Long-term outcome of high-dose chemotherapy and autologous stem cell transplantation in relapsed/refractory Hodgkin’s disease: A cohort of 199 pts from Royal Marsden Hospital

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7622-7622 ◽  
Author(s):  
B. Sirohi ◽  
D. Cunningham ◽  
A. R. Norman ◽  
J. Oates ◽  
A. Wotherspoon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Prognostic Factors ◽  
Stage Iv ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Term Outcome ◽  
Long Term Outcome

7622 Background: The purpose was to assess prognostic factors and outcome of pts with relapsed/refractory Hodgkin disease (HD) who have received high-dose chemotherapy and autologous stem cell transplant (ASCT). Methods: The retrospective study was approved by Research Ethics Committee. Primary end-point was overall (OS) and progression free survival (PFS). OS was defined as death from any cause measured from date of transplant and PFS defined as disease progression or death from any cause. Data on 199 pts who received ASCT between 1985–6/05 was reviewed. Results: Median time from 1st treatment(tx) to ASCT was 2.5 y (0.5–27.3). Demography at ASCT:61% Stage IV, median age 31y(18–69); median prior tx regimens 3 (1–7); median Hasenclever index 3 (0–6); 150 pts had responding disease (53 CR, 97 PR), 49 pts had stable/untested relapse/refractory disease. 62% pts received MBE as conditioning tx and bone marrow was source of stem cells in 57%. Post-ASCT, 61% (122/199) pts attained CR with an overall response (CR+PR) of 85%. 12 pts had non-relapse mortality;10 died before 1990 of interstitial pneumonitis (with higher dose BCNU). Of 122 pts attaining CR, 27 relapsed;3 after attaining CR for >5y and 1 after attaining CR for>10-y. 5-y risk of relapse in patients attaining CR was 21%. Median OS/PFS from ASCT was 9y/2.6y. 105 pts are alive at median follow-up of 10.3y. 5-y OS/PFS was 52/45% and 10-y OS/PFS was 49.5/41% for whole group. 10-y OS/PFS for pts in CR vs PR vs rest at ASCT was 72/66% vs 55/44% vs 11/5%. 20(10%) pts developed 2nd cancer (7 secondary AML/MDS). Probability of developing 2nd cancer at 10y is 6.9% (95%CI 3.6–13%) and 19.8% (95%CI 12–32%) at 20-y. Conclusions: These data provide the longest followup reported for patients receiving ASCT for relapsed/refractory HD. In addition to previously described prognostic factors, our data shows that Hasenclever index <3 influences outcome favorably and attaining CR at ASCT leads to a significantly better outcome. [Table: see text] No significant financial relationships to disclose.

Autologous Stem Cell Transplantation Using BEAM Conditioning Is Highly Effective in Patients with Follicular Lymphoma Regardless of Prior Rituximab Exposure

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2025-2025
Author(s):  
Jaimal Kothari ◽  
Antonia Ljubic ◽  
Karl S Peggs ◽  
Kirsty Thomson ◽  
Emma Morris ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Clinical Symptoms ◽  
Progression Free Survival ◽  
Optimal Timing ◽  
High Dose ◽  
Cell Transplant ◽  
Term Outcome ◽  
Long Term Outcome

