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Sample records for melphalan prednisone thalidomide

  1. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma

    DEFF Research Database (Denmark)

    Zweegman, Sonja; van der Holt, Bronno; Mellqvist, Ulf-Henrik

    2016-01-01

    The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalid......The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone......, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen...... with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS...

  2. Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

    DEFF Research Database (Denmark)

    Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

    2014-01-01

    Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty...

  3. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma

    DEFF Research Database (Denmark)

    Waage, Anders; Gimsing, Peter; Fayers, Peter

    2010-01-01

    In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days......% in the MPT and MP arms, respectively (P constipation, which...... was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did...

  4. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma

    DEFF Research Database (Denmark)

    Waage, Anders; Gimsing, Peter; Fayers, Peter

    2010-01-01

    In this double-blind, placebo-controlled study, 363 patients with untreated multiple myeloma were randomized to receive either melphalan-prednisone and thalidomide (MPT) or melphalan-prednisone and placebo (MP). The dose of melphalan was 0.25 mg/kg and prednisone was 100 mg given daily for 4 days...... every 6 weeks until plateau phase. The dose of thalidomide/placebo was escalated to 400 mg daily until plateau phase and thereafter reduced to 200 mg daily until progression. A total of 357 patients were analyzed. Partial response was 34% and 33%, and very good partial response or better was 23% and 7...... was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did...

  5. [Combination chemotherapy with vincristine, melphalan, CCNA, cyclophosphamide, prednisone in myeloma].

    Science.gov (United States)

    Le Loët, X; Monconduit, M; Menard, J F; Deshayes, P; Grobois, B; Tanguy, A; Prevost, E; Piguet, H

    1984-05-01

    The authors report the results of a prospective, multi-centre trial involving 87 patients with previously untreated myeloma who were treated by combination chemotherapy consisting of melphalan, cyclophosphamide, CCNU, prednisone and vincristine. 83.1% of patients had a high tumour mass (stage III on Durie and Salmon's classification). The response to treatment could be evaluated in 76 patients and 70% were found to respond. The median actuarial survival of the whole population is 30 months. The survival is significantly longer (p less than 0.001) in responders (median 40 months) than in non-responders (median: 17 months); the survival is significantly shorter (p less than 0.01) in subjects with renal failure (median: 10 months) than in subjects without renal failure (median: 36 months). This treatment is sufficiently well tolerated to be administered on an outpatient basis. One case of acute monoblastic leukaemia was observed. These results are similar to those reported in the literature.

  6. Lenalidomide, Melphalan, and Prednisone Association Is an Effective Salvage Therapy in Relapsed Plasma Cell Leukaemia

    Directory of Open Access Journals (Sweden)

    Tommasina Guglielmelli

    2009-01-01

    Full Text Available Plasma cell leukemia (PCL is a rare and aggressive plasma cell disorder, characterized by the presence of a peripheral blood absolute plasma cell count of at least 2×109/l and more than 20% circulating plasma cells. The prognosis of PCL patients remains poor. Even by using autologous or allogenic transplant procedures, median survival does not exceed 3 years (Saccaro et al., 2005. Thalidomide, bortezomib and lenalidomide (Revlimid have emerged as high active agents in the treatment of PCL (Johnston and abdalla, 2002; Musto et al., 2007; Finnegan et al., 2006. In particular, Lenalidomide is a structural analogue of thalidomide with similar but more potent biological activity; it is used as first line therapy in MM (Palumbo et al., 2007; Niesvizky et al., 2007, although information regarding its associated use with dexamethasone use as salvage therapy in PCL derives from anecdotal single case reports (Musto et al., 2008. We would like to describe a case of primary PCL with adverse cytogenetic in which excellent response was achieved with the combination of lenalidomide, melphalan, and prednisone as salvage therapy.

  7. Thalidomide and dexamethasone vs. bortezomib and dexamethasone for melphalan refractory myeloma

    DEFF Research Database (Denmark)

    Hjorth, Martin; Hjertner, Øyvind; Knudsen, Lene Meldgaard

    2012-01-01

    Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives.......Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment, but no randomized trials have been published comparing these two treatment alternatives....

  8. Time to spare newly diagnosed non transplant eligible myeloma (ENDMM) from thalidomide

    DEFF Research Database (Denmark)

    Demarquette, H.; Guidez, S.; Jurczyszyn, A. J.

    2015-01-01

    Background. Thalidomide is one of the most prescribed regimens upfront in eNDMM, e.g. elderly myeloma, essentially as melphalan-prednisone-Thalidomide (MPT). Several options are offered at 1st and 2nd relapse to patients initially exposed to Thalidomide with either bortezomib or lenalidomide-base...

  9. Improvement of Anaemia in Patients with Primary Myelofibrosis by Low-Dose Thalidomide and Prednisone

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    Petra Bělohlávková

    2016-08-01

    Full Text Available Background: A combination of low-dose thalidomide and corticosteroids is a treatment option for anaemic patients with primary myelofibrosis (PMF who are not eligible for allogeneic hematopoietic stem cell transplantation. Methods: We describe the outcomes of 13 patients with PMF treated with thalidomide 50 mg daily in combination with prednisone 0.5 mg/kg daily. Treatment responses were seen in 10/13 (77% patients with a median onset of therapeutic effect at 4 weeks (range 3–7 weeks after treatment initiation. Improvements of anaemia and thrombocytopenia and reduction in splenomegaly were observed in 70%, 38%, and 30% of patients, respectively. Four of six initially transfusion-dependent patients became transfusion independent following the therapy. The median duration of treatment response was 18 months (range 3–35 months. The treatment was well tolerated, with only one patient discontinuing therapy due to toxicity. Responders included both patients with and without JAK2 V617F, and included patients with both newly diagnosed and longstanding PMF. Conclusions: Our retrospective analysis confirmed that the therapy with low-doses thalidomide with prednisone in patients with PMF achieves significant response rate in anaemia with low treatment toxicity.

  10. Mechlorethamine, vincristine, melphalan and prednisone (MOMP) for the treatment of relapsed lymphoma in dogs.

    Science.gov (United States)

    Back, A R; Schleis, S E; Smrkovski, O A; Lee, J; Smith, A N; Phillips, J C

    2015-12-01

    Eighty-eight dogs with relapsed lymphoma were treated with the MOMP (mechlorethamine, vincristine, melphalan and prednisone) protocol on a 28-day treatment cycle. The overall response rate (ORR) to the MOMP protocol was 51.1% for a median of 56 days (range 7-858 days). Twelve percent of dogs experienced a complete response for a median of 81 days (range 42-274 days) and 38.6% experienced a partial response for a median of 49 days (range 7-858 days). Dogs with T-cell lymphoma had an ORR of 55% for a median of 60 days (range 49-858 days) while those with B-cell lymphoma had an ORR of 57% for a median of 81 days (range 7-274 days) (P = 0.783). The overall survival time for all dogs was 183 days (range 17-974 days). Fifty-four percent of dogs experienced toxicity with the majority classified as grade I. The MOMP protocol seems well-tolerated and is an option for dogs with relapsed lymphoma. © 2013 John Wiley & Sons Ltd.

  11. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma

    DEFF Research Database (Denmark)

    Waage, Anders; Gimsing, Peter; Fayers, Peter

    2010-01-01

    % in the MPT and MP arms, respectively (P constipation, which...... was markedly increased in the MPT arm. Constipation, neuropathy, nonneuropathy neurologic toxicity, and skin reactions were significantly more frequent in the MPT arm. The number of thromboembolic events was equal in the 2 treatment arms. In conclusion, MPT had a significant antimyeloma effect, but this did...

  12. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    The role of thalidomide for previously untreated elderly patients with multiple myeloma remains unclear. Six randomized controlled trials, launched in or after 2000, compared melphalan and prednisone alone (MP) and with thalidomide (MPT). The effect on overall survival (OS) varied across trials. We...... interval 0.73-0.94, P = .004), representing increased median OS time of 6.6 months, from 32.7 months (MP) to 39.3 months (MPT). The thalidomide regimen was also associated with superior PFS (hazard ratio = 0.68, 95% confidence interval 0.61-0.76, P ... or better was 59% on MPT and 37% on MP). Although the trials differed in terms of patient baseline characteristics and thalidomide regimens, there was no evidence that treatment affected OS differently according to levels of the prognostic factors. We conclude that thalidomide added to MP improves OS...

  13. Safety of thalidomide in newly diagnosed elderly myeloma patients

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Waage, Anders; Hulin, Cyrille

    2013-01-01

    Background. Melphalan-prednisone-thalidomide (MPT) improves outcome in multiple myeloma (MM) patients, and it is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. Design and Methods. An individual patient data...... was documented in patients treated with MPT vs MP. Grade 3-4 non-hematologic AEs were significantly increased in patients with poor performance status. Occurrence of grade 3-4 non-hematologic AEs negatively impacted on progression-free survival (PFS) (HR 1.24, 95%CI 1.07-1.45) and overall survival (OS), (HR 1...

  14. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.

    2005-01-01

    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy.

  15. Thalidomide neurotoxicity

    DEFF Research Database (Denmark)

    Clemmensen, O J; Olsen, P Z; Andersen, Klaus Ejner

    1984-01-01

    therapy. Since reports on thalidomide neurotoxicity have shown that the neurological symptoms are long standing and possibly irreversible, it is obviously important to inform patients of this possible side effect and to evaluate them closely for the symptoms and electrophysiological signs of evolving...

  16. Melphalan metabolism in cultured cells

    International Nuclear Information System (INIS)

    Seagrave, J.C.; Valdez, J.G.; Tobey, R.A.; Gurley, L.R.

    1985-06-01

    Procedures are presented for the adaptation of reversed-phase-HPLC methods to accomplish separation and isolation of the cancer therapeutic drug melphalan (L-phenylalanine mustard) and its metabolic products from whole cells. Five major degradation products of melphalan were observed following its hydrolysis in phosphate buffer in vitro. The two most polar of these products (or modifications of them) were also found in the cytosol of Chinese hamster CHO cells. The amounts of these two polar products (shown not to be mono- or dihydroxymelphalan) were significantly changed by the pretreatment of cells with ZnC1 2 , one being increased in amount while the other was reduced to an insignificant level. In ZnC1 2 -treated cells, there was also an increased binding of melphalan (or its derivatives) to one protein fraction resolved by gel filtration-HPLC. These observations suggest that changes in polar melphalan products, and perhaps their interaction with a protein, may by involved in the reduction of melphalan cytotoxicity observed in ZnC1 2 -treated cells. While ZnC1 2 is also known to increase the level of glutathione in cells, no significant amounts of glutathione-melphalan derivatives of the type formed non-enzymatically in vitro could be detected in ZnC1 2 -treated or untreated cells. Formation of derivatives of melphalan with glutathione catabolic products in ZnC1 2 -treated cells has not yet been eliminated, however. 17 refs., 5 figs., 1 tab

  17. Melphalan

    Science.gov (United States)

    ... or vomiting blood or brown material that resembles coffee grounds.Keep all appointments with your doctor and the ... bloody vomit or vomited material that looks like coffee grounds unusual bruising or bleeding sore throat, cough, fever, ...

  18. Solution stability of Captisol-stabilized melphalan (Evomela) versus Propylene glycol-based melphalan hydrochloride injection.

    Science.gov (United States)

    Singh, Ramsharan; Chen, Jin; Miller, Teresa; Bergren, Michael; Mallik, Rangan

    2016-12-14

    The objective of this study was to compare the stability of recently approved Captisol-stabilized propylene glycol-free melphalan injection (Evomela™) against currently marketed propylene glycol-based melphalan injection. The products were compared as reconstituted solutions in vials as well as admixture solutions prepared from normal saline in infusion bags. Evomela and propylene glycol-based melphalan injection were reconstituted in normal saline and organic custom diluent, respectively, according to their package insert instructions. The reconstituted solutions were diluted in normal saline to obtain drug admixture solutions at specific drug concentrations. Stability of the solutions was studied at room temperature by assay of melphalan and determination of melphalan-related impurities. Results show that based on the increase in total impurities in propylene glycol-based melphalan injection at 0.45 mg/mL, Evomela admixture solutions are about 5, 9, 15 and 29 times more stable at concentrations of 0.45, 1.0, 2.0 and 5.0 mg/mL, respectively. Results confirmed that reconstituted Evomela solution can be stored in the vial for up to 1 h at RT or for up to 24 h at refrigerated temperature (2-8 °C) with no significant degradation. After storage in the vial, it remains stable for an additional 3-29 h after preparation of admixture solution in infusion bags at concentrations of 0.25-5.0 mg/mL, respectively. In addition, Evomela solution in saline, at concentration of 5.0 mg/mL melphalan was bacteriostatic through 72 h storage at 2-8 °C. Formulation of melphalan with Captisol technology significantly improved stability compared to melphalan hydrochloride reconstituted with propylene-glycol based diluents.

  19. Prednisone Therapy for Duchenne Dystrophy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2005-02-01

    Full Text Available The effects of prednisone on muscle function and the extent of steroid-related adverse effects were studied in 17 ambulant children with Duchenne muscular dystrophy (DMD at University Hospital, Groningen; Rehabilitation Centre, Utrecht; and Leiden University Medical Centre, the Netherlands.

  20. Prednisone/Prednisolone and Pregnancy

    Science.gov (United States)

    ... Prednisone is very similar to the body’s natural hormones, which are needed for milk production and the health of infants. Since people produce these hormones naturally, it is unlikely that the amount of ... in the breast milk would cause harmful effects in the nursing infant ...

  1. Vascular endothelial growth factor (VEGF) gene polymorphisms may influence the efficacy of thalidomide in multiple myeloma

    DEFF Research Database (Denmark)

    Andersen, Niels Frost; Vogel, Ulla Birgitte; Klausen, Tobias W

    2012-01-01

    . Retrospectively, the SNPs -2,578C>A (rs699947), -460C>T (rs833061), +405G>C (rs2010963) and +936C>T (rs3025039) in the VEGF gene were examined in 348 patients with newly diagnosed multiple myeloma initially treated with HDT, where 176 patients were treated with thalidomide at relapse. None of the examined geno...... and prognosis. In this study, we evaluated the association between genetic variations in the VEGF gene in patients with multiple myeloma and time to treatment failure (TTF) after high-dose melphalan and stem cell support (HDT), overall survival (OS) and efficacy of the anti-angiogenic drug thalidomide......- or haplotypes was associated with differences in TTF after initial therapy or OS. A possible relation between the haplotype -2,578A/-460C/+405G (ACG) and effect of thalidomide was seen. Patients with no copies of the haplotype ACG had a longer time to next treatment than patients with one or two copies...

  2. Prednisone

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    ... treat patients with low levels of corticosteroids by replacing steroids that are normally produced naturally by the ... dose. You may mix the concentrated solution with juice, other flavored liquids, or soft foods such as ...

  3. Prednisone

    Science.gov (United States)

    ... improves when the drug is decreased or discontinued. Avascular Necrosis of Bone For reasons that are not known, ... joint damage, most often of the hips. In avascular necrosis (or osteonecrosis, meaning “bone death”) of the hip, ...

  4. Prednisone versus prednisone plus ciclosporin versus prednisone plus methotrexate in new-onset juvenile dermatomyositis: a randomised trial.

    Science.gov (United States)

    Ruperto, Nicolino; Pistorio, Angela; Oliveira, Sheila; Zulian, Francesco; Cuttica, Ruben; Ravelli, Angelo; Fischbach, Michel; Magnusson, Bo; Sterba, Gary; Avcin, Tadej; Brochard, Karine; Corona, Fabrizia; Dressler, Frank; Gerloni, Valeria; Apaz, Maria T; Bracaglia, Claudia; Cespedes-Cruz, Adriana; Cimaz, Rolando; Couillault, Gerard; Joos, Rik; Quartier, Pierre; Russo, Ricardo; Tardieu, Marc; Wulffraat, Nico; Bica, Blanca; Dolezalova, Pavla; Ferriani, Virginia; Flato, Berit; Bernard-Medina, Ana G; Herlin, Troels; Trachana, Maria; Meini, Antonella; Allain-Launay, Emma; Pilkington, Clarissa; Vargova, Veronika; Wouters, Carine; Angioloni, Simona; Martini, Alberto

    2016-02-13

    Most data for treatment of dermatomyositis and juvenile dermatomyositis are from anecdotal, non-randomised case series. We aimed to compare, in a randomised trial, the efficacy and safety of prednisone alone with that of prednisone plus either methotrexate or ciclosporin in children with new-onset juvenile dermatomyositis. We did a randomised trial at 54 centres in 22 countries. We enrolled patients aged 18 years or younger with new-onset juvenile dermatomyositis who had received no previous treatment and did not have cutaneous or gastrointestinal ulceration. We randomly allocated 139 patients via a computer-based system to prednisone alone or in combination with either ciclosporin or methotrexate. We did not mask patients or investigators to treatment assignments. Our primary outcomes were the proportion of patients achieving a juvenile dermatomyositis PRINTO 20 level of improvement (20% improvement in three of six core set variables at 6 months), time to clinical remission, and time to treatment failure. We compared the three treatment groups with the Kruskal-Wallis test and Friedman's test, and we analysed survival with Kaplan-Meier curves and the log-rank test. Analysis was by intention to treat. Here, we present results after at least 2 years of treatment (induction and maintenance phases). This trial is registered with ClinicalTrials.gov, number NCT00323960. Between May 31, 2006, and Nov 12, 2010, 47 patients were randomly assigned prednisone alone, 46 were allocated prednisone plus ciclosporin, and 46 were randomised prednisone plus methotrexate. Median duration of follow-up was 35.5 months. At month 6, 24 (51%) of 47 patients assigned prednisone, 32 (70%) of 46 allocated prednisone plus ciclosporin, and 33 (72%) of 46 administered prednisone plus methotrexate achieved a juvenile dermatomyositis PRINTO 20 improvement (p=0.0228). Median time to clinical remission was 41.9 months in patients assigned prednisone plus methotrexate but was not observable in the

  5. Haemangioma with coagulopathy: sustained response to prednisone.

    Science.gov (United States)

    Evans, J; Batchelor, A D; Stark, G; Uttley, W S

    1975-01-01

    Two cases of giant haemangioma with thrombocytopenia are described. A satisfactory and sustained response to prednisone was achieved in respect of both coagulation abnormalities and tumour size. It is proposed that prednisone is effective by enhancement of thrombosis and reduction of fibrinolysis within the tumour, thus promoting a natural form of resolution. It is suggested that prednisone therapy should be first-choice treatment of complicated haemangiomas. Images Fig. 1 Fig. 3 PMID:147646

  6. Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles.

    Science.gov (United States)

    Vernal, Sebastian; Brochado, Maria Jose Franco; Bueno-Filho, Roberto; Louzada-Junior, Paulo; Roselino, Ana Maria

    2018-01-01

    Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

  7. Thalidomide increases human keratinocyte migration and proliferation.

    Science.gov (United States)

    Nasca, M R; O'Toole, E A; Palicharla, P; West, D P; Woodley, D T

    1999-11-01

    Thalidomide is reported to have therapeutic utility in the treatment of pyoderma gangrenosum, Behçet's disease, aphthous ulcers, and skin wounds. We investigated the effect of thalidomide on human keratinocyte proliferation and migration, two early and critical events in the re-epithelialization of skin wounds. Thalidomide at concentrations less than 1 microM did not affect keratinocyte viability. Using a thymidine incorporation assay, we found that thalidomide, at therapeutic concentrations, induced more than a 2. 5-fold increase in the proliferative potential of the cells. Keratinocyte migration was assessed by two independent motility assays: a colloidal gold assay and an in vitro scratch assay. At optimal concentrations, thalidomide increased keratinocyte migration on a collagen matrix more than 2-fold in the colloidal gold assay and more than 3-fold in the scratch assay over control. Although pro-migratory, thalidomide did not alter the level of metalloproteinase-9 secreted into culture medium. Thalidomide did, however, induce a 2-4-fold increase in keratinocyte-derived interleukin-8, a pro-migratory cellular autocrine factor. Human keratinocyte migration and proliferation are essential for re-epithelialization of skin wounds. Interleukin-8 increases human keratinocyte migration and proliferation and is chemotactic for keratinocytes. Therefore, thalidomide may modulate keratinocyte proliferation and motility by a chemokine-dependent pathway.

  8. Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

    Science.gov (United States)

    Cornett, Wendy R; McCall, Linda M; Petersen, Rebecca P; Ross, Merrick I; Briele, Henry A; Noyes, R Dirk; Sussman, Jeffrey J; Kraybill, William G; Kane, John M; Alexander, H Richard; Lee, Jeffrey E; Mansfield, Paul F; Pingpank, James F; Winchester, David J; White, Richard L; Chadaram, Vijaya; Herndon, James E; Fraker, Douglas L; Tyler, Douglas S

    2006-09-01

    To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

  9. Thalidomide

    Science.gov (United States)

    ... will not have any sexual contact with a male for 4 weeks before your treatment, during your treatment, and for 4 weeks after your treatment.Some medications can cause hormonal contraceptives to be less effective. If you plan to ...

  10. The thalidomide disaster, lessons from the past.

    Science.gov (United States)

    Ridings, James E

    2013-01-01

    It is close to 60 years since thalidomide was created by the German company, Chemie-Grünenthal, and launched as "Contergan." This was soon to be followed in England by the launch of "Distaval." Of all the drugs developed in the intervening years, thalidomide has undoubtedly had the greatest influence on shaping the Pharmaceutical Industry as we know it today.Strong marketing pressure in an Industry hungry for new medicines brought an inadequately tested drug to the market, targeted outsourcing quickly expanded the client base and finally market forces prevented timely withdrawal, even when evidence was emerging of disastrous side-effects. The full story of thalidomide was told by the Sunday Times in "Suffer The Children" (Kingsley et al., Suffer the children: the story of thalidomide, the insight team of the Sunday times (UK), 1979).Many preventative measures have been taken in the intervening years in light of the lessons learned with thalidomide. However, many of the pressures that led to the thalidomide disaster exist today with record high management and shareholder pressures to achieve success, parallel worldwide marketing, increased numbers of targeted outsourcing by small companies forming alliances with "Big Pharma" and, according to some commentators, a breakdown in the system of checks and balances that have existed in the regulatory authorities in the intervening years.Using thalidomide as a point of reference, this chapter looks at drug development and testing, regulatory authorities and guidelines, outsourcing and in-licensing, pharmacovigilance, and factors that influence withdrawal of a drug from the market.

  11. Thalidomide in patients with advanced multiple myeloma.

    Science.gov (United States)

    Yakoub-Agha, I; Moreau, P; Leyvraz, S; Berthou, C; Payen, C; Dumontet, C; Grosbois, B; Beris, P; Duguet, C; Attal, M; Harousseau, J L; Facon, T

    2000-01-01

    Recently, a report has suggested the efficacy and safety of thalidomide in refractory multiple myeloma. In an attempt to assess the efficacy and tolerance of thalidomide in advanced multiple myeloma (on behalf of the Intergroupe Franchophone dy Myelome (IFM)), we report the preliminary experience of the IFM with this drug. Patients with advanced multiple myeloma (n=27) were treated with an oral dose of thalidomide (median 400 mg/day). At the start of treatment, all patients had active disease and 20 patients had received at least one autologous transplantation. Median follow-up was 105 days from the first administration. The serum and/or urine levels of the M-component were reduced by at least 75% in four patients including one patient with a >90% reduction, by at least 50% in five patients and by at least 25% in three patients, giving a total response rate of 45% (12 out of 27 patients). Nine patients had stable disease and six patients had progressed disease. Short-term side-effects of thalidomide were generally moderate. This study confirms that thalidomide is an effective agent in patients with advanced myeloma.

  12. Fetal malformations and early embryonic gene expression response in cynomolgus monkeys maternally exposed to thalidomide

    Science.gov (United States)

    The present study was performed to determine experimental conditions for thalidomide induction of fetal malformations and to understand the molecular mechanisms underlying thalidomide teratogenicity in cynomolgus monkeys. Cynomolgus monkeys were orally administered (±)-thalidomid...

  13. Antitumorigenic Evaluation of Thalidomide Alone and in Combination with Cisplatin in DBA2/J Mice

    Directory of Open Access Journals (Sweden)

    Jean Marie B. Ruddy

    2002-01-01

    thalidomide failed to inhibit cell proliferation. However, cisplatin treatment with or without thalidomide, significantly inhibited the multiplication of both cell lines in a dose dependent manner. Thalidomide does not appear to be a beneficial adjuvant to cisplatin treatment.

  14. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Science.gov (United States)

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2015-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative regimens of a variety of other hematological and non-hematological malignancies. The addition of newer agents to conditioning like bortezomib or lenalidomide for myeloma, or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, while in combination with alemtuzumab may represent a backbone for future cellular therapy due to reliable engraftment and low toxicity profile. This review summarizes the development and the current use of this remarkable drug in hematopoietic stem-cell transplantation. PMID:22922522

  15. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN)

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Bringhen, Sara; Ludwig, Heinz

    2011-01-01

    elderly patients with MM are ineligible for autologous transplantation, and the standard treatment has, until recently, been melphalan plus prednisone. The introduction of novel agents, such as thalidomide, bortezomib, and lenalidomide, has improved outcomes; however, elderly patients with MM are more...

  16. A systematic literature review and network meta-analysis of treatments for patients with untreated multiple myeloma not eligible for stem cell transplantation

    DEFF Research Database (Denmark)

    Weisel, Katja; Doyen, Chantal; Dimopoulos, Meletios

    2017-01-01

    In newly diagnosed multiple myeloma (MM), patients ineligible for front-line autologous stem cell transplantation (ASCT), melphalan and prednisone (MP) with thalidomide (MPT) or bortezomib (VMP) are standard first-line therapeutic options. Despite new treatment regimens incorporating bortezomib o...

  17. Chinese herbal medicine and prednisone increase proportion of ...

    African Journals Online (AJOL)

    Objective: This study investigated the effects of Chinese herbal medicine and prednisone onCD4+FoxP3+ T cells (Tregs) and Th17 cells in the MRL/lpr mouse model of systemic lupus erythematosus. Methods: MRL/lpr mice were treated with herbal medicine (yin-nourishing and heat-clearing therapy), prednisone, and a ...

  18. Organizer formation in Hydra is disrupted by thalidomide treatment.

    Science.gov (United States)

    Brooun, Maria; Manoukian, Armen; Shimizu, Hiroshi; Bode, Hans R; McNeill, Helen

    2013-06-01

    Thalidomide is a drug that is well known for its teratogenic properties in humans. Surprisingly, thalidomide does not have teratogenic effects on mouse development. We investigated the effect of thalidomide on patterning in hydra, an early metazoan with a very simple axial symmetry. Hydra develops asexually via Wnt-dependent organizer formation, leading to the budding of a new organism. We observe both induction and inhibition of organizer formation depending on cellular context. Interestingly, thalidomide treatment altered budding and the developing organizer, but had little effect on the adult. Expression of Hybra1, a marker of the organizer increased upon thalidomide treatment. However when the organizer is induced by ectopic activation of Wnt signaling via GSK3 inhibition, thalidomide suppresses induction. We show that inhibition of Wnt signaling is not mediated by induction of the BMP pathway. We show that thalidomide activity on organizer formation in hydra depends on the activity of casein kinase1 and the abundance of β-catenin. Finally, we find that interstitial cells, multipotent cells which give rise to nemoatocytes, neural, digestive and germline cells, are partially responsible for the inhibitory effect of thalidomide. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Thalidomide-induced Bradycardia in an Old Man

    Directory of Open Access Journals (Sweden)

    Ching-Hsueh Tseng

    2010-12-01

    Full Text Available We presented a case of an 82-year-old man who had classic Kaposi sarcoma. He took thalidomide 100 mg twice daily for 23 days, and then he felt light-headedness and visited our emergency department. The heartbeat changes from baseline 80 beats per minute before administration of thalidomide to 45 beats per minute. About 25–50% of patients using thalidomide had mild bradycardia, and only 1–3% with severe bradycardia needed the assistance of inotropic agent or device (transcutaneous cardiac pacing. Emergency physicians should keep in mind current and concurrent medications in bradycardiac patients who are presented to the emergency department. If patients need thalidomide treatment, avoiding concomitant usage of beta-blocker and doing regular electrocardiogram monitoring are mandatory. In this case, atropine helps to improve the dizziness resulting from thalidomide-related bradycardia.

  20. Thalidomide protects mice against LPS-induced shock

    Directory of Open Access Journals (Sweden)

    Moreira A.L.

    1997-01-01

    Full Text Available Thalidomide has been shown to selectively inhibit TNF-a production in vitro by lipopolysaccharide (LPS-stimulated monocytes. TNF-a has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-a and other cytokines and on animal survival. After injection of 100-350 µg LPS into mice, cytokines including TNF-a, IL-6, IL-10, IL-1ß, GM-CSF and IFN-g were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-a levels were reduced by 93%, in a dose-dependent manner, and TNF-a mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ß or IFN-g. The LD50 of LPS in this model was increased by thalidomide pre-treatment from 150 µg to 300 µg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death

  1. A Novel Green Synthesis of Thalidomide and Analogs

    Directory of Open Access Journals (Sweden)

    Ellis Benjamin

    2017-01-01

    Full Text Available Thalidomide and its derivatives are currently under investigation for their antiangiogenic, immunomodulative, and anticancer properties. Current methods used to synthesize these compounds involve multiple steps and extensive workup procedures. Described herein is an efficient microwave irradiation green synthesis method that allows preparation of thalidomide and its analogs in a one-pot multicomponent synthesis system. The multicomponent synthesis system developed involves an array of cyclic anhydrides, glutamic acid, and ammonium chloride in the presence of catalytic amounts of 4-N,N-dimethylaminopyridine (DMAP to produce thalidomide and structurally related compounds within minutes in good isolated yields.

  2. The Clinical Development of Thalidomide as an Angiogenesis Inhibitor Therapy for Prostate Cancer

    National Research Council Canada - National Science Library

    Dlaiani, Danai

    2002-01-01

    ...), assessed by wound healing and peri-operative bleeding; 2) Efficacy of neo-adjuvant thalidomide treatment, as measured by the rate of tumor reduction I PSA decline while on thalidomide therapy; 3...

  3. Mechanism of melphalan crosslink enhancement by misonidazole pretreatment

    International Nuclear Information System (INIS)

    Taylor, Y.C.; Sawyer, J.M.; Hsu, B.; Brown, J.M.

    1984-01-01

    Sensitization of Chinese hamster ovary cells to melphalan (L-PAM) toxicity by prior treatment with misonidazole is associated with increased levels of DNA crosslinks believed to be the critical lesion for bifunctional alkylating agent toxicity. Enhanced L-PAM crosslinking of DNA could occur by a variety of mechanisms in MISO-pretreated cells including: (1) increased transport or binding of L-PAM, (2) decreased repair of L-PAM monoadducts which would allow more time for their conversion to crosslinks, (3) decreased crosslink repair (unhooking of one arm), or (4) chemical modification of the DNA structure, presumably by bound MISO derivatives, such that crosslink formation is facilitated. Previous studies have eliminated mechanisms (1) and (3). Mechanism (4) was investigated by following MISO-pretreatments of whole cells with L-PAM treatments of the isolated DNA from these cells. Treatment of bare DNA with L-PAM modeled very well the crosslinking behavior in whole cells although it was somewhat more efficient. In the presence of double stranded DNA and absence of repair systems during and after the L-PAM exposure, it was determined that MISO-pretreatments did not increase the crosslinking efficiency of L-PAM

  4. Effect of thalidomide on chemokine production by human microglia.

    Science.gov (United States)

    Lokensgard, J R; Hu, S; van Fenema, E M; Sheng, W S; Peterson, P K

    2000-09-01

    Thalidomide, a psychoactive drug that readily crosses the blood-brain barrier, has been shown to possess immunomodulatory attributes, including the inhibition of cytokine production by monocytes and microglia. In this study, we investigated the effect of thalidomide on chemokine production by human microglial cells. Microglial cells were stimulated with lipopolysaccharide, a key cell-wall component of gram-negative bacteria responsible for meningitis, and production of chemokines (regulated upon activation normally T cell expressed and secreted [RANTES], monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1beta, and interleukin [IL]-8) was examined by ELISA. Thalidomide treatment was found to cause potent and selective inhibition of IL-8 production in a dose-responsive manner. This inhibition was associated with decreased intracellular IL-8 staining as well as reduced transcription of IL-8 mRNA. In addition, thalidomide treatment of lipopolysaccharide-stimulated microglia inhibited the activation of protein NF-kappaB, a transcription factor known to be important for IL-8 production. These results suggest thalidomide could have a therapeutic role in acute bacterial meningitis through inhibition of IL-8-mediated neutrophil chemotaxis.

  5. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takaharu; Kato, Koji [Nagoya First Red Cross Hospital (Japan). Children' s Medical Center; Hanada, Ryoji [Saitama Children' s Medical Center, Iwatsuki (Japan)] [and others

    2002-07-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 {mu}g/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  6. Hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Matsuyama, Takaharu; Kato, Koji

    2002-01-01

    A multicenter comparative study was carried out to investigate the efficacy and safety of hematopoietic stem cell transplantation with conditioning regimens containing melphalan in pediatric patients with acute lymphoblastic leukemia. One hundred twenty three patients at a variety of remission stages were eligible for study participation. Eighty-nine were transplanted with allogeneic grafts and 34 patients with autologous grafts (23 cases with bone marrow and 11 cases with peripheral blood stem cells). Conditioning regimens used were as follows: melphalan and busulfan for 40 patients, melphalan, busulfan and TBI for 44 patients, other regimens for 39 patients. To accelerate engraftment G-CSF (lenograstim) was administered as a 1-hour or 24-hour drip infusion daily at 5 μg/kg from day 5 until hematological recovery. The five year disease free survival (DFS) was 63% for 42 patients at CR1, 41% for 41 patients at CR2 and 33% for 40 patients at other stages. There was no significant difference in the DFS between allogeneic-transplantation and autologous-transplantation in all disease stages. In patients at remission stage for CR1 and CR2, the 5-year DFS by conditioning regimen was 63% for regimen with melphalan and busulfan, 54% for regimen with melphalan, busulfan and TBI and 54% for regimens with melphalan and TBI. There was no significant difference in the DFS between the groups. Serious complications such as renal failure were observed in 11%, veno-occlusive disease in 9%, and interstitial pneumonia in 9%. The most dominating cause of death was relapse in the disease (48% of deaths) which was most commonly observed in autologous transplantation. Contrary to that, treatment related toxic death was the most frequent cause of deaths in allogeneic-transplantation. (author)

  7. MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: a pilot study.

    Science.gov (United States)

    Guadagni, Stefano; Fiorentini, Giammaria; Clementi, Marco; Palumbo, Giancarlo; Masedu, Francesco; Deraco, Marcello; De Manzoni, Giovanni; Chiominto, Alessandro; Valenti, Marco; Pellegrini, Cristina

    2017-10-01

    Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan-Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.

  8. Thalidomide and its analogues in the treatment of Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Latif Tahir

    2012-09-01

    Full Text Available Abstract Multiple myeloma is an incurable malignant disorder of mature B-cells that predominantly affects the elderly. The immunomodulatory drug (IMiD thalidomide and its newer analogs demonstrate increased antitumor activity, and have had a positive impact on the natural history of multiple myeloma. Recent advances in the clinical application of these agents and in our understanding of their mechanism of action, and toxicity have made safer and smarter use of these drugs possible. This review discusses the available information regarding mechanisms of action, toxicity and clinical results on thalidomide, lenalidomide and pomalidomide in the therapy of multiple myeloma.

  9. Pengaruh Prednison terhadap Perbaikan Pendengaran Penderita Lupus Eritematosus

    Directory of Open Access Journals (Sweden)

    Wijana

    2016-06-01

    Full Text Available Systemic lupus erythematosus (SLE is a chronic, multi-system, autoimmune disorder characterized by the production of autoantibodies and immune complexes deposition in tissue. Clinical manifestations may include skin, mucosa, joints, blood, heart, lungs, kidneys, central nervous system (CNS, immune system, and ears. SLE Iin the ears can caused sensorineural hearing loss, tinnitus, and vertigo. This hearing disorder is commonly bilateral and has high frequencies. Prednisone is an oral corticosteroid with glucocorticoid and mineralocorticoid effects. Glucocorticoids have anti-inflammatory and immunosuppressive effects. The aim of this study was to evaluate the effect of prednisone in improving the degree of hearing loss in patients with SLE. This study was conducted in from March–May 2013, at tThe Hearing and Speech Disorder Clinic of Ear Nose Throat-Head and Neck Surgery, Dr. Hasan Sadikin Hospital Bandung, using quasi-experimental method with pre-post design in which the results were statistically calculated using Rank Spearman test. This study involved 28 subjects who had been diagnosed for SLE. Anamnesis, physical examination, and laboratory test were performed, followed by pure tone audiometry, tympanometry, and distortion product optoacoustic emissions (DPOAE. Subjects were given prednisone 1 mg/kgBW/day with a maximum dose of 6o mg/day. Re-evaluation was performed after 4 weeksof treatment. Before treatment, 26 subjects had mild hearing loss and 2 subjects had symmetric moderate hearing loss at high frequencies symmetrically. After therapy, 24 subjects became normal and 4 subjects still had hearing loss (Rs=0.734, p<0.01. In conclusion, prednisone can improve hearing status of SLE patients.

  10. [Immunological mechanism of prednisone in the treatment of infantile spasm].

    Science.gov (United States)

    Chen, Hui; Zhong, Jian-Min; Yi, Zhao-Shi; Zha, Jian; Chen, Yong; Cai, Lan-Yun

    2017-10-01

    To investigate the immunological mechanism of prednisone in the treatment of infantile spasm (IS) by evaluating the immune function of IS children before and after treatment. Thirty children with IS were enrolled as IS group. Thirty healthy infants who underwent physical examination were enrolled as healthy control group. Fasting venous blood was collected for both groups before and after prednisone treatment. Chemiluminescence was used to measure serum levels of interleukin-1B (IL-1B), interleukin-2R (IL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α). Immunoturbidimetric assay was used to measure serum levels of immunoglobulin A (IgA), immunoglobulin M (IgM), and immunoglobulin G (IgG). Flow cytometry was used to measure the percentages of T lymphocyte subsets (CD3 + , CD4 + , and CD8 + ). The clinical outcome and electroencephalographic findings were evaluated for all IS children after prednisone treatment. The IS group had significantly higher serum levels of IL-2R, IL-8, and TNF-α than the healthy control group before treatment (Ptreatment, the IS group had significant reductions in the numbers of daily ictal clusters and total daily seizures, significant improvement in developmental quotient (P<0.05), and significant reductions in serum levels of IL-2R, L-8, and TNF-α, the percentage of CD4 + T lymphocytes, and CD4 + /CD8 + ratio (P<0.05), as well as a significant increase in the percentage of CD8 + T lymphocytes (P<0.05). IS children have immune dysfunction. Prednisone can control seizures in IS children, possibly by regulating and improving immune dysfunction.

  11. High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis

    Directory of Open Access Journals (Sweden)

    Hong-xia Xue

    2015-01-01

    Full Text Available Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

  12. The interaction between oral melphalan and gastric antisecretory drugs: Impact on clinical efficacy and toxicity.

    Science.gov (United States)

    Kitazawa, Fumiaki; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Fuchida, Shin-Ichi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2016-02-01

    The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle-dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co-administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan.

  13. Synergistic antitumor activity of histamine plus melphalan in isolated limb perfusion: preclinical studies.

    NARCIS (Netherlands)

    F. Brunstein (Flavia); S. Hoving (Saske); A.L.B. Seynhaeve (Ann); S.T. van Tiel (Sandra); G. Guetens (Gunther); E.A. de Bruijn (Ernst); A.M.M. Eggermont (Alexander); T.L.M. ten Hagen (Timo)

    2004-01-01

    textabstractBACKGROUND: We have previously shown how tumor response of isolated limb perfusion (ILP) with melphalan was improved when tumor necrosis factor alpha (TNF-alpha) was added. Taking into account that other vasoactive drugs could also improve tumor response to ILP, we

  14. Continuous lenalidomide treatment for newly diagnosed multiple myeloma

    DEFF Research Database (Denmark)

    Palumbo, Antonio; Hajek, Roman; Delforge, Michel

    2012-01-01

    Lenalidomide has tumoricidal and immunomodulatory activity against multiple myeloma. This double-blind, multicenter, randomized study compared melphalan-prednisone-lenalidomide induction followed by lenalidomide maintenance (MPR-R) with melphalan-prednisone-lenalidomide (MPR) or melphalan-prednis...

  15. Treatment of Light Chain Deposition Disease Using Bortezomib-Based Regimen Followed by Thalidomide-Based Regimen in a Saudi Male

    Directory of Open Access Journals (Sweden)

    Bappa Adamu

    2016-01-01

    Full Text Available Light chain deposition disease (LCDD is a rare illness with, as yet, no clear evidence-based guidelines for its treatment. To the best of our knowledge, LCDD has not been previously reported from Saudi Arabia. We present in this report, a 38-year-old Saudi male who presented with clinical features suggestive of hypertensive nephropathy but kidney biopsy later revealed the diagnosis of LCDD. His serum creatinine at presentation was 297 μmol/L which came down to 194 μmol/L on treatment with Bortezomib, Cyclophosphamide and Dexamethasone. His 24-hour protein excretion at presentation was 6 g/L which also came down to less than 1 g/day. He was later placed on Cyclophosphamide, Thalidomide, and Dexamethasone regimen because of persistent high titres of serum free light chains. He went into remission with undetectable serum free light chains and remained so for three years at the time of writing this report. We conclude that LCDD, though rare, does occur in Saudi population. The treatment of LCDD is challenging but the use of Bortezomib, a proteosome inhibitor, is promising. However, suboptimal response may require further treatment with other therapeutic options such as chemotherapy with alkylating agents or high-dose Melphalan with autologous stem cell transplant.

  16. Prednison provokes serum and vasoactive substances in a mice model of immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Ling Zhang

    2016-09-01

    Conclusion: In this study, the β-EP, VIP, 5-HT and NE contents in ITP mice injected with GP-APS were changed by prednison. It shows that prednison as the first-line therapy for ITP with effective hemostasis function is likely to increasing the contents of VIP and 5-HT. These results suggest the therapeutic value of prednison for the treatment of ITP.

  17. Historical perspective and advances in the treatment of multiple myeloma

    Directory of Open Access Journals (Sweden)

    Amir Harandi

    2011-12-01

    Full Text Available Corticosteroids and melphalan were used for decades to treat multiple myeloma. Combination chemotherapy has been extensively studied with similar overall survival rates to melphalan and prednisone. In the last decade, the development of new agents has progressed significantly. Thalidomide and its newer derivatives lenalidomide, bortezomib, and pegylated liposomal doxorubicin have drastically revolutionized treatment approaches. As a result, numerous clinical trials have yielded exciting treatment strategies resulting in therapeutic advances, and improved responses and overall survival of patients. This review summarizes the international uniform response criteria for multiple myeloma and gives a historical perspective on previous therapies with updates on the newest available treatments.

  18. Thalidomide for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy

    Directory of Open Access Journals (Sweden)

    Geng Song

    2017-03-01

    Full Text Available Background Antiemetic guidelines recommend co-administration of agents to maximize the prevention of chemotherapyinduced nausea and vomiting (CINV, however, the control of delayed CINV is still not satisfactory. The purpose of this study was to evaluate the effectiveness and safety of thalidomide in the prevention of CINV. Methods Of 89 patients enrolled, 83 chemotherapy-naïve patients receiving highly emetogenic chemotherapy (cisplatin 70mg/m2 were randomized into two groups: standard therapy group (ondansetron on day 1, metoclopramide and dexamethasone on days one to five and thalidomide group (in addition to standard emesis prevention, patients received oral 100mg thalidomide on days one to five. Patients recorded nausea and vomiting episodes in a diary. The primary end point was the efficacy of thalidomide in controlling vomiting and nausea on days one to five post cisplatin, and the secondary end point was the safety of the thalidomide. Results No significant differences of complete response rates (no emesis, no use of rescue therapy and no nausea were observed between the two groups, while the percentages of patients with complete response of delayed vomiting on day four and day five were higher in the thalidomide group, furthermore, the complete response rate of delayed nausea for thalidomide group and standard therapy group showed significant differences. Thalidomide group showed a similar safety profile as standard emesis prevention group. Conclusion Addition of thalidomide was generally well tolerated and improved prevention of CINV in patients receiving cisplatinbased chemotherapy to some degree, especially for delayed nausea.

  19. Emerging role of thalidomide in the treatment of gastrointestinal bleeding.

    Science.gov (United States)

    McFarlane, Michael; O'Flynn, Lauren; Ventre, Rachel; Disney, Benjamin R

    2018-04-01

    Thalidomide was initially synthesised in 1954 and marketed as a sedative and antiemetic for morning sickness. It was withdrawn in 1961 due to the realisation that it was teratogenic with over 10 000 children born with congenital abnormalities. Since then it has been used for treatment of dermatological and oncological conditions, including myeloma. In 1994, it was found to have a potent antiangiogenic effect via downregulation of vascular endothelial growth factor (VEGF). This has led to its use in gastrointestinal bleeding, as vascular abnormalities such as angiodysplasia have been found to have elevated VEGF levels. This article will review the current evidence of the use of thalidomide in bleeding associated with gastrointestinal vascular malformations, including angiodysplasia, gastric cancer and radiation-induced proctitis.

  20. Synergistic cytotoxicity against human tumor cell lines by oncolytic adenovirus dl1520 (ONYX-015) and melphalan.

    Science.gov (United States)

    Ferguson, Peter J; Sykelyk, Alexander; Figueredo, Rene; Koropatnick, James

    2016-01-01

    In light of the need for more selective anticancer therapy, much work has been directed at developing compounds or biological agents that target functions specific to cancer cells. To this end, numerous viruses have been engineered to exploit the dependence of cancer cells on particular anomalies that contribute to their rogue proliferative activity, such as dysfunctional p53, overactive mitogenic signaling, or a defective interferon response. The oncolytic human adenovirus dl1520 (ONYX-015) was engineered to propagate specifically in p53-deficient tumors, which comprise over half of all tumors. Based on successes in clinical trials, the full potential of dl1520 and other oncolytic viruses may be even better realized by using them in combination with conventional chemotherapy drugs. As a model system in which to test this potential, representative cell lines from 2 common cancer types, oral squamous cell carcinoma (HN-5a) and colon adenocarcinoma (HT-29), were chosen, as well as platinum-drug-resistant variants of each. Following preliminary screening of virus and drug combinations, dl1520 and melphalan were found to synergistically inhibit proliferation of all the cancer cell lines. Melphalan pretreatment or cotreatment with dl1520 enhanced inhibition of proliferation by dl1520 by up to 60% and increased apoptosis by up to 25%. The tight-junction protein CAR (coxsackie and adenovirus receptor), via which adenovirus enters cells, was not upregulated by treatment with melphalan, suggesting that other mechanisms contribute to synergy. The synergy between melphalan and dl1520 suggests that tumor-selective cell killing by oncolytic viruses may be augmented by combining with cytotoxic drugs.

  1. Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica

    DEFF Research Database (Denmark)

    Lund, B; Egsmose, C; Jørgensen, S

    1987-01-01

    following prednisone treatment. Subsequently, in a similar regimen, prednisone was compared with deflazacort at a weight ratio of 1:1.2 in 10 patients, 1:1.5 in another 10 patients, and 1:1.8 in still another 10 patients for purposes of dose titration. Again, significant rises were seen in ESR, plasma...

  2. Efficacy and safety of modified-release prednisone in patients with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Krasselt M

    2016-03-01

    Full Text Available Marco Krasselt, Christoph Baerwald Rheumatology Unit, Clinic for Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University of Leipzig, Leipzig, Germany Abstract: The introduction of modified-release (MR prednisone adds a drug with encouraging potential to the armamentarium of the rheumatologist. In particular, for patients experiencing a reduced quality of life due to prolonged morning stiffness, it is a promising therapeutic approach. Two clinical trials and one open-label observational study investigated the effectiveness of MR prednisone in reducing rheumatoid arthritis-related morning stiffness for both new and current users of corticosteroids. The efficacy and safety of MR prednisone use in rheumatoid arthritis patients are reviewed in this article. This includes pivotal trials as well as pathophysiological considerations and clinical implications. Keywords: modified-release prednisone, rheumatoid arthritis, efficacy, chronotherapy, HPA axis, side effects, low-dose prednisone 

  3. Generation of a predictive melphalan resistance index by drug screen of B-cell cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Martin Boegsted

    Full Text Available BACKGROUND: Recent reports indicate that in vitro drug screens combined with gene expression profiles (GEP of cancer cell lines may generate informative signatures predicting the clinical outcome of chemotherapy. In multiple myeloma (MM a range of new drugs have been introduced and now challenge conventional therapy including high dose melphalan. Consequently, the generation of predictive signatures for response to melphalan may have a clinical impact. The hypothesis is that melphalan screens and GEPs of B-cell cancer cell lines combined with multivariate statistics may provide predictive clinical information. MATERIALS AND METHODS: Microarray based GEPs and a melphalan growth inhibition screen of 59 cancer cell lines were downloaded from the National Cancer Institute database. Equivalent data were generated for 18 B-cell cancer cell lines. Linear discriminant analyses (LDA, sparse partial least squares (SPLS and pairwise comparisons of cell line data were used to build resistance signatures from both cell line panels. A melphalan resistance index was defined and estimated for each MM patient in a publicly available clinical data set and evaluated retrospectively by Cox proportional hazards and Kaplan-Meier survival analysis. PRINCIPAL FINDINGS: Both cell line panels performed well with respect to internal validation of the SPLS approach but only the B-cell panel was able to predict a significantly higher risk of relapse and death with increasing resistance index in the clinical data sets. The most sensitive and resistant cell lines, MOLP-2 and RPMI-8226 LR5, respectively, had high leverage, which suggests their differentially expressed genes to possess important predictive value. CONCLUSION: The present study presents a melphalan resistance index generated by analysis of a B-cell panel of cancer cell lines. However, the resistance index needs to be functionally validated and correlated to known MM biomarkers in independent data sets in order to

  4. Thalidomide increases in vitro sensitivity of childhood acute lymphoblastic leukemia cells to prednisolone and cytarabine.

    Science.gov (United States)

    Czyzewski, Krzysztof; Zaborowska, Agnieszka; Styczyński, Jan

    2006-01-01

    Thalidomide is a derivative of glutamic acid with anti-angiogenic, anti-inflammatory, immunomodulatory and anti-cancer properties that was found to inhibit the production of tumor necrosis factor alpha in vitro, stimulate reactive oxygen species production, and inhibit vascular endothelial growth factor receptor in acute leukemias. The purpose of this study was to determine the in vitro activity of thalidomide as a single agent and in combination with prednisolone or cytarabine in childhood acute lymphoblastic leukemia (ALL). Bone marrow samples of 40 childhood ALL patients, normal lymphocytes of 9 healthy adults, and 3 lymphoid cell lines were evaluated for cytotoxicity of thalidomide (alone and in combination with prednisolone and cytarabine) using the MTT assay. Cell cycle analysis was performed by flow cytometry. Thalidomide as a single agent had weak antileukemic activity to the childhood ALL samples. However, in the presence of thalidomide the cytotoxicities of prednisolone and cytarabine were increased 3.3-fold (p<0.001) and 2.7-fold (p=0.002), respectively. Thalidomide increased apoptosis in lymphoblasts and modulated the cell-cycle arrest caused by prednisolone, but not that by cytarabine, in childhood ALL samples. Thalidomide increases in vitro the sensitivity of childhood ALL cells to prednisolone and cytarabine.

  5. Prednisone and vardenafil hydrochloride for refractory levamisole-induced vasculitis.

    Science.gov (United States)

    Mandrell, Joshua; Kranc, Christina L

    2016-08-01

    Levamisole is an immunomodulatory drug that was previously used to treat various medical conditions, including parasitic infections, nephrotic syndrome, and colorectal cancer. Over the last few years, increasing amounts of levamisole have been used as an adulterant in cocaine. Levamisole-cut cocaine has become a concern because it is known to cause a necrotizing purpuric rash, autoantibody production, and life-threatening leukopenia. Mixed histologic findings of vasculitis and thrombosis are characteristic of levamisole-induced purpura. The recommended management of levamisole-induced vasculitis currently involves withdrawal of the culprit along with supportive treatment. We describe a patient with levamisole-induced vasculitis who continued to develop skin lesions despite self-reported cocaine cessation. Complete resolution of cutaneous disease occurred with the addition of oral prednisone and vardenafil hydrochloride, suggesting the possibility of a new treatment option in patients with refractory disease. In addition, we review the clinical presentation, disease course, diagnostic approach, laboratory findings, histology, and management of levamisole-induced vasculitis. The harmful effects of levamisole-cut cocaine are serious enough that public alerts have been issued to increase awareness. Clinicians should consider the possibility of levamisole exposure in cocaine users presenting with any combination of fever, neutropenia, and necrotic skin lesions, especially in acral areas including the ears.

  6. The alkylating prodrug J1 can be activated by aminopeptidase N, leading to a possible target directed release of melphalan

    DEFF Research Database (Denmark)

    Wickström, Malin; Viktorsson, Kristina; Lundholm, Lovisa

    2010-01-01

    The alkylating prodrug of melphalan, J1 (melphalanyl-l-p-fluorophenylalanyl ethyl ester) is currently in early clinical trials. Preclinical studies have shown that J1-mediated cytotoxicity is dependent on hydrolytic activity of tumor cells. In this report we have analyzed potential peptidases...... and apoptotic signaling. In conclusion, this study demonstrates a role of APN in the activation of the melphalan prodrug J1 and subsequently, its cytotoxicity. Given that APN is shown to be overexpressed in several solid tumors our data suggest that J1 may be activated in a tumor selective manner....

  7. PREDNISONE THERAPY SAFETY FOR TREATMENT OF PATIENTS WITH MIX OF TUBERCULOSIS AND HIV-INFECTION

    Directory of Open Access Journals (Sweden)

    G. V. Maksimov

    2013-01-01

    Full Text Available Abstract. The study of prednisone safety for treatment of TB mixed with HIV-infection has been conducted. Two groups of patients were compared. The first group was consisted of 88 patients who were treated by prednisone and standard tuberculosis therapy, the second group of patients presented by 45 patients received only tuberculosis medicines. It was demonstrated that in case of prednisone using (1st group the number of CD4 limphocytes increased, intoxication symptoms disappeared fast and recovery process accelerated. Increasing of cases with unfavorable course of TB and HIV-infection in patients of first group was not registered in compare with the second group. Thus, using of prednisone therapy to treat TB mixed with HIV-infection was safe, not lead to unfavorable course of TB or HIV-infection. Such kind of treatment especially important for patients with exudative reactions.

  8. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans.

    Science.gov (United States)

    Horber, F F; Marsh, H M; Haymond, M W

    1991-01-01

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation [( 14C]leucine) increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Differential effects of prednisone and growth hormone on fuel metabolism and insulin antagonism in humans

    Energy Technology Data Exchange (ETDEWEB)

    Horber, F.F.; Marsh, H.M.; Haymond, M.W. (Mayo Clinic, Rochester, MN (USA))

    1991-01-01

    Human growth hormone (hGH) and prednisone cause insulin resistance and glucose intolerance. However, it is unknown whether hGH and prednisone antagonize insulin action on protein, fat, and carbohydrate metabolism by a common or independent mechanism. Therefore, protein, fat, and carbohydrate metabolism was assessed simultaneously in four groups of eight subjects each after 7 days of placebo, recombinant DNA hGH (rhGH; 0.1 mg.kg-1.day-1), prednisone (0.8 mg.kg-1.day-1), or rhGH and prednisone administration after an 18-h fast and during gut infusion of glucose and amino acids (fed state). Fasting plasma glucose concentrations were similar during placebo and rhGH but elevated (P less than 0.001) during combined treatment, whereas plasma insulin concentrations were higher (237 +/- 57 pmol/ml, P less than 0.001) during combined than during placebo, rhGH, or prednisone treatment (34, 52, and 91 pM, respectively). In the fed state, plasma glucose concentrations were elevated only during combined treatment (11.3 +/- 2.1 mM, P less than 0.001). Plasma insulin concentrations were elevated during therapy with prednisone alone and rhGH alone (667 +/- 72 and 564 +/- 65 pmol/ml, respectively, P less than 0.001) compared with placebo (226 +/- 44 pmol/ml) but lower than with the combined rhGH and prednisone treatment (1249 +/- 54 pmol/ml, P less than 0.01). Protein oxidation {sup 14}C leucine increased (P less than 0.001) with prednisone therapy, decreased (P less than 0.001) with rhGH treatment, and was normal during the combined treatment.

  10. Tacrolimus Improves Symptoms of Children With Myasthenia Gravis Refractory to Prednisone.

    Science.gov (United States)

    Liu, Chanchan; Gui, Mengcui; Cao, Yayun; Lin, Jing; Li, Yue; Ji, Suqiong; Bu, Bitao

    2017-12-01

    Myasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. Children with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. Fourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P gravis. Randomized clinical trials are needed to confirm the observation. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Synthesis and evaluation of thalidomide and phthalimide esters as antitumor agents

    DEFF Research Database (Denmark)

    Zahran, Magdy A H; Abdin, Yasmin G.; Osman, Amany M A

    2014-01-01

    A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N-chloromethylthalidomide, N-chloromethylphthalimide, and N-(2-bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized...

  12. High-dose melphalan total body irradiation with bone marrow transplantation for refractory malignancies

    International Nuclear Information System (INIS)

    Spitzer, G.; Jagannath, S.; Dicke, K.A.; Nebraska Univ., Omaha

    1986-01-01

    Nineteen adult patients with relapsed disease, 15 of them having hematologic malignancies, were treated with high-dose melphalan (100 mg/m 2 -140 mg/m 2 ) divided over 2 consecutive days followed by a rest period of 4 days before receiving total body irradiation, 850 rad administered in five fractionated doses over 3 days. Subsequently 11 patients received autologous, seven allogeneic and one syngeneic, bone marrow transplantation. All patients had severe myelosuppression and the major extramedullary toxicity was mucositis. There were three early deaths, two related to septicemia and one to graft-versus-host disease with associated cytomegalovirus pneumonitis. All patients were heavily pretreated, and 16 were demonstrating progressive disease on alternative salvage therapies at the time of bone marrow transplantation. Two of the 16 evaluable patients (12.5%) achieved complete remissions, and 10 (63%) achieved partial remissions for a total response rate of 75%. One patient is a long-term disease-free survivor (over 1 yr). The combination of melphalan, an alternative alkylating agent to cyclophosphamide and total body irradiation are associated with moderate gastrointestinal toxicity in heavily pretreated adult patients. (author)

  13. [Thalidomide: Drug of horror and last resort. A review. Part 1: Origin, molecular structure and first pattern of use.].

    Science.gov (United States)

    Jóhannesson, Thornorkell

    2003-10-01

    Thalidomide was originally a hypnotic, sedative and anxiolytic drug that was first used in 1955. It was considered to have little toxicity and have smooth activity. Thalidomide was in fact poorly studied both in animals and for therapeutic purposes. It was nevertheless agressively advertised, and inter alia for use in pregnancy, and accordingly it was a much used drug. During the year 1961 it became evident that intake of thalidomide in therapeutic doses could result in severe peripheral neuritis and, when taken early in pregnancy, in horrendous damage to the fetus. Thalidomide was thus shortly afterwards generally removed from the market and its use prohibited. Nevertheless, interest rose a few years later to use thalidomide on other indications than before. This is the topic of Part 2 of this review as well as discussion of studies pertinent to the mechanisms of action of thalidomide.

  14. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    International Nuclear Information System (INIS)

    Gao, Xiugong; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-01-01

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds

  15. Thalidomide induced early gene expression perturbations indicative of human embryopathy in mouse embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Xiugong, E-mail: xiugong.gao@fda.hhs.gov; Sprando, Robert L.; Yourick, Jeffrey J.

    2015-08-15

    Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72 h after exposure to 0.25 mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment. - Highlights: • Studied genomic changes in mouse embryonic stem cells upon thalidomide exposure • Identified gene expression changes that may represent thalidomide embryotoxicity • The toxicogenomic changes coincide well with known thalidomide clinical outcomes. • The mouse embryonic stem cell model is suitable for developmental toxicity testing. • The model has the potential for high-throughput screening of a multitude of compounds.

  16. Thalidomide Induces Limb Anomalies by PTEN Stabilization, Akt Suppression, and Stimulation of Caspase-Dependent Cell Death▿

    OpenAIRE

    Knobloch, Jürgen; Schmitz, Ingo; Götz, Katrin; Schulze-Osthoff, Klaus; Rüther, Ulrich

    2007-01-01

    Thalidomide, a drug used for the treatment of multiple myeloma and inflammatory diseases, is also a teratogen that causes birth defects, such as limb truncations and microphthalmia, in humans. Thalidomide-induced limb truncations result from increased cell death during embryonic limb development and consequential disturbance of limb outgrowth. Here we demonstrate in primary human embryonic cells and in the chicken embryo that thalidomide-induced signaling through bone morphogenetic proteins (...

