Patients with ALL generally receive threeor four-agent induction chemotherapy based on their initial risk group assignment. Lowand standard-risk patients receive vincristine, prednisone, and L-asparaginase for 4 weeks; high-risk patients also receive an anthracycline (daunorubicin or doxorubicin). During induction, intrathecal instillation of some combination of methotrexate, cytarabine, and hydro-cortisone is given to treat existing CNS leukemia or prevent its development. Following induction of successful remission, which is achieved in nearly all patients with ALL, the remission is consolidated along with CNS-directed therapy. The intensity of therapy depends on risk factors with higher risk patients receiving more intensive chemotherapy. For patients with CNS disease detected at diagnosis and those with T-cell ALL, cranial radiation therapy is usually provided, although the omission of radiation therapy for all pediatric leukemia patients holds great promise. All patients receive continuation therapy for a total duration of therapy of 2 to 3 years. Continuation therapy generally consists of intermittent vincristine and short courses (5 to 7 days) of oral corticosteroid therapy, plus daily oral 6-mercaptopurine, and weekly methotrexate (orally or intramuscularly).
The treatment of AML is quite different from that of ALL because nonmyelosuppressive drugs (vincristine, prednisone, and asparaginase) are not effective. Several cycles of extremely intensive myelosuppressive chemotherapy are necessary to cure childhood AML; there is little evidence that low-dose continuation therapy is helpful in AML (with the exception of acute promyelocytic leukemia).
Induction therapy for AML usually consists of cytarabine, daunomycin, and etoposide (or 6-thioguanine). If a patient has an HLA-matched sibling donor, most experts recommend a stem cell transplantation in the first remission, except in patients with Down syndrome and those with relatively favorable cytogenetics such as inv(16), t(15;17), and t(8;21). Bortezomib, sorafenib and haploidentical natural killer cell transplantation are being studied as an adjuvant therapy for newly diagnosed childhood AML.
Major short-term complications associated with the treatment of leukemia result from bone marrow suppressioncaused by chemotherapy. Patients may have bleeding andsignificant anemia that necessitates transfusion of plateletsor blood. Neutropenia with fewer than 500 neutrophils/mm3, and especially fewer than 100 neutrophils/mm3, greatly predispose the patient to significant bacterial and fungal infection. Cell-mediated immunosuppression increases the risk ofPneumocystis jiroveci (carinii) pneumonia. Prophylaxis withoral trimethoprim-sulfamethoxazole or aerosolized pentamidine is recommended. Prophylaxis with antibiotics andantifungal agents is under investigation. Long-term sequelaeof therapy are less common than in previous treatment erasbut are prevalent in long-term survivors treated in the 1980sand earlier. These sequelae include neurocognitive impairment, short stature, obesity, cardiac dysfunction, infertility,second malignant neoplasms, and psychosocial problems(see Table 154-3).