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1.
Lancet ; 396(10262): 1563-1573, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33189178

RESUMO

BACKGROUND: Selinexor combined with dexamethasone has shown activity in patients with heavily pre-treated multiple myeloma. In a phase 1b/2 study, the combination of oral selinexor with bortezomib (a proteasome inhibitor) and dexamethasone induced high response rates with low rates of peripheral neuropathy, the main dose-limiting toxicity of bortezomib. We aimed to evaluate the clinical benefit of weekly selinexor, bortezomib, and dexamethasone versus standard bortezomib and dexamethasone in patients with previously treated multiple myeloma. METHODS: This phase 3, randomised, open-label trial was done at 123 sites in 21 countries. Patients aged 18 years or older, who had multiple myeloma, and who had previously been treated with one to three lines of therapy, including proteasome inhibitors, were randomly allocated (1:1) to receive selinexor (100 mg once per week), bortezomib (1·3 mg/m2 once per week), and dexamethasone (20 mg twice per week), or bortezomib (1·3 mg/m2 twice per week for the first 24 weeks and once per week thereafter) and dexamethasone (20 mg four times per week for the first 24 weeks and twice per week thereafter). Randomisation was done using interactive response technology and stratified by previous proteasome inhibitor therapy, lines of treatment, and multiple myeloma stage. The primary endpoint was progression-free survival in the intention-to-treat population. Patients who received at least one dose of study treatment were included in the safety population. This trial is registered at ClinicalTrials.gov, NCT03110562. The trial is ongoing, with 55 patients remaining on randomised therapy as of Feb 20, 2020. FINDINGS: Of 457 patients screened for eligibility, 402 were randomly allocated-195 (49%) to the selinexor, bortezomib, and dexamethasone group and 207 (51%) to the bortezomib and dexamethasone group-and the first dose of study medication was given between June 6, 2017, and Feb 5, 2019. Median follow-up durations were 13·2 months [IQR 6·2-19·8] for the selinexor, bortezomib, and dexamethasone group and 16·5 months [9·4-19·8] for the bortezomib and dexamethasone group. Median progression-free survival was 13·93 months (95% CI 11·73-not evaluable) with selinexor, bortezomib, and dexamethasone and 9·46 months (8·11-10·78) with bortezomib and dexamethasone (hazard ratio 0·70 [95% CI 0·53-0·93], p=0·0075). The most frequent grade 3-4 adverse events were thrombocytopenia (77 [39%] of 195 patients in the selinexor, bortezomib, and dexamethasone group vs 35 [17%] of 204 in the bortezomib and dexamethasone group), fatigue (26 [13%] vs two [1%]), anaemia (31 [16%] vs 20 [10%]), and pneumonia (22 [11%] vs 22 [11%]). Peripheral neuropathy of grade 2 or above was less frequent with selinexor, bortezomib, and dexamethasone (41 [21%] patients) than with bortezomib and dexamethasone (70 [34%] patients; odds ratio 0·50 [95% CI 0·32-0·79], p=0·0013). 47 (24%) patients in the selinexor, bortezomib, and dexamethasone group and 62 (30%) in the bortezomib and dexamethasone group died. INTERPRETATION: A once-per-week regimen of selinexor, bortezomib, and dexamethasone is a novel, effective, and convenient treatment option for patients with multiple myeloma who have received one to three previous lines of therapy. FUNDING: Karyopharm Therapeutics.


Assuntos
Antineoplásicos/administração & dosagem , Bortezomib/administração & dosagem , Dexametasona/administração & dosagem , Hidrazinas/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Triazóis/administração & dosagem , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/efeitos adversos , Dexametasona/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Hidrazinas/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Triazóis/efeitos adversos
2.
Haematologica ; 105(1): 201-208, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278209

RESUMO

Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs 19.3%; P=NS.) and relapse (54.5% vs 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs 46.5 months).Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 9.1 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Plasmocitoma , Península Balcânica , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Recidiva Local de Neoplasia , Plasmocitoma/diagnóstico , Plasmocitoma/terapia , Estudos Retrospectivos , Transplante Autólogo , Universidades
3.
N Engl J Med ; 372(2): 142-52, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-25482145

RESUMO

BACKGROUND: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. METHODS: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. RESULTS: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. CONCLUSIONS: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Talidomida/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Lenalidomida , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Oligopeptídeos/efeitos adversos , Recidiva , Talidomida/administração & dosagem , Talidomida/efeitos adversos
4.
Blood ; 128(9): 1174-80, 2016 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-27439911

RESUMO

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Adolescente , Adulto , Idoso , Dexametasona/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Recidiva , Fatores de Risco , Taxa de Sobrevida , Talidomida/administração & dosagem , Talidomida/análogos & derivados
5.
Br J Haematol ; 177(3): 404-413, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28211560

