Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T-Cell Lymphomas As Front-Line Consolidation or in the Relapsed/Refractory Setting: A Meta-Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4493-4493
Author(s):  
Jessica El-Asmar ◽  
Tea Reljic ◽  
Ernesto Ayala ◽  
Taiga Nishihori ◽  
Mehdi Hamadani ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Retrospective Studies ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
High Dose ◽  
Secondary Malignancies ◽  
Front Line ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Histologic Subtypes

Abstract Background: No prospective randomized trials exist comparing high-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) against conventional therapy for management of peripheral T-cell lymphomas (PTCL) as upfront consolidation or in the relapsed/refractory (R/R) settings. Available data supporting this approach is limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature using PUBMED/MEDLINE from date of inception until March 4, 2015. Patients and methods: Our search identified 1586 publications, but only 27 (n=1368) met our inclusion criteria. Data were collected on treatment benefits (progression-free (PFS) and overall survival (OS)) and harms (transplant-related mortality (TRM) and secondary malignancies). Results: Specifically pertaining to HDT/auto-HCT as front-line consolidation data were available from 3 single-arm prospective (n=179) and 16 retrospective (n=599) studies. Moreover, for HDT/auto-HCT for R/R disease, 14 eligible retrospective (n=581) studies were identified. Pooled analysis of only prospective studies showed rates of PFS (2 studies, n=158) 33% (95%CI=14-56%), OS (3 studies, n=179) 54% (95%CI=32-75%), and TRM (2 studies, n=136) 2% (0.3-5%) for HDT/auto-HCT as front-line consolidation. When only retrospective studies were analyzed, pooled analysis showed rates of PFS (12 studies, n=518) 55% (95%CI=40-69%), OS (16 studies, n=599) 68% (95%CI=56-78%), TRM (7 studies, n=226) 6% (95%CI=2-11%), and incidence of secondary malignancies (4 studies, n=153) of 7% (95%CI=2-14%) with HDT/auto-HCT as front-line consolidation. Alternatively, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the R/R setting showed rates of PFS (11 studies, n=511) 36% (95%CI=32-40%), OS (14 studies, n=581) 47% (95%CI=43-51%), TRM (5 studies, n=338) 10% (95%CI=5-17%), and incidence of secondary malignancies (1 study, n=29) of 3.4%. Additionally, we evaluated the efficacy of HDT/auto-HCT in various histologic subtypes both as front-line consolidation and in R/R disease. Only 1 prospective study using HDT/auto-HCT as front-line consolidation showed an apparently higher 5-year PFS and OS for ALK-negative anaplastic large cell lymphoma (ALK-neg-ALCL) (PFS=61%, OS=70%) compared to PTCL-NOS (PFS=38%, OS=47%) or angioimmunoblastic (AILT) (PFS=49%, OS=52%). Moreover, 2 retrospective studies using HDT/auto-HCT as front-line consolidation also showed higher rates of PFS and OS for ALCL (PFS=68%, OS=78%) compared to PTCL-NOS (PFS=64%, OS=75%) or AILT (PFS=48%, OS=63%). Finally, in the R/R setting, outcomes following HDT/auto-HCT from one retrospective study showed higher PFS for ALCL (67%) vs. PTCL-NOS (23%). The observed heterogeneity was statistically significant for PFS and OS among prospective (p=0.008 and p=0.0009) and retrospective (p<0.0001 and p<0.0001) studies evaluating HDT/auto-HCT as front-line consolidation but not for studies evaluating this strategy in the R/R setting (p=0.8 and p=0.7). Conclusion: These results suggest that HDT/auto-HCT is a reasonable treatment option to offer as front-line consolidation with resulting OS ranging from 54% to 68% and a relatively low TRM ranging from 2% to 6%. In the R/R setting, HDT/auto-HCT is also a reasonable option yielding an OS of 47% but with slightly higher TRM of 10%. Among the various histologic subtypes, PFS and OS rates appear to be higher in ALCL but larger appropriately powered comparative prospective studies will be needed to confirm these findings. Patients should be made aware of the increased risk of secondary malignancies of up to 7% when considering HDT/auto-HCT. Disclosures No relevant conflicts of interest to declare.

Meta-Analysis Evaluating Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation As Front-Line Consolidation in Chronic Lymphocytic Leukemia: Results Do Not Justify This Treatment Approach

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1306-1306
Author(s):  
Tea Reljic ◽  
Ambuj Kumar ◽  
Benjamin Djulbegovic ◽  
Mohamed A Kharfan-Dabaja
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Lymphocytic Leukemia ◽  
Secondary Malignancy ◽  
High Dose ◽  
Front Line ◽  
High Dose Therapy ◽  
Total N ◽  
Free Survival ◽  
Secondary Mds

