Summary:
In an effort to improve the outcome of poor-risk lymphoma patients, we evaluated a novel regimen of tandem high-dose chemotherapy (THDC) with autologous stem cell transplantation. A total of 41 patients (median age 40 years, range 15–68 years) with poor-risk non-Hodgkin's lymphoma and Hodgkin's disease were enrolled. THDC consisted of melphalan (180 mg/m2) and escalating dose mitoxantrone (30–50 mg/m2) (MMt) for the first conditioning regimen, and thiotepa (500 mg/m2), carboplatin (800 mg/m2), and escalating dose etoposide phosphate (400–850 mg/m2), (ETCb) as the second regimen. In all, 31 patients (76%) completed both transplants, with a median time between transplants of 55 days (range 26–120). The maximum tolerated dose was determined as 40 mg/m2 for mitoxantrone and 550 mg/m2 for etoposide phosphate. The overall toxic death rate was 12%. Following high-dose chemotherapy, 10 of 24 evaluable patients (42%) were in CR. The two-year overall survival and event-free survival is 67% (95% CI, 52–81%) and 45%, (95% CI, 29–61%) for the 41 patients enrolled; and 69% (95% CI, 525–586%) and 48% (95% CI, 30–67%) for the 31 patients completing both transplants. This THDC regimen is feasible but with notable toxicity in heavily pretreated patients; its role in the current treatment of high-risk lymphoma remains to be determined.
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References
Hahn T, Wolff SN, Czuczman M et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of diffuse large cell B-cell non-Hodgkin's lymphoma: an evidence-based review. Biol Blood Marrow Transplant 2001; 7: 308–331.
Vitolo U, Cortellazzo S, Liberati AM et al. Intensified and high-dose chemotherapy with granulocyte colony-stimulating factor and autologous stem-cell transplantation support as first-line therapy in high-risk diffuse large-cell lymphoma. J Clin Oncol 1997; 15: 491–498.
Stoppa AM, Bouabdallah R, Chabannon C et al. Intensive sequential chemotherapy with repeated blood stem-cell support for untreated poor-prognosis non-Hodgkin's lymphoma. J Clin Oncol 1997; 15: 1722–1729.
Santini G, Coser P, Congiu AM et al. VACOP-B, high-dose cyclophosphamide and high-dose therapy with peripheral blood progenitor cell rescue for aggressive non-Hodgkin's lymphoma with bone marrow involvement: a study by the non-Hodgkin's Lymphoma Co-operative Study Group. Haematologica 2000; 85: 160–166.
Cortelazzo S, Rambaldi A, Rossi A et al. Intensification of salvage treatment with high-dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Br J Haematol 2001; 114: 333–341.
Gryn J, Johnson E, Goldman N et al. The treatment of relapsed or refractory intermediate grade non-Hodgkin's lymphoma with autologous bone marrow transplantation followed by cyclosporine and interferon. Bone Marrow Transplant 1997; 19: 221–226.
Fitoussi O, Simon D, Brice P et al. Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins's disease or non-Hodgkin's lymphoma. Bone Marrow Transplant 1999; 24: 747–755.
Philip T, Bouabdallah R, Brice P . Phase II study testing a double intensification in aggressive non-Hodgkin's lymphoma relapsing less than one year after initial treatment (PARMA2 study). Bone Marrow Transplant 2000; 25: 5180 (Abstract P5559).
Ballestrero A, Clavio M, Ferrando F et al. High-dose chemotherapy with tandem autologous transplantation as part of the initial therapy for aggressive non-Hodgkin's lymphoma. Int J Oncol 2000; 17: 1007–1013.
Brice P, Divine M, Simon D et al. Feasibility of tandem autologous stem-cell transplantation (ASCT) in induction failure or very unfavorable (UF) relapse from Hodgkin's disease (HD). SFGM/GELA Study Group. Ann Oncol 1999; 10: 1485–1488.
Le Gouill S, Moreau P, Morineau N et al. Tandem high-dose therapy followed by autologous stem-cell transplantation for refractory or relapsed high grade non-Hodgkin's lymphoma with poor prognosis factors: a prospective pilot study. Haematologica 2002; 87: 333–334.
Haioun C, Mounier N, Quesnel B et al. Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients. Ann Oncol 2001; 12: 1749–1755.
Barlogie B, Jagannath S, Vesole DH et al. Superiority of tandem autologous transplantation over standard therapy for previously untreated multiple myeloma. Blood 1997; 89: 789–793.
Attal M, Harousseau JL, Facon T et al. Single versus double autologous stem-cell transplantation for multiple myeloma. N Eng J Med 2003; 349: 2495–2502.
Corradini P, Astolfi M, Cherasco C et al. Molecular monitoring of minimal residual disease in follicular and mantle cell non-Hodgkin's lymphomas treated with high-dose chemotherapy and peripheral blood progenitor cell autografting. Blood 1997; 89: 724–731.
Vahdat LT, Balmaceda C, Papadopoulos K et al. Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer. Bone Marrow Transplant 2002; 30: 149–155.
Papadopoulos KP, Garvin JH, Fetell M et al. High-dose thiotepa and etoposide-based regimens with autologous hematopoietic support for high-risk or recurrent CNS tumors in children and adults. Bone Marrow Transplant 1998; 22: 661–667.
Hainsworth JD, Utley SM, Greco FA . Phase I study of high dose etoposide phosphatase with filgrastim (G-CSF) in the treatment of advanced refractory malignancies. Invest New Drugs 1997; 15: 325–329.
Tarella C, Zallio F, Caracciolo D et al. High-dose mitoxantrone+elphalan (MITO/L-PAM) as conditioning regimen supported by peripheral blood progenitor cell (PBPC) autograft in 113 lymphoma patients: high tolerability with reversible cardiotoxicity. Leukemia 2001; 15: 256–263.
Papadopoulos KP, Noguera-Irizarry W, Hesdorffer CS . Tandem transplantation in lymphoma. Bone Marrow Transplant 2001; 28: 529–535.
Malek SN, Flinn IW . Incorporating monoclonal antibodies in blood and marrow transplantation. Semin Oncology 2003; 30: 520–530.
Horwitz SM, Negrin RS, Blume KG et al. Rituximab as adjuvant to high-dose therapy and autologous hematopoietic cell transplantation for aggressive non-Hodgkin lymphoma. Blood 2004; 103: 777–783.
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This work was supported in part by the Julie Gould Fund (KPP) and an unrestricted grant from Bristol Myers Squibb.
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Papadopoulos, K., Noguera-Irizarry, W., Wiebe, L. et al. Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma. Bone Marrow Transplant 36, 491–497 (2005). https://doi.org/10.1038/sj.bmt.1705103
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DOI: https://doi.org/10.1038/sj.bmt.1705103
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