[Show abstract][Hide abstract] ABSTRACT: The market approval of medical devices in Germany does not yet require a benefit assessment. Thus, there is a lack of high quality studies that clearly prove the benefit of medical innovations. In the past, the Federal Joint Committee in Germany (G-BA) did not have the opportunity to adequately address this issue of lacking evidence. A law for the improvement of the care structure in the statutory health insurance offers the possibility for the G-BA to obtain evidence for the benefit of medical practice. With an integrated regulation for testing of medical devices the manufacturers have the option to apply for an assessment of new and established treatment methods and to provide scientific evidence for the benefit of medical devices as a requirement for inclusion in the catalogue of services of the statutory health insurance. However, this expanded scope of action is also a challenge for clinicians. The already existing problem of integrating multicenter clinical trials in the surgical routine will remain. The Surgical Study Network Germany (CHIR-Net) offers an ideal way to cope with the increased requirements on studies in the field of medical devices through established partnerships with methodological institutions and practitioners in clinical settings.
Der Chirurg 05/2014; DOI:10.1007/s00104-013-2654-1 · 0.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prognostic relevance of minimal residual disease (MRD) in patients with multiple myeloma (MM) is still an open question. In the bone marrow (BM) the level of residual myeloma cells is associated with treatment outcome, but the role of clonotypic cells in the peripheral blood (PB) for the prognosis of patients is not identified yet. In this study, we retrospectively analyzed MRD by quantitative real-time IgH-PCR (IgH-qPCR) in the PB of 42 patients undergoing high-dose therapy (HDT) followed by autologous blood stem cell transplantation (PBSCT) as first-line therapy for MM. The MRD level of PB samples was in median 40-fold lower than in BM samples, collected on the same day, with a wide intra- and inter-individual variation (range: 0.4-4628 fold). The presence or absence of detectable MRD levels in PB did not correlate with the serological remission status. Still, patients with negative PCR results in PB three months after HDT and PBSCT had lower ISS stage (p=0.01), lower levels of β2-microglobulin (p=0.02), higher hemoglobin levels (p=0.01) and a prolonged event-free (median: 15 vs 4 months, p=0.004) and overall (median: 52 vs 17 months, p=0.03) survival. Importantly, by sequential monitoring of clonotypic cells in PB, in 19 of 29 patients (66 %) with progressive disease an increase of the 2IgH/ß-actin ratio of at least one log step could be detected in median 4 months (range: 0.8-13 months) before the relapse was diagnosed on the basis of the EBMT criteria. These patients with a molecular relapse in PB prior to a serological relapse had a significantly shorter OS than other patients (median: 17 months vs median not reached, p=0.02). In conclusion, IgH-qPCR is a sensitive technique for the detection of clonotypic cells in PB, which precede clinical relapse. Future studies are needed to evaluate whether these circulating tumor cells play a role in promoting disease recurrence.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2013; 19(7). DOI:10.1016/j.bbmt.2013.04.025 · 3.40 Impact Factor
[Show abstract][Hide abstract] 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.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2011; 18(3):423-431.e3. DOI:10.1016/j.bbmt.2011.07.002 · 3.40 Impact Factor