Systemic ALCL is a progressive disease that can ultimately prove fatal. Therefore, treatment of systemic ALCL is more aggressive than treatment of primary cutaneous ALCL and targets the lymphoma cells wherever they are in the body.

The treatment of systemic ALCL should be directed by an experienced oncologist.   Advances made in the use of combined chemotherapy and radiotherapy for malignant lymphomas over the past half-century have resulted in durable remission rates as first-line therapy in early stage disease. Patients diagnosed with systemic ALCL are often treated with CHOP as a first approach to therapy. CHOP is a combination of several chemotherapy drugs (Cyclophosphamide, Hydroxydaunomycin (doxorubicin), Oncovin® (vincristine), and Prednisone). Other combinations of chemotherapy may also be used as a first option.

In addition, radiation therapy can be an important adjunct to therapy when there are particularly large masses of lymphoma in a localized area or when local large lymph nodes are compressing or invading normal organs or structures and chemotherapy cannot control the problem.

Treatment options following first-line combination therapy may include alternative higher dose chemotherapy regimens combined with radiation therapy. High dose combination therapy such as this targets the lymphoma cells in the tumor as well as lymphoma cells which may be located in the bone marrow. However, normal blood forming cells in the bone marrow may also be killed. Because of this, bone marrow transplantation or transplantation of circulating blood stem cells collected from the patient's own blood or that of a tissue-matched relative or unrelated donor is required. Such management is associated with high incidence of long-term survival.