Autologous tandem transplantation: almost complete reduction of neutropenic fever following the second transplantation by ex vivo expanded autologous myeloid postprogenitor cells

Abstract

Reduced post-transplant performance status because of infectious complications is still a problem following autologous peripheral blood stem cell transplantation (aPBSCT). In this study, a tandem transplantation scheme for 15 patients with breast cancer including etoposide (1500 mg/m(2)), ifosfamide (12 g/m(2)) and carboplatin (1500 mg/m(2)) as conditioning regimens, followed by aPBSCT, was used to evaluate the potential clinical benefit of the additional retransfusion of low numbers of ex vivo expanded committed myeloid postprogenitor cells (PPCs) (median 408 x 103 CFU-c/kg BW, range 0.93-1995) following the second transplantation. Following a 7+2 days expansion (using recombinant human SCF, IL-1beta, IL-3, IL-6 + G-CSF), CFU-c generated from CD34-positive cells from leukapheresis products could be expanded by a median factor of 153 (range 5-434). Flow cytometric analysis and morphology of CFUs have shown a nearly exclusive expansion and differentiation of committed myeloid progenitor cells and a significant reduction of CD34-positive cells. In an intra- and interindividual comparison it could be shown that the retransfusion of committed myeloid postprogenitor cells significantly accelerates myeloid recovery. Although retransfusion of PPCs fails to abrogate severe neutropenia following aPBSCT, it significantly ameliorates infectious complications and shortens the duration of hospital stay.