Combined positive/negative purging and transplantation of peripheral bloodprogenitor cell autografts in breast cancer patients: a pilot study

This trial studied the feasibility and efficiency of a novel procedure of d ouble purging to eliminate tumor cells from leukapheresis products of stage IV breast cancer patients, After induction and mobilization therapy, 35 le ukapheresis products from 16 breast cancer patients were subjected to CD34( +) enrichment (i.e., positive selection) with the Isolex 300(TM) device and subsequent immunomagnetic depletion of tumor cells (i.e., negative selecti on) using a cocktail of three monoclonal antibodies directed against epithe lial antigens, Patients with clinical response to induction chemotherapy pr oceeded to tandem high-dose chemotherapy, which consisted of melphalan (140 mg/m(2)) followed by retransfusion of the purged graft. After hematologic recovery, patients received ifosfamide 14 g/m(2), carboplatin 1.5 g/m2, and etoposide 1.5g/m(2) (ICE), again followed by autografting. After positive selection, a median purity of 96.6% CD34% cells (range 48.4-99.2%) and a re covery of 56.8% (range 25.8-92.6%) were achieved. Subsequent negative purgi ng resulted in a median CD34(+) purity of 97.2%, Overall CD34(+) recovery a fter both purging procedures was 51.1% (range 18.5-82.4%). Tumor cells were detectable in 8 of 16 (50%) starting fractions before purging. After both purging cycles, only 1 of 16 autografts remained positive for tumor cells c ompared to 3 of 16 after CD34(+) selection. A calculated purging efficiency of 2 to >4 log was achieved. Engraftment was rapid, reaching greater than or equal to 500/mu L neutrophils on day +10 after melphalan and on day +9 a fter ICE. A platelet count of greater than or equal to 20.000/mu L was reac hed on day +12 after melphalan and on day +11 after ICE. Thus, combining po sitive and negative purging is feasible, further enhances purging efficienc y, and does not compromise the quality of the graft, leading to rapid engra ftment after high-dose chemotherapy, (C) 1999 International Society for Exp erimental Hematology. Published by Elsevier Science Inc.