Search

There is a need to explore new alternatives for root canal disinfection in regenerative endodontics, since the current strategies are far from ideal. Currently, the potential use of diclofenac (DC) is being investigated for controlling root canal infections. The objective was to evaluate the antimicrobial efficacy of novel DC-based hydrogels (DCHs) against polymicrobial biofilms grown in radicular dentine and root canals and to compare results with triantibiotic (TAH) and diantibiotic (DAH) hydrogels, and calcium hydroxide (Ca[OH]The in vitro antimicrobial activity of intracanal medicaments was evaluated against 3-week-old polymicrobial root canal biofilms grown on human radicular dentine. Dentine samples were obtained and randomly divided into the study groups (n = 4/group): (1) 1 mg/ml TAH; (2) 1 mg/ml DAH; (3) 5% diclofenac (DCH); (4) 2.5% DCH; (5) 1.25% DCH; (6) 1 mg/ml DAH + 5% DCH; (7) Ca(OH)Confocal scanning laser microscopy analysis indicated that the greatest effectiveness was obtained with 5% DCH, showing significant differences with respect to the other groups (p .001). In root canals, the highest LogSodium DC hydrogels demonstrate antimicrobial efficacy against endodontic biofilms.

Introduction: Dimethyl sulfoxide (DMSO) is the most frequently used cryoprotective agent for freezing hematopoietic progenitors for transplantation. DMSO can cause adverse effects during cellular product infusion. In this setting, we reduced the DMSO concentration from 10% to 5% as a strategy to reduce toxicity. Methods: We retrospectively analyzed the characteristics of hematopoietic progenitor products and infusion tolerance in 240 adult patients who underwent autologous peripheral blood transplantation between January 2008 and February 2019. Patients were divided into two groups according to DMSO concentrations, 10% versus 5%. Results Post-thawing cell viability was signicantly higher in the 5% DMSO group (69.15% vs. 63.85%; p=0.028). In both groups, no statistically signicant differences were observed in the total content of CD34+×106/kg progenitor cells infused (DMSO 5% 2.98 vs. DMSO 10% 3.20, p=0.409), or graft recovery and transfusion needs. In all patients, the overall rate of adverse reactions was 7.5% (n=18); the rate was 4.6% (n=5) in the 5% DMSO group compared with 9.8% (n=13) in 10% DMSO (p=0.127). Severe adverse events were observed in the 10% DMSO group. Conclusion: Reducing the DMSO concentration from 10% to 5% is safe for the patient and product, improving viability and the absence of severe adverse infusion reactions.

This is the first case of acquired severe neutropenia in the context of COVID‐19 reported to date. This could illustrate another less frequent hematological disorder related to this novel viral infection.

PURPOSE: To compare the agreement between whole-body (WB) magnetic resonance (MR) imaging, 18F-FDG PET/CT, and skeletal survey (SS) in patients with multiple myeloma (MM) for diagnosis, initial staging, response evaluation, and early detection of complications. METHODS: This is a retrospective cohort study including MM patients who were diagnosed, treated, and followed in 2 institutions. These patients were studied with SS, WB-MR, and/or 18F-FDG PET/CT. We studied bone lesions by anatomical locations and analyzed the concordance between SS and a tomographic technique (WB-MR or 18F-FDG PET/CT) and between both tomographic techniques (WB-MR and PET/CT). RESULTS: Forty-four MM patients with a mean age of 62.6 years (range, 38-85 years) were included from January 2012 to February 2016. Whole-body MR and 18F-FDG PET/CT found more lesions than SS in every location except in the skull. Concordance between WB-MR and 18F-FDG PET/CT was either good or excellent in most of the locations and in plasmacytoma studies. However, WB-MR was better than 18F-FDG PET/CT in the study of complications (medullar compression and vascular necrosis). CONCLUSIONS: Our results suggest the study of MM patients should include WB-MR and/or 18F-FDG PET/CT, whereas SS is only useful for the skull. Whole-body MR and 18F-FDG PET/CT are complementary techniques, because both of them show good concordance in almost every location. It is still necessary to individualize the indication of each technique according to patient characteristics., None declared

Summary Gangliocytic paraganglioma (GP) is an uncommon finding in the periampullary region of the duodenum. In the Department of General and Digestive Surgery of the Albacete University Hospital Complex, a 45-years-old patient was diagnosed with a 17x13mm hypervascular nodular lesion in the descending part of the duodenum during an examination for hepatic hemangiomas. Ampullectomy was performed, followed by a favourable postoperative period. Histological analysis proved GP. There were no involvement of lymph nodes and a malignancy potential, so the clinical and radiological follow-up opted. In conclusion, because such tumours have unpredictable behavior, we recommend local resection of the tumour, except in cases in which local or ganglionic progression is suspected or confirmed, and thus cephalic pancreaticoduodenectomy (CPD) and lymphadenectomy are suggested.

© The Author(s) 2021., This study reports on 382 COVID-19 patients having undergone allogeneic (n = 236) or autologous (n = 146) hematopoietic cell transplantation (HCT) reported to the European Society for Blood and Marrow Transplantation (EBMT) or to the Spanish Group of Hematopoietic Stem Cell Transplantation (GETH). The median age was 54.1 years (1.0–80.3) for allogeneic, and 60.6 years (7.7–81.6) for autologous HCT patients. The median time from HCT to COVID-19 was 15.8 months (0.2–292.7) in allogeneic and 24.6 months (−0.9 to 350.3) in autologous recipients. 83.5% developed lower respiratory tract disease and 22.5% were admitted to an ICU. Overall survival at 6 weeks from diagnosis was 77.9% and 72.1% in allogeneic and autologous recipients, respectively. Children had a survival of 93.4%. In multivariate analysis, older age (p = 0.02), need for ICU (p < 0.0001) and moderate/high immunodeficiency index (p = 0.04) increased the risk while better performance status (p = 0.001) decreased the risk for mortality. Other factors such as underlying diagnosis, time from HCT, GVHD, or ongoing immunosuppression did not significantly impact overall survival. We conclude that HCT patients are at high risk of developing LRTD, require admission to ICU, and have increased mortality in COVID-19., JA acknowledges the support of the UK NIHR Imperial College Biomedical Research Centre.

