Blood stem cell transplantation for breast cancer: new approaches using pre- peri- post-transplant immunotherapy

Autologous peripheral blood stem cell transplantation (auto-PBSCT) after high dose chemotherapy is usually offered to breast cancer patients carrying a high risk of relapse or having chemosensitive metastatic disease. Whether progression free and overall survival of such patients is improved after auto-PBSCT compared to conventional chemotherapy is a matter of debate. Currently available results of randomised trials could not uniformly prove or disprove auto-PBSCT being advantageous. Yet such studies have not employed any manipulation of the stem cell graft or any post-transplant immunomodulation exploiting the unique immunological environment for tumour eradication which exists only after auto-PBSCT. Preliminary data have discussed the ex vivo and in vivo generation of cytotoxic effector cells employing IL-2 and/or IFN-alpha/gamma in the auto-PBSCT setting. Other cytokines such as IL-12, IL-15 and prolactin have likewise been considered. Several anticancer vaccine protocols after auto-PBSCT are ongoing using monovalent vaccines or anti-idiotypic antibodies. Polyvalent anticancer vaccines, cytokine secreting tumour cells, tumour pulsed or hybridised dendritic cells (DC) enhanced with cytokines are studied. Monoclonal antibodies (mAb) could assist: unlabelled for pretransplant exvivo purging, post-transplant for enhancing antibody-dependent cell mediated cytotoxicity (ADCC) or radioimmunoconjugated as an additive cytotoxic part of the conditioning regimen. Autologous graft versus host induction and allogeneic stem cell transplantation (probably with non-myeloablative conditioning followed by donor lymphocyte infusions) are other approaches. Evaluation of successful combinations, optimal dosages and appropriate timing schedules is the subject of future investigations. Since breast cancer patients belong to countless subgroups, a large number of protocols need to be addressed in order to avoid over treatment and prevent relapse.