  17. Thalidomide Ameliorates Inflammation and Vascular Injury but Aggravates Tubular Damage in the Irradiated Mouse Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Scharpfenecker, Marion, E-mail: m.scharpfenecker@nki.nl [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Floot, Ben [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands); Russell, Nicola S. [Division of Radiotherapy, The Netherlands Cancer Institute, Amsterdam (Netherlands); Coppes, Rob P. [Departments of Radiation Oncology and Cell Biology, University Medical Centre Groningen, University of Groningen, Groningen (Netherlands); Stewart, Fiona A. [Division of Biological Stress Response, The Netherlands Cancer Institute, Amsterdam (Netherlands)

    2014-07-01

    Purpose: The late side effects of kidney irradiation include vascular damage and fibrosis, which are promoted by an irradiation-induced inflammatory response. We therefore treated kidney-irradiated mice with the anti-inflammatory and angiogenesis-modulating drug thalidomide in an attempt to prevent the development of late normal tissue damage and radiation nephropathy in the mouse kidney. Methods and Materials: Kidneys of C57Bl/6 mice were irradiated with a single dose of 14 Gy. Starting from week 16 after irradiation, the mice were fed with thalidomide-containing chow (100 mg/kg body weight/day). Gene expression and kidney histology were analyzed at 40 weeks and blood samples at 10, 20, 30, and 40 weeks after irradiation. Results: Thalidomide improved the vascular structure and vessel perfusion after irradiation, associated with a normalization of pericyte coverage. The drug also reduced infiltration of inflammatory cells but could not suppress the development of fibrosis. Irradiation-induced changes in hematocrit and blood urea nitrogen levels were not rescued by thalidomide. Moreover, thalidomide worsened tubular damage after irradiation and also negatively affected basal tubular function. Conclusions: Thalidomide improved the inflammatory and vascular side effects of kidney irradiation but could not reverse tubular toxicity, which probably prevented preservation of kidney function.

  18. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70-80% initial...

  19. Improvement Thresholds for Morning Stiffness Duration in Patients Receiving Delayed- Versus Immediate-Release Prednisone for Rheumatoid Arthritis.

    Science.gov (United States)

    Buttgereit, Frank; Kent, Jeffrey D; Holt, Robert J; Grahn, Amy Y; Rice, Patricia; Alten, Rieke; Yazici, Yusuf

    2015-07-01

    Morning stiffness, a common patient reported symptom in rheumatoid arthritis, is associated with an increase in early morning inflammatory cytokines and significant disability. Little is known about categorical morning stiffness responses to glucocorticoid use in rheumatoid arthritis patients. Chronic pain threshold models have indicated previously that response rates of 15% to 30% indicate minimally important relief, 40% to 50% indicate substantial pain relief, and greater than 70% represents extensive pain relief. The objective of the present analysis was to assess differences in the percentages of patients achieving 25%(minimally important change), 50% (substantial change), and 75% (extensive change) reduction in the duration of patient-reported morning stiffness between patients receiving DR- and IR-prednisone in the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) trial. The CAPRA-1 trial was a 12-week, double-blind study followed by an additional 9-month open-label extension. Patients in the CAPRA-1 trial were randomized to IR-prednisone in the morning or DR-prednisone at bedtime in addition to stable disease modifying antirheumatic drug therapy. After the double-blind phase, patients randomized to IR-prednisone (N =110) were switched to DR-prednisone and followed at 3, 6, and 9 months in an open-label extension phase. Patients originally randomized to DR-prednisone (N = 97) continued that therapy in the open-label extension. Patient morning stiffness diary entries from 4 weeks before and 4 weeks after each scheduled visit were analyzed over 1 year for threshold response. The number of patients reaching threshold response (25%, 50%, and 75% improvement) and time to morning stiffness response were examined. The DR-prednisone arm had significantly more responders in all three morning stiffness threshold response categories at the end of the double-blind period compared with IR-prednisone (p ≤ 0.05). Patients who switched from IR- to DR-prednisone

  20. The Curious Case of Thalidomide and the Absent Eugenic Clause in Canada's Amended Abortion Law of 1969.

    Science.gov (United States)

    Chisholm, Christine

    This essay traces the role of the drug thalidomide in the reform of Canadian abortion law during the late 1960s. Like elsewhere in the British Commonwealth, discussion of the "thalidomide disaster" of the early 1960s intensified leading up to the debates that culminated in the 1969 amendment to Canadian abortion law. Although thalidomide was a rallying point for advocates of eugenic abortion, a majority of Canadian MPs, unlike their British and Commonwealth counterparts, rejected this argument. Widespread public and political considerations of the thalidomide tragedy were thus unable to inspire support for a eugenic clause in Canada's new abortion law, in spite of the nation's infamous eugenic past.

  1. Elucidation of the pharmacokinetics of prednisone and prednisolone: elimination and the effect of estrogen

    International Nuclear Information System (INIS)

    Gustavson, L.E.

    1985-01-01

    Several aspects of the pharmacokinetics of the interconvertible glucocorticoids prednisone and prednisolone have been studied. The pharmacokinetics of prednisolone were examined in postmenopausal women taking conjugated estrogens and age-matched control women. The subjects received iv bolus doses of 0.14 and 0.55 mg/kg prednisolone. Expected increases in clearance and volume of distribution with increasing dose were observed for total prednisolone in all subjects. At both doses, significant decreases in total and unbound prednisolone clearance were observed in the women taking estrogen compared to the controls. Volume of distribution was unchanged. The decreases in clearance are smaller than those observed in young women taking oral contraceptives indicating that factors other than estrogen administration may influence prednisolone clearance in oral contraceptive users. While the protein binding of prednisolone is well characterized, little is known about the protein binding of prednisone. Equilibrium dialysis employing [ 3 H]prednisone was used to study the binding of prednisone in human plasma containing endogenous hydrocortisone. Plasma was obtained from volunteers with normal and elevated transcortin binding capacities (CAP/sub T/). Prednisolone binding exhibits marked concentration dependence and sensitivity to CAP/sub T/. In contrast, prednisone binding is independent of concentration and CAP/sub T/

  2. Melphalan Injection

    Science.gov (United States)

    ... or vomiting blood or brown material that resembles coffee grounds.Keep all appointments with your doctor and the ... bloody vomit or vomited material that looks like coffee grounds unusual bruising or bleeding seizures decreased consciousness loss ...

  3. Management of isolated nonresectable liver metastases in colorectal cancer patients: a case-control study of isolated hepatic perfusion with melphalan versus systemic chemotherapy

    NARCIS (Netherlands)

    van Iersel, L. B. J.; Koopman, M.; van de Velde, C. J. H.; Mol, L.; van Persijn van Meerten, E. L.; Hartgrink, H. H.; Kuppen, P. J. K.; Vahrmeijer, A. L.; Nortier, J. W. R.; Tollenaar, R. A. E. M.; Punt, C.; Gelderblom, H.

    2010-01-01

    To compare the median overall survival of patients with isolated nonresectable liver metastases in comparable groups of patients treated with either isolated hepatic perfusion (IHP) with melphalan or systemic chemotherapy. Colorectal cancer patients with isolated liver metastases, who underwent IHP,

  4. High dose melphalan in the treatment of advanced neuroblastoma: results of a randomised trial (ENSG-1) by the European Neuroblastoma Study Group

    NARCIS (Netherlands)

    Pritchard, Jon; Cotterill, Simon J.; Germond, Shirley M.; Imeson, John; de Kraker, Jan; Jones, David R.

    2005-01-01

    High dose myeloablative chemotherapy ("megatherapy"), with haematopoietic stem cell support, is now widely used to consolidate response to induction chemotherapy in patients with advanced neuroblastoma. In this study (European Neuroblastoma Study Group, ENSG1), the value of melphalan myeloablative

  5. Ovarian irradiation and prednisone therapy following surgery and radiotherapy for carcinoma of the breast

    International Nuclear Information System (INIS)

    Meakin, J.W.; Allt, W.E.C.; Beale, F.A.

    1979-01-01

    Following mastectomy, patients with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy, ovarian irradiation (2000 rads in 5 days), or ovarian irradiation in the same dosage plus prednisone, 7.5 mg daily. A total of 705 patients received the randomly assigned treatment and were followed for up to 10 years. In premenopausal patients who received ovarian irradiation the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more ovarian irradiation plus prednisone therapy significantly delayed the recurrence of breast cancer (P=0.02) and prolonged survival (P=0.02); the survival expectancy of these patients was similar to that of the general population of the same age from the third year after the cancer operation. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. (author)

  6. Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Hakeam, Hakeam A; Arab, Amal; Azzam, Ayman; Alyahya, Zyad; Eldali, Abdelmoneim M; Amin, Tarek

    2018-02-10

    Cytopenia after hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported in non-comparative studies with various chemotherapeutic regimens. This study compared the incidence of leukopenia and thrombocytopenia in patients who underwent CRS/HIPEC and received melphalan or cisplatin plus mitomycin-c (CIS + MMC). This retrospective study included patients who underwent CRS/HIPEC at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from March 2011 to March 2017 and received melphalan 60 mg/m 2 or CIS 100 mg/m 2 combined with MMC 30 mg/m 2 . Incidences and severity of leukopenia, neutropenia, thrombocytopenia, and anemia were compared between groups. This study included 46 patients who received CIS + MMC and 35 patients who received melphalan. The leukopenia incidence was 25.7% in the melphalan group and 17.3% in the CIS + MMC group (P = 0.362), with one patient (2.8%) in the melphalan group developed grade V leukopenia. The number of days to leukocyte nadir was 32.8 days for CIS + MMC group compared to 9.8 days for melphalan group(P = 0.035). Thrombocytopenia occurred at a similar rate in the melphalan (60%) and CIS + MMC (68.8%) groups (P = 0.4). Grade III thrombocytopenia developed in 3.2% and 5% of patients in the melphalan and the CIS + MMC groups, respectively. Neutropenia did not occur in any patient. In multivariate analysis, leukopenia predictors were female gender (P = 0.047) and baseline leukocyte counts (P = 0.029). Baseline platelet count predicted thrombocytopenia (P leukopenia and thrombocytopenia. Severe leukopenia and severe thrombocytopenia were rare following CRS/HIPEC using both chemotherapy regimens.

  7. An inverse switch in DNA base excision and strand break repair contributes to melphalan resistance in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Mirta M L Sousa

    Full Text Available Alterations in checkpoint and DNA repair pathways may provide adaptive mechanisms contributing to acquired drug resistance. Here, we investigated the levels of proteins mediating DNA damage signaling and -repair in RPMI8226 multiple myeloma cells and its Melphalan-resistant derivative 8226-LR5. We observed markedly reduced steady-state levels of DNA glycosylases UNG2, NEIL1 and MPG in the resistant cells and cross-resistance to agents inducing their respective DNA base lesions. Conversely, repair of alkali-labile sites was apparently enhanced in the resistant cells, as substantiated by alkaline comet assay, autoribosylation of PARP-1, and increased sensitivity to PARP-1 inhibition by 4-AN or KU58684. Reduced base-excision and enhanced single-strand break repair would both contribute to the observed reduction in genomic alkali-labile sites, which could jeopardize productive processing of the more cytotoxic Melphalan-induced interstrand DNA crosslinks (ICLs. Furthermore, we found a marked upregulation of proteins in the non-homologous end-joining (NHEJ pathway of double-strand break (DSB repair, likely contributing to the observed increase in DSB repair kinetics in the resistant cells. Finally, we observed apparent upregulation of ATR-signaling and downregulation of ATM-signaling in the resistant cells. This was accompanied by markedly increased sensitivity towards Melphalan in the presence of ATR-, DNA-PK, or CHK1/2 inhibitors whereas no sensitizing effect was observed subsequent to ATM inhibition, suggesting that replication blocking lesions are primary triggers of the DNA damage response in the Melphalan resistant cells. In conclusion, Melphalan resistance is apparently contributed by modulation of the DNA damage response at multiple levels, including downregulation of specific repair pathways to avoid repair intermediates that could impair efficient processing of cytotoxic ICLs and ICL-induced DSBs. This study has revealed several novel

  8. A multi-centered randomized trial of the treatment of pemphigus vulgaris patients with infliximab and prednisone compared to prednisone alone

    Science.gov (United States)

    Hall, R.P.; Fairley, J.; Woodley, D.; Werth, V.P.; Hannah, D.; Streilein, R.D.; McKillip, J.; Okawa, J.; Rose, M.; Keyes-Elstein, L.L.; Pinckney, A.; Overington, A.; Wedgwood, J.; Ding, L.; Welch, B.

    2014-01-01

    Background Pemphigus vulgaris (PV) is a blistering disease in which TNF-α has a role in the pathogenesis. Objectives The objective was to evaluate the safety of infliximab (IFX) with prednisone compared to prednisone alone in the treatment of PV. In addition, treatment response was assessed and mechanistic studies were performed. Methods PV subjects who had ongoing disease activity while maintained on prednisone were randomized to receive either IFX or placebo in addition to prednisone. Response status and IgG anti-DSG1 and DSG3 antibodies were assessed at 18 and 26 weeks. . Results 10 subjects were randomized to each group. There were no safety signals during the course of the study. At week 18, 1 subject in each group had responded. At week 26, 3 IFX treated subjects vs. none in the placebo group had responded (p =0 .21). At weeks 18 and 26, the median IgG anti-DSG1 and anti-DSG3 levels were lower in the IFX treated-patients (IgG anti DSG-1: week 18 p =0.035, week 26 p = 0.022; IgG anti-DSG3; week 18 p=0.035, week 26 p = 0.05)). Limitations This study is limited by the relative small sample size. Conclusions There was no significant difference between study arms in the proportion of subjects with treatment-related Adverse Events > Grade 3. IFX therapy was not shown to be effective for the treatment of patients with PV in this randomized, placebo-controlled trial, although IFX treatment may be associated with a decrease in anti-DSG1 and DSG3 antibodies. PMID:25123295

  9. Prednisone treatment alters the serum amylase and lipase activities in normal dogs without causing pancreatitis.

    OpenAIRE

    Fittschen, C; Bellamy, J E

    1984-01-01

    In order to test the hypothesis that treatment with glucocorticoids causes pancreatitis in dogs, 18 mongrel dogs were divided into three groups of six individuals, each group receiving prednisone at different doses orally or intramuscularly for two weeks. Two groups consisting of six dogs each served as controls. Treatment for two weeks with oral prednisone at 1.2 mg/kg body weight or at 4 mg/kg body weight daily decreased the serum amylase activities, but increased the serum lipase activitie...

  10. High cereblon expression is associated with better survival in patients with newly diagnosed multiple myeloma treated with thalidomide maintenance

    NARCIS (Netherlands)

    A. Broyl (Annemiek); R. Kuiper (Ruud); M. van Duin (Mark); B. van der Holt (Bronno); L. Jarari (Laila); U. Bertsch (Uta); S. Zweegman (Sonja); A. Buijs (Arjan); D. Hose (Dirk); H.M. Lokhorst (Henk); H. Goldschmidt (Hartmut); P. Sonneveld (Pieter)

    2013-01-01

    textabstractRecently, cereblon (CRBN) expression was found to be essential for the activity of thalidomide and lenalidomide. In the present study, we investigated whether the clinical efficacy of thalidomide in multiple myeloma is associated with CRBN expression in myeloma cells. Patients with newly

  11. Follow-up of Thalidomide treatment in patients with Hereditary Haemorrhagic Telangiectasia.

    Science.gov (United States)

    Hosman, A; Westermann, C J J; Snijder, R; Disch, F; Mummery, C L; Mager, J J

    2015-12-01

    Patients with a hereditary vascular disorder called Rendu-Osler-Weber syndrome (Hereditary Haemorrhagic Telangiectasia, HHT) haemorrhage easily due to weak-walled vessels. Haemorrhage in lungs or brain can be fatal but patients suffer most from chronic and prolonged nosebleeds (epistaxis), the frequency and intensity of which increases with age. Several years ago, it was discovered serendipitously that the drug Thalidomide had beneficial effects on the disease symptoms in several of a small group of HHT patients: epistaxis and the incidence of anaemia were reduced and patients required fewer blood transfusions. In addition, they reported a better quality of life. However, Thalidomide has significant negative side effects, including neuropathy and fatigue. We followed up all HHT patients in the Netherlands who had been taking Thalidomide at the time the original study was completed to find out (i) how many had continued taking Thalidomide and for how long (ii) the nature and severity of any side-effects and (iii) whether side-effects had influenced their decision to continue taking Thalidomide. Only a minority of patients had continued taking the drug despite its beneficial effects on their symptoms and that the side effects were the primary reason to stop. Despite symptom reduction, alternative treatments are still necessary for epistaxis in HHT patients and a large-scale clinical trial is not justified although incidental use in the most severely affected patients can be considered.

  12. Oral administration of prednisone to control refractory vertigo in Ménière's disease: a pilot study.

    Science.gov (United States)

    Morales-Luckie, Elizabeth; Cornejo-Suarez, Arnulfo; Zaragoza-Contreras, Miguel A; Gonzalez-Perez, Oscar

    2005-09-01

    To establish whether the oral administration of moderate doses of prednisone reduces refractory vertigo in Ménière's disease. Blinded, randomized, controlled trial. Tertiary referral center. Patients with Ménière's disease with limited vertigo control (Class C) and severe disability (Scale 3). Two groups (n = 8 per group) were treated orally with either diphenidol (25 mg/d) plus acetazolamide (250 mg/48 h) (control group), or the same treatment plus prednisone (0.35 mg/kg) daily for 18 weeks (prednisone group). The variables evaluated were the frequency and duration of vertigo, tinnitus, aural fullness, and audiographic parameters. The clinical surveillance was performed for 12 months after prednisone withdrawal. The frequency and duration of vertigo episodes were reduced by 50% and 30%, respectively, by prednisone treatment. Prednisone-treated patients manifested a significant reduction in tinnitus. No changes were observed in aural fullness or hearing. No metabolic or infectious disorders were observed. Oral prednisone helps to control refractory vertigo in Ménière's disease. These preliminary data suggest that prednisone can be a good noninvasive antivertigo management regimen for these patients.

  13. Effects of prednisone and splenectomy in patients with idiopathic thrombocytopenic purpura : only splenectomy induces a complete remission

    NARCIS (Netherlands)

    Louwes, H; Vellenga, E; Houwerzijl, EJ; de Wolf, JTM

    2001-01-01

    Idiopathic thrombocytopenic purpura (ITP) is a heterogeneous disease, whereby it is unclear if and in which way prednisone and splenectomy affect the platelet kinetics leading to a complete remission. To determine the effects of prednisone and splenectomy on the mean platelet life (MPL) and platelet

  14. Surgical versus percutaneous isolated pelvic perfusion (IPP) for advanced melanoma: comparison in terms of melphalan pharmacokinetic pelvic bio-availability.

    Science.gov (United States)

    Guadagni, Stefano; Palumbo, Giancarlo; Fiorentini, Giammaria; Clementi, Marco; Marsili, Luca; Giordano, Aldo Victor; Masedu, Francesco; Valenti, Marco

    2017-08-15

    Isolated pelvic perfusion (IPP) can be used to treat unresectable melanoma metastases of the pelvis. IPP can be performed either by surgical or percutaneous approaches, using different balloon catheters. The aim of this study was to examine whether the surgical and percutaneous approaches were comparable with respect to tumor drug exposure in the pelvis. A pharmacokinetic study was performed in 5 melanoma patients treated with surgical IPP and five with percutaneous IPP. Both groups received melphalan at the dose of 30 mg/m 2 . Melphalan pharmacokinetic analyses were performed and the main parameter used to evaluate pelvic tumor drug-exposure was the ratio of areas under the melphalan plasma concentration curves in the pelvis and the systemic compartment, during the perfusion time (AUC 0 to 20 ). Non-parametric Mann-Whitney tests were employed for statistical comparisons. The median and interquartile range (IQR) values of the ratios between melphalan AUC 0 to 20 in pelvic and systemic compartments were 7.9 (IQR 7.2 to 9.9) and 5 (IQR 4 to 7.9) for surgical and percutaneous IPPs, respectively (p = 0.209). Tumor exposure to drug using these two methods did not statistically differ and both methods, therefore, can be adopted interchangeably, utilizing a perfusion blood flow rate of approximately 120 ml/min. The small sample size is a limitation of this study but our preliminary results can be used to calculate the effect size of a larger trial. Trial Registration Clinical Trials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.

  15. Relapsing insulin-induced lipoatrophy, cured by prolonged low-dose oral prednisone: a case report

    Directory of Open Access Journals (Sweden)

    Chantelau Ernst A

    2011-12-01

    Full Text Available Abstract Introduction Circumscript, progressing lipoatrophy at the insulin injection sites is an unexplained, however rare condition in diabetes mellitus. Case presentation We report a case of severe localised lipoatrophy developing during insulin pump-treatment (continuous subcutaneous insulin infusion with the insulin analogue lispro (Humalog® in a woman with type-1 diabetes mellitus. After 11 months of progressing lipoatrophy at two spots on the abdomen, low-dose prednisone (5-10 mg p.o. was given at breakfast for 8 months, whereby the atrophic lesions centripetally re-filled with subcutaneous fat tissue (confirmed by MRI despite ongoing use of insulin lispro. However, 4 weeks after cessation of prednisone, lipoatrophy relapsed, but resolved after another 2 months of low-dose prednisone. No further relapse was noted during 12 months of follow-up on insulin-pump therapy with Humalog®. Conclusion Consistent with an assumed inflammatory nature of the condition, low-dose oral prednisone appeared to have cured the lipoatrophic reaction in our patient. Our observation suggests a temporary intolerance of the subcutaneous fat tissue to insulin lispro (Humalog®, triggered by an unknown endogenous mechanism.

  16. Anxiety, depression and personality traits in severe, prednisone-dependent asthma

    NARCIS (Netherlands)

    Amelink, Marijke; Hashimoto, Simone; Spinhoven, Philip; Pasma, Henk R.; Sterk, Peter J.; Bel, Elisabeth H.; ten Brinke, Anneke

    2014-01-01

    Anxiety and depression are prevalent in patients with asthma, and associated with more exacerbations and increased health care utilization. Since psychiatric intervention might improve asthma control, we examined whether patients with severe, prednisone-dependent asthma are at higher risk of these

  17. Inhibition of Uterine Contractility by Thalidomide Analogs via Phosphodiesterase-4 Inhibition and Calcium Entry Blockade

    Directory of Open Access Journals (Sweden)

    Eduardo Fernández-Martínez

    2016-10-01

    Full Text Available Uterine relaxation is crucial during preterm labor. Phosphodiesterase-4 (PDE-4 inhibitors have been proposed as tocolytics. Some thalidomide analogs are PDE-4 inhibitors. The aim of this study was to assess the uterus-relaxant properties of two thalidomide analogs, methyl 3-(4-nitrophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4NO2PDPMe and methyl 3-(4-aminophthalimido-3-(3,4-dimethoxyphenyl-propanoate (4APDPMe and were compared to rolipram in functional studies of spontaneous phasic, K+-induced tonic, and Ca2+-induced contractions in isolated pregnant human myometrial tissues. The accumulation of cAMP was quantified in HeLa cells. The presence of PDE-4B2 and phosphorylated myosin light-chain (pMLC, in addition to the effect of thalidomide analogs on oxytocin-induced pMLC, were assessed in human uterine myometrial cells (UtSMCs. Thalidomide analogs had concentration-dependent inhibitory effects on spontaneous and tonic contractions and inhibited Ca2+-induced responses. Tonic contraction was equipotently inhibited by 4APDPMe and rolipram (IC50 = 125 ± 13.72 and 98.45 ± 8.86 µM, respectively. Rolipram and the thalidomide analogs inhibited spontaneous and tonic contractions equieffectively. Both analogs increased cAMP accumulation in a concentration-dependent manner (p < 0.05 and induced changes in the subcellular localization of oxytocin-induced pMLC in UtSMCs. The inhibitory effects of thalidomide analogs on the contractions of pregnant human myometrium tissue may be due to their PDE-4 inhibitory effect and novel mechanism as calcium-channel blockers.

  18. Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients.

    Science.gov (United States)

    Berenson, James R; Crowley, John J; Grogan, Thomas M; Zangmeister, Jeffrey; Briggs, Adrienne D; Mills, Glenn M; Barlogie, Bart; Salmon, Sydney E

    2002-05-01

    The role of maintenance therapy in multiple myeloma is controversial. Recent studies have shown an improvement in both progression-free and overall survival for patients receiving maintenance treatment with a combination of interferon and glucocorticoids, compared with interferon alone. The role of glucocorticoids alone as maintenance therapy has not been previously addressed. We compared alternate-day, oral prednisone at 2 different dose levels (10 mg versus 50 mg) for remission maintenance among previously untreated myeloma patients following a response to induction with standard-dose vincristine, doxorubicin, and dexamethasone with prednisone (VAD-P) or VAD-P plus quinine (VAD-P/Q). There were 250 eligible patients registered on Southwest Oncology Group study 9210 and randomized to receive VAD-P or VAD-P/Q. There were 125 patients achieving at least a 25% tumor reduction following induction therapy who were randomized to either physiologic (10 mg) or pharmacologic (50 mg) doses of alternate-day, oral prednisone until disease progression. At the time of study entry, patient characteristics were similar in VAD-P and VAD-P/Q patients and in the 2 arms randomized to maintenance therapy. After a median follow-up of 53 months, there was no difference in either progression-free or overall survival between the 2 induction regimens. However, from the time of maintenance randomization, both progression-free (14 versus 5 months; P =.003) and overall survival (37 versus 26 months; P =.05) were significantly improved in patients receiving 50 mg as compared with 10 mg alternate-day prednisone. There was no difference in treatment-related adverse events between the groups. Thus, 50 mg, oral, alternate-day prednisone is effective maintenance treatment for multiple myeloma patients who achieve a response to induction chemotherapy. (Blood. 2002;99:3163-3168)

  19. A Phase II dose titration study of thalidomide for cancer-associated anorexia.

    Science.gov (United States)

    Davis, Mellar; Lasheen, Wael; Walsh, Declan; Mahmoud, Fade; Bicanovsky, Leslie; Lagman, Ruth

    2012-01-01

    Sixty-five percent of people with advanced cancer suffers from loss of appetite. Several inflammatory cytokines appear to cause appetite loss in animal models. Thalidomide is an immunomodulatory drug that has been associated with improved appetite in those with HIV infections and cancer. We completed a two-stage Phase II dose titration study of thalidomide, the primary purpose of which was to assess appetite response to thalidomide in cancer-associated anorexia. Individuals older than 18 years of age with active cancer, loss of appetite by numerical rating scale (NRS), life expectancy of at least four weeks, and Eastern Cooperative Oncology Group performance status of 0-3 were entered into the study. Pretreatment screening included medical history, neurologic examination, and symptoms by NRS and categorical scale (CAT). Patients received 50mg of thalidomide by mouth at bedtime for two weeks. Individuals who did not respond were dose escalated to 100mg at night for two weeks. Assessment of appetite, early satiety, fatigue, insomnia, night sweats, pain, and quality of life (QOL) occurred at two-week intervals. Toxicity also was assessed. The primary outcome was appetite response defined as a two-point reduction in the NRS or a one-point improvement in the CAT. Thirty-five patients entered the study; 33 completed 14 days of therapy and were analyzed for efficacy and toxicity. Sixty-four percent who completed at least two weeks of thalidomide had improved appetite. The CAT scores for appetite, insomnia, and QOL improved significantly. The 95% confidence intervals did not overlap. Five participants dropped out because of toxicity: two before two weeks and three later. Thalidomide reduced multiple symptoms commonly associated with cancer-related anorexia and improved QOL. Our findings confirmed and validated a previously published single-arm trial. A recent randomized trial demonstrated greater benefits when thalidomide is used combined with other agents to treat cancer

  20. Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

    International Nuclear Information System (INIS)

    Anscher, Mitchell S.; Garst, Jennifer; Marks, Lawrence B.; Larrier, Nicole; Dunphy, Frank; Herndon, James E.; Clough, Robert B.S.; Marino, Christine R.N.; Vujaskovic, Zeljko; Zhou, Sumin; Dewhirst, Mark W.; Shafman, Timothy D.; Crawford, Jeffrey

    2006-01-01

    Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status ≥70, and life expectancy ≥6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m 2 ) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 of chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity

  1. Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan

    2014-01-01

    /d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. RESULTS: Overall, 873 patients were randomly assigned to receive sunitinib (n.......762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P

  2. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

    Science.gov (United States)

    Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

    2017-03-01

    Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

  3. The glutathione synthesis inhibitor buthionine sulfoximine synergistically enhanced melphalan activity against preclinical models of multiple myeloma

    International Nuclear Information System (INIS)

    Tagde, A; Singh, H; Kang, M H; Reynolds, C P

    2014-01-01

    Melphalan (L-PAM) has been an integral part of multiple myeloma (MM) treatment as a conditioning regimen before stem cell transplant (SCT). After initial response, most treated patients experience relapse with an aggressive phenotype. Increased glutathione (GSH) in MM may mediate resistance to L-PAM. We demonstrated that the GSH synthesis inhibitor buthionine sulfoximine (BSO) synergistically enhanced L-PAM activity (inducing 2–4 logs of cell kill) against nine MM cell lines (also in the presence of marrow stroma or cytokines) and in seven primary MM samples (combination indices <1.0). In MM cell lines, BSO significantly (P<0.05) depleted GSH, increased L-PAM-induced single-strand DNA breaks, mitochondrial depolarization, caspase cleavage and apoptosis. L-PAM depleted GSH, but GSH rapidly recovered in a L-PAM-resistant MM cell line unless also treated with BSO. Treatment with N-acetylcysteine antagonized BSO+L-PAM cytotoxicity without increasing GSH. In human MM xenografted into beige-nude-xid mice, BSO significantly depleted MM intracellular GSH and significantly increased apoptosis compared with L-PAM alone. BSO+L-PAM achieved complete responses (CRs) in three MM xenograft models including maintained CRs >100 days, and significantly increased the median event-free survival relative to L-PAM alone. Combining BSO with L-PAM warrants clinical testing in advanced MM

  4. Evidence for different mechanisms of ‘unhooking’ for melphalan and cisplatin-induced DNA interstrand cross-links in vitro and in clinical acquired resistant tumour samples

    International Nuclear Information System (INIS)

    Spanswick, Victoria J; Hartley, John A; Lowe, Helen L; Newton, Claire; Bingham, John P; Bagnobianchi, Alessia; Kiakos, Konstantinos; Craddock, Charles; Ledermann, Jonathan A; Hochhauser, Daniel

    2012-01-01

    DNA interstrand cross-links (ICLs) are critical lesions produced by several cancer chemotherapy agents including platinum drugs and nitrogen mustards. We have previously shown in haematological (multiple myeloma) and solid tumours (ovarian cancer) that clinical sensitivity to such agents can result from a defect in DNA ICL processing leading to their persistence. Conversely, enhanced repair can result in clinical acquired resistance following chemotherapy. The repair of ICLs is complex but it is assumed that the ‘unhooking’ step is common to all ICLs. Using a modification of the single cell gel electrophoresis (Comet) assay we measured the formation and unhooking of melphalan and cisplatin-induced ICLs in cell lines and clinical samples. DNA damage response in the form of γ-H2AX foci formation and the formation of RAD51 foci as a marker of homologous recombination were also determined. Real-time PCR of 84 genes involved in DNA damage signalling pathways was also examined pre- and post-treatment. Plasma cells from multiple myeloma patients known to be clinically resistant to melphalan showed significant unhooking of melphalan-induced ICLs at 48 hours, but did not unhook cisplatin-induced ICLs. In ovarian cancer cells obtained from patients following platinum-based chemotherapy, unhooking of cisplatin-induced ICLs was observed at 48 hours, but no unhooking of melphalan-induced ICLs. In vitro, A549 cells were proficient at unhooking both melphalan and cisplatin-induced ICLs. γ-H2AX foci formation closely followed the formation of ICLs for both drugs, and rapidly declined following the peak of formation. RPMI8226 cells unhooked melphalan, but not cisplatin-induced ICLs. In these cells, although cross-links form with cisplatin, the γ-H2AX response is weak. In A549 cells, addition of 3nM gemcitabine resulted in complete inhibition of cisplatin-induced ICL unhooking but no effect on repair of melphalan ICLs. The RAD51 foci response was both drug and cell line

  5. Efficacy of cryotherapy associated with laser therapy for decreasing severity of melphalan-induced oral mucositis during hematological stem-cell transplantation: a prospective clinical study.

    Science.gov (United States)

    de Paula Eduardo, Fernanda; Bezinelli, Leticia Mello; da Graça Lopes, Roberta Marques; Nascimento Sobrinho, Jairo Jose; Hamerschlak, Nelson; Correa, Luciana

    2015-09-01

    Melphalan followed by hematopoietic stem-cell transplantation (HSCT) is the standard treatment for multiple myeloma and other hematopoietic neoplasms. However, high doses of melphalan cause severe oral mucositis (OM). The objective was to verify the efficacy of cryotherapy plus laser therapy on reduction of OM severity. HSCT patients undergoing melphalan chemotherapy (n = 71) were randomly divided into two groups according to OM treatment: oral cryotherapy performed with ice chips for 1 h 35 min followed by low-level laser therapy (InGaAIP, 660 nm, 40 mW, 6 J/cm(2) ) (n = 54) and laser therapy alone with the same protocol (n = 17). A control group (n = 33) was composed of HSCT patients treated with melphalan who received no specific treatment for OM. OM scores and clinical information were collected from D0 to D + 11. The cryotherapy/laser therapy group showed the lowest OM scores (maximum Grade I) and the lowest mean number of days (8 days) with OM in comparison with the other groups (p cryotherapy with laser therapy was effective in reducing OM severity in HSCT patients who underwent melphalan conditioning. Copyright © 2014 John Wiley & Sons, Ltd.

  6. Proof of the concept to use a malignant B cell line drug screen strategy for identification and weight of melphalan resistance genes in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Martin Bøgsted

    Full Text Available In a conceptual study of drug resistance we have used a preclinical model of malignant B-cell lines by combining drug induced growth inhibition and gene expression profiling. In the current report a melphalan resistance profile of 19 genes were weighted by microarray data from the MRC Myeloma IX trial and time to progression following high dose melphalan, to generate an individual melphalan resistance index. The resistance index was subsequently validated in the HOVON65/GMMG-HD4 trial data set to prove the concept. Biologically, the assigned resistance indices were differentially distributed among translocations and cyclin D expression classes. Clinically, the 25% most melphalan resistant, the intermediate 50% and the 25% most sensitive patients had a median progression free survival of 18, 32 and 28 months, respectively (log-rank P-value  = 0.05. Furthermore, the median overall survival was 45 months for the resistant group and not reached for the intermediate and sensitive groups (log-rank P-value  = 0.003 following 38 months median observation. In a multivariate analysis, correcting for age, sex and ISS-staging, we found a high resistance index to be an independent variable associated with inferior progression free survival and overall survival. This study provides clinical proof of concept to use in vitro drug screen for identification of melphalan resistance gene signatures for future functional analysis.

  7. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma.

    Science.gov (United States)

    Sidra, Gamal; Williams, Cathy D; Russell, Nigel H; Zaman, Sonya; Myers, Bethan; Byrne, Jennifer L

    2006-06-01

    We evaluated the combination of thalidomide, pulsed dexamethasone and weekly cyclophosphamide (CTD) for the treatment of patients with newly diagnosed, relapsed or VAD-refractory multiple myeloma. We found that this combination was highly effective in inducing responses in all treatment groups with an overall response rate of 83.8%. CTD was well tolerated and did not impair stem cell mobilization.

  8. Genetic Factors Underlying the Risk of Thalidomide-Related Neuropathy in Patients With Multiple Myeloma

    NARCIS (Netherlands)

    Johnson, David C.; Corthals, Sophie L.; Walker, Brian A.; Ross, Fiona M.; Gregory, Walter M.; Dickens, Nicholas J.; Lokhorst, Henk M.; Goldschmidt, Hartmut; Davies, Faith E.; Durie, Brian G. M.; Van Ness, Brian; Child, J. Anthony; Sonneveld, Pieter; Morgan, Gareth J.

    2011-01-01

    Purpose To indentify genetic variation that can modulate and predict the risk of developing thalidomide-related peripheral neuropathy (TrPN). Patients and Methods We analyzed DNA from 1,495 patients with multiple myeloma. Using a custom-built single nucleotide polymorphism (SNP) array, we tested the

  9. O renascimento de um fármaco: talidomida The rebirth of a drug: thalidomide

    Directory of Open Access Journals (Sweden)

    Lídia Moreira Lima

    2001-10-01

    Full Text Available Thalidomide, first synthesized in 1953, was widely prescribed for morning sickness of pregnant women from 1957 to 1961, when it was found to be seriously teratogenic, having caused serious birth defect. Nowadays, a quarter of a century later, it appears that it may be a miracle drug for such diseases as leprosy, AIDS, cancer and tuberculosis.

  10. Phase II Study of Temozolomide and Thalidomide in Patients with Unresectable or Metastatic Leiomyosarcoma

    Directory of Open Access Journals (Sweden)

    Michelle S. Boyar

    2008-01-01

    Full Text Available We assessed the efficacy of combined temozolomide and thalidomide in patients with unresectable or metastatic leiomyosarcoma in a phase II single-institution trial. Twenty-four patients were enrolled. Temozolomide (150 mg/m2/day for 7 days every other week was administered with concomitant thalidomide (200 mg/day, and continued until unacceptable toxicity or disease progression. There were no complete responses and two (10% partial responses. Five patients (24% had stable disease for at least six months. Fourteen patients (67% progressed after a median of two-month treatment. The median overall survival (twenty-two assessable patients was 9.5 months [95% CI 7–28 months]. There were no treatment-related deaths or CTC grade 4 toxicities. Thirteen patients were dose-reduced or discontinued thalidomide due to toxicity. In conclusion, this combination of temozolomide and thalidomide provided disease stabilization in a subset of patients with advanced leiomyosarcoma. We hypothesize that temozolomide is the active agent in this regimen, and should be further studied.

  11. Efficacy of thalidomide in a girl with inflammatory calcinosis, a severe complication of juvenile dermatomyositis

    Directory of Open Access Journals (Sweden)

    Inayama Yoshiaki

    2010-02-01

    Full Text Available Abstract We report a 14-year-old girl with juvenile dermatomyositis (JDM complicated by severe inflammatory calcinosis successfully treated with thalidomide. She was diagnosed as JDM when she was 4 years old after a few months of increasing lethargy, muscle pain, muscle weakness, and rash. During three months, clinical manifestations and abnormal laboratory findings were effectively treated with oral prednisolone. However, calcinosis was recognized 18 months after disease onset. Generalized calcinosis rapidly progressed with high fever, multiple skin/subcutaneous inflammatory lesions, and increased level of CRP. Fifty mg/day (1.3 mg/kg day of oral thalidomide was given for the first four weeks, and then the dose was increased to 75 mg/day. Clinical manifestations subsided, and inflammatory markers had clearly improved. Frequent high fever and local severe pain with calcinosis were suppressed. The levels of FDP-E, IgG, and tryglyceride, which were all elevated before the thalidomide treatment, were gradually returned to the normal range. Over the 18 months of observation up to the present, she has had no inflammatory calcinosis, or needed any hospitalization, although established calcium deposits still remain. Her condition became painless, less extensive and less inflammatory with the CRP level below 3.08 mg/dL. Recent examination by whole-body 18F-FDG-PET-CT over the 15 months of thalidomide treatment demonstrated fewer hot spots around the subcutaneous calcified lesions.

  12. A phase II study of thalidomide in patients with brain metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Vestermark, Lene; Larsen, Susanne; Lindeløv, Birgit

    2008-01-01

    Introduction. Brain metastases develop in nearly half of the patients with advanced melanoma and in 15 to 20% of these patients CNS is the first site of relapse. Overall median survival is short, ranging from 2 to 4 months. Thalidomide has antiangiogenic and immunomodulatory effects. Results...

  13. Thalidomide for Epistaxis in Patients with Hereditary Hemorrhagic Telangiectasia: A Preliminary Study.

    Science.gov (United States)

    Fang, Jia; Chen, Xiaomeng; Zhu, Bijun; Ye, Haibo; Zhang, Weitian; Guan, Jian; Su, Kaiming

    2017-08-01

    To evaluate the effectiveness of thalidomide for epistaxis in hereditary hemorrhagic telangiectasia (HHT), 7 HHT patients with recurrent epistaxis were treated with thalidomide at an initial dose of 50 mg/d, gradually increasing to 100 mg/d if needed. The Epistaxis Severity Score (ESS) was used to evaluate the treatment effects. Patients reported that epistaxis improved 1 to 3 weeks after starting thalidomide. The mean ESS before treatment, at the end of treatment, and 3 months after stopping treatment was 5.03 ± 2.05, 0.90 ± 0.84 ( P = .003), and 1.98 ± 1.33 ( P = .006), respectively. Four patients reported mild to moderate side effects, including drowsiness, dizziness, constipation, nausea, and peripheral neuropathy. Two patients stopped the treatment because of adverse effects. Those results showed that thalidomide may be a treatment choice for recurrent epistaxis in HHT patients, although the side effects should be considered. Further study should focus on guidelines for dosing and course and investigate how to reduce the adverse effects.

  14. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ch' ang, Hui-Ju, E-mail: hjmc@nhri.org.tw [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Radiation Oncology, National Cheng Kung University Hospital, Tainan, Taiwan (China); Hsu, Chiun [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Chen, Chien-Hung [Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Chang, Ya-Hui; Chang, Jeffrey S. [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Chen, Li-Tzong [National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan (China); Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan (China)

    2012-02-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 {+-} 48.9 vs. 148 {+-} 6.2 days, p = .15), or median overall survival (258 {+-} 45.6 vs. 241 {+-} 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-{alpha} levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1

  15. Phase II Study of Concomitant Thalidomide During Radiotherapy for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Ch’ang, Hui-Ju; Hsu, Chiun; Chen, Chien-Hung; Chang, Ya-Hui; Chang, Jeffrey S.; Chen, Li-Tzong

    2012-01-01

    Purpose: Thalidomide has been demonstrated to possess antitumor activity in patients with advanced hepatocellular carcinoma (HCC). The objective of the present study was to determine whether the combined treatment of thalidomide with radiotherapy (RT) is associated with acceptable toxicity and an improved clinical outcome in HCC patients. Methods and Materials: A total of 24 patients were enrolled to receive RT combined with thalidomide. A total dose of 50 Gy was delivered in 2-Gy fractions within 5 weeks. Thalidomide was administered 100 mg twice daily starting 3 days before RT until the development of unacceptable toxicity or disease progression. Blood samples were collected before, during, and after treatment to measure the levels of angiogenic factors and cytokines. The results of patients receiving the combined therapy were compared with those from 18 HCC patients receiving RT only. Results: No significant difference in the clinical parameters was noted between the two groups, except for the baseline interleukin-6 level, which was greater in the concomitant group (p = .05). The most common toxicities related to thalidomide use were skin rash (54.2%), somnolence (37.5%), and constipation (33.3%). No significant differences were seen in the response rate (55.6% vs. 58.3%, p = .48), median progression-free survival (182 ± 48.9 vs. 148 ± 6.2 days, p = .15), or median overall survival (258 ± 45.6 vs. 241 ± 38.6, p = .16) between those who received concomitant therapy and those who received RT alone. Thalidomide suppressed the serum basic fibroblast growth factor level significantly during RT (p = .03) and, to a lesser extent, the interleukin-6 and tumor necrosis factor-α levels. After adjusting for other potential prognostic factors in the multivariate analysis, only the baseline interleukin-6 level and stem cell-derived factor-1 during RT independently predicted the progression-free survival. A decreased serum stem cell-derived factor-1 level 1 month after RT

  16. Elderly-Onset Neuromyelitis Optica Spectrum Disorder with Pre-Existing Prednisone Allergy

    Directory of Open Access Journals (Sweden)

    Christopher Hollen

    2018-01-01

    Full Text Available We present a case of an 82-year-old man with new-onset neuromyelitis optica (NMO spectrum disorder, the treatment of which was complicated by a severe pre-existing prednisone allergy. His age caused much initial doubt about his diagnosis, and his corticosteroid allergy altered our management as we attempted to minimize risk to the patient. Our patient was a healthy 82-year-old, right-handed man who presented with sensory loss of the bilateral lower extremities and progressive, painless vision loss. MRI showed bilateral pre-chiasmatic optic nerve and optic chiasm enhancement, along with enhancement within the thoracic spinal cord from T3 to T7. Serum NMO-IgG was positive with a titer >1: 100,000. Due to concern of allergic reaction, our patient initially refused high-dose Solu-Medrol and opted to try plasma exchange alone, but due to worsening of his symptoms we attempted to use dexamethasone as it had a theoretically lower risk of adverse reaction with a known prednisone allergy. There are several cases of elderly-onset NMO in the literature but this is the only case we could find of NMO accompanied by a rare severe allergy to prednisone. This case demonstrates the relative safety of dexamethasone as an alternative to methylprednisolone for acute management of NMO spectrum disorder, though efficacy has not been established in major trials. Cross-reactivity between various systemic corticosteroids is not as well established as topical corticosteroids, so it is difficult to assess the probability of a reaction between prednisone and methylprednisolone.

  17. Pediatric Pemphigus Vulgaris: Durable Treatment Responses Achieved with Prednisone and Mycophenolate Mofetil (MMF)

    Science.gov (United States)

    Baratta, Andrea; Camarillo, Diana; Papa, Christine; Treat, James R.; Payne, Aimee S.; Rozenber, Suzanne S.; Yan, Albert C.

    2013-01-01

    Pemphigus vulgaris (PV) is a chronic autoimmune blistering disease of the skin and mucous membranes. Most cases occur in adults; cases in children are rare. This report describes the clinical presentations and treatment responses of three children with PV, as confirmed according to histology and indirect immunofluorescence studies. In all three cases, oral prednisone used in conjunction with mycophenolate mofetil (MMF) resulted in complete clinical remission, during which all pharmacotherapy was successfully discontinued. Resolution of the skin and mucosal blistering tended to occur quickly with prednisone, and after initiation of treatment with MMF, discontinuation of all pharmacotherapy was achieved within a range of 10 to 30 months in the three patients. One patient experienced a recurrence of genital lesions 19 months after discontinuation of therapy, but the condition remitted within 2 weeks with topical corticosteroid therapy. At the time of this report, the duration of complete remission ranged from 6 to 19 months. In summary, combination therapy with prednisone and MMF for pediatric PV appears to be a safe and effective approach that is associated with durable remission. PMID:22747679

  18. Clinical Predictors of Response to Prednisone Plus Cyclophosphamide in Patients with Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Li, Shu; Wang, Ling; Zhang, Minfang; Zhou, Wenyan; Fang, Wei; Wang, Qin; Qi, Chaojun; Mou, Shan; Shao, Xinghua; Ni, Zhaohui

    2017-01-01

    Complete remission (CR) and partial remission (PR) are beneficial to the long-term outcome of patients with idiopathic membranous nephropathy (iMN). However, we are lacking in studies that evaluate the clinical predictors of response to treatment with prednisone plus cyclophosphamide (CP). The objectives of the study are to identify clinical factors that could predict clinical remission or relapse in patients with iMN who were treated with prednisone plus i.v. CP therapy. This retrospective study recruited a total of 102 eligible patients diagnosed with biopsy-proven iMN between January 2010 and December 2013 in our center. All subjects were treated with prednisone plus i.v. CP for at least 6 months. Primary outcome was remission, including both CR and PR. Demographic data and clinical data at baseline and month 3 of treatment with CP were assessed. The proportion of patients with remission (both CR and PR) was 82.4%, over an average follow-up duration of 15 (10-27.5) months. Fifty-two of them experienced a CR. Baseline proteinuria and the reduction of proteinuria at month 3 of CP treatment were independent predictors of remission (p 150, p proteinuria at baseline and high reduction of proteinuria at month 3 of treatment with CP were more likely to achieve remission and CR. The presence of only a PR may act as a useful predictor of relapse after completion of CP therapy. © 2016 S. Karger AG, Basel.

  19. The effect on memory of chronic prednisone treatment in patients with systemic disease.

    Science.gov (United States)

    Keenan, P A; Jacobson, M W; Soleymani, R M; Mayes, M D; Stress, M E; Yaldoo, D T

    1996-12-01

    There have been no systematic investigations of the effects of glucocorticoid treatment on memory in a clinical population despite experimental and clinical evidence that such treatment could cause memory disturbance. We conducted both cross-sectional and longitudinal studies. In Study 1, we administered tests of both hippocampal-dependent explicit memory and hippocampal-independent implicit memory to twenty-five prednisone-treated patients with systemic disease without CNS involvement and 25 matched clinical controls. All treated patients were taking doses of 5 to 40 mg of prednisone daily for at least 1 year. The glucocorticoid-treated group performed worse than the controls on tests of explicit memory, but the groups did not differ on the implicit memory task. Multiple regression analyses suggested that elderly patients are more susceptible to memory impairment with less protracted treatment. The results of Study 2, a prospective, longitudinal study of the effects of prednisone on memory across 3 months of therapy, suggest that even acute treatment can adversely affect memory. The observed alteration in memory was not secondary to inattention, affective disturbance, generalized global cognitive decline, or severity of disease. Results reported here, combined with previous clinical and experimental reports, indicate that the risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids. Conversely, use of glucocorticoids should be considered in the differential diagnosis of memory loss. Finally, the potential benefit of anti-inflammatory treatment in Alzheimer's disease might be counterbalanced by possible iatrogenic memory impairment, at least when synthetic glucocorticoids are considered.

  20. Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Bisgaard, Thue; Schulze, S.; Hjortso, N.C.

    2008-01-01

    Background Intravenous administration of dexamethasone 90 min before laparoscopic cholecystectomy improves surgical outcome but may be impractical. The objective of this study was to assess the clinical efficacy of oral self-administration of prednisone 2 h before ambulatory laparoscopic cholecys......Background Intravenous administration of dexamethasone 90 min before laparoscopic cholecystectomy improves surgical outcome but may be impractical. The objective of this study was to assess the clinical efficacy of oral self-administration of prednisone 2 h before ambulatory laparoscopic...... cholecystectomy. Methods In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain......-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy Udgivelsesdato: 2008/2...

  1. Randomized double-blind trial of prednisone versus radiotherapy in Graves' ophthalmopathy

    Energy Technology Data Exchange (ETDEWEB)

    Prummel, M.F.; Mourits, M.; Blank, L.; Berghout, A.; Koornneef, L.; Wiersinga, W.M. (Univ. of Amsterdam (Netherlands))

    1993-10-16

    Corticosteriods are usually given for management of Graves' ophthalmopathy, but they have many and serious side-effects. By comparison, retrobulbar irradiation is well tolerated, although its efficacy has been evaluated only in uncontrolled studies. Therefore, the authors did a double-blind randomized trial, in which 28 patients with moderately severe Graves' ophthalmopathy were treated with a 3-month course of oral prednisone and sham irradiation, and 28 received retrobulbar irradiation (20 Gy) and placebo capsules. Therapeutic outcome, assessed twenty-four weeks after the start of treatment, was determined by the change in the highest NOSPECS class. A successful outcome was observed in 14 prednisone-treated and in 13 irradiated patients. Responders to treatment (but not nonresponders) in both groups showed improvements in total and subjective eye score and a decrease in eye-muscle volume. Response to either treatment was due largely to changes in soft-tissue involvement and eye-muscle motility. Radiotherapy and oral prednisone appear to be equally effective as initial treatment in patients with moderately severe Graves' ophthalmopathy. In view of its better tolerability, radiotherapy should be considered the treatment of first choice.

  2. Expression of human organic cation transporter 3 in kidney carcinoma cell lines increases chemosensitivity to melphalan, irinotecan, and vincristine.

    Science.gov (United States)

    Shnitsar, Volodymyr; Eckardt, Ronny; Gupta, Shivangi; Grottker, Julia; Müller, Gerhard A; Koepsell, Hermann; Burckhardt, Gerhard; Hagos, Yohannes

    2009-02-15

    Renal cell carcinoma (RCC) is usually chemoresistant. This chemoresistance could be overcome if specific cytostatics are applied for which the RCC expresses an uptake transporter. In the present study, we investigated the expression of solute carrier (SLC) transporters in different RCC lines and their ability to interact with chemotherapeutics. We tested five RCC lines for the expression of different SLCs by reverse transcription-PCR and TaqMan real-time PCR. In two of five RCC lines, A498 and 7860, we observed a highly significant expression of SLC22A3 (hOCT3). Uptake of the organic cation [(3)H]MPP (4-methyl-pyridinium iodide) into these cells and also into hOCT3 stably transfected Chinese hamster ovary (CHO) cells was inhibited by irinotecan, vincristine, and melphalan. The K(i) values [determined from Dixon plots] for irinotecan, vincristine, and melphalan were 1.72 +/- 0.45 micromol/L, 17 +/- 4.81 micromol/L, and 366 +/- 51 micromol/L, respectively. Cytotoxic activities of the selected drugs were tested by [(3)H]thymidine incorporation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays on CHO-hOCT3, A498 (high expression of hOCT3), and ACHN cell lines (low expression of hOCT3). The growth of CHO-hOCT3 was inhibited by 20% more with irinotecan and by 50% more with vincristine compared with nontransfected CHO cells. Melphalan produced 20% to 30% more inhibition in hOCT3-expressing cells compared with nonexpressing control cells. Similar results were obtained for A498 and ACHN cells. Thus, our data support the hypothesis that the sensitivity of tumor cells to chemotherapeutic treatment depends on the expression of transporter proteins mediating specific drug accumulation into target cells.

  3. Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver.

    Science.gov (United States)

    de Leede, Eleonora M; Burgmans, Mark C; Martini, Christian H; Tijl, Fred G J; van Erkel, Arian R; Vuyk, Jaap; Kapiteijn, Ellen; Verhoef, Cornelis; van de Velde, Cornelis J H; Vahrmeijer, Alexander L

    2016-07-31

    Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

  4. A Phase III Study of Conventional Radiation Therapy Plus Thalidomide Versus Conventional Radiation Therapy for Multiple Brain Metastases (RTOG 0118)

    International Nuclear Information System (INIS)

    Knisely, Jonathan P.S.; Berkey, Brian; Chakravarti, Arnab; Yung, Al W.K.; Curran, Walter J.; Robins, H. Ian; Movsas, Benjamin; Brachman, David G.; Henderson, Randall H.; Mehta, Minesh P.

    2008-01-01

    Purpose: To compare whole-brain radiation therapy (WBRT) with WBRT combined with thalidomide for patients with brain metastases not amenable to resection or radiosurgery. Patients and Methods: Patients with Zubrod performance status 0-1, MRI-documented multiple (>3), large (>4 cm), or midbrain brain metastases arising from a histopathologically confirmed extracranial primary tumor, and an anticipated survival of >8 weeks were randomized to receive WBRT to a dose of 37.5 Gy in 15 fractions with or without thalidomide during and after WBRT. Prerandomization stratification used Radiation Therapy Oncology Group (RTOG) Recursive Partitioning Analysis (RPA) Class and whether post-WBRT chemotherapy was planned. Endpoints included overall survival, progression-free survival, time to neurocognitive progression, the cause of death, toxicities, and quality of life. A protocol-planned interim analysis documented that the trial had an extremely low probability of ever showing a significant difference favoring the thalidomide arm given the results at the time of the analysis, and it was therefore closed on the basis of predefined statistical guidelines. Results: Enrolled in the study were 332 patients. Of 183 accrued patients, 93 were randomized to receive WBRT alone and 90 to WBRT and thalidomide. Median survival was 3.9 months for both arms. No novel toxicities were seen, but thalidomide was not well tolerated in this population. Forty-eight percent of patients discontinued thalidomide because of side effects. Conclusion: Thalidomide provided no survival benefit for patients with multiple, large, or midbrain metastases when combined with WBRT; nearly half the patients discontinued thalidomide due to side effects

  5. High-dose melphalan followed by radical radiotherapy for the treatment of massive plasmacytoma of the chest wall.

    Science.gov (United States)

    Das-Gupta, E P; Sidra, G M; Bessell, E M; Lush, R J; Byrne, J L; Russell, N H

    2003-10-01

    We report three cases of massive chest wall plasmacytoma, each greater than 10 cm in diameter, without evidence of overt myeloma, whom we treated with a combination of VAD chemotherapy consolidated by high-dose melphalan and autologous peripheral blood stem cell transplantation and radical radiotherapy. All three patients completed all components of their therapy without experiencing any major side effects and one patient has had a durable remission. The other two patients have had disease progression but at sites other than the original tumour.

  6. Vorinostat Combined with High-Dose Gemcitabine, Busulfan, and Melphalan with Autologous Stem Cell Transplantation in Patients with Refractory Lymphomas.

    Science.gov (United States)

    Nieto, Yago; Valdez, Benigno C; Thall, Peter F; Ahmed, Sairah; Jones, Roy B; Hosing, Chitra; Popat, Uday; Shpall, Elizabeth J; Qazilbash, Muzaffar; Gulbis, Alison; Anderlini, Paolo; Alousi, Amin; Shah, Nina; Bashir, Qaiser; Liu, Yan; Oki, Yasuhiro; Hagemeister, Frederick; Fanale, Michelle; Dabaja, Bouthaina; Pinnix, Chelsea; Champlin, Richard; Andersson, Borje S

    2015-11-01

    More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination. Patients ages 12 to 65 with refractory diffuse large B cell lymphoma (DLCL), Hodgkin (HL), or T lymphoma were eligible. Vorinostat was given at 200 mg/day to 1000 mg/day (days -8 to -3). Gemcitabine was infused continuously at 10 mg/m(2)/minute over 4.5 hours (days -8 and -3). Busulfan dosing targeted 4000 μM-minute/day (days -8 to -5). Melphalan was infused at 60 mg/m(2)/day (days -3 and -2). Patients with CD20(+) tumors received rituximab (375 mg/m(2), days +1 and +8). We enrolled 78 patients: 52 DLCL, 20 HL, and 6 T lymphoma; median age 44 years (range, 15 to 65); median 3 prior chemotherapy lines (range, 2 to 7); and 48% of patients had positron emission tomography-positive tumors at high-dose chemotherapy (29% unresponsive). The vorinostat dose was safely escalated up to 1000 mg/day, with no treatment-related deaths. Toxicities included mucositis and dermatitis. Neutrophils and platelets engrafted promptly. At median follow-up of 25 (range, 16 to 41) months, event-free and overall survival were 61.5% and 73%, respectively (DLCL) and 45% and 80%, respectively (HL). In conclusion, vorinostat/gemcitabine/busulfan/melphalan is safe and highly active in refractory/poor-risk relapsed lymphomas, warranting further evaluation. This trial was registered at ClinicalTrials.gov (NCI-2011-02891). Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights

  7. A framework to identify gene expression profiles in a model of inflammation induced by lipopolysaccharide after treatment with thalidomide

    Directory of Open Access Journals (Sweden)

    Paiva Renata T

    2012-06-01

    Full Text Available Abstract Background Thalidomide is an anti-inflammatory and anti-angiogenic drug currently used for the treatment of several diseases, including erythema nodosum leprosum, which occurs in patients with lepromatous leprosy. In this research, we use DNA microarray analysis to identify the impact of thalidomide on gene expression responses in human cells after lipopolysaccharide (LPS stimulation. We employed a two-stage framework. Initially, we identified 1584 altered genes in response to LPS. Modulation of this set of genes was then analyzed in the LPS stimulated cells treated with thalidomide. Results We identified 64 genes with altered expression induced by thalidomide using the rank product method. In addition, the lists of up-regulated and down-regulated genes were investigated by means of bioinformatics functional analysis, which allowed for the identification of biological processes affected by thalidomide. Confirmatory analysis was done in five of the identified genes using real time PCR. Conclusions The results showed some genes that can further our understanding of the biological mechanisms in the action of thalidomide. Of the five genes evaluated with real time PCR, three were down regulated and two were up regulated confirming the initial results of the microarray analysis.

  8. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma : Three time periods at risk for amputation

    NARCIS (Netherlands)

    van Ginkel, Robert J.; Thijssens, Katja M. J.; Pras, Elisabeth; van der Graaf, Winette T. A.; Suurmeijer, Albert J. H.; Hoekstra, Harald J.

    Background: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). Methods: From 1991 to 2003, 73 patients (36 men, 37 women,

  9. Isolated limb perfusion with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma: three time periods at risk for amputation.

    NARCIS (Netherlands)

    Ginkel, R.J. van; Thijssens, K.M.; Pras, E.; Graaf, W.T.A. van der; Suurmeijer, A.J.H.; Hoekstra, H.J.

