title: The level of minimal residual disease in the bone marrow of patients with multiple myeloma before high-dose therapy and autologous blood stem cell transplantation is an independent predictive parameter.
abstract: The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma is still an open question. We measured MRD levels in bone marrow (BM) samples of 53 patients treated with high-dose therapy (HDT) and autologous peripheral blood stem cell transplantation using real-time quantitative (RQ)-IgH-PCR with allel-specific oligonucleotide probes. We identified a prognostically relevant threshold level of 0.2% 2IgH/β-actin ratio in the BM before HDT. Twenty-six patients with MRD levels below this value were termed as the "low-MRD group," whereas 27 patients with levels above this threshold were allocated to the "high-MRD group." Median event-free-survival (EFS) in the low-MRD group was significantly (P = .001) longer than in the high-MRD group with 35 versus 20 months, respectively. Overall survival (OS) within the low-MRD group was also significantly longer with 70 versus 45 months (P = .04). Using multivariate analysis, we found that the pretransplantation MRD level was an independent prognostic factor for EFS (P = .003) and OS (P = .05). Further, EFS of patients in the high-MRD could be improved (P = .005) when they achieved a low MRD level after HDT. In conclusion, measuring MRD is of prognostic relevance in patients with MM, and low MRD levels should be a goal of treatment.
authors: Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University, Duesseldorf, Germany.
authors: Mark
authors: M
authors: Korthals
authors: Nina
authors: N
authors: Sehnke
authors: Ralf
authors: R
authors: Kronenwett
authors: Ingmar
authors: I
authors: Bruns
authors: Jochen
authors: J
authors: Mau
authors: Fabian
authors: F
authors: Zohren
authors: Rainer
authors: R
authors: Haas
authors: Guido
authors: G
authors: Kobbe
authors: Roland
authors: R
authors: Fenk
mesh_terms: D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology* / Q000601:surgery / Q000628:therapy*; D018365:Neoplasm, Residual; D036102:Peripheral Blood Stem Cell Transplantation; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007143:Immunoglobulin Heavy Chains