Preparation and successful engraftment of purified CD34+ bone marrow progenitor cells in patients with non-Hodgkin's lymphoma

Abstract

From September 1992 to January 1994, we evaluated the use of the CEPRATE SC stem cell concentrator (CellPro, Inc, Bothell, WA) to select CD34+ cells from the bone marrow (BM) of 25 patients with non-Hodgkin's lymphoma in complete remission. This system uses the biotinylated 12.8 IgM MoAb to select CD34+ cells. Cells are retained on an avidin column and detached by agitation. Fifteen patients have been transplanted with the CD34+ purified fraction. The CD34+ purified fraction of the 25 processed BMs contained a median of 0.54% of the original nucleated cells in a volume of 5 to 10 mL. The median concentration of CD34+ cells was 49% (range, 12% to 80%), and the median enrichment of CD34+ cells was 33-fold (range, 9- to 85-fold). This selected CD34+ fraction retained 60% (range, 15% to 95%) of late granulocyte-macrophage colony- forming units (CFU-GM), 55% (range, 12% to 99%) of early CFU-GM, and 31% (range, 2% to 100%) erythroid burst-forming units (BFU-E) corresponding to median enrichments of 22-fold (range, 1- to 71-fold), 19-fold (range, 2- to 58-fold), and 14-fold (range, 2- to 200-fold), respectively. There was a correlation between immune phenotypes and progenitor cells. In the initial buffy-coat fractions, the percentage of CD34+ cells was correlated to the cloning efficiency of both late CFU-GM (P < .05) and early CFU-GM (P < .001). In the final selected fraction, there was a correlation between the percentage of CD34+/CD33- and the cloning efficiency of early CFU-GM (P < .05) and between the percentage of CD34+/CD33+ and the cloning efficiency of late CFU-GM (P < .05). Lymphoma cells positive for t(14; 18) were found by polymerase chain reaction in 9 of 14 buffy coats tested before CD34+ cell purification. In 8 cases, the CD34(+)-selected fraction was found to be negative, and the CD34- fraction was found to be positive. After cryopreservation, the recoveries of progenitor cells in the CD34(+)- purified fraction were 79% for late CFU-GM, 71% for early CFU-GM, and 73% for BFU-E. The 15 patients transplanted with the concentrated CD34+ fraction received a median dose of 1 x 10(6) CD34+ cells/kg (range, 0.3 to 2.96) and 10.62 x 10(4) early CFU-GM/kg (range, 0.92 to 25.55). Median days to recovery to 0.5 x 10(9)/L neutrophils and 50 x 10(9)/L platelets were days 15 (range, 10 to 33) and 23 (range, 11 to 68), respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Immunomagnetic selection of CD34+peripheral blood stem cells for autografting in patients with breast cancer

“…Selection of CD34 þ cells from bone marrow or peripheral blood following mobilization with G-CSF without chemotherapy resulted in CD34 þ cell preparations with a purity around 80% (Civin et al, 1996;Alcorn et al, 1996;Lane et al, 1995). The median purity reported for columnbased immunoadsorption selection procedures ranged between 49% and 72% (Berenson et al, 1991;Shpall et al, 1994;Gorin et al, 1995;Brugger et al, 1994;Mahé et al, 1996). The recovery that we observed inversely depended on the content of CD34 þ cells and the number of mononuclear cells in the unseparated product.…”

Purging Peripheral Blood Progenitor Cell Grafts from Lymphoma Cells: Quantitative Comparison of Immunomagnetic CD34 + Selection Systems

“…Recent reports suggest that with a lower initial tumor contamination of the stem cell graft chances are higher to obtain CD34 + -selected products without detectable tumor cells [33]. Thus efficient in vivo purging prior to stem cell collection appears to be highly important.…”

G‐CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma and lymphoma

“…There is recent evidence for a malignant contamination of most of the blood cell grafts (Bird et al, 1994;Lambrechts et al, 1993). Therefore further reducing the quantity of contaminating tumour cells is necessary, methods targeting the CD34 antigen expressed on haemopoietic progenitors, but not on NHL and MM malignant cells (Berenson et al, 1987;Vescio et al, 1994), enable isolation of haemopoietic PBPC and should result in tumour cell depletion (Shpall et al, 1994;Gorin et al, 1995). Previous studies demonstrated that CD34 cells isolated by a biotinavidin immunoadsorption method were capable of reconstituting haemopoiesis in patients with solid cancers (Shpall et al, 1994;Brugger, 1994) and NHL (Gorin et al, 1995).…”

“…Therefore further reducing the quantity of contaminating tumour cells is necessary, methods targeting the CD34 antigen expressed on haemopoietic progenitors, but not on NHL and MM malignant cells (Berenson et al, 1987;Vescio et al, 1994), enable isolation of haemopoietic PBPC and should result in tumour cell depletion (Shpall et al, 1994;Gorin et al, 1995). Previous studies demonstrated that CD34 cells isolated by a biotinavidin immunoadsorption method were capable of reconstituting haemopoiesis in patients with solid cancers (Shpall et al, 1994;Brugger, 1994) and NHL (Gorin et al, 1995). We have investigated the feasibility of CD34 cell positive selection from G-CSF-mobilized PBPC, in MM and NHL patients and the ability of selected cells to restore haemopoiesis after total body irradiation and/or intensive chemotherapy.…”