-
1.
Autologous hematopoietic cell transplantation versus whole-brain radiotherapy consolidation in primary central nervous system lymphoma: A systematic review and meta-analysis
Epperla, N., Reljic, T., Chowdhury, S. M., Ferreri, A. J. M., Kumar, A., Hamadani, M.
Hematological oncology. 2022
Abstract
The management of newly diagnosed primary central nervous system lymphoma (PCNSL) includes administration of high-dose methotrexate based regimens followed by consolidation therapy to minimize the risk of relapse. However, the best consolidation strategy (autologous hematopoietic cell transplant [auto-HCT] vs. whole-brain radiotherapy [WBRT]) is controversial. Hence, we performed a systematic review and meta-analysis of all randomized controlled trials that compared auto-HCT versus WBRT consolidation for patients with PCNSL after first-line treatment.The primary outcome was overall survival (OS), while the secondary outcomes included progression-free survival (PFS), response rates (overall response rate [ORR] and complete remission [CR]), relapse rate, treatment-related mortality (TRM), and neuropsychological adverse events. We performed a pooled analysis of the single-arm studies that incorporated auto-HCT or WBRT consolidation and evaluated neurocognitive outcomes. Only two studies met the inclusion criteria (n = 240). There was no significant difference in OS (HR = 1.50; 95% CI = 0.95-2.36), PFS (HR = 0.99; 95% CI = 0.44-2.22), ORR (RR = 1.48; 95% CI = 0.90-2.44), CR rate (RR = 1.21; 95% CI = 0.90-1.63), relapse rate (RR = 0.46; 95% CI = 0.05-4.28), and TRM (RR = 5.67; 95% CI = 1.01-31.91). The neuropsychological tests to assess neurocognitive domains were different and inconsistently reported in the two studies and therefore we were unable to perform a meta-analysis but provide a descriptive assessment. Both the studies showed a significant decline in the attention/executive function (based on the trail making test A and trail making test B) in those receiving WBRT compared to auto-HCT. We found 9 single-arm phase II studies that reported data on outcomes associated with either auto-HCT (5 studies) or WBRT (4 studies) consolidation. Of these, two studies (n = 43) reported data on neurocognitive decline following auto-HCT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 6% (95% CI, 0%-17%) for those receiving auto-HCT and there was no heterogeneity between studies (I(2) = 0%). Three studies (n = 122) reported data on neurocognitive decline following WBRT consolidation. Pooled proportion of patients with neurocognitive decline in these studies was 43% (95% CI, 11%-78%) for those receiving WBRT and there was high heterogeneity between studies (I(2) = 94%). There was significant heterogeneity between subgroups (p = 0.035). The outcomes were not significantly different in patients with PCNSL receiving auto-HCT or WBRT consolidation therapies, however, there is a higher degree of neurocognitive decline associated with WBRT compared to auto-HCT consolidation. The decision to choose a consolidation strategy needs to be individualized based on age, frailty, and co-morbidities.
-
2.
Myeloablative vs. reduced-intensity hematopoietic cell transplantation in myelodysplastic syndromes: a systematic review and meta-analysis
Rashidi, A., Meybodi, M. A., Cao, W., Chu, H., Warlick, E. D., Devine, S., Pasquini, M. C., Weisdorf, D. J., Hamadani, M.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
In a systematic review and meta-analysis, we compared allogeneic transplant outcomes after myeloablative (MAC) vs. reduced-intensity (RIC) conditioning in patients with MDS. Only two published randomized clinical trials were found, with a pooled sample size of 183 (RIC: 92; MAC: 91). Both studies suggested an overall survival advantage after RIC, with a pooled hazard ratio (HR) of 0.67 (95% confidence interval [CI] 0.41-1.09) for RIC vs. MAC. Relapse results were also concordant, with a pooled HR of 1.55 (95%CI 0.74-3.25) for RIC vs. MAC. Neither result was statistically significant. Comparisons for other outcomes were unremarkable. In conclusion, the evidence for the optimal conditioning intensity in MDS is weak. Post-transplant maintenance strategies and incorporation of genomic information into decision-making may improve post-transplant outcomes.
-
3.
Upfront autologous hematopoietic stem cell transplantation consolidation for patients with aggressive B-cell lymphomas in first remission in the rituximab era: A systematic review and meta-analysis
Epperla, N., Hamadani, M., Reljic, T., Kharfan-Dabaja, M. A., Savani, B. N., Kumar, A.
