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 <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<0.0001 and p<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 <0.0001 for EFSR and SAR, respectively; p values between B and D <0.05 and =0.01 for EFSR and SAR, respectively Patients 87 59 29 30 5-year
 EFSR 24% (15–34) 44% (31–56) 42% (21–62) 67% (42–86) 5-year
 SAR 32% (22–42) 62% (45–73) 70% (42–86) 92% (71–98) Figure Figure

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.

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.

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.

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.

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

High-Dose Therapy and Autologous Stem Cell Transplant (HD-ASCT) for Transformed Non-Hodgkin Lymphoma (NHL) In the Rituximab Era

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2393-2393
Author(s):  
Makiko Ban-Hoefen ◽  
Jonathan W. Friedberg ◽  
Jennifer L. Kelly ◽  
Steven H. Bernstein ◽  
Jane L. Liesveld ◽  
...  
Keyword(s):  
Stem Cell ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Indolent Lymphoma ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
Indolent Disease

Abstract Abstract 2393 Background: The transformation of indolent non-Hodgkin's lymphoma (NHL) to a more aggressive histology remains a therapeutic challenge. For younger patients with a favorable performance status, high-dose therapy and autologous stem cell transplantation (HD-ASCT) results in a prolonged progression-free survival (PFS) in a substantial subset, based upon retrospective single and multi-institutional experiences. Rituximab improves PFS and overall survival (OS) in both follicular and aggressive NHL when combined with chemotherapy. However, the impact of prior rituximab on outcome of HD-ASCT for transformed NHL has not been elucidated. Methods: We therefore analyzed consecutive patients with indolent NHL (including follicular lymphoma and marginal zone lymphoma) who developed histologically confirmed transformation to diffuse large B-cell lymphoma (DLBCL) and subsequently underwent HD-ASCT at the University of Rochester Medical Center between 1998 – 2009. Patients who transformed within 6 months of the diagnosis of indolent lymphoma were excluded from the study. Progression free survival (PFS) was defined as time from HD-ASCT to date of disease relapse, progression, or death due to any cause. Kaplan-Meier survival curves were estimated, and differences in PFS between those who received rituximab prior to transformation versus those who were rituximab-naïve at transformation were assessed using the log-rank test. Results: 19 patients were identified, (10 female) who received rituximab-containing therapy at transformation. The median age at HD-ASCT was 59 years (range 40–66). Patients were treated with a median of 3 (range 1–9) chemotherapy regimens prior to HD-ASCT. Median time from the diagnosis of indolent lymphoma to transformation was 55 months (range 8–276). Conditioning regimens at HD-ASCT were BEAM (N=15), BEAC (N=1) and Cy/TBI (N=3). With a median follow-up of 47 months, the 2-year PFS was 58% and the 2-year OS was 84%. There were no treatment-related mortalities. Seven patients relapsed after HD-ASCT (2 with indolent histologies and 5 with DLBCL); 3 of these patients have died. Two additional patients have died of myelodysplastic syndrome-acute myeloid leukemia after HD-ASCT. Eight patients did not receive rituximab for indolent disease prior to transformation; this group had a significantly better PFS at 2 years (86% vs 36%, p = 0.049) compared to 11 patients who were treated with rituximab for indolent disease prior to ASCT. The patients who did not receive rituxmiab prior to ASCT had similar characteristics to patients who received rituximab, except that the time from indolent diagnosis to transformation was longer in the rituximab-naïve group (90 months vs 39 months). Conclusions: HD-ASCT remains an effective therapeutic option for transformed NHL in the rituximab era. However, transformed patients exposed to rituximab prior to HD-ASCT appear to have inferior outcomes, similar to the experience of patients with de novo NHL treated with rituximab prior to HD-ASCT in the recently reported CORAL study (JCO, published online ahead of print July 26, 2010). Patients who transform after rituximab-containing therapy may represent a higher risk group of patients with a unique biology, who may benefit from novel conditioning and maintenance regimens in the setting of HD-ASCT. Disclosures: No relevant conflicts of interest to declare.

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.

scholarly journals High-Dose Therapy and Autologous Hematopoietic Progenitor Cell Transplantation for Recurrent or Refractory Hodgkin's Disease: Analysis of the Stanford University Results and Prognostic Indices

Blood ◽  
1997 ◽  
Vol 89 (3) ◽  
pp. 801-813 ◽  
Author(s):  
Sandra J. Horning ◽  
Nelson J. Chao ◽  
Robert S. Negrin ◽  
Richard T. Hoppe ◽  
Gwynn D. Long ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Progenitor Cell ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Event Free Survival ◽  
High Dose Therapy ◽  
Hematopoietic Progenitor ◽  
Free Survival ◽  
Dose Therapy ◽  
History Of

Abstract One hundred nineteen patients with relapsed or refractory Hodgkin's disease (HD) received high-dose therapy followed by autologous hematopoietic progenitor cell transplantation. Three preparatory regimens, selected on the basis of prior therapy and pulmonary status, were employed. Twenty-six patients without a history of prior chest or pelvic irradiation were treated with fractionated total body irradiation, etoposide (VP) 60 mg/kg and cyclophosphamide (Cy) 100 mg/kg. Seventy-four patients received BCNU 15 mg/kg with identical doses of VP and Cy. A group of 19 patients with a limited diffusing capacity or history of pneumonitis received a novel high-dose regimen consisting of CCNU 15 mg/kg, VP 60 mg/kg and Cy 100 mg/kg. Twenty-nine patients (24%) had failed induction therapy and 35 (29%) had progressive HD within 1 year of initial chemotherapy. At 4 years actuarial survival was 52%, event-free survival was 48% and freedom from progression (FFP) was 62%. No significant differences were seen in survival data with the three preparatory regimens. Six patients died within 100 days of transplantation and 5 died at a later date of transplant-related complications. Secondary malignancies have developed in 6 patients, including myelodysplasia/leukemia in four patients and solid tumors in two patients. Regression analysis identified systemic symptoms at relapse, disseminated pulmonary or bone marrow disease at relapse and more than minimal disease at the time of transplantation as significant prognostic factors for overall and event-free survival and FFP. Patients with none of these factors enjoyed an 85% FFP at 4 years compared with 41% for patients with one or more unfavorable prognostic factors (P = .0001). Our results confirm the efficacy of high-dose therapy and autografting in recurrent or refractory HD. Although longer follow-up is necessary to address ultimate cure rates and toxicity, our data indicate that a desire to reduce late effects should drive future research efforts in favorable patients whereas new initiatives are needed for those with less favorable prognoses.

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

Abstract 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 &lt; .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.

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