title: Phagocyte function decreases after high-dose treatment with melphalan and autologous stem cell transplantation in patients with multiple myeloma.
abstract: High-dose melphalan with autologous hematopoietic stem cell transplantation (ASCT) is the standard of care for younger patients with newly diagnosed multiple myeloma and is aimed at achieving as deep and complete a response as possible after various combinations of induction therapy. However, it is frequently associated with infectious complications. This study investigated the effects of high-dose treatment with autologous stem cell support on patients' innate immunity, with a focus on subpopulations and functioning of recently released polymorphonuclear leukocytes (PMNs) and monocytes in peripheral blood. Flow cytometry-based analysis was used to measure the degree of PMN maturation and activation, before and after ASCT and compared with healthy controls. After high-dose treatment and ASCT, a smaller proportion of patients' PMNs had the capacity for oxidative burst. Moreover, patients' PMNs, both before and after ASCT, had a reduced capacity for phagocytosis. Eosinophils, which recently have been suggested to play a role in promoting malignant plasma cell proliferation, were markedly reduced after ASCT, with slow regeneration. HLA-DR expression by monocytes was significantly depressed after ASCT, a characteristic often attributed to monocytic myeloid-derived suppressor cells. Our results suggest that several aspects of phagocytic function are impaired for at least 20 days after ASCT.
authors.affiliation: Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden. Electronic address: Stina.Wichert@med.lu.se.
authors.forename: Stina
authors.initials: S
authors.lastname: Wichert
authors.affiliation: Department of Nephrology, Clinical Sciences in Lund, Lund University, Lund, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Pettersson
authors.affiliation: Department of Nephrology, Clinical Sciences in Lund, Lund University, Lund, Sweden.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hellmark
authors.affiliation: Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden; Clinical Immunology and Transfusion Medicine, University and Regional Laboratories Region Skåne, Lund, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Johansson
authors.affiliation: Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden.
authors.forename: Markus
authors.initials: M
authors.lastname: Hansson
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008558:Melphalan / Q000627:therapeutic use*; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009101:Multiple Myeloma / Q000628:therapy*; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D016897:Respiratory Burst / Q000187:drug effects; D013997:Time Factors; D014182:Transplantation, Autologous
chemical_list: D018906:Antineoplastic Agents, Alkylating; D006684:HLA-DR Antigens; D008558:Melphalan