scholarly journals 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 Systematic Review/Meta-Analysis

2016 ◽  
Vol 22 (5) ◽  
pp. 802-814 ◽  
Author(s):  
Jessica El-Asmar ◽  
Tea Reljic ◽  
Ernesto Ayala ◽  
Mehdi Hamadani ◽  
Taiga Nishihori ◽  
...  
Keyword(s):  
Systematic Review ◽  
T Cell ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
High Dose ◽  
Front Line ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Autologous Hematopoietic Cell Transplantation ◽  
Peripheral T Cell Lymphomas

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.

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.

Second-Line Therapy with ICE Followed by High Dose Therapy and Autologous Stem Cell Transplantation for Relapsed/Refractory Peripheral T-Cell Lymphomas: Minimal Benefit When Analyzed by Intent To Treat.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2679-2679 ◽  
Author(s):  
Steven Horwitz ◽  
Craig Moskowitz ◽  
Tarun Kewalramani ◽  
Paul Hamlin ◽  
David Straus ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Refractory Disease ◽  
Second Line ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

Abstract Background: Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with a poorer prognosis than their B-cell counterparts. Second -line chemotherapy (SLT) followed by high dose therapy and autologous stem cell transplantation (HDT/ASCT) is a common approach to patients (pts) with relapsed PTCL. Reports evaluating this approach have analyzed the outcome of transplanted patients. Our goal was to identify pts with relapsed or refractory disease, treated in a uniform manner, with the intent to induce a remission and proceed to HDT/ASCT. Patients and Methods: From our ICE database we identified 40 pts with a diagnosis of a mature T or NK lymphoma who received ICE as SLT therapy prior to planned HDT/ASCT. Histologic subtypes were as follows: PTCL NOS (n=15), anaplastic large cell lymphoma (n=11), angioimmunoblastic T-cell lymphoma (n=5), NK/T cell lymphoma (n=4), subcutaneous panniculitis-like T-cell lymphoma (n=2), and one each of hepatosplenic γ/δ T-cell lymphoma, enteropathy associated T-cell lymphoma, and transformed mycosis fungoides. Median age was 48 years (24–73), five pts were ≥ 60 years. Twenty-five men and 15 women were treated. Initial chemotherapy regimens included: CHOP/CHOP-like (n=32), NHL-15 (n=5), and other (n=4). Twenty-two pts responded to their initial therapy and 18 had primary refractory disease. At time of relapse, 24 pts had stage IV disease, 23 had elevated LDH, and 9 had a performance status ≤ 70%. Thirty-one pts had at least one extranodal site. Complete second line International Prognostic Index (IPI) factors (AA stage, LDH, PS) were available for 36 pts. IPI scores were LR (n=3), LIR (n=12), HIR (n=13), and HR (n=8). Results: All pts received at least one cycle of ICE, 36 received all three planned cycles. Fourteen patients (35%) achieved a complete response, 14 (35%) had a partial response, four (10%) had stable disease, and eight (20%) progressed on therapy. Twenty-seven (68%) pts went on to receive HDT/ASCT. Median follow-up for surviving pts was 45 months (range 7–104). By 3 years, 33/40 (83%) of pts had relapsed with a median progression free survival (PFS) of 6 months from last ICE treatment. Twenty-eight (70%) pts relapsed within 1 year. Neither second-line IPI nor histologic subtype was predictive of continuous remission. Relapsed pts had a superior 3 year PFS compared to primary refractory pts 20% vs 6% (p=0.0005). Despite high relapse rate, 18/40 (45%) of pts were alive at last follow-up. Conclusion: SLT and HDT/ASCT is a common treatment strategy for pts with relapsed PTCL. However, when examined by intention to treat from initiation of SLT and not from time of transplant few pts have durable benefit from this approach. Despite the high response rate to SLT, consolidation with HDT/ASCT provides little clinically meaningful benefit for most pts. The number of pts alive with other therapies despite early relapse underscores the need to study alternative or maintenance strategies for those who achieve remissions.

Novel Therapies and Role of Transplant in the Treatment of Peripheral T-Cell Lymphomas

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 289-296 ◽  
Author(s):  
Steven M. Horwitz
Keyword(s):  
T Cell ◽  
Case Series ◽  
New Drugs ◽  
High Dose ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Phase Ii Studies ◽  
Prospective Trials ◽  
Peripheral T Cell Lymphomas

AbstractPeripheral T-cell lymphomas (PTCL) are an uncommon, heterogeneous group of non-Hodgkin lymphomas that carry a much poorer prognosis than their more common B-cell counterparts. The most commonly used treatment is CHOP or its variations. However, while the results with CHOP are inadequate, there is little compelling data to suggest a preferred alternate strategy. Many of these alternate strategies have been assembled from retrospective data, small case series, subset analyses, phase II studies and individual experience. The greatest experience with alternative treatments has been with the use of high-dose therapy as consolidation. These approaches are promising, but most of the studies are retrospective and include patients with diverse prognoses, making interpretation difficult. Preliminary results of prospective trials in PTCL are only recently being reported. Perhaps more exciting have been the increasing numbers of new therapies being studied for patients with PTCL. The activities of new drugs are being described in studies specifically for PTCL, and attempts at novel combinations are beginning.

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.

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