    2007-01-01

    BACKGROUND: The aim of this study was to investigate the long-term limb salvage rate and overall survival after isolated limb perfusion (ILP) with tumor necrosis factor alpha and melphalan for locally advanced soft tissue sarcoma (STS). METHODS: From 1991 to 2003, 73 patients (36 men, 37 women,

  10. Value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin during hyperthermic isolated limb perfusion with tumor necrosis factor-alpha and melphalan

    NARCIS (Netherlands)

    van Ginkel, RJ; Limburg, PC; Piers, DA; Hoekstra, HJ; Schraffordt Koops, H.

    Background: The aim of this study was to analyze the value of continuous leakage monitoring with radioactive iodine-131-labeled human serum albumin (RISA) in patients treated with hyperthermic isolated limb perfusion with tumor necrosis factor-alpha (TNFalpha) and melphalan. Methods: Forty-eight

  11. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, H. M.; Sonneveld, P.; Cornelissen, J. J.; Joosten, P.; van Marwijk Kooy, M.; Meinema, J.; Nieuwenhuis, H. K.; van Oers, M. H.; Richel, D. J.; Segeren, C. N.; Veth, G.; Verdonck, L. F.; Wijermans, P. W.

    1999-01-01

    We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77

  12. Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma

    NARCIS (Netherlands)

    Lokhorst, H. M.; Sonneveld, P.; Wijermans, P. W.; van Marwijk Kooy, M.; Meuwissen, O. J.; van Oers, R. H.; van der Griend, R.; Dekker, A. W.

    1996-01-01

    Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received

  13. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT

    DEFF Research Database (Denmark)

    Gimsing, P; Hjertner, Ø; Abildgaard, N

    2015-01-01

    Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...

  14. Effect of melphalan on growth curves and cell cycle distribution of four human small cell carcinomas of the lung grown in nude mice

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1986-01-01

    Four human small cell carcinomas of the lung grown in nude mice were exposed to melphalan. Two of the tumors were derived from subpopulations isolated by in vitro cloning from the same tumor biopsy. The chemosensitivity of the tumors was determined by calculating the specific growth delay. Drug...

  15. The penumbra of thalidomide, the litigation culture and the licensing of pharmaceuticals

    OpenAIRE

    Lachmann, P.J.

    2012-01-01

    Fifty years ago several thousand children were born with severe limb defects after their mothers had been given thalidomide in pregnancy. This tragedy caused procedures for licensing new medicines to become much stricter. Where, nevertheless, significant side effects were found it became common to sue for damages. These consequences have caused possibly an even greater disaster damaging many more people and threatening ruin to health services everywhere. The huge increase in both time and cos...

  16. Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

    Directory of Open Access Journals (Sweden)

    T.B.M. Castro

    2016-01-01

    Full Text Available In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61% vs 23 (39% males, and of whites, 49 (83.1% vs 10 (16.9% blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6. Regarding staging at diagnosis, 27 (45.7% patients were in stage III-A, with 12 (20.3% patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40 were: neutropenia (42.5%, diarrhea (47.5%, and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26 and sc (n=14 administration routes (P=0.343. In the group treated with thalidomide (n=19, 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038. Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%. Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

  17. A Phase II Study of Everolimus Plus Oral Prednisone in Patients with Metastatic Renal Cell Cancer.

    Science.gov (United States)

    Lolli, Cristian; Gallà, Valentina; Schepisi, Giuseppe; Barone, Domenico; Burgio, Salvatore Luca; Maugeri, Antonio; Vertogen, Bernadette; Amadori, Dino; De Giorgi, Ugo

    2017-07-01

    The combination of everolimus and low-dose prednisone administered daily was hypothesized to prevent noninfectious pneumonitis (NIP) and mucositis, two common adverse events related to everolimus. Although mucositis was detected in only one case, all-grade NIP occurred in four of eight cases (50%), and this was considered enough to stop accrual of the study.These data suggest the need for careful monitoring of patients receiving everolimus who are treated with corticosteroids. Everolimus is standard of care in the treatment of patients affected by metastatic renal cell carcinoma (mRCC) that has progressed after at least one previous line of treatment. Stomatitis and noninfectious pneumonitis (NIP) are common adverse events (AEs) in patients treated with everolimus. Prednisone could reduce the incidence of stomatitis, and it is commonly used to treat NIP. We hypothesized that low doses of prednisone could reduce the incidence and/or the severity of everolimus-induced NIP and stomatitis. We have conducted an open-label, single-arm, phase II trial of prednisone 5 mg b.i.d. added to everolimus 10 mg/day in patients with mRCC. We planned to evaluate the safety, tolerability, and activity of this combination in mRCC patients. We aimed to reduce incidence of drug discontinuations due to stomatitis or NIP from 25% to 10%. Three (38%) of the first eight patients enrolled experienced grade ≥2 pneumonitis and stopped treatment. Grade 1 stomatitis occurred in only one patient (13%). Five of eight patients experienced disease progression at the 2-month evaluation. Two patients (25%) were reported free of disease progression at 1 year of treatment. The incidence of NIP in these patients was considered too high for completing accrual of this study. These results may be of interest for investigating the pathogenesis of NIP and suggest that patients should be carefully followed if treated with chronic corticosteroids while receiving everolimus. © AlphaMedPress; the data

  18. Efficacy and tolerability of high-dose prednisone in Chinese children with infantile spasms.

    Science.gov (United States)

    Yi, Zhao-Shi; Wu, Hua-Ping; Yu, Xiong-Ying; Chen, Yong; Zhong, Jian-Min

    2015-01-01

    The aim of this study is to preliminarily evaluate the clinical efficacy and safety of high-dose prednisone in the treatment of infantile spasms (IS) in China, and to provide additional choice of the therapy of IS. Twenty patients aged 3-53 months with IS were collected in the Department of Neurology of Jiangxi Children's Hospital from May in 2011 to December in 2012, who were placed on high-dose prednisone (took prednisone tablet of 10mg four times a day) for 2 weeks during admission to our hospital. The assessment of spasms seizure and video-EEG monitoring were preformed before treatment and after 2 weeks and the end of treatment of the regimen (7 weeks), respectively. All of the children were followed-up for 2-14 months. Among 20 cases, there were 16 cases (80.0%) with complete cessation of spasms after 2 weeks and 13 cases (65.0%) after 7 weeks. There were 19 cases with typical or modified hypsarrhythmia in 20 cases. No matter after 2 or 7 weeks, there were 12 cases showed complete resolution of hypsarrhythmia and 7 cases with only a partial remission of hypsarrhythmia. After a follow-up of 2-14 months, the longest spasm-free interval was 14 months and the shortest one was 11 days. Six cases relapsed in different periods, and the relapse rate was 35.3%. Amongst the main adverse events, there were Cushing's symptoms in 15 cases (75.0%), irritability in 8 cases (40.0%), drosiness in 3 cases (15.0%), high blood pressure in 3 cases (15.0%), and infections in 8 cases (40.0%), but no one stopped the treatment because of the adverse reactions. In total, high-dose prednisone was effective and well-tolerated in children with IS in China. Maybe the regimen will become a new choice in the treatment of IS. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Valproate, thalidomide and ethyl alcohol alter the migration of HTR-8/SVneo cells

    Directory of Open Access Journals (Sweden)

    Rout Ujjwal K

    2006-08-01

    Full Text Available Abstract Background Valproate, thalidomide and alcohol (ethanol exposure during the first trimester of pregnancy is known to cause several developmental disorders. All these teratogens are known to pass the placental barrier and interfere directly with the normal development of the fetus. However, these teratogens also alter the formation and function of the placenta itself which may in turn affect the proper nourishment and development of the fetus. Optimum development of the placenta requires adequate invasion of trophoblast into the maternal uterine tissues. Changes in the migratory behavior of trophoblast by maternal exposure to these teratogens during placentogenesis may therefore alter the structure and function of the placenta. Methods In the present study, the effects of sodium valproate, thalidomide and alcohol on the migration of human first trimester trophoblast cell line (HTR-8/SVneo were examined in vitro. Cells were cultured in the wells of 48-well culture plates as mono or multilayers. Circular patches of cells were removed from the center of the wells by suction, and the migration of cells into the wound was studied using microscopy. Effects of low and high concentrations of valproate, thalidomide and alcohol were examined on the healing of wounds and on the migration rate of cells by determining the wound areas at 0, 3, 6, 12, 24 and 48 h. Effects of drugs and alcohol on the proliferation and the expression levels of integrin subunits beta1 and alpha5 in cells were examined. Results The migration rates of trophoblast differed between wounds created in mono and multilayers of cells. Exposure to teratogens altered the migration of trophoblast into mono and multilayer wounds. The effects of valproate, thalidomide and alcohol on the proliferation of cells during the rapid migratory phase were mild. Drug exposure caused significant changes in the expression levels of beta1 and alpha5 integrin subunits. Conclusion Results suggest that

  20. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    International Nuclear Information System (INIS)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T.

    2005-01-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans

  1. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of)

    2005-07-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans.

  2. Resolving a double standard for risk management of thalidomide: an evaluation of two different risk management programmes in Japan.

    Science.gov (United States)

    Ooba, Nobuhiro; Sato, Tsugumichi; Watanabe, Hikaru; Kubota, Kiyoshi

    2010-01-01

    Thalidomide, once withdrawn because of its teratogenicity, has now been re-launched worldwide. In Japan, thalidomide has been imported by individual doctors since around the year 2000. In October 2008, it was approved for the treatment of multiple myeloma (MM) by the Ministry of Health, Labour and Welfare (MHLW) on the condition that the manufacturer implemented a risk management programme termed the Thalidomide Education and Risk Management System (TERMS). It is likely that the imports of thalidomide will be used off-label to treat diseases other than MM. Thus, the MHLW is also planning to introduce a web-based registration system, referred to as the Safety Management System for Unapproved Drugs (SMUD), for thalidomide imported by individual doctors. To evaluate the difference between TERMS and SMUD and establish a way to resolve the 'double standard' for risk management of thalidomide treatment in Japan. The fraction of patients with disorders other than MM was estimated by the volume of annual imports obtained from the MHLW and records of the imports for patients with MM, other oncological diseases (ODs) and non-ODs in 2007 through a major supplier covering 63% of the total imported thalidomide. The information for TERMS was obtained from web pages of the manufacturer and the MHLW. The components of TERMS were compared with those in SMUD. Provided that the distribution of the indication for thalidomide (MM) in 2007, estimated from the records of imports through the major supplier, is representative of the entire nation, it is estimated that on average 866 patients, including 851 (98.3%) with MM, are using thalidomide on any one day. However, if the major supplier's imports, which account for 63% of the total imports, are not representative of the nation as a whole, possibly only half of the patients treated with thalidomide in Japan have MM. This would be the case in a scenario where the remaining 37% of imports are exclusively used to treat disorders other than

  3. Renal-protective effect of thalidomide in streptozotocin-induced diabetic rats through anti-inflammatory pathway

    Directory of Open Access Journals (Sweden)

    Zhang H

    2018-01-01

    Full Text Available Hongxia Zhang,1 Yanlan Yang,2 Yanqin Wang,1 Baodong Wang,1 Rongshan Li1 1Department of Nephrology, 2Department of Endocrinology, Affiliated People’s Hospital of Shanxi Medical University, Shanxi Provincial People’s Hospital, Taiyuan, Shanxi, People’s Republic of China Background: Diabetic nephropathy (DN is a major microvascular complication in diabetes. An increasing body of evidence has shown that DN is related to chronic inflammation, kidney hypertrophy, and fibrosis. While thalidomide has been shown to have anti-inflammatory and antifibrotic effects, the effects of thalidomide on the pathogenesis of DN are unclear. This study was undertaken to explore whether thalidomide has renal-protective effects in diabetic rats.Methods: Male Sprague Dawley rats were injected intraperitoneally with 50 mg/kg streptozotocin to induce diabetes. Diabetic rats were treated with thalidomide (200 mg/kg/d for 8 weeks, and then blood and urine were collected for measurement of renal function-related parameters. Histopathology, immunohistochemistry, enzyme-linked immunosorbent assay, and Western blot analyses were performed to assess renal proinflammatory cytokines, fibrotic protein, and related signaling pathways.Results: Diabetic rats exhibited obvious renal structural and functional abnormalities, as well as renal inflammation and fibrosis. Compared with diabetic control rats, those treated with thalidomide showed significantly improved histological alterations and biomarkers of renal function, as well as reduced expression of renal inflammatory cytokines, including NF-κB and MCP-1. Furthermore, renal fibrotic proteins, such as TGF-β1, TβRII, TβRI, smad3, collagen IV, and fibronectin were also remarkably suppressed. Treatment with thalidomide markedly stimulated the phosphorylation of AMPKα.Conclusion: In this study, thalidomide suppressed the inflammatory and fibrotic processes in DN. These effects were partly mediated by the activation of AMPK

  4. Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

    Directory of Open Access Journals (Sweden)

    Tânia R.C. Vergara

    2017-09-01

    Conclusions: Short-term use of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4+ cell count without changes to the CD8+ cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication.

  5. Thalidomide suppresses Up-regulation of human immunodeficiency virus coreceptors CXCR4 and CCR5 on CD4+ T cells in humans

    NARCIS (Netherlands)

    Juffermans, N. P.; Verbon, A.; Olszyna, D. P.; van Deventer, S. J.; Speelman, P.; van der Poll, T.

    2000-01-01

    Concurrent infection in patients with human immunodeficiency virus (HIV) infection increases the expression of HIV coreceptors CXCR4 and CCR5. Thalidomide has beneficial effects in a number of HIV-associated diseases. The effect of thalidomide on CXCR4 and CCR5 expression on CD4+ T cells was

  6. Double-blind trial of the efficacy of pentoxifylline vs thalidomide for the treatment of type II reaction in leprosy

    Directory of Open Access Journals (Sweden)

    A.M. Sales

    2007-02-01

    Full Text Available Type II reaction in leprosy, or erythema nodosum leprosum (ENL, is often characterized by severe clinical symptoms together with nerve function impairment leading to permanent disabilities. Thalidomide has been shown to be a highly effective drug for the treatment of ENL. It is, however, contraindicated for women of childbearing age due to its teratogenicity. On the other hand, pentoxifylline, used to treat hypercoagulable states, is not teratogenic and, like thalidomide, can inhibit the synthesis of tumor necrosis factor-a and other cytokines. In the present randomized double-blind clinical study we compared the effectiveness of orally administered pentoxifylline vs thalidomide in treating type II reaction in 44 patients. Daily doses of 300 mg thalidomide or 1.2 g pentoxifylline were administered for 30 days to multibacillary leprosy patients undergoing type II reaction. Randomly chosen patients were included in the study before, during, and after specific multidrug therapy. Clinical evaluations were performed on the 1st, 7th, 14th, 21st, and 30th days of treatment and laboratory tests were carried out on the 1st and 30th days. As expected, overall, thalidomide proved to be more effective in the treatment of type II leprosy reaction. Nevertheless, continuous treatment with pentoxifylline was effective in relieving the clinical signs of ENL, especially limb edema and systemic symptoms, in 62.5% of the patients.

  7. Clinical use and control of the dispensing of thalidomide in Brasilia-Federal District, Brazil, from 2001 to 2012

    Directory of Open Access Journals (Sweden)

    Francisco José Roma Paumgartten

    2013-11-01

    Full Text Available The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction. Babies with birth defects compatible with the thalidomide embryopathy phenotype were born after 1965, an indication that control on drug dispensing and use failed in the country. The article reports data on thalidomide dispensing and clinical uses in the Federal District in 2011/12, when new rules were put into effect, and data on drug dispensing and use obtained ten years earlier. It was found that the number of patients making use of thalidomide declined from 819 in 2001 to 369 in 2011/12. Leprosy accounted for over 70% of prescriptions in both time periods analyzed in this study. In the same time interval, however, use for lupus erythematosus decreased from 13.7 to 4.9%, while that for multiple myeloma increased from 2.9 to 20.3% of all prescriptions. Thalidomide prescription for the remaining approved indications was far less frequent, and so was the use for off label indications that accounted for <1% of prescriptions in 2001 and 2011/12. Registration of prescribing doctors, patients and dispensing units at the state department of health, apparently rendered this control more effective and reliable.

  8. Clinical use and control of the dispensing of thalidomide in Brasilia-Federal District, Brazil, from 2001 to 2012.

    Science.gov (United States)

    Paumgartten, Francisco José Roma; de Souza, Nair Ramos

    2013-11-01

    The use of thalidomide was never discontinued in Brazil where it is prescribed for leprosy type 2 reaction. Babies with birth defects compatible with the thalidomide embryopathy phenotype were born after 1965, an indication that control on drug dispensing and use failed in the country. The article reports data on thalidomide dispensing and clinical uses in the Federal District in 2011/12, when new rules were put into effect, and data on drug dispensing and use obtained ten years earlier. It was found that the number of patients making use of thalidomide declined from 819 in 2001 to 369 in 2011/12. Leprosy accounted for over 70% of prescriptions in both time periods analyzed in this study. In the same time interval, however, use for lupus erythematosus decreased from 13.7 to 4.9%, while that for multiple myeloma increased from 2.9 to 20.3% of all prescriptions. Thalidomide prescription for the remaining approved indications was far less frequent, and so was the use for off label indications that accounted for <1% of prescriptions in 2001 and 2011/12. Registration of prescribing doctors, patients and dispensing units at the state department of health, apparently rendered this control more effective and reliable.

  9. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

    DEFF Research Database (Denmark)

    de Bono, Johann Sebastian; Oudard, Stephane; Ozguroglu, Mustafa

    2010-01-01

    Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer with progre...

  10. Acne fulminans successfully treated with prednisone and dapsone Acne fulminans tratada com prednisona associada à dapsona

    Directory of Open Access Journals (Sweden)

    Rafael Bandeira Lages

    2012-08-01

    Full Text Available Acne fulminans is a rare condition and the most severe form of acne. It involves the sudden onset of febrile and multisystemic symptoms, with poor response to ordinary therapy in patients who previously had mild to moderate acne. It is characterized by hemorrhagic ulcerative crusting lesions on the face, chest and upper back. The authors report a case of acne fulminans that was successfully treated with oral prednisone and dapsone.A acne fulminans é uma condição rara e a mais severa forma de acne. Manifesta-se com um quadro agudo, febril e multissistêmico, resistente à terapêutica convencional em doentes com antecedente de acne leve ou moderada. As lesões são caracteristicamente úlcero-hemorrágicas e acometem preferencialmente tórax e face. Os autores relatam um caso de acne fulminans com excelente resposta terapêutica ao tratamento empregado.

  11. Randomized clinical trial comparing oral prednisone (50 mg) with placebo before laparoscopic cholecystectomy

    DEFF Research Database (Denmark)

    Bisgaard, Thue; Schulze, S.; Hjortso, N.C.

    2008-01-01

    cholecystectomy. Methods In a double-blind placebo-controlled study, 200 patients were randomized to oral administration of prednisone (50 mg) or placebo 2 h before laparoscopic cholecystectomy. Patients received a similar standardized anaesthetic, surgical, and analgesic treatment. The primary outcome was pain...... the first 24 h. Side-effects and 30-day follow-up for morbidity were registered. Results Data from 184 patients were available for statistical analysis. There were no significant differences in side-effects or complications between the surgical groups (P > 0.05). No significant intergroup differences in 24......-h pain, fatigue or malaise scores or any other variables were found (P > 0.05). Conclusion There is no important clinical gain of preoperative oral steroid administration compared with placebo in patients undergoing laparoscopic cholecystectomy Udgivelsesdato: 2008/2...

  12. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

    Directory of Open Access Journals (Sweden)

    Yuzbasiyan-Gurkan Vilma

    2008-08-01

    Full Text Available Abstract Background Canine cutaneous mast cell tumor (MCT is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI and overall survival times (OS of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Results Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. Conclusion and clinical importance This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs.

  13. Evaluation of the effectiveness of treatment with prednisone and azathioprine of autoimmune hepatitis in children.

    Science.gov (United States)

    Pniewska, Anna; Sobolewska-Pilarczyk, Małgorzata; Pawłowska, Małgorzata

    2016-01-01

    Autoimmune hepatitis is rarely diagnosed in children, but the course of the disease is often aggresive. Combination therapy with prednisone and azathioprine improves the prognosis of patients. To evaluate the effectiveness of combination therapy with prednisone and azathioprine of autoimmune hepatitis (AIH) in children. There was a retrospective analysis of the medical records of 15 patients with AIH, diagnosed before18 years of age, treated in the Provincial Infectious Diseases Hospital in Bydgoszcz in the years 2002 to 2013. We analysed the results of laboratory tests, ultrasound examination, endoscopy, and morphological liver pictures, as well as periods of exacerbation of inflammation and side effects of therapy. Biochemical remission of the disease was achieved on average after 36 days of treatment. Histopathological regression in the control liver biopsy was found in 7/15 patients and progression in 2/15 patients. In the study group 10/15 patients experienced exacerbation of the disease from 1 to 3 times during observation, with an increase of ALT activity to greater than 3 norm, and the remaining 5/15 patients had no increase of ALT activity. In total, 10 patients in the study group experienced 17 exacerbations. In 13/17 cases of exacerbations they were associated with a reduction in the dose of immunosuppressive drugs. There was no correlation between the biochemical exacerbation and changes in the histopathological image. Steroidside effects occurred in 14/15 patients. The treatment allows for biochemical remission of the disease and significantly improves the prognosis of most patients. However, significant side effects of treatment indicate the need for further exploration of effective and safe therapy, especially in the paediatric population.

  14. Effect of low-dose prednisone (with calcium and calcitriol supplementation) on calcium and bone metabolism in healthy volunteers

    NARCIS (Netherlands)

    Lems, W. F.; van Veen, G. J.; Gerrits, M. I.; Jacobs, J. W.; Houben, H. H.; van Rijn, H. J.; Bijlsma, J. W.

    1998-01-01

    The administration of moderate to high doses of corticosteroids is associated with bone loss. This probably results from the uncoupling of bone formation (decreased) and bone resorption (unchanged or increased). We examined the effect of low-dose (10 mg/day) prednisone (LDP) and the possible

  15. The Influence of Prednisone on the Efficacy of Cabazitaxel in Men with Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Buonerba, Carlo; Sonpavde, Guru; Vitrone, Francesca; Bosso, Davide; Puglia, Livio; Izzo, Michela; Iaccarino, Simona; Scafuri, Luca; Muratore, Margherita; Foschini, Francesca; Mucci, Brigitta; Tortora, Vincenzo; Pagliuca, Martina; Ribera, Dario; Riccio, Vittorio; Morra, Rocco; Mosca, Mirta; Cesarano, Nicola; Di Costanzo, Ileana; De Placido, Sabino; Di Lorenzo, Giuseppe

    2017-01-01

    Background: Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients. Patients and methods: Medical records of deceased patients with documented mCRPC treated with cabazitaxel following prior docetaxel between January, 2011 and January, 2017 were reviewed at the single participating center. Patients who were receiving daily doses of systemic corticosteroids other than low dose daily prednisone or prednisolone (30% PSA decline at 12 weeks. Prednisone use was not significantly prognostic for overall survival or PSA decline ≥30% rates on regression analyses. Importantly, a >30% PSA decline at 12, but not at 3, 6, 9 weeks, was prognostic for improved survival at multivariate analysis Conclusions: The data presented here support the hypothesis that omitting daily corticosteroids in cabazitaxel-treated patients has no negative impact on either survival or safety profile. In the large prospective trial CABACARE, cabazitaxel-treated patients will be randomized to receive or not receive daily prednisone. The CABACARE (EudraCT n. 2016-003646-81) study is currently ongoing at University Federico II of Naples and at other multiple participating centers in Italy. PMID:28928853

  16. Biotransformation of prednisone and dexamethasone by cytochrome P450 based systems - Identification of new potential drug candidates.

    Science.gov (United States)

    Putkaradze, Natalia; Kiss, Flora Marta; Schmitz, Daniela; Zapp, Josef; Hutter, Michael C; Bernhardt, Rita

    2017-01-20

    Prednisone and dexamethasone are synthetic glucocorticoids widely used as anti-inflammatory and immunosuppressive drugs. Since their hydroxylated derivatives could serve as novel potential drug candidates, our aim was to investigate their biotransformation by the steroid hydroxylase CYP106A2 from Bacillus megaterium ATCC13368. In vitro we were able to demonstrate highly selective 15β-hydroxylation of the steroids with a reconstituted CYP106A2 system. The reactions were thoroughly characterized, determining the kinetic parameters and the equilibrium dissociation constant. The observed lower conversion rate in the case of dexamethasone hydroxylation was clarified by quantum chemical calculations, which suggest a rearrangement of the intermediately formed radical species. To identify the obtained conversion products with NMR, CYP106A2-based Bacillus megaterium whole-cell systems were applied resulting in an altered product pattern for prednisone, yet no significant change for dexamethasone conversion compared to in vitro. Even the MS941 control strain performed a highly selective biotransformation of prednisone producing the known metabolite 20β-dihydrocortisone. The identified novel prednisone derivatives 15β, 17, 20β, 21-tetrahydroxy-preg-4-en-3,11-dione and 15β, 17, 20β, 21-tetrahydroxy-preg-1,4-dien-3,11-dione as well as the 15β-hydroxylated variants of both drugs are promising candidates for drug-design and development approaches. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Prednisone treatment of elderly-onset rheumatoid arthritis: Disease activity and bone mass in comparison with chloroquine treatment

    NARCIS (Netherlands)

    D. van Schaardenburg (Dirkjan); R. Valkema (Roelf); B.A.C. Dijkmans (Ben); S.E. Papapoulos (Socrates); A.H. Zwinderman (Ailko); K.H. Han (Hubert); E.K.J. Pauwels (Ernest K.J); F.C. Breedveld (Ferdinand)

    1995-01-01

    textabstractObjective. Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to

  18. Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children.

    Science.gov (United States)

    Tang-Wai, Richard; Mailo, Janette; Rosenblatt, Bernard

    2017-04-01

    Because immune mediated mechanisms are suspected in epileptogenesis, IVIg and corticosteroids have been used as alternatives to treat refractory seizures. We present our experience treating intractable epileptic children with IVIg and prednisone. Children with intractable epilepsy treated with prednisone or IVIg between 2005-2016 were reviewed retrospectively. Children with infantile spasms and autoimmune epilepsy were excluded. Data analyzed include epilepsy type and etiology, duration of epilepsy prior to treatment, seizure outcome, time to best seizure outcome, and adverse effects. Fifty-one patients were included: 26 received IVIg; 25 received prednisone. Etiologies were similar between cohorts: genetic (13 IVIg; 10 prednisone), lesional (8 IVIg; 7 prednisone), and unknown (5 IVIg; 8 prednisone). In the prednisone cohort, 92.0% had generalized epilepsy compared to 61.5% for IVIg. Among the IVIg treated, 84.6% responded (10 genetic, 4 unknown, and 8 lesional) with mean seizure reduction of 77.3% and mean time to best response of 9.8 weeks. With prednisone, 24.0% responded (2 genetic, 3 unknown, and 1 lesional) with a mean seizure reduction of 95.0% and mean time to best response of 2.7 weeks. Adverse effects occurred in 2 and 16 patients treated with IVIg and prednisone, respectively. The difference in responders and seizure reduction was statistically significant (p<0.0001 and p=0.001, respectively). IVIg had greater responders and lower adverse effects and honeymoon effect. This response was independent of epilepsy type, etiology, and duration suggesting different mechanisms of action between prednisone and IVIg and a common, reversible, immune-mediated pathway to intractability. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  19. The penumbra of thalidomide, the litigation culture and the licensing of pharmaceuticals.

    Science.gov (United States)

    Lachmann, P J

    2012-12-01

    Fifty years ago several thousand children were born with severe limb defects after their mothers had been given thalidomide in pregnancy. This tragedy caused procedures for licensing new medicines to become much stricter. Where, nevertheless, significant side effects were found it became common to sue for damages. These consequences have caused possibly an even greater disaster damaging many more people and threatening ruin to health services everywhere. The huge increase in both time and cost in bringing medicines to market is increasing their price to unsupportable levels; and only wealthy companies are now able to do so. This requires reform as does litigation for 'statistical' harmful effects.

  20. Severe Gastrointestinal Bleeding in a Patient With Subvalvular Aortic Stenosis Treated With Thalidomide and Octreotide

    DEFF Research Database (Denmark)

    Hvid-Jensen, Helene S; Poulsen, Steen H; Agnholt, Jørgen S

    2015-01-01

    by an acquired coagulopathy known as Heyde's syndrome. Multiple factors are involved in the pathogenesis of angiodysplastic bleeding including genetic factors and increased levels of vascular intestinal growth factor at tissue levels. Endoscopic coagulation therapy is the primary treatment but often fails...... transcoronary ethanol ablation. No further bleeding episodes occurred, and thalidomide and octreotide were arrested. To our knowledge, this case report is the first to describe how this new drug combination therapy is an effective treatment of GB from angiodysplasias and can be used to bridge to surgical...

  1. Combination of thalidomide and cisplatin in an head and neck squamous cell carcinomas model results in an enhanced antiangiogenic activity in vitro and in vivo.

    Science.gov (United States)

    Vasvari, Gergely P; Dyckhoff, Gerhard; Kashfi, Farzaneh; Lemke, Britt; Lohr, Jennifer; Helmke, Burkhard M; Schirrmacher, Volker; Plinkert, Peter K; Beckhove, Philipp; Herold-Mende, Christel C

    2007-10-15

    Thalidomide is an immunomodulatory, antiangiogenic drug. Although there is evidence that it might be more effective in combination with chemotherapy the exact mechanism of action is unclear. Therefore, we investigated its effect in combination with metronomically applied cisplatin in a xenotransplant mouse model characteristic for advanced head and neck squamous cell carcinomas, its possible synergistic action in vitro, and which tumor-derived factors might be targeted by thalidomide. Although thalidomide alone was ineffective, a combined treatment with low-dose cisplatin inhibited significant tumor growth, proliferation and angiogenesis in vivo as well as migration and tube formation of endothelial cells in vitro. Noteworthy, the latter effect was enhanced after coapplication of cisplatin in nontoxic doses. An inhibitory effect on tumor cell migration was also observed suggesting a direct antitumor effect. Although thalidomide alone did not influence cell proliferation, it augmented antiproliferative response after cisplatin application emphasizing the idea of a potentiated effect when both drugs are combined. Furthermore, we could show that antiangiogenic effects of thalidomide are related to tumor-cell derived factors including vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and Il-8 some known and with, granulocyte colony stimulating growth factor and granulocyte macrophage colony stimulating growth factor, some new target molecules of thalidomide. Altogether, our findings reveal new insights into thalidomide-mediated antitumor and antiangiogenic effects and its interaction with cytostatic drugs. (c) 2007 Wiley-Liss, Inc.

  2. Combined treatment with low dose prednisone and escin improves the anti-arthritic effect in experimental arthritis.

    Science.gov (United States)

    Du, Yuan; Song, Yanqin; Zhang, Leiming; Zhang, Menglin; Fu, Fenghua

    2016-02-01

    The present study was aimed at investigating whether low dose oral prednisone combined with escin could inhibit the progression of adjuvant-induced arthritis (AIA) in rats. Adjuvant arthritis was induced in SD rats began day 1 for 28 days. Prednisone at doses of 2, 10 mg/kg/day alone or escin at doses of 5, 10 mg/kg/day alone, or prednisone at dose of 2 mg/kg/day with escin at doses of 5 or 10 mg/kg/day were given to different groups of rats intragastrically from day 13 to 28 respectively. Paw swelling, arthritic index, histological and radiographic changes were assessed to evaluate the anti-arthritic effect. Weight growth, spleen and thymus indexes were also calculated. Serum samples were collected for estimation of pro-inflammatory cytokines. Rats developed erosive arthritis of the hind paw when immunized with adjuvant. Prednisone 2 mg/kg combined with escin 5 or 10 mg/kg significantly inhibited the paw swelling. Histopathological and radiographic analysis showed a marked decrease of synovial inflammatory infiltration, synovial hyperplasia and bone erosion by combination therapy, which also markedly suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). No significant changes were found in monotherapy group except prednisone 10 mg/kg group. Furthermore, combined treatment rescued some of GCs' adverse effects evidenced by increase in body weight and decrease in index of spleen compared with untreated AIA rats. In conclusion, the combination therapy possessed synergistic anti-arthritic efficacy and reduced adverse effect, which may play a role in the management of human RA. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Efficacy of mizoribine followed by low-dose prednisone in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria.

    Science.gov (United States)

    Matsumoto, Yoshihiro; Shimada, Yasushi; Nojima, Youichi; Moriki, Toshiaki

    2013-08-01

    Idiopathic membranous nephropathy (IMN) patients with persistent high-grade proteinuria are at the highest risk for developing end-stage renal failure. We previously reported the effects of treatment with mizoribine followed by low-dose prednisone treatment in 4 IMN patients. The purpose of the present study was to further assess the effects of this combined treatment in a larger study group. Thirteen patients with IMN and nephrotic-range proteinuria received combined treatment. Mizoribine was initiated at a dose of 150 mg/day, and 2-3 months later, 20 mg/day prednisone was added to the mizoribine regimen. The dosage of prednisone and/or mizoribine was tapered according to the urinary protein-to-creatinine ratio (P/C). We evaluated patient responses for up to 12 months after the initiation of combination therapy. Before treatment, patient urinary P/C ranged from 3.7 to 15.9 g/g. Although these values did not decrease during mizoribine monotherapy, all patients showed dramatic P/C decreases over the course of combination therapy. At 3, 6, and 12 months after combination therapy, 15%, 31%, and 62% of patients attained complete remission, respectively, and all patients were in partial or complete remission 6 months after combination therapy. No notable side effects were observed. The addition of prednisone after mizoribine monotherapy can be beneficial for all IMN patients with nephrotic-range proteinuria syndrome. The risks associated with immunotherapy can be decreased by initially prescribing mizoribine alone, which might act as a base for establishing therapy, followed by low-dose prednisone treatment.

  4. Long-term event-free and overall survival after risk-adapted melphalan and SCT for systemic light chain amyloidosis.

    Science.gov (United States)

    Landau, H; Smith, M; Landry, C; Chou, J F; Devlin, S M; Hassoun, H; Bello, C; Giralt, S; Comenzo, R L

    2017-01-01

    Stem cell transplantation (SCT), an effective therapy for amyloid light chain (AL) amyloidosis patients, is associated with low treatment-related mortality (TRM) with appropriate patient selection and risk-adapted dosing of melphalan (RA-SCT). Consolidation after SCT increases hematologic complete response (CR) rates and may improve overall survival (OS) for patients with SCT with or without consolidation. Melphalan was administered at 100 (14%), 140 (52%) and 200 (34%) mg/m 2 . The TRM rate at 100 days was 5%. RA-SCT resulted in CR in 24% (3 months) and 48% (12 months) of patients. The CR rate was particularly high (62%) in patients offered bortezomib consolidation. With a median follow-up among survivors of 7.7 years, median event-free survival (EFS) with RA-SCT was 4.04 years (95% confidence interval (CI): 3.41-5.01 years); median OS was 10.4 years (95% CI: 7.3-not achieved). Patients with CR at 12 months after SCT had significantly longer EFS (P=0.01) and OS (P=0.04). In a multivariate analysis, melphalan dose had no impact on EFS (P=0.26) or OS (P=0.11). For selected patients, RA-SCT was safe and was associated with extended long-term survival. With the availability of novel agents for consolidation, RA-SCT remains a very effective and important backbone treatment for AL amyloidosis.

  5. After thalidomide - do we have the right balance between public health and intellectual property.

    Science.gov (United States)

    Feldschreiber, Peter; Breckenridge, Alasdair

    2015-01-01

    The current European regulatory and consumer protection legal framework is the legacy of Thalidomide. The disaster led to the introduction of systematic biological and clinical data to endorse the safety and efficacy of new medicines. The European Medicines Directive outlined the pre-clinical, clinical data and product information to evaluate an appropriate benefit. Risk profile of new medicines and also allowed innovative companies to extend patent protection and data/marketing exclusivity periods to compensate for the cost for research and development. However in recent years it has become apparent that the costs and time for research and development are becoming increasingly burdensome, particularly for new drugs with recently discovered mechanisms of action for cancers and neurodegenerative disorders. The costs of development and the commercial uncertainty of such products is reducing commercialisation of these medicines. There is now considerable debate in the regulatory community as to how this regulatory burden may be eased by making earlier review of benefit risk and hence earlier access to authorised medicines. The Courts are moving away from the wide definition of medicinal product to a more nuanced view of the biological and clinical therapeutic mechanisms to satisfy the 'functional' limb definition in the Directive. This may be a move away from the rigorous scientific methodology generated after thalidomide. We discuss the ethical and public health implications of this shift in policy and the implications for intellectual property mechanisms currently available to protect the commercial needs of companies.

  6. Thalidomide in refractory bleeding due to gastrointestinal angiodysplasias Talidomida en la hemorragia recidivante por angiodisplasias gastrointestinales

    Directory of Open Access Journals (Sweden)

    Antonio Garrido

    2012-02-01

    Full Text Available Objectives: to assess the efficacy of thalidomide in the treatment of relapsed or refractory bleeding secondary to gastrointestinal angiodysplasia. Material and methods: we carried out a prospective study of 12 patients with bleeding due to gastrointestinal angiodysplasia refractory to conventional therapy who were treated with thalidomide. For each patient, we considered: age, sex, underlying disease, previous therapies, dose and duration of thalidomide treatment, evolution of haemoglobin levels and adverse effects of treatment. The data obtained were analysed using descriptive statistics with SPSS v. 16. Results: seven men and 5 women with a mean age of 77 years were included in the present study. Five had some underlying pathology and all of them had received prior endoscopic/octreotide treatment. The dose of thalidomide administered was 200 mg/24 h and the duration of the treatment four months, with the exception of two patients in whom treatment was discontinued because of adverse side effects. Mean haemoglobin concentration before onset of treatment was 6.5 g/dL, at two months it was 11.3 g/dL and at the end of treatment 12.1 g/dL. Conclusions: thalidomide is an effective treatment in gastrointestinal bleeding due to angiodysplasia, but it was withdrawn due to side effects in 16% of the patients included in our study.Objetivos: valorar la eficacia de talidomida en la hemorragia recidivante y refractaria por angiodisplasias gastrointestinales. Material y métodos: se realizó un estudio prospectivo de 12 pacientes con hemorragia por angiodisplasias refractarios a la terapia convencional, que recibieron tratamiento con talidomida. Se determinó en cada caso: edad, sexo, patología de base, tratamientos previos, dosis y duración del tratamiento con talidomida, evolución de los valores de hemoglobina y efectos secundarios del tratamiento. Los datos fueron procesados mediante estadística descriptiva con SPSS versión 16. Resultados: se

  7. [Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms].

    Science.gov (United States)

    Zhao, Guangju; Cai, Xiaoxia; She, Xingrong; Li, Dong; Hong, Guangliang; Wu, Bin; Li, Mengfang; Lu, Zhongqiu

    2014-11-01

    To investigate the effects of thalidomide in a mouse model of paraquat-induced acute lung injury and the mechanisms underlying the properties of thalidomide. Male ICR mice were randomly allocated into four groups: nomal control group (n = 30), thalidomide control group (n = 30), paraquat poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA) malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting; Pathological changes of lung tissue were observed under light microscope by HE stain; the lung apoptosis cells were detected by TUNEL. The levels of MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all markedly increased in mice of paraquat poisioning group than those in nomal group at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (Pparaquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein were increased and the lung wet dry ratio were all significantly decreased in mice of THD treatment group at 1 d, 3 d, 7 d (Pparaquat poisioning. The apoptosis index was markedly decreased in THD treatment groups comparing to paraquat piosioning group (Pparaquat poisioning, thalidomide could attenuate paraquat-induced acute lung injury and its mechanism may be activating the Nrf2-ARE signaling pathway to protect mouse from Lipid peroxide damage.

  8. [Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy].

    Science.gov (United States)

    Huang, Ren-fa; Liang, Qun-qing; Cheng, Xin; Long, Yun; Wu, Jin-yu

    2013-08-01

    To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN). Totally 50 SD rats were randomly divided into 4 groups, i.e., the normal group, the model group, the CS group, the prednisone group, and the CS plus prednisone group, 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage, while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot. Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group, the prednisone group, and the CS plus prednisone group. Compared with the normal group, levels of BUN and SCr, semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic cells, and expressions of Notch2 and Hes-1 proteins significantly increased in the model group (P < 0.01). Compared with the model group, the aforesaid indices significantly decreased in the 3 treatment groups (P < 0.01). All indices decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01). Notch2/hes-1 signaling activation might be

  9. Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT.

    Science.gov (United States)

    Voermans, Nicol C; Benveniste, Olivier; Minnema, Monique C; Lokhorst, Henk; Lammens, Martin; Meersseman, Wouter; Delforge, Michel; Kuntzer, Thierry; Novy, Jan; Pabst, Thomas; Bouhour, Françoise; Romero, Norma; Leblond, Veronique; Bergh, Peter van den; Vekemans, Marie-Christiane; van Engelen, Baziel G; Eymard, Bruno

    2014-12-02

    Sporadic late-onset nemaline myopathy (SLONM) is a rare, late-onset myopathy that progresses subacutely. If associated with a monoclonal gammopathy of unknown significance (MGUS), the outcome is unfavorable: the majority of these patients die within 1 to 5 years of respiratory failure. This study aims to qualitatively assess the long-term treatment effect of high-dose melphalan (HDM) followed by autologous stem cell transplantation (SCT) in a series of 8 patients with SLONM-MGUS. We performed a retrospective case series study (n = 8) on the long-term (1-8 years) treatment effect of HDM followed by autologous SCT (HDM-SCT) on survival, muscle strength, and functional capacities. Seven patients showed a lasting moderate-good clinical response, 2 of them after the second HDM-SCT. All of them had a complete, a very good partial, or a partial hematologic response. One patient showed no clinical or hematologic response and died. This case series shows the positive effect of HDM-SCT in this rare disorder. Factors that may portend an unfavorable outcome are a long disease course before the hematologic treatment and a poor hematologic response. Age at onset, level and type of M protein (κ vs λ), and severity of muscle weakness were not associated with a specific outcome. This study provides Class IV evidence that for patients with SLONM-MGUS, HDM-SCT increases the probability of survival and functional improvement. © 2014 American Academy of Neurology.

  10. Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement.

    Science.gov (United States)

    Girnius, S; Seldin, D C; Meier-Ewert, H K; Sloan, J M; Quillen, K; Ruberg, F L; Berk, J L; Doros, G; Sanchorawala, V

    2014-03-01

    In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

  11. The USP Performance Verification Test, Part II: collaborative study of USP's Lot P Prednisone Tablets.

    Science.gov (United States)

    Glasgow, Maria; Dressman, Shawn; Brown, William; Foster, Thomas; Schuber, Stefan; Manning, Ronald G; Wahab, Samir Z; Williams, Roger L; Hauck, Walter W

    2008-05-01

    Periodic performance verification testing (PVT) is used by laboratories to assess and demonstrate proficiency and for other purposes as well. For dissolution, the PVT is specified in the US Pharmacopeia General Chapter Dissolution under the title Apparatus Suitability Test. For Apparatus 1 and 2, USP provides two reference standard tablets for this purpose. For each new lot of these reference standards, USP conducts a collaborative study. For new USP Lot P Prednisone Tablets, 28 collaborating laboratories provided data. The study was conducted with three sets of tablets: Lot O open label, Lot O blinded, and Lot P blinded. The blinded Lot O data were used for apparatus suitability testing. Acceptance limits were determined after dropping data due to failure of apparatus suitability, identification of data as unusual on control charts, or protocol violations. Results yielded acceptance criteria of (47, 82) for Apparatus 1 and (37, 70) for Apparatus 2. Results generally were similar for Lot P compared to results from Lot O except that the average percent dissolved for Lot P is greater than for Lot O with Apparatus 2.

  12. Juvenile osteopetrosis: effects on blood and bone of prednisone and a low calcium, high phosphate diet.

    Science.gov (United States)

    Dorantes, L M; Mejia, A M; Dorantes, S

    1986-07-01

    Four children with juvenile osteopetrosis are described who were treated with a combination of prednisone and a low calcium, high phosphate diet. One of the children, treated as a neonate, achieved complete clinical and radiological remission from the disease after nine months, at which point treatment was stopped. There have been no signs of recurrence for two years. Two who did not start treatment until over 24 months of age have shown a good clinical and radiological response but have remained on treatment for six years. The fourth child started treatment at 6 months and showed a good clinical response, but x ray films showed no change nine months later. He was then lost to follow up, stopped treatment, and died two years later of a septicaemia. These patients provide further evidence for the efficacy of steroids in juvenile osteopetrosis, and the combination with the low calcium, high phosphate diet described offers a potentially effective alternative treatment to marrow transplantation, both for the haematological and skeletal complications of the disorder.

  13. Long-term treatment of thalidomide ameliorates amyloid-like pathology through inhibition of β-secretase in a mouse model of Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Ping He

    Full Text Available Thalidomide is a tumor necrosis factor alpha (TNFα inhibitor which has been found to have abilities against tumor growth, angiogenesis and inflammation. Recently, it has been applied in clinic for the treatment of multiple myeloma as well as some inflammatory diseases. However, whether thalidomide has any therapeutic effects on neurodegenerative disorders, i.e. Alzheimer's disease (AD is not clear. AD is characterized by excessive amount of amyloid β peptides (Aβ, which results in a significant release of inflammatory factors, including TNFα in the brain. Studies have shown that inhibition of TNFα reduces amyloid-associated pathology, prevents neuron loss and improves cognition. Our recent report showed that genetic inhibition of TNFα/TNF receptor signal transduction down-regulates β amyloid cleavage enzyme 1 (BACE1 activity, reduces Aβ generation and improves learning and memory deficits. However, the mechanism of thalidomide involving in the mitigation of AD neuropathological features remains unclear. Here, we chronically administrated thalidomide on human APPswedish mutation transgenic (APP23 mice from 9 months old (an onset of Aβ deposits and early stage of AD-like changes to 12 months old. We found that, in addition of dramatic decrease in the activation of both astrocytes and microglia, thalidomide significantly reduces Aβ load and plaque formation. Furthermore, we found a significant decrease in BACE1 level and activity with long-term thalidomide application. Interestingly, these findings cannot be observed in the brains of 12-month-old APP23 mice with short-term treatment of thalidomide (3 days. These results suggest that chronic thalidomide administration is an alternative approach for AD prevention and therapeutics.

  14. Talidomida, contextos históricos y éticos Thalidomide, historical and ethical contexts

    Directory of Open Access Journals (Sweden)

    José Ángel Chávez Viamontes

    2009-12-01

    Full Text Available A finales de la década del 50, en Europa, Australia, Japón y varios países africanos, la talidomida provocó más de 10 000 casos de defectos congénitos en hijos de madres que la consumieron durante el embarazo. En 1962, es retirada del mercado. Tres décadas después, se reivindica su prescripción en el manejo de enfermedades de pronóstico desfavorable. Sus propiedades antiangiogénicas e inmunorreguladoras la hacen diferente al fármaco de los años 50 en gran medida. A pesar de poseer las mismas propiedades farmacológicas y riesgos teratogénicos, la molécula talidomida tiene otras las indicaciones, dosis, campos de aplicación y condiciones legales de uso. Esta revisión tiene como objetivo reseñar los contextos históricos y éticos que condicionaron la proscripción de la talidomida a principios de los años 60, así como las actuales condiciones clínicas en que se usan o ensayan actualmente sus efectos terapéuticos.In Europe, Australia, Japan, and some African countries in the late 50's, Thalidomide caused more than 10 000 cases of congenital defects in children whose mothers consumed it during pregnancy. In 1962, it was withdrawn from market. Thirty years later, it is used for the management diseases with unfavorable prognosis. Its antiangiogenic and immunoregulatory characteristics distinguish it from the drug of 1950. Although containing the same pharmacological features and teratogenic risks, the molecule thalidomide does have other prescriptions, doses, application fields, and lawful conditions of use. This revision points out both the historical and ethical contexts, which conditioned the banning of Thalidomide in the early 60's, and the clinical conditions in which its therapeutic effects are used and studied today.

  15. An innovative, simple, fast, and less toxic high-performance liquid chromatographic method for determination of prednisone in capsules

    Directory of Open Access Journals (Sweden)

    Pedro Henrique Reis da Silva

    2017-06-01

    Full Text Available ABSTRACT Prednisone is an anti-inflammatory steroid drug widely used in clinical practice. However, no high-performance liquid chromatographic (HPLC method has been described in the literature for the determination of prednisone in capsules until now. Thus, an HPLC method was developed using a C18 (250x4.0, 5 µm column, with methanol:water (70:30 as mobile phase at a flow rate of 1 mL/min and detection at 240 nm. The developed method was validated following current Brazilian legislation. Additionally, linearity was assessed by evaluating the assumptions of normality, homoscedasticity, and independency of residuals, and the fit to the linear model. The method showed linearity (r2>0.99 over the range of 14.0-26.0 µg/mL, selectivity, precision (RSD<2.0%, robustness, and accuracy (average recovery of 100.05%. The chromatographic procedure was applied for assay and uniformity content determination of three different batches of prednisone capsules, showing to be suitable for their quality control.

  16. Initial testing (stage 1) of M6620 (formerly VX-970), a novel ATR inhibitor, alone and combined with cisplatin and melphalan, by the Pediatric Preclinical Testing Program.

    Science.gov (United States)

    Kurmasheva, Raushan T; Kurmashev, Dias; Reynolds, C Patrick; Kang, Min; Wu, Jianwrong; Houghton, Peter J; Smith, Malcolm A

    2018-02-01

    M6620 is a novel inhibitor of the DNA damage repair enzyme ATR, and has potentiated the activity of cisplatin and irinotecan in non-small cell lung cancer and colon cancer xenografts, respectively. M6620 was tested in vitro at concentrations ranging from 1.0 nM to 10.0 μM and at 75 nM in combination with cisplatin or melphalan. M6620 was tested against 24 solid tumor xenografts alone and in combination with cisplatin. Cisplatin was administered intraperitoneally on days 1 and 8 at a dose of 5 mg/kg. M6620 was administered intravenously on days 2 and 9 at 20 mg/m 2 approximately 16 hr after cisplatin. The median relative IC 50 (rIC 50 ) value for M6620 was 0.19 μM (range 0.03-1.38 μM). M6620 reduced the mean IC 50 of cisplatin and melphalan by 1.48- and 1.95-fold, respectively. M6620 as a single agent in vivo induced significant differences in event-free survival (EFS) distribution in 5 of 24 (21%) solid tumor xenografts, but induced no objective responses. Cisplatin as a single agent induced significant differences in EFS distribution compared to control in 18 of 24 (75%) solid tumor xenografts. Three objective responses to cisplatin were observed. The M6620 and cisplatin combination induced significant differences in EFS distribution compared to control in 21 of 24 (88%), with four objective responses. M6620 showed modest potentiation of cisplatin and melphalan activity for some cell lines. M6620 showed little single-agent activity and the addition of M6620 to cisplatin significantly prolonged time to event for a minority of tested xenografts across several histologies. © 2017 Wiley Periodicals, Inc.

  17. Effect of cytarabine, melphalan, and total body irradiation as conditioning for autologous stem cell transplantation for patients with AML in first remission

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Ki Mun; Chai, Gyu Young [College of Medicine, Gyeongsang National Univ., Jinju (Korea, Republic of); Choi, Byung Ock; Kang, Young Nam; Jang, Hong Sek; Choi, Ihl Bohng [College of Medicine, The Catholic Univ., Seoul (Korea, Republic of); Kim, Hee Jae; Min, Wo Sung; Kim, Chun Choo [The Catholic Hematopoietic Stem Cell Transplantation Center, Seoul, (Korea, Republic of)

    2003-09-01

    Current results of autologous stem cell transplantation (SCT) suggest that this procedure may prolong disease free survival in patients with acute myelojd leukemia (AML). Autologous SCT is increasingly used as treatment for AML in first remission. The aim of this study was to evaluate the outcome of autologous SCT for patients with AML in first remission treated by autologous SCT using cytarabine, melphalan and total body irradiation (TBI) as the conditioning regimen. Between January 1995 and December 1999, 29 patients with AML in first remission underwent autologous SCT. The median age of patients was 33 years (range, 16 to 47). The conditioning regimen consisted of cytarabine (3.0 gm/m{sup 2} for 3 days), melphalan (100 mg/m{sup 2} for 1 day) and TBI (total 1000 cGy in five fractions over 3 days). The median follow up was 40 months with a range of 3 to 58 months. The 4-year cumulative probability of disease free survival was 69.0%, and median survival was 41.5 months. The 4-year relapse rate was 27.6%. The factor influencing disease free survival and relapse rate was the French-American-British (FAB) classification (M{sub 3} group vs. other groups; p=0.048, p=O.043). One patient died from treatment-related toxicity. Although the small number of patients does not allow us to draw any firm conclusion, our results were encouraging and suggest that the association of cytarabine, melphalan and TBJ as a conditioning regimen for autologous SCT for AML in first remission appears to be safe and effective.

  18. Variability of high-dose melphalan exposure on oral mucositis in patients undergoing prophylactic low-level laser therapy.

    Science.gov (United States)

    Rodrigues, Gustavo Henrique; Jaguar, Graziella Chagas; Alves, Fabio Abreu; Guollo, Andre; Camandoni, Vanessa Oliveira; Damascena, Aline Santos; Lima, Vladmir Claudio Cordeiro

    2017-07-01

    The present study outlines the clinical impact and risk factors of oral mucositis in 79 patients with multiple myeloma following high-dose melphalan for autologous transplant. All patients underwent daily prophylactic low-level indium gallium aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm 2 , 10 s per point) from the beginning of the conditioning regimen up to day +2. Oral mucositis assessments were made daily until hospital discharge. For analysis, oral mucositis was divided into two groups according to severity: group 1, patients with oral mucositis grade

  19. The therapeutic T-cell response induced by tumor delivery of TNF and melphalan is dependent on early triggering of natural killer and dendritic cells.

    Science.gov (United States)

    Balza, Enrica; Zanellato, Silvia; Poggi, Alessandro; Reverberi, Daniele; Rubartelli, Anna; Mortara, Lorenzo

    2017-04-01

    The fusion protein L19mTNF (mouse TNF and human antibody fragment L19 directed to fibronectin extra domain B) selectively targets the tumor vasculature, and in combination with melphalan induces a long-lasting T-cell therapeutic response and immune memory in murine models. Increasing evidence suggests that natural killer (NK) cells act to promote effective T-cell-based antitumor responses. We have analyzed the role of NK cells and dendritic cells (DCs) on two different murine tumor models: WEHI-164 fibrosarcoma and C51 colon carcinoma, in which the combined treatment induces high and low rejection rates, respectively. In vivo NK-cell depletion strongly reduced the rejection of WEHI-164 fibrosarcoma and correlated with a decrease in mature DCs, CD4 + , and CD8 + T cells in the tumor-draining LNs and mature DCs and CD4 + T cells in the tumor 40 h after initiation of the therapy. NK-cell depletion also resulted in the impairment of the stimulatory capability of DCs derived from tumor-draining LNs of WEHI-164-treated mice. Moreover, a significant reduction of M2-type infiltrating macrophages was detected in both tumors undergoing therapy. These results suggest that the efficacy of L19mTNF/melphalan therapy is strongly related to the early activation of NK cells and DCs, which are necessary for an effective T-cell response. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

    Directory of Open Access Journals (Sweden)

    Alessia Nicotra

    Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

  1. Talidomida: indicações em Dermatologia Thalidomide: indications in Dermatology

    Directory of Open Access Journals (Sweden)

    Rubem David Azulay

    2004-10-01

    Full Text Available A talidomida, descoberta na Alemanha Oriental, em 1954, mostrou vários efeitos terapêuticos: antiemético, sedativo e hipnótico. De 1959 a 1961, foram descritas cerca de 12.000 crianças nascidas com defeitos teratogênicos. Seu uso foi, conseqüentemente, suspenso. Sheskin, entretanto, recomeçou a usar a droga e verificou efeito benéfico no eritema nodoso leprótico. A talidomida é derivada do ácido glutâmico. Sua eliminação urinária é mínima (1%. Tem ações: antiinflamatória, imunomoduladora e antiangiogênica. Tem sido usada, com certo êxito terapêutico, em algumas entidades mais adiante estudadas. O principal efeito adverso é teratogênico: alterações nos membros, orelhas, olhos e órgãos internos. Supõe-se que esses efeitos teratogênicos decorram da ação antiangiogênica. Outros efeitos adversos: cefaléia, secura da pele e da mucosa da boca, prurido, erupção cutânea, aumento de peso, hipotireoidismo, neutropenia, bradicardia ou taquicardia e hipotensão. Interage com outros fármacos: barbitúrico, clorpromazina, reserpina, álcool, acetaminofen, histamina, serotonina e prostaglandina.Thalidomide was discovered in East Germany in 1954. It presented with several therapeutic effects: antiemetic, sedative and hypnotic. From 1959 to 1961, roughly 12,000 children born with teratogenic defects were described. Its use was consequently halted. Sheskin started using the drug again and observed its beneficial effect on erythema nodosa leprosum. Thalidomide is derived from glutamic acid. Its urinary elimination is minimal (1%. It has the following actions: anti-inflammatory, immunomodulary and antiangiogenic. It has been used with a successful therapeutic outcome on some entities, which have been studied further. The main side effect is teratogenic: limb alterations, ears, eyes and internal organs. The teratogenic effects are assumed to result from antiangiogenic action. Other side effects are cephalea, dry skin and mouth

  2. A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation.

    Science.gov (United States)

    Hari, Parameswaran; Aljitawi, Omar S; Arce-Lara, Carlos; Nath, Rajneesh; Callander, Natalie; Bhat, Gajanan; Allen, Lee F; Stockerl-Goldstein, Keith

    2015-12-01

    Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National

  3. Impact of vibration and agitation speed on dissolution of USP prednisone tablets RS and various IR tablet formulations.

    Science.gov (United States)

    Seeger, Nicole; Lange, Sigrid; Klein, Sandra

    2015-08-01

    Dissolution testing is an in vitro procedure which is widely used in quality control (QC) of solid oral dosage forms and, given that real biorelevant test conditions are applied, can also be used as a predictive tool for the in vivo performance of such formulations. However, if a dissolution method is intended to be used for such purposes, it has to deliver results that are only determined by the quality of the test product, but not by other variables. In the recent past, more and more questions were arising on how to address the effects of vibration on dissolution test results. The present study was performed to screen for the correlation of prednisone dissolution of USP Prednisone Tablets RS with vibration caused by a commercially available vibration source as well as to investigate how drug release from a range of immediate release formulations containing class 1-4 drugs of the biopharmaceutical classification scheme is affected by vibration when performing dissolution experiments at different agitation rates. Results of the present study show that the dissolution process of oral drug formulations can be affected by vibration. However, it also becomes clear that the degree of which a certain level of vibration impacts dissolution is strongly dependent on several factors such as drug properties, formulation parameters, and the design of the dissolution method. To ensure the establishment of robust and predictive dissolution test methods, the impact of variation should thus be considered in method design and validation.

  4. New drugs in the therapy of multiple myeloma Novas drogas na terapia do mieloma múltiplo

    Directory of Open Access Journals (Sweden)

    Antonio Palumbo

    2008-06-01

    Full Text Available The advances in the understanding of the pathogenesis of multiple myeloma and the mechanism of drug resistance have led to the development of novel targeted therapies that are able to overcome resistance and show additive or synergistic effects with old chemotherapeutic agents. Thalidomide, its immunomodulatory derivative lenalidomide, and the proteasome inhibitor bortezomib, in combination with oral melphalan in the elderly and with intravenous melphalan in younger patients, are changing the traditional treatment paradigm of multiple myeloma. High-dose melphalan followed by autologous stem cell transplantation in the younger patients and oral melphalan-prednisone-thalidomide in the elderly are the standard of care for newly diagnosed multiple myeloma. In younger patients, combinations incorporating thalidomide or lenalidomide or bortezomib significantly increase the pre-transplant response rate before high-dose melphalan and autologous transplantation, and may further improve the response rate and survival achieved after transplant. Prospective randomized studies incorporating new agents and stratifying patients based on cytogenetic abnormalities, are needed to define the therapeutic algorithm in high-risk disease.O avanço do conhecimento da patogênese do mieloma múltiplo e do mecanismo de resistência a drogas propiciou o desenvolvimento de novas terapias alvo que vençam a resistência e apresentem efeitos sinérgicos e aditivos aos velhos agentes quimioterápicos. A talidomida, e o seu derivado imonumodulador, lenalidomida, e o inibidor da proteasoma bortezomib, em combinação com o melfalano no idoso e intravenoso no jovem, estão mudando os paradigmas tradicionais de tratamento do mieloma múltiplo. Altas doses de melfalano seguidas do transplante de células-tronco autólogo no paciente jovem e o tratamento oral de melfalano-predimisona- talidomida no idoso são agora tratamentos padrões para os portadores de mieloma múltiplo rec

  5. Thalidomide treatment modulates macrophage pro-inflammatory function and cytokine levels in Klebsiella pneumoniae B5055 induced pneumonia in BALB/c mice.

