Citations

Abstract BACKGROUND Electrophoretic separation of serum and urine proteins has played a central role in diagnosing and monitoring plasma cell disorders. Despite limitations in resolution and analytical sensitivity, plus the necessity for adjunct methods, protein gel electrophoresis and immunofixation electrophoresis (IFE) remain front-line tests. METHODS We developed a MALDI mass spectrometry–based assay that was simple to perform, automatable, analytically sensitive, and applicable to analyzing the wide variety of monoclonal proteins (M-proteins) encountered clinically. This assay, called MASS-FIX, used the unique molecular mass signatures of the different Ig isotypes in combination with nanobody immunoenrichment to generate information-rich mass spectra from which M-proteins could be identified, isotyped, and quantified. The performance of MASS-FIX was compared to current gel-based electrophoresis assays. RESULTS MASS-FIX detected all M-proteins that were detectable by urine or serum protein electrophoresis. In serial dilution studies, MASS-FIX was more analytically sensitive than IFE. For patient samples, MASS-FIX provided the same primary isotype information for 98% of serum M-proteins (n = 152) and 95% of urine M-proteins (n = 55). MASS-FIX accurately quantified M-protein to <1 g/dL, with reduced bias as compared to protein electrophoresis. Intraassay and interassay CVs were <20% across all samples having M-protein concentrations >0.045 g/dL, with the ability to detect M-proteins <0.01 g/dL. In addition, MASS-FIX could simultaneously measure κ:λ light chain ratios for IgG, IgA, and IgM. Retrospective serial monitoring of patients with myeloma posttreatment demonstrated that MASS-FIX provided equivalent quantitative information to either protein electrophoresis or the Hevylite™ assay. CONCLUSIONS MASS-FIX can advance how plasma cell disorders are screened, diagnosed, and monitored.

Multiple myeloma (MM) patient frailty has been delineated primarily by age and ECOG performance score (PS) and recently by the IMWG frailty score based on functional status [Activity of Daily Living (ADL) and Instrumental‐ADL scores], comorbidities [Charlson‐comorbidity‐index (CCI)] and age. It was hypothesized that N‐terminal natriuretic peptide type B (NT‐proBNP) might be both a more convenient measure of frailty and a predictor of overall survival (OS). Three‐hundred and fifty‐one consecutive symptomatic MM patients who were seen at Mayo Clinic within 30 days of diagnosis and who had blood stored were eligible. Data from the first visit was abstracted and used to calculate an ADL, CCI, and measure the NT‐proBNP level. The best cutoff of NT‐proBNP predicting OS was 300 ng/L. Variables predictive for OS were ECOG‐PS, age, CCI, ADL, ISS, revised‐ISS, and NT‐proBNP. On multivariate analysis age ≥70, PS ≥2, and NT‐proBNP ≥300 were independent predictors of survival. Patients were assigned a score of 1 for each of these variables, creating stages I–IV with scores of 0–3 points, respectively. The median OS from diagnosis was not reached, 58, 28, and 18 months (P < 0.0001), respectively. This frailty risk schema was independent of initial therapy and the revised‐ISS. NT‐proBNP is a useful predictor of survival independent of age and PS. It is a widely available biomarker that could be added to the panel of laboratory tests of newly diagnosed MM patients and serve as a simple and objective tool of determining frailty in clinical practice. Am. J. Hematol. 91:1129–1134, 2016. © 2016 Wiley Periodicals, Inc.

Recent reports suggest that deep hematologic responses to chemotherapy are associated with improved renal outcomes in monoclonal immunoglobulin deposition disease (MIDD). Here we describe the long term outcomes and identify prognostic factors after first line treatment of the largest reported series of patients with MIDD. Between March 1992 and December 2014, 88 patients with MIDD were seen at Mayo Clinic, MN. Renal responses were defined using criteria used for light chain amyloidosis (AL) or those used by the IMWG. Sixty‐one (69%) patients had a GFR < 30 mL/min/1.73 m2 and 16 (18%) were on renal replacement therapy at diagnosis. The interval between albuminuria or elevation in creatinine and MIDD diagnosis was 12 months suggesting a delay in diagnosis. Thirty‐seven patients (42%) had at least a hematologic CR/VGPR. Fifty‐three (60%) received an autologous stem cell transplant (ASCT) or proteasome inhibitor (PI)‐based treatments. Patients receiving ASCT or PI‐based therapies were more likely to achieve at least a hematologic CR/VGPR compared to those receiving other therapies: 66% vs 2%, p < 0.0001. Patients that achieved a hematologic CR were more likely to achieve a renal response (53% vs 24%, p = 0.001). Five year overall and renal survival for the entire cohort was 67% and 57%, respectively. In multivariate analyses, a baseline GFR < 20 mL/min/1.73 m2 and a renal response (using AL or IMWG criteria) were independently predictive of progression to dialysis. This study confirms that deep hematologic responses, best achieved with ASCT or PI‐based therapies, are a prerequisite to achieving renal responses. Am. J. Hematol. 91:1123–1128, 2016. © 2016 Wiley Periodicals, Inc.

