Long-Term Follow-Up of Patients with Non-Hodgkin Lymphoma Following Myeloablative Therapy and Autologous Transplantation of CD34+-Selected Peripheral Blood Progenitor Cells

Abstract

Graft engineering by CD34⁺ selection of peripheral blood progenitor cells (PBPC) has been used in non‐Hodgkin lymphoma (NHL) with the aim to reduce relapse related to tumor cells within the graft. From September 1995 to January 2000, 39 patients with newly diagnosed (n = 31) or relapsed (n = 8) NHL were treated in our institution with myeloablative therapy followed by CD34⁺ selected autologous PBPC transplantation. Thirty‐one patients were diagnosed with follicular lymphoma, and eight patients with mantle‐cell lymphoma. All patients had advanced disease (26% of patients stage III and 74% stage IV, Ann Arbor classification). Induction therapy resulted in a complete remission in 17 patients and a partial remission in 22 patients. PBPC were mobilized after cytotoxic chemotherapy with granulocyte colony‐stimulating factor support. CD34⁺ selection was performed using immunomagnetic beads (Baxter Isolex 300SA or 300i Magnetic Cell Separation System). Most patients (85%) received total body irradiation and high‐dose cyclophosphamide as myeloablative regimen. Twelve patients also received rituximab 375 mg/m² before radiation and before the start of the cyclophosphamide treatment. The mean CD34⁺ cell number for transplantation was 6.5 × 10⁶ CD34⁺ cells/kg of body weight. Platelet recovery (>20,000/μl median on day 13) and leukocyte recovery (>1,000/μl median on day 12) were within expected range. The estimated median follow‐up was 47 months. The probabilities of freedom from progression, overall survival, and event‐free survival 4 years after transplantation were 96%, 90%, and 87%, respectively, for patients with follicular lymphoma and 42%, 63%, and 33%, respectively, for patients with mantle‐cell lymphoma. Risk factors for relapse were age and extranodal manifestation of disease. The rate of lethal infections in the 12‐month follow‐up period was 8%. We conclude that CD34⁺ selection of autologous transplants following myeloablative therapy is feasible and results in long‐term remission in the majority of patients, but the procedure is probably related to a higher rate of lethal infections.