    Science.gov (United States)

    Kumar, Vijay; Harjai, Kusum; Chhibber, Sanjay

    2010-07-01

    Lung innate immune response plays an important role in the clearance of pathogens from lungs, however, profound activation of innate immune cells (alveolar macrophages or neutrophils) can lead to development of acute lung inflammation or injury by producing various pro-inflammatory molecules (IL-1, TNF-alpha and H2O2 etc.). Present study is designed to investigate the immunomodulatory action of thalidomide in Klebsiella pneumoniae B5055 induced acute lung infection in BALB/c mice. Acute lung inflammation was induced by intranasal instillation of K. pneumoniae B5055 into mice without any anaesthesia and treated with thalidomide (30 mg/kg/day/po) or normal saline orally using a treatment schedule shown to modulate pro-inflammatory innate immune response. Thalidomide treatment modulated pro-inflammatory function of alveolar macrophages by significantly (ppneumonia caused by gram negative bacterial infection. 2010 Elsevier B.V. All rights reserved.

  6. Thromboembolic Events Associated with Thalidomide and Multimodality Therapy for Soft Tissue Sarcomas: Results of RTOG 0330

    Directory of Open Access Journals (Sweden)

    J. M. Kane

    2012-01-01

    Full Text Available Introduction. RTOG 0330 was developed to address the toxicity of RTOG 9514 and to add thalidomide (THAL to MAID chemoradiation for intermediate/high grade soft tissue sarcomas (STSs and to preoperative radiation (XRT for low-grade STS. Methods. Primary/locally recurrent extremity/trunk STS: ≥8 cm, intermediate/high grade (cohort A: >5 cm, low grade (cohort B. Cohort A: 3 cycles of neoadjuvant MAID, 2 cycles of interdigitated THAL (200 mg/day/concurrent 22 Gy XRT, resection, 12 months of adjuvant THAL. Cohort B: neoadjuvant THAL/concurrent 50 Gy XRT, resection, 6 months of adjuvant THAL. Planned accrual 44 patients. Results. 22 primary STS patients (cohort A/B 15/7. Cohort A/B: median age of 49/47 years; median tumor size 12.8/10 cm. 100% preoperative THAL/XRT and surgical resection. Three cycles of MAID were delivered in 93% cohort A. Positive margins: 27% cohort A/29% cohort B. Adjuvant THAL: 60% cohort A/57% cohort B. Grade 3/4 venous thromboembolic (VTE events: 40% cohort A (1 catheter thrombus and 5 DVT or PE versus 0% cohort B. RTOG 0330 closed early due to cohort A VTE risk and cohort B poor accrual. Conclusion. Neoadjuvant MAID with THAL/XRT was associated with increased VTE events not seen with THAL/XRT alone or in RTOG 9514 with neoadjuvant MAID/XRT.

  7. Thalidomide salvage therapy following allogeneic stem cell transplantation for multiple myeloma: a retrospective study from the Intergroupe Francophone du Myélome (IFM) and the Société Française de Greffe de Moelle et Thérapie Cellulaire (SFGM-TC).

    Science.gov (United States)

    Mohty, M; Attal, M; Marit, G; Bulabois, C E; Garban, F; Gratecos, N; Rio, B; Vernant, J P; Sotto, J J; Cahn, J Y; Blaise, D; Jouet, J P; Facon, T; Yakoub-Agha, I

    2005-01-01

    Thalidomide is effective in multiple myeloma (MM), even in patients who have relapsed after high-dose therapy. A potent graft-versus-myeloma (GVM) effect can be induced against MM after allogeneic stem cell transplantation (allo-SCT). In all, 31 MM patients received thalidomide as a salvage therapy after progression following allo-SCT. The median maximum daily dose of thalidomide was 200 mg (range, 50-600). Thalidomide had to be discontinued in six patients (19%) because of toxicity. In all, nine patients (29%; 95% CI, 13-45) achieved an objective response with thalidomide therapy (six partial and three very good partial responses, VGPR). Five patients developed graft-versus-host disease (GVHD) after thalidomide therapy, including the three patients achieving a VGPR. These data demonstrate that thalidomide is potentially effective in MM patients failing allo-SCT.

  8. Effect of Ginkgo biloba extract combined with prednisone on bronchoalveolar lavage fluid related cytokines in patients with IPF

    Directory of Open Access Journals (Sweden)

    Zhen-Chun Shi

    2016-09-01

    Full Text Available Objective: To explore the effect of Ginkgo biloba extract (EGb combined with prednisone on bronchoalveolar lavage fluid (BALF related cytokines in patients with idiopathic pulmonary fibrosis (IPF. Methods: A total of 60 patients with IPF who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the observation group and the control group with 30 cases in each group. The patients in the two groups were given oxygen inhalation, bronchodilator agents, phlegm dissipating and asthma relieving, anti-infection, and other supporting treatments. The patients in the control group were orally given prednisone (0.5 mg/kg•d, continuously for 4 weeks, then in a dose of 0.25 mg/kg•d, continuously for 8 weeks, and finally the dosage was reduced to 0.125 mg/kg•d. On this basis, the patients in the observation group were given additional EGb, ie. ginkgo leaf capsule, 1 g/time, 3 times/d, continuously for 12 weeks. The efficacy was evaluated after 12- week treatment. ELISA was used to detect the levels of TNF-毩, IL-4, IL-10, and IFN-γ in BALF. The radioimmunoassay was used to determine the levels of serum HA, ColⅢ, PCⅢ, and LN. The pulmonary function detector was used to measure TLC, VC, DLCO, and 6MWT. Results: After treatment, TNF-毩 level in the control group was significantly reduced when compared with before treatment (P0.05, while HA, ColⅢ, PCⅢ, and LN levels in the observation group were significantly reduced when compared with before treatment (P<0.05, and the difference between the two groups was statistically significant (P<0.05. After treatment, TLC, VC, DLCO, and 6MWT in the two groups were significantly improved when compared with before treatment (P<0.05, and the difference between the two groups was statistically significant (P<0.05. Conclusions: EGb combined with prednisone can effectively enhance the levels of TNF-毩, IL-4, IL-10, and IFN-γ in BALF in patients with IPF, and

  9. Intermediate-dose melphalan (IDM) combined with G-CSF (filgrastim) is an effective and safe induction therapy for autologous stem cell transplantation in multiple myeloma.

    Science.gov (United States)

    Lokhorst, H M; Sonneveld, P; Wijermans, P W; van Marwijk Kooy, M; Meuwissen, O J; van Oers, R H; van der Griend, R; Dekker, A W

    1996-01-01

    Twenty-one previously untreated multiple myeloma (MM) patients and 10 previously treated patients with refractory or relapsed disease received two or three cycles of intermediate-dose melphalan (70 mg/m2) (IDM), administered intravenously every 6 weeks. Seven previously untreated patients received three and all other patients received two courses of IDM. The objective of the study was to reduce the toxicity of high-dose melphalan (140 mg/m2) (HDM) while maintaining its cytotoxic efficacy and secondly to ensure the possibility of collecting sufficient numbers of peripheral blood stem cells (PBSC) for transplantation. 18 (85%) previously untreated patients responded, of whom four achieved CR (18%). In addition five out of 10 previously treated patients with refractory or relapsed disease responded although bone marrow toxicity in this category was a major drawback. Toxicity was moderate, consisting of alopecia and moderate bone marrow suppression: the granulocyte count dropped below 0.5 x 10(9)/l and platelets below 25 x 10(9)/l for a median of 8 and 6 d, respectively. No serious infections occurred and the majority of patients attended the out-patient clinic. In 12/14 previously untreated patients sufficient peripheral blood CD34+ cells for harvest were present in the repopulation phase after the first IDM. In nine patients peripheral blood stem cells were collected and eight patients have undergone successful transplantation. Repeated IDM followed by filgrastim is highly effective in untreated MM and may be safely administered to reduce tumour load prior to PBSC collection. Autologous stem cells harvested after repeated IDM have a full long-term repopulating capacity.

  10. Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen.

    NARCIS (Netherlands)

    Dam, K. ten; Groot, I.J.M. de; Noordam, C.; Alfen, N. van; Hendriks, J.C.M.; Sie, L.T.L.

    2012-01-01

    Prednisone treatment delays the progressive course of Duchenne muscular dystrophy. The aim of this study was to determine the influence of the 10 day on/10 day off treatment on height and weight. We retrospectively reviewed the growth and weight charts of Duchenne patients born between 1988 and 2006

  11. Mucosal healing with thalidomide in refractory Crohn's disease patients intolerant of anti-TNF-α drugs: report of 3 cases and literature review.

    Science.gov (United States)

    Scribano, Maria Lia; Cantoro, Laura; Marrollo, Marzia; Cosintino, Rocco; Kohn, Anna

    2014-07-01

    Thalidomide is an oral immunomodulatory and anti-inflammatory drug with antitumor necrosis factor-α (TNF-α) activity. Several case reports and some clinical trials have demonstrated its efficacy in the treatment of refractory Crohn's disease (CD). We report the effect and tolerability of thalidomide in 3 patients with moderate-to-severe CD who were not responsive to anti-TNF-α therapies, and review the relevant literature. The first case is of a 28-year-old female affected by Crohn's colitis complicated by a severe fistulizing perianal disease; she was treated with infliximab, adalimumab, and certolizumab pegol, which were stopped because of intolerance. The second case is of a 39-year-old female with fistulizing ileocolitis complicated by severe arthralgias and perianal disease with loss of response to infliximab and intolerance of certolizumab pegol. The third case is of a 39-year-old male with gastric and ileocolonic CD refractory to immunosuppressors and intolerant of infliximab. All the 3 cases achieved complete clinical remission and endoscopic healing of mucosal lesions at a low dose of thalidomide (50 to 150 mg/d). In our CD patients who experienced loss of response or were unable to tolerate anti-TNF-α drugs, thalidomide was an effective and well-tolerated therapy for inducing and maintaining long-term remission.

  12. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials

    DEFF Research Database (Denmark)

    Fayers, Peter M; Palumbo, Antonio; Hulin, Cyrille

    2011-01-01

    carried out a meta-analysis of the 1685 individual patients in these trials. The primary endpoint was OS, and progression-free survival (PFS) and 1-year response rates were secondary endpoints. There was a highly significant benefit to OS from adding thalidomide to MP (hazard ratio = 0.83; 95% confidence...

  13. Effects of Some Natural Immunomodulatory Compounds in Combination with Thalidomide on Survival Rate and Tumor Size in Fibrosarcoma-Bearing Mice

    Directory of Open Access Journals (Sweden)

    Reza Aghebati Maleki

    2014-10-01

    Full Text Available Purpose: Despite significant advances have been achieved in cancer therapy, response to conventional treatments like surgery, radiotherapy and chemotherapy varies among individuals. Immunotherapy is known to be an effective strategy for patients who are resistant to the currently available interventions. Methods: Ninety-six male Balb/c mice (aged 6-8 weeks were selected and divided into twelve groups of eight. Approximately, 1×106of WEHI-164 cells were injected to each mouse for tumor genesis. Five immunotherapy treatments were considered in this study, including Heat Shock Proteins (HSP, Bacillus Calmette-Guérin (BCG, Bifidobacterium, Immuno-Modulator Drug (IMOD and Thalidomide. After tumor formation, the groups were treated with one or more of these therapies. Tumor size and survival rate was regularly monitored. Results: Depending on the treatment group, tumor sizes were different. In some groups, combined treatments demonstrated more inhibitory effects on tumor growth rate. The mice in group (IMOD+ Thalidomide had the lowest survival rate but group (BCG+ HSP+ Thalidomide survived until the end of the experiment. Conclusion: The (HSP+ BCG+ Thalidomide group exhibited satisfactory outcomes and two third of the mice in this group went into complete remission. Some combination therapies in test groups had significant impacts on survival and tumor growth rate.

  14. Thalidomide for treatment of gastrointestinal bleedings due to angiodysplasia : a case report in acquired von Willebrand syndrome and review of the literature

    NARCIS (Netherlands)

    Engelen, E T; van Galen, K P M; Schutgens, R E G

    INTRODUCTION: Acquired von Willebrand syndrome is a rare bleeding disorder and treatment of the associated gastrointestinal (GI) bleeding due to angiodysplasia is challenging. AIM: The aim of this study was to present a new case on the successful use of thalidomide in a patient with acquired von

  15. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept.

    Science.gov (United States)

    Pardo-Yules, Benjamin; Gallego-Durán, Rocío; Eslam, Mohammed; García-Collado, Carlos; Grande, Lourdes; Paradas, Carmen; Morillo, Ramón; Dorantes, Benito; Romero-Gómez, Manuel

    2011-12-01

    fewer than half of patients infected with hepatitis C virus (HCV) achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV) therapy. thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC) patients, who had failed to respond to the (Peg-IFN/RBV), with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study). none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.

  16. Functional and molecular effects of arginine butyrate and prednisone on muscle and heart in the mdx mouse model of Duchenne Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Alfredo D Guerron

    2010-06-01

    Full Text Available The number of promising therapeutic interventions for Duchenne Muscular Dystrophy (DMD is increasing rapidly. One of the proposed strategies is to use drugs that are known to act by multiple different mechanisms including inducing of homologous fetal form of adult genes, for example utrophin in place of dystrophin.In this study, we have treated mdx mice with arginine butyrate, prednisone, or a combination of arginine butyrate and prednisone for 6 months, beginning at 3 months of age, and have comprehensively evaluated the functional, biochemical, histological, and molecular effects of the treatments in this DMD model. Arginine butyrate treatment improved grip strength and decreased fibrosis in the gastrocnemius muscle, but did not produce significant improvement in muscle and cardiac histology, heart function, behavioral measurements, or serum creatine kinase levels. In contrast, 6 months of chronic continuous prednisone treatment resulted in deterioration in functional, histological, and biochemical measures. Arginine butyrate-treated mice gene expression profiling experiments revealed that several genes that control cell proliferation, growth and differentiation are differentially expressed consistent with its histone deacetylase inhibitory activity when compared to control (saline-treated mdx mice. Prednisone and combination treated groups showed alterations in the expression of genes that control fibrosis, inflammation, myogenesis and atrophy.These data indicate that 6 months treatment with arginine butyrate can produce modest beneficial effects on dystrophic pathology in mdx mice by reducing fibrosis and promoting muscle function while chronic continuous treatment with prednisone showed deleterious effects to skeletal and cardiac muscle. Our results clearly indicate the usefulness of multiple assays systems to monitor both beneficial and toxic effects of drugs with broad range of in vivo activity.

  17. Predictive factors of survival after thalidomide therapy in advanced multiple myeloma: long-term follow-up of a prospective multicenter nonrandomized phase II study in 120 patients.

    Science.gov (United States)

    Decaux, Olivier; Renault, Alain; Sébille, Véronique; Moreau, Philippe; Attal, Michel; Voillat, Laurent; Pegourie, Brigitte; Tiab, Mourad; Facon, Thierry; Zerbib, Robert; Grosbois, Bernard; Bellissant, Eric

    2012-12-01

    Thalidomide monotherapy has demonstrated consistent results in the treatment of advanced multiple myeloma. We report a 9-year follow-up of a French multicenter nonrandomized phase II study that evaluated the effect of oral thalidomide in 120 patients with advanced multiple myeloma. Independent predictors of survival were response to last therapy, performance status, serum β(2)-microglobulin level, platelet count, and response at day 60 of treatment. Thalidomide monotherapy has demonstrated consistent results in the treatment of advanced multiple myeloma. We report the 9-year follow-up of a French multicenter, nonrandomized, phase II study that evaluated the effect of oral thalidomide in advanced multiple myeloma. Thalidomide was started at 200 mg/d and increased to 400 mg/d at day 15. One hundred twenty patients were enrolled in 2 months at 33 centers. The overall response rate was 31.7% (38/120) on day 60. Overall survival rates were 47.5% (95% confidence interval [CI], 38.6-56.4), 25.0% (95% CI, 17.3-32.7), 11.7% (95% CI, 5.9-17.4), and 7.5% (95% CI, 2.8-12.2) at 1, 3, 6, and 9 years, respectively. Independent predictors of short survival at 1, 3, 6, and 9 years were multiple myeloma refractory to last therapy, performance status ≥ 2, serum β(2)-microglobulin level ≥ 3.5 mg/L, platelet count < 152 × 10(9)/L, and nonresponse at day 60 (Cox proportional hazards regression model). Our study identified 5 independent unfavorable prognostic factors associated with short survival. These prognostic factors were very robust, allowing the prediction of patient survival not only during the first year but also during 3, 6, and even 9 years after the beginning of treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial

    Energy Technology Data Exchange (ETDEWEB)

    Dodewaard-de Jong, Joyce M. van [VU University Medical Centre, Department of Medical Oncology, Amsterdam (Netherlands); Meander Medical Centre, Department of Medical Oncology, Amersfoort (Netherlands); Klerk, John M.H. de [Meander Medical Centre, Department of Nuclear Medicine, Amersfoort (Netherlands); Bloemendal, Haiko J. [Meander Medical Centre, Department of Medical Oncology, Amersfoort (Netherlands); University Medical Centre Utrecht, Department of Medical Oncology, Utrecht (Netherlands); Oprea-Lager, Daniela E.; Hoekstra, Otto S. [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Berg, H.P. van den [Tergooi Medical Hospital, Department of Medical Oncology, Hilversum (Netherlands); Los, Maartje [St Antonius Hospital Utrecht, Department of Medical Oncology, Utrecht (Netherlands); Beeker, Aart [Spaarne Gasthuis, Department of Medical Oncology, Hoofddorp (Netherlands); Jonker, Marianne A. [VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, Northern Ireland (United Kingdom); Verheul, Henk M.W.; Eertwegh, Alfons J.M. van den [VU University Medical Centre, Department of Medical Oncology, Amsterdam (Netherlands)

    2017-08-15

    Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m{sup 2} 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals. (orig.)

  19. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells

    Directory of Open Access Journals (Sweden)

    Madácsi Ramóna

    2010-06-01

    Full Text Available Abstract Background Cytoplasmic lipid-droplets are common inclusions of eukaryotic cells. Lipid-droplet binding thalidomide analogs (2,6-dialkylphenyl-4/5-amino-substituted-5,6,7-trifluorophthalimides with potent anticancer activities were synthesized. Results Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER, induction of reactive oxygen species (ROS, ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis. Conclusions Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.

  1. Modified high-dose melphalan and autologous SCT for AL amyloidosis or high-risk myeloma: analysis of SWOG trial S0115.

    Science.gov (United States)

    Sanchorawala, V; Hoering, A; Seldin, D C; Finn, K T; Fennessey, S A; Sexton, R; Mattar, B; Safah, H F; Holmberg, L A; Dean, R M; Orlowski, R Z; Barlogie, B

    2013-11-01

    We designed a trial using two sequential cycles of modified high-dose melphalan at 100 mg/m(2) and autologous SCT (mHDM/SCT) in AL amyloidosis (light-chain amyloidosis, AL), AL with myeloma (ALM) and host-based high-risk myeloma (hM) patients through SWOG-0115. The primary objective was to evaluate OS. From 2004 to 2010, 93 eligible patients were enrolled at 17 centers in the United States (59 with AL, 9 with ALM and 25 with hM). The median OS for patients with AL and ALM was 68 months and 47 months, respectively, and has not been reached for patients with hM. The median PFS for patients with AL and ALM was 38 months and 16 months, respectively, and has not been reached for patients with hM. The treatment-related mortality (TRM) was 12% (11/93) and was observed only in patients with AL after SCT. Grade 3 and higher non-hematologic adverse events were experienced by 81%, 67% and 57% of patients with AL, ALM and hM, respectively, during the first and second HDM/SCT. This experience demonstrates that with careful selection of patients and use of mHDM for SCT in patients with AL, ALM and hM, even in the setting of a multicenter study, OS can be improved with acceptable TRM and morbidity.

  2. Allogeneic bone marrow transplantation with conditioning regimen to total body irradiation + thiotepa + melphalan for 35 patients with high-risk leukemia

    International Nuclear Information System (INIS)

    Yumura-Yagi, Keiko; Inoue, Masami; Okamura, Takayuki

    1997-01-01

    Thirty-five children with high-risk leukemia received an allogeneic bone marrow transplantation (BMT) following a pre-conditioning regimen consisting of total body irradiation, thiotepa and melphalan. Twenty-one patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 acute undifferentiated leukemia, 2 acute mixed lineage leukemia, 2 myelodysplastic syndrome and 2 juvenile chronic myeloid leukemia. Sixteen patients received BMT while in complete remission (CR), but 19 were not in CR. Eighteen patients received transplants from HLA-matched related donors, 15 from unrelated donors and 2 from HLA-mismatched related donors. Cyclosporin±methotrexate was used for graft-versus-host disease (GVHD) prophylaxis in the BMTs from related donors and tacrolimus±prednisolone in the BMTs from unrelated donors. Transplant-related death occurred in 12 patients; 5 acute GVHD, 4 infections (3 fungal infections, 1 Cytomegalovirus pneumonia), 1 intracranial haemorrhage and 2 chronic GVHD. Relapses were observed in 6 patients (69, 168, 175, 222, 275 and 609 days post BMT). Event-free survival rate at 2 years is 38.1% in CR patients and 36.9% in nonCR patients. (author)

  3. In a high-dose melphalan setting, palifermin compared with placebo had no effect on oral mucositis or related patient's burden.

    Science.gov (United States)

    Blijlevens, N; de Château, M; Krivan, G; Rabitsch, W; Szomor, A; Pytlik, R; Lissmats, A; Johnsen, H E; de Witte, T; Einsele, H; Ruutu, T; Niederwieser, D

    2013-07-01

    This randomized-controlled trial studied the efficacy of palifermin in a chemotherapy-only, high-dose Melphalan (HDM) transplant setting, to reduce oral mucositis (OM) and its sequelae measured by patient-reported outcomes (PRO) and medical resource use. Palifermin, relative to placebo was given either pre-/post-HDM or pre-HDM in patients with multiple myeloma (MM) undergoing auto-SCT at 39 European centers. Oral cavity assessment (WHO) and PRO questionnaires (oral mucositis daily questionnaire (OMDQ) and EQ 5D) were used in 281 patients (mean age 56, ± s.d.=8 years). 57 patients received placebo. One hundred and fifteen subjects were randomized to pre-/post-HDM receiving palifermin on 3 consecutive days before HDM and after auto-SCT and 109 patients were randomized to pre-HDM, receiving palifermin (60 μg/kg/day) i.v. for 3 consecutive days before HDM. There was no statistically significant difference in maximum OM severity. Severe OM occurred in 37% (placebo), 38% (pre-/post-HDM) and 24% (pre-HDM) of patients. No significant difference was observed with respect to PRO assessments or medical resource use, but more infections and fever during neutropenia were reported in pre-/post-HDM vs placebo (for example, 51 and 26%). To conclude, palifermin was unable to reduce OM or OM-related patient's burden in MM transplant patients.

  4. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Vogel Ulla

    2010-08-01

    Full Text Available Abstract Background The response to treatment varies among patients with multiple myeloma and markers for prediction of treatment outcome are highly needed. Bioactivation of cyclophosphamide and thalidomide, and biodegradation of bortezomib, is dependent on cytochrome P450 metabolism. We explored the potential influence of different polymorphisms in the CYP enzymes on the outcome of treatment. Methods Data was analyzed from 348 patients undergoing high-dose treatment and stem cell support in Denmark in 1994 to 2004. Clinical information on relapse treatment in 243 individual patients was collected. The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion, *6, and CYP2D6 gene duplication. Results In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment. We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome.

  5. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary hemorrhagic telangiectasia: results of a prospective phase II clinical trial

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Caherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2016-01-01

    Summary Background Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anemia. Multiple therapeutic approaches have been tried, but they are largely palliative with variable results.We aimed to assess the efficacy of thalidomide in reducing epistaxis in patients with HHT refractory to standard therapy. Methods HHT patients with severe recurrent epistaxis refractory to mini-invasive surgical procedures were included in an open label, phase II, prospective, non-randomized, single-centre study. Thalidomide was administered at a starting dose of 50 mg/day orally. In the event of no response, thalidomide dosage was increased by 50 mg/day every four weeks until response to a maximum dose of 200 mg/day. After response achievement, patients were treated for eight to16 additional weeks. Monthly follow-up was based on the epistaxis severity score and transfusion need, with adverse events being reported (ClinicalTrials.gov Identifier: NCT01485224). Findings Thirty-one patients, mean age 62∙6 (SD 11∙1) years, were enrolled (median follow-up 15∙9 months, 25th-75th 10∙1-22∙3). Treatment induced cessation of bleeding in three cases (9∙7%) and a significant decrease in all epistaxis parameters in 28 cases (90∙3%). Twenty-five patients (80∙7%) obtained remission with 50 mg/day of thalidomide, five (16∙1%) with 100 mg/day and one (3∙2%) with 150 mg/day. Treatment significantly increased hemoglobin levels (pepistaxis in HHT patients, allowing for a rapid, often durable clinical improvement. Funding Telethon Foundation PMID:26686256

  6. The legal standards for the radioactive or non radioactive drugs research and approval in the European Community and in Germany after the thalidomide catastrophe.

    Science.gov (United States)

    Barsch, Michael; Otte, Andreas

    2010-01-01

    The drug thalidomide was contained in the blockbuster Contergan, which has been used as a non- prescription sedative drug and a potent treatment for occurring morning sickness in pregnant women during the 1950s and the early 1960s. This therapeutic use has led to one of the most prominent disasters in the history of drug development due to peripheral neuritis and malformations, e.g. phocomelia, in babies whose mothers had taken thalidomide within their pregnancies. Moreover, this catastrophe initiated a change of paradigm in Germany as well as in Europe with regard to drug safety and the regulatory setting. This article describes the history of the use of thalidomide and the regulatory framework of drug approval at that time as well as changes after the Contergan disaster including considerations to radiopharmaceuticals. Additionally, aspects of drug safety in the different development phases of pharmaceuticals as well as radiopharmaceuticals, i.e. pre-clinical and clinical phases, are characterised. However, many drugs have been withdrawn from the market after approval due to changes with regard of their risk-benefit balance after the occurrence of adverse drug reactions. Thus, pharmacovigilance activities are also mentioned in this review article. Last, obstacles and future perspectives in the arena of drug research and development also considering the use of radiopharmaceuticals are delineated.

  7. No influence of the polymorphisms CYP2C19 and CYP2D6 on the efficacy of cyclophosphamide, thalidomide, and bortezomib in patients with Multiple Myeloma

    DEFF Research Database (Denmark)

    Vangsted, A. J.; Soeby, K.; Klausen, T.W.

    2010-01-01

    . The patients were genotyped for the non-functional alleles CYP2C19*2 and CYP2D6*3, *4, *5 (gene deletion), *6, and CYP2D6 gene duplication. Results: In patients who were treated with bortezomib and were carriers of one or two defective CYP2D6 alleles there was a trend towards a better time-to-next treatment....... We found no association between the number of functional CYP2C19 and CYP2D6 alleles and outcome of treatment with cyclophosphamide or thalidomide. Neither was the number of functional CYP2C19 and CYP2D6 alleles associated with neurological adverse reactions to thalidomide and bortezomib. Conclusion......: There was no association between functional CYP2C19 and CYP2D6 alleles and treatment outcome in multiple myeloma patients treated with cyclophosphamide, thalidomide or bortezomib. A larger number of patients treated with bortezomib are needed to determine the role of CYP2D6 alleles in treatment outcome....

  8. Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies.

    Science.gov (United States)

    Bhatnagar, Bhavana; Rapoport, Aaron P; Fang, Hong-Bin; Ilyas, Can; Marangoz, Deniz; Akbulut, Vinil; Ruehle, Kathleen; Badros, Ashraf; Yanovich, Saul; Akpek, Görgün

    2014-04-01

    We retrospectively evaluated the tolerability and efficacy of fractionated total body irradiation (TBI) (1,200 cGy) and melphalan (MEL) (100-110 mg/m(2)) myeloablative conditioning in 48 patients with nonremission AML (n = 14), ALL (n = 10), NHL (n = 18), and other refractory hematologic malignancies (n = 6) who received allogeneic stem cell transplantation (SCT) between 2002 and 2011. Median age was 48 years (22 to 68); 14 out of 26 leukemia patients (54 %) had circulating blasts at transplant, 20 (50 %) evaluable patients had poor-risk cytogenetics, 12 (25 %) had prior SCT, and 10 (21 %) received stem cells from a mismatch donor. All patients received tacrolimus with or without methotrexate for GVHD prophylaxis. At the time of analysis, 13 patients (27 %) were alive and disease free. Engraftment was complete in all patients. The median time to ANC recovery (>500) was 12 days (range, 6-28). The most common grade III and IV toxicities were mucositis and infections. Eighteen patients (43 %) developed grade II-IV acute GVHD, and eight (26 %) had extensive chronic GVHD. Of 44 evaluable patients for response, 28 (64 %) achieved a complete remission (CR), and seven (15 %) had a partial remission after the transplant. With a median follow-up of 30 months (4 to 124 months) for surviving patients, the cumulative incidence of relapse was 45 % at 1 year, and the probability of overall survival (OS) at 5 years was 22.5 %. Multivariate analysis showed that platelet count (500 IU/L) at SCT were associated with relapse. Age less than 53 years and CR after SCT were associated with better OS. Our data suggest that TBI-MEL can result in CR in two thirds, durable remission in one third, and 5-year survival in about one quarter of patients with nonremission hematologic malignancies. Further studies with TBI-MEL in standard risk transplant patients are warranted.

  9. Population Pharmacokinetics and Optimal Sampling Strategy for Model-Based Precision Dosing of Melphalan in Patients Undergoing Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Mizuno, Kana; Dong, Min; Fukuda, Tsuyoshi; Chandra, Sharat; Mehta, Parinda A; McConnell, Scott; Anaissie, Elias J; Vinks, Alexander A

    2018-05-01

    High-dose melphalan is an important component of conditioning regimens for patients undergoing hematopoietic stem cell transplantation. The current dosing strategy based on body surface area results in a high incidence of oral mucositis and gastrointestinal and liver toxicity. Pharmacokinetically guided dosing will individualize exposure and help minimize overexposure-related toxicity. The purpose of this study was to develop a population pharmacokinetic model and optimal sampling strategy. A population pharmacokinetic model was developed with NONMEM using 98 observations collected from 15 adult patients given the standard dose of 140 or 200 mg/m 2 by intravenous infusion. The determinant-optimal sampling strategy was explored with PopED software. Individual area under the curve estimates were generated by Bayesian estimation using full and the proposed sparse sampling data. The predictive performance of the optimal sampling strategy was evaluated based on bias and precision estimates. The feasibility of the optimal sampling strategy was tested using pharmacokinetic data from five pediatric patients. A two-compartment model best described the data. The final model included body weight and creatinine clearance as predictors of clearance. The determinant-optimal sampling strategies (and windows) were identified at 0.08 (0.08-0.19), 0.61 (0.33-0.90), 2.0 (1.3-2.7), and 4.0 (3.6-4.0) h post-infusion. An excellent correlation was observed between area under the curve estimates obtained with the full and the proposed four-sample strategy (R 2  = 0.98; p strategy promises to achieve the target area under the curve as part of precision dosing.

  10. Induction therapy with vincristine, adriamycin, dexamethasone (VAD) and intermediate-dose melphalan (IDM) followed by autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma.

    Science.gov (United States)

    Lokhorst, H M; Sonneveld, P; Cornelissen, J J; Joosten, P; van Marwijk Kooy, M; Meinema, J; Nieuwenhuis, H K; van Oers, M H; Richel, D J; Segeren, C N; Veth, G; Verdonck, L F; Wijermans, P W

    1999-02-01

    We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.

  11. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    International Nuclear Information System (INIS)

    Yoshihara, Takao; Fujii, Noriko; Naya, Mayumi

    1999-01-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m 2 x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin's lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  12. Allogeneic bone marrow transplantation with conditioning regimen of total body irradiation/busulfan/melphalan for 16 patients in children with high-risk leukemia and lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Yoshihara, Takao; Fujii, Noriko [Matsushita Memorial Hospital, Moriguchi, Osaka (Japan); Naya, Mayumi [and others

    1999-02-01

    We report the therapeutic results of allogeneic bone marrow transplantations (BMT) for 16 children with high-risk leukemia and lymphoma. The conditioning regimen consisted of total body irradiation (TBI) (12 Gy), busulfan (Bu) (4 mg/kg x 2 days), and melphalan (L-PAM) (70 mg/m{sup 2} x 2 or 3 days). Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporin (CsA) + methotrexate (MTX) (4 cases) and CsA + MTX-methyl-prednisolone (11 cases). Seven patients had acute lymphocytic leukemia, 6 acute nonlymphocytic leukemia, 2 B-cell type non-Hodgkin`s lymphoma, and 1 peripheral T-cell lymphoma. Nine patients were in complete remission (CR) and 7 in non CR at BMT. Nine patients received transplants from HLA-matched related (MR) donors, 4 from HLA-mismatched related (MisR) donors, and 3 from unrelated (UR) donors. Seven of the cases, all of which were transplanted from MR, have continued complete remission for 15-47 (median 27) months. Nine patients, of which seven were transplanted from MisR/UR, died from complications from fungal pneumonia (3), cytomegalovirus pneumonitis (1), GVHD (1), rhabdomyolysis (1), lymphoproliferative disorder (1), rejection (1), and relapse (1). These results suggest that the combination of TBI, Bu, and L-PAM as a BMT regimen has a significant anti-neoplastic benefit and is considered to be useful; however, considering the high rate of fatal transplant-related complications, more refinement is required, especially for transplants from MisR and UR donors. (author)

  13. Novel thalidomide analogues, “me too” drugs and the Brazilian law / Novos análogos da talidomida, medicamentos “me too” e a lei brasileira

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    Francisco José Roma Paumgartten

    2013-08-01

    Full Text Available In Brazil, thalidomide has been used virtually without interruption since it was launched as a new and revolutionary sedative drug in 1956. After 1965, when its effi cacy to treat erythema nodosum leprosum (ENL was discovered, it was regarded as an essential drug because the prevalence of Hansen’s disease is high in the country. In the 1990s and thereafter myriad novel therapeutic uses for thalidomide (autoimmmune diseases, multiple myeloma, aphthous ulcers in AIDS, and others have emerged owing to its immunomodulatory and antiangiogenic activities. Owing to a marked teratogenicity, however, the prescription and dispensing of thalidomide to patients is strictly controlled in Brazil and elsewhere. Notwithstanding the stringent regulations, a number of post-1965 cases of thalidomide embryopathy have occurred in Brazil. In 2003, a federal law (Law 10.651/2003 prohibited the sale and dispensing of thalidomide in commercial pharmacies. The law, however, made no provision for teratogenic drug analogues such as lenalidomide and pomalidomide, which have been cleared for marketing in the USA, Europe and other countries. Although they are much more expensive than thalidomide, the clinical superiority of novel ana-logues over thalidomide in multiple myeloma and other conditions remains unproven. Therefore, so far novel analogues can be considered as thalidomide “me too” drugs. This author strongly recommends that an amendment to the current law prohibiting the sale and dispensing of thalid-omide in commercial pharmacies be extended to thalidomide analogues. Moreover, we consider that a demonstration of clinical superiority over thalidomide (through gold-standard comparative effi cacy trials should be an essential requirement for registration of any teratogenic analogue. ---------------------------No Brasil, a talidomida tem sido usada praticamente sem interrupção desde o seu lançamento como novo e revolucionário medicamento sedativo em 1956

  14. Effects of methotrexate combined with hydroxychloroquine sulfate and prednisone acetate on inflammatory response, immune function and liver and renal function in patients with systemic lupus erythematosus

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    Jiang-Li Xia

    2017-11-01

    Full Text Available Objective: To investigate the effects of methotrexate and hydroxychloroquine sulfate and prednisone on inflammatory response, immune function, liver and renal function in patients with systemic lupus erythematosus (SLE. Methods: A total of 80 cases of SLE patients according to the random data table were divided into the control group (n=40 and observation group (n=40, the control group were treated with hydroxychloroquine sulfate and prednisone treatment, on the basis of treatment of the control group, patients in the observation group in the control group were treated with methotrexate, the levels of inflammatory factors, immune function, liver and kidney function indexes in the two groups between the before treatment and after treatment were compared. Results: Comparison of the levels before treatment, the difference of the CRP, WBC, ESR, IgA, IgG, complement C3, complement C4, ALT, AST, SCr and BUN levels were not statistically significant. After treatment, the levels of CRP, ESR, IgA, IgG, ALT, AST, SCr and BUN in the observation group were significantly lower than those in the control group, and the difference was statistically significant. The levels of WBC and complement C4 in the observation group [(5.18±1.08伊10 9 /L, (0.22±0.05 g/L] were significantly higher than those in the control group [(4.51±0.52伊10 9 /L, (0.18±0.03 g/L], and there was no significant difference in the level of complement C3 between the two groups after treatment. Conclusion: Methotrexate combined with hydroxychloroquine sulfate and prednisone for the treatment of SLE can effectively reduce inflammation, improve immune function, has little effect on kidney function, high safety, which has an important clinical value.

  15. Subcutaneous Administration of Bortezomib in Combination with Thalidomide and Dexamethasone for Treatment of Newly Diagnosed Multiple Myeloma Patients

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    Shenghao Wu

    2015-01-01

    Full Text Available Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM patients with the therapy of subcutaneous (subQ administration of bortezomib and dexamethasone plus thalidomide (VTD regimen. Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group.The efficacy and safety of two groups were analyzed retrospectively. Results. The overall remission (OR after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05. No significant differences in time to 1-year estimate of overall survival (72% versus 75%, P=0.848 and progression-free survival (median 22 months versus 25 months; P=0.725 between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50% than VTD group (80%, P=0.015. Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.

  16. Synthesis and evaluation of novel dapsone-thalidomide hybrids for the treatment of type 2 leprosy reactions.

    Science.gov (United States)

    Yamasaki, Paulo Renato; do Nascimento, Dejair Caetano; Chelucci, Rafael Consolin; de Faria Fernandes Belone, Andréa; Rosa, Patrícia Sammarco; Diório, Suzana Madeira; de Melo, Thais Regina Ferreira; Barbieri, Karina Pereira; Placeres, Marisa Campos Polési; Carlos, Iracilda Zepone; Chung, Man Chin; dos Santos, Jean Leandro

    2014-07-15

    We synthesized a series of novel dapsone-thalidomide hybrids (3a-i) by molecular hybridization and evaluated their potential for the treatment of type 2 leprosy reactions. All of the compounds had analgesic properties. Compounds 3c and 3h were the most active antinociceptive compounds and reduced acetic acid-induced abdominal constrictions by 49.8% and 39.1%, respectively. The hybrid compounds also reduced tumor necrosis factor-α levels in lipopolysaccharide-stimulated L929 cells. Compound 3i was the most active compound; at concentrations of 15.62 and 125 μM, compound 3i decreased tumor necrosis factor-α levels by 86.33% and 87.80%, respectively. In nude mice infected with Mycobacterium leprae in vivo, compound 3i did not reduce the number of bacilli compared with controls. Compound 3i did not have mutagenic effects in Salmonella typhimurium strains TA100 and TA102, with or without metabolic activation (S9 mixture). Our results indicate that compound 3i is a novel lead compound for the treatment of type 2 leprosy reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. ¿Por qué se está usando otra vez la talidomida? Why is thalidomide back?

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    Emilio Sanín Pérez

    2004-02-01

    óxica ni en la Enfermedad crónica injerto contra huésped. Background: in 1998 the FDA approved the restricted commercialization of Thalidomide for the treatment of Erithema Nodosum Leprosum. Brazil and Mexico have also regulated its use. Because of the current use of this teratogenic drug in rheumatological, dermatological, infectious and neoplasic diseases, it is necessary to instruct General Practitioners and specialists on its most relevant topics, active principle, benefic and deleterious effects. We carried out a revision by reading and analyzing controlled clinical trials, randomized or not, case series and reviews about thalidomide and its potential uses, that appeared in Medline from January 1993 to December 2003, to draw indications and contraindications in light of the evidence found in them. Results: forty six randomized controlled studies were found and 22 (with at least 50 patients described were reviewed (complete articles and/or including design and end points measured – expressed abstracts, plus 10 reviews and 22 cases series. The analysis allowed us to inform potential or restricted and not indicated uses of thalidomide in humans, its pharmacokynetic principles which explain its benefic and deleterious effects, and recommendations to prevent teratogenesis. Conclusion: thalidomide is available, with restrictions, for the treatment of Erithema Nodosum Leprosum (first line and Multiple Myeloma (refractory to multiple chemotherapy. It appears to have beneficial effects in many other serious conditions refractory to first line treatments: AIDS, esophagus and prostate cancer and some severe dermatosis, rheumatological or not.

  18. Atrial natriuretic peptide-conjugated chitosan-hydrazone-mPEG copolymer nanoparticles as pH-responsive carriers for intracellular delivery of prednisone.

    Science.gov (United States)

    M, Gover Antoniraj; C, Senthil Kumar; Henry, Linda Jeeva Kumari; Natesan, Subramanian; Kandasamy, Ruckmani

    2017-02-10

    A chitosan-hydrazone-mPEG (CH-Hz-mPEG) copolymer which is stable at extracellular pH and cleaves at slightly acidic intracellular pH was synthesized and characterized. Blank polymeric nanoparticles (B-PNPs) and prednisone-loaded polymeric nanoparticles (P-PNPs) were then formulated by dialysis/precipitation method. The cell-specific ligand, atrial natriuretic peptide (ANP) was then conjugated to P-PNPs (ANP-P-PNPs) by a coupling reaction. Particle size and morphological analyses revealed uniform spherical shape of PNPs. In vitro pH dependent degradation of PNPs was investigated. Drug release profile of ANP-P-PNPs indicated a slow release of prednisone at pH 7.4, but a rapid release at pH 5.0 due to the cleavage of hydrazone linkage. Cytotoxicity studies demonstrated greater compatibility of B-PNPs compared to ANP-P-PNPs. Cellular internalization of ANP-P-PNPs was higher than P-PNPs owing to receptor-mediated endocytosis. The results from this investigation support the hypothesis that chitosan based ANP-P-PNPs could act as an intracellular pH-responsive and targeted drug delivery system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. The involvement of DNA repair genes in the hypoxia-dependent NLCQ-1 (NSC 709257) toxicity and its synergistic interaction with cisplatin or melphalan

    International Nuclear Information System (INIS)

    Papadopoulou, M.V.; Xue, C.-J.; Bloomer, W.D.

    2003-01-01

    4-[3-(2-Nitro-1-imidazolyl)-propylamino]-7-chloro-quinoline hydrochloride (NLCQ-1) is a weakly DNA-intercalating hypoxia selective cytotoxin, which synergistically enhances the antitumor effect of several chemotherapeutic agents or radiation against mouse tumors or human xenografts. Synergy with melphalan (L-PAM) or cisplatin (cisPt) requires hypoxic pre-exposure of cells to NLCQ-1 or, in mice, administration of NLCQ-1 about 1 h before L-PAM or cisPt. This suggests that NLCQ-1 may cause DNA lesions upon reductive metabolism. To indirectly identify such lesions, rodent cell lines defective in specific DNA repair genes (EM9 and UV41) and their repair-proficient parental AA8, were exposed to NLCQ-1 alone and in combination with L-PAM or cisPt under hypoxic/aerobic conditions and appropriate routes, and assessed for clonogenicity. Selected comparisons with tirapazamine (TPZ) were also performed. DNA ssbs were identified by using the alkaline comet assay. Synergism was assessed by isobologramic analysis. EM9, which lack the functional XRCC1 gene and are unable to efficiently repair DNA ssbs, were 3.7x and 4.5x more sensitive to NLCQ-1 and TPZ, respectively, than the parental AA8 cells. Similarly, UV41, which are defective in the ERCC4/XPF gene and thus, hypersensitive to DNA cross-linking agents, were 4.1x more sensitive than AA8 cells to NLCQ-1. Equitoxic concentrations of NLCQ-1 and TPZ gave similar numbers of ssbs in AA8 and EM9 cells exposed to each compound for 1 h under hypoxic conditions. In combination with L-PAM or cisPt, synergy was observed in AA8 but not in EM9 or UV41 cells, with either NLCQ-1 or TPZ. These results suggest that NLCQ-1 is involved in the formation of DNA ssbs and interstrand crosslinks, with the latter being most likely responsible for NLCQ-1 hypoxic toxicity. The synergistic interaction of NLCQ-1 with L-PAM or cisPt is probably due to an enhancement in the L-PAM/cisPt-induced DNA interstrand crosslinks, possibly as a result of an inhibited

  20. Front line treatment of elderly multiple myeloma in the era of novel agents

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    Marie-Dominique Venon

    2008-10-01

    Full Text Available Marie-Dominique Venon2, Aldo M Roccaro1,3, Julie Gay2, Anne-Sophie Moreau1,2, Remy Dulery2, Thierry Facon2, Irene M Ghobrial1, Xavier Leleu1,21Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; 2Service des Maladies du Sang, Hopital Huriez, CHRU, Lille, France; 3Units of Blood Diseases and Cell Therapies, University of Bresica, Medical School, Bresica, ItalyAbstract: Melphalan combined with prednisone (MP has long been the historical treatment of reference for a large proportion of elderly myeloma (MM patients ineligible for autologous stem cell transplantation, and is still the backbone of new regimens that include the new era of novel agents. Melphalan–prednisone–thalidomide (MPT and melphalan–prednisone–bortezomib (Velcade®, MPV, proved superior to MP, currently appear to be the treatments of choice for this population. In the near future melphalan–prednisone–lenalidomide (Revlimid®, MPR will also provide a third therapeutic option (MPT, MPV, and MPR, in elderly multiple myeloma, eventually. These options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel agents have somewhat different toxicity profiles. Dexamethasone-based regimen is another option and questions regarding the relative efficacy of melphalan-based versus low-dose dexamethasone-based regimens will require randomized phase III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated. These new and emerging therapies offer multiple effective treatment options for MM patients and greatly enhanced treatment strategies for clinicians.Keywords: multiple myeloma, elderly, bortezomib, thalidomide, revlimid, IMiDs, supportive care

  1. Efficacy and safety of thalidomide for the treatment of severe recurrent epistaxis in hereditary haemorrhagic telangiectasia: results of a non-randomised, single-centre, phase 2 study.

    Science.gov (United States)

    Invernizzi, Rosangela; Quaglia, Federica; Klersy, Catherine; Pagella, Fabio; Ornati, Federica; Chu, Francesco; Matti, Elina; Spinozzi, Giuseppe; Plumitallo, Sara; Grignani, Pierangela; Olivieri, Carla; Bastia, Raffaella; Bellistri, Francesca; Danesino, Cesare; Benazzo, Marco; Balduini, Carlo L

    2015-11-01

    Hereditary haemorrhagic telangiectasia is a genetic disease that leads to multiregional angiodysplasia. Severe recurrent epistaxis is the most common presentation, frequently leading to severe anaemia. Several therapeutic approaches have been investigated, but they are mostly palliative and have had variable results. We aimed to assess the efficacy of thalidomide for the reduction of epistaxis in patients with hereditary haemorrhagic telangiectasia that is refractory to standard therapy. We recruited patients aged 17 years or older with hereditary haemorrhagic telangiectasia who had severe recurrent epistaxis refractory to minimally invasive surgical procedures into an open-label, phase 2, non-randomised, single-centre study at IRCCS Policlinico San Matteo Foundation (Pavia, Italy). We gave patients thalidomide at a starting dose of 50 mg/day orally. If they had no response, we increased the thalidomide dose by 50 mg/day increments every 4 weeks, until a response was seen, up to a maximum dose of 200 mg/day. After patients had achieved a response, they continued treatment for 8-16 additional weeks. The primary endpoint was the efficacy of thalidomide measured as the percentage of patients who had reductions of at least one grade in the frequency, intensity, or duration of epistaxis. We followed up patients each month to assess epistaxis severity score and transfusion need, and any adverse events were reported. We included all patients who received any study drug and who participated in at least one post-baseline assessment in the primary efficacy population. The safety population consisted of all patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01485224. Between Dec 1, 2011, and May 12, 2014, we enrolled 31 patients. Median follow-up was 15·9 months (IQR 10·1-22·3). Three (10%, 95% CI 2-26) patients had a complete response, with bleeding stopped, 28 (90%, 95% CI 74-98) patients had partial responses

  2. Effect of Ginkgo biloba extract in combined with prednisone on the arterial blood gas and pulmonary function in patients with idiopathic pulmonary fibrosis

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    Zhen-Chun Shi

    2016-09-01

    Full Text Available Objective: To explore the effect of Ginkgo biloba extract (EGb in combined with prednisone on the arterial blood gas and pulmonary function in patients with idiopathic pulmonary fibrosis (IPF. Methods: A total of 76 patients with IPF who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the observation group and the control group. The patients in the two groups were given oxygen inhalation, bronchodilator agents, phlegm dissipating and asthma relieving, anti-infection, and other supporting treatments. The patients in the control group were orally given prednisone (0.5 mg/ kg.d, continuously for 4 weeks, then in a dose of 0.25 mg/kg.d, continuously for 8 weeks, and finally the dosage was reduced to 0.125 mg/kg.d. On this basis, the patients in the observation group were given additional EGb, i.e. Ginkgo leaf capsule, 1 g/time, 3 times/d, continuously for 12 weeks. The efficacy was evaluated after 12-week treatment. PaO2, PaCO2, P(A-aO2, and SaO2 before and after treatment were detected. FVC, FEV1/FVC, MVV, TLC, and DLCO before and after treatment were determined. Results: PaO2, PaCO2, and SaO2 after treatment were significantly elevated, while P(A-aO2 was significantly reduced when compared with before treatment. The comparison of PaO2 and P(A-aO2 between the two groups was statistically significant, while the comparison of PaCO2 and SaO2 between the two groups was not statistically significant. After treatment, FVC, FEV1/FVC, MVV, TLC, and DLCO in the two groups were significantly elevated when compared with before treatment, and those in the observation group were significantly superior to those in the control group. Conclusions: EGb in combined with prednisone in the treatment of IPF can effectively improve the arterial blood gas indicators and pulmonary function, and enhance the patients’ living qualities; therefore, it deserves to be widely recommended.

  3. Efeito da prednisona em lesão medular aguda experimental em ratos Effect of prednisone on acute experimental spinal cord injury in rats

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    C.M.O. Silva

    2008-06-01

    Full Text Available Foram utilizados 25 ratos (Rattus novergicus submetidos a trauma experimental da medula espinhal, empregando-se aparelho estereotáxico com um peso de 50,5g comprimindo a duramáter durante cinco minutos. Após o trauma, os animais foram divididos em cinco grupos de cinco. O grupo A (controle recebeu placebo oito horas após o trauma; os grupos B, C, D e E receberam prednisona oito, 24, 48 e 120 horas após o trauma, respectivamente. A prednisona foi administrada na dose inicial de 2mg/kg, durante cinco dias, com diminuição progressiva até o 26º dia. Os animais foram avaliados conforme a capacidade motora, posicionamento proprioceptivo, reflexo de localização, plano inclinado e sensibilidade dolorosa. Após 33 dias da cirurgia, foram sacrificados para avaliação histológica das medulas espinhais. Observaram-se degeneração das raízes nervosas, necrose medular, inflamação local e reação glial, sem diferenças entre os grupos. Não houve correlação entre os testes neurológicos. A utilização da prednisona na lesão medular aguda não teve efeito diferenciado com o tempo e não foi prejudicial na recuperação neurológica, mesmo quando utilizada tardiamente.Twent-five rats (Rattus novergicus were submitted to an experimental spinal cord injury by using a 50.5g stereotaxic equipament to apply pressure on the duramater during five minutes. After the spinal cord injury, the animals were randomly distributed into five groups of five animals each: one group received placebo 8 hours after injury and the remaining four groups received prednisone at 8, 24, 48, and 120 hours after injury. Prednisone was applied at 2mg/kg dosage during five days and progressively reduced until the 26th day. Animals were evaluated by motor capacity, proprioceptive positioning, locating reflex, inclined plan, and sensibility to pain. The animals were sacrificed 33 days after surgery for histological study of the spinal cords that revealed degeneration of the

  4. Hormone and thalidomide may be effective in the treatment of adult mediastinal T-cell lymphoblastic lymphoma: a case report and literature review

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    Hongyang Wu

    2013-06-01

    Full Text Available A case of a 53-year-old man with adult T-lymphoblastic lymphoma (T-LBL in mediastinum who survived more than 33 months in our hospital was reported. LBL was more common in schoolage and teenage boys than adults. The reported patient manifested progressive dyspnea. Chest CT scanning showed a huge irregular soft tissue shadow in anterior mediastinum which extended into posterior mediastinum and left chest wall. The tumor was 20 cm×15 cm×15 cm in size in left upper mediastinum and its boundaries with pericardium and left lower lung were unclear. The diagnosis of T-lymphoblastic lymphoma was confirmed by immunohistochemical staining. After surgery, he received five chemotherapy courses including Gem, CTX and VCR and biological therapies with IL-2 and IFN-α2b. About 16 months later, he complained of diplopia in the left eye without any evidence of recurrence. Blood examination which showed leukemoid reaction twice returned to normal after dehydration, hormone and thalidomide treatments. Finally, his condition became worse and died of pulmonary infection 33 months after first medical service. In summary, T-LBL is a rare disease which may result in poor prognosis even if the patient has received immediate chemotherapy. Hormone and thalidomide can be applied to treat adult T-LBL.

  5. The Applicability of the International Staging System in Chinese Patients with Multiple Myeloma Receiving Bortezomib or Thalidomide-Based Regimens as Induction Therapy: A Multicenter Analysis

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    Jing Lu

    2015-01-01

    Full Text Available The International Staging System (ISS is the most important prognostic system for multiple myeloma (MM. It was identified in the era of conventional agents. The outcome of MM has significantly changed by novel agents. Thus the applicability of ISS system in the era of novel agents in Chinese patients needs to be demonstrated. We retrospectively analyzed the clinical outcomes and prognostic significance of ISS system in 1016 patients with newly diagnosed multiple myeloma in Chinese patients between 2008 and 2012, who received bortezomib- or thalidomide-based regimens as first-line therapy. The median overall survival (OS of patients for ISS stages I/II/III was not reached/55.4 months/41.7 months (p<0.001, and the median progression-free survival (PFS was 30/29.5/25 months (p=0.072, respectively. Statistically significant difference in survival was confirmed among three ISS stages in thalidomide-based group, but not between ISS stages I and II in bortezomib-based group. These findings suggest that ISS system can predict the survival in the era of novel agents in Chinese MM patients, and bortezomib may have the potential to partially overcome adverse effect of risk factors on survival, especially in higher stage of ISS system.

  6. LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.

    Science.gov (United States)

    Shu, Chang; Zeng, Tianmei; Gao, Shouhong; Xia, Tianyi; Huang, Lifeng; Zhang, Feng; Chen, Wansheng

    2016-08-15

    Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Combination therapy with methotrexate, vincristine, polyethylene-glycol conjugated-asparaginase, and prednisone in the treatment of patients with refractory or recurrent acute lymphoblastic leukemia.

    Science.gov (United States)

    Aguayo, A; Cortes, J; Thomas, D; Pierce, S; Keating, M; Kantarjian, H

    1999-10-01

    L-asparaginase in combination with methotrexate has synergistic antileukemic activity in a schedule-dependent fashion. A new preparation of L-asparaginase, polyethylene-glycol conjugated (PEG)-asparaginase, is a pharmacologically different formulation of L-asparaginase with distinct properties including a longer half-life and less immunogenic properties. Patients with refractory or recurrent acute lymphoblastic leukemia (ALL) were treated with a combination of methotrexate (MTX), vincristine, PEG-asparaginase, and prednisone (MOAP). The treatment was comprised of MTX, 100 mg/m(2) intravenously (i.v.), over 15 minutes on Days 1 and 14; PEG-asparaginase, 2500 IU/m(2), with a maximum dose of 3750 IU i.v. approximately 4-6 hours after MTX on Days 1 and 14; vincristine, 1.4 mg/m(2) (maximum dose, 2 mg) i.v., over 15 minutes on Days 1, 7, and 14; and prednisone, 200 mg daily orally, on Days 1-5 and 14-19. Thirty-two patients with a median age of 34 years (range, 20-74 years) were treated. Eight patients (25%) had ALL that was refractory to prior therapy and 24 patients (75%) had recurrent disease. Seven patients (22%) achieved a complete remission (CR). Five patients (16%) died early due to infections. Features associated with a poor response were high pretreatment lactate dehydrogenase levels and Philadelphia chromosome positive disease. The median duration of CR was 16 weeks and the overall median survival after MOAP therapy was 12 weeks. Anaphylactic reactions were not observed during MOAP combination therapy. MOAP is an active regimen in patients with refractory or recurrent ALL. This regimen is well tolerated and is not associated with allergic reactions. However, further studies regarding the pharmacologic interaction of MTX with PEG-asparaginase are needed to optimize this regimen. Copyright 1999 American Cancer Society.

  8. Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

    Science.gov (United States)

    Bloomfield, D J; Krahn, M D; Neogi, T; Panzarella, T; Smith, T J; Warde, P; Willan, A R; Ernst, S; Moore, M J; Neville, A; Tannock, I F

    1998-06-01

    To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). A treatment that reduces symptoms and improves quality of life has the potential to reduce

  9. Rational Design, Synthesis and Evaluation of γ-CD-Containing Cross-Linked Polyvinyl Alcohol Hydrogel as a Prednisone Delivery Platform

    Directory of Open Access Journals (Sweden)

    Adolfo Marican

    2018-03-01

    Full Text Available This study describes the in-silico rational design, synthesis and evaluation of cross-linked polyvinyl alcohol hydrogels containing γ-cyclodextrin (γ-CDHSAs as platforms for the sustained release of prednisone (PDN. Through in-silico studies using semi-empirical quantum mechanical calculations, the effectiveness of 20 dicarboxylic acids to generate a specific cross-linked hydrogel capable of supporting different amounts of γ-cyclodextrin (γ-CD was evaluated. According to the interaction energies calculated with the in-silico studies, the hydrogel made from PVA cross-linked with succinic acids (SA was shown to be the best candidate for containing γ-CD. Later, molecular dynamics simulation studies were performed in order to evaluate the intermolecular interactions between PDN and three cross-linked hydrogel formulations with different proportions of γ-CD (2.44%, 4.76% and 9.1%. These three cross-linked hydrogels were synthesized and characterized. The loading and the subsequent release of PDN from the hydrogels were investigated. The in-silico and experimental results showed that the interaction between PDN and γ-CDHSA was mainly produced with the γ-CDs linked to the hydrogels. Thus, the unique structures and properties of γ-CDHSA demonstrated an interesting multiphasic profile that could be utilized as a promising drug carrier for controlled, sustained and localized release of PDN.

  10. Toxicities and outcomes among septuagenarians and octogenarians with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy.

    Science.gov (United States)

    Huntington, Scott F; Talbott, Mahsa S; Greer, John P; Morgan, David S; Reddy, Nishitha

    2012-08-01

    The diagnosis of non-Hodgkin lymphoma (NHL) is increasingly common among the elderly and it is well recognized that this patient population may benefit from therapy. No guidelines exist for chemotherapy dosing in the elderly population, and a clear assessment of treatment toxicity and benefits has not been previously reported. In this single-institution study, we report the toxicities and treatment outcomes of septuagenarians and octogenarians with large cell lymphoma treated with chemo-immunotherapy with or without radiation, as primary therapy with curative intent. We identified 37 patients over the age of 70 years diagnosed with large cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and compared their experience with 65 patients aged less than 70 years. Our retrospective analysis suggests that elderly patients are more susceptible to treatment-related toxicity despite more frequent chemotherapy dose reductions and greater utilization of supportive care. While our aged patients experienced greater frequency of hospitalization during R-CHOP treatment, the vast majority were able to receive relative chemotherapy dose-intensity greater than 70% and experienced similar rates of complete remission.

  11. Detection of Asymptomatic Cardiac Metastasis and Successful Salvage Chemotherapy Comprising a Prednisone, Etoposide, Procarbazine, and Cyclophosphamide Regimen in an Elderly Japanese Patient Suffering from a Delayed Recurrence of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Keita Tagami

    2012-01-01

    Full Text Available We report a case of facial diffuse large B-cell lymphoma (DLBCL associated with recurrent metastasis in the heart and other sites in a 76-year-old Japanese woman. Initially, she developed DLBCL in her left upper eyelid that spread into the left orbit (Ann Arbor classification stage I. The lesion went into clinical regression after 4 cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy followed by radiotherapy. More than 3 years later, the lymphoma recurred in her facial skin, together with metastases in the mediastinal lymph nodes and the heart; the tumor in the heart was successfully detected by PET/CT and cardiac MRI. To treat the recurrent lesions, we performed a salvage chemotherapy regimen comprising prednisone, etoposide, procarbazine, and cyclophosphamide, which successfully induced tumor regression.

