Journal of the National Cancer Institute Advance Access originally published online on January 13, 2009
JNCI Journal of the National Cancer Institute 2009 101(2):100-106; doi:10.1093/jnci/djn439
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© The Author 2009. Published by Oxford University Press.
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Tandem Versus Single Autologous Hematopoietic Cell Transplantation for the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis
Affiliations of authors: Department of Health Outcomes and Behavior (AK, BD), Division of Blood and Marrow Transplantation (MAK-D), and Division of Hematologic Malignancies (BD), Moffitt Cancer Center, Tampa, FL; Department of Oncologic Sciences, College of Medicine, University of South Florida, Tampa, FL (MAK-D, BD); Department of Internal Medicine, University of Bonn, Bonn, Germany (AG)
Correspondence to: Ambuj Kumar, MD, MPH, Department of Health Outcomes and Behavior, Moffitt Cancer Center, 12902 Magnolia Dr MRC 232 A, Tampa, FL (e-mail: ambuj.kumar{at}moffitt.org).
Background: Evidence bearing on the efficacy of tandem autologous hematopoietic transplant (AHCT) vs a single AHCT in patients with multiple myeloma (MM) is conflicting. We performed a systematic review and meta-analysis to synthesize the existing evidence related to the effectiveness of tandem vs single AHCT in patients with MM.
Methods: We searched Medline, conference proceedings, and bibliographies of retrieved articles and contacted experts in the field to identify randomized controlled trials (RCTs) reported in any language that compared tandem with single AHCT in patients with MM through March 31, 2008. Endpoints were overall survival (OS), event-free survival (EFS), response rate, and treatment-related mortality (TRM). Data were pooled under a random-effects model.
Results: Six RCTs enrolling 1803 patients met the inclusion criteria. Patients treated with tandem AHCT did not have better OS (hazard ratio [HR] for mortality for patients treated with tandem transplant vs single transplant = 0.94; 95% confidence interval [CI] = 0.77 to 1.14) or EFS (HR = 0.86; 95% CI = 0.70 to 1.05). Response rate was statistically significantly better with tandem AHCT (risk ratio = 0.79, 95% CI = 0.67 to 0.93), but with a statistically significant increase in TRM (risk ratio = 1.71, 95% CI = 1.05 to 2.79). There was statistically significant heterogeneity among RCTs for OS and EFS.
Conclusion: In previously untreated MM patients, use of tandem AHCT did not result in improved OS or EFS. We conclude that tandem AHCT is associated with improved response rates but at risk of clinically significant increase in TRM.
| CONTEXT AND CAVEATS Prior knowledge Evidence from randomized controlled trials as to the relative efficacy of single vs tandem autologous hemopoietic cell transplantation in improving outcomes for patients with multiple myeloma was conflicting. Study design Meta-analysis in which overall survival (OS) and event-free survival (EFS) and response rate and treatment-related mortality (TRM) were pooled and reported as hazard ratios and risk ratios, respectively, using a random-effects model. Contribution The sum of the trial evidence did not suggest that OS or EFS was improved in patients who received tandem transplantation. Tandem transplantation improved response rates but led to increased TRM. Implications Routine use of tandem transplantation to treat patients with multiple myleloma is not justified. Limitations The study did not have access to individual patient data that may have helped to identify subgroups of patients who might benefit from tandem transplantation. From the Editors
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Manuscript received April 30, 2008; revised September 5, 2008; accepted October 30, 2008.
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J Natl Cancer Inst 2009 101: 69.
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  J. Mehta Re: Tandem vs Single Autologous Hematopoietic Cell Transplantation for the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis J Natl Cancer Inst, October 21, 2009; 101(20): 1430 - 1431. [Full Text] [PDF]
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S. Giralt, D. H. Vesole, G. Somlo, A. Krishnan, E. Stadtmauer, P. Mccarthy, M. C. Pasquini;, and on behalf of the Blood and Marrow Transplant Clini Re: Tandem vs Single Autologous Hematopoietic Cell Transplantation for the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis J Natl Cancer Inst, July 1, 2009; 101(13): 964 - 964. [Full Text] [PDF]
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