Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: A report from the Children's Cancer Group
Timed-sequential induction therapy improves postremission outcome in acute myeloid leukemia: A report from the Children's Cancer Group
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DOI：
10.1182/blood.v87.12.4979.bloodjournal87124979
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发表时间：
1996-06-15
期刊：
影响因子：
20.3
通讯作者：
Lange, BJ
中科院分区：
文献类型：
--
作者：
Woods, WG;Kobrinsky, N;Lange, BJ
急性髓性白血病（AML）诱导化疗周期的定时测序已被提出作为一种通过招募和同步残留肿瘤细胞来实现最大白血病细胞杀伤的方法。此外，在存在严重骨髓抑制的情况下是否应该继续强化诱导治疗是一个重要的问题，儿童癌症小组（CCG）进行了一项前瞻性随机试验，其中589名AML患者在诊断时被随机分为两种诱导方法之一，包括5种活性化疗药物的4天周期，第二个周期在第一个周期后10天给药，尽管血细胞计数低或下降（密集定时），或在第一个周期开始后14天或更晚，这取决于骨髓状态（标准定时）。所有达到缓解的患者共接受了4个周期的诱导治疗。然后，如果存在相容的家族供体，则将其分配至异基因骨髓移植（BMT），或随机分配至积极的非清髓性治疗或清除自体BMT补救的清髓性治疗。三个缓解后手臂仍然编码。随机分配至强化定时组的295例患者（75%，99天）与随机分配至标准定时组的294例患者（70%，105天;缓解P = 0.18）的诱导成功率和完成诱导的中位天数相似。然而，随机分配到强化定时组的患者的结局明显改善，3年精算无事件生存率为42% ± 7%（95%置信区间[CI]），而标准定时组患者为27% ± 6%（P = .0005）。诱导结束后3年的无病生存率结果在接受强化定时诱导治疗的患者中为上级（N = 211），55% +/- 9%，标准定时患者为37% +/- 9%（N = 195，P = .0002），从达到缓解开始的中位随访时间为28个月。记录了接受强化时间的患者的上级结果，无论其分配的缓解后治疗如何。AML患者的强化定时诱导治疗显著提高了无事件生存率，即使是接受骨髓清除治疗和BMT补救治疗的患者。如果不控制所接受的诱导治疗的类型，比较不同制备方案的AML中的各种BMT研究的结果将难以解释。(C)1996年，美国血液学会。
Timed sequencing of cycles of induction chemotherapy in acute myeloid leukemia (AML) has been proposed as a way to achieve maximal leukemic cell kill through recruitment and synchronization of residual neoplastic cells. Furthermore, whether intensive induction therapy should be continued in the presence of profound myelosuppression is an important question, The Children's Cancer Group (CCG) conducted a prospective randomized trial in which 589 patients with AML were randomized at diagnosis to one of two induction approaches involving a 4-day cycle of five active chemotherapeutic agents, with the second cycle administered either 10 days after the first cycle, despite low or dropping blood counts (intensive timing), or 14 days or later from the beginning of the first cycle, depending on bone marrow status (standard timing). All patients achieving remission received a total of four cycles of induction therapy. They were then allocated to allogeneic bone marrow transplantation (BMT) if a compatible family donor was present or randomized to aggressive nonmyeloablative therapy or to myeloablative therapy with purged autologous BMT rescue. The three postremission arms remain coded. Induction success and median days to complete induction were similar for the 295 patients randomized to the intensive timing arm (75%, 99 days) compared with the 294 patients randomized to the standard timing arm (70%, 105 days; P = .18 for remission). However, a marked improvement in outcome was demonstrated in patients randomized to the intensive timing arm, with an actuarial event-free survival at 3 years of 42% +/- 7% (95% confidence interval [CI]) versus 27% +/- 6% for patients on the standard timing arm (P = .0005). Disease-free survival results at 3 years from the end of induction were superior for patients receiving intensively timed induction therapy (N = 211), 55% +/- 9% versus 37% +/- 9% for standard timing patients (N = 195, P = .0002), with a median follow-up from achieving remission of 28 months. Superior results were documented for patients receiving intensive timing irrespective of the postremission therapy to which they were allocated. Intensively timed induction therapy for patients with AML markedly improves event-free survival, even for patients undergoing myeloablative therapy with BMT rescue. Without controlling for the type of induction therapy received, results of various BMT studies in AML comparing different preparative regimens will be difficult to interpret. (C) 1996 by The American Society of Hematology.