Abstract Abstract 2025 The benefit of high dose therapy and autologous stem cell transplant (HDT-SCT) using cyclophosphamide/total body irradiation conditioning in patients with relapsed follicular lymphoma (FL) has been demonstrated in the pre-rituximab era (European CUP trial. Schouten JCO 2003 21 3198). The long term outcome following HDT-SCT using BEAM (carmustine 300mg/m2 on d-6, cytarabine 200mg/m2 bd iv on days −5 to −2, etopside 200mg/m2 on days −5 to −2 and melphalan 140mg/m2 on d-1 with stem cell return the next day) conditioning is less well documented. It also remains unknown whether BEAM SCT is of similar efficacy in patients who have previously received rituximab compared with those who were rituximab naïve prior to SCT. In addition the optimal timing for HDT-SCT remains contentious. In order to try and resolve some of these uncertainties we undertook a retrospective analysis of all patients who have undergone BEAM SCT for FL in our institution. Eighty patients (53 male, 27 female) with FL underwent BEAM SCT between 1988 and 2009; all but 2 of these patients received their transplant after 1994. The median time from diagnosis to HDT was 2.8 years (range 0.5– 32.8). The median age at transplant was 52 (range 34–67). The median number of lines of therapy prior to SCT was 3 (range 1–5). The majority were transplanted in either their 2nd (n=41) or 3rd (n=20) response, with 13 in their 1st, and 6 in their 4th or subsequent response. Eight of the 13 transplanted in 1st response had received 2 or more lines of therapy prior to HDT-SCT. Forty-six patients (63%) received rituximab (either as a monotherapy or in combination with chemotherapy) as a treatment line before SCT. The median follow up is 6.8 years (range 0.1–19.2). The 7yr overall survival (OS) and progression free survival (PFS) of the whole group as measured from the date of the transplant were 75.6% and 59.5% respectively. The median OS has not yet been reached (NYR) whilst the median PFS is 12.5yrs. Excluding patients transplanted in 1st remission, the 7yr OS, PFS, median OS and median PFS were 74.6%, 58.0%, NYR and 9.4yrs respectively. There were highly significant differences in survival outcomes for patients transplanted in 2nd versus 3rd response: 7yr OS was 83.5% vs 61.1% (p=0.0201) and 7yr PFS was 67.0% vs 42.1% (p=0.0125) respectively (Fig1a). To date there have been no overt relapses after 6yrs in patients transplanted in 2nd response, with the caveat that patients have not been subjected to regular follow up imaging if they have no clinical symptoms or signs of relapse. When patients who had received rituximab prior to HDT-SCT were compared to those who had not there were no significant differences: 7yr OS 81.4% vs 67.6% (p=0.152) and 7yr PFS 68.0% vs 46.8% (p=0.221) (Fig1b). When analysis was restricted only to patients transplanted in 2nd response, once again no significant differences were found according to prior rituximab exposure: 7yr OS 87.1% vs 76.2% (p=0.297) and 7yr PFS 72.2% vs 53.8% (p=0.125). Conclusions: HDT-SCT using BEAM conditioning appears to be highly efficacious with long PFS and OS times. In our series, patients transplanted in 2nd response fare significantly better than those transplanted in 3rd response though further follow up is needed to clearly establish whether a plateau has been reached in the former group. Finally we have shown that treatment with a rituximab-containing regimen prior to BEAM-SCT does not lessen the benefit of BEAM-SCT when compared with patients who had not received rituximab prior to BEAM-SCT. BEAM-SCT therefore remains a valid treatment option for patients with FL in the rituximab era. Disclosures: Ljubic: Roche: Salary funded by a grant.

High dose chemotherapy with autologous stem cell transplant for patients with transformed B-cell non-Hodgkin lymphoma in the rituximab era

2014 ◽  
Vol 55 (10) ◽  
pp. 2319-2327 ◽  
Author(s):  
Yngvild N. Blaker ◽  
Marianne B. Eide ◽  
Knut Liestøl ◽  
Grete F. Lauritzsen ◽  
Arne Kolstad ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Non Hodgkin Lymphoma

The Addition of Rituximab to Standard High Dose BEAM Chemotherapy for Autologous Stem Cell Transplant in Patients with Lymphoma Does Have a Significant Effect on Engraftment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5325-5325
Author(s):  
Francis K. Buadi ◽  
Brian McClune ◽  
Yoriann S. Hull ◽  
Furhan Yunus ◽  
Sohail Minhas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Neutrophil Recovery ◽  
Cell Dose ◽  
Time Period ◽  
Neutrophil Engraftment

