Primary plasma cell leukemia (PCL) is a rare form of plasma cell neoplasm with a poor prognosis. Conventional melphalan-based treatments have been most disappointing. We report the case of a 62-year-old man with a primary form of PCL treated with VAD combination achieving an objective response, and who received high-dose melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed by interferon-alpha. During the remission time, lasting for 3 years, an infiltration by large granular lymphocytes (LGL) was noted in peripheral blood. However, when the number of LGL declined, a bone marrow relapse was observed. The treatment for PCL and the possible role of these LGL on tumor cell control after autologous PBSC transplantation are discussed.