title: High steady-state plasma levels of flt3-ligand in the peripheral blood is a good predictor for poor mobilization of CD34+ PBSC in patients undergoing high-dose chemotherapy and stem cell rescue.
abstract: flt3-ligand (flt3-L) is a very effective mobilizer of hematopoietic stem cells (HSC) and is capable of inducing multilineage hematopoietic cell differentiation both in vivo and in vitro. We measured, by ELISA, the plasma peripheral blood flt3-L concentrations in 28 non-Hodgkin's lymphoma (NHL) patients before and after mobilization with three different mobilization regimens, including priming with cyclophosphamide (CY) plus G-CSF, CY plus GM-CSF, and CY plus GM-CSF (8 days) followed by G-CSF. We also determined the levels of flt3-L in the peripheral blood during four apheresis collections and 6 months after transplantation. The steady-state level of flt3-L in NHL patients (n = 18) who mobilized > or =2 x 10(6) CD34+ cells/kg in four apheresis collections was 34 +/- 4 pg/ml and was similar to the levels observed in 10 normal controls (27 +/- 7, p = 0.1) regardless of the mobilization protocol used. In contrast, patients who failed to mobilize a total of >0.4 x 10(6) CD34+ cells/kg in two consecutive apheresis collections (n = 10) had flt3-L levels of 106 +/- 11 pg/ml, significantly higher (p = 0.006) than that of the good mobilizers group, regardless of the mobilization protocol used. Similar results were observed in 29 multiple myeloma (MM) patients. A mean of 23.8 +/- 7.9 pg/ml and 450 +/- 85 pg/ml flt3-L was obtained in the good mobilizers (n = 24) and the nonmobilizers (n = 5) groups of patients, respectively. Statistical analysis revealed a significant difference (p = 0.0006) between the two groups of MM patients, but no correlation was observed between the levels of flt3-L and CD34+ cell/microl, in mobilized peripheral blood. Our results also suggest that measurement of plasma levels of flt3-L before mobilization can be clinically useful to predict for patients with poor mobilization outcome.
authors.affiliation: Department of Medicine/Hematology, University of Texas Health Science Center at San Antonio, 78284, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Gazitt
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000097:blood; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016238:Cytapheresis; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000097:blood / Q000628:therapy; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000628:therapy; D011237:Predictive Value of Tests; D018709:Statistics, Nonparametric
chemical_list: D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D008565:Membrane Proteins; C084881:flt3 ligand protein