Dose-Adjusted EPOCH-Rituximab Combined With Fludarabine Provides an Effective Bridge to Reduced-Intensity Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Lymphoid Malignancies
| Autor: | Jeanne Odom, Robert M. Dean, Michael R. Bishop, Daniel H. Fowler, Kieron Dunleavy, Kelly Bryant, Thomas E. Hughes, Frances T. Hakim, Rachel B. Salit, Wyndham H. Wilson, Ronald E. Gress, Seth M. Steinberg, Terry J. Fry, Steven Z. Pavletic |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Oncology Cancer Research medicine.medical_specialty Lymphoma medicine.medical_treatment Antineoplastic Agents Hematopoietic stem cell transplantation Lymphocyte Depletion Antibodies Monoclonal Murine-Derived Internal medicine Original Reports Antineoplastic Combined Chemotherapy Protocols medicine Humans EPOCH (chemotherapy) Cyclophosphamide Aged Etoposide Interleukin-15 Salvage Therapy business.industry Interleukin-7 Hematopoietic Stem Cell Transplantation Middle Aged Flow Cytometry medicine.disease Chemotherapy regimen Fludarabine Surgery Transplantation Regimen Treatment Outcome Doxorubicin Vincristine Prednisone Female Rituximab business Vidarabine Progressive disease medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 30:830-836 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose There is currently no standard chemotherapy regimen for patients with lymphoid malignancies being considered for reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation (RIC-alloHSCT). The ideal regimen would provide disease control and result in lymphocyte depletion to facilitate engraftment. To this end, we developed a novel regimen by adding fludarabine to dose-adjusted continuous-infusion etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus with or without rituximab (DA-EPOCH-F/R). Patients and Methods One hundred forty-seven patients with lymphoid malignancy (median age, 50 years) who had heavily pretreated (median prior regimens, three) and chemo-refractory (47%) disease were treated with DA-EPOCH-F/R before RIC-alloHSCT. Patients received one to three consecutive cycles until achieving lymphocyte depletion (CD4+ count < 200/μL) or progressive disease. Results Overall response rate was 41%; 39% of patients had stable disease. Toxicity included grade 4 neutropenia in 65% and thrombocytopenia in 25% of patients. DA-EPOCH-F/R resulted in lymphocyte depletion (P < .001), which was inversely associated with serum interleukin (IL) 7 and IL-15 levels. Of 147 patients, 143 patients proceeded to RIC-alloHSCT. Patients with lower CD3+ (P < .001), CD4+ (P < .001), and CD8+ (P < .001) T-cell counts after DA-EPOCH-F/R were more likely to achieve full donor lymphoid chimerism by day +14 after transplant. Relative to nonresponders to DA-EPOCH-F/R, patients with complete and partial response had increased event-free survival (77.4 v 4.8 months; P < .001) and overall survival (98.5 v 16.2 months; P < .001). Conclusion DA-EPOCH-F/R safely provides tumor cytoreduction and lymphocyte depletion, thereby offering a bridge to RIC-alloHSCT in patients with aggressive lymphoid malignancies. |
| Databáze: | OpenAIRE |
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