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)

Blood ◽  
2006 ◽  
Vol 108 (8) ◽  
pp. 2540-2544 ◽  
Author(s):  
Catherine Sebban ◽  
Nicolas Mounier ◽  
Nicole Brousse ◽  
Coralie Belanger ◽  
Pauline Brice ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Standard Chemotherapy ◽  
Free Survival ◽  
Dose Therapy

AbstractThe purpose of this study is to compare our standard chemotherapy regimen (CHVP [cyclophosphamide, doxorubicin, teniposide, and prednisone]) plus interferon with 4 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by high-dose therapy with autologous stem cell transplantation (ASCT) in treatment-naive patients with advanced follicular lymphoma. Four hundred one patients were included from July 1994 to March 2001: 209 received 12 cycles of CHVP plus interferon α for 18 months (CHVP-I arm) and 192 received 4 cycles of CHOP followed by high-dose therapy (HDT) with total body irradiation and ASCT (CHOP-HDT arm). Overall response rates were similar in both groups (79% and 78% after induction chemotherapy, respectively). One hundred thirty-one of the 150 patients eligible for HDT underwent transplantation (87%). Intent-to-treat analysis after a median follow-up of 7.5 years showed that there was no difference between the 2 arms for overall survival (P = .53) or event-free survival (P = .11). Patients with a complete response at the end of the induction therapy had a statistically longer event-free survival and overall survival (P = .02 and < .001, respectively). After long-term follow-up, our study showed that there was no statistically significant benefit in favor of first-line high-dose therapy in patients with follicular lymphoma. High-dose therapy should be reserved for relapsing patients.

Remission Duration ≤ 12 Months for Early Relapsed and Refractory Follicular Lymphoma Is Predictive of Early Failures Post-High Dose Therapy and Autologous Stem Cell Rescue.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3136-3136
Author(s):  
Matthew A Lunning ◽  
Jocelyn C Maragulia ◽  
Craig H. Moskowitz ◽  
Matthew J. Matasar ◽  
Hugo Castro-Malaspina ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
Induction Therapy ◽  
High Dose ◽  
High Dose Therapy ◽  
Free Survival ◽  
Stem Cell Rescue ◽  
Remission Duration

