title: Content of endothelial progenitor cells in autologous stem cell grafts predict survival after transplantation for multiple myeloma.
abstract: Multiple myeloma (MM) is considered an incurable B cell malignancy, although many patients can benefit from high-dose therapy with autologous stem cell transplantation (ASCT) as a first-line treatment. In non-Hodgkin lymphoma (NHL), ASCT is usually performed after relapse with curative intent. Disease progression is often associated with increased angiogenesis, in which endothelial progenitor cells (EPC) may have a central role. Here, we investigated the clinical impact of EPC levels in peripheral blood stem cell (PBSC) autografts for MM and NHL patients who received ASCT. EPC were identified by flow cytometry as aldehyde dehydrogenase(hi) CD34(+) vascular endothelial growth factor receptor 2(+) CD133(+) cells in both MM and NHL autografts. In MM, there was a positive correlation between EPC percentage and serum (s)-β2-microglobulin levels (r(2) = .371, P = .002). Unlike for NHL patients, MM patients with high numbers of infused EPC (EPC cells per kilogram) during ASCT had significant shorter progression-free survival (PFS) (P = .035), overall survival (P = .044) and time to next treatment (P = .009). In multivariate analysis, EPC cells per kilogram was a significant independent negative prognostic indicator of PFS (P = .03). In conclusion, the presence of high number of EPC in PBSC grafts is associated with adverse prognosis after ASCT in MM.
authors.affiliation: Immunology Research group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway; Department of Oncology, University Hospital of North Norway, Tromsø, Norway. Electronic address: egil.blix@uit.no.
authors.forename: Egil S
authors.initials: ES
authors.lastname: Blix
authors.affiliation: Surgical Research Laboratory, Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anders B
authors.initials: AB
authors.lastname: Kildal
authors.affiliation: Immunology Research group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Eirin
authors.initials: E
authors.lastname: Bertelsen
authors.affiliation: Department of Hematology, St. Olavs Hospital and IKM, Norwegian University of Technology and Science and KG Jebsen Center for Myeloma Research, Trondheim, Norway.
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.affiliation: Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
authors.forename: June H
authors.initials: JH
authors.lastname: Myklebust
authors.affiliation: Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Kolstad
authors.affiliation: Immunology Research group, Institute of Medical Biology, UiT The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Husebekk
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D064592:Autografts; D018572:Disease-Free Survival; D042783:Endothelial Cells / Q000378:metabolism*; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000378:metabolism; D011237:Predictive Value of Tests; D033581:Stem Cell Transplantation; D015996:Survival Rate; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Aldehyde dehydrogenase; Angiogenesis; Autologous stem cell transplantation; CD133; Endothelial progenitor cells; Multiple myeloma