Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up.

PURPOSE The aim of this retrospective analysis was to determine the outcome of patients with follicular lymphoma who received myeloablative therapy supported by autologous bone marrow transplantation as consolidation of second or subsequent remission, with a minimum follow-up of 12 years. PATIENTS AND METHODS One hundred twenty-one adults received cyclophosphamide (CY) and total-body irradiation (TBI) supported by autologous bone marrow transplantation, with the marrow mononuclear cell fraction having been treated with monoclonal antibodies and complement. Data from St Bartholomew's Hospital and Dana-Farber Cancer Institute were combined for the purpose of this analysis because the patients were treated in an identical manner. RESULTS Fifty-seven patients are alive, 41 without progression between 9 and 19 years; 64 patients have died, 20 without progression. With a median follow-up of 13.5 years, 60 patients have developed recurrent lymphoma. There is an apparent plateau on the remission duration curve at 48% at 12 years. Survival of patients treated in second remission was significantly longer than the survival of patients treated later in the course of the illness. Both remission duration and overall survival were also significantly longer for patients treated in second remission compared with an age-matched, remission-matched group of patients treated at St Bartholomew's Hospital before the introduction of this treatment. However, use of CY+TBI was associated with a significant risk of secondary myelodysplasia and secondary acute myeloblastic leukemia, resulting in 15 patient deaths. CONCLUSION These mature data confirm that prolonged freedom from recurrence may be achieved with myeloablative therapy and that a plateau on the curve seems to emerge with long follow-up.

[1]  W. Hiddemann,et al.  Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a pros , 2006, Blood.

[2]  Max Wolf,et al.  Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. , 2006, Blood.

[3]  G. Salles,et al.  Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d'Etude des Lymphomes de l'Adulte (GELA). , 2006, Blood.

[4]  N. Schmitz,et al.  Long-term follow-up of high-dose treatment (HDT) with autologous haematopoietic progenitor cell support in 702 patients (pts.) with follicular lymphoma (FL). An EBMT registry study. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  N. Schmitz,et al.  Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of t , 2005, Blood.

[6]  R. Gressin,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 GOELAMS. , 2005, Blood.

[7]  J. Friedberg,et al.  Increasing incidence of late second malignancies after conditioning with cyclophosphamide and total-body irradiation and autologous bone marrow transplantation for non-Hodgkin's lymphoma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  R. Marcus,et al.  CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. , 2005, Blood.

[9]  W. Hiddemann,et al.  Moderate increase of secondary hematologic malignancies after myeloablative radiochemotherapy and autologous stem-cell transplantation in patients with indolent lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[10]  V. Diehl,et al.  Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. , 2004, Blood.

[11]  M. Sydes,et al.  High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  J. Vose,et al.  Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. , 2003, Blood.

[13]  R. Bouabdallah,et al.  High-dose therapy with autologous stem-cell transplantation (ASCT) after first progression prolonged survival of follicular lymphoma patients included in the prospective GELF 86 protocol. , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[14]  T. Lister,et al.  Therapy-related myelodysplasia and secondary acute myelogenous leukemia after high-dose therapy with autologous hematopoietic progenitor-cell support for lymphoid malignancies. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  T. Lister,et al.  High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  J. Gribben,et al.  Outcome in patients with myelodysplastic syndrome after autologous bone marrow transplantation for non-Hodgkin's lymphoma. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  N. Schmitz,et al.  Secondary leukaemia and myelodysplasia after autografting for lymphoma: results from the EBMT , 1999, British journal of haematology.

[18]  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.

[19]  M. M. Mac Manus,et al.  Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  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.

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

[22]  W. Chan,et al.  Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies. , 1994, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  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.

[24]  T. Lister,et al.  Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for follicular lymphoma. , 1994, Annals of oncology : official journal of the European Society for Medical Oncology.

[25]  B. Nathwani,et al.  Long-term follow-up of patients with low-grade malignant lymphomas treated with doxorubicin-based chemotherapy or chemoimmunotherapy. , 1993, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  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.

[27]  K. Sullivan,et al.  Autologous marrow transplantation for malignant lymphoma: a report of 101 cases from Seattle. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[28]  S. Reddy,et al.  Stage I and II non-Hodgkin's lymphomas: long-term results of radiation therapy. , 1989, International journal of radiation oncology, biology, physics.

[29]  T. Lister,et al.  Management of localized non‐Hodgkin's lymphoma: The experience at St. Bartholomew's hospital 1972–1985 , 1989, Hematological oncology.

[30]  J. Armitage,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. , 1987, The New England journal of medicine.

[31]  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.

[32]  J. Glick,et al.  Moderate versus aggressive chemotherapy of nodular lymphocytic poorly differentiated lymphoma. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[33]  R. Bast,et al.  ANTI-B1 MONOCLONAL ANTIBODY AND COMPLEMENT TREATMENT IN AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR RELAPSED B-CELL NON-HODGKIN'S LYMPHOMA , 1984, The Lancet.

[34]  S. Rosenberg,et al.  The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation. , 1981, Blood.

[35]  T. Lister,et al.  Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type. , 1978, British medical journal.

[36]  E. Glatstein,et al.  Treatment of advanced non-Hodgkin's lymphomas with favorable histologies: preliminary results of a prospective trial , 1976 .

[37]  L. Craver,et al.  Lymphosarcoma: survival and the effects of therapy. , 1961, The American journal of roentgenology, radium therapy, and nuclear medicine.

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