cyclophosphamide, doxorubicin, vincristine, and prednisone while patients ≤60 years old are given CHOP plus etoposide or one of various other intensive chemotherapy regiments. The intensive chemotherapy regimens give 5 year overall survival rates of 70–93%. The role of radiation therapy for ALK-positive ALCL is unclear but has been used for patients who cannot tolerate or do not achieve complete responses to the drug regimens and to patients with organ-threatening or life-threatening tumorous infiltrates. The role of autologous or less preferably allogenic hematopoietic stem cell transplantation (transplantation using the individuals own bone marrow, i.e. autologous, or a donor's, i.e. allogenic) after achieving a complete remission following induction therapy is also unclear. Individuals with relapsed or refractory disease are treated with brentuximab vedotin if they did not receive the drug previously or had not received it in the previous 6 months. A small study reported overall response rates, complete response rates, and disease-free survival rates at 24 months of 63%, 45%, and 54%, respectively, using this regimen. Those who attain a complete response on this drug and can tolerate it are than treated with bone marrow transplantation. Finally, patients who fail or relapse on these treatments are given salvage therapy regimens that have been used for relapsed or refractory aggressive B cell malignancies such as GDP (i.e. gemcitabine, dexamethasone, and cisplatin), DHAP, and ICE. Drugs that inhibit ALK activity such as crizotinib and alectinib have been successful in establishing complete and partial remissions in a limited number of patients with advanced, refractory ALK-positive ALCL. These and other drugs are undergoing clinical trials to determine there safety and effectiveness in treating ALK-positive ALCL. (Also see clinical trials that use ALK inhibitors in ALK-positive ALCL and clinical trials that use ALK inhibitors in ALK-positive cancers.) ALK-negative anaplastic large-cell lymphoma Signs and symptoms Unlike ALK-positive ALCL, ALK-negative ALCL tends to occur in older adults (median age at diagnosis: 55–60 years) and presents primarily with lymph node involvement; only 20% of patients with ALK-ALCL present with extra-nodal disease in sites such as the skin, bone, and soft tissues. Nonetheless, most individuals (~67%) present with advanced stage grade III or IV disease in which neoplastic infiltrates occur in multiple lymph node locations and/or extra-nodal sites. ALK autoantibodies are not found in this type of ALCL. The prognosis of ALK-negative ALCL is often quoted as being worse than that for ALK-positive ALCL but this may reflect the older