  12. Single nucleotide polymorphisms in the promoter region of the IL1B gene influence outcome in multiple myeloma patients treated with high-dose chemotherapy independently of relapse treatment with thalidomide and bortezomib

    DEFF Research Database (Denmark)

    Vangsted, Annette J.; Klausen, Tobias W.; Abildgaard, Niels

    2011-01-01

    the impact on outcome of HDT, INF-α maintenance treatment, and treatment with thalidomide and bortezomib at relapse, in relation to the major identified functional polymorphisms in the promoter region of IL1B. The wild-type C-allele of IL1B C-3737T and non-carriage of the IL1B promoter haplotype TGT (−3737T...... carriers at both loci. No relation to genotype and outcome was found for relapse patients treated with thalidomide or bortezomib. Our results indicate that a subpopulation of myeloma patients carrying the wild-type C-allele of IL1B C-3737T and non-carriers of the promoter haplotype TGT (−3737T, −1464G...

  13. Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience.

    Science.gov (United States)

    Anderlini, Paolo; Saliba, Rima; Acholonu, Sandra; Giralt, Sergio A; Andersson, Borje; Ueno, Naoto T; Hosing, Chitra; Khouri, Issa F; Couriel, Daniel; de Lima, Marcos; Qazilbash, Muzaffar H; Pro, Barbara; Romaguera, Jorge; Fayad, Luis; Hagemeister, Frederick; Younes, Anas; Munsell, Mark F; Champlin, Richard E

    2008-02-01

    The role of reduced-intensity conditioning allogeneic stem cell transplantation in relapsed/refractory Hodgkin's lymphoma remains poorly defined. We here present an update of our single-center experience with fludarabine-melphalan as a preparative regimen. Fifty-eight patients with relapsed/refractory Hodgkin's lymphoma underwent RIC and allogeneic stem cell transplantation from a matched related donor (MRD; n=25) or a matched unrelated donor (MUD; n=33). Forty-eight (83%) had undergone prior autologous stem cell transplantation. Disease status at transplant was refractory relapse (n=28) or sensitive relapse (n=30). Cumulative day 100 and 2-year transplant-related mortality rates were 7% and 15%, respectively (day 100 transplant-related mortality MRD vs. MUD 8% vs. 6%, p=ns; 2-year MRD vs. MUD 13% vs. 16%, p=ns). The cumulative incidence of acute (grade II-IV) graft-versus-host disease in the first 100 days was 28% (MRD vs. MUD 12% vs. 39%, p=0.04). The cumulative incidence of chronic graft-versus-host disease at any time was 73% (MRD vs. MUD 57% vs. 85%, p=0.006). Projected 2-year overall and progression-free survival rates are 64% (49-76%) and 32% (20-45%), with 2-year disease progression/relapse at 55% (43-70%). There was no statistically significant differences in overall survival progression-free survival, and disease progression/relapse between MRD and MUD transplants. There was a trend for the response status pretransplant to have a favorable impact on progression-free survival (p=0.07) and disease progression/relapse (p=0.049), but not on overall survival (p=0.4) Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in progression-free survival Hodgkin's lymphoma is associated with a significant reduction in transplant-related mortality, with comparable results in MRD and MUD allografts. Optimizing pretransplant response status may improve patients' outcome.

  14. Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats Histamina combinada ao melfalano na perfusão de membro isolado para o tratamento de sarcomas de partes moles localmente avançado: estudos pré-clínicos em ratos

    Directory of Open Access Journals (Sweden)

    Flavia Brunstein

    2005-08-01

    Full Text Available PURPOSE: To evaluate the potential benefit of histamine combined with melphalan in the isolated limb perfusion (ILP as an alternative to TNF-alfa and melphalan combination, for the treatment of irressectable soft tissue sarcomas of the limbs in Brown Norway (BN rats. METHODS: 20 BN rats had small fragments of syngeneic BN-175 fibosarcoma inserted on the right hind limb. In 7-10 days the tumor reached a median diameter of 12-15 mm and they were randomly divided in four groups (sham, melphalan, histamine and escalating doses of histamine combined to melphalan being submitted to experimental ILP for 30 minutes. Tumors were measured daily with a caliper and the volume was calculated. RESULTS: Response curves showed a significant effect of the combination of histamine 200 mg/mL with melphalan, with 66% overall response, including 33% complete responses (pOBJETIVO: Avaliar o potencial benéfico da histamina combinada ao melfalano, na perfusão de membro isolado (PMI, como alternativa à combinação TNF-alfa mais melfalano, no tratamento de sarcomas de partes moles irressecaveis em extremidades, em ratos de linhagem Brown Norway (BN. MÉTODOS: 20 ratos BN foram submetidos a implantação de fragmentos de fibrosarcoma singênico BN-175 na pata traseira direita. Em cerca de 7-10 dias o tumor atingiu um diâmetro médio de 12-15 mm e foram aleatóriamente divididos em quatro grupos (controle, melfalano, histamina em doses progessivas combinada ao melfalano e histamina sendo submetidos a PMI experimental por 30 minutos. Os tumores foram então medidos diariamente com o uso de paquímetro e o volume tumoral calculado. RESULTADOS: As curvas de resposta mostram um efeito significativo da combinação de Histamina na concentração de 200 mg/mL ao melfalano, com 66% de resposta global incluindo 33% de respostas completas (p < 0.01. Não houve efeitos colaterais sistêmicos e localmente apenas edema leve e transitório nos animais tratados com histamine

  15. Talidomida: novas perspectivas para utilização como antiinflamatório, imunossupressor e antiangiogênico Thalidomide: new perspectives for its use as antiinflammatory, immunossupressive and antiangiogenic drug

    Directory of Open Access Journals (Sweden)

    Larissa de Godoy Borges

    2003-01-01

    Full Text Available Esta revisão tem como objetivo apresentar os novos usos da talidomida. O interesse por este fármaco é devido às suas propriedades antiinflamatórias, immunossupressoras, antiangiogênicas e até mesmo antivirais. Embora o seu mecanismo de ação seja desconhecido, resultados demonstram com sucesso o emprego deste fármaco no eritema nodoso leproso, mieloma múltiplo, doença enxerto-versus-hospedeiro e também como inibidor do vírus HIV e tratamento dos sintomas da Aids. O trabalho também mostra que apesar dos benefícios, a talidomida exige um controle muito rigoroso no que diz respeito à sua utilização e sua dispensação, devido às suas propriedades teratogênicas. Contudo, a talidomida constitui-se numa importante alternativa farmacêutica, sendo que o seu verdadeiro potencial ainda está sendo investigado.The new uses of thalidomide are reviewed. It has recently been used as antinflammatory, immunosuppressive, antiangiogenic, and antiviral agent. Although its mechanism of action is not yet understood, the advantage of its use in several diseases, such as erythema nodosum leprosum, multiple myeloma, and graft-versus-host-disease is evident. Owing to its teratogenic properties, the use of thalidomide must be very well controlled. However, thalidomide has become a very important alternative, with new applications being studied.

  16. Expression of CD40 is a positive prognostic factor of diffuse large B-cell lymphoma treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

    Directory of Open Access Journals (Sweden)

    Song G

    2016-06-01

    Full Text Available Guoqi Song,1 Huiyun Ni,1 Linqing Zou,2 Shukui Wang,3 Fuliang Tian,4 Hong Liu,1 William C Cho5 1Department of Hematology, Affiliated Hospital of Nantong University, Nantong, 2Department of Human Anatomy, Nantong University, Nantong, 3Central Laboratory of Nanjing First Hospital, Nanjing Medical University, Nanjing, 4Maternal and Child Health Hospital of Lianyungang, Lianyungang, Jiangsu, People’s Republic of China; 5Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong Objectives: The objective of this study was to investigate the expression level of CD40 and its role in the prognosis of patients with diffuse large B-cell lymphoma (DLBCL who were treated with rituximab-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone.Design and methods: The immunohistochemical expressions of CD40 in 186 well-characterized DLBCL patients were evaluated by tissue microarrays, thereby revealing the relationship of the molecule CD40 with known tumor, patient-related variables, and survival rates.Results: The results showed that CD40 expressions were not statistically different between the germinal center B-cell-like (GCB type and the non-GCB type. We also analyzed the relationships of CD40 expression with overall survival (OS and progression-free survival (PFS in DLBCL patients who were uniformly treated with R-CHOP. A low expression of CD40 compared to high expression is related to poor OS and PFS. Conclusion: Our findings indicate that the CD40 level at onset acts as an independent prognostic predictor of DLBCL patients treated with R-CHOP. Keywords: CD40, diffuse large B-cell lymphoma, R-CHOP, prognostic factor

  17. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial.

    Science.gov (United States)

    Tannock, Ian F; Fizazi, Karim; Ivanov, Sergey; Karlsson, Camilla Thellenberg; Fléchon, Aude; Skoneczna, Iwona; Orlandi, Francisco; Gravis, Gwenaelle; Matveev, Vsevolod; Bavbek, Sevil; Gil, Thierry; Viana, Luciano; Arén, Osvaldo; Karyakin, Oleg; Elliott, Tony; Birtle, Alison; Magherini, Emmanuelle; Hatteville, Laurence; Petrylak, Daniel; Tombal, Bertrand; Rosenthal, Mark

    2013-07-01

    Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285 FINDINGS: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We

  18. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease

    Science.gov (United States)

    van Rhee, Frits; Shaughnessy, John D.; Epstein, Joshua; Yaccoby, Shmuel; Pineda-Roman, Mauricio; Hollmig, Klaus; Alsayed, Yazan; Hoering, Antje; Szymonifka, Jackie; Anaissie, Elias; Petty, Nathan; Kumar, Naveen S.; Srivastava, Geetika; Jenkins, Bonnie; Crowley, John; Zeldis, Jerome B.

    2008-01-01

    Smoldering multiple myeloma (SMM) is usually followed expectantly without therapy. We conducted a phase 2 trial in 76 eligible patients with SMM, combining thalidomide (THAL, 200 mg/d) with monthly pamidronate. In the first 2 years, THAL dose reduction was required in 86% and drug was discontinued in 50%. Within 4 years, 63% improved, including 25% qualifying for partial response (PR); by then, 34 patients had progressed and 17 required salvage therapy. Unexpectedly, attaining PR status was associated with a shorter time to salvage therapy for disease progression (P < .001), perhaps reflecting greater drug sensitivity of more aggressive disease. Low beta-2-microglobulin levels less than 2 mg/L were independently associated with superior overall and event-free survival. Four-year survival and event-free survival estimates of 91% and 60%, respectively, together with a median postsalvage therapy survival of more than 5 years justify the conduct of a prospective randomized clinical trial to determine the clinical value of preemptive therapy in SMM. Trial registered at http://www.clinicaltrials.gov under identifier NCT00083382. PMID:18669874

  19. Updated survivals and prognostic factor analysis in myeloma treated by a staged approach use of bortezomib/thalidomide/dexamethasone in transplant eligible patients

    Directory of Open Access Journals (Sweden)

    Chim Chor

    2010-11-01

    Full Text Available Abstract Background Bortezomib, an NFkB inhibitor, is an active agent for the treatment of myeloma (MM. We have reported a promising complete remission (CR rate for newly diagnosed myeloma patients treated by a staged approach, in which chemosensitive patients underwent autologous haematopoietic stem cell transplantation (auto-HSCT while less chemosensitive patients received salvage therapy with bortezomib/thalidomide/dexamethasone prior to auto-HSCT. Methods Herein, with an additional 13 months of follow-up, we reported the updated survivals, and examined potential prognostic factors impacting event-free (EFS and overall survival (OS. Results With a median follow-up of 30 months, the projected OS was 73% and EFS was 50.2%. Age, gender, clinical stage and DAPK methylation could not account for the differential chemosensitivity. Advanced ISS stage and DAPK methylation adversely impacted OS whereas oligoclonal reconstitution predicted superior EFS. Conclusions Our staged approach illustrated an economical use of expensive targeted agents while preserving a good CR rate and OS. The comparable survivals of chemosensitive and less chemosensitive patients suggested the staged approach might have abolished the adverse prognostic impact of suboptimal chemosensitivity. Finally, the adverse impact of DAPK methylation and favorable impact of oligoclonal reconstitution in myeloma warrants further study.

  20. Apoptosis of human carcinoma cells in the presence of potential anti-cancer drugs: III. Treatment of Colo-205 and SKBR3 cells with: cis -platin, Tamoxifen, Melphalan, Betulinic acid, L-PDMP, L-PPMP, and GD3 ganglioside.

    Science.gov (United States)

    Basu, Subhash; Ma, Rui; Boyle, Patrick J; Mikulla, Brian; Bradley, Mathew; Smith, Bradley; Basu, Manju; Banerjee, Sipra

    2004-01-01

    Breast cancer is the most common type of cancer, predominantly among women over 20, whereas colo-rectal cancer occurs in both men and women over the age of 50. Chemotherapy of both cancers affect rapidly growing normal as well as cancer cells. Cancer cells are non-apoptotic. Seven anti-cancer agents (cis -platin, Tamoxifen, Melphalan, Betulinic acid, D-PDMP, L-PPMP, and GD3) have been tested with human breast (SKBR3) and colon (Colo-205) carcinoma cells for their apoptotic effect and found to be positive by several assay systems. Colo-205 cells were obtained from ATCC, and the SKBR3 cells were a gift from the Cleveland Clinic. All of these six agents killed those two cell lines in a dose-dependent manner. In the early apoptotic stage (6 h), these cells showed only a flopping of phosphatidylserine on the outer lamella of the plasma membranes as evidenced by the binding of a novel fluorescent dye PSS-380. After 24 h of the treatment, those apoptotic cells showed damage of the plasma as well as the nuclear membrane as evidenced by binding of propidium iodide to the nuclear DNA. DNA laddering assay viewed further breakdown of DNA by 1% agarose gel electrophoresis analysis. It is concluded that during apoptosis the signaling by Mitochondrial Signaling Pathway (MSP) is stimulated by some of these agents. Caspase 3 was activated with the concomitant appearance of its p17 polypeptide as viewed by Westernblot analyses. Incorporation of radioactivity from [U-(14)C]-L-serine in total sphingolipid mixture was observed between 2 and 4 micromolar concentrations of most of the agents except ci s-platin. However, apoptosis in carcinoma cells in the presence of cis -platin is induced by a caspase 3 activation pathway without any increase in synthesis of ceramide.

  1. FLUDARABINE-MELPHALAN AS PREPARATIVE REGIMEN FOR REDUCED-INTENSITY ALLOGENEIC STEM CELL TRANSPLANTATION IN RELAPSED AND REFRACTORY HODGKIN’S LYMPHOMA: THE UPDATED M.D. ANDERSON CANCER CENTER EXPERIENCE

    Science.gov (United States)

    Anderlini, Paolo; Saliba, Rima; Acholonu, Sandra; Giralt, Sergio A.; Andersson, Borje; Ueno, Naoto T.; Hosing, Chitra; Khouri, Issa F.; Couriel, Daniel; de Lima, Marcos; Qazilbash, Muzaffar H.; Pro, Barbara; Romaguera, Jorge; Fayad, Luis; Hagemeister, Frederick; Younes, Anas; Munsell, Mark F.; Champlin, Richard E.

    2014-01-01

    Background and Objective The role of reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) in relapsed/refractory (R/R) Hodgkin’s lymphoma (HL) remains poorly defined. We hereby present an update of our single-center experience with fludarabine-melphalan (FM) as preparative regimen. Design and Methods Fifty-eight patients with R/R HL underwent RIC and allo-SCT from a matched related donor (MRD; n=25) or a matched unrelated donor (MUD; n=33). Forty-eight (83%) had received a prior autologous SCT. Disease status at transplant was refractory relapse (n=28) or sensitive relapse (n=30). Results Cumulative day 100 and 2-year transplant-related mortality (TRM) were 7% and 15%, respectively (day 100 TRM MRD vs. MUD 8% vs. 6%, p=ns; 2-year MRD vs. MUD 13% vs. 16%, p=ns). The cumulative incidence of acute (grade II–IV) GVHD (first 100 days) was 28% (MRD vs. MUD 12% vs. 39%, p=0.04). The cumulative incidence of chronic GVHD at any time was 73% (MRD vs. MUD 57% vs. 85%, p=0.006). Projected 2-year overall (OS) and progression-free (PFS) survival are 64% (49–76) and 32% (20–45), with 2-year disease progression/relapse (PD) at 55% (43–70). There was no statistically significant difference between MRD and MUD transplants in OS, PFS and PD. There was a trend for the response status pretransplant to favorably impact PFS (p=0.07) and PD (p=0.049), but not OS (p=0.4). Interpretation and Conclusions FM as preparative regimen for RIC allo-SCT in R/R HL is associated with a significant reduction in TRM, with comparable results in MRD and MUD allografts. Optimizing pretransplant response status may improve patient outcome. PMID:18223284

  2. A potential new enriching trial design for selecting non-small-cell lung cancer patients with no predictive biomarker for trials based on both histology and early tumor response: further analysis of a thalidomide trial.

    Science.gov (United States)

    Lee, Siow Ming; Hackshaw, Allan

    2013-06-01

    There are few predictive biomarkers for antiangiogenic trials in lung cancer. We examine a potential treatment strategy in which a patient group is enriched using both histology and an early assessment of response during standard chemotherapy, and where a new agent is given for the remainder of chemotherapy and as maintenance. We performed a retrospective analysis of 722 stage IIIB/IV non-small-cell lung cancer patients from a double-blind placebo-controlled trial of thalidomide or placebo 100-200 mg/day, combined with gemcitabine/carboplatin (for up to four cycles), then given as single agent maintenance therapy. There was a significant statistical interaction between treatment and histology, with a possible benefit among squamous cell cancer (SCC) patients. We examined 150 SCC patients who were "nonprogressors" (stable disease or complete/partial response) after completing the second chemotherapy cycle. Endpoints were progression-free survival (PFS) and overall survival (OS). Among the 150 patients nonprogressors after cycle 2 (thalidomide, n = 72; placebo, n = 78; baseline characteristics were similar), the hazard ratios (HRs) were: OS = 0.76 (95% CI: 0.54-1.07) and PFS = 0.69 (95% CI: 0.50-0.97). In 57 patients who had a complete/partial response, the HRs were: OS = 0.63 (95% CI: 0.34-1.15) and PFS = 0.50 (95% CI: 0.28-0.88). SCC patients who were nonprogressors after 2 cycles of standard chemotherapy showed evidence of a benefit from thalidomide when taken for the remainder of chemotherapy and as maintenance. This strategy based on histology and, importantly, early assessment of tumor response, as a means of patient enrichment, could be examined in other lung cancer studies. Such an approach might be suitable for trials where there are no predictive biomarkers.

  3. Intravenous immunoglobulin with prednisone and risk-adapted chemotherapy for children with opsoclonus myoclonus ataxia syndrome associated with neuroblastoma (ANBL00P3): a randomised, open-label, phase 3 trial.

    Science.gov (United States)

    de Alarcon, Pedro A; Matthay, Katherine K; London, Wendy B; Naranjo, Arlene; Tenney, Sheena C; Panzer, Jessica A; Hogarty, Michael D; Park, Julie R; Maris, John M; Cohn, Susan L

    2018-01-01

    No previous clinical trial has been conducted for patients with neuroblastoma associated opsoclonus myoclonus ataxia syndrome (OMA), and current treatment is based on case reports. To evaluate the OMA response to prednisone and risk-adapted chemotherapy and determine if the addition of intravenous gammaglobulin (IVIG) further improves response, the Children's Oncology Group designed a randomized therapeutic trial. Eligible subjects were randomized to receive twelve cycles of IVIG (IVIG+) or no IVIG (NO-IVIG) in addition to prednisone and neuroblastoma risk-adapted chemotherapy. All low-risk patients were treated with cyclophosphamide. The severity of OMA symptoms was evaluated at 2, 6, and 12 months using a scale developed by Mitchell and Pike and baseline versus best response scores were compared. A single patient who did not undergo neurologic assessment was excluded from OMA response analysis. This study is registered with Clinical Trials.gov (identifier NCT00033293). Of the 53 patients enrolled in the study, 62% (33/53) were female. There were 44 low-risk, 7 intermediate-risk, and 2 high-risk neuroblastoma patients. Twenty-six subjects were randomized to receive IVIG+ and 27 were randomized to NO-IVIG. The neuroblastoma 3-year event-free survival (95% confidence interval (CI)) was 94.1% (87.3%, 100%) and overall survival was 98.0% (94.1%, 100%). Significantly higher rates of OMA response were observed in patients randomized to IVIG+ compared to NO-IVIG [21/26=80.8% for IVIG+; 11/27=40.7% for NO-IVIG (odds ratio=6.1; 95% CI: (1.5, 25.9), p=0.0029)]. For the majority of patients, the IVIG+ OMA regimen combined with cytoxan or other risk-based chemotherapy was well tolerated, although there was one toxic death in a high-risk subject. This is the only randomized prospective therapeutic clinical trial in children with neuroblastoma-associated OMA. The addition of IVIG to prednisone and risk-adapted chemotherapy significantly improves OMA response rate. IVIG

  4. Tratamento de primeira linha no Mieloma Múltiplo First line treatment in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Gisele W. B. Colleoni

    2007-03-01

    stem-cell mobilization (such as alkylating agents. Thus, their treatment options are: dexamethasone, VAD and thalidomide (with or without dexamethasone. Thalidomide should be preferentially used in the context of clinical trials due to increased risks of neuropathy and thrombosis. Patients older than 65-70 years old and those with bad performance status, concurrent diseases or deterioration of renal function can receive alkylating agents (such as melphalan/prednisone because they are not candidates for stem cell transplantation. The aim of their treatment is to reach a disease plateau with low toxicity rates. Other alkylating agents, thalidomide and corticosteroid combinations have higher response rates than melphalan/prednisone however, these combinations present more side effects and do not increase overall survival.

  5. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  6. Prospective Evaluation of Quality of Life and Neurocognitive Effects in Patients With Multiple Brain Metastases Receiving Whole-Brain Radiotherapy With or Without Thalidomide on Radiation Therapy Oncology Group (RTOG) Trial 0118

    International Nuclear Information System (INIS)

    Corn, Benjamin W.; Moughan, Jennifer M.S.; Knisely, Jonathan P.S.; Fox, Sherry W.; Chakravarti, Arnab; Yung, W.K. Alfred; Curran, Walter J.; Robins, H. Ian; Brachman, David G.; Henderson, Randal H.; Mehta, Minesh P.; Movsas, Benjamin

    2008-01-01

    Purpose: Radiation Therapy Oncology Group (RTOG) 0118 randomized patients with multiple brain metastases to whole-brain radiotherapy (WBRT) ± thalidomide. This secondary analysis of 156 patients examined neurocognitive and quality of life (QOL) outcomes. Methods and Materials: Quality of life was determined with the Spitzer Quality of Life Index (SQLI). The Folstein Mini-Mental Status Exam (MMSE) assessed neurocognitive function. SQLI and MMSE were administered at baseline and at 2-month intervals. MMSE was scored with a threshold value associated with neurocognitive functioning (absolute cutoff level of 23) and with the use of corrections for age and educational level. Results: Baseline SQLI predicted survival. Patients with SQLI of 7-10 vs. <7 had median survival time (MST) of 4.8 vs. 3.1 months, p = 0.05. Both arms showed steady neurocognitive declines, but SQLI scores remained stable. Higher levels of neurocognitive decline were observed with age and education-level corrections. Of patients considered baseline age/educational level neurocognitive failures, 32% died of intracranial progression. Conclusions: Quality of life and neuropsychological testing can be prospectively administered on a Phase III cooperative group trial. The MMSE should be evaluated with adjustments for age and educational level. Baseline SQLI is predictive of survival. Despite neurocognitive declines, QOL remained stable during treatment and follow-up. Poor neurocognitive function may predict clinical deterioration. Lack of an untreated control arm makes it difficult to determine the contribution of the respective interventions (i.e., WBRT, thalidomide) to neurocognitive decline. The RTOG has developed a trial to study the role of preventative strategies aimed at forestalling neurocognitive decline in this population

  7. Colchicine in the treatment of the inflammatory phase of Graves' ophthalmopathy: a prospective and randomized trial with prednisone Colchicina no tratamento da fase inflamatória da oftalmopatia de Graves: um estudo prospectivo e randomizado com prednisona

    Directory of Open Access Journals (Sweden)

    Francisco José da Cunha Stamato

    2006-12-01

    Full Text Available PURPOSE: To investigate if colchicine is valuable in the treatment of Graves' ophthalmopathy (GO, we compared its effect with prednisone in 22 patients during the inflammatory phase of GO. METHODS: All patients, similar in age, sex and smoking habits, were euthyroid for at least 3 months and randomly divided into two groups, one treated with colchicine (1.5 mg/day and the other treated with prednisone (0.75 mg/kg/day. They were monitored with ophthalmologic assessment (clinical activity score-CAS and magnetic resonance imaging, using a signal intensity ratio (SIR of the recti muscles in comparison to the cerebral substantia alba. RESULTS: Amelioration of CAS was seen in 68% of the orbits in both groups. SIR also had a significant reduction after treatment: the initial median of 1.14 in G1 and 1.27 in G2, evolved, after treatment, to 1.07 in G1 and 0.69 in G2. The variation between both groups after treatment was not significant (p=0.22. None of the patients treated with colchicine had side effects; on the other hand, side effects in G2 were weight gain, edema, gastric complaints, hirsutism, weakness, depression, and alterations in blood pressure. CONCLUSION: Colchicine had a beneficial effect on the inflammatory phase of GO without the side effects of prednisone.OBJETIVO: Investigar se a colchicina é eficaz no tratamento da oftalmopatia de Graves, nós comparamos o seu efeito com a prednisona em 22 pacientes tratados na fase inflamatória da doença. MÉTODOS: Todos os pacientes, similares quanto à idade, sexo e hábitos de tabagismo, estavam em eutiroidismo por pelo menos três meses e foram randomizados em dois grupos. O grupo 1 (G1 recebeu colchicina (1,5 mg/dia e o grupo 2 (G2 foi tratado com prednisona (0,75 mg/kg/dia. Os pacientes foram acompanhados com avaliação oftalmológica (escore de atividade clínica - CAS e de imagem por meio da ressonância magnética, usando a relação da intensidade de sinal (SIR dos músculos reto em

  8. Bussulfano e melfalano como regime de condicionamento para o transplante autogênico de células-tronco hematopoéticas na leucemia mielóide aguda em primeira remissão completa Busulfan and melphalan as conditioning regimen for autologous hematopoietic stem cell transplantation in acute myeloid leukemia in first complete remission

    Directory of Open Access Journals (Sweden)

    Nadjanara D. Bueno

    2008-10-01

    Full Text Available Vinte e dois pacientes consecutivos portadores de leucemia mielóide aguda (LMA em primeira remissão completa (1ªRC submetidos a transplante de células-tronco hematopoéticas autogênico (TCTH Auto condicionados com bussulfano e melfalano (Bu/Mel foram selecionados entre 1993 e 2006. A probabilidade de sobrevida global (SG pelo método de Kaplan-Meier foi de 57,5% após 36 meses, com "plateau" aos 20 meses após o transplante. Fatores como sexo, classificação Franco-Americana-Britânica (FAB da LMA, tratamento de indução, consolidação intensiva, remissão após o primeiro ciclo de indução e fonte de células não tiveram impacto na sobrevida. Pela análise citogenética, um paciente de mau prognóstico submetido ao procedimento, foi a óbito um ano após o transplante. Nove pacientes foram a óbito, oito por recidiva e um por hemorragia. Morte antes dos 100 dias ocorreu em dois pacientes, um por recidiva e outro por hemorragia decorrente da plaquetopenia refratária, relacionada ao procedimento. Concluímos que o regime de condicionamento Bu/Mel é opção válida ao uso de outros regimes de condicionamento, apresentando excelente taxa da sobrevida.Twenty-two consecutive patients with acute myeloid leukemia in first complete remission submitted to autologous hematopoietic stem cells transplantation conditioned with busulfan and melphalan were evaluated between 1993 and 2006. The overall survival, according to the Kaplan-Meier curve, was 57.5% at 36 months, with a "plateau" at 20 months after transplant. Factors such as gender, French-American-British (FAB classification of acute myeloid leukemia, induction therapy, intensive consolidation, remission after the first cycle of induction and source of cells had no impact on survival. One patient with poor prognosis before the procedure died a year after transplantation. Nine patients died, eight by relapse and one because of bleeding. Death before 100 days occurred for two patients, one

  9. Cyclophosphamide, vincristine, and prednisone followed by tositumomab and iodine-131-tositumomab in patients with untreated low-grade follicular lymphoma: eight-year follow-up of a multicenter phase II study.

    Science.gov (United States)

    Link, Brian K; Martin, Peter; Kaminski, Mark S; Goldsmith, Stanley J; Coleman, Morton; Leonard, John P

    2010-06-20

    The efficacy and safety of cyclophosphamide, vincristine, and prednisone (CVP) followed by tositumomab and iodine-131 ((131)I) -tositumomab therapy were evaluated in a multicenter phase II study in patients with untreated low-grade follicular lymphoma. Patients received six cycles of CVP followed by one cycle of tositumomab and (131)I-tositumomab (one dosimetric dose and one therapeutic dose). The treatment was evaluated for efficacy and safety. All 30 patients enrolled completed CVP as well as tositumomab and (131)I-tositumomab therapy. The overall response rate after completion of therapy was 100%, with 28 patients (93%) achieving a complete response (CR) and two patients achieving a partial response. Of the 17 patients with bone marrow involvement at enrollment, 15 achieved a confirmed CR. Fourteen of 15 patients with bulky disease (> or = 5 cm) had a CR after treatment completion. After a median follow-up of 8.4 years, the median response duration had not been reached (range, 3 to 111+ months). Five-year progression-free and overall survival rates were 56% and 83%, respectively. The most common grade > or = 3 hematologic adverse events were neutropenia (87%) and thrombocytopenia (37%). Nineteen patients received growth factor support, and three required blood product transfusions. No patients developed human antimurine antibodies. Two patients developed myelodysplastic syndrome/acute myeloid leukemia. These mature data demonstrate that sequential therapy with a non-anthracycline-containing regimen comprising CVP followed by one cycle of tositumomab and (131)I-tositumomab produced high response rates with adequate safety and durable remissions and that this regimen represents a highly active treatment for first-line therapy of follicular non-Hodgkin's lymphoma.

  10. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease.

    Science.gov (United States)

    Rossi, Giacomo; Pengo, Graziano; Caldin, Marco; Palumbo Piccionello, Angela; Steiner, Jörg M; Cohen, Noah D; Jergens, Albert E; Suchodolski, Jan S

    2014-01-01

    Idiopathic inflammatory bowel disease (IBD) is a common chronic enteropathy in dogs. There are no published studies regarding the use of probiotics in the treatment of canine IBD. The objectives were to compare responses to treatment with either combination therapy (prednisone and metronidazole) or probiotic strains (VSL#3) in dogs with IBD. Twenty pet dogs with a diagnosis of IBD, ten healthy pet dogs, and archived control intestinal tissues from three euthanized dogs were used in this open label study. Dogs with IBD were randomized to receive either probiotic (D-VSL#3, n = 10) or combination drug therapy (D-CT, n = 10). Dogs were monitored for 60 days (during treatment) and re-evaluated 30 days after completing treatment. The CIBDAI (Pdogs in the D-VSL#3 group compared to the D-CT group. Changes in apical junction complex molecules occludin and claudin-2 differed depending on treatment. Faecalibacterium and Turicibacter were significantly decreased in dogs with IBD at T0, with a significant increase in Faecalibacterium abundance observed in the animals treated with VSL#3 strains. A protective effect of VSL#3 strains was observed in dogs with IBD, with a significant decrease in clinical and histological scores and a decrease in CD3+ T-cell infiltration. Protection was associated with an enhancement of regulatory T-cell markers (FoxP3+ and TGF-β+), specifically observed in the probiotic-treated group and not in animals receiving combination therapy. A normalization of dysbiosis after long-term therapy was observed in the probiotic group. Larger scale studies are warranted to evaluate the clinical efficacy of VSL#3 in canine IBD.

  11. Primary (AL) amyloidosis with gastrointestinal involvement

    DEFF Research Database (Denmark)

    Madsen, Lone Galmstrup; Gimsing, Peter; Schiødt, Frank V

    2009-01-01

    ). Steatorrhea (2 mild, 1 moderate, 1 severe) was found in 4 of 7 patients examined. At presentation, 9 patients had hypoalbuminemia and 6 patients had anemia. Three patients were treated with home parenteral nutrition. Five patients received conventional chemotherapy (oral melphalan and prednisone) and 5...

  12. Comparing efficacy and survivals of initial treatments for elderly patients with newly diagnosed multiple myeloma: a network meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Liu X

    2016-12-01

    Full Text Available Xiaoping Liu,1,* Jiarui Chen,2,* Yuncen A He,3 Xiangyu Meng,1 Kaili Li,4 Colin K He,5 Shangqin Liu4 1Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, 2School of Basic Medical Science, Wuhan University, Wuhan, Hubei, People’s Republic of China; 3School of Medicine, Case Western Reserve University, Cleveland, OH, USA; 4Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 5Orient Healthcare, New York, NY, USA *These authors contributed equally to this work Objective: The aim of this study was to evaluate the efficacy and clinical outcome of initial therapies for elderly patients with multiple myeloma (MM.Methods: Randomized controlled trials (RCTs were obtained through a comprehensive search. Response rate, progression-free survival (PFS and overall survival (OS were the interested outcome measures. Network meta-analysis (NMA using graph theory methodology to construct an NMA model, and sensitivity analysis were performed.Results: Nineteen RCTs containing 7,235 participants and 17 treatments were included in the NMA. As compared to the classic melphalan plus prednisone (MP regimen, the majority of other initial regimens showed higher rates of complete response/near complete response, overall response rate (ORR and better PFS as well as OS. These four outcomes favored the two lenalidomide plus dexamethasone regimens (continuous lenalidomide and 18 cycles of lenalidomide plus dexamethasone, especially continuous lenalidomide plus dexamethasone regimen, over the majority of other regimens including the two established standard treatments (MP plus thalidomide or bortezomib for elderly patients with newly diagnosed MM.Conclusion: Continuous lenalidomide plus dexamethasone ranked as the best regimen in terms of ORR and OS for the treatment of elderly patients with newly diagnosed MM. Keywords: multiple myeloma, previously untreated, elderly patients

  13. Síndrome de Tolosa-Hunt: dificuldades no diagnóstico e padrão de resposta à prednisona Tolosa-Hunt syndrome: troubles in diagnosing and pattern of response to prednisone

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    Paulo Eduardo Mestrinelli Carrilho

    1997-01-01

    Full Text Available A síndrome de Tolosa-Hunt (STH consiste de oftalmoplegia dolorosa relacionada a processo inílamatório granulomatoso no seio cavernoso. Seu diagnóstico só pode ser firmado quando outras causas potenciais de oftalmoplegia dolorosa forem descartadas. Resposta satisfatória e padronizada a corticosteróides, associada a evolução benigna, pode reforçar essa possibilidade, embora pseudotumor orbitário e neoplasias do tipo linfoma e até meningioma possam suscitar dúvidas no diagnóstico diferencial, pois também podem apresentar boa resposta a essa medicação. Faz-se necessário, portanto, ampla investigação complementar. Apresentamos estudo clínico-radiológico-laboratorial de cinco pacientes com STH. Prednisona foi utilizada em doses entre 40 e 80 mg/dia. Houve resposta analgésica excelente, com remissão da dor em menos de 48 horas em 4 pacientes. Houve melhora mais lenta da oftalmoplegia, que regrediu completamenteentre 4 e 45 dias em todos os pacientes.The Tolosa-Hunt syndrome (THS consists of a painful ophthalmoplegia related to granulomatous inflammatory process in the cavernous sinus. According to recent concepts, the diagnosis is established only when other causes of painful ophthalmoplegia are ruled out. A typical pattern of response to corticosteroids associated with a benign evolution may reinforce this possibility. Tumors such as lymphoma and meningioma and orbital pseudotumors can make difficult the differential diagnosis because they also may respond to steroids. Thus it is always necessary to make an extensive ancillary investigation. We performed a clinical, laboratory and radiologic study of five patients with THS. Prednisone was used in all, with dosages ranging from 40 to 80 mg/day. In four patients there was a dramatic analgesic effect in less than 48 hours. Improvement of the ophthalmoplegia was not so fast but occurred in all with a complete remission in 4 to 45 days.

  14. Role of cranial radiotherapy for childhood T-cell acute lymphoblastic leukemia with high WBC count and good response to prednisone. Associazione Italiana Ematologia Oncologia Pediatrica and the Berlin-Frankfurt-Münster groups.

    Science.gov (United States)

    Conter, V; Schrappe, M; Aricó, M; Reiter, A; Rizzari, C; Dördelmann, M; Valsecchi, M G; Zimmermann, M; Ludwig, W D; Basso, G; Masera, G; Riehm, H

    1997-08-01

    The ALL-BFM 90 and AIEOP-ALL 91 studies share the same treatment backbone and have 5-year event-free survival (EFS) rates close to 75%. This study evaluated the impact of differing presymptomatic CNS therapies in T-cell acute lymphoblastic leukemia (T-ALL) patients with a good response to prednisone (PGR) according to WBC count and Berlin-Frankfurt-Münster (BFM) risk factor (RF). A total of 192 patients (141 boys; median age, 7.5 years) with T-ALL, PGR, RF less than 1.7, and no CNS leukemia diagnosed between 1990 and 1995 were enrolled onto the ALL-BFM 90 (n = 123) or AIEOP-ALL 91 (n = 69) study. Presymptomatic CNS therapy consisted of cranial radiation (CRT) and intrathecal methotrexate (I.T. MTX) (11 doses) in the BFM study and of extended triple intrathecal therapy (T.I.T.) (17 doses) in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) study. Patients were divided into a low-WBC group (WBC count 100,000/microL). EFS was compared using the log-rank test. For patients treated with CRT and I.T. MTX (BFM group), the 3-year EFS rate was 89.8% (SE = 3.5) for 99 patients in the low-WBC group versus 81.9% (SE = 8.2) in the high-WBC group (difference not significant). Conversely, for patients treated with T.I.T. alone (AIEOP group), the EFS rate was 80.6% (SE = 5.6) in 55 patients with a low WBC count versus 17.9% (SE = 11.0) in 14 patients with a high WBC count (P < .001). These data suggest that CRT may not be necessary in PGR T-ALL patients with a WBC count less than 100,000/microL; on the contrary, in patients with a high count, extended T.I.T. may be inferior to CRT and I.T. MTX.

  15. Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Giacomo Rossi

    Full Text Available BACKGROUND: Idiopathic inflammatory bowel disease (IBD is a common chronic enteropathy in dogs. There are no published studies regarding the use of probiotics in the treatment of canine IBD. The objectives were to compare responses to treatment with either combination therapy (prednisone and metronidazole or probiotic strains (VSL#3 in dogs with IBD. METHODOLOGY AND PRINCIPAL FINDINGS: Twenty pet dogs with a diagnosis of IBD, ten healthy pet dogs, and archived control intestinal tissues from three euthanized dogs were used in this open label study. Dogs with IBD were randomized to receive either probiotic (D-VSL#3, n = 10 or combination drug therapy (D-CT, n = 10. Dogs were monitored for 60 days (during treatment and re-evaluated 30 days after completing treatment. The CIBDAI (P<0.001, duodenal histology scores (P<0.001, and CD3+ cells decreased post-treatment in both treatment groups. FoxP3+ cells (p<0.002 increased in the D-VSL#3 group after treatment but not in the D-CT group. TGF-β+ cells increased in both groups after treatment (P = 0.0043 with the magnitude of this increase being significantly greater for dogs in the D-VSL#3 group compared to the D-CT group. Changes in apical junction complex molecules occludin and claudin-2 differed depending on treatment. Faecalibacterium and Turicibacter were significantly decreased in dogs with IBD at T0, with a significant increase in Faecalibacterium abundance observed in the animals treated with VSL#3 strains. CONCLUSIONS: A protective effect of VSL#3 strains was observed in dogs with IBD, with a significant decrease in clinical and histological scores and a decrease in CD3+ T-cell infiltration. Protection was associated with an enhancement of regulatory T-cell markers (FoxP3+ and TGF-β+, specifically observed in the probiotic-treated group and not in animals receiving combination therapy. A normalization of dysbiosis after long-term therapy was observed in the probiotic group. Larger

  16. Thalidomide with peginterferon alfa-2b and ribavirin in the treatment of non-responders genotype 1 chronic hepatitis C patients: proof of concept Talidomida, peginterferón alfa-2b y ribavirina en el tratamiento de pacientes no respondedores con hepatitis crónica C genotipo 1: estudio piloto

    Directory of Open Access Journals (Sweden)

    Benjamín Pardo-Yules

    2011-12-01

    Full Text Available Background: fewer than half of patients infected with hepatitis C virus (HCV achieve sustained viral clearance after peginterferon alfa/ribavirin (Peg-IFN/RBV therapy. Aims: thalidomide posses anti-inflammatory and immunomodulatory properties through inhibition of tumor necrosis factor and costimulatory effect on human CD8+ T cells. Methods: we started a prospective, open label trial of retreatment of very-difficult-to-treat genotype 1 chronic hepatitis C patients (CHC patients, who had failed to respond to the (Peg-IFN/RBV, with a triple therapy consisting in these same antivirals plus thalidomide 200 mg/day (the TRITAL study. Results: none of the eleven patients fulfilling the inclusion criteria and included in the trial reached complete early virological response or sustained virological response. Viral load decline after 12 weeks of triple therapy thalidomide-based retreatment did not differ from viral dynamics during the first course. The triple therapy was well tolerated and only one patient developed mild bilateral neuropathy. Conclusions: thalidomide addition to standard therapy is tolerated and did not increase the SVR rate in very-difficult-to-treat genotype 1 CHC patients. Different schedules are warranted to improve attempting retreatment of non responder CHC patients.Antecedentes: menos de la mitad de los pacientes con hepatitis C logra eliminar el virus de manera sostenida después de la terapia con peginterferón alfa y ribavirina (Peg-IFN/RBV. Objetivos: la talidomida posee propiedades antiinflamatorias e inmunomoduladoras a través de la inhibición del TNF-α y al efecto estimulador sobre las células T CD8+. Métodos: se inició un estudio prospectivo y abierto de re-tratamiento de pacientes con hepatitis crónica C genotipo 1, no respondedores al tratamiento con Peg-IFN/RBV, mediante triple terapia añadiendo a los mismos antivirales 200 mg/día de talidomida. Resultados: ninguno de los once pacientes que fueron incluidos en

  17. Histiocitose de células de Langerhans com acometimento vulvar e com resposta terapêutica à talidomida: relato de caso Langerhans cells histiocytosis with vulvar involvement and responding to thalidomide therapy: case report

    Directory of Open Access Journals (Sweden)

    Lana Bezerra Fernandes

    2011-08-01

    Full Text Available A histiocitose de células de Langerhans é representante de um raro grupo de síndromes histiocitárias, sendo caracterizada pela proliferação das células de Langerhans. Suas manifestações variam de lesão solitária a envolvimento multissistêmico, sendo o acometimento vulvar incomum. Segue-se o relato de caso refratário da doença limitada à pele, em mulher de 57 anos. A paciente apresentava história de pápulas eritematosas ulceradas em couro cabeludo, face, vulva, tronco e axila há seis anos. O diagnóstico da doença é difícil, sendo confirmado neste caso através de estudo imuno-histoquímico e se obteve resposta terapêutica e eficaz, com a administração de talidomidaLangerhans cell histiocytosis is a member of a group of rare histiocytic syndromes and is characterized for the proliferation of histiocytes called Langerhans'cells. Its manifestations vary from a solitary injury to systemic involvement, and vulvar lesions are uncommon. We describe a refractory case of cutaneous limited disease in a 57-year-old woman. She presented with a 6-year history of an erythematous papular eruption of the scalp, face, vulva, trunk and axillae. The diagnosis is difficult and in this case it was confirmed through immunohistochemical study and clinical improvement was achieved with thalidomide

  18. Grau de desmineralização em osso trabecular e cortical por meio de tomografia computadorizada quantitativa em cães submetidos à terapia com prednisona Trabecular and cortical bone demineralization degree by quantitative computed tomography in dogs treated with prednisone

    Directory of Open Access Journals (Sweden)

    Lorena Adão Vescovi Séllos Costa

    2010-12-01

    Full Text Available Os glicocorticóides são fármacos amplamente utilizados na medicina veterinária, entretanto, além dos efeitos benéficos, o seu emprego pode desencadear uma série de efeitos indesejados. Foi realizado um ensaio clínico em oito cães hígidos com o intuito de avaliar possíveis alterações na densidade mineral óssea após a terapia com prednisona, utilizando a tomografia computadorizada helicoidal. Todos os animais receberam a prednisona via oral na dose diária de 2mg kg-1 de peso durante 30 dias. A densidade mineral óssea foi determinada a partir da obtenção de valores de radiodensidade da região de osso cortical e osso trabecular do corpo vertebral da segunda vértebra lombar, imediatamente antes e após o período de administração do medicamento. O protocolo experimental permitiu a caracterização de significativa (PGlucocorticoids are widely used in veterinary medicine. However, beyond the beneficial effects, their use can trigger a series of unwanted effects. A clinical trial was conducted in eight healthy dogs in order to assess possible changes in bone mineral density after therapy with prednisone using helical computed tomography. All animals received oral prednisone at a daily dose of 2mg kg-1 of body weight for 30 days. Bone mineral density was determined by the obtaining of radiodensity values from the cortical region and the trabecular region of the second lumbar vertebra immediately before and after the period of drug administration. The experimental protocol allowed the characterization of a significant (P<0.01 decrease of trabecular bone radiodensity on the second lumbar vertebra, but no significant demineralization was found in the cortical region. None of the dogs used in this experiment had pathological fracture at the end of the experimental protocol. This study showed that in dogs subjected to therapy with prednisone at a dose of 2mg kg-1 changes in bone metabolism occur early in trabecular bone, being

  19. Thalidomide and lenalidomide in primary myelofibrosis.

    NARCIS (Netherlands)

    Holle, N.; Witte, T.J.M. de; Mandigers, C.M.P.W.; Schaap, N.P.M.; Raymakers, R.A.P.

    2010-01-01

    Primary myelofibrosis is a clonal haematopoietic stem cell disease, characterised by marrow stromal fibrosis, extramedullary haematopoiesis, splenomegaly, hepatomegaly and progressive cytopenia. Therapeutic options once cytopenia has developed are limited to supportive care, such as erythrocyte

  20. Talidomida e mieloma múltiplo: verificação dos efeitos terapêuticos através de parâmetros clínico e laboratoriais Thalidomide and multiple myeloma: therapy evaluation using clinical and laboratorial parameters

    Directory of Open Access Journals (Sweden)

    Rosane Bittencourt

    2004-12-01

    mechanisms that interfere in the physiopathogenesis and bone marrow microenvironment are turning control and regression of the malignant plasma cell clone into something achievable, which may change expectations related to this disease. The new idea of using an old drug, thalidomide, has shown to be effective in multiple myeloma. In 1997, using the known effects of immunomodulation and anti-angiogenesis of this drug, clinical trials were started in patients with unresponsive disease. Other therapeutic interventions in the bone marrow microenvironment and plasma cells have been added and proved to be efficacious, not only as a therapy for refractory patients, but also for induction and/or remission maintenance therapy. Thirty-five patients with multiple myeloma were treated with low-dose thalidomide (100 mg and followed up. Thirteen were on maintenance therapy after bone marrow transplantation, eleven started thalidomide after induction therapy, five after relapse, four were refractory to usual therapies and two had induction therapy with thalidomide. The study took place in the Hematology and Bone Marrow Transplantation service of the Hospital de Clínicas de Porto Alegre, from March 2001 to December 2003. Hemoglobin levels, serum or urine immunoglobulin peaks and bone marrow plasma cell counts were evaluated. These parameters were assessed before starting with the drug and after 3.6 and 12 months of usage. The immunoglobulin level was considered the gold standard to evaluate the response. The results showed that 100 mg was the tolerable dose for 51% of the patients. Sixty-five percent of those who used thalidomide for induction therapy showed a 25 to 50% improvement in immunoglobulin serum levels and 90% of the patients on maintenance therapy (13 after bone marrow transplantation, 11 after induction, sustained the same immunoglobulin levels of the initial plateau.

  1. Second cancer incidence in primary mediastinal B-cell lymphoma treated with methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin regimen with or without rituximab and mediastinal radiotherapy: Results from a monoinstitutional cohort analysis of long-term survivors.

    Science.gov (United States)

    De Sanctis, Vitaliana; Alfò, Marco; Di Rocco, Alice; Ansuinelli, Michela; Russo, Eleonora; Osti, Mattia F; Valeriani, Maurizio; Minniti, Giuseppe; Grapulin, Lavinia; Musio, Daniela; Bracci, Stefano; Spagnoli, Alessandra; Moleti, Maria Luisa; Tombolini, Vincenzo; Martelli, Maurizio

    2017-12-01

    Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia. Copyright © 2017 John Wiley & Sons, Ltd.

  2. The role of thalidomide as maintenance after autologous stem cell transplantation in multiple myeloma Papel da talidomida como manutenção após transplante autólogo de células-tronco hematopoéticas em mieloma múltiplo

    Directory of Open Access Journals (Sweden)

    Angelo Maiolino

    2009-08-01

    Full Text Available Major progress was obtained over the last ten years in the treatment of multiple myeloma (MM. High dose chemotherapy with autologous stem cell transplantation (ASCT and new drugs such as thalidomide, lenalidomide and bortezomib have completely changed the scenario of MM treatment. ASCT has become the mainstay of MM treatment for patients up to 65 years old. This strategy has been tested in randomized clinical trials which proved that ASCT can improve overall survival of MM patients. Unfortunately, the great majority of these patients will relapse in a few years after ASCT. Strategies of maintenance have been developed trying to improve the results of ASCT. Thalidomide has been tested in this setting in at least 4 randomized clinical trials with a significant impact on response rate, and event free and overall survival.l.Grandes progressos foram obtidos nos últimos anos no tratamento do mieloma múltiplo (MM. Quimioterapia em altas doses seguida de transplante autólogo de células-tronco hematopoéticas (TCTH e a utilização de novas drogas, como a talidomida, lenalidomida e bortezomibe, mudaram completamente o cenário de tratamento do MM. O TCTH tornou-se padrão na abordagem de pacientes com MM recém-diagnosticado e idade inferior a 65 anos. Esta estratégia foi testada em estudos multicêntricos e randomizados, que demonstraram uma vantagem em termos de sobrevida global para os pacientes submetidos a TCTH. Infelizmente, a grande maioria dos pacientes irá recair em poucos anos após o TCTH. Estratégias de manutenção ou consolidação foram então desenvolvidas com o intuito de melhorar estes resultados. A talidomida foi testada como manutenção em pelo menos quatro estudos randomizados, tendo sido demonstrado um impacto favorável em termos de taxa de resposta e prolongamento da sobrevida global.

  3. THE TREATMENT OF MULTIPLE MYELOMA PATIENTS NOT ELIGIBLE FOR ASCT

    Directory of Open Access Journals (Sweden)

    Anuj Mahindra

    2010-05-01

    Full Text Available

    Advances in therapies for younger patients with multiple myeloma have resulted in significant improvements in outcome over recent years, on the contrary the progress in treatments for elderly patients has remained more modest. Traditionally, patients   who are not eligible for transplantation, like the older patients,  have been treated with the combination of melphalan plus prednisone (MP, which leads to responses in approximately 50% of patients; however, patients rarely achieve a complete response (CR and long-term outcomes are disappointing, with a relapse-free survival of approximately 18 months and an overall survival (OS of approximately 3 years.

    With the arrival of novel agents, including the first–in-class proteasome inhibitor, bortezomib, and the immunomodulatory agents, thalidomide and lenalidomide, a shift in the management of older patients and/or those not eligible for transplantation has taken

  4. Azathioprine and prednisone combination therapy in refractory coeliac disease.

    NARCIS (Netherlands)

    Goerres, MS; Meijer, JW; Wahab, PJ; Kerckhaert, JA; Groenen, PJ; Krieken, JH Van; Mulder, C.J.J.

    2003-01-01

    INTRODUCTION: Refractory coeliac disease (RCD) is a rare syndrome with a poor prognosis, defined by malabsorption due to gluten-related enteropathy after initial or subsequent failure of a strict gluten-free diet and after exclusion of any disorder mimicking coeliac disease. PATIENTS AND METHODS:

  5. Prednisone and Other Corticosteroids: Balance the Risks and Benefits

    Science.gov (United States)

    ... lower legs High blood pressure Problems with mood, memory, behavior and other psychological effects Weight gain, with fat deposits in your abdomen, ... injected corticosteroids Injected corticosteroids can cause temporary ... skin thinning, loss of color in the skin, facial flushing, insomnia and high ...

  6. Duchenne muscular dystrophy quantification of muscular parameters and prednisone therapy

    NARCIS (Netherlands)

    Beenakker, Ernesto Alexander Christiaan

    2005-01-01

    The aims of the study described in this thesis were: 1. to establish reference values for muscle force, functional ability, calf circumference and echogenitcity of muscle tissue; 2. to assess disease severity in ambulant DMD patients by using these reference values;3. to determine the effects of

  7. 21 CFR 522.1890 - Sterile prednisone suspension.

    Science.gov (United States)

    2010-04-01

    ... therapy, reevaluate diagnosis.1 (b) Dogs and cats. 0.25 to 1.0 milligram per pound of body weight for 3 to... to animals may induce the first stage of parturition when administered during the last trimester of pregnancy and may precipitate premature parturition followed by dystocia, fetal death, retained placenta...

  8. Multiple myeloma in Niger Delta, Nigeria: complications and the outcome of palliative interventions

    Directory of Open Access Journals (Sweden)

    Nwabuko OC

    2017-05-01

    (MP double regimen, while 19% and 8% patients were on MP–thalidomide and MP–bortezomib triple regimens, respectively. A total of 3.8% of patients at DS stage IIIB disease had autologous stem-cell transplantation (ASCT. Only 7.6% of the myeloma patients survived up to 5 years post diagnosis. The overall mean survival interval was 39.7 months (95% CI, 32.1–47.2.Conclusion: Late diagnosis and inadequate palliative care account for major complications encountered by MM patients in the Niger-Delta region of Nigeria. This could be responsible for the poor prognostic outcome and low survival interval of MM individuals in this region. There is, therefore, a need to improve the quality of palliative care received by myeloma patients in this region. This is achievable via provision of relevant and affordable health care facilities for diagnosis and treatment of the disease. Keywords: multiple myeloma, palliative care, melphalan-prednisone, bone marrow plasma cells, autologous stem-cell transplantation, Niger Delta

  9. What a Difference Melphalan Makes! Differential Protein Expression in Melphalan Sensitive and Resistant Multiple Myeloma Cells Revealed by SILAC-based Quantitative Proteomics

    DEFF Research Database (Denmark)

    Zub, Kamila Anna; Sousa, Mirta M.L.; Young, Clifford

    quantified by using both Mascot Distiller and MaxQuant. Comparison as well as grouping into appropriate networks and pathways of identified proteins was performed by Ingenuity Pathway Analysis software. Preliminary analyses indicate that a large fraction of the differentially expressed proteins are involved...

  10. Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

    DEFF Research Database (Denmark)

    Kolstad, Arne; Laurell, Anna; Jerkeman, Mats

    2014-01-01

    The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding (90)Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients ...)-maxi-CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0...

  11. Elotuzumab in combination with thalidomide and low-dose dexamethasone

    DEFF Research Database (Denmark)

    Mateos, Maria-Victoria; Granell, Miguel; Oriol, Albert

    2016-01-01

    /discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction...

  12. Síndrome de West: evolução clínica e eletrencefalográfica de 70 pacientes e resposta ao tratamento com hormônio adrenocorticotrófico, prednisona, vigabatrina, nitrazepam e ácido valpróico West syndrome: clinical and eletroencephalographic follow up of 70 patients and response to the adrenocorticotropic hormone, prednisone, vigabatrin, nitrazepam and valproate

    Directory of Open Access Journals (Sweden)

    SÉRGIO A. ANTONIUK

    2000-09-01

    Full Text Available Em estudo retrospectivo avaliamos a evolução clínica e eletrencefalográfica das formas criptogênica e sintomática da síndrome de West e analisamos a eficácia do hormônio adrenocorticotrófico, vigabatrina, prednisona, ácido valpróico e nitrazepam no controle dos espasmos. Participaram do estudo 70 pacientes, acompanhados por período maior que 2 anos. Doze (17% eram criptogênicos e 58 (83% sintomáticos. O grupo criptogênico apresentou percentagem significativamente maior de pacientes que frequentavam escola regular e desenvolvimento motor normal, melhor controle das crises epilépticas, tendência menor a evoluir para síndrome de Lennox Gastaut e 83,3% tiveram controle completo dos espasmos (72,4% dos pacientes do grupo sintomático obtiveram controle completo dos espasmos. O hormônio adrenocorticotrófico e a vigabatrina foram as drogas mais eficazes, controlando 68,75% e 60% dos espasmos, respectivamente, quando utilizados como droga de primeira escolha e 75% e 50%, respectivamente, como drogas de segunda escolha.In a retrospective study we assessed the outcome of the criptogenic and symptomatic forms of West syndrome and evaluated the efficacy of adrenocorticotropic hormone, vigabatrin, prednisone, valproate and nitrazepam in the spasms control. Seventy patients were follwed up by 2 years. Twelve (17% were criptogenics and 58 (83% symptomatics. In criptogenic group significantly more patients were in regular school classes and with normal motor development, better control of seizure, less tendency to evoluate to Lennox Gastaut syndrome and 83.3% had control of spasms (72.4% of patients from symptomatic group had control of spasms. Adrenocorticotropic hormone and vigabatrin were the most efective drugs, with 68.75% and 60% of spasms control, respectivelly, when used as first line of therapy and 75% and 50%, respectivelly, as second line of therapy.

  13. Escleromixedema: um caso tratado com prednisona oral Scleromyxedema: a case treated with oral prednisone

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    Pedro Bezerra da Trindade Neto

    2006-02-01

    Full Text Available O escleromixedema é uma mucinose cutânea idiopática caracterizada por erupção papulosa, induração da pele e paraproteinemia. Histologicamente, se observa proliferação de fibroblastos na derme superior associada a depósito de mucina. O tratamento é difícil, não existindo na atualidade modalidade terapêutica totalmente eficaz para controlar a enfermidade. Relata-se o caso de um paciente de 68 anos com escleromixedema, sem manifestação sistêmica, que respondeu à terapia oral com corticosteróide.Scleromyxedema is an idiopathic cutaneous mucinosis characterized by a papular eruption, skin induration and paraproteinemia. Histologically, fibrolast proliferation can be observed in the upper dermis associated with a mucine deposition. Treatment is difficult and at present there is no totally effective therapeutic modality to control the disease. The present report is on a 68-year-old patient with scleromyxedema without systemic manifestation, who responded to oral steroid therapy.

  14. Phase I/II study on docetaxel, gemcitabine and prednisone in castrate refractory metastatic prostate cancer

    DEFF Research Database (Denmark)

    Buch-Hansen, Trine Zeeberg; Bentzen, Lise Nørgaard; Hansen, Steinbjoern

    2010-01-01

    DGP, maximum of eight courses, until progression or unacceptable toxicity. Docetaxel 75 mg/m(2) was administered intravenously day 1, gemcitabine was given day 1 and 8 in doses increasing from 600 to 1,000 mg/m(2) every third week. Patients had castrate refractory metastatic prostate cancer (CRMPC......), adequate function of liver, kidney and bone marrow; ECOG performance status...

  15. Light chain (AL amyloidosis: update on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Rosenzweig Michael

    2011-11-01

    Full Text Available Abstract Light chain (AL amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM followed by autologous hematopoietic stem cell transplantation (SCT or oral melphalan with dexamethasone (MDex. The use of novel agents (thalidomide, lenalidomide and bortezomib alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

  16. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death.

