Highly purified CD34+ cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients

Abstract

Summary:The primary objective of this study was to evaluate the safety of infusion of CD34 + cells, selected using a clinical scale magnetically activated cell sorting device, assessed by time to hematological engraftment and incidence of adverse events. Secondary objectives included evaluation of device performance in terms of purity and recovery of the CD34 + cell product. Breast cancer patients suitable for transplantation received cyclophosphamide and filgrastim for mobilisation, followed by three leukaphereses. The products of the first two leukaphereses underwent CD34+ cell selection. The product of the third leukapheresis was cryopreserved unmanipulated. Following high-dose cyclophosphamide, thiotepa and carboplatin, selected CD34 + cells were infused. In 54 patients who received selected cells only, the median time to platelet recovery and neutrophil recovery was 11 days (range 5-51) and 9 days (range 5-51), respectively. There were no adverse events associated with infusion of selected cells. A total of 126 leukapheresis samples was available before and after selection for central CD34 + analysis. The median purity was 96.1% (27.4-99.4) and the median recovery was 52.3% (15.2-146.3). These data show that cells selected using magnetically activated cell selection provide safe and rapid engraftment after high-dose therapy. Bone Marrow Transplantation (2000) 25, 243-249.

Selective loss of progenitor subsets following clinical CD34+ cell enrichment by magnetic field, magnetic beads or chromatography separation

“…The development of a large scale clinical system has been reported by McNiece et al 27 documenting a median purity of 96% and yield 78% selected from leukapheresis products from rhG-CSF primed normal donors, starting with a 0.51% content of CD34 ϩ cells. In a subsequent clinical study in breast cancer, 28 we have confirmed these results obtaining a median purity of 95% (range 27-99%) and yield 64% (range 27-146%) from CEF/rhG-CSF primed leukapheresis products containing a median of 1.45% CD34 ϩ cells. These enriched autografts were reinfused after high-dose therapy with absolute neutrophil recovery day 9 (median, range 7-11) and platelet recovery day 11 (median, range 9-15) and no engraftment failures.…”

Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution in non-Hodgkin's lymphoma (NHL): results of Japanese phase II study

“…When infused after high-dose chemotherapy, the selected cells resulted in rapid engraftment in the present study (Table 3), which is quite similar to published data using the same pre-conditioning regimen (MCEC) and autologous unselected stem cell transplantation. 9 Using the CliniMACS, the same favorable hematopoietic reconstitution after CD34 þ cell transplantation has been reported, 11 and the engraftment times obtained with the CliniMACS system compare well to those seen with unselected cells and CD34 þ cells selected using other technologies. 12,13 A unique aspect of the CliniMACS system is that the antibody conjugate, once bound to the CD34 þ cells, is not removed and is then infused into the patient after high-dose chemotherapy, which might cause an allergic reaction.…”

Blood progenitor cell separation from clinical leukapheresis product by magnetic nanoparticle binding and magnetophoresis

“…The purity and recovery results were in the range reported for commercial catch-and-release, batch-wise high gradient magnetic separators when used for CD34þ progenitor cell enrichment from leukapheresis samples (Richel et al, 2000). The throughput was lower than reported previously by us for a different version of the annular flow channel, not equipped for sterile operation and is lower than necessary for scaledup, clinical applications, requiring throughput on the order of 10 6 cells/s (Lara et al, 2006).…”

“…5, coded F and H in Table I). The reported clinical (Richel et al, 2000) and pre-clinical (McNiece and Briddell, 2001) applications of magnetic cell separation all show satisfactory cell tolerance of magnetic label binding and release when used in combination with the batch-wise, high gradient magnetic separators. The addition of continuous cell sorting capability from flowing cell suspensions, as described in this work, is designed to improve the quantitative control over the magnetic sorting process by relating sorter performance to the magnetophoretic mobility of the cell-label complex, and expand the range of potential, clinical applications.…”