Treatment of adult acute leukemia

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.