Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma
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High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is widely used as a salvage therapy in the treatment of refractory malignant lymphoma. To investigate the safety and feasibility of a high-dose MCNU, carboplatin, etoposide and cyclophosphamide (MCVC) regimen, we conducted a prospective multicenter trial. Thirty patients with relapsed/refractory/poor-risk non-Hodgkin lymphoma (NHL n = 27) or Hodgkin lymphoma (HD n = 3) were uniformly treated with an MCVC regimen and underwent auto-SCT. The median follow-up duration of the surviving patients was 67 months (56–133 months). The major toxicities were anorexia (94 %), diarrhea (80 %), nausea (79 %), febrile neutropenia (70 %), alopecia (67 %) and mucositis (60 %). Three patients developed severe left ventricular dysfunction, and two patients developed severe sinusoidal obstructive syndrome (SOS). Of these patients, two died without disease progression. Treatment-related mortality was 6.6 %. Late-onset adverse events including two cases of cytomegalovirus pneumonia and one of interstitial pneumonia were observed. In DLBCL (n = 13) and transformed FL (n = 2) patients, OS and EFS at 3 years were 72 and 46 %, respectively. These results suggest that the MCVC regimen followed by auto-SCT is a feasible and tolerable therapy for relapsed/refractory malignant lymphoma. However, cardiac toxicity due to high-dose cyclophosphamide and development of SOS can occur and should be carefully monitored. Further follow-up is needed to evaluate the long-term efficacy and safety of this regimen.
- Philip T, Armitage JO, Spitzer G, Chauvin F, Jagannath S, Cahn JY, et al. High-dose therapy and autologous bone marrow transplantation after failure of conventional chemotherapy in adults with intermediate-grade or high-grade non-Hodgkin’s lymphoma. N Engl J Med. 1987;316:1493–8. CrossRef
- Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333:1540–5. CrossRef
- Blay J, Gomez F, Sebban C, Bachelot T, Biron P, Guglielmi C, et al. The International Prognostic Index correlates to survival in patients with aggressive lymphoma in relapse: analysis of the PARMA trial Parma Group. Blood. 1998;92:3562–8.
- Reimer P, Rüdiger T, Geissinger E, Weissinger F, Nerl C, Schmitz N, et al. Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study. J Clin Oncol. 2009;27:106–13. CrossRef
- Gyan E, Foussard C, Bertrand P, Michenet P, Le Gouill S, Berthou C, et al. High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years. Blood. 2009;113:995–1001. CrossRef
- Numata A, Miyamoto T, Ohno Y, Kamimura T, Kamezaki K, Tanimoto T, et al. Long-term outcomes of autologous PBSCT for peripheral T-cell lymphoma: retrospective analysis of the experience of the Fukuoka BMT group. Bone Marrow Transpl. 2001;45:311–6. CrossRef
- Salar A, Sierra J, Gandarillas M, Caballero MD, Marín J, Lahuerta JJ, et al. Autologous stem cell transplantation for clinically aggressive non-Hodgkin’s lymphoma: the role of preparative regimens. Bone Marrow Transpl. 2001;27:405–12. CrossRef
- Weaver CH, Schwartzberg L, Zhen B, et al. High-dose chemotherapy and peripheral blood stem cell infusion in patients with non-Hodgkin’s lymphoma: results of outpatient treatment in community cancer centers. Bone Marrow Transpl. 1997;20(9):753–60. CrossRef
- Jantunen E, Itälä M, Juvonen E, Mangum M, Leff R, Tauer K, et al. Autologous stem cell transplantation in elderly (>60 years) patients with non-Hodgkin’s lymphoma: a nation-wide analysis. Bone Marrow Transpl. 2006;37:367–72. CrossRef
- Han LN, Zhou J, Hirose T, Imai Y, Ishiguro T, Chou T. Feasibility and efficacy of high-dose melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED) chemotherapy with or without rituximab followed by autologous stem cell transplantation for aggressive and relapsed non-Hodgkin’s lymphoma. Int J Hematol. 2006;84:174–81. CrossRef
- Takaue Y, Watanabe T, Hoshi Y, Abe T, Matsunaga K, Saito S, et al. Effectiveness of high-dose MCNU therapy and hematopoietic stem cell autografts treatment of childhood acute leukemia/lymphoma with high risk features. Cancer. 1991;67:1830–7. CrossRef
- Kato J, Mori T, Yokoyama K, Tsukada Y, Ueda T, Shimizu T, et al. Safety and efficacy of high-dose ranimustine, cytarabine, etoposide and CY (MCVAC) regimen followed by autologous peripheral blood stem cell transplantation for high-risk diffuse large B-cell lymphoma. Bone Marrow Transpl. 2011;46:923–8. CrossRef
- Wakabayashi T, Yoshida J, Kito A, Inoue I, Kobayashi T, Kageyama N. Effect of MCNU on brain tumors. Part II: Clinical experience with MCNU on malignant brain tumors. Jpn J Cancer Chemother. 1984;11:2729–37.