Cancer. 2019
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
BACKGROUND The outcomes for patients with diffuse large B-cell lymphoma (DLBCL) with adverse clinical prognostic factors such as a high age-adjusted International Prognostic Index (aaIPI) are not optimal. In the current study, the authors performed a systematic review and meta-analysis to assess the totality of evidence pertaining to the efficacy of autologous hematopoietic stem cell transplantation (auto-HCT) consolidation for patients with DLBCL in first remission. METHODS The authors searched the Cochrane and MEDLINE/PubMed databases through December 1, 2018, for studies comparing conventional chemotherapy with rituximab (R-chemo) versus R-chemo and auto-HCT. Two authors independently reviewed all references for study inclusion and extracted data related to benefits (overall survival, progression-free survival, and response rates) and harms (treatment-related mortality and adverse events). RESULTS Four studies (1173 patients) met the inclusion criteria and were included in the current analysis. The median duration of follow-up ranged from 42 to 76 months. There was no difference noted with regard to the overall survival (hazard ratio, 1.01; 95% CI, 0.74-1.37), progression-free survival (hazard ratio, 0.77; 95% CI, 0.58-1.04), or response rates (risk ratio, 0.98; 95% CI, 0.92-1.04) between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone. CONCLUSIONS The findings from what to the authors' knowledge is the first meta-analysis performed in the rituximab era demonstrated no beneficial effect of upfront auto-HCT consolidation in patients with aggressive B-cell non-Hodgkin lymphoma, including high-risk clinical groups (high aaIPI).
PICO Summary
Population
Patients with diffuse large B-cell lymphoma (4 studies, 1173 pts)
Intervention
Chemotherapy with rituximab + autologous stem cell transplantation. (R-chemo and auto-HCT)
Comparison
Chemotherapy with rituximab (R-chemo)
Outcome
There was no difference noted with regard to the overall survival, progression-free survival, or response rates between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAE grade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone.
-
4.
HLA-haploidentical vs matched-sibling hematopoietic cell transplantation: a systematic review and meta-analysis
Meybodi, M. A., Cao, W., Luznik, L., Bashey, A., Zhang, X., Romee, R., Saber, W., Hamadani, M., Weisdorf, D. J., Chu, H., et al
Blood advances. 2019;3(17):2581-2585
-
-
Free full text
-
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.
-
5.
Antithymocyte globulin for graft-versus-host disease prophylaxis: an updated systematic review and meta-analysis
Kumar, A., Reljic, T., Hamadani, M., Mohty, M., Kharfan-Dabaja, M. A.
Bone marrow transplantation. 2018
Abstract
Graft-versus-host disease (GVHD) remains a limiting factor for successful allogeneic hematopoietic cell transplantation (allo-HCT). Conflicting data exist on the benefit of ATG on post-transplant survival. We performed a systematic review of randomized controlled trials (RCTs) to assess benefits and harms of thymoglobulin and Fresenius (re-branded as Grafalon) ATG formulations in patients undergoing allo-HCT for a variety of hematologic malignancies and bone marrow failure syndromes. A comprehensive search of MEDLINE, EMBASE, and Cochrane Library was performed. Data on methodological quality, benefits, and harms were extracted for each trial and pooled under a random-effects model. Eight RCTs (1134 patients) met the inclusion criteria. Methodological quality ranged from moderate to very low. Pooled results showed no difference in overall survival (OS) with the use of ATG (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.74-1.28; P = 0.83). ATG reduced grade II/III acute GVHD (risk ratio (RR) = 0.61; 95% CI = 0.48-0.77; P < 0.0001), grade III/IV acute GVHD (RR = 0.52; 95% CI = 0.34-0.81; P = 0.004), and chronic GVHD (RR = 0.52; 95% CI = 0.40-0.69; P < 0.00001) without an increase in non-relapse mortality (NRM) (RR = 0.91; 95% CI = 0.74-1.13; P = 0.40). Future studies with better methodological quality are needed to provide conclusive answers related to optimal dosing and timing of ATG for prevention of GVHD.
-
6.