COVID-19 is a severe infectious complication in patients with underlying medical conditions such as having undergone hematopoietic stem cell transplantation (HCT). This prospective survey reports outcome on 272 COVID-19 patients from 19 countries having undergone allogeneic (n = 175) or autologous (n = 97) HCT reported to the EBMT registry or to the GETH. All patients had the diagnosis of SARS-CoV-2 documented by PCR. Patients were included in this analysis if COVID-19 diagnosis was before April 10, 2020. The overall survival was estimate by using the Kaplan Meier methods, considering the death due to any cause as an event and the time from COVID-19 infection to the latest follow-up as survival time; difference between groups were tested by the log-rank test. Univariate and multivariate risk factor analysis for overall survival were performed with the Cox regression model. The median age was 54.4 years (1.0 - 80.3) for allogeneic and 60.9 years (7.7 - 73.4) for autologous HCT patients. 20 patients were children (< 18 years of age; median age 11.3 (1.0 - 16.9)). The median time from HCT to diagnosis of COVID-19 was 13.7 months (0.2 - 254.3) in allogeneic and 25.0 months (-0.9 - 350.3) in autologous recipients. Lower respiratory tract disease (LRTD) developed in 84.8% and 21.5% were admitted to an intensive care unit (ICU). At the time of analysis, 68/238 (28.6%) patients had died (47/155 allogeneic patients; 21/83 autologous patients). No follow-up had been received on 34 patients. The median time from infection to death was 19 days (0-102). Five patients were reported to have other primary causes of death than COVID-19. Of the patients reported to be alive, the median follow-up was 44 days. 144 (84.7%) patients (93 allogeneic; 51 autologous) had virologic resolution of the COVID-19 infection having at least one negative PCR. 26 patients were alive and known to be still COVID-19 positive (15 allogeneic; 11 autologous). For 34 patients the resolution status was unknown. Factors influencing the likelihood of resolution in multivariate analysis were underlying diagnosis (p=.01) and longer time from transplant to diagnosis of COVID-19 (p=.035). Overall survival at 6 weeks from COVID-19 diagnosis was 76.8% and 83.8% in allogeneic and autologous HCT recipients (p =ns), respectively (figure 1). Children (n=20) tended to do better with a 6-week survival of 95.0% although the difference was not significantly different (p =.12). In multivariate analysis of the total population older age (HR 1.26; 95% CI 1.05 - 1.51; p = .01) increased the risk and better performance status decreased the risk for fatal outcome (HR 0.79; 95% CI 0.69 - 0.90; p = .0003). The same factors had significant impact on overall survival in allogeneic HCT recipients (age HR 1.28; 95% CI 1.05 - 1.55; p=.01; performance status HR 0.79; 95% CI 0.68 - 0.92); p=.002) while only age impacted survival among autologous HCT patients (data not shown). Other transplant factors such as underlying diagnosis, time from HCT to diagnosis of COVID-19, graft-vs-host disease, or ongoing immunosuppression did not have a significant impact on overall survival. We conclude that HCT patients are at an increased risk compared to the general population to develop LRTD, require admission to ICU, and have increased mortality in COVID-19. Figure 1 Disclosures Duarte: Incyte Corporation: Other: Has received speaker and advisor fees. Kwon:Jazz: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Mielke:Novartis: Honoraria, Other: received via my institution, Speakers Bureau; Celgene/BMS: Honoraria, Other: received via my institution , Speakers Bureau; Bellicum: Honoraria, Other: received via my institution, Speakers Bureau; Kite/Gilead: Honoraria, Other: received via my institution , Speakers Bureau; Miltenyi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: received via my institution , Speakers Bureau; KIADIS Pharma: Honoraria, Other: received via my institution , Speakers Bureau; DNA Prime: Honoraria, Other: received via my institution , Speakers Bureau. López Jiménez:MSD: Speakers Bureau; Roche: Research Funding, Speakers Bureau; Takeda: Speakers Bureau; Janssen: Research Funding, Speakers Bureau; Abbvie: Research Funding, Speakers Bureau; Gilead: Research Funding, Speakers Bureau.

INTRODUCTION COBE SPECTRA [COBE] (Terumo, BCT Lakewood CO) apheresis system has been the most used device for hematopoietic progenitor cells (HPC) collection. Recently, it has been replaced by the SPECTRA OPTIA [OPTIA] (Terumo, BCT Lakewood CO) apheresis system. The aim of our study is to compare both methods for HPC collection. MATERIAL AND METHODS We retrospectively compared 302 HPC collection apheresis procedures (115 allogeneic donors and 187 autologous). The study cohort was divided according to the apheresis system used to analyze the differences between COBE and OPTIA, specifically efficacy of apheresis procedure and product characteristics. RESULTS OPTIA collections result in a higher CD34+ collection efficiency in both groups (autologous 45.3% vs 41%, P

Background: Heavily pretreated relapsed and refractory multiple myeloma (RR MM) constitutes a specific and unmet medical need. Median survival ranges from as little as 6 to 9 months, and responses to treatment are characteristically short (Richardson et al. 2007). Belantamab Mafodotin (BM), a novel anti-BCMA antibody conjugated to microtubule-disrupting agent monomethyl auristatin F, showed single-agent activity in the phase 1 DREAMM-1 and phase 2 DREAMM-2 studies in heavily pre-treated patients with RRMM (Lonial et al, 2019 & 2021). We aim to assess efficacy and safety of BM treatment administered via the expanded access compassionate care program for triple class MMRR patients in the region of Madrid (Spain). Methods: An observational, retrospective and multicenter study has been performed including all patients who received at least one dose of BM under the expanded access program in the region of Madrid (Spain) from Nov 2019 to Jun 2021. Hematology centers provided data from the medical records and entered them in a case report form distributed to the sites. Primary endpoint was overall response rate (ORR). Secondary endpoints were progression free survival (PFS), overall survival (OS) and the incidence of treatment emergent adverse events (TEAEs), with a major focus on ocular and hematologic toxicity. Results: A total of 33 patients (pts), from 14 different centers, were included from February 2020 till May 2021. Median age was 70 (46-79) years. 55% of the pts were women. Median time from diagnosis was 71 (10-858) months. 30.3% were high-risk cytogenetic features. Median of prior therapy lines was 5 (3-8) and at least 88% of the pts were triple class refractory. The median number of BM doses per patient was 3 (1-16) and the median follow-up was 11 months (95%CI 6.34-15.66). ORR was 42.2%, and 18.2% achieved ≥VGPR. Median PFS was 3 months (95%CI 0.92-5.08). Median PFS for patients who achieved ≥PR was 11 months (HR 0,26; 95% CI 0,10-0,68). No significant differences were found in PFS according to age, cytogenetic risk and prior therapy lines. OS was 424 days (95% CI 107-740). The incidence of non-hematological TEAEs was 57.6% and the most common of which was ocular toxicity (45.5%). The incidence of ≥G3 non-hematological TEAEs was 30.3%. 51.5% of the pts were diagnosed of keratopathy and 21.2% was ≥G3. 30.3% of the pts showed a reduced visual acuity, but this event was resolved in 92.9% of the pts. The most common symptoms were blurry vision (30.3%, n=10) and dry eye (24.2%, n=8). The incidence of ≥G3 hematological TEAEs was 18.2% and thrombocytopenia was the most frequent (21.2%). Dose reductions of BM were required in 30.3% of the pts and delayed in 36.4% due to TEAEs. Main causes for treatment discontinuation (81%, n=27) were disease progression (54.5%, n=18), toxicity (15.2%, n=5), death (6.1%, n=3) and due to patient's decision (3%, n=1). Conclusion: Compassionate use of BM in heavily pretreated RR MM pts showed a relevant anti-myeloma activity with a manageable safety profile.These results are similar to those observed in the DREAMM-1 and DREAMM-2 clinical trials. Disclosures No relevant conflicts of interest to declare.

Peter Paschka and Hartmut Döhner contributed equally. Background. SARS-CoV-2 infection (COVID-19) has had a great impact worldwide and its mortality has been reported to be higher in patients with haematological malignancies. However, description of its effects and outcomes among recipient of hematopoietic stem cell transplantation (HSCT) is scarce. Objectives. To describe the characteristics, treatment and outcome of COVID-19 in recipients of HSCT reported to the Madrid registry of COVID-19 ("HEMATO-MADRID COVID-19 registry"). Results. Data of 842 patients from 23 hospitals with haematological malignancies and COVID-19 infection were reported in the Madrid registry between March and June 2020. Among those, 87 (10.3%) patients were HSCT recipients: 58 auto-HSCT and 29 allo-HSCT (7 of them from matched related donor (MRD), 12 matched unrelated donor (MUD) and 10 haplo-HSCT). Characteristics of the population are described in Table 1. Median age at COVID-19 infection was 61 years (IQR, 53-67) and 35 patients (40%) were female. Recipients of auto-HSCT with COVID-19 were older and showed a trend towards a higher incidence of arterial hypertension (28% vs 10%, p=0.067) without statistical differences in other comorbidities; active disease requiring treatment at COVID-19 diagnosis was more frequent in auto-HSCT recipients (65% vs. 21%, p Conclusion. In our multicentric experience in a high COVID-19 impacted area, the median time of COVID-19 infection presentation was relatively late in transplanted patients, however shorter in allo-transplanted patients. COVID-19 related mortality was high in HSCT recipients, significantly higher in allo-transplanted patients. Factors associated to this higher mortality should be further investigated to promptly identify high-risk patients since the pandemic is still highly active worldwide. Disclosures Kwon: Gilead: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Jazz: Consultancy, Honoraria. Duarte:Incyte Corporation: Other: Has received speaker and advisor fees. Hernandez-Rivas:Rovi: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees. Jimenez Yuste:NovoNordisk: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Grifols: Honoraria, Research Funding; Bayer: Honoraria; Sobi: Consultancy, Honoraria, Research Funding; CSL: Honoraria; Octapharma: Honoraria.

