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.

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.

Autotransplants for Multiple Myeloma (MM) – An Update of the Arkansas Experience Since 1989 In Almost 4000 Patients with Special Emphasis on Third and Further Transplants.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1352-1352
Author(s):  
Bijay Nair ◽  
Elias J. Anaissie ◽  
Sarah Waheed ◽  
Yazan Alsayed ◽  
Rachael Sexton ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Outcome Data ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Front Line ◽  
High Dose Therapy ◽  
Free Survival ◽  
Treatment Groups ◽  
Dose Therapy ◽  
Previously Treated

Abstract Abstract 1352 Background: The Arkansas program has emphasized high hematopoietic progenitor cell (HPC) yields since its inception in 1989, in order to enable further high-dose therapy for relapse, rescue patients from hematopoietic compromise due to extensive cumulative genotoxic or novel agent dosing, and provide a fall-back option in the case MDS develops. Here we are examining the overall outcome data among 3888 patients undergoing HPC-supported therapy since 1989. Patients and Methods: Patients were grouped according to whether they received front-line Total Therapy (TT) protocols (TT-P, n=1452), non-TT protocols for previously treated MM (non-TT-P, n= 1155) or non-protocol therapies (non-P, n=1281). Overall survival (OS) and event free survival (EFS) were measured from the 1st high-dose therapy (Tx-1) intervention and examined in the context of baseline variables present prior to Tx-1, the aforementioned 3 treatment groups, and intervals between successive Tx interventions. Results: OS/EFS from Tx-1 was longest with TT-P (5-yr estimates, 67%/52%) followed by non-TT-P (5-yr estimates, 43%/30%) and non-P (5-yr estimates, 36%/27%) (p<0.0001, p<0.0001). Among all 3888 patients, 2773 (71%) received Tx-2 including 2385 (86%) within 6 months of Tx-1; 405 (10%) received Tx-3 including 140 (35%) within 2yr of Tx-2; 58 (1.5%) received Tx-4 including 44 (76%) within 2yr form Tx-3; 12 (0.3%) received Tx-5 all within 2yr from Tx-4; and 3 patients had Tx-6. When examined in the context of the 3 different treatment groups, 1157/1231 (94%) of the TT-P group had Tx-2 within 6mo, 51/169 (30%) had Tx-3 within 2yr of Tx-2, 51/169 (30%) had Tx-4 within 2yr of Tx-3, and 7/7 (100%) had a Tx-5 within 2 yr of Tx-4. Among 1155 non-TT-P patients, 646/822 (79%) had Tx-2 within 6mo of Tx-1, 37/129 (29%) had Tx-3 within 2yr of Tx-2, 14/18 (78%) had Tx-4 within 3yr of Tx-3, and all 4 (100%) receiving Tx-5 had done so within 2yr of Tx-4. Among 1281 non-P patients, 582/720 (81%) had received Tx-2 within 6mo of Tx-1, 52/107 (49%) had received Tx-3 within 2yr of Tx-2, 7/10 (70%) had received Tx-4 within 2yr of Tx-3, and 1 patient received Tx-5 within 2yr of Tx-4. KM plots from Tx-3 were similar among the 3 treatment groups with median OS of 16mo for TT-P, 14mo for non-TT-P and 11mo for non-P (p=0.13); median EFS were 7, 8, and 6 months (P=0.17). Timely application within 6mo resulted in superior OS and EFS from Tx-2 (OS: 79 v 23 months, EFS: 48 v 14 months; both P<0.0001). Multivariate Cox analyses examining post-Tx EFS and OS revealed TT-P superiority from Tx-1 and Tx-2 over non-TT-P and non-P; Tx-2 within 6mo of Tx-1 provided superior post-Tx-2 EFS and OS; while benefit from Tx-3 was not apparent until at least 2yr had elapsed since Tx-2. CA within 1 year of Tx-1 adversely affected EFS and OS from Tx-1, Tx-2 and Tx-3. Other adverse baseline parameters included low albumin for EFS and OS post-Tx-1; and B2M >=3.5mg/L for EFS and OS post-Tx-1 and post-Tx-2. Conclusions: We confirm that front-line TT-P provides superior clinical outcomes in comparison with back-up/salvage non-TT-P and non-P Tx, emphasizing the benefit from planned upfront protocol therapy. Timely application of Tx-2 within 6 months of Tx-1 extended both EFS and OS from Tx-2, validating our concept of maximum tumor cyto-reduction and avoiding MM re-growth. Tx-3 was useful when applied beyond 2yr from Tx-2, in support of the notion that longer disease control prior to relapse favorably impacts subsequent salvage Tx. 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.

scholarly journals HLA-haploidentical vs matched-sibling hematopoietic cell transplantation: a systematic review and meta-analysis

2019 ◽  
Vol 3 (17) ◽  
pp. 2581-2585 ◽  
Author(s):  
Mohamad A. Meybodi ◽  
Wenhao Cao ◽  
Leo Luznik ◽  
Asad Bashey ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Meta Analysis ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
Relative Contribution ◽  
Haploidentical Hematopoietic Cell Transplantation ◽  
Matched Sibling ◽  
Outcome Differences

Abstract HLA haploidentical hematopoietic cell transplantation (haplo-HCT) using posttransplantation cyclophosphamide (PT-Cy) is an alternative strategy when a matched sibling donor (MSD) is not available. We performed a systematic review and meta-analysis to compare the outcomes of MSD vs haplo-HCT. Eleven studies (1410 haplo-HCT and 6396 MSD recipients) were meta-analyzed. All studies were retrospective and high quality, and 9 were multicenter. Haplo-HCT was associated with ~50% lower risk of chronic graft-versus-host disease (GVHD) (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.41-0.74), but higher risk of nonrelapse mortality (HR, 1.36; 95% CI, 1.12-1.66). Relapse, survival, acute GVHD, and GVHD-free relapse-free survival were not significantly different between the groups. Deciphering the relative contribution of PT-Cy and HLA disparity to the observed outcome differences between the groups requires further research.

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