Querfeld et al have written a comprehensive evaluation of primary cutaneous and systemic anaplastic large cell lymphoma (ALCL). The important similarities between them are outlined in the article, for example tumor cells expressing the CD30 antigen for both subtypes. In addition, important differences such as the wide spectrum of CD30+ lymphoproliferative disorders of the skin and the large differences in outcomes of the primary cutaneous vs systemic types of ALCL are discussed. Other important differences include expression of the anaplastic lymphoma kinase (ALK) protein. The ALK protein is activated most frequently through the nonrandom t(2;5) chromosome translocation, resulting in fusion of the nucleophosim (NPM) gene located at 5q35 to 2p23 and encoding the receptor tyrosine kinase, ALK. Most patients with primary cutaneous ALCL are ALK-negative, yet their 5-year disease-free survival rate is > 90%. Systemic ALCL is divided into ALK-positive and ALK-negative cases. Patients with systemic ALCL that is ALK-positive have a much higher 5-year survival rate of 70%, compared with a rate of 49% for those with systemic ALCL that is ALK-negative.
Unfortunately, many standard chemotherapies, including anthracycline-based regimens, do not produce long-term disease-free survival for many individuals with peripheral T-cell lymphomas. This is not the case with ALK-positive systemic ALCL, for which a high cure rate is possible. New modalities and treatments are needed for patients with relapsed ALK-positive ALCL and also for many patients with higher risk ALK-negative ALCL. The best use of stem cell transplantation is discussed by Querfeld et al, although its use as a standard of care for relapsed patients is not well emphasized. For younger patients, this should be the top consideration for relapsed systemic ALCL. Novel therapies are also outlined, such as several CD30 monoclonal antibodies or immunotoxins, histone deacetylase (HDAC) inhibitors, proteasome inhibitors, immunomodulatory agents, and possible ALK kinase inhibitors. Of these agents, the immunoconjugate SGN-35 appears to have highly significant activity in patients with relapsed systemic ALCL. In summary, the article by Querfeld and colleagues is extensive and covers all the updated currently available information about assessment and management of ALCL.
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