title: Peripheral blood monoclonal B-cells predict the event free survival in multiple myeloma.
abstract: Reinfusion of myeloma progenitor cells may contribute to relapse of multiple myeloma after autologous stem cell transplantation. The aim of our study was to investigate whether monoclonal B-cells are present in the apheresis product and to evaluate the clinical relevance of these cells. Leukapheresis products of 55 patients were purged with anti-B-cell-Monoclonal antibodies (MoAbs) and immunobeads. Monoclonal B-cells were found in 85% of patients within the B-cell population. In one third of all myeloma patients, the majority of B-cells was represented by monoclonal myeloma progenitor B-cells, whereas in two thirds of patients monoclonal cells only represented a small part of the entire B-cell population. As shown by sequence analysis, monoclonal precursor B-cells and malignant plasma cells had the identical genetic CDR III sequence. The purging efficacy, using a negative selection system, was a median of 3 logs (range 1,5-3,5). No statistical difference in the purging efficacy was found when 3, 4 or 5 MoAbs against B-cells antigens were used. However, a tumor specific signal could be detected in the purged harvest of all patients, when the highly sensitive ASO-PCR approach was used. Furthermore, we found a direct correlation between the amount of remaining monoclonal cells after negative selection and the event free survival of myeloma patients. 10/15 patients with a median of 20 x 10(3) monoclonal cells in the purged product relapsed at a median of 1,4 years, whereas only 6/24 patients with an oligoclonal pattern including a low number of remaining monoclonal cells relapsed at a median of 2,2 years. The event free survival (EFS) was statistically different between the two groups (p = 0,014).
authors.affiliation: Department of Haematology and Bone Marrow Transplantation Centre; L. Böhlerstrasse 5, I-39100 Bozen/Bolzano, Italy. mitman@dnet.it
authors.forename: M
authors.initials: M
authors.lastname: Mitterer
authors.forename: A J
authors.initials: AJ
authors.lastname: Lanthaler
authors.forename: B
authors.initials: B
authors.lastname: Schnabel
authors.forename: M
authors.initials: M
authors.lastname: Svaldi
authors.forename: F
authors.initials: F
authors.lastname: Oduncu
authors.forename: P
authors.initials: P
authors.lastname: Coser
authors.forename: B
authors.initials: B
authors.lastname: Emmerich
authors.forename: H
authors.initials: H
authors.lastname: Huemer
authors.forename: C
authors.initials: C
authors.lastname: Straka
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016465:Bone Marrow Purging / Q000379:methods; D022801:Complementarity Determining Regions / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000628:therapy*; D009194:Myeloma Proteins / Q000032:analysis*; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007136:Immunoglobulins; D009194:Myeloma Proteins; C017551:myeloma immunoglobulins