Summary The variations of the cystic duct are so common that only 30% of all humans present the classical anatomical arrangement between the common bile duct (CBD), the cystic duct, and adjacent arteries. Thus, it could be considered that anomalies of the biliary tree are a rule rather than an exception. Duplication of the cystic duct, however, is a very uncommon anatomical finding. In the Department of General and Digestive Surgery of the University Hospital Complex Albacete, a 73-year-old patient was admitted with symptoms of cholangitis. He underwent emergency surgery that found exacerbated chronic cholecystitis and dilation of the CBD. Cholecystectomy was performed with identification of a double cystic duct that drained separately in the CBD and exploration of the last revealed cholangitis without choledocholithiasis. The postoperative period progressed favourably, proceeding to discharge from the hospital with Kehr drainage closed. In conclusion, we consider that the routine use of intraoperative cholangiography when there is suspicion of anatomical variations of the biliary tree is mandatory to rule out lesions or alterations thereof.

Lymphoblastic lymphomas (LBLs) are uncommon malignant neoplasms derived from immature T- or B-lymphoid progenitor cells. Although cutaneous involvement may reach 33% in B-LBL, only 12 cutaneous cases of T-LBL have been published. We report the case of a 49-year-old woman with 2-month history of erythematous-violaceous plaques in the sternal region and breasts. Histopathologic examination showed a dense monomorphus infiltrate in dermis and positive immunostainings for CD3, CD99 and terminal deoxynucleotidyl transferase, thus indicating T-LBL. Staging work-up only revealed a mediastinal mass at diagnosis. After a 51-month follow-up and different treatment regimens, the patient remains alive although she has presented four relapses, all of them extramedullary.

The proportion of multiple myeloma patients in long-term complete response (LTCR-MM) for more than 6 years after autologous stem cell transplantation (ASCT) is small. To evaluate whether this LTCR is associated with a particular immune signature, peripheral blood samples from 13 LTCR-MM after ASCT and healthy blood donors (HBD) were analysed. Subpopulations of T-cells (naive, effector, central memory and regulatory), B-cells (naive, marginal zone-like, class-switched memory, transitional and plasmablasts) and NK-cells expressing inhibitory and activating receptors were quantified by multiparametric flow cytometry (MFC). Heavy/light chains (HLC) were quantified by nephelometry. The percentage of CD4+ T-cells was lower in patients, whereas an increment in the percentage of CD4+ and CD8+ effector memory T-cells was associated with the LTCR. Regulatory T-cells and NK-cells were similar in both groups but a particular redistribution of inhibitory and activating receptors in NK-cells were found in patients. Regarding B-cells, an increase in naive cells and a corresponding reduction in marginal zone-like and class-switched memory B-cells was observed. The HLC values were normal. Our results suggest that LTCR-MM patients express a particular immune signature, which probably reflects a 'high quality' immune reconstitution that could exert a competent anti-tumor immunological surveillance along with a recovery of the humoral immunity.

Background The use of antimicrobial solutions has been recommended to disinfect demineralized dentin prior to placing the filling material. The aim of this study was to evaluate the ability of several antimicrobials in controlling Streptococcus mutans (SM) biofilm formed in dentin. Methods Antimicrobial activity of 0.2% and 2% chlorhexidine (CHX), 0.2% cetrimide (CTR) and 0.2%, 0.5%, 1% and 2% alexidine (ALX) was assayed on 1-week SM biofilm formed on standardized coronal dentin blocks. Results of SM biofilm antimicrobial activity by different protocols were expressed as the kill percentage of biofilm and the term “eradication” was used to denote the kill of 100% of the bacterial population. To compare the efficacies of the different protocols the Student t test was used, previously subjecting data to the Anscombe transformation. Results All ALX concentrations tested and 0.2% CTR achieved a kill percentage higher than 99%, followed by 2% CHX with percentages above 96% (no statistically significant difference among them). Whereas 2% ALX and 0.2% CTR respectively showed eradication in 10 and 9 of the twelve specimens, 0.2% CHX did not produce eradication in any case. Conclusions The present study shows that, when used for one minute, 2% and 1% alexidine, and 0.2% cetrimide, achieve eradication of Streptococcus mutans biofilm in most specimens when applied to a dentin-volumetric model., This study was supported by Research Group CTS-167 of the Junta de Andalucía, Spain.

INTRODUCTION: Ibrutinib is a first-in-class Bruton kinase inhibitor (BTK) registered for the treatment of Chronic Lymphocytic Leukemia (CLL), mantle cell linphoma (MCL) and Waldenström Macroglobulinemia (WM). Increased risk of bleeding events is asociated with ibrutinib, mostly grade ≤2. Alleged mechanism for this risk could be the role of BTK in platelet activation via GPIb, GPVI and FVW. We here present our experience regarding hemorragic events and hemostasis tests alterations in CLL patients (pts) treated with ibrutinib. PATIENTS AND METHODS: 15 pts with relapsed CLL were started on ibrutinib between december/2012 and july/2016. Median age was 69 years (range: 42-83 years). 12 of them were male. Median exposure to the drug was 17 month (range 1- 38). After 9 to 36 months from initiation of treatment (median 22 months) 6/15 were thouroughly interviewed about personal history of bleeding events and the following laboratory work was performed: factor VIII level, FVW antigen and activity, platelet function analysis (PFA-100TM) with ADP and epinephrine, and aggregation studies with colagen, ADP and arachidonic acid. Along these tests all patients had blood counts with platelets more than 100 x 10e9/L. RESULTS: 3 out of 15 pts had bleeding events (grade 1 or 2), 2 consisting in spontaneus bruising and 1 in upper grastrointestinal bleeding, in the first weeks of treatment. 4 pts underwent minor invasive procedures with no complications, witholding the drug at least 3 days before and after. 2 pts were on concomitant antiplatelet (1) or anticoagulant (1, LMWH, due to AF) and had no bleeding events. All pts tested (6/6) had normal or slightly elevated leves of F VIII, FVW:Ag and FVW:Ac. 2 pts had abnormal PFA-100TM and abnormal aggregations with any agonist. One case had normal PFA-100 TM while aggregations with colagen and AA were mildly altered. COMMENTS: Our limited experience shows a moderate risk of minor bleedings consisting with a platelet disfunction drug-driven effect. Despite the fact that we have no baseline tests done, alterations in primary hemostasis test, including PFA-100TM and specially aggregometry could be expected early on after exposure to ibrutinib. Disclosures Loscertales: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Speakers Bureau. Alegre:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

To increase the angiogenic response and clinical efficacy of TMR, the potential synergy and safety of combining TMR with concentrated autologous bone marrow derived stem cells was evaluated. Fourteen patients with diffuse coronary artery disease and medically refractory class III/IV angina who were not candidates for conventional therapies were treated using TMR in combination with intramyocardial injection of concentrated stem cells. At the time of surgery, autologous bone marrow (120 cc) was aspirated from the iliac crest and processed over 15 min into 20 cc of concentrated mononuclear cells using a centrifugal system (HARVEST, Boston, MA). A single device performed holmium: YAG:TMR (CardioGenesis, Irvine, CA) with injection of 1 cc of concentrated stem cells through three multi-holed needles into the border zone around each laser channel. There were no perioperative adverse events including no arrhythmias. Mean number of injected cells per milliliter were: total mononuclear cells (81.3 x 10(6)), CD34(+) cells (0.6 x 10(6)), and CD133(+) cells (0.37 x 10(6)). At 7 months mean follow-up average angina class was significantly improved (3.5+/-0.5 vs 1.4+/-0.5; p=0.004). There was no death during the follow-up. Efficient delivery of stem cells combined with TMR in a single device seems to be safe and effective for treating unmanageable angina.

