Adult acute leukemia

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires (1) differentiation of acute myeloid leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognition of clinically relevant subtypes; (2) identification of patients who are more likely or less likely than average to benefit from a conventional treatment; and (3) selection of therapy that provides a reasonable likelihood of response with acceptable risk of toxic effects. The diagnosis of acute leukemia is established in most cases by a bone marrow aspirate that demonstrates at least 30% blast cells. The traditional criteria to distinguish between AML and ALL rely on morphology and cytochemical reactions. Immunologic analysis of antigen expression and analysis for numerical or structural chromosomal abnormalities of leukemia cells are routinely feasible. Karyotypic analysis is of prognostic importance and should be performed on all diagnostic specimens of bone marrow aspirate. Immunophenotypic analysis may be useful to confirm the disease classification in selected cases. The importance of the routine immunophenotypic characterization of acute leukemia, however, is controversial. The subtypes that must be recognized because of the need for specific treatment include (a) acute promyelocytic leukemia (APL), which is the M3 subtype of AML, and (b) the L3 subtype or mature B-cell ALL. Induction therapy for acute leukemia is treatment intended to achieve induction of complete remission (CR). Complete remission is defined as the absence of morphologic evidence of leukemia after recovery of the peripheral blood cell counts. Failure to achieve CR may be attributed to death during chemotherapy-induced bone marrow hypoplasia or to drug resistance manifested either as failure to achieve hypoplasia or as persistent leukemia after recovery from hypoplasia. Postremission therapy is treatment administered in CR to prevent or delay relapse of the leukemia. However, the majority of patients have disease relapse. Intensification of therapy is a treatment strategy designed to overcome resistance to chemotherapy. Recent clinical trials of intensified induction or postremission therapy suggest improved outcome. However, the toxic effects of dose intensification can be substantial, limiting any potential benefit of this approach. Identification of prognostic factors may allow one to estimate the likelihood of an outcome, to determine an optimal treatment strategy. It is well established that age at the time of diagnosis, leukemia cell karyotype, and whether the leukemia is de novo or secondary are factors that influence treatment decisions. Patients with favorable prognostic factors should probably receive conventional therapy. Patients with unfavorable prognostic factors have shown little benefit from conventional therapy. In addition, factors that indicate poor outcome with conventional therapy are also predictive of poor outcome with intensified therapy. Consequently, these patients should be considered for investigational therapeutic strategies. The bias may be to counsel them to accept the potential increased morbidity of such treatment before there is definite evidence of the possibility of improved outcome. Induction chemotherapy for younger patients with AML (less than 55 years of age) in general consists of one or more courses of cytarabine (ara-C) and an anthracycline or an anthracycline derivative. Randomized trials have failed to confirm that treatment with either etoposide or high-dose ara-C induces disease remission. Patients with secondary AML, high levels of CD34 antigen expression, or an unfavorable karyotype, however, may benefit from ind