Tiedemann K, Waters K D, Tauro G P, Tucker D, Ekert H
Department of Clinical Haematology, Royal Children's Hospital, Parkville Vic, Australia.
Blood. 1993 Dec 15;82(12):3730-8.
Childhood acute myeloid leukemia (AML) has a poor prognosis with standard chemotherapy. Allogeneic bone marrow transplantation (BMT) in remission improves the outlook only for the one third of patients with sibling donors. Autologous BMT with a lower morbidity and mortality is available to all. In this study, maximum cytoreduction was achieved by intensive early chemotherapy. Final intensification, with autologous BMT was offered to all those remaining in first complete remission (CR). Patients received two induction and two consolidation courses of intensively scheduled chemotherapy. Cytoreduction was assessed on day 14 and remission was assessed after courses 2 and 4. Bone marrow was harvested after recovery from the second consolidation course or after the first maintenance course and separated on a discontinuous percoll gradient before cryopreservation. Twenty-eight of 31 consecutively enrolled patients achieved CR. Three relapsed early and, of the 25 eligible, 24 underwent autologous BMT. Twenty-three patients received high-dose melphalan and 1 received busulphan and cyclophosphamide before autologous BMT at a median of 113 days (range, 86 to 301) after initial CR. Trilineage engraftment occurred in all. Neutrophil recovery to greater than 0.5 x 10(9)/L occurred at a median of 46 days (range, 13 to 92) after autologous BMT. Platelet recovery was delayed, with a median time to achieve greater than 20 x 10(9)/L of 42 days (range, 18 to 215). With a minimum follow up of 25 months following autologous BMT only 3 children have relapsed. The 5-year event-free survival rate (EFS) from diagnosis is 68% (95% confidence interval, 46% to 90%). Five-year EFS following autologous BMT is 87% (95% confidence interval, 67% to 100%). Autologous BMT with high-dose melphalan administration after intensive chemotherapy has produced EFS equivalent to allogeneic BMT and is associated with a strikingly low relapse rate. High-dose melphalan appears to be a valuable agent for conditioning therapy in AML.
儿童急性髓系白血病（AML）采用标准化疗预后较差。缓解期进行异基因骨髓移植（BMT）仅能改善三分之一有同胞供者患者的预后。自体BMT发病率和死亡率较低，所有患者均可采用。在本研究中，通过强化早期化疗实现最大程度的细胞减灭。对于所有仍处于首次完全缓解（CR）的患者，给予最终强化治疗并进行自体BMT。患者接受两个诱导疗程和两个强化疗程的密集化疗。在第14天评估细胞减灭情况，在第2和第4疗程后评估缓解情况。在从第二个强化疗程恢复后或第一个维持疗程后采集骨髓，在冷冻保存前通过不连续的Percoll梯度进行分离。连续入组的31例患者中有28例实现CR。3例早期复发，在25例符合条件的患者中，24例接受了自体BMT。23例患者在自体BMT前接受了大剂量美法仑，1例接受了白消安和环磷酰胺，自体BMT时间中位数为初始CR后的113天（范围86至301天）。所有患者均实现三系造血重建。自体BMT后中性粒细胞恢复至大于0.5×10⁹/L的时间中位数为46天（范围13至92天）。血小板恢复延迟，达到大于20×10⁹/L的时间中位数为42天（范围18至215天）。自体BMT后最少随访25个月，仅有3例儿童复发。从诊断开始计算的5年无事件生存率（EFS）为68%（95%置信区间，46%至90%）。自体BMT后的5年EFS为87%（95%置信区间，67%至100%）。强化化疗后给予大剂量美法仑的自体BMT产生的EFS与异基因BMT相当，且复发率极低。大剂量美法仑似乎是AML预处理治疗的一种有价值的药物。