- Kaplan EL, Meier P. Nonparametric estimation for incomplete observations. J Am Stat Assoc. 1958;53:457–81. CrossRef
- Kewalramani T, Zelenetz AD, Hedrick EE, Donnelly GB, Hunte S, Priovolos AC, et al. High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis. Blood. 2000;96:2399–404.
- Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO, et al. Autologous transplantation for diffuse aggressive non-Hodgkin’s lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol. 2001;19:406–13.
- Prince HM, Imrie K, Crump M, Stewart AK, Girouard C, Colwill R, et al. The role of intensive therapy and autologous blood and marrow transplantation for chemotherapy-sensitive relapsed and primary refractory non-Hodgkin’s lymphoma: identification of major prognostic groups. Br J Haematol. 1996;92:880–9. CrossRef
- Caballero MD, Rubio V, Rifon J, Heras I, García-Sanz R, Vázquez L, et al. BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transpl. 1997;20:451–8. CrossRef
- Jo JC, Kang BW, Jang G, Sym SJ, Lee SS, Koo JE, et al. BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: comparative analysis of efficacy and toxicity. Ann Hematol. 2008;87:43–8. CrossRef
- Carreras E, Bertz H, Arcese W, Vernant JP, Tomás JF, Hagglund H. Incidence and outcome of hepatic veno-occlusive disease after blood or marrow transplantation: a prospective cohort study of the European Group for Blood and Marrow Transplantation. European Group for Blood and Marrow Transplantation Chronic Leukemia Working Party. Blood. 1998;92:3599–604.
- Morgan M, Dodds A, Atkinson K, Szer J, Downs K, Biggs J. The toxicity of busulphan and cyclophosphamide as the preparative regimen for bone marrow transplantation. Br J Haematol. 1991;77:529–34. CrossRef
- Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, et al. Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med. 2004;350:1287–95. CrossRef
- Wang EH, Chen YA, Corringham S, Bashey A, Holman P, Ball ED, et al. High-dose CEB vs BEAM with autologous stem cell transplant in lymphoma. Bone Marrow Transpl. 2004;34:581–7. CrossRef
- Kuittinen T, Husso-Saastamoinen M, Sipola P, Vuolteenaho O, Ala-Kopsala M, Nousiainen T, et al. Very acute cardiac toxicity during BEAC chemotherapy in non-Hodgkin’s lymphoma patients undergoing autologous stem cell transplantation. Bone Marrow Transpl. 2005;36:1077–82. CrossRef
- Alessandrino EP, Bernasconi P, Colombo A, Caldera D, Martinelli G, Vitulo P, et al. Pulmonary toxicity following carmustine-based preparative regimens and autologous peripheral blood progenitor cell transplantation in hematological malignancies. Bone Marrow Transpl. 2000;25:309–13. CrossRef
- Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma
International Journal of Hematology
Volume 96, Issue 5 , pp 624-630
- Cover Date
- Print ISSN
- Online ISSN
- Springer Japan
- Additional Links
- Malignant lymphoma
- Industry Sectors
- Author Affiliations
- 1. Department of Hematology, Akita University Graduate School of Medicine, Akita, Japan
- 9. Division of Hematology and Oncology, Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan
- 8. Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan
- 3. 3rd Department of Internal Medicine, Yamagata University, Yamagata, Japan
- 4. Department of Oncology, Hirosaki University, Hirosaki, Japan
- 5. Division of Hematology, Miyagi Cancer Center, Natori, Japan
- 6. School of Medical Hematology and Oncology, Iwate Medical University, Morioka, Japan
- 7. Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan
- 2. School of Medicine, Akita University, Akita, Japan