现和持续时间所衡量的细胞毒性，并用于预测对阿糖胞苷TST的最终临床结果，其中生长和有利的药代动力学是药物方案成功的内在因素。
A predictable increase in the proliferative rate of malignant cells remaining after initial cytoreduction in vivo forms the rationale for timed sequential therapy (TST) with 1-B-D-arabinofuranosylcytosine (ara-C) for adult acute myelogenous leukemia (AML). The relationship between in vivo leukemic cell growth, intracellular ara-C metabolism, and clinical response to ara-C-containing TST was evaluated by comparing AML marrow cell growth kinetic and biochemical pharmacologic determinants obtained before therapy (day 0) and at the predicted peak of in vivo postdrug residual tumor proliferation (day 8). Serial measurements of DNA synthesis and net intracellular ara-C metabolism demonstrated marked increases in both determinants in day 8 residual tumor when compared with the pretreatment cells for newly diagnosed adults achieving complete remission but not for TST-refractory patients. The interrelationship of AML cell proliferation and biochemical pharmacology together quantitate cytotoxicity measured by both achievement and duration of remission and serve to predict eventual clinical outcome in response to TST with ara-C where both growth and favorable pharmacokinetics are intrinsic to the success of the drug schedule.