Büchner T
Department of Internal Medicine, University of Münster, Germany.
Curr Opin Oncol. 1997 Jan;9(1):18-25. doi: 10.1097/00001622-199701000-00004.
In 1996 progress has been made toward a better understanding of acute leukemias, their biology, the effects of different intensity or subtype-specific chemotherapy, and the contribution of bone marrow transplantation. In acute lymphoblastic leukemia, high-dose cytarabine in induction and in postremission treatment improves the cure rate, whereas dose reduction of daunorubicin in older patients worsens response and increases mortality. After acute promyelocytic leukemia has been successfully treated by retinoids, another subtype-specific chemotherapy containing high-dose methotrexate has overcome the primarily poor prognosis of B-cell acute lymphoblastic leukemia. The leukemic stem cell of acute myeloid leukemia representing minimal residual disease, producing disease progression in the patients, and initiating long-term growth in cultures or immunodeficient mice appears as a primitive multipotent cell. Leukemic transformation is reflected either by the specific balanced chromosome translocations or by chromosome deletions or losses. They are associated with histories of cytotoxic drugs such as epipodophylotoxins and anthracyclines or alkylating agents. Alternatively, both kinds of aberrations develop spontaneously with ethnic differences in special subtypes. Cytogenetics also determine favorable and unfavorable prognosis both for chemotherapy and bone marrow transplantation. In acute lymphoblastic leukemia high-risk and nonstandard-risk patients seem to benefit from allogeneic transplantation, whereas in acute myeloid leukemia there is no adequate basis for risk-adapted stratification between treatment modalities. New prospects lie in a more successful use of the effects of treatment intensification possibly supported by autologous blood stem cell transplantation. On the basis of standardized treatment, future clinical research can address the role of biologic features of the individual leukemia such as specific chromosome aberrations, fusion genes, expression of oncogenes, and monitoring of minimal residual disease.
1996年，在对急性白血病、其生物学特性、不同强度或亚型特异性化疗的效果以及骨髓移植的作用的认识方面取得了进展。在急性淋巴细胞白血病中，诱导和缓解后治疗中使用大剂量阿糖胞苷可提高治愈率，而老年患者中柔红霉素剂量减少则会使反应恶化并增加死亡率。在急性早幼粒细胞白血病通过维甲酸成功治疗后，另一种含大剂量甲氨蝶呤的亚型特异性化疗克服了B细胞急性淋巴细胞白血病原本较差的预后。急性髓系白血病的白血病干细胞代表微小残留病，可导致患者疾病进展，并在培养物或免疫缺陷小鼠中启动长期生长，它表现为原始多能细胞。白血病转化可通过特定的平衡染色体易位或染色体缺失或丢失来反映。它们与细胞毒性药物如依托泊苷和蒽环类药物或烷化剂的使用史有关。或者，这两种畸变在特殊亚型中会因种族差异而自发发生。细胞遗传学也决定了化疗和骨髓移植的预后好坏。在急性淋巴细胞白血病中，高危和非标准风险患者似乎从异基因移植中获益，而在急性髓系白血病中，在治疗方式之间进行风险适应性分层尚无充分依据。新的前景在于更成功地利用可能由自体血干细胞移植支持的强化治疗效果。在标准化治疗的基础上，未来的临床研究可以探讨个体白血病的生物学特征的作用，如特定的染色体畸变、融合基因、癌基因表达以及微小残留病的监测。
