Workshop on immune reconstitution after BMT

There is evidence that patients undergoing ABMT for the treatment of breast cancer can have marked delays in reconstitution of their cellular immunity and this immune defect may be responsible for the development of opportunistic infections. In a direct comparison between ABMT and PBSCT, the data from the University of Nebraska group suggest that T cell proliferative responses to mitogens normalize sooner in patients who receive PBSCT whereas proliferative responses in patients who receive ABMT remain low after 1 yr. In the same two groups of patients, natural suppressor activity remained elevated beyond a year in the ABMT patients and returned towards normal rapidly in the PBSCT patients. In contrast, the data from Wayne State University suggest that anti-CD3 (TCR)-induced proliferative responses of PBL from ABMT recipients who received PBSCT were not different from PBL of those who received ABMT alone. Cytokine secretion by PBSC and PBL from ABMT + PBSCT recipients was not different from controls. The combination of PBSC with ABMT may alter the kinetics of immune reconstitution after PBSCT alone. However, the number of recipients in WSU data was too small to be statistically significant. Additional numbers in direct comparative studies are needed to clarify these differences. TCD delayed immune reconstitution in patients transplanted at the Medical College of Wisconsin and at Memorial Sloan-Kettering Cancer Center. Immune responses to PHA or anti-CD3 Mab were delayed in adult recipients after TCD at MSKCC until > 18 mos and in unrelated BMTs after use of ATG in the preparative regimen. Several recipients of TCD marrows developed EBV associated lymphoproliferative disorders. The lymphoproliferative disorders were successfully treated with T cell infusions, suggesting a greater role of T cells in mediating graft-vs-leukemia/tumor effects in future autologous and allogeneic BMTs. Taken together with the data in the literature, the workshop participants felt that reimmunizations should be performed in healthy allografted recipients. In conclusion, the data presented at the workshop suggest that ABMT or PBSCT recipients may have immune defects that are qualitatively and quantitatively different than allogeneic BMT recipients depending on the type of transplant, manipulation, or mobilization technique used to obtain PBSC.