Abstract Abstract 3136 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL) in the Western hemisphere and is likely incurable with chemotherapy alone. Despite a median overall survival exceeding 12 years in the modern era, a fraction of patients experience an aggressive clinical course characterized by short remission duration(s) and/or chemorefractory disease. While high-dose therapy and autologous stem cell rescue (HDT-ASCR) is an accepted treatment modality for prolonging progression-free survival (PFS) it is unlikely to provide cure. Allogeneic stem cell transplantation (alloSCT) is a definitive therapy that has been shown to produce long-term disease free remissions. Unfortunately, alloSCT is limited by the risk of transplant-related mortality (TRM) despite the advent of non-myeloablative (NMA) conditioning regimens. Given that many FL patients whom fail HDT-ASCR may not proceed to alloSCT, and the inherent difficulty in deciding the appropriate consolidative transplant modality, we conducted a retrospective exploratory analysis of clinical features of early and multiply relapsed FL patients undergoing first HDT-ASR or alloSCT at a single center in the modern, post-rituximab era. Methods: We retrospectively reviewed all patients with early relapsed and/or refractory FL that proceeded to HDT-ASCR or NMA alloSCT as first transplant at MSKCC between 2006 and 2010. Chemosensitive disease was defined as a partial response (PR) or complete response (CR) to the last treatment regimen prior to transplant by computed tomography scans per IWG Criteria (Cheson et al JCO 1999). Events were defined as progression of FL post-transplant or death from any cause. Event-free survival (EFS) and overall-survival (OS) were estimated using Kaplan-Meier method. Results: We identified 40 patients with relapsed or refractory FL who had undergone either first HDT-ASCR (N=20) or alloSCT (N=20). All patients had FL grade 1–3a without pathologic evidence of transformation at the time of re-induction prior to transplant consolidation. Patient characteristics are outlined in the table below: All HDT-ASCR patients received BEAM (carmustine, etoposide, cytarabine, melphalan) conditioning. All alloSCT patients received a uniform non-myeloablative conditioning regimen (cyclophosphamide, fludarabine, total body irradiation 200 cGy). The median follow-up for survivors is 34 months. The estimated 3 year-EFS and OS was 60% and 62% with HDT-ASCR and 79% and 85% with alloSCT respectively (p=ns). FL patients with remission duration ≤ 12 months prior to re-induction therapy proceeding to consolidative HDT-ASCR had significantly shorter EFS compared to those patients with previous remission duration > 12 months (p<0.05, figure 1). Furthermore, when HDT-ASCR and alloSCT patients with a previous remission duration ≤ 12 months prior to re-induction therapy were compared the estimated 3-year EFS was 79% for alloSCT and 36% for HDT-ASCR (p<0.03, figure 2). With relatively short follow-up, there was no difference in OS for these two groups. In the HDT-ASCR cohort eight events were related to progression of FL with three of the eight patients subsequently undergoing alloSCT. In the alloSCT cohort four events occurred with one patient developing DLBCL and three TRM (2-related to graft-versus-host disease; 1-cytomegalovirus infection). Conclusion: The management of relapsed/refractory follicular lymphoma remains a clinically complex topic. In this exploratory analysis we demonstrated that remission duration of ≤ 12 months prior to re-induction chemotherapy is suggestive of inferior disease control with HDT-ASCR. Longer follow-up is necessary to determine the OS impact. Given the relatively unfavorable pre-transplant characteristics of the alloSCT cohort, FL appears to be exquisitely sensitive to an allogeneic effect. TRM continues to limit the benefit of alloSCT. Disclosures: Matasar: GSK: Research Funding; Genentech: Consultancy.

scholarly journals High-dose therapy and autologous peripheral blood stem cell transplantation for patients with lymphoma

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
DM Smith ◽  
JD Landmark ◽  
PJ Bierman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy

Abstract Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.

Randomized trial of high-dose chemotherapy with autologous haematopoietic stem cell support vs. standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: Overall survival after 6 years of follow up

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 672-672 ◽  
Author(s):  
A. R. Zander ◽  
N. Kroeger ◽  
C. Schmoor ◽  
W. Krueger ◽  
V. Moebus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Standard Dose ◽  
Interactive Effect ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade Iii

672 Background: Investigation of high dose chemotherapy (HD-CT) supported by autologous hematopoietic stem cell transplantation compared with standard dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more axillary lymph nodes. Methods: Between November 1993 and September 2000 307 patients were randomized to receive the following cycles of Epirubicin (90 mg/m2), Cyclophosphamide (600 mg/m2) intervenously (every 21 days) either HD-CT of Cyclophosphamide (1500 mg/m2), Thiotepa (150 mg/m2) and Mitoxantrone (10 mg/m2) intervenously for 4 consecutive days followed by stem cell transplantation or standard dose chemotherapy SDCT in 3 cycles of Cyclophosphamide (500 mg/m2), Methotrexate (40 mg/m2) and Fluoruracil (600 mg/m2) intervenously on days 1 and 8 every 28 days. The primary end points were event-free survival and overall survival. Results: After a median follow-up of 6.1 years 166 events with respect to event-free survival (SD-CT: 91, HD-CT: 75) and 123 with respect to overall survival (SD-CT: 66 and HD-CT: 57) have been observed. The hazard ratio of HD-CT versus SD-CT is estimated as 0,80, p = 0,15. The hazard ratio for overall survival for high dose chemotherapy versus standard dose chemotherapy is estimated as 0,84, p = 0,33. Analysing the effect of treatment on event-free survival premenopausal patients, patients with tumor grade III and ER-positive patients had a better outcome with HD-CT with an interactive effect of 2.5 and 1.4. The significance was only shown in grade III patients in favour of HD-CT, (p = 0,049). The interactive effect of HD-CT with prognostic factors did not reach significance for overall survival. Conclusion: Even with a follow-up of 6.1 years there was only a trend in favour of high dose chemotherapy with respect to overall survival but without a statistical significance. A proper meta-analysis needs to be undertaken for an evaluation of subgroups of patients which might benefit from this treatment approach. No significant financial relationships to disclose.