    Science.gov (United States)

    Muchtar, Eli; Gertz, Morie A; Kumar, Shaji K; Lacy, Martha Q; Dingli, David; Buadi, Francis K; Grogan, Martha; Hayman, Suzanne R; Kapoor, Prashant; Leung, Nelson; Fonder, Amie; Hobbs, Miriam; Hwa, Yi Lisa; Gonsalves, Wilson; Warsame, Rahma; Kourelis, Taxiarchis V; Russell, Stephen; Lust, John A; Lin, Yi; Go, Ronald S; Zeldenrust, Steven; Kyle, Robert A; Rajkumar, S Vincent; Dispenzieri, Angela

    2017-04-13

    In light of major advances in immunoglobulin light chain (AL) amyloidosis, we evaluated the trends in presentation, management, and outcome among 1551 newly diagnosed AL amyloidosis patients seen in our institution from 2000 to 2014. As compared with the 2 intervals 2000-2004 and 2005-2009, patients diagnosed in 2010-2014 were less likely to have >2 involved organs. Utilization of autologous stem cell transplant (ASCT) was similar across all periods, about one-third of patients, but there was an increase in the use of pre-ASCT bortezomib induction and of unattenuated melphalan conditioning in 2010-2014 compared with earlier periods. Non-ASCT first-line regimen changed with 65% of patients in 2010-2014 received bortezomib-based therapy, 79% of patients in 2005-2009 received melphalan-dexamethasone, and 64% of patients in 2000-2004 received melphalan-prednisone. The rate of better than very good partial response (VGPR) was higher in more recent periods (66% vs 58% vs 51%; P = .001), a change largely driven by improved VGPR rates in the non-ASCT population. Overall survival (OS) has improved, with inflection points for improvement differing for the ASCT and non-ASCT groups. In the ASCT population, the greatest gains were after 2010 (4-year OS, 91% compared with 73% and 65%). In the non-ASCT group, greatest gains were after 2005 (4-year OS, 38%, 32%, and 16%). Fewer patients died within 6 months of diagnosis in the 2 later periods (24% vs 25% vs 37%; P < .001). Overall, outcomes among patients with AL amyloidosis have improved with earlier diagnosis, higher rates of VGPR, lower early mortality, and improved OS. © 2017 by The American Society of Hematology.

  17. Different aspects of thalidomide treatment and stem cell transplantation in multiple myeloma patients

    NARCIS (Netherlands)

    Marion, A.M.W. van

    2006-01-01

    Multiple myeloma (MM) is an haematological malignancy caused by an unrestrained proliferation of plasma cells (monoclonally differentiated B-cells), and part of the white blood cell count. This proliferation infiltrates the blood forming skeletal bone marrow, producing osteoclastic factors, causing

  18. Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide?

    DEFF Research Database (Denmark)

    Beksac, Meral; Waage, Anders; Bringhen, Sara

    2015-01-01

    BACKGROUND/AIM: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. PATIENTS: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups...

  19. Improvement in bronchodilation following deep inspiration after a course of high-dose oral prednisone in asthma

    NARCIS (Netherlands)

    Slats, Annelies M.; Sont, Jacob K.; van Klink, Rik H. C. J.; Bel, Elisabeth H. D.; Sterk, Peter J.

    2006-01-01

    BACKGROUND: Bronchodilation following deep inspiration is usually impaired in patients with asthma. This might be due to changes in airway mechanics in the presence of inflammation or structural changes within the airways. Although inhaled corticosteroid treatment has been shown to improve airway

  20. Diagnostic accuracy of short-time inversion recovery sequence in Graves' ophthalmopathy before and after prednisone treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tortora, Fabio; Belfiore, Maria Paola; Romano, Francesco; Cappabianca, Salvatore; Cirillo, Sossio [' ' F. Magrassi-A. Lanzara' ' Second University, Naples (Italy). Dept. of Clinical and Experimental Medicine and Surgery; Prudente, Mariaevelina [Second University, Naples (Italy). Medicine Dept.; Vita Salute San Raffaele Univ., Milan (Italy). Dept. of Neuroradiology; Cirillo, Mario [Second University, Naples (Italy). Neuroradiological Services; Elefante, Andrea [Federic II Univ., Naples (Italy). Neuroradilogical Dept.; Carella, Carlo [Polidiagnostic Center Check-Up, Salerno (Italy)

    2014-05-15

    In Graves' Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS < 3) from active Graves' Ophthalmopathy (GO) (CAS > 3) subjects and, second, to follow post-steroid treatment disease. An observational study was executed on 32 GO consecutive patients in different phases of disease, based on clinical and orbital Magnetic Resonance Imaging parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced neuroradiologist blinded to the clinical examinations. In pre-therapy patients, compared to controls, a medial rectus muscle statistically significant signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE) sequence was found, as well as when comparing patients before and after treatment, both medial and inferior rectus muscle SIR resulted significantly statistically different in STIR. These increased outcomes explain the inflammation oedematous phase of disease, moreover after steroid administration, compared to controls; patients presented lack of that statistically significant difference, thus suggesting treatment effectiveness. In our study, we proved STIR signal intensities increase in inflammation oedematous phase, confirming STIR sequence to define active phase of disease with more sensibility and reproducibility than CAS alone and to evaluate post-therapy involvement. (orig.)

  1. Diagnostic accuracy of short-time inversion recovery sequence in Graves' Ophthalmopathy before and after prednisone treatment.

    Science.gov (United States)

    Tortora, Fabio; Prudente, Mariaevelina; Cirillo, Mario; Elefante, Andrea; Belfiore, Maria Paola; Romano, Francesco; Cappabianca, Salvatore; Carella, Carlo; Cirillo, Sossio

    2014-05-01

    In Graves' Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS  3) subjects and, second, to follow post-steroid treatment disease. An observational study was executed on 32 GO consecutive patients in different phases of disease, based on clinical and orbital Magnetic Resonance Imaging parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced neuroradiologist blinded to the clinical examinations. In pre-therapy patients, compared to controls, a medial rectus muscle statistically significant signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE) sequence was found, as well as when comparing patients before and after treatment, both medial and inferior rectus muscle SIR resulted significantly statistically different in STIR. These increased outcomes explain the inflammation oedematous phase of disease, moreover after steroid administration, compared to controls; patients presented lack of that statistically significant difference, thus suggesting treatment effectiveness. In our study, we proved STIR signal intensities increase in inflammation oedematous phase, confirming STIR sequence to define active phase of disease with more sensibility and reproducibility than CAS alone and to evaluate post-therapy involvement.

  2. Diagnostic accuracy of short-time inversion recovery sequence in Graves' ophthalmopathy before and after prednisone treatment

    International Nuclear Information System (INIS)

    Tortora, Fabio; Belfiore, Maria Paola; Romano, Francesco; Cappabianca, Salvatore; Cirillo, Sossio

    2014-01-01

    In Graves' Ophthalmopathy, it is important to distinguish active inflammatory phase, responsive to immunosuppressive treatment, from fibrotic unresponsive inactive one. The purpose of this study is, first, to identify the relevant orbital magnetic resonance imaging signal intensities before treatment, so to classify patients according to their clinical activity score (CAS), discriminating inactive (CAS 3) subjects and, second, to follow post-steroid treatment disease. An observational study was executed on 32 GO consecutive patients in different phases of disease, based on clinical and orbital Magnetic Resonance Imaging parameters, compared to 32 healthy volunteers. Orbital Magnetic Resonance Imaging was performed on a 1.5 tesla Magnetic Resonance Unit by an experienced neuroradiologist blinded to the clinical examinations. In pre-therapy patients, compared to controls, a medial rectus muscle statistically significant signal intensity ratio (SIR) in short-time inversion recovery (STIR) (long TR/TE) sequence was found, as well as when comparing patients before and after treatment, both medial and inferior rectus muscle SIR resulted significantly statistically different in STIR. These increased outcomes explain the inflammation oedematous phase of disease, moreover after steroid administration, compared to controls; patients presented lack of that statistically significant difference, thus suggesting treatment effectiveness. In our study, we proved STIR signal intensities increase in inflammation oedematous phase, confirming STIR sequence to define active phase of disease with more sensibility and reproducibility than CAS alone and to evaluate post-therapy involvement. (orig.)

  3. Phase I/II Trial of Epothilone Analog BMS-247550, Mitoxantrone, and Prednisone in HRPC Patients Previously Treated with Chemotherapy

    Science.gov (United States)

    2006-07-01

    RENAL/GENITOURINARY Urinary retention (including neurogenic bladder ) Urinary retention (including neurogenic bladder ) VASCULAR Acute vascular...enrollment. 15. Patients with serious intercurrent infections , or nonmalignant medical illnesses that are uncontrolled or whose control may be...HEMORRHAGE/BLEEDING Hemorrhage, GI: rectum HEPATOBILIARY/PANCREAS Liver dysfunction/failure (clinical) INFECTION Febrile neutropenia (fever of

  4. Salvianolic acid B prevents bone loss in prednisone-treated rats through stimulation of osteogenesis and bone marrow angiogenesis.

    Directory of Open Access Journals (Sweden)

    Liao Cui

    Full Text Available Glucocorticoid (GC induced osteoporosis (GIO is caused by the long-term use of GC for treatment of autoimmune and inflammatory diseases. The GC related disruption of bone marrow microcirculation and increased adipogenesis contribute to GIO development. However, neither currently available anti-osteoporosis agent is completely addressed to microcirculation and bone marrow adipogenesis. Salvianolic acid B (Sal B is a polyphenolic compound from a Chinese herbal medicine, Salvia miltiorrhiza Bunge. The aim of this study was to determine the effects of Sal B on osteoblast bone formation, angiogenesis and adipogenesis-associated GIO by performing marrow adipogenesis and microcirculation dilation and bone histomorphometry analyses. (1 In vivo study: Bone loss in GC treated rats was confirmed by significantly decreased BMD, bone strength, cancellous bone mass and architecture, osteoblast distribution, bone formation, marrow microvessel density and diameter along with down-regulation of marrow BMPs expression and increased adipogenesis. Daily treatment with Sal B (40 mg/kg/d for 12 weeks in GC male rats prevented GC-induced cancellous bone loss and increased adipogenesis while increasing cancellous bone formation rate with improved local microcirculation by capillary dilation. Treatment with Sal B at a higher dose (80 mg/kg/d not only prevented GC-induced osteopenia, but also increased cancellous bone mass and thickness, associated with increase of marrow BMPs expression, inhibited adipogenesis and further increased microvessel diameters. (2 In vitro study: In concentration from 10(-6 mol/L to 10(-7 mol/L, Sal B stimulated bone marrow stromal cell (MSC differentiation to osteoblast and increased osteoblast activities, decreased GC associated adipogenic differentiation by down-regulation of PPARγ mRNA expression, increased Runx2 mRNA expression without osteoblast inducement, and, furthermore, Sal B decreased Dickkopf-1 and increased β-catenin mRNA expression with or without adipocyte inducement in MSC. We conclude that Sal B prevented bone loss in GC-treated rats through stimulation of osteogenesis, bone marrow angiogenesis and inhibition of adipogenesis.

  5. Hematological approaches to multiple myeloma: trends from a Brazilian subset of hematologists. A cross-sectional study

    Directory of Open Access Journals (Sweden)

    Lucila Nassif Kerbauy

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: For the last nine years, hematologists and oncologists have gathered annually at an educational symposium organized by a Brazilian and an American hospital. During the 2015 Board Review, a survey among the attendees evaluated the differences in management and treatment methods for multiple myeloma (MM. DESIGN AND SETTING: Cross-sectional study during an educational hematology symposium in São Paulo, Brazil. METHODS: Hematologists present at the symposium gave responses to an electronic survey by means of mobile phone. RESULTS: Among the 350 attendees, 217 answered the questionnaire. Most of the participants believed that immunotargeting agents (iTA might be effective for slowing MM progression in heavily pretreated patients (67% and that continued exposure to therapy might lead to emergence of resistant clones in patients with MM (76%. Most of the physicians use maintenance therapy after hematopoietic stem cell transplantation (95% and 45% of them would further restrict it to post-transplantation patients with underlying high-risk disease. The first-line drugs used for transplantation-ineligible patients (TI-MM were bortezomib-thalidomide-dexamethasone (31%, bortezomib-dexamethasone (28%, lenalidomide-dexamethasone (Rd; 17% and melphalan-based therapy (10%. Lenalidomide was the drug of choice for post-transplantation maintenance for half of the participants. No significant differences were observed regarding age or length of experience. CONCLUSION: The treatment choices for TI-MM patients were highly heterogenous and the melphalan-based regimen represented only 10% of the first-line options. Use of maintenance therapy after transplantation was a common choice. Some results from the survey were divergent from the evidence in the literature.

  6. Plasmablastic Lymphoma: A Review of Current Knowledge and Future Directions

    Directory of Open Access Journals (Sweden)

    Ghaleb Elyamany

    2015-01-01

    Full Text Available Plasmablastic lymphoma (PBL is an aggressive subtype of non-Hodgkin’s lymphoma (NHL, which frequently arises in the oral cavity of human immunodeficiency virus (HIV infected patients. PBL shows diffuse proliferation of large neoplastic cells resembling B-immunoblasts/plasmablasts, or with plasmacytic features and an immunophenotype of plasma cells. PBL remains a diagnostic challenge due to its peculiar morphology and an immunohistochemical profile similar to plasma cell myeloma (PCM. PBL is also a therapeutic challenge with a clinical course characterized by a high rate of relapse and death. There is no standard chemotherapy protocol for treatment of PBL. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP or CHOP-like regimens have been the backbone while more intensive regimens such as cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine (CODOX-M/IVAC, or dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH are possible options. Recently, a few studies have reported the potential value of the proteasome inhibitor bortezomib and thalidomide in PBL patients. The introduction of genes encoding artificial receptors called chimeric antigen receptors (CARs and CAR-modified T cells targeted to the B cell-specific CD19 antigen have demonstrated promising results in multiple early clinical trials. The aim of this paper is to review the recent advances in epidemiology; pathophysiology; clinical, pathologic, and molecular characteristics; therapy; and outcome in patients with PBL.

  7. New Rising Infection: Human Herpesvirus 6 Is Frequent in Myeloma Patients Undergoing Autologous Stem Cell Transplantation after Induction Therapy with Bortezomib

    Directory of Open Access Journals (Sweden)

    Netanel Horowitz

    2012-01-01

    Full Text Available Herpesvirus 6 (HHV-6 infection is a common complication during immunosuppression. Its significance for multiple myeloma (MM patients undergoing autologous stem cell transplantation (ASCT after treatment with novel agents affecting immune system remains undetermined. Data on 62 consecutive MM patients receiving bortezomib-dexamethasone (VD (; 66% or thalidomide-dexamethasone (TD (, 34% induction, together with melphalan 200 mg/m2 autograft between 01.2005 and 09.2010, were reviewed. HHV-6 reactivation was diagnosed in patients experiencing postengraftment unexplained fever (PEUF in the presence of any level of HHHV-6 DNA in blood. There were no statistically significant differences in patient characteristics between the groups, excluding dexamethasone dosage, which was significantly higher in patients receiving TD. Eight patients in TD and 18 in VD cohorts underwent viral screening for PEUF. HHV-6 reactivation was diagnosed in 10 patients of the entire series (16%, accounting for 35% of those screened; its incidence was 19.5% ( in the VD group versus 9.5% ( in the TD group. All patients recovered without sequelae. In conclusion, HHV-6 reactivation is relatively common after ASCT, accounting for at least a third of PEUF episodes. Further studies are warranted to investigate whether bortezomib has an impact on HHV-6 reactivation development.

  8. Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

    Directory of Open Access Journals (Sweden)

    Catriona Elizabeth Mactier

    2012-10-01

    Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

  9. Treatment of multiple myeloma in Celje general hospital in the five-year period from 2007–2011

    Directory of Open Access Journals (Sweden)

    Mateja Grat

    2012-12-01

    Full Text Available We found 55 newly diagnosed patients with multiple myeloma in the five-year observation period. There were 8 to 13 new patients per year; patient’s average age was 67.8.years. 20/55 (36.4 % of patients were under 65 years old and 19/55 (34.6 % were 75 years or older. We assessed the international prognostic score (ISS in most patients (50/55; 90.9 % and cytogenetic analysis of bone marrow before initial treatment. These findings influenced our choice of regimens for initial therapy based on bortezomib and thalidomide. Treatment regimens based on melphalan and farmorubicin were used less frequently. In 19/55 (34.6 % of patients the treatment regimen included avtologous stem-cell transplantation (ASCT. Patients treated with ASCT have longer time to progression (median 12.4 months versus 8.7 months and better survival (44.3 months versus 33.3 months. New active agents have changed responses to treatment (partial response in 46/55 and very good partial response in 19/55 patients. In five-year period 18 patients died, most of them due to progression of the disease. Despite the era of new active agents, multiple myeloma is still incurable disease.

  10. Fludarabine Phosphate, Melphalan, Total-Body Irradiation, Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Bone Marrow Failure Disorders

    Science.gov (United States)

    2017-11-29

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Fanconi Anemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Paroxysmal Nocturnal Hemoglobinuria; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Waldenström Macroglobulinemia

  11. Intermediate-dose melphalan compared with myeloablative treatment in multiple myeloma : long-term follow-up of the Dutch cooperative group HOVON 24 trial

    NARCIS (Netherlands)

    Sonneveld, Pieter; van der Holt, Bronno; Segeren, Christine M.; Vellenga, Edo; Croockewit, Alexandra J.; Verhoef, Gregor E. G.; Cornelissen, Jan J.; Schaafsma, Martijn R.; van Oers, Marinus H. J.; Wijermans, Pierre W.; Westveer, Petra H. M.; Lokhorst, Henk M.

    Background and Objectives The Dutch-Belgian HOVON group performed a randomized phase 3 trial to compare single non-myeloablative intensive treatment with double, intensive treatment in previously untreated patients with multiple myeloma (MM). Design and Methods Three hundred and three patients with

  12. Inhibition of homologous recombination repair with Pentoxifylline targets G2 cells generated by radiotherapy and induces major enhancements of the toxicity of cisplatin and melphalan given after irradiation

    International Nuclear Information System (INIS)

    Bohm, Lothar

    2006-01-01

    The presentation reviews the modus operandi of the dose modifying drug Pentoxifylline and the dose enhancement factors which can be achieved in different cell types. Preclinical and clinical data show that Pentoxifylline improves the oxygenation of hypoxic tumours and enhances tumour control by irradiation. In vitro experiments demonstrate that Pentoxifylline also operates when oxygen is not limiting and produces dose modifying factors in the region of 1.2 – 2.0. This oxygen independent effect is poorly understood. In p53 mutant cells irradiation induces a G2 block which is abrogated by Pentoxifylline. The enhancement of cell kill observed when Pentoxifylline and irradiation are given together could arise from rapid entry of damaged tumour cells into mitosis and propagation of DNA lesions as the result of curtailment of repair time. Recovery ratios and repair experiments using CFGE after high dose irradiation demonstrate that Pentoxifylline inhibits repair directly and that curtailment of repair time is not the explanation. Use of the repair defective xrs1 and the parental repair competent CHO-K1 cell line shows that Pentoxifylline inhibits homologous recombination repair which operates predominantly in the G2 phase of the cell cycle. When irradiated cells residing in G2 phase are exposed to very low doses of cisplatin at a toxic dose of 5 %. (TC: 0.05) massive toxicity enhancements up to a factor of 80 are observed in melanoma, squamous carcinoma and prostate tumour cell lines. Enhancements of radiotoxicity seen when Pentoxifylline and radiation are applied together are small and do not exceed a factor of 2.0. The capacity of Pentoxifyline to inhibit homologous recombination repair has not as yet been clinically utilized. A suitable application could be in the treatment of cervical carcinoma where irradiation and cisplatin are standard modality. In vitro data also strongly suggest that regimes where irradiation is used in combination with alkylating drugs may also benefit

  13. Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial

    DEFF Research Database (Denmark)

    Marchetti, Monia; Barosi, Giovanni; Balestri, Francesca

    2004-01-01

    and transfusions were eliminated in 39% of transfusion-dependent patients. Platelet count increased by 50 x 10(9)/L or more in 22% of patients with an initial count lower than 100 x 10(9)/L. Splenomegaly decreased by more than 50% of the initial size in 19% of patients. Reduction of an overall disease severity...

  14. Second and third responses to the same induction regimen in relapsing patients with multiple myeloma.

    Science.gov (United States)

    Paccagnella, A; Chiarion-Sileni, V; Soesan, M; Baggio, G; Bolzonella, S; De Besi, P; Casara, D; Frizzarin, M; Salvagno, L; Favaretto, A

    1991-09-01

    From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

  15. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations.

    Science.gov (United States)

    Bladé, Joan; Dimopoulos, Meletios; Rosiñol, Laura; Rajkumar, S Vincent; Kyle, Robert A

    2010-02-01

    To provide an overview on smoldering (asymptomatic) multiple myeloma (SMM) including current diagnostic criteria, predictors of progression, pattern of progression, and outcome. A comprehensive review of the literature on risk factors for progression, treatment attempts to delay progression and outcome in patients with SMM. The risk factors for progression of SMM include: plasma cell mass including M-protein size and percentage of bone marrow clonal plasma cells (BMPC), abnormal free light chain ratio, proportion of phenotypically abnormal BMPC, immunoparesis, evolution pattern (evolving v nonevolving), and pattern of magnetic resonance imaging abnormalities. Most patients with SMM progress with anemia and/or skeletal involvement. Immediate therapy with cytotoxic agents, such as melphalan/prednisone has not resulted in improved outcome. Patients should not be treated until progressive disease with end-organ damage occurs. Increasing anemia is the most reliable indicator of progression. These recently recognized predictors of outcome may be helpful for better disease monitoring and for investigation of new treatment approaches. Thus, recommendations for follow-up every to 3 to 6 months depending on the risk of progression are suggested, and clinical trials with new noncytotoxic biologically derived agents to delay progression, particularly in high-risk patients, are ongoing.

  16. Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

    Directory of Open Access Journals (Sweden)

    Yijuan Sun

    2012-01-01

    Full Text Available AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

  17. Immunomodulatory treatment with intravenous immunoglobulin and prednisone in patients with recurrent miscarriage and implantation failure after in vitro fertilization/intracytoplasmic sperm injection

    DEFF Research Database (Denmark)

    Nyborg, Kathinka Marie; Kolte, Astrid Marie; Larsen, Elisabeth Clare

    2014-01-01

    . SETTING: Tertiary care university hospital. PATIENT(S): Fifty-two patients with a history of at least three consecutive pregnancy losses after ART who underwent at least one further ART cycle with concurrent immunomodulation in 2003-2012. INTERVENTION(S): Immunomodulation with IV immunoglobulin......OBJECTIVE: To assess outcome in terms of live-birth rate after fresh or frozen IVF/intracytoplasmic sperm injection assisted reproductive technology (ART) cycles where immunomodulation was given to patients with recurrent pregnancy loss after prior ART treatments. DESIGN: Retrospective cohort study...

  18. Prognostic impact of sarcopenia in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.

    Science.gov (United States)

    Go, Se-Il; Park, Mi Jung; Song, Haa-Na; Kim, Hoon-Gu; Kang, Myoung Hee; Lee, Hyang Rae; Kim, Yire; Kim, Rock Bum; Lee, Soon Il; Lee, Gyeong-Won

    2016-12-01

    Sarcopenia is known to be related to an increased risk of chemotherapy toxicity and to a poor prognosis in patients with malignancy. We assessed the prognostic role of sarcopenia in patients with diffuse large B-cell lymphoma (DLBCL). In total, 187 consecutive patients with DLBCL treated with induction rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy were reviewed. Sarcopenia was defined as the lowest sex-specific quartile of the skeletal muscle index, calculated by dividing the pectoralis muscle area by the height. Clinical outcomes were compared between the sarcopenic and non-sarcopenic groups. A nomogram was constructed from the Cox regression model for overall survival (OS). Treatment-related mortality (21.7 vs. 5.0%, P  = 0.002) and early discontinuation of treatment (32.6 vs. 14.9%, P  = 0.008) were more common in the sarcopenic group than in the non-sarcopenic group. The 5 year progression-free survival (PFS) rates were 35.3% in the sarcopenic group and 65.8% in the non-sarcopenic group ( P  Sarcopenia and the five variables of the International Prognostic Index (IPI) were independent prognostic factors in a multivariate analysis for PFS and OS and were used to construct the nomogram. The calibration plot showed good agreement between the nomogram predictions and actual observations. The c index of the nomogram (0.80) was higher than those of other prognostic indices (IPI, 0.77, P  = 0.009; revised-IPI, 0.74, P  Sarcopenia is associated with intolerance to standard R-CHOP chemotherapy as well as a poor prognosis. Moreover, sarcopenia itself can be included in prognostic models in DLBCL.

  19. Lenalidomide for refractory cutaneous manifestations of pediatric systemic lupus erythematosus.

    Science.gov (United States)

    Wu, E Y; Schanberg, L E; Wershba, E C; Rabinovich, C E

    2017-05-01

    Objective Cutaneous manifestations of pediatric systemic lupus erythematosus cause significant morbidity. Lenalidomide, a thalidomide analogue, has shown promise treating cutaneous lupus erythematosus in adults. Our objective was to evaluate lenalidomide's efficacy and safety in treating refractory cutaneous manifestations of pediatric systemic lupus erythematosus. Methods We performed a retrospective chart review of 10 adolescents who received lenalidomide for recalcitrant cutaneous lupus erythematosus. Information was gathered at drug initiation and 6-month follow-up. The Wilcoxon matched-pairs signed-rank test was used to assess change in quantitative parameters of disease activity. Results Nine subjects were girls and six were African-American. Indications for lenalidomide treatment included alopecia, nasal and oral ulcers, extensive malar rash, discoid lesions, bullous lesions, panniculitis, cutaneous vasculitis, and Raynaud's phenomenon with digital ulcerations. Within 6 months, all patients demonstrated complete or near resolution based on physician report. Prednisone dose decreased from a mean 23.5 mg (SD± 13.3) to 12.25 mg (SD± 9.2) ( P= 0.008). Sedimentation rate decreased from a mean 29 mm/hour (SD± 31.5) to 17 mm/hour (SD± 18.1) ( P= 0.004). Lenalidomide was well tolerated. Conclusion Lenalidomide is an effective and safe treatment for a spectrum of dermatological conditions in pediatric systemic lupus erythematosus. Its use may allow a reduction in prednisone dose and decreased disfigurement. Prospective study is needed to clarify lenalidomide's role in treating cutaneous manifestations of systemic lupus erythematosus.

  20. New approaches to smoldering myeloma.

    Science.gov (United States)

    Mateos, María-Victoria; San Miguel, Jesús F

    2013-12-01

    Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder characterized by the presence of one or both features of serum M-protein ≥ 30 g/L and bone marrow plasma cell infiltration ≥ 10 %. However, myeloma-related symptomatology is absent from this condition. The risk of progression to active MM is not uniform, and several markers are useful for identifying SMM patients at high risk of progression to active MM. These include the size of the M-protein and the infiltration in the bone marrow, the serum-free light-chain ratio, the presence of immunoparesis and percentage of plasma cell with aberrant phenotype by flow cytometry, or the presence of focal lesions in magnetic resonance imaging. Overall, the presence of these factors identifies patients who have a 50 % probability of progression at 2 years, and the forthcoming challenge will be to identify ultra-high-risk patients who have an 80 % risk of progression at 2 years. The current standard of care is not to treat until progression to symptomatic disease occurs. Several trials of melphalan, thalidomide and bisphosphonates have been conducted in the overall SMM patient population to examine the delay in time to progression (TTP) to symptomatic disease, but these have shown no significant benefit. However, a randomized trial that focused on high-risk SMM patients allocated to receive early treatment with lenalidomide plus dexamethasone versus observation did report a significant benefit with respect to TTP and overall survival. In summary, high-risk SMM patients should be targetted for early treatment, and more so efforts should be made to identify the ultra-high-risk subgroup within the high-risk SMM patient population which may be considered as early MM and thereby candidates for receiving therapy before they develop myeloma-related symptomatology.

  1. Review of pharmacological interactions of oral anticancer drugs provided at pharmacy department

    Directory of Open Access Journals (Sweden)

    E. Sánchez Gómez

    2014-07-01

    Full Text Available Abstract: Objective: To identify the pharmacologic interactions of oral anti-cancer drugs provided at an outpatient clinic. Material and methods: Anti-cancer drugs included in the Phamacotherapeutic Guideline of the Hospital were identified. A literature search was carried out on the pharmacologic interactions in MEDLINE® and EMBASE® (with the filer language English or Spanish, and the descriptors: “name of the anti-cancer drug” AND (“drug interactions” OR “pharmacokinetic”, Up-to-date®, MICROMEDEX® and the drug information sheet for the EMA and the FDA. Information was also gathered from the abstract presented to European and Spanish scientific meetings for the last 4 years. When an interaction was analyzed and had clinical relevance, the best pharmacotherapeutic interaction-free alternative was sought. Results: Twenty-three drugs were identified, of which Chlorambucil, Fludarabine, Lenalidomide, Melphalan, and Thalidomide were the active compounds with the lowest likelihood of producing a pharmacologic interaction. Tyrosine kinase inhibitors (particularly Erlotinib, Imatinib, Lapatinib, and Pazopanib are the drugs with highest number of pharmacologic interactions described, many of them with severe clinical consequences, with increases and decreases of the plasma levels of anti-cancer drugs. The active compounds identified that may have pharmacologic interactions with anticancer drugs were mainly: Allopurinol, Amiodarone, Carbamazepine, Dabigatran, Digoxin, Spironolactone, Phenytoin, Itraconazol, Repaglinide, Silodosin, Tamoxifen, Verapamil, and Warfarin. Pharmacologic interactions through the cytochrome P450 1A2, 2D6, 2C8, 2C9, 3A4 were the most important for tyrosine kinase inhibitors. Other non-pharmacologic compounds, with an important potential of producing relevant pharmacologic interaction were immunomodulators (Echinacea extracts and Hypericum perforatum. Conclusions: Oral anticancer drugs have numerous pharmacologic

  2. Effects of hypoxia on human cancer cell line chemosensitivity

    Science.gov (United States)

    2013-01-01

    Background Environment inside even a small tumor is characterized by total (anoxia) or partial oxygen deprivation, (hypoxia). It has been shown that radiotherapy and some conventional chemotherapies may be less effective in hypoxia, and therefore it is important to investigate how different drugs act in different microenvironments. In this study we perform a large screening of the effects of 19 clinically used or experimental chemotherapeutic drugs on five different cell lines in conditions of normoxia, hypoxia and anoxia. Methods A panel of 19 commercially available drugs: 5-fluorouracil, acriflavine, bortezomib, cisplatin, digitoxin, digoxin, docetaxel, doxorubicin, etoposide, gemcitabine, irinotecan, melphalan, mitomycin c, rapamycin, sorafenib, thalidomide, tirapazamine, topotecan and vincristine were tested for cytotoxic activity on the cancer cell lines A2780 (ovarian), ACHN (renal), MCF-7 (breast), H69 (SCLC) and U-937 (lymphoma). Parallel aliquots of the cells were grown at different oxygen pressures and after 72 hours of drug exposure viability was measured with the fluorometric microculture cytotoxicity assay (FMCA). Results Sorafenib, irinotecan and docetaxel were in general more effective in an oxygenated environment, while cisplatin, mitomycin c and tirapazamine were more effective in a low oxygen environment. Surprisingly, hypoxia in H69 and MCF-7 cells mostly rendered higher drug sensitivity. In contrast ACHN appeared more sensitive to hypoxia, giving slower proliferating cells, and consequently, was more resistant to most drugs. Conclusions A panel of standard cytotoxic agents was tested against five different human cancer cell lines cultivated at normoxic, hypoxic and anoxic conditions. Results show that impaired chemosensitivity is not universal, in contrast different cell lines behave different and some drugs appear even less effective in normoxia than hypoxia. PMID:23829203

  3. Management of mantle cell lymphoma in the elderly: current and potential strategies.

    Science.gov (United States)

    Vignon, Marguerite; Venon, Marie-Dominique; Hermine, Olivier; Delarue, Richard

    2013-12-01

    Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.

  4. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy.

    NARCIS (Netherlands)

    Sonneveld, P.; Hajek, R.; Nagler, A.; Spencer, A.; Blade, J.; Robak, T.; Zhuang, S.H.; Harousseau, J.L.; Orlowski, R.Z.

    2008-01-01

    BACKGROUND: Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In the current

  5. Combined pegylated liposomal doxorubicin and bortezomib is highly effective in patients with recurrent or refractory multiple myeloma who received prior thalidomide/lenalidomide therapy

    NARCIS (Netherlands)

    P. Sonneveld (Pieter); R. Hajek (Roman); A. Nagler (Arnon); A. Spencer (Andrew); J. Bladé (Joan); T. Robak (Tadeusz); S.H. Zhuang (Sen); J-L. Harousseau (Jean-Luc); R.Z. Orlowski (Robert)

    2008-01-01

    textabstractBACKGROUND. Recently, the authors reported improved time to disease progression (TTP) with a combination of pegylated liposomal doxorubicin (PLD) and bortezomib compared with bortezomib alone in a phase 3 randomized trial in patients with recurrent/refractory multiple myeloma (MM). In

  6. TREATMENT OF PRIMARY PLASMA CELL LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    Peter Černelč

    2003-04-01

    Full Text Available Background. The author describes long-term survival in 3 patients with primary plasma cell leukaemia (PL after different therapeutic regimen and maintenance treatment with interferon alpha (INF.Patients and treatment. In a 52-year-old male patient, a partial remission of PL was achieved after 6 months of treatment with melphalan and prednisone. The patient did not consent to stem cell transplantation (SCT. An 86-year-old female patient with PL achieved a complete remission after 6 months of treatment with vincristine, doxorubicin and dexamethasone. A 31-year-old male patient experienced a complete remission of PL after 6 months of treatment with cyclophosphamide, vincristine, doxorubicin, methilprednisone, followed by autologous SCT. All three patients were placed on maintenance therapy with INF-2b (Intron A 3 × 106 IU given subcutaneously on two days per week. In the 52-year-old man, the remission lasted 9 months and in the woman 23 months, whereupon they developed a relapse with signs of disseminated plasmacytoma. In both patients the former chemotherapy was applied again, resulting in a slight improvement. The man died 37 months and the woman 43 months after the diagnosis of PL, while the youngest patient has been in complete remission for 82 months.Conclusions. Long remission achieved in our patients confirmed the favourable effect of INF in terms of prolongation of the remission duration in this patients. The effect of maintenance treatment with INF is usually directly dependent on the degree of remission induced by different therapeutic regimen.

  7. Macroglossia como primeira manifestação clínica da amiloidose primária Macroglossia as initial clinical manifestation of primary amyloidosis

    Directory of Open Access Journals (Sweden)

    Carla de Oliveira Alambert

    2007-02-01

    Full Text Available A amiloidose é uma doença rara causada pelo depósito patológico de substância amilóide no meio extracelular. Relatamos o caso de um paciente de 50 anos de idade, masculino, com história de edema de lábios e língua associado à equimose periorbitária bilateral há 6 meses. Ao exame físico, observamos importante macroglossia. Foram realizados exames complementares, e o diagnóstico foi confirmado pela análise histopatológica da biópsia de língua. O paciente recebeu tratamento com prednisona e melfalan com resposta insatisfatória. Evoluiu com insuficiência cardíaca congestiva e infecções urinárias e respiratórias de repetição. Após 7 meses do diagnóstico, o paciente foi internado com infecção pulmonar complicada com sepse e evoluiu a óbito.Amyloidosis is a rare disease caused by pathological deposit of an amyloid extracellular proteinaceus material. We report a case of a 50-year-old man with history of lips and tongue swelling associated to periorbital ecchimosys for 6 months. At the physical examination an important macroglossia was observed. Complementary tests were accomplished, and the pathological examination of the tongue biopsy confirmed the diagnosis. The patient was treated with prednisone and melphalan with an unsatisfactory response. Along the follow up the patient developed heart failure, and died 7 months after diagnosis of pulmonary infection and sepsis.

  8. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial.

    NARCIS (Netherlands)

    Sternberg, C.N.; Petrylak, D.P.; Sartor, O.; Witjes, J.A.; Demkow, T.; Ferrero, J.M.; Eymard, J.C.; Falcon, S.; Calabro, F.; James, N.; Bodrogi, I.; Harper, P.; Wirth, M.; Berry, W.; Petrone, M.E.; McKearn, T.J.; Noursalehi, M.; George, M.; Rozencweig, M.

    2009-01-01

    PURPOSE: This multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy

  9. International Myeloma Working Group Recommendations for the Diagnosis and Management of Myeloma-Related Renal Impairment.

    Science.gov (United States)

    Dimopoulos, Meletios A; Sonneveld, Pieter; Leung, Nelson; Merlini, Giampaolo; Ludwig, Heinz; Kastritis, Efstathios; Goldschmidt, Hartmut; Joshua, Douglas; Orlowski, Robert Z; Powles, Raymond; Vesole, David H; Garderet, Laurent; Einsele, Hermann; Palumbo, Antonio; Cavo, Michele; Richardson, Paul G; Moreau, Philippe; San Miguel, Jesús; Rajkumar, S Vincent; Durie, Brian G M; Terpos, Evangelos

    2016-05-01

    The aim of the International Myeloma Working Group was to develop practical recommendations for the diagnosis and management of multiple myeloma-related renal impairment (RI). Recommendations were based on published data through December 2015, and were developed using the system developed by the Grading of Recommendation, Assessment, Development, and Evaluation Working Group. All patients with myeloma at diagnosis and at disease assessment should have serum creatinine, estimated glomerular filtration rate, and electrolytes measurements as well as free light chain, if available, and urine electrophoresis of a sample from a 24-hour urine collection (grade A). The Chronic Kidney Disease Epidemiology Collaboration, preferably, or the Modification of Diet in Renal Disease formula should be used for the evaluation of estimated glomerular filtration rate in patients with stabilized serum creatinine (grade A). International Myeloma Working Group criteria for renal reversibility should be used (grade B). For the management of RI in patients with multiple myeloma, high fluid intake is indicated along with antimyeloma therapy (grade B). The use of high-cutoff hemodialysis membranes in combination with antimyeloma therapy can be considered (grade B). Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B). Thalidomide is effective in patients with myeloma with RI, and no dose modifications are needed (grade B). Lenalidomide is effective and safe, mainly in patients with mild to moderate RI (grade B); for patients with severe RI or on dialysis, lenalidomide should be given with close monitoring for hematologic toxicity (grade B) with dose reduction as needed. High-dose therapy with autologous stem cell transplantation (with melphalan 100 mg/m(2) to 140 mg/m(2)) is feasible in patients with RI (grade C). Carfilzomib can be safely

  10. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND M...

  11. [Synthesis of 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives].

    Science.gov (United States)

    Yang, Yue; Xiang, Dong; Guo, Ju; Zheng, Yong-sheng; Ye, Bin; Yang, Jin-liang; Cheng, Li

    2008-07-01

    To synthesize a series of derivatives of Thalidomide. The N-Phthaloyl-L-glutamic anhydride was ammonolyzed with amino acid benzyl esters, followed by hydrogenization. The reaction between the hydogenized products and ammonia gas produced ammonium salt, 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives. Four new derivatives of Thalidomide were obtained and confirmed by spectral detection. The derivatives of Thalidomide can be efficiently synthesized under mild conditions.

  12. 77 FR 74669 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

    Science.gov (United States)

    2012-12-17

    ... Phenoxybenzamine hydrochloride Q Quinine sulfate R Risedronate sodium T Tacrolimus Thalidomide Tinidazole For a... Gabapentin P Piroxicam S Sodium Phosphate, dibasic, anhydrous; sodium phosphate, monobasic, monohydrate [[Page 74670

  13. RELATIONSHIPS BETWEEN ABLATION OF DISTINCT HEMATOPOIETIC-CELL SUBSETS AND THE DEVELOPMENT OF DONOR BONE-MARROW ENGRAFTMENT FOLLOWING RECIPIENT PRETREATMENT WITH DIFFERENT ALKYLATING DRUGS

    NARCIS (Netherlands)

    DOWN, JD; BOUDEWIJN, A; DILLINGH, JH; FOX, BW; PLOEMACHER, RE

    1994-01-01

    A number of different alkylating chemotherapeutic agents - busulphan, dimethylbusulphan (DMB), isopropylmethane sulphonate (IMS), melphalan, cyclophosphamide (CY) and bischloroethylnitrosourea (BCNU)- were investigated for their cytotoxic effects on different haemopoietic cell populations in host

  14. The Development and Application of Cellular Sensitivity Biomarkers for the Detection and Measurement of Toxic Effects in Normal and Malignant Cells From Patients Receiving High-Dose Meiphalan (L-PAM) With Autologous Peripheral Blood Progenitor Cell Rescue in the Treatment of Metastatic Breast Cancer.

    Science.gov (United States)

    1995-09-01

    Toxic Effects in Normal and Malignant Cells From Patients Receiving High-Dose Melphalan (L-PAM) With Autologous Peripheral Blood Peripheral Blood...Progenitor Cell Rescue in the Treatment of Metastatic Breast Cancer PRINCIPAL INVESTIGATOR: Atif M. Hussein, M.D. CONTRACTING ORGANIZATION: Duke University...for the Detection and Measurement of Toxic Effects in Normal and Malignant DAMD17-94-J-4285 Cells From Patients Receiving High-Dose Melphalan... 6

  15. Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.

    Science.gov (United States)

    Chiappella, Annalisa; Martelli, Maurizio; Angelucci, Emanuele; Brusamolino, Ercole; Evangelista, Andrea; Carella, Angelo Michele; Stelitano, Caterina; Rossi, Giuseppe; Balzarotti, Monica; Merli, Francesco; Gaidano, Gianluca; Pavone, Vincenzo; Rigacci, Luigi; Zaja, Francesco; D'Arco, Alfonso; Cascavilla, Nicola; Russo, Eleonora; Castellino, Alessia; Gotti, Manuel; Congiu, Angela Giovanna; Cabras, Maria Giuseppina; Tucci, Alessandra; Agostinelli, Claudio; Ciccone, Giovannino; Pileri, Stefano A; Vitolo, Umberto

    2017-08-01

    The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3). At enrolment, patients were stratified according to aa-IPI score and randomly assigned (1:1:1:1) to receive R-CHOP (intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 on day 1, plus oral prednisone 100 mg on days 1-5) delivered in a 14-day cycle (R-CHOP-14) for eight cycles; high-dose R-CHOP-14 (R-MegaCHOP-14; R-CHOP-14 except for cyclophosphamide 1200 mg/m 2 and doxorubicin 70 mg/m 2 ) for six cycles; R-CHOP-14 for four cycles followed by R-MAD (intravenous rituximab 375 mg/m 2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m 2 and dexamethasone 4 mg/m 2 every 12 h on days 1-3 plus intravenous mitoxantrone 8 mg/m 2 on days 1-3) plus BEAM (intravenous carmustine 300 mg/m 2 on day -7, intravenous cytarabine 200 mg/m 2 twice a day on days -6 to -3, intravenous etoposide 100 mg/m 2 twice a day on days -6

  16. The Prevalence and Management of Systemic Amyloidosis in Western Countries.

    Science.gov (United States)

    Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

    2016-04-01

    , evidence of systemic deposition, reliable typing, precursor assessment, severity of organ disease, risk assessment and prognosis, choice of treatment, and planned monitoring during follow-up. (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by autologous stem cell transplantation (ASCT) is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent studies in China and the US indicate that bortezomib induction prior to ASCT increases the response rate. Thalidomide and lenalidomide have shown benefit, but toxicity and lack of clinical evidence exclude these agents from first-line therapy. The green tea extract epigallocatechin-3-gallate is under investigation as an inhibitor of AL amyloid formation and a compound that might dissolve amyloid.

  17. In vitro and in vivo activity of melflufen (J1)in lymphoma

    International Nuclear Information System (INIS)

    Delforoush, Maryam; Strese, Sara; Wickström, Malin; Larsson, Rolf; Enblad, Gunilla; Gullbo, Joachim

    2016-01-01

    Melphalan has been used in the treatment of various hematologic malignancies for almost 60 years. Today it is part of standard therapy for multiple myeloma and also as part of myeloablative regimens in association with autologous allogenic stem cell transplantation. Melflufen (melphalan flufenamide ethyl ester, previously called J1) is an optimized derivative of melphalan providing targeted delivery of active metabolites to cells expressing aminopeptidases. The activity of melflufen has compared favorably with that of melphalan in a series of in vitro and in vivo experiments performed preferentially on different solid tumor models and multiple myeloma. Melflufen is currently being evaluated in a clinical phase I/II trial in relapsed or relapsed and refractory multiple myeloma. Cytotoxicity of melflufen was assayed in lymphoma cell lines and in primary tumor cells with the Fluorometric Microculture Cytotoxicity Assay and cell cycle analyses was performed in two of the cell lines. Melflufen was also investigated in a xenograft model with subcutaneous lymphoma cells inoculated in mice. Melflufen showed activity with cytotoxic IC 50 -values in the submicromolar range (0.011-0.92 μM) in the cell lines, corresponding to a mean of 49-fold superiority (p < 0.001) in potency vs. melphalan. In the primary cultures melflufen yielded slightly lower IC 50 -values (2.7 nM to 0.55 μM) and an increased ratio vs. melphalan (range 13–455, average 108, p < 0.001). Treated cell lines exhibited a clear accumulation in the G2/M-phase of the cell cycle. Melflufen also showed significant activity and no, or minimal side effects in the xenografted animals. This study confirms previous reports of a targeting related potency superiority of melflufen compared to that of melphalan. Melflufen was active in cell lines and primary cultures of lymphoma cells, as well as in a xenograft model in mice and appears to be a candidate for further evaluation in the treatment of this group of malignant

  18. Pulse therapy in pemphigus: report of 11 cases

    OpenAIRE

    Fernandes, Nurimar Conceicao; Menezes, Mariana

    2013-01-01

    In this study, five cases of pemphigus vulgaris and two cases of pemphigus foliaceus were treated with cyclophosphamide pulse therapy associated with prednisone, resulting in the need for a smaller maintenance dose of prednisone. In three cases of pemphigus vulgaris and one case of pemphigus foliaceus, dexamethasone and cyclophosphamide pulse therapy associated with prednisone helped the lesions to heal more rapidly. Neither treatment however prevented the recurrence of the disease. Amenorrhe...

  19. ENVIRONMENTAL EDUCATION: A SINE-QUA-NON FOR ...

    African Journals Online (AJOL)

    JONATHAN

    . Introduction .... Education, Social Studies, Home Economics and Integrated Science could be galvanized and projected on coming ... Thus created a comparative unison in acceptance of an impending environmental thalidomide if business as.

  20. Federal Protection for Human Research Subjects: An Analysis of the Common Rule and Its Interactions with FDA Regulations and the HIPAA Privacy Rule

    National Research Council Canada - National Science Library

    Williams, Erin D

    2005-01-01

    .... In 1974, 45 CFR 46 was published following some cases of harm to human subjects, such as those caused by thalidomide drug trials and the United States Public Health Service syphilis study in Tuskeegee, Alabama...

  1. Exposure to antidepressants during pregnancy--prevalences and outcomes

    DEFF Research Database (Denmark)

    Jimenez-Solem, Espen

    2014-01-01

    Pharmacological treatment during pregnancy has been a huge challenge since the establishment of thalidomide's teratogenicity in the early sixties. Analyses of possible risks associated with drug intake during pregnancy are not possible by performing randomized trials, and interspecies extrapolation...

  2. Disease: H00546 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available nylketonuria Maternal progestational diabetes Maternal f...588] Sulfasalazine [CPD:C07316] Thalidomide [CPD:C07910] Trimethoprim-sulfonamide [DR:D00285] Retinoic acid [CPD:C00777] Maternal phe

  3. Disease: H00547 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ylketonuria Maternal progestational diabetes Maternal febrile illness Maternal infl...16] Thalidomide [CPD:C07910] Trimethoprim-sulfonamide [DR:D00285] Retinoic acid [CPD:C00777] Maternal phen

  4. Primary Myelofibrosis

    Science.gov (United States)

    ... Approved for Myeloproliferative Neoplasms for more information. Surgery Splenectomy ( surgery to remove the spleen) may be done ... Donor stem cell transplant . Thalidomide, lenalidomide, or pomalidomide. Splenectomy . Radiation therapy to the spleen , lymph nodes , or ...

  5. Hump on upper back (dorsocervical fat pad)

    Science.gov (United States)

    ... of certain glucocorticoid medicines, including prednisone, cortisone, and hydrocortisone Obesity (usually causes more generalized fat deposition) High level of the hormone cortisol (caused by Cushing syndrome ) ...

  6. Transarterial hepatic chemoperfusion of uveal melanoma metastases. Survival and response to treatment

    Energy Technology Data Exchange (ETDEWEB)

    Heusner, T.A.; Wittkowski-Sterczewski, A.; Ladd, S.C.; Forsting, M.; Verhagen, R. [Universitaetsklinik Essen, Duisburg-Essen Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie; Antoch, G. [Duesseldorf Univ. (Germany). Inst. fuer Diagnostische und Interventionelle Radiologie; Scheulen, M. [Duisburg-Essen Univ., Essen (DE). Klinik fuer Innere Medizin (Tumorforschung)

    2011-12-15

    Purpose: To assess the survival of patients with hepatic uveal melanoma metastases undergoing sequential transarterial hepatic chemoperfusion. Materials and Methods: 61 patients (mean age, 60.3 {+-} 13.8y) underwent a total of 249 hepatic chemoperfusion procedures (mean: 4 chemoperfusion procedures; range, 1 - 7 chemoperfusion procedures; standard deviation, 2.3 chemoperfusion procedures). All patients started with melphalan. In the case of progressive disease, melphalan was replaced by a different chemoperfusion agent. 38 patients were treated with melphalan only, 23 patients were treated with a combination of melphalan and other drugs. The median overall survival time was calculated for the overall population and several sub-groups. Differences in the survival rate between the sub-groups were assessed for statistical significance. The complication rate was assessed. Results: The median overall survival of the entire population was 10 months. The patients in the subgroups with a maximum number of 9 hepatic metastases as well as the patients in the subgroup without extrahepatic metastases at the beginning of therapy survived significantly longer than patients with more than 9 metastases/extrahepatic metastases (p = 0.019, p = 0.008). One patient (0.4 %) died from liver failure after initial infusion of melphalan. Conclusion: Intraarterial sequential hepatic chemoperfusion offers a minimally invasive treatment in patients with hepatic uveal melanoma metastases with good survival times and an acceptable major complication rate. (orig.)

  7. Electroretinogram monitoring of dose-dependent toxicity after ophthalmic artery chemosurgery in retinoblastoma eyes: six year review.

    Directory of Open Access Journals (Sweden)

    Jasmine H Francis

    Full Text Available To report electroretinogram responses of retinoblastoma children under anesthesia before and after treatment with chemotherapeutic drugs (melphalan, topotecan, carboplatin delivery by ophthalmic artery chemosurgery (OAC.A cohort study of 81 patients with retinoblastoma treated with OAC. All patients treated with OAC at our center through May 2012 for whom the requisite ERG data were available are included in the analysis. This study recorded the ERG 30 Hz flicker amplitude response changes from baseline, at 3 and 12 months following OAC treatment completion. Both univariate and multivariate linear regression models were evaluated, with generalized estimating equations to correct for correlations within patients. Independent numerical variables included maximum doses and cumulative doses of melphalan, topotecan and carboplatin.By univariate analysis, both melphalan and topotecan appear to be associated with changes in ERG amplitude at both 3 and 12 months; but for the most part, these changes are minimal and likely clinically insignificant. By multivariate analysis, maximum and cumulative melphalan have a modest, temporary effect on the ERG amplitude change, which is apparent at 3 months but no longer evident at 12 months after completing treatment. By multivariate analysis, topotecan and carboplatin do not appear to adversely effect the change in ERG response.Melphalan has the strongest, and carboplatin the weakest association with reduction in ERG response amplitudes; but for the most part, these changes are minimal and likely clinically insignificant. These conclusions apply only over the dose ranges used here, and should be applied with caution.

  8. Chemosensitivity of human small cell carcinoma of the lung detected by flow cytometric DNA analysis of drug-induced cell cycle perturbations in vitro

    DEFF Research Database (Denmark)

    Engelholm, S A; Spang-Thomsen, M; Vindeløv, L L

    1986-01-01

    A method based on detection of drug-induced cell cycle perturbation by flow cytometric DNA analysis has previously been described in Ehrlich ascites tumors as a way to estimate chemosensitivity. The method is extended to test human small-cell carcinoma of the lung. Three tumors with different...... sensitivities to melphalan in nude mice were used. Tumors were disaggregated by a combined mechanical and enzymatic method and thereafter have incubated with different doses of melphalan. After incubation the cells were plated in vitro on agar, and drug induced cell cycle changes were monitored by flow...

  9. Download this PDF file

    African Journals Online (AJOL)

    Proff.Adewunmi

    Abstract. Objective: This study investigated the effects of Chinese herbal medicine and prednisone on CD4+FoxP3+ T cells (Tregs) and Th17 cells in the. MRL/lpr mouse model of systemic lupus erythematosus. Methods: MRL/lpr mice were treated with herbal medicine (yin-nourishing and heat-clearing therapy), prednisone, ...

  10. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra...

  11. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the fina...

  12. Treatment of prolymphocytic leukemia

    International Nuclear Information System (INIS)

    Hollister, D. Jr.; Coleman, M.

    1982-01-01

    Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remission. There were no complete remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported

  13. Treatment of prolymphocytic leukemia

    International Nuclear Information System (INIS)

    Hollister, S. Jr.; Coleman, M.

    1982-01-01

    Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported

  14. Expression of CD64 on Circulating Neutrophils Favoring Systemic Inflammatory Status in Erythema Nodosum Leprosum.

    Directory of Open Access Journals (Sweden)

    Veronica Schmitz

    2016-08-01

    Full Text Available Erythema Nodosum Leprosum (ENL is an immune reaction in leprosy that aggravates the patient´s clinical condition. ENL presents systemic symptoms of an acute infectious syndrome with high leukocytosis and intense malaise clinically similar to sepsis. The treatment of ENL patients requires immunosuppression and thus needs to be early and efficient to prevent both disabilities and permanent nerve damage. Some patients experience multiple episodes of ENL and prolonged use of immunosuppressive drugs may lead to serious adverse effects. Thalidomide treatment is extremely effective at ameliorating ENL symptoms. Several mechanisms have been proposed to explain the efficacy of thalidomide in ENL, including the inhibition of TNF production. Given its teratogenicity, thalidomide is prohibitive for women of childbearing age. A rational search for molecular targets during ENL episodes is essential to better understand the disease mechanisms involved, which may also lead to the discovery of new drugs and diagnostic tests. Previous studies have demonstrated that IFN-γ and GM-CSF, involved in the induction of CD64 expression, increase during ENL. The aim of the present study was to investigate CD64 expression during ENL and whether thalidomide treatment modulated its expression. Leprosy patients were allocated to one of five groups: (1 Lepromatous leprosy, (2 Borderline leprosy, (3 Reversal reaction, (4 ENL, and (5 ENL 7 days after thalidomide treatment. The present study demonstrated that CD64 mRNA and protein were expressed in ENL lesions and that thalidomide treatment reduced CD64 expression and neutrophil infiltrates-a hallmark of ENL. We also showed that ENL blood neutrophils exclusively expressed CD64 on the cell surface and that thalidomide diminished overall expression. Patient classification based on clinical symptoms found that severe ENL presented high levels of neutrophil CD64. Collectively, these data revealed that ENL neutrophils express CD64

  15. O papel da terapia de manutenção no Mieloma Múltiplo The role of maintenance therapy for Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Rosane Bittencourt

    2007-03-01

    periods (plateau or even as an effective therapy for minimal residual disease. It may also bring higher rates of complete response to patients with an initial partial response. Over more than two decades, maintenance therapy for MM has been discussed and proposed. Since then various drugs and their combinations have been studied for this purpose, such as interferon-alpha, glucocorticoids - including dexamethasone and prednisone - and the more recently antiangiogenic drugs including thalidomide and its analogs. Clinical trials with each of these agents have shown advantages and, sometimes, disadvantages in terms of disease-free survival, overall survival and toxicity. A general review of these studies draws attention to the lack of evidence favoring unequivocal benefits in overall survival. In a time when novel and promising therapies arrive we shall emphasize the need of individual therapeutic approaches in terms of maintenance therapy, considering the prognosis and risk factors of each patient.

  16. Effects of Tea Polyphenols on the Expression of NF-κB, COX-2 and Survivin 
in Lewis Lung Carcinoma Xenografts in C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Jing WANG

    2012-05-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide. The anti-angiogenic effect of tea polyphenols (TPs on lung carcinoma was confirmed in our previous study. The effect of TPs on the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB, cyclooxygenase-2 (COX-2, and Survivin in Lewis lung cancer xenograft in mice was observed to explore the anti-angiogenic mechanism of TPs. Methods Lewis lung carcinoma was successfully implanted in 32 C57BL/6 mice, which were then randomly divided into the model control group, the Thalidomide group, the TPs group and the TPs combined with Thalidomide group. The tumor inhibition rates in these groups were determined, whereas the expressions of NF-κB, COX-2 and Survivin were detected using immunohistochemical techniques to investigate the molecular mechanism of the anti-tumor effect of TPs. Results (1 The tumor inhibition rates in the Thalidomide control group, the TPs group and the TPs plus Thalidomide group were 17.26%, 20.81%, 44.32% respectively. Compared with the model control group, the tumor inhibition rate was significantly higher in the TPs plus Thalidomide group (P<0.05; (2 Compared with the model control group, the expression of NF-κB was significantly decreased in the TPs group and the TPs plus Thalidomide group, and it was significantly downregulated in the latter (P<0.05; (3 The expression of COX-2 decreased in all treatment groups, and was significantly downregulated in the TPs plus Thalidomide group compared with the model control group (P<0.05; (4 Compared with the model control group, Survivin expression was significantly downregulated in all treatment groups (P<0.05, and was most obviously reduced in the TPs plus the Thalidomide group (P<0.01. Conclusion TPs plus Thalidomide significantly inhibits Lewis lung cancer growth. TPs possibly downregulates the expression of NF-κB, COX-2 and Survivin in tumor tissue, thereby

  17. History, heresy and radiology in scientific discovery.

    Science.gov (United States)

    McCredie, J

    2009-10-01

    Nowadays, most drugs reach the market after research has established their pharmacology, safety and efficacy. That was not always the case 50 years ago. Thalidomide was used before its target cell or mode of action were known. Commencing with the thalidomide catastrophe--an epidemic of gross birth defects (1958-1962)--thalidomide's origins are revisited to show how this drug came to be made and sold in the 1950s. Thalidomide intersected with Australian radiology in the 1970s. The site and mode of action of the drug was deduced from X-rays of thalidomide-induced bone defects, which have classical radiological signs of sensory neuropathic osteoarthropathy. The longitudinal reduction deformities follow the distribution of segmental sensory innervation of the limb skeleton, indicating neural crest as the target organ. Injury to one level of neural crest halts normal neurotrophism and deletes the dependent segment--a previously unrecognised embryonic mechanism that explains most non-genetic birth defects. The final common pathway is neural crest injury and failure of normal neurotrophism to result in longitudinal reduction deformities, for example, phocomelia.

  18. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma

    NARCIS (Netherlands)

    Cobben, DCP; Koopal, S; Tiebosch, ATMG; Jager, PL; Elsinga, PH; Wobbes, T; Hoekstra, HJ

    2002-01-01

    The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection. in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research,

  19. The polymorphism IL-1 beta T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT

    DEFF Research Database (Denmark)

    Vangsted, A.J.; Klausen, T.W.; Ruminski, W.

    2009-01-01

    high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1 beta T-31C significantly influenced overall survival (OS; P = 0.02) and that carriers...

  20. Multiple Myeloma

    African Journals Online (AJOL)

    The results of the use of melphalan in 52 patients with multiple myeloma have been analysed. The median survival of the whole group of patients was 30 months, and of those w:th renal insufficiency only 12,5 months. Bence-lones proteinuria was also a poor prognostic finding,. but only because of its association with renal ...

  1. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  2. Quantum Mechanical Study of γ-Fe2O3 Nanoparticle as a Nanocarrier for Anticancer Drug Delivery

    Science.gov (United States)

    Lari, Hadi; Morsali, Ali; Heravi, Mohammad Momen

    2018-05-01

    Using density functional theory (DFT), noncovalent interactions and four mechanisms of covalent functionalization of melphalan anticancer drug onto γ-Fe2O3 nanoparticles have been studied. Quantum molecular descriptors of noncovalent configurations were investigated. It was specified that binding of melphalan onto γ-Fe2O3 nanoparticles is thermodynamically suitable. Hardness and the gap of energy between LUMO and HOMO of melphalan are higher than the noncovalent configurations, showing the reactivity of drug increases in the presence of γ-Fe2O3 nanoparticles. Melphalan can bond to γ-Fe2O3 nanoparticles through NH2 (k1 mechanism), OH (k2 mechanism), C=O (k3 mechanism) and Cl (k4 mechanism) groups. The activation energies, the activation enthalpies and the activation Gibbs free energies of these reactions were calculated. Thermodynamic data indicate that k3 mechanism is exothermic and spontaneous and can take place at room temperature. These results could be generalized to other similar drugs.

