Chemotherapy for relapsed childhood acute lymphoblastic leukemia

Relapse of childhood acute lymphoblastic leukemia (ALL) requires a second round of chemotherapy to achieve remission, and, in face of lack of donors for bone marrow transplant, remains the only therapeutic option for the majority of affected children. Prior to chemotherapy, the diagnosis of relapse must be beyond any doubts. Diagnostic procedures have to follow the same rules as at the first manifestation of ALL. Remission rates as well as long-term results are dependent on time and site of recurrence. The prognosis is dismal for children who have early relapses, in particular in bone marrow (BM) while still receiving first-line therapy. In contrast, about 50% of children with late BM relapses can be cured with intensive chemo-therapy. A second course of preventive treatment to the central nervous system (CNS) is mandatory even if the CNS is not apparently involved. The prognosis for children with BM relapse is better if extramedullary sites are concomitantly involved. Extramedullary relapse requires systemic therapy supplemented by local treatment to the involved site. For children with CNS relapse, radiation therapy still appears inevitable, and adverse late sequelae will have to be accepted, considering the possible cure rate of about 40%. Treatment results in boys with late testicular relapse are in the same range as for newly diagnosed ALL. Current treatment cannot retain fertility, but endocrine function can be preserved in the majority of patients. About one-third of children with relapsed ALL can be cured with chemotherapy. Particular problems remain the treatment for early BM relapse and relapse of T-cell ALL. In both conditions, drug resistance cannot be overcome by currently available treatment options. The search for novel approaches will constitute a formidable challenge well into the next millenium.