Abstract The addition of Rituximab to standard combination chemotherapy has significantly improved outcomes in both young and elderly patients with Non-hodgkins lymphoma (NHL). High dose chemotherapy with autologous stem cell transplant is currently the standard of care for patients with relapsed hodgkins lymphoma (HL) and NHL. However the effect of the addition of Rituximab to standard high dose chemotherapy regimen for autologous stem cell transplant on neutrophil and platelet engraftment is unknown. There are however, reported cases of neutropenia developing in patients treated with Rituximab. We performed a retrospect review of all patients with HL and NHL treated in our institution with RBEAM (Rituximab, Carmustine, Etoposide, Cytarabine, Melphalan) chemotherapy between July 2000 and June 2005 and compared it to patients receiving BEAM in the same time period. Rituximab was given at a dose of 375mg/m2 one day prior to beginning standard BEAM high dose chemotherapy. Peripheral blood was the main source of stem cells. The purpose of this study was to determine the effect of the addition of Rituximab on neutrophil and platelet engraftment. A total of 46 patients were treated during this time period. Twelve patients received RBEAM and 34 received BEAM. There was a statistical significant difference in age between the two groups. There was however no difference between the two groups in terms of race, sex and primary diagnosis. Median stem cell dose was not significantly different between the two groups. Characteristic of both groups are shown in Table: 1 Characteristics of Both Groups Median Age (yrs) Race Diagnosis Median Stem Cell Dose(x10^6) AA White HL NHL RBEAM 50.5 3 9 3 9 3.9 BEAM 36 13 21 17 17 3.8 P-VALUE 0.01 0.49 0.2 0.54 Neutrophil engraftment was defined as the first day of ANC &gt; 500 on 3 consecutive days. Platelet engraftment was defined as the first day of platelet count &gt; 20,000 with no platelet transfusion in the next seven days. The median time to neutrophil engraftment was 12 day in RBEAM compared to 11 days in BEAM (p=0.09). Platelet engraftment was however significantly delayed in patients receiving RBEAM 18days versus 12 days for BEAM (p= 0.02). Looking at both cohorts together we found that patients with HL had a significant delay in platelet engraftment compared to those with NHL (p=0.04). However there was no difference in neutrophil recovery. Although, stem cell dose affected neutrophil recovery, it had no effect on platelet engraftment. There was no increased toxicity in the early post transplant period associated with the addition of Rituximab. No bleeding complications resulted form the delay in platelet engraftment in the patients who received RBEAM. In a linear regression model the only factor that significantly affected engraftment was conditioning regimen. We conclude that the addition of Rituximab to standard high dose BEAM chemotherapy for autologous stem cell transplant has no effect on neutrophil engraftment; however platelet engraftment may be delayed. The continue use of this regimen despite the small delay in platelet engraftment will depend on whether there is any benefit, in terms of response rate, progression free and overall survival.

Role of High-Dose Chemotherapy with Autologous Stem Cell Transplantation in Primary Systemic Amyloidosis: A Systematic Review and Meta-Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2872-2872
Author(s):  
Madhusmita Behera ◽  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Benjamin Djulbegovic
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
High Dose Chemotherapy ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Conventional Chemotherapy

Abstract Background: Primary systemic amyloidosis (AL) is a rare plasma cell clonal disorder(8/million) characterized by extracellular deposits of material composed mainly of fragments of light chain immunoglobulin throughout a body. Standard chemotherapy (e.g. melphalan and prednisone) is associated with poor outcomes (typical median survival is between 12–18 months with less than 5% survive 10 years). Autologous stem cell transplant (ASCT) has been increasingly advocated for treatment of AL. However, it is uncertain whether ASCT is better than standard chemotherapy. To address this uncertainty, we undertook a systematic review/meta-analysis to evaluate the efficacy of high-dose chemotherapy and autologous stem-cell transplant (HSCT) versus conventional chemotherapy in patients with AL. Methods: Data search of published studies included Medline [all randomized controlled trials (RCTs)], Cochrane library and hand search of references. Studies were included if they were comparison trials of HSCT versus conventional chemotherapy, regardless if they were RCTs, prospective studies with historical control, or single arm studies. The studies were eligible if patients had biopsy proven AL with at least one major organ involved. Data were extracted on benefits as well as harms (overall survival, event-free survival, response, treatment related mortality, treatment-related morbidity). Results: Out of 34 identified studies only 13 met the inclusion criteria for the current systematic review (2 RCTs, 2 prospective non-randomized trials involving historical control, and 9 single arm trials). Altogether these trials enrolled 1056 patients. Pooled data from 4 trials with controls (RCT and non-RCT) found similar overall survival for ASCT and conventional therapy arms [hazard ratio (HR) of 1.10 (95% CI 0.88, 1.36, p=0.4); p= 0.6]. Analysis of data according to trial design also did not find any difference in survival [HR for RCTs was 1.10 (95% CI 0.88, 1.37) and for non RCTs HR was 0.98 (95% CI 0.29, 3.35)]. The complete hematological response was also similar in both arms in RCTs (Odds ratio [OR]=1.38, 95%CI 0.67, 2.85; p=0.4) and non RCTs (OR=1.78, 95%CI 0.22, 14.65; p=0.32). The pooled proportion of treatment-related deaths in the single arm studies for AHCT was 0.119 (95% CI = 0.09 to 0.14)]. Conclusion: The results from the meta-analysis indicate that there is no statistically significant difference between the treatment effects from high-dose chemotherapy with ASCT and conventional chemotherapy. Hence, the efficacy of ASCT in improving overall survival and complete hematological response remains to be proven.

