Experience in Using Hypercvad Combined with Alemtuzumab in Treating Peripheral T-Cell and T/NK-Cell Neoplasms

Peripheral T-cell and T/NK-cell neoplasms (T/NK-cell neoplasms) are rare, representing less than 15% of non-Hodgkin lymphoma in the western hemisphere. The optimal therapy for peripheral T-cell and T/NK-cell neoplasms is an area of controversy due to rarity of the diseases, their variable clinical course, and the lack of randomized trials. Fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone (hyperCVAD) alternating with high doses of methotrexate and cytarabine has proven to be an effective cytoreductive regimen in patients with aggressive histopathologic variants of mantle cell lymphoma. Alemtuzumab (Campath®) is a humanized monoclonal antibody that targets CD52, a cell surface protein present at high density on most normal and malignant B and T lymphocytes. We report our experience in using six cycles of hyperCVAD in combination with alemtuzumab D1 +/− D4 for the treatment of newly diagnosed peripheral T-cell and T/NK-cell neoplasms in our institution. Seven females and five males diagnosed with peripheral T-cell and T/NK-cell neoplasms (N_{T and T/NK-cell lymphoma} = 5, N_{T-cell leukemia} = 5, N_{NK-cell leukemia} = 2) from 2006 to 2008 were treated with alemtuzumab-hyperCVAD regime. Three patients completed alemtuzumab-hyperCVAD regime and achieved response within four cycles. Among the three patients who completed hyperCVAD regime with only three to five doses of alemtuzumab, two achieved complete response and one had progressive disease. There were six patients who did not complete the alemtuzumabhyperCVAD regime. Three of them stopped at fifth cycle due to cytomegalovisrus (CMV) complication. Two patients died after forth cycle due to neutropenic sepsis although they achieved complete response after two cycles. The other patient did not respond to the treatment, hence discontinued. Both the NK-cell leukemia patients did not respond to the treatment. It was noted that patients with at least one dose of alemtuzumab per hyperCVAD cycle were more likely to survive (62.5%) than the other (25.0%) (95%CI of difference = −0.176 – 0.689). Among the complete respondents, the median disease free duration (from the day achieved response to date or relapse) is 216 days. CMV reactivation occurred in four out of seven patients who received at least five doses of alemtuzumab. In conclusion, alemtuzumab-hyperCVAD seems to be useful in treating peripheral T-cell lymphoma, T/NK-cell lymphoma and T-cell leukemia but not NK-cell leukemia. At least one dose of alemtuzumab per hyperCVAD cycle should be administered to achieve favourable survival. Although CMV complication is common in alemtuzumab-hyperCVAD regime, it does not seem to affect the outcome of the treatment. A proper randomized controlled trial should be conducted to evaluate the effectiveness of alemtuzumab-hyperCVAD in the treatment of peripheral T-cell and T/NK-cell neoplasms.