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

Background and Objectives. Positive selection of peripheral blood stem cell s (PBSC) has been investigated in multiple myeloma (MM) with the aims of re ducing plasma cell (PC) contamination of the leukaphereses and improving cl inical outcome of autografted patients. Design and Methods. In our center 39 untreated patients with stage II and I II 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) melpha lan. The leukaphereses from 23/39 patients (59%) were processed for positiv e 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 t he post-selection products by a flow-cytometric technique using the monoclo nal antibody Co 138 alternatively coupled with CD38 and cytoplasmatic kappa or lambda 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 unse lected cells (UNSEL group). No significant differences were observed betwee n the 2 groups with regards to the median duration of neutropenia and throm bocytopenia, the hematologic support required, the incidence of febrile epi sodes and bacteremias. At a median follow-up of 18 months (range 5-34) afte r ASCT, there were 7/23 (32%) continuous complete remissions (CR) in the SE L group and 4/16 (25%) in the UNSEL group; there were 10/23 (44%) continuou s partial remissions (PR) and 5/16 (31%) in the SEL and UNSEL groups, respe ctively. Two patients in the UNSEL group and one patient in the SEL group d ied 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 mon ths after ASCT, a longer follow-up is needed to evaluate definitively the e ffect of CD34(+) selection on the clinical outcome after ASCT. (C) 2000, Fe rrata Storti Foundation.