High Dose Therapy / ASCT with Rituximab for In-Vivo Purging and Post-ASCT Consolidation in Relapsed Follicular Lymphoma Achieves Prolonged Clinical and Molecular Remissions.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 914-914 ◽  
Author(s):  
Anthony C. Woods ◽  
Rena Buckstein ◽  
Joy Mangel ◽  
Kevin Imrie ◽  
David Spaner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Patient Specific ◽  
High Dose ◽  
Molecular Remission ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Grade 3

Abstract High-dose therapy and autologous stem cell transplantation (HDT/ASCT) is associated with prolonged remissions in relapsed follicular lymphoma (FL). Molecular remission in the graft and post ASCT predicts durable remissions and is a desirable endpoint. Rituximab (R) as an in vivo purge prior to HDT/ASCT and as consolidation after ASCT may help achieve this. To study this question, patients with relapsed FL were enrolled in a prospective, non-comparative phase II study between January 1998 and April 2000. Methods: 23 consecutive patients age <65 yrs with <3 relapses underwent HDT/ASCT with CBV (Cyclophosphamide, BCNU and VP-16) following salvage with CHOP or DHAP. Patients achieving ≥75% reduction in bulk and <15% marrow involvement underwent stem cell mobilization with chemotherapy plus G-CSF 10 μg/kg daily x 5. R 375 mg/m2 was given as a single-dose purge prior to collection, and repeated as 4 weekly courses at 2 and 6 months post-ASCT. Samples for PCR detection of minimal residual disease (MRD) were taken from stem cell grafts, as well as blood and marrow for all patients with detectable disease at baseline. Response assessments were clinical, laboratory and radiologic, and analysis was intention-to-treat. Results: Median cohort age at assessment was 50 yrs (32–57). Median number of prior regimens was 3 (1–7) and total treatment cycles was 9 (3–28). Median response duration to the preceding regimen was 10 months (1–86). Transplants were a median 2.4 years after diagnosis. At median follow-up of 4.5 yrs (1.3–6.3), there have been 10 relapses at a median of 2.8 yrs. 3 patients have died, 2 with relapse and one of presumptive sudden cardiac death. Significant toxicities were seen: 11 episodes of pneumonia (1 fungal), 4 episodes of herpes zoster (1 grade 3), 4 early episodes of grade 3/4 interstitial pneumonitis, and 1 episode each of grade 4 TTP and grade 3 optic neuritis. One patient developed AML at 4.7 years post-ASCT. Immune recovery has been delayed; at 600 days post ASCT, 16/18 (89%) of evaluable patients had not recovered IgG levels to normal. At baseline, 12/23 patients had detectable markers by PCR analysis (sensitivity 0.01%) for t(14;18) or patient-specific VDJ rearrangements in marrow or blood. Of these, all achieved at least a brief molecular remission in blood and marrow, 11/12 doing so pre-R consolidation. 5/12 patients have since relapsed at a median 3 yrs (2–4.5) post ASCT. Molecular relapse preceded clinical in 3/5 cases. 6/12 have had prolonged (median 4.8 yrs, range 3–5) molecular and clinical remissions. Median event-free survival for all patients is 63 months, with median overall survival not reached. Conclusions: HDT/ASCT with R for in vivo purging and post-ASCT consolidation for relapsed FL is feasible and associated with prolonged clinical and molecular remission. Delay in recovery of humoral immunity may play a role in the high incidence of infectious complications. A single infusion of Rituximab for in-vivo purging did not eradicate PCR detectable disease in the graft, although sustained molecular remissions of at least 24 months were achieved in 75% of evaluable patients post transplant, possibly due to post ASCT Rituximab consolidation. Whether this translates into survival benefit will require longer follow-up and further comparative studies.

