Abstract

G-CSF mobilized peripheral blood stem cells are increasingly used as a source of cells for sibling allogeneic transplantation. In comparison with bone marrow transplants (BMT), peripheral blood stem cell transplants (PBSCT) have been associated with increased chronic graft-versus-host disease (cGVHD). In order to examine the relationship between CD34+ and CD3+ counts and the development of cGVHD, we analyzed the outcome of patients from an international database of nine randomized trials comparing PBSCT and BMT. There were a total of 1111 patients: 305 patients developed extensive cGVHD, 261 limited cGVHD, 368 had no cGVHD and 177 did not have adequate information concerning cGVHD for analysis. We excluded patients with limited cGVHD because this can be a difficult diagnosis to make with certainty. We also excluded those without adequate data and thus the analysis is based on 673 patients (305 with extensive cGVHD and 368 with no cGVHD). There was no common baseline hazard for the development of extensive cGVHD among studies and thus the analysis was stratified by study. The primary outcomes were time to development of extensive cGVHD and time to the composite endpoint of death or relapse. Harvest CD34+ and CD3+ counts were analyzed as dichotomous variables based on the median cell counts. In the PBSCT group, the median CD34+ and CD3+ counts were 6.05 and 288.01×106/kg and in the BMT group, the median CD34+ and CD3+ counts were 2.89 and 32.79×106/kg respectively. As previously reported, there was an increased risk of developing extensive cGVHD with PBSCT compared to BMT (hazard ratio 1.77, 95% CI 1.39–2.23). The time to develop extensive cGVHD was not affected by the CD34+ or CD3+ count within either the PBSCT or BMT group. In addition, the composite endpoint of death or relapse was also not affected by either the CD34+ or CD3+ count in the PBSCT group. However, in the BMT group, a higher median CD3+ count was associated with an increased risk of death or relapse (p=0.04). Furthermore, a higher median CD34+ count was associated with a trend to a decreased risk of death or relapse (p=0.09). In summary, we confirm the higher risk of developing extensive cGVHD with PBSCT compared to BMT. In this analysis, we did not find a relationship between CD34+ and CD3+ counts and the risk of extensive cGVHD within either the PBSCT or BMT groups. However, our analysis suggests an association between higher median CD3+ counts and an increased risk of death or relapse in the BMT group. If this observation is confirmed, further studies are required to determine whether the higher CD3+ cell content of the marrow graft exerts a direct effect on the risk of relapse or death, or whether it is a surrogate for a less effective marrow harvest.

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