  3. Consolidation therapy with autologous stem cell transplantation in plasma cell leukemia after VAD, high-dose cyclophosphamide and EDAP courses : a report of three cases and a review of the literature

    NARCIS (Netherlands)

    Hovenga, S; deWolf, JTM; Klip, H; Vellenga, E

    1997-01-01

    Plasma cell leukemia (PCL) is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in blood and bone marrow, Treatment of primary PCL has been mostly disappointing, Three patients with primary PCL are described who received high-dose melphalan with

  4. Characteristics of recovery from the euthyroid sick syndrome induced by tumor necrosis factor alpha in cancer patients

    NARCIS (Netherlands)

    Feelders, R. A.; Swaak, A. J.; Romijn, J. A.; Eggermont, A. M.; Tielens, E. T.; Vreugdenhil, G.; Endert, E.; van Eijk, H. G.; Berghout, A.

    1999-01-01

    Cytokines have been implicated in the pathogenesis of the euthyroid sick syndrome. Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor alpha (rTNF) and melphalan in patients with melanoma or sarcoma is accompanied by high systemic TNF levels. We examined the prolonged effects

  5. Bortezomib before and after high-dose therapy in myeloma : Long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; Kooy, M. van Marwijk; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  6. Bortezomib before and after high-dose therapy in myeloma: long-term results from the phase III HOVON-65/GMMGHD-4 trial

    NARCIS (Netherlands)

    Goldschmidt, H.; Lokhorst, H. M.; Mai, E. K.; van der Holt, B.; Blau, I. W.; Zweegman, S.; Weisel, K. C.; Vellenga, E.; Pfreundschuh, M.; Kersten, M. J.; Scheid, C.; Croockewit, S.; Raymakers, R.; Hose, D.; Potamianou, A.; Jauch, A.; Hillengass, J.; Stevens-Kroef, M.; Raab, M. S.; Broijl, A.; Lindemann, H. W.; Bos, G. M. J.; Brossart, P.; van Marwijk Kooy, M.; Ypma, P.; Duehrsen, U.; Schaafsma, R. M.; Bertsch, U.; Hielscher, T.; Jarari, Le; Salwender, H. J.; Sonneveld, P.

    2018-01-01

    The Dutch-Belgian Cooperative Trial Group for Hematology Oncology Group-65/German-speaking Myeloma Multicenter Group-HD4 (HOVON-65/GMMG-HD4) phase III trial compared bortezomib (BTZ) before and after high-dose melphalan and autologous stem cell transplantation (HDM, PAD arm) compared with classical

  7. Role of nitric oxide in recombinant tumor necrosis factor-alpha-induced circulatory shock : A study in patients treated for cancer with isolated limb perfusion

    NARCIS (Netherlands)

    Zwaveling, JH; Maring, JK; Moshage, H; vanGinkel, RJ; Hoekstra, HJ; Donse, IF; Girbes, ARJ; Schraffordt Koops, H.

    1996-01-01

    Objectives: To analyze the mechanism of vasodilation and circulatory shock occurring in patients who are treated with isolated limb perfusion with melphalan and recombinant tumor necrosis factor (TNF)-alpha for locally advanced malignant tumors, To determine the role of nitric oxide, if any, by

  8. Association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms ...

    Indian Academy of Sciences (India)

    SITI MAZIRAS MAKHTAR

    2017-08-28

    Aug 28, 2017 ... sitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide. Cancer Res. 56, 3577–3582. Bora P. S., Guruge B. L., Miller D. D., Chaitman B. R. and Fort- son W. 1997 Human fatty acid ethyl ester synttiase-III gene: genomic organization, nucleotide sequencing and chromoso-.

  9. Extremity perfusion for sarcoma

    NARCIS (Netherlands)

    Hoekstra, Harald Joan

    2008-01-01

    For more than 50 years, the technique of extremity perfusion has been explored in the limb salvage treatment of local, recurrent, and multifocal sarcomas. The "discovery" of tumor necrosis factor-or. in combination with melphalan was a real breakthrough in the treatment of primarily irresectable

  10. [Observation on therapeutic effect of chronic fatigue syndrome treated with coiling dragon needling and moving cupping on back].

    Science.gov (United States)

    Xu, Wei; Zhou, Ri-Hua; Li, Lei; Jiang, Ming-Wei

    2012-03-01

    To compare the differences of therapeutic effect of chronic fatigue syndrome treated with the combined therapy of coiling dragon needling and cupping on back and the western medicine therapy with Prednisone. Seventy-two cases were randomly divided into an acupuncture and cupping group (37 cases) and a Prednisone group (35 cases). In acupuncture and cupping group, Jiaji (EX-B 2) points of T1--L5 were applied with coiling dragon needling (once a day), combined with moving cupping on back (once every two days); in Prednisone group, Prednisone tablets were orally taken for 10 mg at 8:00 am. Seven days made one course, and 2 courses were carried on totally. FS-14 scale and BELL's chronic fatigue syndrome integral table were applied to evaluate the fatigue degree of patients before and after treatment, and the therapeutic effects of both groups were compared. After one course of treatment, the BELL's scores of both groups were obviously improved (both P 0.05); after two courses of treatment, the BELL's score in acupuncture and cupping group improved more obviously than that in Prednisone group, and the total effective rate of 91.9% (34/37) in acupuncture and cupping group was superior to that of 71.4% (25/35) in Prednisone group (P cupping on back is positive, superior to that of Prednisone with oral administration.

  11. Vitamin D3 Adjuvant Treatment Stimulate Interleukin-10 Expression in Children with Nephrotic Syndrome Without Affecting to Clinical Outcome and Glucocorticoid Receptor Expression

    Directory of Open Access Journals (Sweden)

    Husnul Asariati

    2014-11-01

    Full Text Available Idiopathic nephrotic syndrome (INS is the most glomerular disease that occurred in childhood with high rate morbidity. Glucocorticoid is drug of choice for INS and responsiveness to this drug determined prognosis.Glucocorticoid upregulate transcription of anti-inflammatory cytokines such as IL-4 and IL-10. IL-10 is an anti-inflammatory cytokine and has multiple role in immune response include modulate Th1/Th2 response. Vitamin D3 interact with glucocorticoid signaling. Administered active form of vitamin D3 increase dexamethasone-induced IL-10 expression by regulatory T cells in steroid resistant asthmatic patient. Here we showed increase of CD4+ IL10+ expression after treatment both prednisone only and combination prednison with vitamin D3. Both in new-onset NS or rare relaps NS, combination treatment prednisone + vitamin D3 increase CD4+ IL10+ expression significantly compared to prednisone-only treated group (p= 0.003, which first group (new-onset nephrotic syndrome + prednisone and vitamin D3 treatment showed the most CD4+ IL10+ expression enhancement (9.53±3.89. However this study failed to show a correlation between CD4+ IL-10+ expression after prednisone and vitamin D3 treatment with clinical outcome (linear regression test, p= 0,125. This study also showed that there was a no correlation between CD4+ IL-10+ expression and CD3+ GR expression after prednison + vitamin D3 treatment (p= 0.088. CD4+ IL-10+ expression in new-onset and rarely relapsing nephrotic syndrome patients higher in prednisone + vitamin D3 treated group than prednisone-only treated group. There is no correlation between CD4+ IL-10+ expression and CD3+ GR expression nor CD4+ IL-10+ expression and clinical outcome.

  12. César Augusto Restrepo Valencia, Consuelo Vélez Álvarez Abstract Objective. To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods. Patients with lupus nephritis class IV-G who despite receiving therapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results. Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months

    Directory of Open Access Journals (Sweden)

    César Augusto Restrepo Valencia

    2014-10-01

    Full Text Available Objective: To evaluate the effectiveness of calcineurin ciclosporin and tacrolimus inhibitors to induce remission in patients with refractory lupus nephritis. Patients, materials and methods: Patients with lupus nephritis class IV-G who despite receiving the rapy with high doses of steroid and with a cytostatic (cyclophosphamide or mycophenolate for 3 months had not been able to induce some kind of remission.The exclusion criteria were creatinine levels greater than 3 mg / dl, pregnancy, previous history of exposure to calcineurin inhibitors, cancer, active infections, uncontrolled hypertension, and negligence with medication intake. The recommended dose of cyclosporine was 3 mg / kg / day and tacrolimus 0.1 mg / kg / day, in joint with prednisone 0.3 mg / kg / day, cyclophosphamide 1 mg / kg / day or mycophenolate mofetil 1 gram every 12 hours. The cyclophosphamide was administered only during 6 months, after which it was changed to azathioprine at doses of 1 mg / kg / day. Still, mycophenolate was continued at the same dose. All patients completed a minimum period of 12 months follow-up, it was considered that patients achieved partial remission when proteinuria decreased by 50% of the baseline value or its value decreased to less than 1 gram in 24 hours, decrease of leukocytes count and red blood cells in urine of 50%, and creatinine values were stable. A complete remission was considered when there was a reduction in proteinuria in a value less than 300 mg per 24 hours, urinary sediment with less than 3 red blood cells, less than 5 leukocyte for each high power microscopic field, and a creatinine value reduction by 50% or reaching a normal value. Results: Twelve patients met the inclusion criteria and initiated the calcineurin inhibitor protocol. Two presented accelerated deterioration in their function and required chronic dialysis therapy. Ten patients with active treatment completed 12 months of followup, of which 4 (40% had partial

  13. Chemotherapeutic agents increase the risk for pulmonary function test abnormalities in patients with multiple myeloma.

    Science.gov (United States)

    Bruce, Jarrod T; Tran, Jerry M; Phillips, Gary; Elder, Pat; Mastronarde, John G; Devine, Steven M; Hofmeister, Craig C; Wood, Karen L

    2012-10-01

    Case reports of pulmonary toxicity have been published regarding bortezomib, lenalidomide, and thalidomide but there are no published reports looking at the possible long-term pulmonary effects of these medications. This article describes a possible relationship between the administration of bortezomib and thalidomide and the development of pulmonary function test (PFT) abnormalities. It also suggests that routine pulmonary function testing may be required in patients receiving these medications until larger studies can be performed to confirm this observation. Multiple myeloma is a common malignancy accounting for approximately 1% of all malignancies worldwide. Bortezomib, lenalidomide, and thalidomide are immunomodulatory derivatives that are used in the treatment of multiple myeloma (MM). There have been case reports of pulmonary disease associated with these agents, but the effect of these agents on pulmonary function test (PFT) results is unknown. We reviewed the records of 343 patients with MM who underwent PFTs before autologous stem cell transplantation. One hundred nine patients had not received any of the 3 medications, whereas 234 had received 1 or more of these agents. Patients exposed to bortezomib were more likely to have obstructive PFT results (P = .015) when compared with patients not exposed to this medication. Restrictive PFT results were more likely after exposure to thalidomide (P = .017). A logistic regression model was performed and when adjusted for age, sex, Durie-Salmon (DS) stage, body mass index (BMI), time from diagnosis to transplantation in days, and smoking history, the odds of obstruction were 1.96 times higher for patients who received bortezomib. The odds of restriction were 1.97 times higher after exposure to thalidomide. There appears to be a risk of PFT abnormalities developing in patients treated with bortezomib and thalidomide. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. EVALUATION OF TREATMENT FOR ELDERLY PATIENTS WITH MULTIPLEMYELOMA

    Directory of Open Access Journals (Sweden)

    Amela Kobaklić

    2008-04-01

    The result of our study indicates that combination chemotherapy with thalidomide iseffective treatment for elderly patients with multiple myeloma. Thalidomide in combination with other medications significantly extended medial overall survival, thereforthalidomide should be the reference treatment for elderly patients with multiple myelomafor the time being.Compering overall survival among different treatment centers we observed better survivalin our clinic, nevertheless multiple myeloma is stil a disease with severe prognosis. Withthat in mind we have high hopes for treating multiple myeloma with introduction of newdrugs (bortezomib, lenalomid

  15. Drug-induced lupus erythematosus

    Science.gov (United States)

    ... kidney inflammation (nephritis) can develop with drug-induced lupus caused by TNF inhibitors or with ANCA vasculitis due to hydralazine or levamisole. Nephritis may require treatment with prednisone and immunosuppressive medicines. Avoid taking the ...

  16. Drug treatment for myotonia (Review)

    NARCIS (Netherlands)

    Trip, J.; Drost, G.; Engelen, B.G.M. van; Faber, C.G.

    2006-01-01

    BACKGROUND: Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. Sodium channel blockers, tricyclic antidepressive drugs, benzodiazepines, calcium-antagonists, taurine and prednisone may be of use in reducing myotonia. OBJECTIVES: To

  17. 42 CFR 410.31 - Bone mass measurement: Conditions for coverage and frequency standards.

    Science.gov (United States)

    2010-10-01

    ...) Monitoring beneficiaries on long-term glucocorticoid (steroid) therapy of more than 3 months. (ii) Allowing... receive) glucocorticoid (steroid) therapy equivalent to an average of 5.0 mg of prednisone, or greater...

  18. Avascular Necrosis

    Science.gov (United States)

    ... blood vessels and reduce blood flow to bones. Steroid use. High-dose use of corticosteroids, such as prednisone, ... common substance blocking blood supply to bones. Monitor steroid use. Make sure your doctor knows about any past ...

  19. Primidone

    Science.gov (United States)

    ... acid (Depakene, Depakote); oral contraceptives (birth control pills); oral steroids such as dexamethasone (Decadron, Dexone) and prednisone (Deltasone); sedatives; sleeping pills; and tranquilizers. Your doctor may need to change the doses ...

  20. Metolazone

    Science.gov (United States)

    ... Urex); other medications for high blood pressure; sedatives; oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone); tranquilizers; and vitamin D. Your doctor may need to ...

  1. Phenobarbital

    Science.gov (United States)

    ... seizures such as phenytoin (Dilantin) and valproate (Depakene); oral steroids such as dexamethasone (Decadron, Dexone), methylprednisolone (Medrol), and prednisone (Deltasone);sedatives; sleeping pills; and tranquilizers. Your doctor may need to change the doses ...

  2. High Blood Cholesterol

    Science.gov (United States)

    ... inflammatory diseases such as psoriasis or to prevent rejection after a transplant Steroids such as prednisone that ... LDL cholesterol levels . Read more Levels of one type of blood fat can signal your risk of developing heart ...

  3. Cerebral angiography as a guide for therapy in isolated central nervous system vasculitis

    International Nuclear Information System (INIS)

    Stein, R.L.; Martino, C.R.; Weinert, D.M.; Hueftle, M.; Kammer, G.M.

    1987-01-01

    The authors present a case of isolated central nervous system vasculitis documented by cerebral arteriography in which remission, using a treatment regimen of prednisone and cyclophosphamide, was guided by serial arteriography during a 15-month period

  4. Cardiac amyloidosis

    Science.gov (United States)

    ... heart signals Prednisone, an anti-inflammatory medicine A heart transplant may be considered for people with some types ... accountability. A.D.A.M. is among the first to achieve this important distinction for online health ...

  5. Histoplasmosis

    Science.gov (United States)

    ... term corticosteroids (such as prednisone) are taking anti-rejection medicines after an organ transplant. A chronic infection ... Health Tools Dictionary Symptom Checker BMI Calculator myhealthfinder Immunization Schedules Nutrient Shortfall Questionnaire Diseases and Conditions Prevention ...

  6. Spontaneous recovery of dermatomyositis and unspecified myositis in three adult patients

    NARCIS (Netherlands)

    Van de Vlekkert, J.; Hoogendijk, J. E.; Frijns, C. J. M.; de Visser, M.

    2008-01-01

    Dermatomyositis (DM), polymyositis and unspecified myositis are idiopathic inflammatory myopathies in which prednisone is usually started as soon as the diagnosis has been established. Therefore, little is known about the natural history of these diseases and spontaneous recovery may escape

  7. Oral prednisolone suppresses allergic but not irritant patch test reactions in individuals hypersensitive to nickel

    DEFF Research Database (Denmark)

    Anveden, Ingegärd; Lindberg, Magnus; Andersen, Klaus E

    2004-01-01

    A multicentre, randomized, double-blind, crossover study was designed to investigate the effects of prednisone on allergic and irritant patch test reactions. 24 subjects with known allergy to nickel were recruited and patch tested with a nickel sulfate dilution series in aqueous solution, 5% nickel...... sulfate in petrolatum and 2 dilution series of the irritants nonanoic acid and sodium lauryl sulfate. The subjects were tested x2, both during treatment with prednisone 20 mg oral daily and during placebo treatment. The total number of positive nickel patch test reactions decreased significantly...... in patients during prednisone treatment. The threshold concentration to elicit a patch test reaction increased and the overall degree of reactivity to nickel sulfate shifted towards weaker reactions. The effect of prednisone treatment on the response to irritants was divergent with both increased...

  8. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP

    DEFF Research Database (Denmark)

    Xu-Monette, Zijun Y; Wu, Lin; Visco, Carlo

    2012-01-01

    TP53 mutation is an independent marker of poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL) treated with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP) therapy. However, its prognostic value in the rituximab immunochemotherapy era remains undefined. ...

  9. Abiraterone Acetate: A Review in Metastatic Castration-Resistant Prostrate Cancer.

    Science.gov (United States)

    Scott, Lesley J

    2017-09-01

    Oral abiraterone acetate (Zytiga ® ) is a selective inhibitor of CYP17 and thereby inhibits androgen biosynthesis, with androgen signalling crucial in the progression from primary to metastatic prostate cancer (PC) and subsequently, in the development of metastatic castration-resistant PC (mCRPC). In large phase 3 trials and in the clinical practice setting, oral abiraterone acetate in combination with prednisone was an effective treatment and had an acceptable, manageable tolerability and safety profile in chemotherapy-naive and docetaxel-experienced men with mCRPC. In the pivotal global phase 3 trials, relative to placebo (+prednisone), abiraterone acetate (+prednisone) prolonged overall survival (OS) at data maturity (final analysis) and radiographic progression-free survival (rPFS) at all assessed timepoints. Given its efficacy in prolonging OS and its convenient once-daily oral regimen, in combination with prednisone, abiraterone acetate is an important first-line option for the treatment of mCRPC.

  10. Acute Myocardial Injury in a Child with Duchenne Muscular Dystrophy: Pulse Steroid Therapy?

    OpenAIRE

    CINTEZA, Eliza; STOICESCU, Claudiu; BUTOIANU, Niculina; BALGRADEAN, Mihaela; NICOLESCU, Alin; ANGRÉS, Matthias

    2017-01-01

    Heart implication in Duchenne muscular dystrophy usually is present in the form of dilated cardiomyopathy, manifested as heart failure and arrhythmias. To delay progression, including heart deterioration, prednisone is recommended as preventive treatment. We report the case of an 11-year-old boy diagnosed with Duchenne muscular dystrophy at the age of seven, who was on preventive treatment with oral prednisone (0.75 mg/kg/day) and beta blocker (metoprolol, 1 mg/kg/day). Suddenly, the patient ...

  11. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology.

    Science.gov (United States)

    Gloss, David; Moxley, Richard T; Ashwal, Stephen; Oskoui, Maryam

    2016-02-02

    To update the 2005 American Academy of Neurology (AAN) guideline on corticosteroid treatment of Duchenne muscular dystrophy (DMD). We systematically reviewed the literature from January 2004 to July 2014 using the AAN classification scheme for therapeutic articles and predicated recommendations on the strength of the evidence. Thirty-four studies met inclusion criteria. In children with DMD, prednisone should be offered for improving strength (Level B) and pulmonary function (Level B). Prednisone may be offered for improving timed motor function (Level C), reducing the need for scoliosis surgery (Level C), and delaying cardiomyopathy onset by 18 years of age (Level C). Deflazacort may be offered for improving strength and timed motor function and delaying age at loss of ambulation by 1.4-2.5 years (Level C). Deflazacort may be offered for improving pulmonary function, reducing the need for scoliosis surgery, delaying cardiomyopathy onset, and increasing survival at 5-15 years of follow-up (Level C for each). Deflazacort and prednisone may be equivalent in improving motor function (Level C). Prednisone may be associated with greater weight gain in the first years of treatment than deflazacort (Level C). Deflazacort may be associated with a greater risk of cataracts than prednisone (Level C). The preferred dosing regimen of prednisone is 0.75 mg/kg/d (Level B). Over 12 months, prednisone 10 mg/kg/weekend is equally effective (Level B), with no long-term data available. Prednisone 0.75 mg/kg/d is associated with significant risk of weight gain, hirsutism, and cushingoid appearance (Level B). © 2016 American Academy of Neurology.

  12. Isothermal microcalorimetry as a quality by design tool to determine optimal blending sequences.

    Science.gov (United States)

    Al-Hallak, M H D Kamal; Azarmi, Shirzad; Xu, Zhenghe; Maham, Yadollah; Löbenberg, Raimar

    2010-09-01

    This study was designed to assess the value of isothermal microcalorimetry (ITMC) as a quality by design (QbD) tool to optimize blending conditions during tablet preparation. Powder mixtures that contain microcrystalline cellulose (MCC), dibasic calcium phosphate dihydrate (DCPD), and prednisone were prepared as 1:1:1 ratios using different blending sequences. ITMC was used to monitor the thermal activity of the powder mixtures before and after each blending process. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were performed on all final powder mixtures. Final powder mixtures were used to prepare tablets with 10 mg prednisone content, and dissolution tests were performed on all tablet formulations. Using ITMC, it was observed that the powder mixtures had different thermal activity depending on the blending sequences of the ingredients. All mixtures prepared by mixing prednisone with DCPD in the first stage were associated with relatively fast and significant heat exchange. In contrast, mixing prednisone with MCC in the first step resulted in slower heat exchange. Powder mixture with high thermal activity showed extra DSC peaks, and their dissolution was generally slower compared to the other tablets. Blending is considered as a critical parameter in tablet preparation. This study showed that ITMC is a simple and efficient tool to monitor solid-state reactions between excipients and prednisone depending on blending sequences. ITMC has the potential to be used in QbD approaches to optimize blending parameters for prednisone tablets.

  13. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  14. Randomized Trial of Thymectomy in Myasthenia Gravis.

    Science.gov (United States)

    Wolfe, Gil I; Kaminski, Henry J; Aban, Inmaculada B; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J Gabriel; Heckmann, Jeannine M; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O; Beydoun, Said R; Chalk, Colin H; Barboi, Alexandru C; Amato, Anthony A; Shaibani, Aziz I; Katirji, Bashar; Lecky, Bryan R F; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T; Rivner, Michael H; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M; Jackson, Carlayne E; Garcia Ramos, Guillermo S; Verschuuren, Jan J G M; Massey, Janice M; Kissel, John T; Werneck, Lineu C; Benatar, Michael; Barohn, Richard J; Tandan, Rup; Mozaffar, Tahseen; Conwit, Robin; Odenkirchen, Joanne; Sonett, Joshua R; Jaretzki, Alfred; Newsom-Davis, John; Cutter, Gary R

    2016-08-11

    Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, Pgravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).

  15. A study on limb reduction defects in six European regions

    NARCIS (Netherlands)

    Stoll, C; Calzolari, E; Cornel, M; GarciaMinaur, S; Garne, E; Nevin, N

    1996-01-01

    Limb reduction defects (LRD) gained especial attention after the thalidomide tragedy in 1962, LRD are common congenital malformations which present as obvious congenital anomalies recognized at birth, Therefore it might be assumed that they are well documented, However classification of LRDs is

  16. 77 FR 18831 - Government-Owned Inventions; Availability for Licensing

    Science.gov (United States)

    2012-03-28

    ... injection and have limited brain access. The classical drug, thalidomide is being increasingly used in the clinical management of a wide spectrum of immunologically-mediated and infectious diseases, and cancers... studies focus the compounds activity in classical models of neurodegeneration as well as cancer. Potential...

  17. LINKING ETIOLOGIES IN HUMANS AND ANIMAL MODELS: STUDIES OF AUTISM. (R824758)

    Science.gov (United States)

    AbstractThalidomide has been shown to lead to a high rate of autism when exposure occurs during the 20th to 24th d of gestation. Both the critical period and the neurological deficits of the autistic cases indicate that they have sustained injuries to the cranial nerv...

  18. Drug safety in pregnancy - monitoring congenital anomalies

    NARCIS (Netherlands)

    Morgan, Margery; De Jong-Van Den Berg, Lolkje T. W.; Jordan, Sue

    Aim This paper outlines research into the causes of congenital anomalies, and introduces a pan-European study. The potential roles of nurses and midwives in this area are illustrated by a case report. Background Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored

  19. Pattern and clinical profile of children with complex cardiac anomaly ...

    African Journals Online (AJOL)

    2012-11-25

    Nov 25, 2012 ... defects of the cardiac outflow tract including TOF.[4]. Known antenatal environmental factors include maternal infections (Rubella), drugs (alcohol, hydantoin, lithium, and thalidomide), and maternal illness (diabetes mellitus, phenylketonuria, and systemic lupus erythematosus).[5]. A congenital heart defect ...

  20. Pyoderma Gangranosum of the Penis

    Science.gov (United States)

    Kim, Tae Heung; Oh, Seung Young

    2009-01-01

    We report a patient who developed pyoderma gangrenosum in the penis with invasion of the distal urethra. The patient was treated with prednisolone and thalidomide, followed by a reconstructive surgical repair using a scrotal island flap. We report this case with a brief review of the literature. PMID:19949683

  1. Management of multiple myeloma

    African Journals Online (AJOL)

    2007-06-15

    Jun 15, 2007 ... pain to pathological fractures, symptomatic anaemia, recurrent infections and acute renal failure. The increased protein in the blood may lead to hyperviscosity (Table ... thalidomide, with response rates of up to 90%.6 New agents called proteosome inhibitors are very promising induction therapy agents, but ...

  2. Improved survival of multiple myeloma patients with late relapse after high-dose treatment and stem cell support, a population-based study of 348 patients in Denmark in 1994-2004*

    DEFF Research Database (Denmark)

    Vangsted, Annette Juul; Klausen, Tobias W; Andersen, Niels

    2010-01-01

    the introduction of thalidomide (1995-1999), before the introduction of bortezomib and lenalidomide (2000-2002) and when patients had access to all treatment modalities (2003-2008). RESULTS: Two hundred and forty-three patients suffered from relapse which required treatment. The median follow-up time was 91...

  3. Interferon-alpha in the treatment of multiple myeloma

    DEFF Research Database (Denmark)

    Khoo, T.L.; Joshua, D.; Gibson, J.

    2011-01-01

    in myeloma. Its role as maintenance therapy in the plateau phase of myeloma also remains uncertain. More recently, the use of interferon must now compete with the "new drugs" - thalidomide, lenalidomide and bortezomib in myeloma treatment. Will there be a future role of interferon in the treatment...

  4. Drug: D04687 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available genetic abnormality [DS:H01484] Mantle cell lymphoma [DS:H01464] ... Thalidomide [DR:... ... DG01936 ... TNF inhibitor ATC code: L04AX04 Chemical group: DG00744 myelodysplastic syndromes (MDS) associated with a deletion 5q cyto

  5. Antiretroviral therapy and HIV-associated cancers: Anti- angiogenic ...

    African Journals Online (AJOL)

    thalidomide (83 %) (F = 1.000, p = 0.341). Conclusion: Being a first-line drug in both HAART and combination treatment of HIV-1, efavirenz may ... reported for lung cancers [6] in relation to the use of “highly active antiretroviral therapy” .... longer showed angiogenic activity in the CAM but instead, had excessive fibrotic tissue ...

  6. Humero-radio-ulnar synostosis: a new case and review.

    Science.gov (United States)

    Hersh, J H; Joyce, M R; Profumo, L E

    1989-06-01

    We report on a patient with humero-radio-ulnar synostosis and upper limb oligoectrosyndactyly. All cases have been sporadic including discordance in monozygotic twins, and similar findings have occurred in thalidomide embryopathy. Further observations of similarly affected patients are needed to elucidate the nature of this upper limb defect and its cause.

  7. Child Friendly Medicines : Availability, Pharmaceutical design, Usability and patient outcomes

    NARCIS (Netherlands)

    Nales, D.A.

    2014-01-01

    Introduction Child and maternal health are key to overall human life expectancy, implying an urgent need for medicines that keep (unborn) children and mothers healthy and alive. Unfortunately, medicines may bring harm as well. For example, limb malformation due to the use of thalidomide by pregnant

  8. The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP

    DEFF Research Database (Denmark)

    Vangsted, Annette Juul; Klausen, Tobias Wirenfeldt; Gimsing, Peter

    2011-01-01

    with interferon-a (INF-a) as maintenance treatment, 177 patients treated with thalidomide, and 74 patients treated with bortezomib at relapse and address if the effects of polymorphisms in CD3EAP and RAI are modified by a functional polymorphism in NF¿B1. By linkage disequilibrium mapping, we found that variant...

  9. Overall survival patterns in patients with multiple myeloma in the era of novel agents and the role of initial clinical presentation and comorbidities: A population-based study

    NARCIS (Netherlands)

    Oortgiesen, Berdien; Van Roon, Eric N.; Joosten, Peter; Kibbelaar, Robby; Storm, Huib; Hovenga, Sjoerd; Van Rees, Bas P.; Woolthuis, Gerhard; Veeger, Nic J. G. M.; Hoogendoorn, Mels

    2014-01-01

    Introduction Clinical trials have shown improved response rates, progression-free survival and overall survival (OS) in patients with multiple myeloma (MM) when using the novel agents thalidomide, lenalidomide and bortezomib. However, outcome data provided by population-based registries, reflecting

  10. The human placenta--an alternative for studying foetal exposure

    DEFF Research Database (Denmark)

    Myren, Maja; Mose, Tina; Mathiesen, Line

    2007-01-01

    of the foetus (e.g. cigarette smoke) and development of the foetal organs (e.g. methylmercury and thalidomide). The scope of this review is to give insight to the placental anatomy, development and function. Furthermore, the compounds physical properties and the transfer mechanism across the placental barrier...

  11. Fulltext PDF

    Indian Academy of Sciences (India)

    Rajaram Nityananda, Chief Editor. Email: rajaram.nityananda@gmail.com. Our closing issue of 2016 has a distinctly mathematical flavor. Unlike other theme issues, this was not ... a mirror image of food molecules. A more tragic case is a drug known as thalidomide, from the late 1950s. The beneficial effects came from one ...

  12. Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity

    NARCIS (Netherlands)

    Eichner, Ruth; Heider, Michael; Fernández-Sáiz, Vanesa; van Bebber, Frauke; Garz, Anne-Kathrin; Lemeer, Simone; Rudelius, Martina; Targosz, Bianca-Sabrina; Jacobs, Laura; Knorn, Anna-Maria; Slawska, Jolanta; Platzbecker, Uwe; Germing, Ulrich; Langer, Christian; Knop, Stefan; Einsele, Herrmann; Peschel, Christian; Haass, Christian; Keller, Ulrich; Schmid, Bettina; Götze, Katharina S; Kuster, Bernhard; Bassermann, Florian

    Immunomodulatory drugs (IMiDs), such as thalidomide and its derivatives lenalidomide and pomalidomide, are key treatment modalities for hematologic malignancies, particularly multiple myeloma (MM) and del(5q) myelodysplastic syndrome (MDS). Cereblon (CRBN), a substrate receptor of the CRL4 ubiquitin

  13. Current multiple myeloma treatment strategies with novel agents

    DEFF Research Database (Denmark)

    Ludwig, Heinz; Beksac, Meral; Bladé, Joan

    2010-01-01

    The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents...

  14. Renal amyloidosis: a synopsis of its clinical presentation, diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Elena V. Zakharova

    2015-04-01

    Full Text Available Amyloidosis is a heterogeneous group of hereditary and acquired diseases in which normally soluble plasma proteins are deposited in the extracellular and/or intracellular space in abnormal, insoluble, fibrillar form. Renal damage is one of the most common features of systemic amyloidosis, and the presentation is most commonly due to the consequences of renal involvement, with proteinuria and progressive renal decline. Progression to end-stage renal failure is common. Early diagnosis of systemic amyloidosis is difficult. Renal amyloidosis typically presents with nephrotic syndrome and/or renal failure. Treatment of AL amyloidosis aims to reduce production of the monoclonal immunoglobulin precursor via chemotherapy. Current options for treatment include melphalan+dexamethasone or cyclophosphamide-bortezomib-dexamethasone regimens, or in selected patients, high-dose melphalan with autologous stem cell transplantation. The focus of current research is on pharmacological therapy to solubilize amyloid fibrils and increase tissue catabolism of amyloid deposits.

  15. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL...... AND METHODS: A total of 84 perfusions were performed (53 women, 31 men, median age 63 years) from 1993 to 2010. 95% of the perfusions were administered to the lower limbs and 5% to the upper limbs. The inclusion criteria were recurrent and/or clinically apparent cutaneous/subcutaneous extremity in....... Time from ILP to recurrence was a median of seven months (range 1-37 months) for patients with CR or PR. Survival was longer for patients with CR or PR than for patients showing NC or progression. Several patients had mild or moderate local toxicity reactions, two patients developed severe local...

  16. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL......-transit melanoma metastases. RESULTS: The response rate after ILP was 85%; 42% had complete response (CR), 43% partial response (PR), 12% no change (NC) and 3% progression. Two- and five-year survival rates were 57% and 31%, respectively, and they were higher for patients with than without lymph node metastases...... toxicity. CONCLUSION: ILP induces tumour regression in the vast majority of patients. One patient, i.e. 1% of the group, died from surgical complications. Otherwise, ILP treatment had an acceptable morbidity in this group of very sick patients. We are convinced that the treatment should be offered...

  17. Outcomes of autologous transplantation for multiple myeloma according to different induction regimens

    Directory of Open Access Journals (Sweden)

    Edvan de Queiroz Crusoe

    2014-01-01

    Full Text Available Background: Induction therapy followed by high-dose chemotherapy and autologous transplantation is the standard treatment for suitable patients with multiple myeloma. Objective: The aim of this study was to assess whether induction therapy with thalidomidecontaining regimens was associated with improved results compared to vincristine, doxorubicin, and dexamethasone, and whether cyclophosphamide, thalidomide, and dexamethasone were associated with better results than thalidomide and dexamethasone. Methods: The records of 152 patients who underwent autologous transplantation at this institution from August of 2004 to January of 2012 were reviewed, selecting those with at least partial response to a maximum of eight cycles of induction therapy and sufficient follow-up information for analysis. Results: This study included 89 patients; 44 were female, with a mean age of 55 years (there was a significant trend for increasing age over the years of the study.The median number of induction therapy cycles was four, again with a trend of increase over the years.At least a very good partial response to induction therapy was achieved more often in the cyclophosphamide, thalidomide, and dexamethasone group (61.1% and in the thalidomide and dexamethasone group (59.2% than in the vincristine, doxorubicin, and dexamethasone group (16.2%. The overall median progression-free survival was 34 months, with no statistically significant difference between the three groups. The overall median survival was not reached, and there was no significant difference between the three groups; the estimated five-year overall survival was 55%. Conclusion: Although the quality of responses appeared to be better with thalidomidecontaining regimens, these improvements did not translate into improved long-term outcomes. Given its track record, cyclophosphamide, thalidomide, and dexamethasone is currently considered the preferred regimen for first-line induction therapy in the

  18. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS)

    OpenAIRE

    Mailankody, Sham; Pfeiffer, Ruth M.; Kristinsson, Sigurdur Y.; Korde, Neha; Bjorkholm, Magnus; Goldin, Lynn R.; Turesson, Ingemar; Landgren, Ola

    2011-01-01

    Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n = 8740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed between 1986 and 2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and nonhematologic malignancies for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem cell transplantation [HDM-ASCT]) and 2000 (introduction of immunomodulatory d...

  19. High-dose therapy for patients with primary multifocal and early relapsed Ewing's tumors: results of two consecutive regimens assessing the role of total-body irradiation.

    Science.gov (United States)

    Burdach, S; Meyer-Bahlburg, A; Laws, H J; Haase, R; van Kaik, B; Metzner, B; Wawer, A; Finke, R; Göbel, U; Haerting, J; Pape, H; Gadner, H; Dunst, J; Juergens, H

    2003-08-15

    Risk stratification of metastatic and relapsed Ewing's tumors (ETs) has been a matter of debate during the last decade. Patients with bone or bone marrow metastases or early or multiple relapses constitute the worst risk group in ET and have a poorer prognosis than patients with primary lung metastases or late relapses. In this article, the results of the present Meta European Intergroup Cooperative Ewing Sarcoma Study (MetaEICESS) (tandem melphalan/etoposide [TandemME]) were compared with the result of the previous study (hyper melphalan/etoposide [HyperME]), both at 5 years, in a patient population within the same high-risk stratum to determine toxicity. Among 54 eligible patients, 26 were treated according to the HyperME protocol, and 28 were treated according to TandemME protocol. Patients received six cycles of the Cooperative Ewing Sarcoma Study treatment in HyperME and six cycles of the EICESS treatment in TandemME as induction chemotherapy. Patients also received involved-compartment irradiation for local intensification and myeloablative systemic intensification consolidation with hyperfractionated total-body irradiation (TBI) combined with melphalan/etoposide in HyperME or two times the melphalan/etoposide in TandemME followed by autologous stem-cell transplantation. The event-free survival (EFS) rate +/- SD in HyperME and TandemME was 22% +/- 8% and 29% +/- 9%, respectively. The dead of complication rate was 23% in HyperME and 4% in TandemME. TandemME offers a decent, albeit still not satisfactory, rate of long-term remissions in most advanced ETs (AETs), with short-term treatment and acceptable toxicity. TBI was not required to maintain EFS level in this setting but was associated with a high rate of toxic death. Future prospective studies in unselected patients are warranted to evaluate high-dose therapy in an unselected group of patients with AET.

  20. Autologous Stem Cell Transplant for AL Amyloidosis

    OpenAIRE

    Roy, Vivek

    2012-01-01

    AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors) has increased treatment options. Autologous stem cell transplant (ASCT) has been used in the treatment of ...

  1. Monitoring system for isolated limb perfusion based on a portable gamma camera

    Energy Technology Data Exchange (ETDEWEB)

    Orero, A.; Muxi, A.; Rubi, S.; Duch, J. [Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain); Vidal-Sicart, S.; Pons, F. [Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain); Inst. d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona (Spain); Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Barcelona (Spain); Roe, N. [Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain); CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain); Rull, R. [Servei de Cirurgia, Hospital Clinic, Barcelona (Spain); Pavon, N. [Inst. de Fisica Corpuscular, CSIC - UV, Valencia (Spain); Pavia, J. [Servei de Medicina Nuclear, Hospital Clinic, Barcelona (Spain); Inst. d' Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona (Spain); CIBER de Bioingenieria, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona (Spain)

    2009-07-01

    Background: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-{alpha}) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. Methods: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-{alpha} and melphalan. Results: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is {+-}1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-{alpha} and melphalan. Conclusion: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-{alpha} and melphalan has been indicated. (orig.)

  2. Risk factors for severe neutropenia following intra-arterial chemotherapy for intra-ocular retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Ira J Dunkel

    Full Text Available PURPOSE: Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥ grade 3 neutropenia. METHODS: Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1 blood count results were available in the 7 to 14 days post-treatment interval and (2 concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: 54 cycles (29% were associated with grade 3 (n = 43 or grade 4 (n = 11 neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33-12.73, p = 0.01, but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis. CONCLUSIONS: Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.

  3. Updated interim efficacy analysis and long-term safety of abiraterone acetate in metastatic castration-resistant prostate cancer patients without prior chemotherapy (COU-AA-302).

    Science.gov (United States)

    Rathkopf, Dana E; Smith, Matthew R; de Bono, Johann S; Logothetis, Christopher J; Shore, Neal D; de Souza, Paul; Fizazi, Karim; Mulders, Peter F A; Mainwaring, Paul; Hainsworth, John D; Beer, Tomasz M; North, Scott; Fradet, Yves; Van Poppel, Hendrik; Carles, Joan; Flaig, Thomas W; Efstathiou, Eleni; Yu, Evan Y; Higano, Celestia S; Taplin, Mary-Ellen; Griffin, Thomas W; Todd, Mary B; Yu, Margaret K; Park, Youn C; Kheoh, Thian; Small, Eric J; Scher, Howard I; Molina, Arturo; Ryan, Charles J; Saad, Fred

    2014-11-01

    Abiraterone acetate (an androgen biosynthesis inhibitor) plus prednisone is approved for treating patients with metastatic castration-resistant prostate cancer (mCRPC). Study COU-AA-302 evaluated abiraterone acetate plus prednisone versus prednisone alone in mildly symptomatic or asymptomatic patients with progressive mCRPC without prior chemotherapy. Report the prespecified third interim analysis (IA) of efficacy and safety outcomes in study COU-AA-302. Study COU-AA-302, a double-blind placebo-controlled study, enrolled patients with mCRPC from April 2009 to June 2010. A total of 1088 patients were stratified by Eastern Cooperative Oncology Group performance status (0 vs 1). Patients were randomised 1:1 to abiraterone 1000mg plus prednisone 5mg twice daily by mouth versus prednisone. Co-primary end points were radiographic progression-free survival (rPFS) and overall survival (OS). Median times to event outcomes were estimated using the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were derived using the Cox model, and treatment comparison used the log-rank test. The O'Brien-Fleming Lan-DeMets α-spending function was used for OS. Adverse events were summarised descriptively. With a median follow-up duration of 27.1 mo, improvement in rPFS was statistically significant with abiraterone treatment versus prednisone (median: 16.5 vs 8.2 mo; HR: 0.52 [95% CI, 0.45-0.61]; ppatient-reported outcomes improved. While the post hoc nature of the long-term safety analysis is a limitation, the safety profile with longer treatment exposure was consistent with prior reports. The updated IA of study COU-AA-302 in patients with mCRPC without prior chemotherapy confirms that abiraterone delays disease progression, pain, and functional deterioration and has clinical benefit with a favourable safety profile, including in patients treated for ≥24 mo. Study COU-AA-302, ClinicalTrials.gov number, NCT00887198. The updated results of this ongoing study

  4. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia.

    Science.gov (United States)

    Ye, Dingwei; Huang, Yiran; Zhou, Fangjian; Xie, Keji; Matveev, Vsevolod; Li, Changling; Alexeev, Boris; Tian, Ye; Qiu, Mingxing; Li, Hanzhong; Zhou, Tie; De Porre, Peter; Yu, Margaret; Naini, Vahid; Liang, Hongchuan; Wu, Zhuli; Sun, Yinghao

    2017-04-01

    This double-blind, placebo-controlled phase 3 study was designed to compare efficacy and safety of abiraterone acetate + prednisone (abiraterone) to prednisone alone in chemotherapy-naïve, asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients from China, Malaysia, Thailand and Russia. Adult chemotherapy-naïve patients with confirmed prostate adenocarcinoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) grade 0-1, ongoing androgen deprivation (serum testosterone <50 ng/dL) with prostate specific antigen (PSA) or radiographic progression were randomized to receive abiraterone acetate (1000 mg, QD) + prednisone (5 mg, BID) or placebo + prednisone (5 mg, BID), until disease progression, unacceptable toxicity or consent withdrawal. Primary endpoint was improvements in time to PSA progression (TTPP). Totally, 313 patients were randomized (abiraterone: n  = 157; prednisone: n  = 156); and baseline characteristics were balanced. At clinical cut-off (median follow-up time: 3.9 months), 80% patients received treatment (abiraterone: n  = 138, prednisone: n  = 112). Median time to PSA progression was not reached with abiraterone versus 3.8 months for prednisone, attaining 58% reduction in PSA progression risk (HR = 0.418; p  < 0.0001). Abiraterone-treated patients had higher confirmed PSA response rate (50% vs. 21%; relative odds = 2.4; p  < 0.0001) and were 5 times more likely to achieve radiographic response than prednisone-treated patients (22.9% vs.  4.8%, p  = 0.0369). Median survival was not reached. Most common (≥10% abiraterone vs.  prednisone-treated) adverse events: bone pain (7% vs. 14%), pain in extremity (6% vs. 12%), arthralgia (10% vs. 8%), back pain (7% vs. 11%), and hypertension (15% vs. 14%). Interim analysis confirmed favorable benefit-to-risk ratio of abiraterone in chemotherapy-naïve men with mCRPC, consistent with global study, thus supporting use of

  5. Preventive effects ofPolygonum multiflorumon glucocorticoid-induced osteoporosis in rats.

    Science.gov (United States)

    Zhou, Manru; Li, Jin; Wu, Jingkai; Yang, Yajun; Zeng, Xiaobing; Lv, Xiaohua; Cui, Liao; Yao, Weimin; Liu, Yuyu

    2017-09-01

    In Traditional Chinese Medicine, Polygonum multiflorum (PM) is known for its anti-aging properties. A previous study by our group showed that extracts of PM were able to prevent and treat bone loss in vivo , and the active components emodin and 2,3,5,4,-tetrahydroxystilbene-2- O -β-glucoside (TSG) promoted the osteogenic differentiation of mesenchymal stem cells in vitro . The aim of the present study was to investigate the preventive effects of PM on glucocorticoid-induced osteoporosis (GIO) in rats. A crude extract of PM was prepared with 75% ethanol, purified and enriched using a D-101 macroresin column and elution with 30% ethanol, and the material obtained was assessed by high-performance liquid chromatography. Male or female Sprague Dawley rats (n=180) were randomly divided into nine groups: Control, prednisone, prednisone plus calcitriol (CAL), prednisone plus 30% ethanolic eluate of PM [high (H), medium (M) and low (L) dose] and prednisone plus crude extract of PM (H, M and L dose). Prednisone was orally administered to the osteoporosis model rats for 21 weeks, alongside which they received PM extracts. The weight of the viscera, anterior tibial muscle and other tissues was recorded at the end of the experiment. The femur and lumbar vertebra were collected for the measurement of three-dimensional microarchitecture by micro-computed tomography scanning, assessment of biomechanical properties and determination of bone mineral density (BMD). In the 30% ethanolic eluate of the PM extract, the content of TSG and combined anthraquinone was 9.20 and 0.15%, respectively, and that in the crude extract of PM was 2.23 and 0.03%, respectively. Over 6 weeks, the weight of the rats the in prednisone group decreased (P<0.05), while the weight of rats treated with M and H doses of 30% ethanolic eluate was increased compared with that in the prednisone group (P<0.05). Rats exposed to prednisone exhibited a deteriorated bone microarchitecture, low BMD, decreased bone volume

  6. Preventive effects of Polygonum multiflorum on glucocorticoid-induced osteoporosis in rats

    Science.gov (United States)

    Zhou, Manru; Li, Jin; Wu, Jingkai; Yang, Yajun; Zeng, Xiaobing; Lv, Xiaohua; Cui, Liao; Yao, Weimin; Liu, Yuyu

    2017-01-01

    In Traditional Chinese Medicine, Polygonum multiflorum (PM) is known for its anti-aging properties. A previous study by our group showed that extracts of PM were able to prevent and treat bone loss in vivo, and the active components emodin and 2,3,5,4,-tetrahydroxystilbene-2-O-β-glucoside (TSG) promoted the osteogenic differentiation of mesenchymal stem cells in vitro. The aim of the present study was to investigate the preventive effects of PM on glucocorticoid-induced osteoporosis (GIO) in rats. A crude extract of PM was prepared with 75% ethanol, purified and enriched using a D-101 macroresin column and elution with 30% ethanol, and the material obtained was assessed by high-performance liquid chromatography. Male or female Sprague Dawley rats (n=180) were randomly divided into nine groups: Control, prednisone, prednisone plus calcitriol (CAL), prednisone plus 30% ethanolic eluate of PM [high (H), medium (M) and low (L) dose] and prednisone plus crude extract of PM (H, M and L dose). Prednisone was orally administered to the osteoporosis model rats for 21 weeks, alongside which they received PM extracts. The weight of the viscera, anterior tibial muscle and other tissues was recorded at the end of the experiment. The femur and lumbar vertebra were collected for the measurement of three-dimensional microarchitecture by micro-computed tomography scanning, assessment of biomechanical properties and determination of bone mineral density (BMD). In the 30% ethanolic eluate of the PM extract, the content of TSG and combined anthraquinone was 9.20 and 0.15%, respectively, and that in the crude extract of PM was 2.23 and 0.03%, respectively. Over 6 weeks, the weight of the rats the in prednisone group decreased (P<0.05), while the weight of rats treated with M and H doses of 30% ethanolic eluate was increased compared with that in the prednisone group (P<0.05). Rats exposed to prednisone exhibited a deteriorated bone microarchitecture, low BMD, decreased bone volume

  7. A randomized study of the prevention of acute graft-versus-host disease

    International Nuclear Information System (INIS)

    Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E. Jr.

    1982-01-01

    Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants

  8. Management of rheumatic chorea: an observational study

    Directory of Open Access Journals (Sweden)

    Araújo Alexandra Prufer de Queiroz Campos

    2002-01-01

    Full Text Available BACKGROUND: Rheumatic chorea (RC has recently been linked to an antibody-mediated immune mechanism. OBJECTIVE/METHOD: To verify if this knowledge reflected in management changes we conceived a descriptive study. RESULTS: The medical charts of 20 children (13 females aged 6 to 12 years (mean 8 years, diagnosed as RC from June 1996 to June 1999, were reviewed. All patients received some medical treatment. Haloperidol was the most prescribed medication (15 patients - 75 %. Sulpiride, diazepam and valproate were also used as symptomatic treatment. Imune-modulating therapy with prednisone was prescribed for seven children. The shortest course of chorea (16 days occurred in a patient treated with prednisone. CONCLUSION: Prednisone has been prescribed for rheumatic chorea besides the traditional symptomatic approach. A great variety of antichoreic drugs are being employed.

  9. Diagnosis and treatment of thymoma associated with pure red cell aplasia: three cases report

    International Nuclear Information System (INIS)

    Wang Wencai; Xu Wuyin

    2000-01-01

    Objective: To discuss how to diagnose and treat thymoma associated with pure red cell aplasia (PRCA). Methods: Three patients of thymoma associated with PRCA were treated with thymothymectomy, and the local radiotherapy was conducted after operation for avoiding the thymoma reproduction. Determining of their peripheral blood hemoglobin was used to evaluate the postoperation result in PRCA. If PRCA can not be relieved, oral prednisone and cyclosporin A were given. Results: One patient with PRCA was cured, the second patient remained in remission by treatment with prednisone and CsA, and the third patient was in progress. Conclusion: The treatment by means of 'thymothymectomy-local radiotherapy-use of prednisone and CsA', is effective for thymoma associated with PRCA

  10. Systemic therapy in men with metastatic castration-resistant prostate cancer:American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline.

    Science.gov (United States)

    Basch, Ethan; Loblaw, D Andrew; Oliver, Thomas K; Carducci, Michael; Chen, Ronald C; Frame, James N; Garrels, Kristina; Hotte, Sebastien; Kattan, Michael W; Raghavan, Derek; Saad, Fred; Taplin, Mary-Ellen; Walker-Dilks, Cindy; Williams, James; Winquist, Eric; Bennett, Charles L; Wootton, Ted; Rumble, R Bryan; Dusetzina, Stacie B; Virgo, Katherine S

    2014-10-20

    To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 ((223)Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or (223)Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to evaluate optimal sequences or

  11. The Steroids in the Maintenance of Remission of Proliferative Lupus Nephritis (SIMPL Pilot Trial

    Directory of Open Access Journals (Sweden)

    Lauren Galbraith

    2014-11-01

    Full Text Available Background: Patients with proliferative lupus nephritis are at risk of frequent relapses. Whether low- dose prednisone prevents relapses is uncertain. Objectives: We undertook a pilot RCT to determine the feasibility of a larger trial. Design: Pilot randomized controlled trial. Setting: Single center Canadian outpatient nephrology clinic. Patients: Participants with systemic lupus erythematosus (SLE and a history of class III or IV lupus nephritis that achieved at least partial remission and remained on prednisone were eligible. Measurements: Feasibility: proportion of eligible patients randomized and adherence to tapering regimen. Clinical: occurrence of renal or major non-renal flare of SLE. Methods: We conducted a blinded, two-parallel-group randomized controlled trial of prednisone 7.5 mg/day (continuation compared to a matching placebo (withdrawal. Results: Of nineteen eligible patients screened, 15 (79% were recruited and randomized; 8 to prednisone continuation and seven to withdrawal. All participants adhered to the tapering protocol to their assigned withdrawal or low-dose maintenance target. Over 36 months, the primary outcome occurred in four (50% patients in the continuation group (three renal and one major non-renal flare, compared with one patient (14% in the withdrawal group (one renal flare. Three participants (38% in the continuation group had minor flares, while no patients in the withdrawal group did. Limitations: This pilot RCT was small and not designed to assess the efficacy or safety of maintenance with low-dose prednisone. Conclusions: The high proportion of eligible patients recruited, and success of protocol adherence suggest a large trial of prednisone maintenance therapy compared to withdrawal is feasible. Trial registration: Current Controlled Trials ISRCTN31327267.

  12. Blood Vessel Normalization in the Hamster Oral Cancer Model for Experimental Cancer Therapy Studies

    Energy Technology Data Exchange (ETDEWEB)

    Ana J. Molinari; Romina F. Aromando; Maria E. Itoiz; Marcela A. Garabalino; Andrea Monti Hughes; Elisa M. Heber; Emiliano C. C. Pozzi; David W. Nigg; Veronica A. Trivillin; Amanda E. Schwint

    2012-07-01

    Normalization of tumor blood vessels improves drug and oxygen delivery to cancer cells. The aim of this study was to develop a technique to normalize blood vessels in the hamster cheek pouch model of oral cancer. Materials and Methods: Tumor-bearing hamsters were treated with thalidomide and were compared with controls. Results: Twenty eight hours after treatment with thalidomide, the blood vessels of premalignant tissue observable in vivo became narrower and less tortuous than those of controls; Evans Blue Dye extravasation in tumor was significantly reduced (indicating a reduction in aberrant tumor vascular hyperpermeability that compromises blood flow), and tumor blood vessel morphology in histological sections, labeled for Factor VIII, revealed a significant reduction in compressive forces. These findings indicated blood vessel normalization with a window of 48 h. Conclusion: The technique developed herein has rendered the hamster oral cancer model amenable to research, with the potential benefit of vascular normalization in head and neck cancer therapy.

  13. Modulation of the toxicity of photons by non-conventional drugs

    International Nuclear Information System (INIS)

    Bohm, L.; Theron, T.; Serafin, A.; Verheye, F.

    1997-01-01

    The 3 drugs under investigation Pentoxifylline, Ouabain and Thalidomide are non-conventional in the sense that they have a low toxicity and do not damage DNA. Pentoxifylline reduces blood viscosity ad enhances peripheral blood flow. When combined with irradiation in a mouse rhabdomyosarcoma model we found markedly enhanced tumour growth delay and in cultured cells dose modifying factors for SF2 and alpha in the region of 1.2-1.7 (Strahlentherapie 1995;170:595-01). The drug also alters cell regulation by inhibiting the radiation induced G2/M block and suppressing control of DNA synthesis (Theron and Boehm, unpubl.). When Thalidomide was added in the absence of irradiation to the myelo-blastic cell line K-562 we found characteristic changes of cell morphology and cell surface markers suggesting differentiation and expression of a megacaryocytic lineage (Leukemia Research 1991;15:129-136). A summary of the current state of research is given. (authors)

  14. Genetic variations in multiple myeloma II

    DEFF Research Database (Denmark)

    Vangsted, A.; Klausen, T.W.; Vogel, U.

    2012-01-01

    - and bortezomib-based therapy, maintenance treatment with interferon-α and in relation to therapy-related adverse effects caused by treatment. Candidate genes for prediction of effect of HDT include DNA repair genes, CYP genes and genes involved in inflammation and apoptosis such as IL1B and RAI. In thalidomide......- and bortezomid-based therapy, candidate genes include TNFA and genes involved in the nuclear factor kappa B pathway (NFKB2 and TRAF3), respectively. In maintenance treatment with interferon-α, a polymorphism in gene NFKB1 is a candidate gene for prediction for effect. Adverse effect includes infection......Association studies on genetic variation to treatment effect may serve as a predictive marker for effect of treatment and can also uncover biological pathways behind drug effect. Single-nucleotide polymorphisms (SNPs) have been studied in relation to high-dose treatment (HDT), thalidomide...

  15. Severe hyperkalemia as a complication of timolol, a topically applied beta-adrenergic antagonist

    International Nuclear Information System (INIS)

    Swenson, E.R.

    1986-01-01

    Severe hyperkalemia occurred in a patient with radiation pneumonitis and glaucoma shortly after beginning prednisone therapy. There was no evidence of renal failure, diabetes, acidosis, increased potassium intake, or significant tissue trauma. Medications having adverse effects on potassium metabolism were considered, and the patient's use of timolol maleate eyedrops was discontinued. His serum potassium level normalized despite continuation of the prednisone therapy. He became hyperkalemic on rechallenge with timolol and normokalemic following its withdrawal. This case indicates that the potential for beta-blocker-induced hyperkalemia exists even with topical appreciation

  16. Treatment relapsed subcutaneous panniculitis-like T-cell lymphoma together HPS by Cyclosporin A

    Directory of Open Access Journals (Sweden)

    Ren'an Chen

    2010-11-01

    Full Text Available A 25-year-old man was diagnosised subcutaneous panniculitis-like T-cell lymphoma (SPTCL through biopsy of a nodule from the anterior chest. After the treatment with prednisone 90 mg 3 weeks and tapered off in 1 month, the disease released, but relapsed together with symptions of hemophagocytic syndrome eight months after the termination of prednisone. CHOEP recipe was given but with unsatisfactory result until cyclosporine was prescribed. Cyclosporine was removed 6 months later. There is no evidence of clinical relapse 1 year later. This case suggest that cyclosporine could be a selectable treatment even in relapsed SPTCL.

  17. Primær kutan kryptokokkose hos dueavler

    DEFF Research Database (Denmark)

    Andersen, Kjeld; Ravn, Pernille; Bangsborg, Jette Marie

    2011-01-01

    A Danish 73 year-old male patient with polymyalgia rheumatica and in prednisone treatment presented with a cutaneous ulcer on the hand caused by a scratch from a pigeon. Initial treatment with antibiotics was unsuccessful. Biopsy revealed Cryptococcus neoformans and the patient recovered on antif......A Danish 73 year-old male patient with polymyalgia rheumatica and in prednisone treatment presented with a cutaneous ulcer on the hand caused by a scratch from a pigeon. Initial treatment with antibiotics was unsuccessful. Biopsy revealed Cryptococcus neoformans and the patient recovered...

  18. Idiopathic giant oesophageal ulcer and leucopoenia after renal transplantation.

    Science.gov (United States)

    van Boekel, G A J; Volbeda, M; van den Hoogen, M W F; Hilbrands, L B; Berden, J H M

    2012-10-01

    A 45-year-old male recipient of a renal allograft was admitted because of a giant oesophageal ulcer coinciding with leucopoenia. An extensive workup revealed no explanation for the ulcer and leucopoenia. Our final diagnosis by exclusion was an idiopathic giant oesophageal ulcer and late-onset neutropenia as consequences of rituximab induction therapy given during the transplant procedure. The patient fully recovered after treatment with prednisone. However, after four months, the ulcer and leucopoenia recurred and again successfully responded to treatment with prednisone.

  19. Eosinophilic cystitis

    DEFF Research Database (Denmark)

    Mosholt, Karina Sif Søndergaard; Dahl, Claus; Azawi, Nessn Htum

    2014-01-01

    frequency, dysuria, urgency, pain and haematuria. Common clinical findings were presence of bladder mass, peripheral eosinophilia and thickened bladder wall. A variety of medical treatments were used, most frequently steroids, antibiotics and antihistamines. Recurrence occurred in patients on tapering...... or discontinuing prednisone, among other reasons. There is no consensus about the treatment of EC, but In light of our findings in this review, the treatment of choice in our department will be tapered prednisone over 6-8 weeks in combination with antihistamine....

  20. Rosai-Dorfman Disease with nodal and extranodal involvements: A case report

    Directory of Open Access Journals (Sweden)

    Mehri Najafi-Sani

    2011-01-01

    Full Text Available Rosai-Dorfman disease (RDD is a rare lymphoproliferative disorder with nodal and extranodal involvements. Here we report a case of RDD in a 15-year-old female who presented with epigastric pain, fatigue, Raynaud phenomenon in fingers, submandibular lymphadenopathy, proptosis, hepatosplenomegaly, and round shape painless patches on the extensor surfaces. Histological examination of the submandibular lymph nodes and skin biopsy demonstrated evidences of RDD. Patient was treated with prednisone and thereafter, with azathioprine. After one year, prednisone was discontinued and all of the symptoms and signs, except proptosis, were resolved. This report highlights the extranodal manifestations of RDD. The presentation, differential diagnosis, and treatment are discussed.

  1. Clinical pharmacology in the UK, c. 1950–2000: industry and regulation

    OpenAIRE

    2008-01-01

    Clinical pharmacology in the UK in the 1950s and 1960s was an exciting profession. Many important new drugs were developed and brought to market and a more systematic knowledge of drug effects in humans was needed, as well as ensuring the safety and efficacy of new and existing drugs, especially following the unexpected problems arising from the use of thalidomide. This Witness Seminar followed an earlier meeting on the history of the general development of clinical pharmacology and focuses o...

