ALK-negative ALCL cells overexpress overactive STAT3 in 47% of cases and JAK1 in many cases. Many of these gene abnormalities appear to contribute to the development of ALK-negative ALCL. Treatment and prognosis
The various treatments of ALK-negative ALCL generally follow those used for ALK-positive ALCL. However ALK-negative individuals more often present at an advanced stage of disease that requires intensive therapy. The aggressive treatments outline in the section on ALK-positive ALCL are used with the exception that patients with more favorable clinical and tumor tissue indicators as defined by having an International Prognostic Index score above 2 (particularly those who are under the age of 66) who obtain a complete remission after initial therapy are recommended for follow-up bone marrow transplantation. The International T-Cell Project reported on the treatment of 220 patients with ALK-negative ALCL; 15 received only supportive care, 168 were treated with anthracycline-containing chemotherapeutic regimens, 31 with anthracycline plus etoposide–containing chemotherapeutic regimens, 6 with other regimens; 16 with high-dose chemotherapy plus autologous stem cell bone marrow transplantation, and 4 with radiotherapy alone. Of the 205 patients that had more that supportive therapy, the overall and complete response rates were 77% and 63%, respectively. After a median follow-up of 52 months, the median progression free and overall survival times were 41 months and 55 months, respectively; 3- and 5-year progression-free rates were 52% and 43%, respectively; and 3- and 5-year overall survival rates were 60% and 49%, respectively.
BPI-ALCL is associated with occasional mutations in one or two genes but has not been reported to be associated with products of gene translocations or rearrangements. ALK-positive anaplastic large cell lymphoma
Signs and symptoms
ALK-positive ALCL occurs mostly but not exclusively in children and young adults and is slightly more common in males. Most individuals present with stage III or IV (i.e. advanced) disease. They evidence systemic symptoms including B symptoms such as fever, night sweats, and weight loss in 75% of cases; lymph node enlargement (90%) including those in the mediastinum (36%); and lymphomatous lesions in the skin (26%), bone (14%), soft tissues (15%), lung (12%), and/or liver (8%). Tumor cells are found in the bone marrow in up to 40% of the cases when immunohistochemical analysis is performed. Involvement of the central nervous system or a leukemia-like circulation of malignant cells in the blood occurs only very rarely. Most patients, including up to 90% of young children and adolescents, have circulating autoantibodies directed against the ALK fusion protein expressed by their tumor cells. Diagnosis
ALK-positive ALCL is diagnosed by histological and immunological examinations of involved tissues, typically lymph nodes. These tissues have lymphoma-like infiltrates that have variable numbers of ALCL "hallmark" cells, i.e. cells with kidney- or horseshoe-shaped nuclei that strongly express CD30 as detected by immunohistochemistry and an ALK fusion protein as detected by fluorescence in situ hybridization. These cells are scattered throughout the infiltrates.