Abstract Background: High-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) has been offered to patients with chronic lymphocytic leukemia (CLL), both as front-line consolidation and in the relapsed setting. Uncertainty remains in regards to the role of HDT in the front-line consolidation setting in CLL. Accordingly, we performed a systematic review and meta-analysis aiming at evaluating the totality of evidence pertaining to the efficacy (or lack thereof) of HDT and auto-HCT as front-line consolidation in subjects with CLL. Materials and methods: A total of 475 references were identified through a systematic search of PUBMED/MEDLINE and Cochrane through June 26, 2014. Only four randomized controlled trials which included a total of 600 subjects were eligible for inclusion in this meta-analysis. Data was meta-analyzed for benefits: progression-free survival (PFS) (data from 2 studies (total n=178)), event-free survival (EFS) (data from 2 studies (total n=422)), PFS or EFS (data from 4 studies (total n=600)), and overall survival (OS) (data from 4 studies (total n=600)); and harms: treatment related mortality (TRM) (data from 2 studies (total n=276)), development of any secondary malignancy ((data from 4 studies (total n=581)), or development of secondary MDS/AML in particular (data from 4 studies (total n=581)). Results: These results are reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Four studies enrolled a total of 301 subjects in the HDT/auto-HCT arm and 299 subjects in the control arm. Offering front-line HDT/auto-HCT did not improve PFS [Hazard ratio (HR)=0.70 (95%CI= 0.32, 1.52), p=0.37] or OS [HR=0.91 (95%CI= 0.62, 1.33), p=0.64]. An advantage favoring HDT/auto-HCT was observed in terms of EFS (HR=0.46 (95%CI= 0.26, 0.83), p=0.01] or when analysis included PFS or EFS [HR=0.54 (95%CI= 0.35, 0.82), p=0.004]. Moreover, HDT/auto-HCT did not result in higher TRM (Risk ratio (RR)=1.32 (95%CI= 0.43, 4.06), p=0.63]. When analyzing development of any secondary malignancy, no difference was observed whether subjects were offered HDT/auto-HCT or not [RR=1.06 (95%CI=0.55, 2.05), p=0.86]. A two-fold higher incidence of secondary MDS/AML, albeit not statistically significant, was observed with the HDT/auto-HCT approach [RR=1.95 (95%CI=0.60, 6.34), p=0.27]. Conclusion: Offering HDT/auto-HCT as front-line consolidation in patients with CLL does not improve OS. At the present time, this approach should be offered only in the context of a clinical trial. Disclosures No relevant conflicts of interest to declare.

Secondary Malignancies Following High Dose Therapy and Autologous Hematopoietic Cell Transplantation - Systematic Review and Meta Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4633-4633
Author(s):  
Iuliana Vaxman ◽  
Ron Ram ◽  
Anat Gafter-Gvili ◽  
Liat Vidal ◽  
Moshe Yeshurun ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
High Dose ◽  
Secondary Malignancies ◽  
Lymphoproliferative Diseases ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Solid Malignancies ◽  
Autologous Hct

Background High dose chemo/radiotherapy with autologous hematopoietic cell transplantation (HCT) has been shown to be an effective therapy for a variety of malignancies. However, as more patients survive both the disease and the early post HCT period, it has become apparent that other potential long term complications, mainly secondary malignancies may hamper patients' prospects. Objectives We analyzed the incidence of different secondary malignancies occurring after consolidation with autologous HCT compared to other modalities for the treatment of various hematological and non-hematological malignancies. Methods Systematic review and meta-analysis of randomized controlled trials comparing high dose therapy with autologous HCT to other treatment modalities (observation, immunotherapy or chemotherapy). We searched the Cochrane Library, MEDLINE and conference proceedings. Outcomes assessed were rates of AML/MDS, solid tumors and overall secondary malignancies. Relative risks (RR) with 95% confidence intervals (CIs) were estimated and pooled. Heterogeneity is given when approporiate. Results Our search yielded 74 trials fulfilling inclusion criteria; among them 38 trials recruiting 10131 patients reporting secondary malignancies were included. Baseline diseases were lymphoproliferative diseases (n=17), plasma cell dyscrasias [PCD] (n=5) and solid tumors (n=16). The studies were conducted between the years 1987 and 2007. Median follow up was 55 (range 12-144) months. High dose therapy consisted of variety of regimens. Comparative arm regimens were either observation (n= 6), intensive chemotherapy [>6 gr/m2 of cyclophosphamide or high doses of etoposide] (n= 6), or standard chemotherapy (n= 24). Overall, the RR for secondary malignancies was 1.25 (95% CI 0.99-1.57) (38 studies, 10131 pts). Among all patients, there was a higher rate of MDS/AML in patients given HCT compared to other treatments [RR=1.71 (95% CI 1.18-2.48)], (33 studies, 8778 patients), Figure. Subgroup analysis showed similar results in patients with lymphoproliferative diseases [RR=2.35 (95% CI 1.36-4.05), (16 studies, 3090 patients)]. However, the rate of AML/MDS was not increased in patients treated for PCD or solid malignancies [RR=1.41 (95% CI 0.28-7.08), 3 studies, 304 patients and RR=1.24 (95% CI 0.72-2.15), 14 studies, 5384 pts, respectively], Figure. Subgroup analysis based on the comparator's intensity- showed a higher rate of MDS/AML merely in patients given HCT compared to observation and to low intensity [RR=4.86 (95% CI 1.43-16.47), (5 studies, 732 patients) and RR=2.09 (95% CI 1.30-3.35), (19 studies, 6036 patients)]. Overall, there was no difference in the rate of secondary solid malignancies between patients given HCT and patients given other treatments [RR=0.95 (95% CI 0.67-1.32), (19 studies, 5925 patients)], with similar results in subgroup analysis according to the baseline diseases. Conclusions The rate of secondary MDS/AML is higher in patients given high dose therapy and autologous HCT compared to other treatment options, with statistically significant higher rates only in the subgroup of patients with lymphoproliferative diseases. The rate of secondary solid malignancies is similar among all patients given either high dose therapy or alternative therapy. Disclosures: No relevant conflicts of interest to declare.

