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/m 2 before radiation and before the start of the cyclophosphamide treatment. The mean CD34؉ cell number for transplantation was 6.5 ؋ 10 6 CD34 ؉ cells/kg of body weight. Platelet recovery (>20,000/l median on day 13) and leukocyte recovery (>1,000/l 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. STEM CELLS 2007;25:228 -235

Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens

“…60,61 Defects in immune reconstitution in this setting may be due to an inability of the residual T cells in the graft to generate mature T cells with adequate function. 62 Several studies suggest that the risk of infectious complications, especially those of viral origin, is increased in patients receiving CD34 þ cell selected grafts, [63][64][65][66] although not all studies have noted this association. 58,67,68 35 NHL 274 ALC-15 independent prognostic factor for PFS and OS Joao 36 NHL/MCL 42 ALC-15 an independent prognostic factor for PFS and OS Tiwari 37 NHL 268 no association with ALC-15 and DFS or OS Porrata 39 NHL 50 NK cell recovery independent predictor for survival Porrata 28 MM 126 ALC-15 associated with better PFS and OS Hiwase 38 MM 119 ALC-30 associated with better PFS and OS Porrata 33 AL 145 ALC-15 independent prognostic factor for PFS and OS Nieto 31 MBC Optimizing blood graft content in auto-SCT E Jantunen and S Fruehauf…”

Evaluation of Autologous Hematopoietic Stem Cell Transplantation Results of the Patients with Hodgkin Lymphoma: A Single Center Experience

“…[4][5][6][7][8][9][10][11][12][13] Unlikely; effects of gender, bone marrow involvement at diagnosis, histology, conditioning regimen, origin of stem cells, mobilization regimen, year of transplantation and immunotherapy were not analyzed in our study. Patient numbers were not enough for making a comparison between groups for some parameters.…”

Hematopoietic stem cell transplantation for autoimmune diseases: What have we learned?

“…(6) Treating earlier in the disease course while the disease is still inflammatory, before organ dysfunction, and before exposure to long term immunosuppression will likely improve safety and efficacy for both myeloablative and non-myeloablative regimens. (7) Manipulation or CD34 selection of the graft will increase infections [19] and to date has not been demonstrated to improve efficacy. The only publication comparing selected to unselected grafts suggests that this maneuver may even shorten remission duration [20].…”