Depth of response assessed by quantitative ASO-PCR predicts the outcome after stem cell transplantation in multiple myeloma.
Achievement of complete response (CR) is a new goal of therapy for multiple myeloma (MM). By sensitive methods, the depth of response can be measured even among the patients in CR. We used a sensitive real-time quantitative polymerase chain reaction by allele-specific primers (qASO-PCR) to assess the level of minimal residual disease (MRD) in bone marrow of 37 patients with myeloma who had achieved CR/near-to-CR after autologous or allogeneic stem cell transplantation (SCT). Allele-specific primers could be successfully designed for 86% of patients. Three to six months after autotransplantation, the PCR target was not detectable in 53% of patients (16/30 patients), and the respective figure after allotransplantation was 71% (5/7 patients); the median sensitivity of PCR assay was <0.002%. The proportion of patients without detectable PCR target was 22% of all autotransplanted patients. A threshold level of 0.01% in the qASO-PCR assay 3-6 months after SCT was found to be a useful cut-off limit to divide the patients into two prognostic groups: MRD low/negative vs. MRD high. Low/negative MRD after SCT was a significant predictive factor for the prolongation of progression free (70 vs. 19 months; P = 0.003) and suggestively also for overall survival. We conclude that not only CR but also its depth is important for the long-term outcome in MM.
Putkonen
Mervi
M
Department of Medicine, Turku University Central Hospital, Vaasa, Finland. mervi.putkonen@tyks.fi
Kairisto
Veli
V
Juvonen
Vesa
V
Pelliniemi
Tarja-Terttu
TT
Rauhala
Auvo
A
Itälä-Remes
Maija
M
Remes
Kari
K
D000328:Adult; D000368:Aged; D000483:Alleles; D001853:Bone Marrow / Q000473:pathology; D017931:DNA Primers; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D018365:Neoplasm, Residual / Q000175:diagnosis*; D016133:Polymerase Chain Reaction / Q000379:methods* / Q000592:standards; D011237:Predictive Value of Tests; D011379:Prognosis; D012074:Remission Induction / Q000379:methods; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
D017931:DNA Primers