Background.Sarcoma is a rare malignancy, and more recent management algorithms emphasize a multidisciplinary approach and limb salvage, which has resulted in an increase in overall survival and limb preservation. However, limb salvage has resulted in a higher rate of wound complications.Objective.To compare the complications between immediate and delayed (>three weeks) reconstruction in the multidisciplinary limb salvage sarcoma patient population.Methods.A ten-year retrospective review of patients who underwent sarcoma resection was performed. The outcome of interest was wound complication in the postoperative period based on timing of reconstruction. We defined infection as any infection requiring intravenous antibiotics, partial flap failure as any flap requiring a debridement or revision, hematoma/seroma as any hematoma/seroma requiring drainage, and wound dehiscence as a wound that was not completely intact by three weeks postoperatively.Results.70 (17 delayed, 53 immediate) patients who underwent sarcoma resection and reconstruction met the inclusion criteria. Delayed reconstruction significantly increased the incidence of postoperative wound infection and wound dehiscence. There was no difference in partial or total flap loss, hematoma, or seroma between the two groups.Discussion and Conclusion.Immediate reconstruction results in decreased wound complications may reduce the morbidity associated with multidisciplinary treatment in the limb salvage sarcoma patient.

SummaryThe diagnosis of Waldenström macroglobulinaemia (WM) can be challenging given the variety of signs and symptoms patients can present. Furthermore, once the diagnosis of WM is established, the initial evaluation should be thorough as well as appropriately directed. During the 8th International Workshop for WM in London, United Kingdom, a multi‐institutional task force was formed to develop consensus recommendations for the diagnosis and initial evaluation of patients with WM. In this document, we present the results of the deliberations that took place to address these issues. We provide recommendations for history‐taking and physical examination, laboratory studies, bone marrow aspiration and biopsy analysis and imaging studies. We also provide guidance on the initial evaluation of special situations, such as anaemia, hyperviscosity, neuropathy, Bing‐Neel syndrome and amyloidosis. We hope these recommendations serve as a practical guidance to clinicians taking care of patients with a suspected or an established diagnosis of WM.

There is no consensus on whether patients with immunoglobulin light chain amyloidosis (AL) should receive induction therapy prior to an autologous stem cell transplant (ASCT). This study investigated the relationships between baseline bone marrow plasmacytosis (BMPC), cardiac staging, and pre‐transplant induction in AL patients. All patients who received ASCT for AL within 12 months of diagnosis were included. Patient characteristics and outcomes were abstracted. Univariate and multivariate modeling was performed. Among 415 AL patients, 35% had induction prior to ASCT. Post‐ASCT hematologic CR plus VGPR rates were significantly higher in those with baseline BMPC ≤ 10% compared to BMPC >10% (58% versus 40%, P = 0.0013). Significant risk factors for lack of attainment of CR included attenuated dose melphalan conditioning, baseline BMPC > 10%, no induction, and male gender. The 5‐year OS for the entire group was 65%. On multivariate analysis, risk factors for inferior OS included no induction therapy, advanced AL amyloid staging, BMPC > 10%, attenuated conditioning melphalan dose, and male gender. Patients with Mayo 2012 stage I–II patients with BMPC ≤ 10%, who comprised 56% of the ASCT population fared exceedingly well regardless of whether or not they received induction therapy with a 5‐year OS of 81 to 83%. Induction therapy pre‐ASCT may improve outcomes among AL patients due to a rapid reduction of toxic light chains or alternatively by elimination of less fit patients by “testing” their ability to tolerate chemotherapy. Prospective studies will be required to sort out these and other questions. Am. J. Hematol. 91:984–988, 2016. © 2016 Wiley Periodicals, Inc.