  2. Prenatal Effects of Exposure to High-Level Noise,

    Science.gov (United States)

    1982-03-01

    major variables: * The genotype of the species and perhaps of the individual; * The developmental stage ( gestational age) at which the ex- posure occurs...the best documented are maternal syphilis , maternal rubella, maternal toxoplasmosis, and maternal ingestion of thalidomide (see Bergsma, 1973, for...made measurements of one pregnant woman at 37 weeks of gestation . External sounds -- pure tones of 200, 500, 1000, 2000, and 4000 Hz -- were delivered

  3. Bortezomib Prescription Pattern for the Treatment of Multiple Myeloma by Hematologists in Nigeria

    Directory of Open Access Journals (Sweden)

    Kaladada I. Korubo

    2017-10-01

    Full Text Available Purpose: Novel therapy has dramatically changed the outcome of patients with myeloma. Current National Comprehensive Cancer Network guidelines give bortezomib-based combinations a central role in the management of multiple myeloma (MM. The aim of this survey is to assess the use of bortezomib for the treatment of MM by hematologists practicing in Nigeria. Materials and Methods: This is a cross-sectional observational survey. A structured, prevalidated questionnaire was self-administered to different cadres of hematologists. Data collected were analyzed using SPSS software version 21 (IBM, Chicago, IL. Results: There were 54 respondents from 24 centers across the country. The most frequently used drugs for first-line therapy were thalidomide (66.7%, dexamethasone (54.2%, and bortezomib (48%, and a combination of bortezomib, thalidomide, and dexamethasone (16.7% was the most frequently used first-line regimen. Of the 54 hematologists, 39 (72.2% had prescribed bortezomib previously; no one had used bortezomib as monotherapy. Drug unavailability (86.7% and cost (46.7% were the major reasons for those who had not prescribed bortezomib. Approximately 56.4% of responders had patients who had experienced adverse effects, of which neuropathy was the most common (86.3%. Conclusion: Bortezomib, thalidomide, and dexamethasone was the most frequently used first-line regimen to treat myelomatosis. Thalidomide and dexamethasone were the most frequently used drugs in myeloma treatment. Despite poor access to health care, coupled with the high cost and poor availability of bortezomib in our low- or middle-income country, those who prescribed bortezomib did so frequently (in more than half of their patients.

  4. THE TREATMENT OF MULTIPLE MYELOMA PATIENTS NOT ELIGIBLE FOR ASCT

    Directory of Open Access Journals (Sweden)

    Paul Richardson

    2010-05-01

    With the arrival of novel agents, including the first–in-class proteasome inhibitor, bortezomib, and the immunomodulatory agents, thalidomide and lenalidomide, a shift in the management of older patients and/or those not eligible for transplantation has taken place. Increasingly, novel agents are now being incorporated into therapy, based on the positive findings from clinical trials in this setting, and outcomes have improved accordingly.

  5. Standardization of a method to study angiogenesis in a mouse model

    Directory of Open Access Journals (Sweden)

    DAVID FEDER

    2013-01-01

    Full Text Available In the adult organism, angiogenesis is restricted to a few physiological conditions. On the other hand, uncontrolled angiogenesis have often been associated to angiogenesis-dependent pathologies. A variety of animal models have been described to provide more quantitative analysis of in vivo angiogenesis and to characterize pro- and antiangiogenic molecules. However, it is still necessary to establish a quantitative, reproducible and specific method for studies of angiogenesis factors and inhibitors. This work aimed to standardize a method for the study of angiogenesis and to investigate the effects of thalidomide on angiogenesis. Sponges of 0.5 x 0.5 x 0.5 cm were implanted in the back of mice groups, control and experimental (thalidomide 200 mg/K/day by gavage. After seven days, the sponges were removed. The dosage of hemoglobin in sponge and in circulation was performed and the ratio between the values was tested using nonparametric Mann-Whitney test. Results have shown that sponge-induced angiogenesis quantitated by ratio between hemoglobin content in serum and in sponge is a helpful model for in vivo studies on angiogenesis. Moreover, it was observed that sponge-induced angiogenesis can be suppressed by thalidomide, corroborating to the validity of the standardized method.

  6. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation and or Treated with Immunomodulatory Agents

    Directory of Open Access Journals (Sweden)

    Alhossain A. Khalafallah

    2010-04-01

    Full Text Available There are few data available regarding the prevalence of infection in multiple myeloma (MM patients in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide or post autologous stem cell transplantation.  We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequently to thalidomide, because of disease progression and 22 patients underwent autologous stem cell transplantation.   The median age was 64 years (range 37-86, with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe infections. All patients except 3 received intravenous immunoglobulin (IVIG therapy with a significant decline of the rate of infection thereafter. Our analysis shows that IVIG appears to be an effective strategy to prevent infection in MM patients. Further studies to confirm these findings are warranted.

  7. Molecular Action of Lenalidomide in Lymphocytes and Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Jessica M. McDaniel

    2012-01-01

    Full Text Available The immunomodulatory agent, lenalidomide, is a structural analogue of thalidomide approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS and multiple myeloma (MM. This agent is also currently under active investigation for the treatment of chronic lymphocytic leukemia (CLL and non-Hodgkin’s lymphoma (NHL, as well as in drug combinations for some solid tumors and mantle cell lymphoma (MCL. Although treatment with lenalidomide has translated into a significant extension in overall survival in MM and MDS and has superior safety and efficacy relative to thalidomide, the mechanism of action as it relates to immune modulation remains elusive. Based on preclinical models and clinical trials, lenalidomide, as well as other structural thalidomide derivatives, enhances the proliferative and functional capacity of T-lymphocytes and amplifies costimulatory signaling pathways that activate effector responses and suppress inflammation. This paper summarizes our current understanding of T- and natural killer (NK cell pathways that are modified by lenalidomide in hematopoietic neoplasms to inform future decisions about potential combination therapies.

  8. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study.

    Science.gov (United States)

    Vogl, Thomas J; Koch, Silvia A; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-06-01

    Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study. Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients' life quality was assessed using four-point scale questionnaires. Of 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6-41.0 months). Median progression-free survival time was 12.4 months (range 0.9-41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients' self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment. PIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  9. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    International Nuclear Information System (INIS)

    Vogl, Thomas J.; Koch, Silvia A.; Lotz, Gösta; Gebauer, Bernhard; Willinek, Winfried; Engelke, Christoph; Brüning, Roland; Zeile, Martin; Wacker, Frank; Vogel, Arndt; Radeleff, Boris; Scholtz, Jan-Erik

    2017-01-01

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  10. Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.de; Koch, Silvia A., E-mail: silvia.koch@web.de [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany); Lotz, Gösta, E-mail: goesta.lotz@kgu.de [University Hospital Frankfurt, Department of Anesthesiology, Intensive-Care Medicine and Pain Therapy (Germany); Gebauer, Bernhard, E-mail: bernhard.gebauer@charite.de [Universitätsmedizin Berlin, Department of Diagnostic and Interventional Radiology, Campus Charité Mitte (Germany); Willinek, Winfried, E-mail: w.willinek@bk-trier.de [Brüderkrankenhaus Trier, Department of Diagnostic and Interventional Radiology (Germany); Engelke, Christoph, E-mail: engelke@ekweende.de [Evangelisches Krankenhaus Göttingen-Weende gGmbH, Department of Diagnostic and Interventional Radiology (Germany); Brüning, Roland, E-mail: r.bruening@asklepios.com; Zeile, Martin, E-mail: m.zeile@asklepios.com [Asklepios Klinik Barmbek, Department of Diagnostic and Interventional Radiology (Germany); Wacker, Frank, E-mail: wacker.frank@mh-hannover.de [Medizinische Hochschule Hannover, Department of Diagnostic and Interventional Radiology (Germany); Vogel, Arndt, E-mail: vogel.arndt@mh-hannover.de [Medizinische Hochschule Hannover, Department of Gastroenterology, Hepatology and Endocrinology (Germany); Radeleff, Boris, E-mail: boris.radeleff@med.uni-heidelberg.de [Heidelberg University Hospital, Department of Diagnostic and Interventional Radiology (Germany); Scholtz, Jan-Erik, E-mail: janerikscholtz@gmail.com [University Hospital Frankfurt, Department of Diagnostic and Interventional Radiology (Germany)

    2017-06-15

    PurposePercutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study.Materials and MethodsBetween 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients’ life quality was assessed using four-point scale questionnaires.ResultsOf 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6–41.0 months). Median progression-free survival time was 12.4 months (range 0.9–41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients’ self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment.ConclusionPIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

  11. Evaluation of the anticancer potential of six herbs against a hepatoma cell line

    Directory of Open Access Journals (Sweden)

    Weerapreeyakul Natthida

    2012-06-01

    Full Text Available Abstract Background Six herbs in the Plant Genetics Conservation Project that have been used as complementary medicines were chosen on the basis of their medicinal value, namely Terminalia mucronata, Diospyros winitii, Bridelia insulana, Artabotrys harmandii, Terminallia triptera, and Croton oblongifolius. This study aims to evaluate the potential anticancer activity of 50% ethanol-water extracts of these six herbs. Methods Fifty percent ethanol-water crude extracts of the six herbs were prepared. The cytotoxicity of the herbal extracts relative to that of melphalan was evaluated using a hepatoma cell line (HepG2, and examined by neutral red assays and apoptosis induction by gel electrophoresis and flow cytometry after 24 h. Results A significant difference was found between the cytotoxicity of the 50% ethanol-water crude extracts and melphalan (P = 0.000. The 50% ethanol-water crude extracts of all six herbs exhibited cytotoxicity against HepG2 cells, with IC50 values ranging from 100 to 500 μg/mL. The extract of T. triptera showed the highest cytotoxicity with an IC50 of 148.7 ± 12.3 μg/mL, while melphalan had an IC50 of 39.79 ± 7.62 μg/mL. The 50% ethanol-water crude extracts of D. winitii and T. triptera, but not A. harmandii, produced a DNA ladder. The 50% ethanol-water crude extracts of D. winitii, T. triptera, and A. harmandii induced apoptosis detected by flow cytometry. Conclusion The 50% ethanol-water crude extracts of D. winitii, T. triptera, and A. harmandii showed anticancer activity in vitro.

  12. Vorinostat synergizes with ridaforolimus and abrogates the ridaforolimus-induced activation of AKT in synovial sarcoma cells.

    Science.gov (United States)

    Morgan, Sherif S; Cranmer, Lee D

    2014-11-18

    Curative treatments for patients with metastatic synovial sarcoma (SS) do not exist, and such patients have a poor prognosis. We explored combinations of molecularly-targeted and cytotoxic agents to identify synergistic treatment combinations in SS cells. Two SS cell lines (HS-SY-II and SYO-I) were treated with single agents or combinations of molecularly targeted therapies (HDAC inhibitor, vorinostat; mTOR inhibitor, ridaforolimus) and cytotoxic agents. After 72 hours, cell viability was measured using the MTS cell proliferation assay. Combination Indices (CI) were calculated to determine whether each combination was synergistic, additive, or antagonistic. Western Blot analysis assessed alterations in total and phospho-AKT protein levels in response to drug treatment. We determined the single-agent IC50 for ridaforolimus, vorinostat, doxorubicin, and melphalan in HS-SY-II and SYO-I. Synergism was apparent in cells co-treated with ridaforolimus and vorinostat: CI was 0.28 and 0.63 in HS-SY-II and SYO-I, respectively. Ridaforolimus/doxorubicin and ridaforolimus/melphalan exhibited synergism in both cell lines. An additive effect was observed with combination of vorinostat/doxorubicin in both cell lines. Vorinostat/melphalan was synergistic in HS-SY-II and additive in SYO-I. Western blot analysis demonstrated that ridaforolimus increased pAKT-ser473 levels; this effect was abrogated by vorinostat co-treatment. The combination of ridaforolimus and vorinostat demonstrates in vitro synergism in SS. Addition of vorinostat abrogated ridaforolimus-induced AKT activation. Since AKT activation is a possible mechanism of resistance to mTOR inhibitors, adding vorinostat (or another HDAC inhibitor) may be a route to circumvent AKT-mediated resistance to mTOR inhibitors.

  13. GWAS of 972 autologous stem cell recipients with multiple myeloma identifies 11 genetic variants associated with chemotherapy-induced oral mucositis

    DEFF Research Database (Denmark)

    Coleman, Elizabeth Ann; Lee, Jeannette Y; Erickson, Stephen W

    2015-01-01

    PURPOSE: High-dose chemotherapy and autologous stem cell transplant (ASCT) to treat multiple myeloma (MM) and other cancers carries the risk of oral mucositis (OM) with sequelae including impaired nutritional and fluid intake, pain, and infectious complications. As a result of these problems...... protocol, baseline estimated glomerular filtration rate, and melphalan dose along with baseline serum albumin and female gender predicted 43.6 % of grades 2-4 OM cases. Eleven SNPs located in or near matrix metalloproteinase 13, JPH3, DHRS7C, CEP192, CPEB1/LINC00692, FBN2, ALDH1A1, and DMRTA1/FLJ35282 were...

  14. Vindesine in plasma cell tumors.

    Science.gov (United States)

    Salvagno, L; Paccagnella, A; Chiarion Sileni, V; De Besi, P; Frizzarin, M; Casara, D; Fiorentino, M V

    1985-12-31

    Twenty-one patients with plasma cell tumors received vindesine (VDS) at the dose of 3 mg/m2 i.v. on day 1 plus prednisone at the dose of 100 mg p.o. from day 1 to 5, recycling every 8 days 3 times and then every 10-12 days. In 3 patients with gastric or duodenal ulcer prednisone was not administered. All but one patient were heavily pretreated and resistant to M-2 regimen. Overall there were 4 objective responses (19%): 2 among 15 patients (13%) with multiple myeloma and 2 among 6 patients (33%) with extramedullary plasmacytoma (EMP). The responses lasted for 2, 12, 15 and 48+ months. One previously untreated EMP patient received VDS without prednisone and obtained a complete long-lasting remission. The association of VDS with high-dose prednisone seems to have some activity in plasma cell tumors; probably in multiple myeloma the objective responses are due to the high dose of cortisone rather than to VDS. On the contrary, in EMP patients, VDS may be an active agent, even if administered without cortisone.

  15. ِAssessment of lupus nephritis by measuring urinary retinol binding ...

    African Journals Online (AJOL)

    Ehab

    Background: Renal disease is a common manifestation of systemic lupus erythematosus (SLE). Both glomerular and ... Objective: The study was aimed to assess the urinary RPB level in SLE patients with and without evidence of .... Twenty-one patients were receiving prednisone (1-2 mg/Kg/day) either alone (n= 13) or.

  16. Tumor necrosis at FDG-PET is an independent predictor of outcome in diffuse large B-cell lymphoma

    NARCIS (Netherlands)

    Adams, Hugo J A; De Klerk, John M H; Fijnheer, Rob; Heggelman, Ben G F; Dubois, Stefan V.; Nievelstein, Rutger A J; Kwee, Thomas C.

    2016-01-01

    Purpose To determine the prognostic performance of tumor necrosis at FDG-PET in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who are treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Materials and methods 108 patients with

  17. Alternative modes of cyclophosphamide and azathioprine therapy in lupus nephritis

    NARCIS (Netherlands)

    Dinant, H. J.; Decker, J. L.; Klippel, J. H.; Balow, J. E.; Plotz, P. H.; Steinberg, A. D.

    1982-01-01

    Forty-one patients with systemic lupus erythematosus and glomerulonephritis were studied in a randomized drug trial. Thirteen patients received prednisone only (Group 1), 16 received oral cyclophosphamide and oral azathioprine (1 mg/kg body weight . d of each initially) (Group 2), and 12 were given

  18. Sirolimus-induced lymphoedema

    African Journals Online (AJOL)

    prednisolone and byclosporine for induction immune suppression and then triple therapy with cyclosporine, ... receiving tacrolimus, MMF and prednisone for immune suppression, and his graph function has remained .... Nonetheless, we needed to consider the psychological effect of his deformity and the effect it might have ...

  19. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group

    DEFF Research Database (Denmark)

    Pfreundschuh, Michael; Kuhnt, Evelyn; Trümper, Lorenz

    2011-01-01

    The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-ter...

  20. chronic Lymphocytic Leukemia (cLL)

    African Journals Online (AJOL)

    Tablets Diclofenac for pain relief, Capsules. Amoxycillin to treat the chest infection were prescribed. Prednisone and Chlorambucil was prescribed to treat CLL. DIscUssIOn. The natural history of CLL is heterogeneous. Some patients die rapidly, within 2-3 years of diagnosis, the majority of patients live 5-10 years. During the.

  1. Lymphoedème unilatéral du membre supérieur au cours d'une ...

    African Journals Online (AJOL)

    exceptionnellement signalés au cours de la polyarthrite rhumatoïde (PR). Nous rapportons l'observation d'une patiente âgée de 63 ans ayant une PR diagnostiquée depuis dix ans et traitée par hydroxychloroquine, prednisone et méthotrexate avec une ...

  2. Hypermethylation of DAPK1 is an independent prognostic factor predicting survival in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Kristensen, Lasse Sommer; Asmar, Fazila; Dimopoulos, Konstantinos

    2014-01-01

    Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin's lymphoma. Improvements in overall survival have been observed with the introduction of rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), however, prognostic markers...

  3. FDA Expands Abiraterone Approval for Prostate Cancer

    Science.gov (United States)

    The FDA has expanded the approval of abiraterone (Zytiga) to treat men with metastatic prostate cancer. The agency approved abiraterone, in combination with prednisone, for men whose cancer that is responsive to hormone-blocking treatments (also known as castration-sensitive) and is at high risk of progressing.

  4. Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Nielsen, Ole Haagen; Ainsworth, Mark Andrew

    2013-01-01

    A 35-year-old man presents with an exacerbation of Crohn's ileocolitis. He received a diagnosis of Crohn's disease 8 years ago and has been treated on three previous occasions with prednisone. Because of a recurrent need for glucocorticoids, treatment with azathioprine (150 mg per day) was starte...

  5. Intraperitoneal granulomatous foreign body reaction after accidental perforation of the abdominal wall. Case report

    DEFF Research Database (Denmark)

    Lanng, C; Winther-Nielsen, H; Hougen, H P

    2013-01-01

    After an accidental perforation by a wooden stake of the abdominal wall and distal ileum a 28-year-old man developed an aggressive granulomatous foreign body reaction of the greater omentum with high fever and abdominal pain. The patient was cured by omental resection and prednisone treatment....

  6. The management of nephrotic syndrome in children | Hodson ...

    African Journals Online (AJOL)

    Data from RCTs supports the use of alkylating agents (cyclophosphamide, chlorambucil), cyclosporin and levamisole in these children to achieve prolonged periods of remission after induction of remission with prednisone. Steroid resistant nephrotic syndrome is more common in Africa. Few therapies are effective. In such ...

  7. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy

    NARCIS (Netherlands)

    Harland, S.; Staffurth, J.; Molina, A.; Hao, Y.; Gagnon, D.D.; Sternberg, C.N.; Cella, D.; Fizazi, K.; Logothetis, C.J.; Kheoh, T.; Haqq, C.M.; Bono, J.S. de; Scher, H.I.; Mulders, P.F.; et al.,

    2013-01-01

    BACKGROUND: In a recent randomised, double-blind, phase III clinical trial among 1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly prolong overall survival compared with prednisone alone.

  8. Blistering rash in a young male child | Sanders | South African ...

    African Journals Online (AJOL)

    ... lower limbs. He had visited three different general practitioners prior to presentation and had been given several drugs and ointments, including three different classes of antibiotics. During his admission, the diagnosis of linear IgA bullous dermatitis was made. Dapsone and prednisone were given and he recovered well.

  9. Ernstige anemie door infectie met het Humaan parvovirus B19 bij een patiënt met een auto-immuun-hemolytische anemie en een B-cel-non-hodgkinlymfoom

    NARCIS (Netherlands)

    van Dam, I. E.; Kater, A. P.; Hart, W.; van den Born, B. J. H.

    2008-01-01

    A 65-year-old man with a 15-year history of 'leukemicised' low-grade lymphocytic B-cell non-Hodgkin lymphoma with a low-titre of IgM kappa paraprotein was admitted with severe anaemia and reticulocytopenia. Treatment with prednisone and chlorambucil had been started two weeks earlier because of a

  10. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using br...

  11. Results and conclusions of the European intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma

    NARCIS (Netherlands)

    Landmann, E. (Eva); B. Burkhardt (Birgit); M. Zimmermann (Martin); Meyer, U. (Ulrike); Woessmann, W. (Wilhelm); W. Klapper (Wolfram); G. Wrobel (Grazyna); A. Rosolen (Angelo); Pillon, M. (Marta); G. Escherich (Gabriele); A. Attarbaschi (Andishe); A. Beishuizen (Auke); K. Mellgren (Karin); R.F. Wynn (Robert F.); R. Ratei (Richard); Plesa, A. (Adriana); M. Schrappe (Martin); A. Reiter (Alfred); C. Bergeron (Christophe); C. Patte (Catherine); Y. Bertrand (Yves)

    2017-01-01

    textabstractIn the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with

  12. Muscular visualisation on a bone scan in paraneoplastic ...

    African Journals Online (AJOL)

    Immunosuppressive therapy based on oral prednisone and endoxan followed by molecular targeted therapy (Herceptin and taxotere) improved the myositis and cutaneous eruption. Tree months later, creatine kinase level and muscular uptake of 99mTc-MDP dramatically decreased (B). Pan African Medical Journal 2016; ...

  13. Past and Future Prospects of Orthoptic Liver Transplantation

    OpenAIRE

    Starzl, Thomas E.; Klintmalm, Goran B. G.; Iwatsuki, Shunzaburo; Fernandez-Bueno, Carlos

    1981-01-01

    The hopes for liver transplantation have been increased by experience with the new immunosuppresive drug cyclosporin A. Optimal therapy with cyclosporin A has required steroid therapy, but the amounts of prednisone used have been a small fraction of those used in the past.

  14. Hypercalcemia due to Primary Hepatic Lymphoma

    Directory of Open Access Journals (Sweden)

    Andrew Hsu

    2016-01-01

    Full Text Available A 65-year-old female with a history of mixed connective tissue disease and pulmonary fibrosis on azathioprine, hydroxychloroquine, and prednisone (osteoporosis on teriparatide presented with a 1-month history of hypercalcemia. After discontinuation of teriparatide, the patient’s hypercalcemia persisted. Further evaluation revealed primary hepatic lymphoma as the source of her hypercalcemia.

  15. Crusted scabies in a chid with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Nurimar C.F. Wanke

    1992-03-01

    Full Text Available A child with systemic lupus erythematosus who has been treated with prednisone for three years, developed crusted scabies. Scrapings from lesions revealed Sarcoptes scabiei adult mites mad eggs. The patient died with septicemia and renal failure soon after starting topical 20% sulfur. A marked improvement was observed in the cutaneous lesions.

  16. De behandeling van de idiopathische facialisverlamming

    NARCIS (Netherlands)

    Enting, R H; Lensing, A W; de Visser, B W

    1998-01-01

    Current drug treatment of Bell's palsy often consists of prednisone for patients with a complete paralysis. Since it was demonstrated that herpes simplex plays a role in the pathogenesis of Bell's palsy, antiviral therapy may become the treatment of choice. Six randomized controlled trials comparing

  17. hy viral hepatitis?

    African Journals Online (AJOL)

    randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional. Therapy Group. N Engl J Med 1990; 323: 295-301. 14. Ncayiyana DJ. Coming to grips with the future of health care - the ANC National. Health Plan. 5 Air Med J 1994; ...

  18. Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients

    DEFF Research Database (Denmark)

    Olgaard, K; Storm, Tina; van Wowern, N

    1992-01-01

    The long-term effects of high dose steroid treatment with either prednisone (PDN) or deflazacort (DFZ) were examined on various parts of the skeleton in 29 patients with nephrotic syndrome. All had normal skeleton at the start of the steroid treatment. At the beginning, PDN was given as 80 mg/day...

  19. Urinary albumin and beta 2-microglobulin excretion rates in patients with systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Parving, H H; Sørensen, S F; Mogensen, C E

    1980-01-01

    prednisone, 5-20 mg/day. None of the patients had proteinuria as judged by the "Albustix" test, and all had normal serum creatinine. The daily urinary albumin and beta 2-microglobulin excretion rates were nearly the same as those previously found by us in 27 adult control subjects with a mean age of 44 years...

  20. Salvage therapy of progressive and recurrent Hodgkin's disease: results from a multicenter study of the pediatric DAL/GPOH-HD study group.

    NARCIS (Netherlands)

    Schellong, G.; Dorffel, W.; Claviez, A.; Korholz, D.; Mann, G.; Scheel-Walter, H.G.; Bökkerink, J.P.M.; Riepenhausen, M.; Luders, H.; Potter, R.; Ruhl, U.

    2005-01-01

    PURPOSE: To evaluate a salvage therapy (ST-HD-86) for patients with progressive and relapsed Hodgkin's disease after primary treatment in the pediatric DAL/GPOH studies. The essential chemotherapeutic regimens were ifosfamide, etoposide, and prednisone (IEP) and doxorubicin, bleomycin, vinblastine,

  1. CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Doorduijn, JK; van der Holt, B; van Imhoff, GW; van der Hem, KG; Kramer, MHH; van Oers, MHJ; Ossenkoppele, GJ; Verdonck, LF; Verhoef, GEG; Steijaert, MMC; Buijt, I.; Uyl-de Groot, CA; van Agthoven, M; Mulder, AH; Sonneveld, P; Schaafsma, M.

    2003-01-01

    Purpose : To investigate whether the relative close-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

  2. CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Doorduijn, J. K.; van der Holt, B.; van Imhoff, G. W.; van der Hem, K. G.; Kramer, M. H. H.; van Oers, M. H. J.; Ossenkoppele, G. J.; Schaafsma, M. R.; Verdonck, L. F.; Verhoef, G. E. G.; Steijaert, M. M. C.; Buijt, I.; Uyl-de Groot, C. A.; van Agthoven, M.; Mulder, A. H.; Sonneveld, P.

    2003-01-01

    PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

  3. Mitral and aortic regurgitation in Behçet's syndrome.

    OpenAIRE

    Peńa, J M; Garcia-Alegria, J; Garcia-Fernandez, F; Arnalich, F; Barbado, F J; Vazquez, J J

    1985-01-01

    A 35-year-old man with definite Behçet's disease developed acute mitral and aortic regurgitation. Valvular disease, we believed, was another manifestation of this disease. Cardiac involvement in Behçet's disease and the role of prednisone therapy are discussed.

  4. Addition of rituximab to chemotherapy overcomes the negative prognostic impact of cyclin E expression in diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Frei, E; Visco, C; Xu-Monette, Z Y

    2013-01-01

    High levels of cyclin E (CCNE) are accompanied by shorter survival in cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (CHOP)-treated diffuse large B-cell lymphomas (DLBCL), independent of the international prognostic index (IPI). Data on the prognostic role of CCNE in the 'rituximab...

  5. Acute effects of etidronate on glucocorticoid-induced bone degradation

    NARCIS (Netherlands)

    A. Struijs (Ard); A. Smals; S.A. de Witte; W.H. Hackeng; H. Mulder (Hans)

    2000-01-01

    textabstractOBJECTIVES: To study the acute short-term effects on the biochemical parameters of calcium and bone homeostasis in post-menopausal women treated with a high dose of prednisone alone or with additional etidronate, before and during 5 days of treatment.

  6. an unusual presentation of acute lymphoblastic leukaemia with peri ...

    African Journals Online (AJOL)

    2013-06-11

    Jun 11, 2013 ... history and progression was later reported by Chia et al in 1973, (12). In this case we have presented, peri-cardial effusion did not reoccur most likely because of prednisone which was incorporated in the initial treatment after she presented with tamponade. In conclusion, we report a very unusual case of.

  7. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide

    NARCIS (Netherlands)

    Beckers, Marielle M.; Huls, Gerwin

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  8. Therapy refractory angioimmunoblastic T-cell lymphoma in complete remission with lenalidomide.

    NARCIS (Netherlands)

    Beckers, M.M.; Huls, G.A.

    2013-01-01

    The prognosis of therapy refractory angioimmunoblastic lymphoma (AITL) is very poor. In this report we describe a patient with AITL refractory to 2 lines of chemotherapy. He was treated with lenalidomide 15 mg continuously and prednisone. After 2 yr follow-up, the patient has no detectable disease.

  9. Repository corticotropin for Chronic Pulmonary Sarcoidosis.

    Science.gov (United States)

    Baughman, Robert P; Sweiss, Nadera; Keijsers, Ruth; Birring, Surinder S; Shipley, Ralph; Saketkoo, Lesley Ann; Lower, Elyse E

    2017-06-01

    The dose of repository corticotropin (RCI) and need for a loading dose in sarcoidosis patients receiving chronic corticosteroids are unclear. We performed a single-blind prospective study, comparing two doses of RCI in sarcoidosis. Chronic pulmonary sarcoidosis patients receiving prednisone therapy with deterioration by 5% in FVC in the previous year were studied. RCI was administered subcutaneously at a loading dose of 80 units RCI for 10 days. Patients were randomized at day 14 to receive either 40- or 80-unit RCI twice a week. The dose of prednisone was modified by the clinician who was blinded to the patient's dosage of RCI. Sixteen patients completed the full 24 weeks of the study. At week 24, there was a decrease in the dose of prednisone, and improvements in DLCO, King's Sarcoidosis Questionnaire health status and fatigue score. There was no significant change in FVC % predicted. For the PET scan, there was a significant fall in the standard uptake value (SUV) of the lung lesions. Only 3/8 patients remained on 80 units RCI for full 24 weeks. There was no significant difference in the response to therapy for those treated with 40- versus 80-unit RCI. Repository corticotropin treatment was prednisone-sparing and associated with significant improvement in DLCO, PET scan, and patient-reported outcome measures. A dose of 40-unit RCI twice a week was as effective as 80-unit RCI and was better tolerated.

  10. Local Experience in the Treatment of Acute Non-Lymphoblastic ...

    African Journals Online (AJOL)

    Seventy-six patients suffering from various forms of acute non-lymphoblastic leukaemia were seen at the Johannes- burg Hospital over an 8-year period. During this time various forms of therapy were used. Results with 6-mer- captopurine and prednisone were very poor, with less than. 10% of patients achieving complete ...

  11. Abiraterone Acetate for the Treatment of Chemotherapy-Naive Metastatic Castration-Resistant Prostate Cancer : An Evidence Review Group Perspective of an NICE Single Technology Appraisal

    NARCIS (Netherlands)

    Ramaekers, Bram L. T.; Riemsma, Rob; Tomini, Florian; van Asselt, Thea; Deshpande, Sohan; Duffy, Steven; Armstrong, Nigel; Severens, Johan L.; Kleijnen, Jos; Joore, Manuela A.

    The National Institute for Health and Care Excellence (NICE) invited Janssen, the company manufacturing abiraterone acetate (AA; tradename Zytiga(A (R))), to submit evidence for the clinical and cost effectiveness of AA in combination with prednisone/prednisolone (AAP) compared with watchful waiting

  12. Reactivation of cutaneous and mucocutaneous tegumentary leishmaniasis in rheumatoid arthritis patients: an emerging problem?

    Directory of Open Access Journals (Sweden)

    Regina Maia de Souza

    Full Text Available ABSTRACT Rheumatoid arthritis (RA is a chronic condition that is frequent in patients living in tropical areas exposed to leishmaniasis. RA therapy involves immunosuppressant drugs such as methotrexate (MTX, monoclonal antibodies (mAbs and prednisone. We report an unusual presentation of cutaneous (CL or mucocutaneous leishmaniasis (ML in RA patients from an endemic area of leishmaniasis. A 51-year-old woman noted a cutaneous ulcer on her left ankle during MTX and prednisone RA therapy. Initially diagnosed as a venous stasis ulcer, the aspirate of the injury revealed the presence of Leishmania DNA. A 73-year-old woman presenting non-ulcerated, infiltrated and painful erythematous nodules inside her nostrils while receiving MTX, anti-TNF mAb, and prednisone for RA, had also the aspirate of injuries showing the presence of Leishmania DNA. Both patients healed after the therapy with liposomal amphotericin. The RA therapy has changed to low-dose prednisone, without further reactivation episodes. Both cases suggest that CL or ML can reactivate after administration of an immunosuppressant for RA treatment. Therefore, immunosuppressive treatments for RA should be carefully prescribed in patients from endemic areas or with a history of CL and ML.

  13. Download

    African Journals Online (AJOL)

    abp

    2015-06-24

    Jun 24, 2015 ... left ankle. Skin biopsy showed at the back of the right hand an aspect of PG and at the infiltrated plaques of the ankle an aspect of SS. Prednisone was started with improvement of the skin lesions and a recovery condition. The combination of PG and SS has already been described in cases of hematologic ...

  14. Cognitive Function in Children with Lupus Nephritis: A Cross-Sectional Comparison with Children with Other Glomerular Chronic Kidney Diseases.

    Science.gov (United States)

    Knight, Andrea; Kogon, Amy J; Matheson, Matthew B; Warady, Bradley A; Furth, Susan L; Hooper, Stephen R

    2017-10-01

    To identify factors contributing to cognitive impairment in children with lupus nephritis. A cross-sectional analysis of a large multicenter national cohort of children with chronic kidney disease (CKD) using standardized measures to determine baseline neuropsychiatric function and health-related quality of life (HRQoL) in children with lupus nephritis (n = 34), and to compare baseline function with that in children with other forms of glomerular CKD (gCKD; n = 171). We used inverse probability weighting via a logistic model for propensity score analysis to achieve balance between children with lupus nephritis and those with other glomerular causes of CKD, adjusting for known confounders. We used linear regression models to compare neurocognitive outcomes between exposure groups, adjusting for current prednisone use and testing for an interaction between current prednisone use and lupus nephritis, and to test for an association between cognitive function and HRQoL. Current prednisone use was independently associated with worse attention (P children with lupus nephritis on prednisone (P = .047). Better parent-reported HRQoL was associated with better visual memory (P = .01), and better child-reported HRQoL was associated with better attention (P Children with lupus nephritis have comparable or better cognitive function than their peers with other gCKDs, which is reassuring given the multiorgan and lifelong complications associated with lupus. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Author Details

    African Journals Online (AJOL)

    Ning, L. Vol 12, No 3 (2015) - Articles Chinese herbal medicine and prednisone increase proportion of splenic CD4+CD25-FOXP3+ cells and alleviate glomerular lesion in MRL/LPRmice. Abstract PDF. ISSN: 0189-6016. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

  16. Growth hormone treatment in growth-retarded adolescents after renal transplant

    NARCIS (Netherlands)

    Hokken-Koelega, A. C.; Stijnen, T.; de Ridder, M. A.; de Muinck Keizer-Schrama, S. M.; Wolff, E. D.; de Jong, M. C.; Donckerwolcke, R. A.; Groothoff, J. W.; Blum, W. F.; Drop, S. L.

    1994-01-01

    Growth failure is a psychosocial problem for many patients who have undergone renal transplantation. 18 adolescents (mean age 15.6, range 11.3-19.5) with severe growth retardation after renal transplantation were treated with biosynthetic growth hormone (GH) for 2 years. All received prednisone,

  17. Rituximab for the Treatment of Relapses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis

    NARCIS (Netherlands)

    Miloslavsky, E. M.; Specks, U.; Merkel, P. A.; Seo, P.; Spiera, R.; Langford, C. A.; Hoffman, G. S.; Kallenberg, C. G. M.; Clair, E. W. St.; Tchao, N. K.; Viviano, L.; Ding, L.; Ikle, D.; Villarreal, M.; Jepson, B.; Brunetta, P.; Allen, N. B.; Fervenza, F. C.; Geetha, D.; Keogh, K.; Kissin, E. Y.; Monach, P. A.; Peikert, T.; Stegeman, C.; Ytterberg, S. R.; Stone, J. H.

    2014-01-01

    Objective. Disease relapses are frequent in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re-treated with rituximab (RTX) and prednisone for severe disease relapses. Methods. The Rituximab in AAV trial

  18. Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis: A single-center, retrospective study of 70 patients.

    Science.gov (United States)

    Ly, Kim Heang; Dalmay, François; Gondran, Guillaume; Palat, Sylvain; Bezanahary, Holy; Cypierre, Anne; Fauchais, Anne-Laure; Liozon, Eric

    2016-10-01

    Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ± 13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should be

  19. Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis

    Science.gov (United States)

    Ly, Kim Heang; Dalmay, François; Gondran, Guillaume; Palat, Sylvain; Bezanahary, Holy; Cypierre, Anne; Fauchais, Anne-Laure; Liozon, Eric

    2016-01-01

    Abstract Although a glucocorticoid (GC)-sparing strategy is needed for patients with giant cell arteritis (GCA) suffering from refractory disease or serious treatment-related complications, evidence of efficacy in this setting of immunosuppressive drugs and biotherapies is lacking. Herein, we evaluated the GC-sparing effects and tolerability of addition of dapsone (DDS) to prednisone therapy in patients with GCA. We retrospectively assessed data on 18 GCA patients who received DDS as a first-line treatment (DDS-1 group) and 52 patients who received it as a second- or third-line treatment for refractory GCA, with or without excessive GC-related toxicity (DDS-2 group). Of these 70 patients, 63 belonged to an inception cohort of 478 patients, whereas the remaining 7 were referred to our department for resistant GCA. In all, 52 patients were assessable for DDS efficacy. The baseline characteristics of the DDS-1 patients were similar to those of 395 GCA patients (control group) who received prednisone alone. DDS-1 patients had a more sustained decrease in GC dose with a lower mean prednisone dose at 12 months, and they comprised higher proportions who achieved GC withdrawal within the first year, who stopped prednisone treatment, and who recovered from GCA (P < 0.001 for each variable). Patients in the DDS-2 group achieved a mean rate of prednisone reduction of 65% and a prednisone dose reduction of 16.9 ± 13.3 mg/d. The monthly decreases in the prednisone dose were 2.4 and 1.25 mg in DDS-1 and DDS-2 patients, respectively. DDS-induced side effects were recorded in 44 (64%) assessable patients. These side effects led to lowering of the DDS dose by 25 mg/d in 11 (16%) patients and permanent cessation of DDS in 14 patients (20%), due to allergic skin rash in 7, agranulocytosis in 2, icteric hepatitis in 2, and excessive hemolysis in 2 patients. DDS is a potent GC-sparing agent in GCA that should be evaluated in prospective studies. However, DDS use should

  20. Late Acute Rejection Occuring in Liver Allograft Recipients

    Directory of Open Access Journals (Sweden)

    Eric M Yoshida

    1996-01-01

    Full Text Available To study the effect of immunosuppressive reduction on the incidence and consequence of late acute rejection (LAR in liver allograft recipients, mean daily prednisone dose, mean cyclosporine A (CsA trough and nadir levels were retrospectively reviewed for the nearest 12-week period preceding six episodes of LAR in five liver allograft recipients (group 1. Results were compared with those from a cohort of 12 liver allograft recipients who did not develop LAR (group 2. LAR was defined as acute rejection occurring more than 365 days post-transplantation. Median follow-up for both groups was similar (504 days, range 367 to 1050, versus 511 days, range 365 to 666, not significant. Mean trough CsA levels were lower in patients with LAR compared with those without (224±66 ng/mL versus 233±49 ng/mL but the difference was not statistically significant. In contrast, mean daily prednisone dose (2.5±1.6 mg/ day versus 6.5±2.9 mg/day, P=0.007 and CsA nadir values (129±60 ng/mL versus 186±40 ng/mL, P=0.03 were significantly lower in patients who developed LAR compared with those who did not. Five of six episodes (83% of LAR occurred in patients receiving less than 5 mg/day of prednisone, versus a single LAR episode in only one of 12 patients (8% receiving prednisone 5 mg/day or more (P=0.004. In all but one instance, LAR responded to pulse methylprednisolone without discernible affect on long term graft function. The authors conclude that liver allograft recipients remain vulnerable to acute rejection beyond the first post-transplant year; and reduction of immunosuppressive therapy, particularly prednisone, below a critical, albeit low dose, threshold increases the risk of LAR.

  1. The impact of steroids, methotrexate, and biologics on clinical and radiographic outcomes in patients with rheumatoid arthritis undergoing fusions at the craniovertebral junction

    Directory of Open Access Journals (Sweden)

    Ryan Khanna

    2015-01-01

    Full Text Available Objective: Rheumatoid arthritis (RA is an inflammatory disease that affects the craniovertebral junction (CVJ. Patients may suffer from atlantoaxial instability (AAI and basilar invagination (BI with variable presentations ranging from pain to quadriparesis. Managing these patients is often challenging due to their chronic use of steroids, methotrexate, and biologics; which impedes bone and wound healing. We report our experience with the surgical management of these patients undergoing fusions at the CVJ. Materials and Methods: We conducted a retrospective study identifying all patients with the diagnosis of RA who underwent spinal fusions at our institution over the past 11 years. A total of 205 patients were identified amongst which 18 patients (8.8% who underwent 20 fusions involving the CVJ. Demographic, clinical, and radiographic data were analyzed. Results: Five patients had AAI and 13 patients had BI. Two patients with C1-2 fusions underwent reoperation: One for pseudoarthrosis and one for BI. The average preoperative Nurick was 1.4 and improved to 0.5 postoperatively (P < 0.001. After conducting analyses stratified by dichotomous preoperative variables, the presence of steroids, methotrexate, biologics, and prednisone dosage less than 7.5 mg did not affect outcomes. Prednisone dosages ≥7.5 mg had significantly smaller improvements in Nurick score compared to patients not on steroids or on prednisone dosages <7.5 mg (0.40 vs 1.36, P = 0.042. Similarly, patients on biologics had significantly smaller improvements in Nurick score compared to patients not on biologics (0.27 vs 1.16, P = 0.038. Conclusion: Fusions at the CVJ in patients with RA on daily prednisone dosages of less than 7.5 mg and/or methotrexate can be performed safely with good outcomes, fusion rates, and acceptable complication profiles. Daily prednisone dosages of more than 7.5 mg or biologics may impact clinical outcomes.

  2. A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis.

    Science.gov (United States)

    Pasnoor, Mamatha; He, Jianghua; Herbelin, Laura; Burns, Ted M; Nations, Sharon; Bril, Vera; Wang, Annabel K; Elsheikh, Bakri H; Kissel, John T; Saperstein, David; Shaibani, J Aziz; Jackson, Carlayne; Swenson, Andrea; Howard, James F; Goyal, Namita; David, William; Wicklund, Matthew; Pulley, Michael; Becker, Mara; Mozaffar, Tahseen; Benatar, Michael; Pazcuzzi, Robert; Simpson, Ericka; Rosenfeld, Jeffrey; Dimachkie, Mazen M; Statland, Jeffrey M; Barohn, Richard J

    2016-07-05

    To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG). We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living. Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%). We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials. This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy. © 2016 American Academy of Neurology.

  3. Targeting proliferating cell nuclear antigen and its protein interactions induces apoptosis in multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Rebekka Müller

    Full Text Available Multiple myeloma is a hematological cancer that is considered incurable despite advances in treatment strategy during the last decade. Therapies targeting single pathways are unlikely to succeed due to the heterogeneous nature of the malignancy. Proliferating cell nuclear antigen (PCNA is a multifunctional protein essential for DNA replication and repair that is often overexpressed in cancer cells. Many proteins involved in the cellular stress response interact with PCNA through the five amino acid sequence AlkB homologue 2 PCNA-interacting motif (APIM. Thus inhibiting PCNA's protein interactions may be a good strategy to target multiple pathways simultaneously. We initially found that overexpression of peptides containing the APIM sequence increases the sensitivity of cancer cells to contemporary therapeutics. Here we have designed a cell-penetrating APIM-containing peptide, ATX-101, that targets PCNA and show that it has anti-myeloma activity. We found that ATX-101 induced apoptosis in multiple myeloma cell lines and primary cancer cells, while bone marrow stromal cells and primary healthy lymphocytes were much less sensitive. ATX-101-induced apoptosis was caspase-dependent and cell cycle phase-independent. ATX-101 also increased multiple myeloma cells' sensitivity against melphalan, a DNA damaging agent commonly used for treatment of multiple myeloma. In a xenograft mouse model, ATX-101 was well tolerated and increased the anti-tumor activity of melphalan. Therefore, targeting PCNA by ATX-101 may be a novel strategy in multiple myeloma treatment.

  4. Total Marrow Irradiation as Part of Autologous Stem Cell Transplantation for Asian Patients with Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Shih-Chiang Lin

    2013-01-01

    Full Text Available To compare the outcomes of melphalan 200 mg/m2 (HDM200 and 8 Gy total marrow irradiation (TMI delivered by helical tomotherapy plus melphalan 140 mg/m2 (HDM140 + TMI 8 Gy in newly diagnosed symptomatic multiple myeloma (MM Asian patients. Between 2007 and 2010, nine consecutive myeloma patients who were scheduled to undergo autologous stem cell transplantation (ASCT were studied. The patients received three cycles of vincristine-adriamycin-dexamethasone (VAD regimen as induction chemotherapy, and if they had a partial response, peripheral blood stem cells were collected by dexamethasone-etoposide-cyclophosphamide-cisplatin (DECP. In arm A, six patients received the HDM200. In arm B, three patients received HDM140 + TMI 8 Gy. In arm B, the neutropenic duration was slightly longer than in arm A (P=0.048. However, hematologic recovery (except for neutrophils, transfusion requirement, median duration of hospitalization, and the dose of G-CSF were similar in both arms. The median duration of overall survival and event-free survival was similar in the two arms (P=0.387. As a conditioning regiment, HDM140 + TMI 8 Gy provide another chance for MM Asian patients who were not feasible for HDM200.

  5. [Treatment and course of a man with systemic sclerosis before and after hematopoetic blood stem cell transplantation].

    Science.gov (United States)

    Blank, N; Lorenz, H M

    2013-09-01

    A 66-year-old patient presented in our clinic with increasing painful swelling of his hands, whole body stiffness, weight loss and dyspnoea upon exercise. The physical examination revealed a marked skin sclerosis of hands, extremities and the face. Fist closure was impossible. Pulmonary CT scan showed lung fibrosis and ground glass opacities. Antinuclear antibodies and antibodies against Scl70 were positive. CRP, LDH, NT-Pro-BNP were elevated. A diffuse cutaneous systemic sclerosis with an active interstitial pneumonia and lung fibrosis was diagnosed. Three pulses of cyclophosphamide 1.4 g every three weeks were ineffective to halt the progression of skin sclerosis, joint contractures and decline of pulmonary function. Mobilisation chemotherapy was initialized and blood stem cells were harvested. Blood stem cells were reinfused after myeloablative chemotherapy with melphalan. A maintainance therapy with mycophenolic acid was initiated after recovery of hematopoiesis. Six months after blood stem cell transplantation a decrease of skin sclerosis and an increasing recovery of joint mobility and physical strength was observed. Patients with a progressive systemic sclerosis and further risk factors should be treated with high-dose chemotherapy with blood stem cell transplantation before organ function is severely compromised. In cases with contraindications against cyclophosphamide or anti-thymocyte-globulin melphalan can be discussed as an alternative. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Icing oral mucositis: Oral cryotherapy in multiple myeloma patients undergoing autologous hematopoietic stem cell transplant.

    Science.gov (United States)

    Chen, Joey; Seabrook, Jamie; Fulford, Adrienne; Rajakumar, Irina

    2017-03-01

    Background Up to 70% of patients receiving hematopoietic stem cell transplant develop oral mucositis as a side effect of high-dose melphalan conditioning chemotherapy. Oral cryotherapy has been documented to be potentially effective in reducing oral mucositis. The aim of this study was to examine the effectiveness of the cryotherapy protocol implemented within the hematopoietic stem cell transplant program. Methods A retrospective chart review was conducted of adult multiple myeloma patients who received high-dose melphalan conditioning therapy for autologous hematopoietic stem cell transplant. Primary endpoints were incidence and severity of oral mucositis. Secondary endpoints included duration of oral mucositis, duration of hospital stay, parenteral narcotics use and total parenteral nutrition use. Results One hundred and forty patients were included in the study, 70 patients in both no cryotherapy and cryotherapy groups. Both oral mucositis incidence and severity were found to be significantly lower in the cryotherapy group. Fifty (71.4%) experienced mucositis post cryotherapy compared to 67 (95.7%) in the no cryotherapy group (p cryotherapy group (p = 0.03). Oral mucositis duration and use of parenteral narcotics were also significantly reduced. Duration of hospital stay and use of parenteral nutrition were similar between the two groups. Conclusion The cryotherapy protocol resulted in a significantly lower incidence and severity of oral mucositis. These results provide evidence for the continued use of oral cryotherapy, an inexpensive and generally well-tolerated practice.

  7. Autologous hematopoietic stem cell transplantation in elderly patients (≥ 70 years) with non-Hodgkin's lymphoma: A French Society of Bone Marrow Transplantation and Cellular Therapy retrospective study.

    Science.gov (United States)

    Hermet, E; Cabrespine, A; Guièze, R; Garnier, A; Tempescul, A; Lenain, P; Bouabdallah, R; Vilque, J P; Frayfer, J; Bordessoule, D; Sibon, D; Janvier, M; Caillot, D; Biron, P; Legros, L; Choufi, B; Drenou, B; Gorin, N C; Bilger, K; Tamburini, J; Soussain, C; Brechignac, S; Bay, J O

    2015-09-01

    Limited data is available on the feasibility of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) in elderly patients over 70 years of age with non-Hodgkin's lymphoma (NHL). In the setting of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) group, we retrospectively analyzed 81 consecutive patients with NHL over 70 years of age who received AHSCT. The median age at AHSCT was 72.3 years [70-80]. Patients' were diagnosed with diffuse large B-cell lymphoma (n=40), follicular lymphoma (n=16), mantle cell lymphoma (n=15), T-cell lymphoma (n=5), and other (n=5). Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) was 0 in 73% of patients. Main conditionings were BEAM (Carmustine-Etoposide-Cytarabine-Melphalan, n=61) and melphalan alone (n=14). Median delays to reach 0.5×10⁹/L neutrophils and 20 × 10(9)/L platelets were of 12 [9-76] days and 12 [0-143] days, respectively. One hundred day and one year cumulative incidence of NRM was 5.4% and 8.5%, respectively. The main cause of death remains relapse. In conclusion, this study revealed that AHSCT seemed to be acceptable in patients over 70 years of age with NHL. Patient age is not a limiting factor if clinical condition is adequate. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Carboplatin +/- topotecan ophthalmic artery chemosurgery for intraocular retinoblastoma.

    Directory of Open Access Journals (Sweden)

    Jasmine H Francis

    Full Text Available PURPOSE: Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/- topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery. METHODS: This retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/- topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated. RESULTS: 57 carboplatin +/- topotecan infusions (of 111 total were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1-97.9% for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses. CONCLUSION: Carboplatin +/- topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival.

  9. Interaction between corticosteroid and beta-agonist drugs. Biochemical and cardiovascular effects in normal subjects.

    Science.gov (United States)

    Taylor, D R; Wilkins, G T; Herbison, G P; Flannery, E M

    1992-08-01

    The aim of this study was to investigate whether the administration of prednisone potentiates any of the acute biochemical and cardiovascular effects of high-dose inhaled beta-agonist drugs. These agents are known to cause dose-related changes in plasma potassium and glucose, as well as ECG changes in heart rate, corrected QT interval (QTc), T wave, and U wave. On theoretical grounds, the concomitant use of systemic corticosteroids might enhance these actions. Twenty-four healthy subjects were randomized to receive one of three treatments: salbutamol 5 mg or fenoterol 5 mg or normal saline solution. Each drug was administered twice, 30 min apart by nebulizer, and the procedure was repeated after each subject had received prednisone 30 mg daily for one week. Plasma potassium and glucose levels were measured, and ECGs were obtained after each treatment, together with 12-h Holter monitoring for arrhythmias. Changes in plasma potassium and glucose following nebulized beta-agonist were significantly greater after treatment with prednisone. Baseline potassium level fell from 3.75 mmol/L (95 percent CI 3.61, 3.89) to 3.50 mmol/L (95 percent CI 3.36, 3.64), and thereafter all values were significantly lower at each time point (p = 0.003). The lowest mean plasma potassium was obtained 90 min after fenoterol administration with prednisone pretreatment: 2.78 mmol/L (95 percent CI 2.44, 3.13). Increases in heart rate and QTc interval following both beta-agonist drugs were significant, but T-wave amplitude reductions did not reach significance. Prednisone treatment did not significantly alter the cardiovascular responses. Supraventricular and ventricular ectopic activity was related to beta-agonist use, but no potentiating effect was noted following steroid treatment. We conclude that the acute biochemical effects of beta-agonist administration are augmented by prior treatment with prednisone, but this is not the case for ECG effects. However, the degree of hypokalemia noted as

  10. Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302.

    Science.gov (United States)

    Saad, Fred; Shore, Neal; Van Poppel, Hendrik; Rathkopf, Dana E; Smith, Matthew R; de Bono, Johann S; Logothetis, Christopher J; de Souza, Paul; Fizazi, Karim; Mulders, Peter F A; Mainwaring, Paul; Hainsworth, John D; Beer, Tomasz M; North, Scott; Fradet, Yves; Griffin, Thomas A; De Porre, Peter; Londhe, Anil; Kheoh, Thian; Small, Eric J; Scher, Howard I; Molina, Arturo; Ryan, Charles J

    2015-10-01

    Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Patients were grouped by concomitant BTT use or no BTT use. Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; pAA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and

  11. Effect of Immunoglobulin Therapy on the Rate of Infections in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation and or Treated with Immunomodulatory Agents

    Directory of Open Access Journals (Sweden)

    Gerald Bates

    2010-02-01

    Full Text Available

    There are few data available regarding the prevalence of infection in multiple myeloma (MM patients in conjunction with newer generations of immunomodulatory drugs (thalidomide, bortezomib, lenalidomide or post autologous stem cell transplantation.  We retrospectively analyzed 47 patients with MM from March 2006 to June 2009 at our institution. All patients received thalidomide and steroid therapy for at least 6 months. Nine patients received bortezomib and 11 lenalidomide subsequently to thalidomide, because of disease progression and 22 patients underwent autologous stem cell transplantation.   The median age was 64 years (range 37-86, with a female–to-male ratio of 18:29. The median residual-serum IgG-level at time of infection was 3.2 g/L, IgA 0.3 g/L and IgM 0.2 g/L. Most patients suffered from recurrent moderate to severe infections. All patients except 3 received intravenous immunoglobulin (IVIG therapy with a significant decline of the rate of infection thereafter. Our analysis shows that IVIG appears to be an effective strategy to prevent infection in MM patients. Further studies to confirm these findings are warranted.

  12. Atypical Primary Cutaneous Rosai Dorfman Disease: A Case Report.

    Science.gov (United States)

    Kinio, Anna E; Sawchuk, Michael A; Pratt, Melanie

    Rosai Dorfman disease (RDD) is a rare disorder that typically presents with bilateral cervical lymphadenopathy and follows a benign course. We present a case of late-onset atypical primary cutaneous RDD that is resistant to treatment modalities described in the literature. Case report. An 84-year-old woman presented with a 7-year history of cutaneous lesions histologically consistent with RDD. She later failed initial treatments of acitretin and thalidomide. Physicians must be aware of unusual presentations of RDD. Also, further treatment options must be explored for patients resistant to classical management of RDD.

  13. Pharmacovigilance in developing countries (part I): importance and challenges.

    Science.gov (United States)

    Elshafie, Shaimaa; Zaghloul, Iman; Roberti, Anne Marie

    2017-12-16

    The thalidomide disaster was the significant historical event that acted as a catalyst for pharmacovigilance activity. Following this event developed countries initiated drug monitoring systems that evolved and now extend their scope to broader drug-related safety issues; however, this was not the case in developing countries. Pharmacovigilance is still a relatively new concept with low priority in developing countries although various issues are raising concerns that magnify the need for systems to monitor post marketing drug safety in these countries. This article analyzes the barriers to introducing robust pharmacovigilance systems in developing countries.

  14. Substâncias enantiomericamente puras (SEP: a questão dos fármacos quirais Pure enantiomeric substances: the question of chiral drugs

    Directory of Open Access Journals (Sweden)

    Eliezer J. Barreiro

    1997-12-01

    Full Text Available The thalidomide disaster, in the 60,s, is the most painful reminder of the importance of chirality for biological activity. After this episode, much attention has been devoted to study the correlations between toxicological and pharmacological properties and chirality. Actualy, to get a licence for a new chiral drug in EUA, European community and Japan, it is necessary to study the biological properties of each enatiomer independently. This article presents an overview about the importance of the chirality of organic compounds and its relationships with biological activity, asymmetric synthetic methodologies and market.

  15. Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Roberta Martiniani

    2012-01-01

    Full Text Available Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN as a possible mediator of its therapeutical effects.

  16. Cytogenetic Alterations in Multiple Myeloma: Prognostic Significance and the Choice of Frontline Therapy.

    Science.gov (United States)

    Stella, Flavia; Pedrazzini, Estela; Agazzoni, Mara; Ballester, Oscar; Slavutsky, Irma

    2015-01-01

    Multiple myeloma tumor cells demonstrate multiple and often complex genetic lesions as evaluated by standard cytogenetic/FISH studies. Over the past decade, specific abnormalities have been associated with standard or high-risk clinical behavior and they have become strong prognostic indicators. Further, as evidenced by recent randomized clinical trials, the choice of front-line therapy (transplant vs. no transplant, inclusion of novel drugs such as bortezomib, thalidomide, and lenalidomide) may be able to overcome the adverse effect of high-risk genetic lesions.

  17. Recurrent hemorrhagic pericardial effusion in a child due to diffuse lymphangiohemangiomatosis: a case report

    Directory of Open Access Journals (Sweden)

    Bakhshi Sameer

    2010-02-01

    Full Text Available Abstract Introduction Recurrent hemorrhagic pericardial effusion in children with no identifiable cause is a rare presentation. Case presentation We report the case of a 4-year-old Indian girl who presented with recurrent hemorrhagic pericardial effusion. Diffuse lymphangiomatosis was suspected when associated pulmonary involvement, soft tissue mediastinal mass, and lytic bone lesions were found. Pericardiectomy and lung biopsy confirmed the diagnosis of diffuse lymphangiohemangiomatosis. Partial clinical improvement occurred with thalidomide and low-dose radiotherapy, but our patient died from progressive respiratory failure. Conclusion Diffuse lymphangiohemangiomatosis should be considered in the differential diagnosis of hemorrhagic pericardial effusion of unclear cause.

  18. Non-syndromic bilateral ulnar aplasia with humero-radial synostosis and oligo-ectro-dactyly.

    Science.gov (United States)

    McVeigh, Terri P; Soye, Jonathan A; Gordon, Emma; Lynch, Sally A

    2018-02-10

    Congenital anomalies of the upper limbs are rare and etiologically heterogeneous. Herein, we report a male infant with non-syndromic bilateral Type Vb ulnar longitudinal dysplasia with radiohumeral synostosis (apparent humeral bifurcation), and bilateral oligo-ectro-syndactyly who was born following an uncomplicated pregnancy, with no maternal use of prescription or illicit medication. Array CGH (60,000 probes) and chromosomal breakage analysis (DEB) were normal. Similar appearances have been reported in children exposed to thalidomide or cocaine, but sporadic patients have also been reported without a prior history of exposure to known teratogens. © 2018 Wiley Periodicals, Inc.

  19. Daratumumab – breakthrough drug in multiple myeloma therapy

    Directory of Open Access Journals (Sweden)

    Artur Jurczyszyn

    2014-11-01

    Full Text Available Multiple myeloma (MM remains incurable despite important recent advances in treatment. Over the last 2 years, an anti-CD38 monoclonal antibody daratumumab (DARA has emerged as a breakthrough targeted therapy for patients with MM. Early-stage clinical trials have found DARA to be safe and to have encouraging clinical activity as a single agent and in combination with lenalidomide in heavily pretreated, relapsed patients in whom other novel agents (such as bortezomib, thalidomide and lenalidomide as well as stem cell transplant has already failed. This review discusses the preclinical and clinical development of DARA, its pathophysiological basis, and its prospects for future use in MM.

  20. Myeloma: making sense of a complex blood cancer.

    LENUS (Irish Health Repository)

    Kelly, Mary B

    2012-01-31

    Myeloma is a challenging blood cancer characterized by bone destruction, hypercalcaemia, renal insufficiency and anaemia. Although myeloma remains incurable, recent advancements in treatments have resulted in significant improvements in morbidity. The use of immunomodulatory drugs-thalidomide, lenalidomide, pomalidomide (in clinical trials)-and the proteasome inhibitor, bortezomib, in conjunction with conventional chemotherapy and supportive therapies, have resulted in a significant shift in approaches to treatment and an improvement in patients\\' quality of life. Nurses must remain up-to-date with current treatments for myeloma and their related side-effects. In addition, nurses play a key role in the coordination of a multidisciplinary approach to care for myeloma patients.