nodular sclerosis pattern of Hodgkin lymphoma (3% of cases); and a composite pattern consisting of two or more of the just described patterns (15% of cases). Detection of circulating autoantibody against ALK supports the diagnosis. Individuals with low levels of these autoantibodies are at an increase risk of relapsing after treatment. Gene and molecular abnormalities In 80–85% of cases, the ALK detected in ALK-positive ALCL is a NPM1-ALK fusion protein. It is made by a fusion of NPM1 gene, which makes nucleophosmin 1, located on the long or "q" arm of chromosome 5 at position 35 (notated as 5q35) with the ALK gene located on the short or "p" arm of chromosome 2 at position 23 (notated as 2p23) to form a chimeric gene notated as (2;5)(p23;q35). In 13% of cases ALK fuses with the TPM3 gene or in <1% of cases for each of the following genes: TFG, ATIC, CLTC, TPM4, MSN, RNF213 (also termed ALO17), MYH9, or TRAF1. All of these fusion proteins are considered to act like NPMI-ALK in possessing high ALK activity that promotes the development and progression ALK-positive ALCL by activating the cell signaling pathways cited in the Introduction. 15% Of individuals with ALK-positive ALCL also have point mutations in the NOTCH1 gene. While most of these abnormalities are thought to be detrimental not all are. For example, DUSP22 gene rearrangements are associated with favorable outcomes in ALK-positive (as well as ALK-negative) ALCL. Treatment and prognosis A recommended induction therapy for ALK-positive ALCL in individuals with lesions containing more than 10 percent CD30-positive cells consists of brentuximab vedotin (a drug consisting of an anti-CD30 antibody attached to a cell-killing agent, monomethyl auristatin E); two chemotherapy drugs, cyclophosphamide and the anthracycline, doxorubicin; and the corticosteroid, prednisone. This regimen gave a progression-free survival rate of 48.2 months in one study and overall survival rates of 70–90% at five years in other studies. For >60 year old and medically unfit individuals of any age, the standard CHOP regimen (cyclophosphamide, doxorubicin, prednisone, and the chemotherapeutic agent, vincristine) is used. For younger, medically fit individuals, the chemotherapeutic agent etoposide is added to the CHOP regimen (CHOP plus etoposide is termed the "CHOEP" regimen). For patients with lesions that contain <10% CD30-positive neoplastic cells, brentuximab vedotin, which targets these cells, is not used. Rather, patients are treated with an anthracycline-based chemotherapy regimen. Patients >60 years or less medically fit are given