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Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis

From the Division of Hematologic Oncology, Dana-Farber Cancer Institute, and Harvard School of Public Health, Boston, MA.

Address reprint requests to Corey Cutler, MD, FRCPC, Dana-Farber Cancer Institute, 44 Binney St, G540, Boston, MA 02115; email: corey_cutler{at}dfci.harvard.edu

PURPOSE: Controversy exists as to whether the incidence of graft-versus-host disease (GVHD) is increased after peripheral-blood stem-cell transplantation (PBSCT) when compared with bone marrow transplantation (BMT). We performed a meta-analysis of all trials comparing the incidence of acute and chronic GVHD after PBSCT and BMT reported as of June, 2000. Secondary analyses examined relapse rates after the two procedures.

METHODS: An extensive MEDLINE search of the literature was undertaken. Primary authors were contacted for clarification and completion of missing information. A review of cited references was also undertaken. Sixteen studies (five randomized controlled trials and 11 cohort studies) were included in this analysis. Data was extracted by two pairs of reviewers and analyzed for the outcomes of interest. Meta-analyses, regression analyses, and assessments of publication bias were performed.

RESULTS: Using a random effects model, the pooled relative risk (RR) for acute GVHD after PBSCT was 1.16 (95% confidence interval [CI], 1.04 to 1.28; P= .006) when compared with traditional BMT. The pooled RR for chronic GVHD after PBSCT was 1.53 (95% CI, 1.25 to 1.88; P < .001) when compared with BMT. The RR of developing clinically extensive chronic GVHD was 1.66 (95% CI, 1.35 to 2.05; P < .001). The excess risk of chronic GVHD was explained by differences in the T-cell dose delivered with the graft in a meta-regression model that did not reach statistical significance. There was a trend towards a decrease in the rate of relapse after PBSCT (RR = 0.81; 95% CI, 0.62 to 1.05).

CONCLUSION: Both acute and chronic GVHD are more common after PBSCT than BMT, and this may be associated with lower rates of malignant relapse. The magnitude of the transfused T-cell load may explain the differences in chronic GVHD risk.

Presented in part at the Forty-Second Annual Meeting of the American Society of Hematology, San Francisco, CA, December 1-5, 2000.

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