Plasma cell leukemia (PCL) represents the most aggressive form of monoclonal gammopathy for which new treatment approaches are needed. Here we report the effect of Bortezomib on cells from 4 patients with PCL, as well as the in vivo efficacy on a patient with secondary PCL. Bortezomib reduced PCL numbers and was more efficient in cell growth inhibition than dexamethasone or doxorubicin. Treatment with Bortezomib induced procaspase-3 and poly(ADP-ribose) polymerase cleavage and decreased the amount of extracellular signal regulated kinase (Erk1/2) and phospho-Erk1/2. However, Bortezomib did not substantially affect the levels of the Erk1/2 upstream activating kinase (MEK1), p27 or p21. Finally, we had the opportunity to use Bortezomib in a heavily pretreated patient with overt secondary PCL and severe anemia and thrombocytopenia. Following Bortezomib treatment, circulating plasma cells disappeared; what is more striking, the peripheral blood counts returned to normal, becoming transfusion-independent. These data support the inclusion of Bortezomib in the therapeutic armamentarium of PCL.

Here we report the efficacy, safety and health-related quality-of-life (HRQoL) associated with long-term lenalidomide and dexamethasone (Len + Dex) treatment in patients with relapsed or refractory multiple myeloma (RRMM) enrolled in the Spanish cohort of the MM-018 study. In this open-label, multicenter, single-arm expanded access study, 63 patients received Len + Dex until disease progression. The overall response rate was 78%, with 21% of the patients achieving a complete response. The quality of response improved with continuous treatment. The median duration of response was 18.4 months. Median time-to-progression and progression-free survival was 13.3 months for both; median overall survival was not reached. Len + Dex had a manageable safety profile consistent with previously reported phase III studies. HRQoL assessments (n = 42) at baseline and 6 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ MY-20 questionnaires revealed that patients with RRMM treated with long-term lenalidomide reported clinically relevant improvements in certain QoL and symptoms scores regardless of treatment response (ClinicalTrials.gov: NCT00420849).

Introduction The prognosis of patients with multiple myeloma (MM) has improved in the last years due to the important advances in the knowledge of the biology of the disease, the implementation of new drugs and the incorporation of autologous hematopoietic stem cell transplant (autoHSCT). The allogenic hematopoietic stem cell transplant (alloHSCT) continues to be controversial: it offers a curative potential but with the cost of high toxicity, limiting the procedure to those young patients with a high-risk disease. This procedure shall be performed in expert centers and, whenever possible, in the context of a clinical trial. In the following we describe the experience of our center with alloHSCT in advance multiple myeloma patients. Patients and methods A total of 18 patients were diagnosed with multiple myeloma received an alloHSCT during a 13 year period (1996-2013), with a median age of 46 ± 5.9 years. All of our patients received an allogenic HLA matched sibling donor with reduced-intensity conditioning. The majority of patients were transplanted because of advanced disease, relapse after an autologous transplant or as part of a sequential transplant in patient with a high risk disease. One patient received, in two occasions, an alloHSCT. Around 70% of patients had received more than 3 previous lines of treatment including, in nearly 95%, an autoHSCT. Patient's characteristics can be found on table 1, characteristics of the procedure can be found in table 2.Table 1.Patient«s CharacteristicsN (%)GenderMale Female10 (55,5%) 9 (44,4%)Secreted ProteinIgGκ IgG λ IgA κ BJ Plasmocitoma8 (44,4%) 4 (22,2%) 2 (11,1%) 3 (16,7%) 1 (5,6%)Debut DS stageII-A II-B III-A III-B Plasmocitoma5 (27,8%) 1 (5,6%) 8 (44,4%) 3 (16,7%) 1 (5,6%)Cytogentics at diagnosisMissing Unfavorable Favorable10 (55,5%) 6 (33,3%) 2 (11,1%)Previous lines of treatment²2 3-4 ³56 (33,3%) 10 (55,5%) 2 (11,1%)Previous autoHSCTYes No17 (94,5%) 1 (5,6%)Previous radiotherapyYes No8 (44,4%) 10 (55,6%)Disease status at transplantComplete remission Partial remission Relapse9 (50,0%) 3 (16,7%) 6 (33,3%)Table 2.Treatment characteristicsN (%)Conditioning regimenMyeloablative Reduced-intensity6 (33,3%) 12 (66.7%)Stem cell sourceBone marrow Peripheral blood4 (22.2%) 14 (77.8%)GVHD prophylaxisCsA+MTXCsA+CSCsA+MMF10 (55.6%) 3 (16.7%) 5 (27.8%)InfectionsYes No16 (88.9%) 2 (11.1%)MucositisYes No12 (66.7%) 6 (33.3%)Acute GVHDYes II-IV III-IV No4 (22.3%) 3 (16.7%) 1 (5.6%) 14 (77.8%)Chronic GVHDNo Limited Extensive8 (44.3%) 5 (27.8%) 5 (27.8%) Results: Transplant related mortality (TRM) before day 100th was one case due to a thromboembolic event. Global TRM was 16.6% (3 cases). The incidence of acute graft versus host disease (aGVHD) was 22%, controlled on most cases when corticosteroids were initiated. More than half of the patients developed chronic graft versus host disease (cGVHD), with an equal distribution on either presentation as limited or extensive. (Table 2) The total number of patients eligible for analysis was 17 (one patient was lost on follow-up). With a median follow up of 11 years, the overall survival (OS) was of 8.06 years [IC 95% 4,33-11,78] (figure 1.) and the estimated progression free survival (PFS) was of 25.83 months [IC 95% 8.87-42.79](figure 2). A total of 5 (29,4%) patients are still alive and 2 (11,7%) of them are in complete remission, of these 1 patient did not have a previous autoHSCT with a follow up of almost 15 years. Conclusions: Our results are similar to those reflected on the literature1-2. However we have to point out that our population is homogenous with advanced MM with more than 3 previous lines of treatment including in most cases auto-HSCT. In spite of this, morbility and mortality in our cohort was acceptable with the limitation of a high rate of cGVHD. There is a need of more studies including more patients to evaluate the role of alloHSCT in the era of new drugs for MM. References 1. Rosi-ol L et al. Allogeneic hematopoietic SCT in multiple myeloma: long-term results from a single institution. Bone Marrow Transplant. 2015. 2. Beaussant Y et al. Hematopoietic Stem Cell Transplantation in Multiple Myeloma: A Retrospective Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC). Biol Blood Marrow Transplant. 2015 Disclosures Alegre: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.

Plasmacytoma is a frequent complication of multiple myeloma, either at diagnosis or within disease progression. The extramedullary disease confers a poorer prognosis and is biologically distinct with high-risk molecular and histological features, being resistant to conventional treatments. Radiation therapy remains the most effective treatment for extramedullary lesions to achieve local control. There are very limited data from randomized trials regarding the most appropriate systemic treatment. Case reports such as those presented here, as well as retrospective analysis of series, suggest that lenalidomide is an effective agent, in combination with dexamethasone, in this setting. Additional studies are needed to define the proper management of this condition.