Results of high-dose therapy for 1000 patients with multiple myeloma: durable complete remissions and superior survival in the absence of chromosome 13 abnormalities

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 4008-4010 ◽  
Author(s):  
Raman Desikan ◽  
Bart Barlogie ◽  
Jeffrey Sawyer ◽  
Dan Ayers ◽  
Guido Tricot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Chromosome 13 ◽  
Dose Therapy ◽  
Reactive Protein ◽  
Beta 2 Microglobulin

High-dose therapy (HDT) has increased complete remission (CR) rates and survival in multiple myeloma (MM). We now report on continuous CR (CCR) and associated prognostic factors in 1000 consecutive patients receiving melphalan-based tandem HDT. Five-year CCR was 52% among 112 CR patients without chromosome 13 (▵13) abnormalities and with beta-2-microglobulin ≤ 2.5 mg/L, C-reactive protein ≤ 4 mg/L, and pre-HDT standard chemotherapy ≤ 12 months. Of all 390 CR patients without ▵13 abnormalities, 35% enjoyed 5-year CCR but none of 54 with ▵13 abnormalities. ▵13 abnormalities, present in overall 16%, reduced 5-year event-free survival from 20% to 0% and overall survival from 44% to 16% (both P < .0001). CR and a second HDT cycle applied within 6 months both extended event-free and overall survival significantly, justifying further pursuit of HDT, especially toward curing non-▵13 MM.

Impact of Rituximab and/or High-Dose Therapy With Autotransplant at Time of Relapse in Patients With Follicular Lymphoma: A GELA Study

2008 ◽  
Vol 26 (21) ◽  
pp. 3614-3620 ◽  
Author(s):  
Catherine Sebban ◽  
Pauline Brice ◽  
Richard Delarue ◽  
Corinne Haioun ◽  
Bertrand Souleau ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose ◽  
Dramatic Improvement ◽  
Cell Transplant ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Salvage Regimen ◽  
Long Term Outcome ◽  
Free Survival ◽  
Dose Therapy

Purpose The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy (HDT) with autologous stem-cell transplant then with rituximab. The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared. Patients and Methods We analyzed two cohorts of patients treated in two successive randomized studies with the same treatment, cyclophosphamide, doxorubicin, teniposide, and prednisolone plus interferon, to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse. Results Of the 364 patients included in these two studies, 254 progressed or relapsed and constitute the population of this analysis. Among them, 98 had been treated with HDT, including 33 of them after rituximab-containing salvage regimen, and 69 with rituximab alone or combined with chemotherapy but without HDT. Patients’ characteristics at diagnosis were similar in all subgroups. If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires (GELF) -86 or GELF-94 studies, overall survival was longer in GELF-94 study. HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse (SAR). Rituximab was associated with a greater benefit than HDT for these two end points. When both treatments were combined, patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90%. Conclusion In follicular lymphoma, for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome.

scholarly journals High-dose therapy and autologous stem-cell transplantation can improve event-free survival for indolent lymphoma

Cancer ◽  
2007 ◽  
Vol 109 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Steéphane Vignot ◽  
Nicolas Mounier ◽  
Jeérôme Larghero ◽  
Pauline Brice ◽  
Laurent Quero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
High Dose ◽  
Indolent Lymphoma ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy

Effect of Rituximab and/or High-Dose Therapy with Autotransplant at Time of Relapse in Patients with Follicular Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 386-386 ◽  
Author(s):  
Bertrand Coiffier ◽  
Pauline Brice ◽  
Richard Delarue ◽  
Corinne Haioun ◽  
Bertrand Souleau ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Event Free Survival ◽  
First Line ◽  
High Dose Therapy ◽  
Salvage Regimen ◽  
P Values ◽  
Free Survival ◽  
Dose Therapy

