Peripheral blood monoclonal B-cells predict the event free survival in multiple myeloma.
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).
Mitterer
M
M
Department of Haematology and Bone Marrow Transplantation Centre; L. Böhlerstrasse 5, I-39100 Bozen/Bolzano, Italy. mitman@dnet.it
Lanthaler
A J
AJ
Schnabel
B
B
Svaldi
M
M
Oduncu
F
F
Coser
P
P
Emmerich
B
B
Huemer
H
H
Straka
C
C
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
D000911:Antibodies, Monoclonal; D022801:Complementarity Determining Regions; D007136:Immunoglobulins; D009194:Myeloma Proteins; C017551:myeloma immunoglobulins