Autologous stem cell transplantation in follicular lymphoma

A systematic review and meta-analysis

Murtadha Al Khabori, John R. De Almeida, Gordon H. Guyatt, John Kuruvilla, Michael Crump

Research output: Contribution to journalArticle

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Abstract

Background: The impact of high-dose therapy and autologous stem cell transplantation (ASCT) vs conventional-dose chemotherapy in the initial management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. We performed a systematic review of the randomized clinical trials addressing this question. Methods: We searched MEDLINE, EMBASE, CENTRAL, American Society of Hematology, American Society of Clinical Oncology, BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries, and bibliographies of relevant studies for randomized clinical trials comparing myeloablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced FL. We performed a meta-analysis using random effects models to estimate overall survival, event-free survival, and risks of adverse outcomes. Statistical heterogeneity was calculated by using the I 2 statistic. Results: Seven trials proved eligible, four of which provided data from 941 patients that could be included in a meta-analysis and three of which remain unpublished. In two of the trials, patients in both arms received rituximab during the induction treatment. Moderate quality evidence from the three trials that reported overall survival (n = 701 patients) suggests that ASCT did not result in improved overall survival (hazard ratio of death = 0.99, 95% confidence interval [CI] = 0.73 to 1.33). Low-quality evidence from the four trials of 941 patients suggests improvement in event-free survival in favor of ASCT (hazard ratio of death = 0.54, 95% CI = 0.36 to 0.82) with substantial heterogeneity (I 2 = 80%). Adverse outcomes of treatment-related mortality, myelodysplastic syndrome, acute myeloid leukemia, and solid tumors were not different between the two arms (relative risk [RR] of treatment-related mortality = 1.04, 95% CI = 0.29 to 3.70; RR of myelodysplastic syndrome/acute myeloid leukemia = 2.19, 95% CI = 0.45 to 10.55; I 2 = 48%; and RR of solid tumors = 1.30, 95% CI = 0.33 to 5.08). The absolute risk of death from treatment was 14 per 1000 patients for those who received chemotherapy and 15 per 1000 for those who received ASCT (range = 4-52). Conclusions: Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival. Future trials of ASCT in the context of current chemoimmunotherapy approaches to FL are needed.

Original languageEnglish
Pages (from-to)18-28
Number of pages11
JournalJournal of the National Cancer Institute
Volume104
Issue number1
DOIs
Publication statusPublished - Jan 4 2012

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Follicular Lymphoma
Stem Cell Transplantation
Meta-Analysis
Confidence Intervals
Survival
Drug Therapy
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Disease-Free Survival
Therapeutics
Randomized Controlled Trials
Mortality
Bibliography
MEDLINE
Registries
Neoplasms
Clinical Trials

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Autologous stem cell transplantation in follicular lymphoma : A systematic review and meta-analysis. / Al Khabori, Murtadha; De Almeida, John R.; Guyatt, Gordon H.; Kuruvilla, John; Crump, Michael.

In: Journal of the National Cancer Institute, Vol. 104, No. 1, 04.01.2012, p. 18-28.

Research output: Contribution to journalArticle

Al Khabori, Murtadha ; De Almeida, John R. ; Guyatt, Gordon H. ; Kuruvilla, John ; Crump, Michael. / Autologous stem cell transplantation in follicular lymphoma : A systematic review and meta-analysis. In: Journal of the National Cancer Institute. 2012 ; Vol. 104, No. 1. pp. 18-28.
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abstract = "Background: The impact of high-dose therapy and autologous stem cell transplantation (ASCT) vs conventional-dose chemotherapy in the initial management of adults with advanced follicular lymphoma (FL) on overall survival remains uncertain. We performed a systematic review of the randomized clinical trials addressing this question. Methods: We searched MEDLINE, EMBASE, CENTRAL, American Society of Hematology, American Society of Clinical Oncology, BIOSIS, PAPERSFIRST, PROCEEDINGS, clinical trials registries, and bibliographies of relevant studies for randomized clinical trials comparing myeloablative chemotherapy with ASCT to any chemotherapy in adults with untreated advanced FL. We performed a meta-analysis using random effects models to estimate overall survival, event-free survival, and risks of adverse outcomes. Statistical heterogeneity was calculated by using the I 2 statistic. Results: Seven trials proved eligible, four of which provided data from 941 patients that could be included in a meta-analysis and three of which remain unpublished. In two of the trials, patients in both arms received rituximab during the induction treatment. Moderate quality evidence from the three trials that reported overall survival (n = 701 patients) suggests that ASCT did not result in improved overall survival (hazard ratio of death = 0.99, 95{\%} confidence interval [CI] = 0.73 to 1.33). Low-quality evidence from the four trials of 941 patients suggests improvement in event-free survival in favor of ASCT (hazard ratio of death = 0.54, 95{\%} CI = 0.36 to 0.82) with substantial heterogeneity (I 2 = 80{\%}). Adverse outcomes of treatment-related mortality, myelodysplastic syndrome, acute myeloid leukemia, and solid tumors were not different between the two arms (relative risk [RR] of treatment-related mortality = 1.04, 95{\%} CI = 0.29 to 3.70; RR of myelodysplastic syndrome/acute myeloid leukemia = 2.19, 95{\%} CI = 0.45 to 10.55; I 2 = 48{\%}; and RR of solid tumors = 1.30, 95{\%} CI = 0.33 to 5.08). The absolute risk of death from treatment was 14 per 1000 patients for those who received chemotherapy and 15 per 1000 for those who received ASCT (range = 4-52). Conclusions: Available evidence suggests that high-dose therapy and ASCT as part of FL initial treatment does not improve overall survival. Future trials of ASCT in the context of current chemoimmunotherapy approaches to FL are needed.",
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