Efficacy and Safety Of Treatments For Relapsed Or Refractory DLBCL: Results Of a Systematic Literature Review

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5104-5104 ◽  
Author(s):  
Ann Colosia ◽  
Peter C Trask ◽  
Robert Olivares ◽  
Shahnaz Khan ◽  
Adeline Abbe ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Career Development Award

Abstract Background Diffuse large B-cell lymphoma (DLBCL) accounts for 30% to 40% of non-Hodgkin’s lymphoma (NHL) cases in Western countries. Although two-thirds of patients may be cured with combination chemotherapy, in the event of treatment failure and for those who are refractory to treatment, survival is usually measured in months. Several therapeutic modalities have been utilized for patients with relapsed or refractory disease, but among patients who are not eligible for high-dose chemotherapy with stem cell transplant, a comprehensive assessment of efficacy and safety is lacking. This systematic literature review (SLR) was designed to exhaustively collect and review information on the clinical efficacy and safety of the different interventions used in the treatment of refractory or relapsed DLBCL, and if possible to perform a meta-analysis. Methods Electronic databases (PubMed, Cochrane Library, Embase) were searched for relevant studies published from 1997 to August 2, 2012. In addition, conference abstracts, bibliographic reference lists of included articles and recent reviews, and the Clinicaltrials.gov database were searched for phase 2, 3, or 4 studies displaying results, potentially unpublished in peer-reviewed journals. Main efficacy outcomes included objective response rate (ORR), complete response, partial response, duration of response, progression-free survival (PFS), and overall survival (OS). Safety endpoints focused on grade 3/4 toxicities and treatment discontinuation due to toxicity. Studies had to report on relapsed or refractory DLBCL after at least one standard treatment and patients who were not eligible to receive high-dose chemotherapy or stem cell transplant (autologous or allogeneic). Mixed type NHL studies were required to report DLBCL outcomes separately for inclusion. Results A total of 3,308 publications were identified in the first pass of a broad SLR on NHL; of these, 57 provided relevant data for DLBCL representing 54 unique studies. Of the 54 studies, there was 1 phase 3 study, 33 phase 2 studies, and 4 phase 1/2 studies (15 studies did not report the study phase and 1 was an observational study). Six studies were comparative (3 randomized trials; 3 nonrandomized trials) with two treatment arms; 48 studies were single arm. Of the 48 regimens evaluated, few regimens were represented more than once. Overall survival and PFS were often not reported or not reported separately for the patients with DLBCL in studies that enrolled patients with any of the multiple lymphoma histologies. Refractory and relapsed criteria were often not defined, and definitions were heterogeneous when available. The ORR from the few comparative studies ranged from 27% to 100%, with most estimates between 40% and 70%. PFS with low and high doses of obintuzumab was 2 months and 3 months, respectively in one study, and OS was 4 months with MEP and 7 months with C-MEP in another study. There was a common regimen in two of the randomized controlled trials, but the patient populations in these studies differed too greatly to allow a valid meta-analysis to be performed. In the single-arm studies, ORR ranged from 11% to 100%, with the estimates evenly distributed across that range. Progression-free survival was approximately 1 to 10 months. Reported median OS ranged from 1 to 13 months. Main safety concerns included thrombocytopenia, leukopenia, and neutropenia. Conclusions There is a high unmet need for effective therapies for patients with relapsed or refractory DLBCL who are ineligible for stem cell transplant. Although numerous regimens have been evaluated in single-arm trials and a handful in comparative studies, there is no clearly superior regimen for patients with relapsed or refractory DLBCL, especially in third- and later lines of therapy. FA is supported by a Clinical Career Development Award from the Lymphoma Research Foundation Disclosures: Colosia: RTI Health Solutions: Employment. Trask: Sanofi: Employment. Olivares: Sanofi: Employment. Khan: RTI Health Solutions: Employment. Abbe: Sanofi: Employment. Police: RTI Health Solutions: Employment. Njue: RTI Health Solutions: Employment. Wang: RTI Health Solutions: Employment. Sherrill: RTI Health Solutions: Employment. Ruiz-Soto: Sanofi: Employment. Kaye: RTI Health Solutions: Employment. Awan: Lymphoma Research Foundation (Career Development Award): Research Funding.

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