Is There Really a Difference in Outcome and Incidence of Acute/Chronic GVHD in Patients Undergoing Unmanipulated MUD-PBSCT vs MUD-BMT? Single Large Pediatric Center Experience

There is an unresolved question whether unmanipulated matched unrelated donor (MUD) PBSCT leads to a worse overall outcome and higher incidence of severe GvHD in comparison with well established MUD-BMT. It is well known that PBSC grafts contain ca 1 log more mature T cells, which may result in higher rate of severe and often fatal acute/chronic GvHD after MUD-PBSCT. The aim of our study was to compare the results of MUD-PBSCT vs MUD-BMT in a large mostly pediatric patient population. We analyzed the records of 177 consecutive pts (with hematologic malignancies, n = 148 and non-malignant disorders, n = 29), who underwent MUD-BMT (42 pts) or MUD-PBSCT (135 pts) between 1999 and February 2008 in our department. Probability of overall survival for all pts after MUD-PBSCT was 0.54 and after MUD-BMT was 0.46 (p = NS). Median follow-up of surviving 97 pts (55%) was 3 years. Furthermore, there was no difference between the probability of incidence of both acute GvHD grade III-IV between the recipients of MUD-PBSCT (0.2) or MUD-BMT (0.25) and extensive chronic GvHD (0.21 for MUD-PBSCT recipients and 0.18 for MUD-BMT recipients). With regard to “high resolution” HLA match, 84 donor-recipient pairs were fully matched, whereas 64 were mismatched at one, 24 at two and 5 at three loci. Probability of survival, acute GvHD grades III-IV and extensive cGvHD were for respective groups as follows: 0.53, 0.18, 0.17 for 10 of 10 allele matched group, 0.47, 0.21, 0.18 for 9 of 10 allele matched group and surprisingly 0.58, 0.27 and 0.27 for 8 of 10 allele matched group. In the latter group, however, if two HLA antigens were mismatched the probability of survival decreased to 0.38, probability of severe aGvHD increased to 0.46 and of extensive cGvHD to 0.6. If only one antigen + one allele or two alleles were mismatched, the probability of survival was as high as 0.65 and probability of severe aGvHD as low as 0.19. In conclusion, the results of MUD-PBSCT in a large prospective cohort of pts are similar if not better than the results of MUD-BMT. There seems to be no increased risk of severe GvHD after MUD-PBSCT. MUD-PBSCT might offer a better disease control in patients with malignancies, especially with AML. With regard to the degree of HLA match it seems that transplants from 8 of 10 allele matched donors (with maximum 1 mismatched antigen) influence neither survival nor incidence of severe GvHD, whereas one should avoid performing transplants from two antigen mismatched donors.