Myeloablative chemotherapy for chemo-sensitive recurrent follicular lymphoma: potential benefit in second relapse

Defining the role of high-dose therapy with autologous stem cell rescue in the therapeutic algorithm of follicular lymphoma remains a major challenge. In contrast to the acknowledged poor outcome associated with cyclophosphamide/total body irradiation conditioning in heavily pretreated patients, the prognostic impact of the number of previous therapy lines in patients treated with the chemotherapy-only containing regimen, BEAM, is unknown. From 1997 to 2008 80 patients (41 males, 39 females; median age, 51 years; range, 31-67) received high-dose therapy with autologous stem cell rescue with BEAM for relapsed follicular lymphoma at our center. Overall survival and time-to-progression were analyzed according to the number of prior treatment lines. The median number of previous treatment lines was three, with 61% of the patients having received more than three lines (including rituximab in 47%). After a median follow-up of 76 months (range, 14-160), three patients developed secondary myelodysplastic syndrome. The 5-year overall survival rate was 71% and 5-year time-to-progression was 44%. There were no differences in time-to-progression or overall survival according to the number of previous treatment lines or episodes of disease. In conclusion, high-dose therapy with autologous stem cell rescue with BEAM appears to be equally effective in second or third remission of follicular lymphoma.

[1]  G. Salles,et al.  Impact of the use of autologous stem cell transplantation at first relapse both in naïve and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study , 2011, Haematologica.

[2]  S. Mackinnon,et al.  T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  S. Montoto,et al.  Surveillance investigations after high-dose therapy with stem cell rescue for recurrent follicular lymphoma have no impact on management , 2010, Haematologica.

[4]  E. Kimby,et al.  Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin's lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  N. Schmitz,et al.  Characteristics of relapse after autologous stem-cell transplantation for follicular lymphoma: a long-term follow-up. , 2009, Annals of oncology : official journal of the European Society for Medical Oncology.

[6]  R. Gascoyne,et al.  Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 Study. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  E. Deconinck,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. , 2009, Blood.

[8]  B. Coiffier,et al.  Impact of rituximab and/or high-dose therapy with autotransplant at time of relapse in patients with follicular lymphoma: a GELA study. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  A. Levis,et al.  Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. , 2008, Blood.

[10]  G. Mufti,et al.  Outcome of BEAM‐autologous and BEAM‐alemtuzumab allogeneic transplantation in relapsed advanced stage follicular lymphoma , 2008, British journal of haematology.

[11]  N. Schmitz,et al.  Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study , 2007, Leukemia.

[12]  J. Gribben,et al.  Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  Sigrid Stroobants,et al.  Revised response criteria for malignant lymphoma. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  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.

[15]  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.

[16]  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.

[17]  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.

[18]  M. Ghielmini,et al.  Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. , 2004, Blood.

[19]  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.

[20]  T. Lister,et al.  Detection of chromosome abnormalities pre-high-dose treatment in patients developing therapy-related myelodysplasia and secondary acute myelogenous leukemia after treatment for non-Hodgkin's lymphoma. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  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.

[22]  J. Armitage,et al.  Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  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.

[24]  M. Pike,et al.  Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data. , 1973, Biometrics.

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

[26]  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.