Autologous Transplantation for Newly Diagnosed Multiple Myeloma in the Era of Novel Agent Induction: A Systematic Review and Meta-analysis
Dhakal, B., Szabo, A., Chhabra, S., Hamadani, M., D'Souza, A., Usmani, S. Z., Sieracki, R., Gyawali, B., Jackson, J. L., Asimakopoulos, F., et al
JAMA Oncology. 2018;4(3):343-350
-
-
Free full text
-
Abstract
IMPORTANCE The role of high-dose therapy with melphalan followed by autologous stem cell transplant (HDT/ASCT) in patients with multiple myeloma continues to be debated in the context of novel agent induction. OBJECTIVE To perform a systematic review, conventional meta-analysis, and network meta-analysis of all phase 3 randomized clinical trials (RCTs) evaluating the role of HDT/ASCT. DATA SOURCES We performed a systematic literature search of Cochrane Central, MEDLINE, and Scopus from January 2000 through April 2017 and relevant annual meeting abstracts from January 2014 to December 2016. The following search terms were used: "myeloma" combined with "autologous," "transplant," "myeloablative," or "stem cell." STUDY SELECTION Phase 3 RCTs comparing HDT/ASCT with standard-dose therapy (SDT) using novel agents were assessed. Studies comparing single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone consolidation and tandem transplantation were included for network meta-analysis. DATA EXTRACTION AND SYNTHESIS For the random effects meta-analysis, we used hazard ratios (HRs) and corresponding 95% CIs. MAIN OUTCOMES AND MEASURES The primary outcome was progression-free survival (PFS). Overall survival (OS), complete response, and treatment-related mortality were secondary outcomes. RESULTS A total of 4 RCTs (2421 patients) for conventional meta-analysis and 5 RCTs (3171 patients) for network meta-analysis were selected. The combined odds for complete response were 1.27 (95% CI, 0.97-1.65; P = .07) with HDT/ASCT when compared with SDT. The combined HR for PFS was 0.55 (95% CI, 0.41-0.74; P < .001) and 0.76 for OS (95% CI, 0.42-1.36; P = .20) in favor of HDT. Meta-regression showed that longer follow-up was associated with superior PFS (HR/mo, 0.98; 95% CI, 0.96-0.99; P = .03) and OS (HR/mo, 0.90; 95% CI, 0.84-0.96; P = .002). For PFS, tandem HDT/ASCT had the most favorable HR (0.49; 95% CI, 0.37-0.65) followed by single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone (HR, 0.53; 95% CI, 0.37-0.76) and single HDT/ASCT alone (HR, 0.68; 95% CI, 0.53-0.87) compared with SDT. For OS, none of the HDT/ASCT-based approaches had a significant effect on survival. Treatment-related mortality with HDT/ASCT was minimal (<1%). CONCLUSIONS AND RELEVANCE The results of the conventional meta-analysis and network meta-analysis of all the phase 3 RCTs showed that HDT/ASCT was associated with superior PFS with minimal toxic effects compared with SDT. Both tandem HDT/ASCT and single HDT/ASCT with bortezomib, lenalidomide, and dexamethasone were superior to single HDT/ASCT alone and SDT for PFS, but OS was similar across the 4 approaches. Longer follow-up may better delineate any OS benefit; however, is likely to be affected by effective postrelapse therapy.
-
7.
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. [Review]
El-Asmar, J., Reljic, T., Ayala, E., Hamadani, M., Nishihori, T., Kumar, A., Kharfan-Dabaja, M. A.
Biology of Blood & Marrow Transplantation. 2016;22(5):802-14
Abstract
To date, 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 either as upfront consolidation or in the relapsed/refractory setting. Available data supporting this approach are limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature. Our search identified 1586 publications, but only 27 (n = 1368) met our inclusion criteria. In the front-line setting, pooled analysis of only prospective studies showed rates of progression-free survival (PFS) of 33% (95% confidence interval [CI], 14% to 56%), overall survival (OS) of 54% (95% CI, 32% to 75%), relapse/progression of 26% (95% CI, 20% to 33%), and transplantation-related mortality (TRM) of 2% (95% CI, 0% to 5%); for retrospective studies, rates of PFS, OS, relapse/progression, TRM, and secondary malignancies were 55% (95% CI, 40% to 69%), 68% (95% CI, 56% to 78%), 36% (95% CI, 24% to 48%), 6% (95% CI, 2% to 11%), and 7% (95% CI, 2% to 14%), respectively. On the other hand, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the relapsed/refractory setting showed pooled rates of PFS, OS, relapse/progression, and TRM of 36% (95% CI, 32% to 40%), 47% (95% CI, 43% to 51%), 51% (95% CI, 39% to 62%), and 10% (95% CI, 5% to 17%), respectively. Among the various histologic subtypes, PFS and OS rates appear to be higher in anaplastic large cell lymphoma, regardless of disease stage. In the absence of a multicenter, randomized controlled trial comparing HDT/auto-HCT to a nontransplantation strategy, the findings of this systematic review/meta-analysis may represent the best evidence supporting the role of HDT/auto-HCT for treatment of peripheral T cell lymphomas as front-line consolidation or in the relapsed/refractory setting. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
-
8.
Reduced-intensity or myeloablative allogeneic hematopoietic cell transplantation for mantle cell lymphoma: a systematic review. [Review]
Kharfan-Dabaja, M. A., Reljic, T., El-Asmar, J., Nishihori, T., Ayala, E., Hamadani, M., Kumar, A.
Future Oncology. 2016;12(22):2631-2642
Abstract
Allogeneic hematopoietic cell transplantation (allo-HCT) is the only known treatment that can offer a cure in mantle cell lymphoma, but it is unclear if regimen dose-intensity offers any advantage. We performed a systematic review/meta-analysis to assess efficacy of allo-HCT using myeloablative or reduced-intensity conditioning. We report results according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. On the basis of a relatively lower nonrelapse mortality and a slightly better progression-free survival/event-free survival and overall survival rates, reduced-intensity allo-HCT regimens appear to be the preferred choice when an allo-HCT is being considered for mantle cell lymphoma. The higher rate of relapse when offering reduced-intensity regimens cannot be ignored but certainly highlights opportunities to incorporate post-transplant strategies to mitigate this risk. A prospective comparative study is ultimately needed to generate more conclusive evidence.