Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Metastatic Breast Cancer.

Abstract

We postulated that it is possible to safely extend the benefits of allografting to metastatic breast cancer by combining cytoreduction achieved with high-dose therapy and autologous stem cell transplant (HDT/ASCT) and graft versus tumor effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT). Seventeen patients, 41 years of age (range, 31–57), with heavily pretreated disease were given HDT/ASCT. No patient died after HDT/ASCT. Thirty-one to 92 days (median, 51 days) after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and donor PBPC from HLA-identical siblings. Postgrafting immunosuppression consisted of cyclosporine and methotrexate. Donor lymphocyte infusions were given to 11 patients with stable mixed chimerism and/or progressive disease, who did not show signs of GVHD. Thirteen patients (76%) achieved sustained donor engraftment. Three patients achieved partial remission (PR) after HDT/ASCT and complete remission (CR) after RICT; another no-responsive patient achieved PR for an overall response rate of 4/17 (22%). The first signs of responsiveness in CR patients began at day +80, +90 and +110 and the maximal response was achieved on day +240, +300 and +390. The 3 remitters patients achieved full chimerism and developed GVHD before regression of the disease. Grade ≥II aGVHD occurred in 5 patients (29%) and extensive cGVHD in 5 patients (29%). No transplant-related deaths (TRD) were observed during the first 100 days. Three patients died of extensive cGVHD in the first year. At April 2004, 5/17 patients (29%) are alive 90–2160 days (median, 1320) from RICT. In conclusion, this 2-step approach is a feasible procedure in metastatic breast cancer patients; the exploitation of graft versus tumor effect is a promising finding.