Acute
leukemia is the most common form of childhood
cancer and is the primary cause of
cancer-related mortality in children. In the United approximately 3250 cases are diagnosed annually in children and adolescents younger than 20 years, of whom 2400 have
acute lymphoblastic leukemia (ALL). Treatment results in
childhood ALL continue to improve, and the expected current cure rates approach 75 to 80% of all children with ALL, including
T-ALL and mature B-cell ALL, the two variants that, not too long ago, had a considerably poorer prognosis compared with the common form of BpALL. The most significant new development in the past 2 years has been the development of further evidence for fetal origin of childhood
leukemias, and additional evidence to support the notion that postnatal events modulating the events of immune-mediated elimination of these leukemic clones play a major role in the eventual development of clinical disease. Other epidemiologic developments include (1) increased appreciation of the role of
drug-metabolizing
enzymes, both in determining the predisposition to
leukemia and response to
therapy; and (2) both clinical observations and gene expression studies seeming to identify a new approach to the evaluation and treatment of children with MLL (11q23) rearrangements. A most remarkable new development in the induction
therapy of childhood
leukemia and
lymphoma in the United States is the use of
urate oxidase for prevention of
tumor lysis syndrome and the associated
uric acid nephropathy. Drug resistance, determined either on leukemic blast cells in vitro or by studies of MRD, is being looked at critically in an effort to improve the treatment results further. Consolidation with HDMTX has gained wider popularity with the realization that effective CNS prophylaxis can be achieved with intrathecal
therapy plus HDMTX for consolidation. In contrast to ALL, the progress in the
therapy of
acute myeloid leukemia (AML) lags behind, with cure rates of approximately 40 to 50%. There is no convincing evidence for substitution of
daunorubicin with other
anthracyclines, nor evidence for using high-dose
cytarabine during induction in childhood AML. Rather, a 3 + 10 regimen with total
daunorubicin 180 mg/m2 and
cytarabine 100 to 200 mg/2 for 10 days appears to yield the best results. The most important component of the postremission
chemotherapy continues to be several courses of high-dose
cytarabine. The results from the MRC 10, LAME 89/91 studies and the recent BFM 93 trial with high-dose
cytarabine and
mitoxantrone suggest that there may be some benefit to including this combination in the postremission phase of AML. Despite these improvements in
chemotherapy, allogeneic BMT from a matched family donor remains the best option for most patients (excluding
Down syndrome, APL, and possibly those with inv16). Newer prognostic markers of interest include FLT3/ITD and
minimal residual disease at the end of induction
therapy.