We evaluated the clinical results of lenalidomide (Len) as a compassionate salvage therapy in refractory/relapsed multiple myeloma (MM) patients. A nationwide multi-centre, retrospective research study was performed to evaluate clinical data from patients with advanced MM for which compassionate use of lenalidomide was requested. The primary endpoints were the overall response rate (ORR) and the time to progression (TTP). Secondary objectives included safety and overall survival (OS) since starting of lenalidomide therapy. Data collected from the Spanish Compassionate Use Registry included 111 patients treated in 2006–2008. The median (range) number of previous treatment lines was 3 (1–8). The median duration of lenalidomide treatment while on study was of 4.9 months (1–18). Dexamethasone was given concomitantly with Len in 89% of patients. The ORR was 66% (4% of patients had stringent complete, 11% complete and 11% very good partial responses). Median TTP and OS were 13.0 and 17.4 months, respectively. The depth of response was significantly associated with a longer OS. Toxicity, mainly myelosuppression, was predictable and manageable with Len dose adjustments and cytokine support. Lenalidomide as salvage compassionate therapy in refractory/relapsed MM showed, in this series of heavily pre-treated patients, similar efficacy to that reported in pivotal clinical trials with acceptable tolerance.

Introduction: Conventional radiography remains the “gold standard” technique for bone involvement assessment in patients with multiple myeloma (MM). Newer imaging modalities such as whole-body Magnetic Resonance (MR) and 18FDG-PET/CT have emerged as more sensitive techniques than routine skeletal survey in the detection of bone involvement in the diagnostic and follow up of patients with MM. The advantages and disadvantages of MR and 18FDG-PET/CT are discussed. Patients and methods: We have retrospectively analyzed 12 patients since 2012 to 2014 with multiple myeloma in our institution whose bone involvement was evaluated with MR and 18FDG-PET/CT. Age range: 36-70. Seven patients were female and five were male. Eight cases were treated with an induction regimen containing bortezomib, three cases with chemotherapy with alternating VBCMP/VBAD and one of them with VAD. After induction, ten of them received autologous stem cell transplantation (ASCT), one patient allogeneic stem cell transplantation and one patient no transplantation. Results: All patients presented bone lesions on MR and all of them were also positive at PET/CT. One showed leptomeningeal involvement on RM and PET. Regarding extramedullar disease two patients presented soft tissue masses and in other two cases there was ganglionar involvement, all of them positives by both techniques. Of nine evaluable patients after complete treatment, six of them have a negative PET and three have a low positive SUV value, however eight of them still had persistent residual lesions on MR, what could indicate not stringent complete response. The patient with leptomeningeal involvement had both MR and PET negative result after treatment. Comments and conclusions: Our data suggest that whole-body MR and 18FDG-PET/CT provide valuable complementary information, MR could be superior to assess extent of lesions and PET to monitor disease activity and to detect asymptomatic relapse. The optimal imaging technique for the management of patients with MM is not well defined and our proposal is a multimodality imaging approach according to individualized criteria. References: Caers J et al. The role of positron emission tomography-computed and magnetic resonance imaging in diagnosis and follow-up of multiple myeloma. Haematologica 2014;99(4):629-637. doi:10.3324/haematol.2013.091918. Agarwal A et al. Evolving Role of FDG PET/CT in Multiple Myeloma Imaging and Management. AJR 2013;200:884-890. Dimopoulos D et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia 2009, 1–12. doi:10.1038/leu.2009.89 Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

BACKGROUND: Peripheral T/NK–cell lymphomas (PTCL) are a heterogeneous group of neoplasms with a median survival of 2-3 years. Currently, there is not standard treatment although consolidation of response with autologous stem cell transplantation (ASCT) is recommended as front line therapy, except in anaplastic ALK+ and T/NK nasal localized lymphomas. AIM: To analyze the outcome of patients with PTCL diagnosed and treated in our center between 2000 and 2012. METHODS: An Intention to treat analysis has been performed to assess the response rate, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty eight patients were identified in this period, 2 were excluded, 1 due to misdiagnosis and the other was not treated in our Department. There were 28 men and 8 women with a median age of 62 years (20-85 y), ECOG ≥ 2: 19%, B symptoms: 61%, IPI ≥ 2: 56% and PIT ≥2: 47%. The histological subtypes are described in Table 1. Five patients died during diagnosis (aspergillosis, septic shock, intestinal perforation, Evans syndrome and hemophagocytic syndrome) and 2 rejected treatment. We treated 29 patients (80.5%) mainly with CHOP-like chemotherapy (77%) adding other schemas in order to achieve best response if needed. In 15 patients ASCT was not indicated (9 due to age and 6 due to histological subtype). After induction, 4 patients achieved complete remission (CR), 3 partial response (PR) and 8 progressed (NR / P). Median number of treatments was 1 (range 1 to 3). Fourteen patients were candidates for transplant but 4 of them could not receive it due to progression, early death, lost to follow-up and medical decision. Finally, 10 patients (71%) proceeded to transplant: 9 ASCT and 1 allo-SCT. The median number of treatments was 2 (1 - 3). Three patients were transplanted in CR, 6 PR and 1 NR/P; no patient improved the response. Three patients died during the procedure (RSV pneumonia, CMV and gram positive sepsis). The allo-SCT patient died of grade IV acute GVHD. Currently, 7 out of 36 patients are alive in CR, 24 have died and in 5 were lost to follow-up. Causes of death were: lymphoma (58%), infection (25%), toxicity (4%) and unknown (13%). With a median follow-up for alive patients was 72 months, OS was 15.34 months (95% CI, 3.98-26.71) and PFS 13.61 months (95% CI, 10.15-17.07). In Table 2 and figure 1 we show the median PFS and OS obtained in transplant- eligible and non-eligible patients. CONCLUSIONS: We confirm the difficulty of long-term control of PTCL with current first-line treatments recommended by guidelines. Even in those patients receiving more intensive treatment with SCT, no improvement in PFS or OS was observed. New drugs and strategies are needed to improve the prognosis of these patients. Table 1. HISTOLOGICAL SUBTYPES N= 36 Peripheral T-cell lymphoma NOS 12 (33%) Angioimmunoblastic T-cell lymphoma 7 (19%) Anaplastic large T-cell lymphoma, ALK+ 6 (17%) Anaplastic large T-cell lymphoma, ALK- 5 (14%) T/NK-cell lymphoma, nasal type 4 (11%) Intestinal T-cell lymphoma 1 (3%) Hepatosplenic γ/d T-cell lymphoma 1 (3%) Table 2. SCT candidates No SCT candidates OS months (CI 95%) 13.97 (6.40-21.53) 11.67 (2.86-20.48) PFS months (CI 95%) 13.61 (7.09-20.12) 11.51 (4.76-18.25) Figure 1. Figure 1. Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Plasma cell leukemia (PCL) represents the most aggressive form of monoclonal gammopathy for which new treatment approaches are needed. Here we report the effect of Bortezomib on cells from 4 patients with PCL, as well as the in vivo efficacy on a patient with secondary PCL. Bortezomib reduced PCL numbers and was more efficient in cell growth inhibition than dexamethasone or doxorubicin. Treatment with Bortezomib induced procaspase-3 and poly(ADP-ribose) polymerase cleavage and decreased the amount of extracellular signal regulated kinase (Erk1/2) and phospho-Erk1/2. However, Bortezomib did not substantially affect the levels of the Erk1/2 upstream activating kinase (MEK1), p27 or p21. Finally, we had the opportunity to use Bortezomib in a heavily pretreated patient with overt secondary PCL and severe anemia and thrombocytopenia. Following Bortezomib treatment, circulating plasma cells disappeared; what is more striking, the peripheral blood counts returned to normal, becoming transfusion-independent. These data support the inclusion of Bortezomib in the therapeutic armamentarium of PCL.