Abstract Follicular lymphoma (FL) is considered as an incurable disease but treatments have changed with the introduction of high-dose therapy with autologous stem cell transplant (HDT) then of rituximab (RTX). The effect of these 2 strategies on the outcome of FL patients is well described in first line but not for relapsing patients. We analyzed 2 cohorts of patients treated in 2 successive randomized studies with the same treatment, CHVP plus interferon, to evaluate the role of RTX and HDT in first disease progression or relapse. Of the 364 patients &lt;61 years old included in these 2 studies, 255 progressed or relapsed and constitute the analyzed population. Among them, 93 had been treated with HDT, 63 with RTX alone or combined with chemotherapy, and 30 with RTX followed by HDT. Characteristics of the patients were similar in all subgroups. If event-free survival (EFS) was similar in patients treated within GELF-86 or GELF-94 studies(10-year EFS of 20% and 23%), overall survival (OS) was longer in GELF-94 study (10-year OS of 66% compared to 48%, p=0.014) witnessing a change in the management of relapsing patients. HDT was associated with a statistically significant benefit in terms of event-free survival from relapse (EFSR) and survival after relapse (SAR), p=0.004 and p=0.01, respectively (Table). Rituximab during salvage therapy was associated with a larger benefit than HDT for these 2 endpoints: p&lt;0.0001 and p&lt;0.0001, respectively. When both treatments were combined, 5-year SAR is over 90% (Table). In follicular lymphoma patients treated with chemotherapy in first line, the combination of salvage regimen containing rituximab followed by HDT seems to be superior to rituximab-containing chemotherapy alone. These retrospective results must be confirmed within a prospective study. Salvage without rituximab without HDT (A) Salvage without rituximab with HDT (B) Salvage with rituximab without HDT (C) Salvage with rituximab * p values between A and C =0.0002 and &lt;0.0001 for EFSR and SAR, respectively; p values between B and D &lt;0.05 and =0.01 for EFSR and SAR, respectively Patients 87 59 29 30 5-year&#x2028; EFSR 24% (15–34) 44% (31–56) 42% (21–62) 67% (42–86) 5-year&#x2028; SAR 32% (22–42) 62% (45–73) 70% (42–86) 92% (71–98) Figure Figure

scholarly journals High-dose therapy and autologous peripheral blood stem cell transplantation for patients with lymphoma

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1260-1265 ◽  
Author(s):  
A Kessinger ◽  
JO Armitage ◽  
DM Smith ◽  
JD Landmark ◽  
PJ Bierman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy

Forty patients with refractory Hodgkin's disease (24 patients) or non- Hodgkin's lymphoma (16 patients) who were considered for high-dose therapy but not for autologous bone marrow transplantation (ABMT) due to BM metastases, previous pelvic irradiation, a history of marrow involvement by tumor or hypocellular marrow in conventional harvest sites received high-dose therapy and autologous peripheral blood (PB) hematopoietic stem cell transplantation. Disappearance of circulating neutrophils and development of RBC and platelet transfusion-dependence was followed, in the evaluable patients, by reappearance of 0.5 x 10(9)/L circulating granulocytes and sufficient platelets to obviate the need for platelet transfusions at a median of 25 days after transplantation. Twenty-three patients experienced a clinical complete remission (CR). The projected 2-year event-free survival was 24% for all 40 patients and 49% for the non-Hodgkin's lymphoma patients. The projected 18-month event-free survival for the Hodgkin's disease patients was 15%. PB stem cell transplantation provided an opportunity to administer high-dose salvage therapy to patients with refractory lymphoma who otherwise were not candidates for such therapy. For some of those patients, the high-dose therapy produced prolonged survival, free of tumor progression.

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