Minimal residual disease (MRD) assessment is standard in many hematologic malignancies but is considered investigational in multiple myeloma (MM). We report a prospective analysis of the prognostic importance of MRD detection by multiparameter flow cytometry (MFC) in 295 newly diagnosed MM patients uniformly treated in the GEM2000 protocol VBMCP/VBAD induction plus autologous stem cell transplantation [ASCT]). MRD status by MFC was determined at day 100after ASCT. Progression-free survival (PFS; median 71 vs 37 months, P < .001) and overall survival (OS; median not reached vs 89 months, P ‫؍‬ .002) were longer in patients who were MRD negative versus MRD positive at day 100 after ASCT. Similar prognostic differentiation was seen in 147 patients who achieved immunofixation-negative complete response after ASCT. Moreover, MRD ؊ immunofixation-negative (IFx ؊ ) patients and MRD ؊ IFx ؉ patients had significantly longer PFS than MRD ؉ IFx ؊ patients. Multivariate analysis identified MRD status by MFC at day 100 after ASCT as the most important independent prognostic factor for PFS (HR ‫؍‬ 3.64, P ‫؍‬ . IntroductionIn most hematologic malignancies, response to front-line therapy is a good predictor of prognosis, with the longest survival seen in patients achieving an optimal response. This paradigm is represented by chronic myeloid leukemia (CML), in which hematologic, cytogenetic, and molecular remissions define progressively better response to therapy. In consequence, investigations to define these levels of remission are mandatory in routine clinical practice for treatment stratification and assessment of prognosis. 1 The situation is similar for other malignancies such as acute promyelocytic leukemia (APL) or acute lymphoblastic leukemia (ALL). 2,3 For this reason, there are continuous efforts to improve the sensitivity of the methods used to assess response to therapy, mainly through the introduction and refinement of both molecular and immunophenotyping approaches, as well as imaging techniques.Multiple myeloma (MM) should be no exception to this paradigm. For many years, the major goal of MM therapy was to achieve partial response (PR) or disease stabilization. 4,5 With the introduction of high-dose therapy plus autologous stem cell transplantation (HDT/ASCT), the new goal became the achievement of complete response (CR), defined as absence of M-protein by immunofixation (IFx) and less than 5% plasma cells (PCs) in bone marrow (BM). 6,7 More recently, the International Myeloma Working Group proposed a new response category of "stringent CR," which requires normalization of the free light chain ratio and the absence of residual clonal cells in the BM by immunohistochemistry or immunofluorescence. 8 As noted previously, the assessment of minimal residual disease (MRD), residual tumor cells persisting after therapy, is part of the standard of care in many hematologic malignancies, whereas in MM this is still considered investigational. Thus, MRD studies in MM have involved mainly small series of patients or have...

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions.

Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10 ؊4 cells), and none have relapsed thus far; 37 were at low risk (10 ؊4 to 10 ؊3 cells); and 64 were at intermediate risk (fewer than 10 ؊3 to 10 ؊2 cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10 ؊2 residual aberrant cells) and had a 3-year relapse rate of 84% (P ‫؍‬ .0001). MRD level not only influences relapse-free survival but also overall survival (P ‫؍‬ .003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML. (Blood. 2001;98:1746-1751)