Abstract 5049 Background. Treatment of frail or elderly patients with relapsing symptomatic/active Multiple Myeloma (MM) is very difficult due to concomitant diseases, impaired bone marrow reserve, systemic toxicity, relatively decreased renal function and general problems of old age. Dexamethasone and new agents (thalidomide, lenalidomide, bortezomib and bendamustine) have been used in this setting, in most cases with doses adapted to the clinical situation. Aims. To retrospectively analyze the management of frail and/or very elderly MM patients with relapsed and active disease treated with reduced doses of the aforementioned agents in five hospitals in Madrid, Spain. Methods. The files of this group of MM patients were studied. The most common treatment has been the combination of low doses of lenalidomide (len) and of dexamethasone (dex), whereas treatment with reduced doses of other agents has been anecdotal; therefore we analyzed the results of len/dex combinations. Len and dex have been used in lower than standard doses, adapted to the individual initial situation of the patients and tailored according to effect and toxicity throughout treatment. There was no specific protocol and the management of the patients has depended exclusively on the practice and criteria of the treating physicians. Patient risk was stratified following the Salmon and Durie (S&D) score and the International Staging System (ISS). Response was assessed with the IMWG criteria. The study has been approved by the Ethics Committee of Hospital Ramon y Cajal, as coordinating center. Results. 38 patients were included in the study. Mean age was 79 years (range 68–90). 30 pts (79%) were older than 75 years and 10 pts had over 85 years. More than half of the patients (21) had two or more comorbidities. Patients had previously received 1 to 5 (m=1. 8) different treatment modalities, including steroids, melphalan (25), bortezomib (20), thalidomide (6) (or their combinations), and others or even APBSCT (3). 23 pts (60%) had IgG (m=4087 mg/dl, range 868–13000); 13 (34%) IgA (m=2115, range 355–4930) and 2 (5%) only light chains. 22 had κ and 15 λ light chains. 19 (50%) had BJ proteinuria. Mean Hemoglobin level was 10. 7 gr/dl (7. 5–14. 1) and mean creatinine level 1. 3 mg/dl (0. 4–12. 9); 28 (74%) had bone disease. 3 pts had S&D stage I, 22 stage II, and another 13 stage III. 13 pts had ISS stage I, 17 had stage II and 7 stage III. Patients received between 1 and 30 cycles of len/dex (m= 8). Median initial Len dose was 10 mg, the majority between 5 and 15mg, although 4 received 25 mg that were rapidly reduced. Mean initial dex dose was 20mg/day for 4 days. 4 pts (10. 5%) achieved Complete Remission (CR) (3 with negative IF), 27 (71%) Partial Remission (PR) (5 with VGPR) and 2 (5%) a significant, but lesser than 50%, reduction of the M-component (Stable Disease, Std). Altogether, overall response (CR+PR+Std) occurred in 33 pts (86%). The best response occurred after 2 to 9 cycles (m=4) of len/dex. Treatment was stopped in 15 patients due to neurological (4) or hematological (1) toxicity, pulmonary embolism (1), unrelated causes (4) and after achieving a plateau response (5). Time to next treatment was 1–30 months, (m=8 mo). 7 pts relapsed after 3–21 months (m=7). 10 patients died, 5 of related (disease progression, cardiac amyloidosis, renal progression to ESRF) and 5 of unrelated (cancer, sepsis, myocardial infarction, congestive heart failure) causes. Grade III-IV bone marrow toxicity occurred in 9 pts and neurological toxicity (PNP) in 5 (all of them had previously been treated with bortezomib or thalidomide). Conclusions. Personalized low doses of len/dex have been the most common treatment for frail/very elderly patients with relapsed MM in our centers and it is an active and tolerable option in this setting. The haematological toxicity was expectable and manageable, but prior treatments with bortezomib or thalidomide were associated with limiting neurotoxicity. Disclosures: No relevant conflicts of interest to declare.

Abstract 4035 Introduction: Bendamustine is a dual alkylating agent with demonstrated efficacy in de novo multiple myeloma (MM) and in relapsed/refractory (R/R MM). We present the preliminary results from the experience of Spanish compassionate use registry of this agent in different treatment schedules of R/R MM, promoted by the GEM/PETHEMA Group (Benda-MMRR-11). This study has been approved by local ethical committee, CEIC, HUP, Madrid, Spain. Patients and Methods: 72 patients, 42 males and 30 females, with advanced R/R MM after several lines of previous treatment received a schedule containing Bendamustine (Levact®, Mundipharma, UK). Median age was 66 (35–86), with a median of 4 previous salvage lines (1–11). Bendamustine dose used ranged between 60 and 120 mg/m2 iv on days 1 and 2 for each 28 days cycle. The median of cycles was 2 (1–9). The combinations used were: Bendamustine + Prednisone in 27 patients, Bendamustine + Thalidomide + Prednisone in 11 cases, Bendamustine + Dexamethasone in 14 patients, Bendamustine + Bortezomib + Dexamethasone in 7 patients, Bendamustine + Bortezomib + Prednisone in 3 patients, Bendamustine + Thalidomide + Dexamethasone in 2 cases, Bendamustine monotherapy in 5 patients, Bendamustine + Thalidomide in 1 case, Bendamustine with Caelyx in 1 case and Bendamustine with Rituximab in 1 case. Results: In the 69 evaluable patients, the response was: overall response rate (ORR) 30.24%%, with complete response (CR) 11.5%, partial response (PR) 13.04%. Minimal response (MR) was 5.7%, and stable disease (SD) was 17.39%. Progression was documented in 52.1% of patients. In general, treatment was well tolerated; the most common adverse effect was hematological toxicity with grade 3–4 neutropenia in 31.8%, grade 3–4 thrombocytopenia in 30.4% and grade 3–4 anemia in 17.3%. Other toxicities included grade 3–4 infections in 27% of patients and grade 3–4 asthenia in 11.5%. Clinical results will be updated with more details regarding TTP, OS and efficacy and toxicity with each schedule. Comments: Bendamustine is an effective salvage therapy in patients with advanced R/R MM. Our results are consistent with previous published data in larger series of patients. More experience is needed with this agent to define the best combination and to assess its grade of efficacy that will be probably superior in earlier stages of myeloma evolution. Disclosures: Off Label Use: compassionate use.

Lenalidomide is an oral immunomodulatory drug that has helped improve outcomes in multiple myeloma (MM) patients. Combination lenalidomide and dexamethasone (Len+Dex) has been shown to increase response rates and prolong survival compared with dexamethasone alone in patients with relapsed or refractory MM (RRMM). Clinical benefit may be greatest when Len+Dex is given at first relapse, and continued treatment appears to provide greater depth of response and improved survival outcomes. The most common adverse events associated with Len+Dex are cytopenias, which are predictable and manageable. Len+Dex is associated with an increased risk of venous thromboembolism, which necessitates adequate prophylaxis. The risk of second primary malignancies does not appear to be increased in patients with RRMM treated with lenalidomide-based therapy. Here we review the safety and efficacy of Len+Dex in RRMM, and provide an overview of data from Spain on the use of Len+Dex in RRMM.

Abstract 1181 Introduction: Stem cells (SC) show a potential of cellular therapy in diffuse coronary disease with controverted results. We present here an analysis of a group of patients treated with TMLR plus ABMC. (Caiber Program Advanced Therapy Proyect FIS 2009). Patients and methods: 19 patients with DCD were included. Age 66 (range: 52–78). ABMC were obtained by aspiration and processed using HARVEST-TM system -TALEX (Harvest Technologies Inc. GMBH, Munich) to obtain 20 ml. Surgery consisted of anterior thoracotomy incision at the fourth and fifth intercostal space. Between 15–30 transmyocardial channels were realized with TLMR PHOENIX-TM (Cardiogenesis, Irvine, CA, USA) and CrystalFlex 1 mm optical fibre. 0.5–2 cc of MO were administered in each channel. Total number CMN were determined by automatic cell counter and flow cytometry and were typified specific cell populations such as CD34+ and CD133+. Results: The duration of stem cell collection was less than 30 minutes. All the procedure was performed on surgery in 1 step. Any complications were observed with this technique. Correlation between the cellular count and demographic data was not observed. After a follow up of 22 months (5-36) only one patient has died (20m) of DCD. Initial clinical results are satisfactory with a significant reduction in the functional grade of angina. Comments and conclusions: Our data show that TMLR plus ABMC is a safe method with clinical efficacy in patients with DCD that are not candidate to other therapy options. The described method offers efficiency and simplicity to obtain cells. More cases and follow-up are required, as well as later functional evaluations. Disclosures: Alegre: Celgene: Honoraria. Off Label Use: Lenalidomide is not approved for the treatment of smoldering multiple myeloma.

