The Role of Alemtuzumab in the Management of T-Cell Malignancies

T-cell malignancies are rare, making up 10% to 15% of all lymphoid neoplasms in adults. They include many different types of disorders such as T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, adult T-cell leukemia/lymphoma, cutaneous T-cell lymphoma, and peripheral T-cell lymphoma, which are themselves divided into multiple subcategories. Most T-cell malignancies arise as a result of chromosomal abnormalities, including T-cell receptor rearrangement anomalies. Viral infections are implicated in the development of adult T-cell leukemia/lymphoma and some cases of peripheral T-cell lymphoma have been linked to Epstein-Barr virus or human immunodeficiency virus infection. With the possible exception of T-cell large granular lymphocytic leukemia, which often has an indolent course, T-cell malignancies have not responded well to conventional chemotherapeutic treatment. The introduction of monoclonal antibodies for the treatment of cancer has changed the outlook for patients with T-cell malignancies. Recent studies with single-agent alemtuzumab, an anti-CD52 monoclonal antibody, have shown improved response rates and survival in patients with T-cell prolymphocytic leukemia and cutaneous T-cell lymphoma. Preliminary data also suggest that alemtuzumab may have activity in patients with heavily pretreated peripheral T-cell lymphoma who are refractory to conventional chemotherapy. Preclinical studies with mice bearing human adult T-cell leukemia/lymphoma cells suggest that alemtuzumab may have a potential therapeutic role in this setting. Treatment of T-cell hematologic malignancies with alemtuzumab appears promising. Earlier treatment and combination with chemotherapeutic agents may improve treatment outcome for patients with these malignancies and allow for consolidation with stem cell transplant strategies in selected patients.