In vitro cytotoxicity and surface topography evaluation of additive manufacturing titanium implant materials

Custom-designed patient-specific implants and reconstruction plates are to date commonly manufactured using two different additive manufacturing (AM) technologies: direct metal laser sintering (DMLS) and electron beam melting (EBM). The purpose of this investigation was to characterize the surface structure and to assess the cytotoxicity of titanium alloys processed using DMLS and EBM technologies as the existing information on these issues is scarce. "Processed" and "polished" DMLS and EBM disks were assessed. Microscopic examination revealed titanium alloy particles and surface flaws on the processed materials. These surface flaws were subsequently removed by polishing. Surface roughness of EBM processed titanium was higher than that of DMLS processed. The cytotoxicity results of the DMLS and EBM discs were compared with a "gold standard" commercially available titanium mandible reconstruction plate. The mean cell viability for all discs was 82.6% (range, 77.4 to 89.7) and 83.3% for the control reconstruction plate. The DMLS and EBM manufactured titanium plates were non-cytotoxic both in "processed" and in "polished" forms.Peer reviewe

Autologous bone marrow transplantation for acute myeloblastic leukemia in Europe: further evidence of the role of marrow purging by mafosfamide. European Co-operative Group for Bone Marrow Transplantation (EBMT).

Fifty-nine European teams have reported 919 autografts for the consolidation of acute myelocytic leukemia (AML) up to December 31, 1989. The distribution for autologous bone marrow transplantation (ABMT) was 671 in first complete remission (CR1) and 196 in CR2. Pretransplantation regimes were: total-body irradiation (TBI), 456; busulfan plus cyclophosphamide (BU-CY) 174; marrow purging with mafosfamide, 269 (corresponding to 26% of all patients in CR1 and 41% in CR2). Patients autografted in CR1 with no high risk factor (standard risk) had a leukemia-free survival (LFS) and relapse rate at 7 years of 48 +/- 2 and 41 +/- 3%, respectively. Of all the prognostic factors studied, only secondary leukemia was correlated with a poorer LFS (19 +/- 9% at 1 year) and a higher relapse rate (76 +/- 11%) (p less than 0.0001). For patients autografted in CR2, the LFS and relapse rate were 34 +/- 4 and 54 +/- 5%. With the restriction of a shorter follow-up, the results achieved with the BU-CY combinations (LFS and relapse rate at 3 years, CR1 47 +/- 6 and 45 +/- 7%; CR2, 37 +/- 9 and 50 +/- 10%) did not differ from those with TBI or other chemotherapy combinations. LFS and relapse rates were correlated with several pretransplant intervals: in CR1, patients reaching CR more rapidly (less than or equal to 40 days) had a better LFS (53 +/- 3 versus 42 +/- 3%; p = 0.03) and a lower relapse rate (46 +/- 3 versus 57 +/- 3%; p = 0.03). In patients autografted less than 3 months, 3-6 months and more than 6 months after CR, the LFS was 26 +/- 5, 49 +/- 3, and 55 +/- 4%, respectively, and the relapse rates 63 +/- 5, 38 +/- 3, and 36 +/- 4% (p less than 0.0001 for both). In CR2, patients autografted more than 18 months after the initial diagnosis had a better LFS (42 +/- 5 versus 24 +/- 5%; p less than 0.001) and a lower relapse rate (45 +/- 6 versus 65 +/- 6%; p less than 0.001). For those autografted less than 3 months, 3-6 months and more than 6 months after CR, the probability of LFS was 30 +/- 5, 30 +/- 7, and 50 +/- 9% (p = 0.06), respectively and the relapse rates 63 +/- 6, 50 +/- 8, and 36 +/- 8% (p = 0.01).(ABSTRACT TRUNCATED AT 400 WORDS

Multiparametric Flow Cytometry Profiling of Neoplastic Plasma Cells in Multiple Myeloma

Background and aim: The clinical impact of multiparametric flow cytometry (MFC) in multiple myeloma (MM) is still unclear and under evaluation. Further progress relies on multiparametric profiling of the neoplastic plasma cell (PC) compartment to provide an accurate image of the stage of differentiation. The primary aim of this study was to perform global analysis of CD expression on the PC compartment and subsequently to evaluate the prognostic impact. Secondary aims were to study the diagnostic and predictive impact. Design and methods: The design included a retrospective analysis of MFC data generated from diagnostic bone marrow (BM) samples of 109 Nordic patients included in clinical trials within NMSG. Whole marrow were analyzed by MFC for identification of end-stage CD45(-)/CD38(++) neoplastic PC and registered the relative numbers of events and mean fluorescence intensity (MFI) staining for CD19, CD20, CD27, CD28, CD38, CD44, CD45, CD56, and isotypes for cluster analysis. Results: The median MFC-PC number was 15%, and the median light microscopy (LM)-PC number was 35%. However, the numbers were significant correlated and the prognostic value with an increased relative risk (95% Cl) of 3.1 (1.7-5.5) and 2.9 (1.4-6.2), P < 0.0003 and P < 0.004 of MFC-PC and LM-PC counts, respectively. Unsupervised clustering based on global MFI assessment on PC revealed two clusters based on CD expression profiling. Cluster I with high intensity for CD56, CD38, CD45, right-angle light-scatter signal (SSC), forward-angle light-scatter signal (FSC), and low for CD28, CD19, and a Cluster II, with low intensity of CD56, CD38, CD45, SSC, FSC, and high for CD28, CD19 with a median survival of 39 months and 19 months, respectively (P = 0.02). Conclusions: The MFC analysis of MM BM samples produces diagnostic, prognostic, and predictive information useful in clinical practice, which will be prospectively validated within the European Myeloma Network (EMN). (C) 2010 International Clinical Cytometry Societ

A prospective study of lenalidomide monotherapy for relapse after Allo-SCT for multiple myeloma

Allogeneic stem cell transplantation (Allo-SCT) can result in long-term remissions in patients with multiple myeloma (MM), although its overall role in disease management remains controversial. We evaluated lenalidomide monotherapy response and tolerability among patients with MM who progressed (PD) or relapsed after Allo-SCT. Eighteen patients, enrolled a median of 12 months (range 3–104) following transplant. Treatment duration of lenalidomide was 8 months (range 1–57). Ten patients required dose reductions from 25 mg to 5–20 mg at a median of 3 cycles (range 1–12); 8 for neutropenia; 1 for thrombocytopenia, and 1 for myalgias and weakness. Serious adverse events N=5, included H1N1 influenza (2), bacterial pneumonia (2), and fever, myalgia and hypoxia. Two patients died at 3 and 5 months of gastrointestinal or hepatic GVHD occurring within 1 month of dosing. Responses included CR (5), VGPR (2), PR (3), MR (1) and SD (2) for an overall response rate (≥PR) of 56%. Ten patients discontinued therapy for PD a median of 8.5 (1–43) months. Six patients died from PD. Five patients remain on therapy at 39 months (range 14–57), 4 in CR. Lenalidomide for relapse of MM after Allo-SCT can result in extended disease control (>12 months) in 50% of patients