Seipelt G, Hofmann W K, Martin H, Wassmann B, Boehme A, Ottmann O G, Hoelzer D
Medizinische Klinik III, Hämatologie/Onkologie, Universitätsklinik Frankfurt, Germany.
Ann Hematol. 1998 Mar-Apr;76(3-4):145-51. doi: 10.1007/s002770050379.
The toxicity and outcome after high-dose ara-C/daunorubicin (HDara-C/DNR) consolidation therapy in de novo AML was compared in 11 patients who received an idarubicin-containing induction therapy (IDA; from June 1995 to March 1997) and 16 patients pretreated with daunorubicin (DNR; from July 1990 to May 1995) for induction. The DNR group consisted of two cohorts, one (n = 6) of patients who had received, as had the IDA group, two induction and one intermediate-dose ara-C consolidation courses, and another (n = 10) of patients who had been pretreated with one induction and one consolidation course prior to HDara-C/DNR. There was no difference in the relative dose between the three cohorts. Following HDara-C/DNR, the IDA-pretreated patients experienced a more prolonged myelosuppression during consolidation therapy compared with the DNR group. Duration of neutropenia (< 500 neutrophils/microl) following HDara-C/DNR was 31.2 +/- 16 days (mean +/- SEM) in the IDA group compared with 18.7 +/- 5 days in the DNR group (p < .001 Mann-Whitney U-test). The duration 'of thrombocytopenia (platelets < 25000/microl) was 34.8 +/- 20 days in the IDA group vs. 18.5 +/- 6 days in the DNR group (p < .005). The more prolonged myelosupression was associated with a longer duration of fever (18.9 +/- 24 vs. 6.9 +/- 5.2 days). A greater incidence, length (11 +/- 8 vs. 1.2 +/- 2 days), and severity of diarrhea were observed in the IDA-pretreated group. Three of 11 IDA patients experienced WHO grade III-IV diarrhea. In the IDA group two patients developed severe enterocolitis with Candida septicemia, and one of these patients died. One patient in the IDA group died during prolonged aplasia. In the DNR group 6/16 patients experienced grade I-II diarrhea. Two patients in each group died during consolidation therapy. The CR rate was 87% in the IDA group and 79% in the DNR group. Relapse-free survival after HDara-C is 50% at a median follow-up of 60 months in the DNR group and 45% after a median follow-up of 17 months in the IDA group. Whether the advantage of the superior response rate in the IDA-treated patients may be lost during HDara-C consolidation treatment due to increased toxicity remains to be proven in larger trials.
对11例接受含去甲氧柔红霉素诱导治疗（IDA；1995年6月至1997年3月）的初发急性髓系白血病（AML）患者和16例接受柔红霉素诱导治疗（DNR；1990年7月至1995年5月）的患者进行大剂量阿糖胞苷/柔红霉素（HDara-C/DNR）巩固治疗后的毒性和结局比较。DNR组由两个队列组成，一个队列（n = 6）的患者与IDA组一样接受了两个诱导疗程和一个中剂量阿糖胞苷巩固疗程，另一个队列（n = 10）的患者在HDara-C/DNR之前接受了一个诱导疗程和一个巩固疗程。三个队列之间的相对剂量没有差异。HDara-C/DNR治疗后，与DNR组相比，IDA预处理的患者在巩固治疗期间骨髓抑制时间更长。HDara-C/DNR后，IDA组中性粒细胞减少（<500个中性粒细胞/微升）的持续时间为31.2±16天（平均值±标准误），而DNR组为18.7±5天（p <.001，曼-惠特尼U检验）。IDA组血小板减少（血小板<25000/微升）的持续时间为34.8±20天，而DNR组为18.5±6天（p <.005）。更长时间的骨髓抑制与更长的发热持续时间相关（18.9±24天对6.9±5.2天）。在IDA预处理组中观察到腹泻的发生率更高、持续时间更长（11±8天对1.2±2天）且更严重。11例IDA患者中有3例出现世界卫生组织III-IV级腹泻。在IDA组中，2例患者发生严重小肠结肠炎伴念珠菌败血症，其中1例死亡。IDA组中有1例患者在长期再生障碍期间死亡。DNR组中16例患者中有6例出现I-II级腹泻。每组各有2例患者在巩固治疗期间死亡。IDA组的完全缓解率为87%，DNR组为79%。在DNR组中，HDara-C后的无复发生存率在中位随访60个月时为50%，在IDA组中，中位随访17个月后的无复发生存率为45%。IDA治疗患者较高的缓解率优势在HDara-C巩固治疗期间是否会因毒性增加而丧失，仍有待更大规模试验证实。
