Hurtado R, Candelaria M, Vargas F, Majluf A, Bolaños F, Labardini J R
Departament of Hemato-Oncology, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico City, Mexico.
Stem Cells. 1995 Mar;13(2):112-22. doi: 10.1002/stem.5530130203.
Post-remission high-dose chemotherapy has been an important advance in the treatment of adult acute leukemia (AAL). Without the use of colony-stimulating factors (CSFs) in this program, the mortality rate varies from 5 to 17%, and infectious complications arise in more than 50%. These findings limit the widespread use of such forms of therapy. The use of high-dose ara-C (HIDAC) alone or in combination with other drugs is the most common regimen studied, however neither other drug combinations nor the addition of supporting CSFs have been extensively explored. For this reason we studied the effect of high-dose cyclosphosphamide-etoposide (CECY) plus recombinant human granulocyte-macrophage (rHuGM)-CSF with the intention of decreasing morbimortality and prolonging disease-free survival (DFS). Since 1992 we have included 51 complete remission patients with AAL in the CECY plus rHuGM-CSF protocol. The maximal myelosuppression occurred in a mean of 6.4 days, and the mean days required for absolute neutrophil count recovery was 13 days and for platelets 21 days (p < 0.0001). No toxic deaths occurred and only two serious infectious complications were seen. After two years of follow-up, 50% of de novo acute myelogenous leukemia patients had relapsed at 13 months, and 50% of de novo adult acute lymphocytic leukemia patients had relapsed at 15 months. In a recent update, we have not seen a significant difference when compared to historic groups. The CECY protocol does not appear to be superior in prolonging DFS compared to HIDAC as a post-remission strategy for newly diagnosed AAL. The main difference was the absence of toxic deaths and minimal serious infectious complications in the CECY protocol. Therefore, we suggest that the use of rHuGM-CSF in post-remission programs should be included in future studies.
缓解期后大剂量化疗是成人急性白血病（AAL）治疗的一项重要进展。在该方案中不使用集落刺激因子（CSF）时，死亡率在5%至17%之间，超过50%的患者会出现感染并发症。这些发现限制了这种治疗形式的广泛应用。单独使用大剂量阿糖胞苷（HIDAC）或与其他药物联合使用是研究最普遍的方案，然而其他药物组合以及添加支持性CSF的情况尚未得到广泛探索。因此，我们研究了大剂量环磷酰胺-依托泊苷（CECY）联合重组人粒细胞-巨噬细胞（rHuGM）-CSF的效果，旨在降低病死率并延长无病生存期（DFS）。自1992年以来，我们将51例AAL完全缓解患者纳入CECY联合rHuGM-CSF方案。最大骨髓抑制平均发生在6.4天，绝对中性粒细胞计数恢复的平均天数为13天，血小板恢复的平均天数为21天（p<0.0001）。未发生毒性死亡，仅出现两例严重感染并发症。经过两年随访，初发急性髓系白血病患者中有50%在13个月时复发，初发成人急性淋巴细胞白血病患者中有50%在15个月时复发。在最近的更新中，与历史组相比，我们未发现显著差异。作为新诊断AAL缓解期后的策略，CECY方案在延长DFS方面似乎并不优于HIDAC。主要区别在于CECY方案中没有毒性死亡且严重感染并发症极少。因此，我们建议在未来的研究中应纳入在缓解期方案中使用rHuGM-CSF的内容。