Background To evaluate the midterm results of patients with angina and diffuse coronary artery disease treated with transmyocardial revascularization in combination with autologous stem cell therapy. Methods Nineteen patients with diffuse coronary artery disease and medically refractory class III/IV angina were evaluated between June 2007 and December 2009 for sole therapy TMR combined with intramyocardial injection of concentrated stem cells. At the time of surgery, autologous bone marrow (120cc) was aspirated from the iliac crest. A cardiac MRI and an isotopic test were performed before and after the procedure. Follow-up was performed by personal interview. Results There were no perioperative adverse events including no arrhythmias. Mean number of laser channels was 20 and the mean total number of intramyocardially injected cells per milliliter were: total mononuclear cells(83.6 × 106), CD34+ cells(0.6 × 106), and CD133+ cells(0.34 × 106). At 12 months mean follow-up average angina class was significantly improved (3.4 ± 0.5 vs 1.4 ± 0.6; p = 0.004). In addition, monthly cardiovascular medication usage was significantly decreased (348 ± 118 vs. 201 ± 92; p = 0.001). At six months follow up there was a reduction in the number of cardiac hospital readmissions (2.9 ± 2.3 vs. 0.5 ± 0.8; p < 0.001). MRI showed no alterations regarding LV volumes and a 3% improvement regarding ejection fraction. Conclusions The stem cell isolator efficiently concentrated autologous bone marrow derived stem cells while the TMR/stem cell combination delivery device worked uneventfully. An improvement in clinical status was noticed in the midterm follow-up. Images test showed no morphological alterations in the left ventricle after the procedure.

Introduction: Stem cell (SC) based therapy in ischemic heart disease is actually in development with the aim of improving cardiac regeneration. The way of administration, source of SC and the mechanisms of its clinical effects are yet not well defined. We present preliminary results of a group of patients treated with laser revascularization and autologous bone marrow (BM) cells administration, evaluating cells immunophenotype and clinical results. Patients and methods: Fourteen patients (57–78 y) with diffuse coronary disease and medically refractory class III/IV angina were prospectively evaluated for cell-based therapy combined with laser transmyocardial revascularization (TMR) PHOENIX-TM (Cardiogenesis, Irvine, CA, USA). BM mononuclear cells (MC), were obtained by BM aspiration (120 mL) and processed for concentration using HARVEST-TM system (Harvest Technologies Inc. GMBH, Munich). Immunophenotypic characterization of the final infused product was performed by standard four-color flow cytometry with monoclonal antibodies directed against the human surface antigens CD29, CD49a, CD105, CD106, CD117, CD34, CD133 and CD45, to evaluate different cell populations. Results and conclusions: Patients received a median of 56.8×106 (43.7–79) BMMC/ mL 0.5×106 (0.05–1) CD34+ cells/mL and 0.23×106 (0.001–0.7) CD133+ cells/mL. All the patients are alive after this treatment: median of 9 months, (1–15), with improvement of their cardiological clinical status and QoL. As observed (Table 1) the BMMC used in the therapy contained a significant proportion of CD133+ and CD34+ hematopoietic SC. In addition, the samples contained cells with CD105+ CD45− or CD29+ CD45− CD34− phenotypes which have been described as mesenchymal stem cells (MSC). Bone marrow CD106+ positive cells represent a multipotent subpopulation of MSC including endotelial. Correlation between the relative quantity of the different cell subsets and clinical results of the patients will be presented. TABLE 1 CD34 CD133 CD117 CD29 CD49a CD105 CD106 Mean 3.53 2.42 7.37 2.23 0.75 6.75 0.33 Std. Deviation 1.72 1.68 2.60 0.97 0.75 3.34 0.23 25% Percentile 1.95 0.85 4.95 1.25 0.15 3.10 0.2 Median 3.20 2.15 6.70 2.30 0.40 7.05 0.25 75% Percentile 5.45 4.25 10.45 3.15 1.70 10.10 0.55

Aim: To evaluate the efficacy of Lenalidomide (Len) as compassionate use in relapsed or progressive Multiple Myeloma (MM) up to its approval in Spain. Patients and Methods: GEM-PETHEMA designed a transverse and retrospective, multicenter analysis of MM cases which Len compassionate use was requested until December, 2007. The decision to treat these patients was previous and independent from the decision to conduct the present analysis and depended only on the clinical criteria of the responsible doctors. At least, one response assessment was a must for efficacy analysis. Results: 111 MM patients have been included. Eligible patients for efficacy were 103. Mean age was 65.7 (38–85); 53 m, 50 f. Previous median lines of therapy were 3 (1–8): 92 (89.3%) have received bortezomib; 37 (35.9%) autologous PBSCT and 26 (25.2%) thalidomide. Extramedullary plasmocitomas were present in 25 (24.3%). Mean Len dose was 22.8 mg (± 4.9): 82 (79.6%) received the standard dose and schedule (25 mg d for 3 w every 4 w) and 21 (20.4%) received less dose and/or different schedule. 92 (89.3%) received Dexametasone (mean dose 58.33 mg/w) [± 35.8]). Response: 4 (3.9%) sCR, 11 CR (10.7%), 12 VGPR (11.7%), 41 PR (39.8%), 20 SD (19.4%), 13 PD (12.6%), 2 NE (1.9). Among groups, response equal or superior to PR was observed in all settings: 64.1% in prior exposed to bortezomib, 46.1% in prior exposed to thalidomide and 40.0% in patients with extramedullary plasmocitomas. Previous transplant, the number of previous lines received, renal failure, age, or cytogenetic did not affect significantly the overall response rate. Median duration of treatment was 7.7 m (1–21); median TTP was 8.3 m and median global survival since starting Len therapy was 11 m (6–22). Median survival since diagnostic was 49 m (40–60). At the time of analysis, 46 (45.5%) patients were still on Len therapy, and 72 (79.6%) were alive. Toxicity: ≥ grade II: neutropenia, 51 (46.4%); thrombocytopenia, 39 (35.5%); DVT, 5 (4.5%); rash, 3 (2.7%); neutropenic fever, 8 (7.3%); others, 13 (11.8%). DVT/PE prophylaxis was used in 89 (86.4%) patients: LWMH in 43.8 % and low dose aspirin in 48.3 %. No PE was reported. Conclusions: Lenalidomide is effective in this heavily pre-treated MM population-progressive or refractory to standard therapy-even in different clinical settings. The most frequent association to Len was intermediate dose of Dex. Although response rate was superior in patients exposed previously to bortezomib, no differences on duration and survival were observed. Patients with extramedullary plasmocitomas showed also response. Toxicity, mainly myelosupression was predictable and manageable with dose adjustments and cytokine support.

