High-dose therapy in multiple myeloma: effect of positive selection of CD34+ peripheral blood stem cells on hematologic engraftment and clinical outcome

Abstract

BACKGROUND AND OBJECTIVE: Positive selection of peripheral blood stem cells (PBSC) has been investigated in multiple myeloma (MM) with the aims of reducing plasma cell (PC) contamination of the leukaphereses and improving clinical outcome of autografted patients. DESIGN AND METHODS: In our center 39 untreated patients with stage II and III MM, younger than 65 years, started high-dose therapy consisting of 4 VAD cycles, collection of PBSC mobilized by 7 g/m(2) cyclophosphamide + G-CSF, and myeloablative treatment with 12 mg/kg busulfan plus 120 mg/m(2) melphalan. The leukaphereses from 23/39 patients (59%) were processed for positive selection of CD34(+) cells using an avidin-biotin immunoaffinity device. RESULTS: A reduction of PC contamination of as much as 2 log was found in the post-selection products by a flow-cytometric technique using the monoclonal antibody CD 138 alternatively coupled with CD38 and cytoplasmatic k or l light chains in separate samples. Hematologic reconstitution and clinical outcome of the 23 patients reinfused with selected CD34(+) cells (SEL group) were compared with those of the 16 patients reinfused with unselected cells (UNSEL group). No significant differences were observed between the 2 groups with regards to the median duration of neutropenia and thrombocytopenia, the hematologic support required, the incidence of febrile episodes and bacteremias. At a median follow-up of 18 months (range 5-34) after ASCT, there were 7/23 (32%) continuous complete remissions (CR) in the SEL group and 4/16 (25%) in the UNSEL group; there were 10/23 (44%) continuous partial remissions (PR) and 5/16 (31%) in the SEL and UNSEL groups, respectively. Two patients in the UNSEL group and one patient in the SEL group died of progressive disease. INTERPRETATION AND CONCLUSIONS: Our data show that positive selection allows rapid engraftment of hematopoiesis and low morbidity. Although no significant difference was detected between the two groups in the frequency of CR and PR 3 and 18 months after ASCT, a longer follow-up is needed to evaluate definitively the effect of CD34(+) selection on the clinical outcome after ASCT.