The role of growth factor administration and T-cell recovery after peripheral blood progenitor cell transplantation in the treatment of solid tumors: results from a randomized comparison of G–CSF and GM–CSF |
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Authors: | Luca Pierelli Alessandro Perillo Gabriella Ferrandina Giovanna Salerno Sergio Rutella rea Fattorossi Alessandra Battaglia Aurelia Rughetti Marianna Nuti Enrico Cortesi Giuseppe Leone Salvatore Mancuso Giovanni Scambia |
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Affiliation: | Hematology and Hemotransfusion Service, Institute of Obstetrics and Gynecology, Sacred Heart Catholic University, Rome, Italy. luca@pierelli.it |
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Abstract: | BACKGROUND: Peripheral blood progenitor cell (PBPC) transplantation (PBPCT) combined with post-PBPCT administration of myelopoietic growth factors is a valid therapeutic intervention to rapidly restore hematopoiesis after the delivery of intensive, myeloablative cancer chemotherapy. On the other hand, the best growth factor regimen to potentiate PBPC-mediated immunohematopoietic recovery has yet to be determined. STUDY DESIGN AND METHODS: In a randomized evaluation, the effects produced by post-PBPCT G-CSF and GM-CSF on myeloid/lymphoid recovery and transplant outcome in women with chemosensitive cancer were compared. Thirty-seven ovarian cancer patients and 34 breast cancer patients ranging in age from 24 to 60 years were treated with carboplatin, etoposide, and melphalan (CEM) high-dose chemotherapy and then randomly assigned to receive G-CSF (5 microg/kg subcutaneously) or GM-CSF (5 microg/kg subcutaneously) until Day 13 after PBPCT. Patients were compared in regard to hematopoietic recovery, posttransplant clinical management, and immune recovery. Finally, clinical outcome was estimated as time to progression and overall survival. RESULTS: Hematopoietic recovery and posttransplant clinical management were comparable in both the G-CSF and GM-CSF series. Conversely, significantly higher T-cell counts were observed in G-CSF-treated patients during the early and late posttransplant follow-up. Patients who received G-CSF showed a significantly longer median time to progression. A parallel analysis revealed that patients in whom a higher CD3+ count was recovered had a significantly longer overall survival and time to progression. CONCLUSION: The enhancement of post-PBPCT T-cell recovery observed in G-CSF-treated patients encourages the use of G-CSF to ameliorate immune recovery, which seems to play a role in post-PBPCT control of disease in cancer patients. GM-CSF might be administered to prolong immunosuppression after autologous PBPCT for autoimmune diseases or allogeneic PBPCT. |
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Keywords: | BrCa = breast cancer CAP = cisplatin, doxorubicin, and cyclophosphamide CEF = 5-fluorouracil, epirubicin, and cyclophosphamide CEM = carboplatin, etoposide, and melphalan DCFH = dichlorofluorescein ED = epirubicin and docetaxel ETP = cisplatin, epirubicin, and paclitaxel IDS = interval-debulking surgery OS = overall survival OvCa = ovarian cancer PBPC(s) = peripheral blood progenitor cell(s) PBPCT = PBPC transplantation PC(s) = platelet concentrate(s) PerCP = peridinin chlorophyll protein PMA = phorbol myristate acetate TTP = time to progression |
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