Role of Front-Line High Dose Therapy with Stem Cell Transplant in Peripheral T-Cell Lymphomas. A Single Center Experience.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2733-2733
Author(s):  
Giuseppe Gritti ◽  
Andrea Rossi ◽  
Anna Maria Barbui ◽  
Anna Grassi ◽  
Alessandra Algarotti ◽  
...  
Keyword(s):  
T Cell ◽  
Progressive Disease ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Front Line ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 2733 Introduction: The best treatment of peripheral T-cell lymphomas (PTCLs) currently remains a matter of debate. Some retrospective study and few phase II trials have shown that first line high dose therapy (HDT) with autologous stem cell transplant (SCT) may apparently offer better results. However, no comparative trials are currently available. Material and Methods: We retrospectively evaluated the outcome of previously untreated patients with PTCL, excluding mycosis fungoides and Sézary syndrome, referred to our Center between 1996 and 2012. An in-house histologic revision was performed to confirm the diagnosis according to the latest WHO criteria. From this analysis we excluded patients with diagnosis of ALK positive anaplastic large cell lymphoma (ALCL). We stratify patients according to treatment. Conventional therapy (CT) consisted of CHOP, CHOEP or MACOP(-B). From early 90s at our Center was adopted the strategy to consolidate response to initial treatment with either autologous or allogeneic SCT, whenever possible, in patients aged <65 years. These patients were assigned to HDT group. Results: The specific diagnosis of the 124 patients evaluated was PTCL-not otherwise specified (n=70), angioimmunoblastic T-cell lymphoma (n=21), ALCL ALK negative (n=19), other subtypes (n=14). At diagnosis, 43 patients were planned to receive HDT plus SCT but only 26 (60%) eventually received it (22 autologous, 4 allogeneic) while the remaining experienced early death (8 patients), progression (8 patients) or mobilization failure (1 patient). The median age of this first cohort was 47.9 years (range 23–63), that also showed an advanced Ann-Arbor stage (III-IV) or an int-high/high IPI in 77% and 58% of the cases, respectively. The rate of complete remission (CR) was 57% with 21% of patients dying during treatment (5 patients not evaluable for response, 3 responders and 1 with progressive disease). Eighty-one patients were treated according to a CT strategy. The median age of this latter group was 66.7 years (25–85), an advanced stage (III-IV) or an int-high/high IPI was present in 73% and 61%, respectively. The CR rate was 57% with 19% of the patient dying during treatment (11 patients not evaluable for response, 2 responders and 1 with progressive disease). With a median follow up of 1.63 years (0–25) and 82 deaths, by intention to treat analysis the 5-years overall survival (OS) was 43% and 32% for HDT and CT (p=.90, figure 1), respectively, while the 5-years OS of those patients eventually receiving SCT was 64%. Irrespectively from the adopted treatment strategy, patients who achieved a CR showed a similar 5-years OS and disease free survival that were 57% and 52% in the CT group and 80% and 64% in the HDT cohort (p=.43 and p=.44), respectively. Of the 54 patients with relapsed or refractory disease, 9 underwent salvage SCT (4 autologous, 5 allogeneic) with 3 patients achieving a sustained remission. Conclusions: The overall clinical outcome of most PTCL patients remains unsatisfactory, with a large fraction of patients not responding to front-line treatment. The advantage of a post-remission consolidation with SCT has to be confirmed by appropriate ad hoc designed clinical studies. On the contrary, allogeneic SCT, despite remaining a potentially curative treatment option for these patients, unfortunately has a limited applicability due to the frequent advanced age and comorbidities as well as to the difficulty in finding a donor. Disclosures: No relevant conflicts of interest to declare.

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

Blood ◽  
2009 ◽  
Vol 113 (5) ◽  
pp. 995-1001 ◽  
Author(s):  
Emmanuel Gyan ◽  
Charles Foussard ◽  
Philippe Bertrand ◽  
Patrick Michenet ◽  
Steven Le Gouill ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Multicenter Study ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Secondary Malignancies ◽  
First Line ◽  
High Dose Therapy ◽  
Acute Myeloid

Abstract Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%; P = .004). A PFS plateau was observed in the HDT group after 7 years. On multivariate analysis, OS and PFS were independently affected by the per-formance status score, the number of nodal areas involved, and the treatment group. Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia, P = .01). The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT. However, the increased rate of secondary malignancies may discourage the use of purged ASCT in combination with TBI as first-line treatment for FL. This trial has been registered with ClinicalTrials.gov under identifier NCT00696735.

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