Introduction Intensification therapy in MM with autologous PBSCT is widely indicated for younger patients with favourable results regarding response, OS and PFS. However, there is no clear plateau in the survival curve. To improve these results and to prolong remission duration, various maintenance treatments have been proposed. Interpheron alpha2b s.c, at low dose, steroids on alternate days and most recently, low dose oral thalidomide, have demonstrated improvements in EFS and OS times but these results needs confirmation. Recently a new formulation of interpheron alpha2b (Pegintron®) is available conjugated with polietilenglicol with the advantage of being administered on a unique weekly dose. This new formulation of Interpheron alpha has been tested scarcely in MM. We present the preliminary results of a spanish, phase II, non comparative, multicentric study (PI-MM-01) with Pegintron® (Schering-Plough) as maintenance treatment after autologous PBSCT. Patients y Methods From May 2003 to March 2007, 30 patients were included in this study, 64% female and 36% male, with a median 56 years, received Pegintron® once a week subcutaneously as maintenance treatment after favourable response post-HDT with autologous PBSCT when the engraftement was stable and complete. The initial dose was 15 mg/week × 2 week and this dose was escalated to 25 mg/week and then 35 mg/week. The final dose was adopted according clinical and hematological tolerance. The maintenance treatment was continued at least 5 years postransplant or until toxicity, relapse or progressión. Results 30 patients were evaluable for this preliminary analysis. The median time from transplant to IFN treatment was 3.8m. The median dose of Pegintron was 15 mg/week. 9 patients have suspended the treatment (30%). 5 cases (16%) due to progression, 2 (4%) for toxicity and 2(4%) for other reason. The remainder 21 patients (76%) continue the treatment with clinical response, with median duration of 16 months (2–42). At present all patients are alive. Astenia, “pseudo-flu” symptoms and thrombopenia and neutropenia were the most common adverse effects observed, that limited the dose escalation, being 15 mg/week the best tolerated and mos frequent dose (70%). One patient suspended the treatment due to dermatological reaction with pruritus. Conclusions and Comments Although these results need completion and further analysis, maintenance treatment with a weekly dose of Interpheron-a2b conjugated with Polietilenglicol (Pegintron®) is well tolerated after autologous PBSCT in MM. No major adverse effects were observed and no relevant negative impact was observed on the autologous graft. Pegintron® sc could be an alternative to standard interpheron sc with the main advantage of therapy simplification with only one dose weekly. More experiences and longer follow up are needed to evaluate the role of this strategy in the global treatment of MM and new approaches for maintenance have to be investigated, including association and comparison with steroids or new drugs as thalidomide, bortezomib or lenalidomide.

Introduction and Objectives. Lenalidomide is a new inmunomodulatory drug which has shown effectiveness, in combination with dexamethasone, in relapsed or progressive Multiple Myeloma (MM). In our country, little experience outside clinical trials exists since lenalidomide is only currently available in the compassionate use program, for patients with advanced MM. With the purpose of sharing the clinical practical experience with this drug, we considered it interesting to gather the outstanding data on the use of lenalidomide in a multicentric registry, throughout the Spanish scope. We present the preliminary results of this registry. Patients and methods. We designed a registry, canalized through GEM-PETHEMA, in which main clinical data of MM patients relapsed or progressive treated with lenalidomide within the compassionate use program, were collected. The decision to treat these patients was prior to and independent of the decision to make this registry and was only based on clinical criteria. The selected patients had at least one response assessment. Results. 19 valid questionnaires have been received, 14 patients (pts.) being assessable for response. The treatment was started between 03/06 and 04/07. Average age: 63 years (40–77); 9 men and 5 women. Type of MM: IgG 9 pts, IgA 3 pts, 1 non-secretory, 1 Bence Jones K. Average M-protein 3.25 g/dL(SD: 3,32); average creatinine 1,05 (SD: 0.36); average bm plasma cells infiltration: 36%. Median lines of previous treatments: 4 (2–8). 13 pts had received bortezomib, 8 pts had received thalidomide, and 7 had undergone autologous PBSCT. 7 pts showed extramedullary plasmocytomas.2 patients received the standard dose (25 mg daily, P.O. 21 days every 4 weeks). 2 patients received lower doses. All the patients, except one, received Dexamethasone simultaneously (average 56 mg per week). Prophylaxis for DVT: 7 pts with LWMH and 3 pts with salicylates. 4 patients did not receive prophylaxis. At the time of data collection 10 patients where still on the treatment. Lenalidomide was discontinued in 2 patients due to progression (median time to progression 6 months (1–8); 1 pts underwent PBSCT after reaching PR and discontinued the treatment due to stable disease after 6 months. Response: 2 CR (14%), 1 VGPR (7%), 6 PR (43%), 3 SD (21%). Among the 9 pts with a favorable response (64%): 8 had previously received bortezomib, 4 had received thalidomide, and 4 had undergone PBSCT - Toxicity: Neutropenia G3: 5 pts/G4: 2 pts; 5 patients needed G-CSF. Thrombocytopenia G3: 3 pts/G4: 3 pts. Skin rash in 1 pt. Neither TVP/TEP nor neutropenic fever were observed. Conclusions. Although a more detailed analysis and a longer follow-up is needed the results of our registry are consistent with other published clinical trials: lenalidomide associated with dexamethasone induces durable objective responses in a high percentage of patients with relapsed or progressive MM, after several treatment lines. The tolerance of this drug is acceptable, being the mielosuppression the most relevant toxicity. The role of this drug at low dose for long term maintenance have to be investigated.

Introduction Plasma Cell Leukemia (PCL) is characterized by a high number of plasma cells in peripheral blood (>2 × 109/L) and more than 20% of circulating plasmocytes on differential count. Primary PCL or secondary form, after previous multiple myeloma (MM), represent the most aggressive forms of clonal gammapathy with very poor outcome from both conventional chemotherapy and autologous or allogeneic transplant. For this reasons new effective treatment approaches are required. The proteasome inhibitor Bortezomib has been shown to be effective in advanced MM with a rapid response but few reports have been published regarding its potential role on PCL. We report here the clinical results of a serie of PCL patients that received proteasome inhibitor, Bortezomib (Velcade®), as induction therapy. Patients and Clinical Results We describe 10 patients with PCL treated with Bortezomib. Median age was 58 y (30–70). 4 cases were primary, de novoPCL and 6 cases were secondary forms of relapsed or progressive MM. Patients with secondary PCL had received a median of 3 previous lines of therapy including autologous transplantation (5 cases). Bortezomib at standard dose iv: 1.3 mg/m2 days 1,4, 8,11 every 21 days were used alone in 2 patients and in combination with high dose of Dexamethasone +/− Adryamicin in the rest. 3 cases recived the BDD scheme (Bortezomib iv, Pegylated Doxorrubicin iv and oral Dexamethasone). 9 patients were evaluable for drug efficacy with 7 cases showing some grade of favourable response with the first cycle, including 3 cases of CR. 4 patients have died: 1 during first weeks and 3 for progression, 2–3 months after initial response. 3 cases received allogeneic transplant with related donor and reduced conditioning and are alive 12, 14 and 30 months postransplant. The median follow up since PCL diagnosis of 6 alive patients is 14 months (3–39 months). 3 patients received maintenance therapy that included low dose thalidomide. Grade 2 thrombopenia, neutropenia and gastrointestinal symptoms were the main secondary toxicity. No complicated tumoral lysis syndrome were observed. Conclusions and Comments Bortezomib has been shown to be effective by several mechanisms in patients with MM resistant to multiple previous treatments and as induction therapy alone or in combination with other drugs. The favourable responses observed in these cases of PCL; including de novo patients, and the biological ex vivo results in PCL cell lines, suggest the potential efficacy of this agent combined with dexamethasone and doxorubicin. Although more experience is necessary these data support future trials with Bortezomib combined with other drugs for example BDD scheme in the induction treatment of PCL. The role of allogeneic intensification therapy has also to be investigated in young patients after control of PCL with this approach. For maintenance of response, the role of this drug or other new drugs as thalidomide or lenalidomide has to be investigated.