Dexamethasone, Carmustine, Etoposide, Cytarabine, and Melphalan (Dexa-BEAM) Followed by High-Dose Chemotherapy and Stem Cell Rescue - A Highly Effective Regimen for Patients with Refractory or Relapsed Indolent Lymphoma

We performed a phase II study to determine the efficacy of maximal cytoreductive therapy with up to five cycles of Dexa-BEAM (dexamethasone, carmustine [BCNU], etoposide, cytarabine, and melphalan) followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) for patients with advanced relapsed or refractory indolent lymphoma. Thirty-two patients with primary refractory or relapsed indolent lymphoma were treated with the Dexa-BEAM regimen. Thirteen patients had primary refractory disease, 4 patients partial remission, and 15 patients first or subsequent relapse. Patients achieving PR or CR received HDCT with ASCT. The conditioning regimen used was BEAM (carmustine [BCNU], etoposide, cytarabine, and melphalan). Twenty-two patients responded to Dexa-BEAM resulting in a response rate of 78%. Maximum response was observed after 3.2 (range 2–5) courses. One patient with progressive disease died in septic shock during neutropenia. Nineteen patients with partial or complete remission after Dexa-BEAM received HDCT. Hematopoietic stem cells (HSC) were collected after two cycles of Dexa-BEAM. The median number of CD34+ HSC reinfused was 3.1 × 106/kg (range 1.6–8.2 × 106/kg). There was no transplantation-related death. All patients receiving HDCT achieved complete remission. Overall survival (OS) and freedom from treatment failure (FFTF) for all patients are estimated to be 68% and 65% at two years, respectively. With a mean follow-up of 20 months (range 8–42 months), 16/19 patients receiving HDCT are in continuous complete remission. The Dexa-BEAM regimen is effective in overcoming drug resistance in patients with indolent lymphoma who failed to respond to conventional treatment or who relapsed. The CR rate of 100% of those patients receiving HDCT and ASCT after maximal cytoreductive treatment with Dexa-BEAM suggests the use of HDCT at the time of maximal response.

[1]  V. Diehl,et al.  Favorable outcome of patients with relapsed or refractory Hodgkin's disease treated with high-dose chemotherapy and stem cell rescue at the time of maximal response to conventional salvage therapy (Dex-BEAM). , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[2]  H. Tilly,et al.  Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d'Etude des Lymphomes Folliculaires. Groupe d'Etude des Lymphomes de l'Adulte. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  J. Armitage,et al.  High-dose therapy with autologous hematopoietic rescue for follicular low-grade non-Hodgkin's lymphoma. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Gupta Rk,et al.  Current management of follicular lymphoma. , 1996 .

[5]  T. Lister,et al.  Current management of follicular lymphoma. , 1996, Current opinion in oncology.

[6]  A. Hagenbeek,et al.  Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. , 1995, The New England journal of medicine.

[7]  G. Salles,et al.  Intensive therapy with peripheral blood progenitor cell transplantation in 60 patients with poor-prognosis follicular lymphoma. , 1995, Blood.

[8]  T. Lister,et al.  Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. , 1995, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[10]  H. Goldschmidt,et al.  Sequential high-dose therapy with peripheral-blood progenitor-cell support in low-grade non-Hodgkin's lymphoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  A. López-Guillermo,et al.  Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  A. Norton,et al.  Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  T. Lister,et al.  Management of follicular lymphoma , 1991, Current opinion in oncology.

[14]  P. Colombat,et al.  Autologous bone marrow transplantation for low-grade non-Hodgkin's lymphoma: The European Bone Marrow Transplant Group experience , 1994 .

[15]  M. A. Tanner,et al.  One hundred autotransplants for relapsed or refractory Hodgkin's disease and lymphoma: value of pretransplant disease status for predicting outcome. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  F. Berger,et al.  Prognostic factors in follicular lymphomas. , 1993, Seminars in oncology.

[17]  S. Horning Natural history of and therapy for the indolent non-Hodgkin's lymphomas. , 1993, Seminars in oncology.

[18]  M. Crump,et al.  High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  J. Armitage,et al.  The role of high-dose therapy with hematopoietic stem cell rescue in low-grade non-Hodgkin's lymphoma. , 1993, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  W. Velasquez,et al.  Therapy of relapsed or refractory low-grade follicular lymphomas: factors associated with complete remission, survival and time to treatment failure. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  P. Biron,et al.  High dose chemotherapy with autologous marrow transplantation in follicular lymphomas. , 1992, Leukemia & lymphoma.

[22]  D. Neuberg,et al.  Autologous bone marrow transplantation in 69 patients with a history of low-grade B-cell non-Hodgkin's lymphoma. , 1991, Blood.

[23]  F. Berger,et al.  Follicular lymphomas: assessment of prognostic factors in 127 patients followed for 10 years. , 1991, Annals of oncology : official journal of the European Society for Medical Oncology.

[24]  R. Kurzrock,et al.  Fludarabine therapy in macroglobulinemic lymphoma. , 1990, Blood.

[25]  D. Weisenburger,et al.  Autologous bone marrow transplantation in follicular non-Hodgkin's lymphoma before and after histologic transformation. , 1989, Blood.

[26]  E. Jaffe,et al.  The treatment of indolent lymphomas: watchful waiting v aggressive combined modality treatment. , 1988, Seminars in hematology.

[27]  G. Fillet,et al.  [Treatment of non-Hodgkin's lymphoma]. , 1987, Revue medicale de Liege.

[28]  T. Lister,et al.  Follicular lymphoma: prognostic factors for response and survival. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  S. Horning,et al.  The natural history of initially untreated low-grade non-Hodgkin's lymphomas. , 1984, The New England journal of medicine.

[30]  C. Osborne,et al.  An autopsy study of histologic progression in non‐Hodgkin's lymphomas 192 cases from the national cancer institute , 1983, Cancer.

[31]  H. Skipper General motors cancer research foundation awards. Charles F. Kettering Award. Stepwise progress in the treatment of disseminated cancers , 1983 .

[32]  V. Devita,et al.  Malignant lymphoma II. Prognostic factors and response to treatment of 473 patients at the national cancer institute , 1982, Cancer.

[33]  E. Frei,et al.  Dose: a critical factor in cancer chemotherapy. , 1980, The American journal of medicine.

[34]  W. R. Bruce,et al.  Comparison of the Sensitivity of Normal Hematopoietic and Transplanted Lymphoma Colony-Forming Cells to Chemotherapeutic Agents Administered In Vivo , 1966 .

[35]  H. Ozer,et al.  Studies on the mechanism of isoantigenic variant formation in heterozygous mouse tumors. IV. H-2 component analysis of an (A-Sn x A.SW)F1 lymphoma. , 1966, Journal of the National Cancer Institute.

[36]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .