Acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for 25% of childhood cancer. Clinical and biological parameters define prognostic categories and therapeutic approaches. For the majority of children with B-progenitor ALL, age (1-9 yrs) and white blood count (WBC<50,000) indicate standard risk disease; WBC>50,000 and age >9 yrs. define eligibility for high-risk protocols. Infants (<1 yr. old) are high-risk, frequently associated with chromosomal t(4;11) translocation and extramedullary disease. T-cell immunophenotype is usually associated with clinical high-risk features, including older age, high WBC, and extramedullary disease. Current regimens include induction chemotherapy, consolidation (often including high-dose systemic methotrexate, MTX), and continuation phases; intensification or reinduction is incorporated for high-risk disease. Preventive CNS therapy is e critical component of therapy. Intrathecal (IT) chemotherapy (MTX +/- cytosine-arabinoside and hydrocortisone) and systemic agents provide adequate CNS therapy in standard risk patients. The 'threshold' for using preventive cranial irradiation (Crl, 18 Gy) varies among protocols, but systematically includes those with T-cell ALL and WBC~50,000; other criteria may include B- progenitor ALL with WBC> 100,000, philadelphia chromosome positive ALL, residual marrow disease at day 7, or male gender. For the 5% of children with CNS leukemia at diagnosis (defined as CSF with 5 or greater WBC/uL end positive cytology), Crl is administered at does of 18 to 24 Gy. Recent series show a CNS relapse rate approximating 5%. Reinduction chemotherapy, IT therapy, and subsequent craniospinal irradiation (typically 24 Gy Crl, 15 Gy spine) achieve durable secondary disease control in greater than 60% of cases with isolated CNS relapse. High-dose systemic MTX has virtually eliminated testicular relapse. CNS toxicities (including leukoencephalopathy) relate to systemic and IT MTX as well as Crl. Late neuropsychologicral data following Crl at 18 Gy show little intellectual deficit compared with children receiving MTX-based preventive therapy alone. Neuroendocrine dysfunction is apparent in long-term survivors following Crl at 24 Gy. The relative efficacy and toxicities of Crl versus more intensive MTX-based regimens are yet controversial. Overall disease-free survival in ALL approximates 70% in contemporary series.