RESUMO

A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR, 0·753). For patients <70 years the overall response rate (ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib-lenalidomide-dexamethasone has a favourable benefit-risk profile for patients with RMM, including elderly patients ≥70 years old. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01080391.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Dexametasona/administração & dosagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Lenalidomida , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagem , Recidiva , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do Tratamento
6.
Transfusion ; 57(11): 2629-2638, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28840942

RESUMO

BACKGROUND: Patients treated with intravenous immunoglobulins (IVIG) rarely experience symptomatic hemolysis. Although anti-A and anti-B isoagglutinins from the product are involved in most cases, the actual mechanisms triggering hemolysis are unclear. STUDY DESIGN AND METHODS: A prospective, open-label, multicenter, single-arm clinical trial in 57 patients with immune thrombocytopenia treated with IVIG (Privigen, CSL Behring) was conducted. RESULTS: Twenty-one patients received one infusion (1 g/kg) and 36 received two infusions (2 × 1 g/kg) of IVIG. After a study duration of more than 2 years, no cases of clinically significant hemolysis as defined in the protocol were identified. Data of patients with mild hematologic and biochemical changes were analyzed in more detail. Twelve cases (10/23 patients with blood group A1 and 2/11 patients with blood group B, all having received 2 g/kg IVIG) were adjudicated as mild hemolysis (median hemoglobin [Hb] decrease, -3.0 g/dL); Hb decreases were transient, with partial or full recovery achieved by last visit. Eighteen patients (31.6%), all with non-O blood group, of whom 16 (88.9%) received 2 g/kg IVIG, fulfilled post hoc criteria for hemolytic laboratory reactions. Red blood cell (RBC) eluates of all direct antiglobulin test-positive samples were negative for non-ABO blood group antibodies. Blood groups A and B antigen density on RBCs appeared to be a risk factor for hemolytic laboratory reactions. Platelet response to treatment was observed in 42 patients (74%); eight of 12 patients with complete response had blood group A1. CONCLUSION: Isoagglutinins are involved in clinically nonsignificant hemolysis after treatment with IVIG, but individual susceptibility varies greatly.


Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Hemólise/imunologia , Imunoglobulinas Intravenosas/efeitos adversos , Adolescente , Adulto , Idoso , Anticorpos/sangue , Especificidade de Anticorpos , Suscetibilidade a Doenças , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto Jovem
7.
Lancet Oncol ; 17(1): 27-38, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26671818

RESUMO

BACKGROUND: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. METHODS: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m(2); intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. FINDINGS: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p<0·0001). On-study death due to adverse events occurred in 18 (4%) of 464 patients in the carfilzomib group and in 16 (3%) of 465 patients in the bortezomib group. Serious adverse events were reported in 224 (48%) of 463 patients in the carfilzomib group and in 162 (36%) of 456 patients in the bortezomib group. The most frequent grade 3 or higher adverse events were anaemia (67 [14%] of 463 patients in the carfilzomib group vs 45 [10%] of 456 patients in the bortezomib group), hypertension (41 [9%] vs 12 [3%]), thrombocytopenia (39 [8%] vs 43 [9%]), and pneumonia (32 [7%] vs 36 [8%]). INTERPRETATION: For patients with relapsed or refractory multiple myeloma, carfilzomib with dexamethasone could be considered in cases in which bortezomib with dexamethasone is a potential treatment option. FUNDING: Onyx Pharmaceuticals, Inc., an Amgen subsidiary.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Idoso , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Hipertensão/induzido quimicamente , Masculino , Oligopeptídeos/administração & dosagem , Oligopeptídeos/efeitos adversos , Pneumonia/induzido quimicamente , Retratamento , Taxa de Sobrevida , Trombocitopenia/induzido quimicamente
9.
Am J Hematol ; 90(1): 42-9, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25294016

RESUMO

We compared the safety and efficacy of siltuximab (S), an anti-interleukin-6 chimeric monoclonal antibody, plus bortezomib (B) with placebo (plc) + B in patients with relapsed/refractory multiple myeloma in a randomized phase 2 study. Siltuximab was given by 6 mg/kg IV every 2 weeks. On progression, B was discontinued and high-dose dexamethasone could be added to S/plc. Response and progression-free survival (PFS) were analyzed pre-dexamethasone by European Group for Blood and Marrow Transplantation (EBMT) criteria. For the 281 randomized patients, median PFS for S + B and plc + B was 8.0 and 7.6 months (HR 0.869, P = 0.345), overall response rate was 55 versus 47% (P = 0.213), complete response rate was 11 versus 7%, and median overall survival (OS) was 30.8 versus 36.8 months (HR 1.353, P = 0.103). Sustained suppression of C-reactive protein, a marker reflective of inhibition of interleukin-6 activity, was seen with S + B. Siltuximab did not affect B pharmacokinetics. Siltuximab/placebo discontinuation (75 versus 66%), grade ≥3 neutropenia (49 versus 29%), thrombocytopenia (48 versus 34%), and all-grade infections (62 versus 49%) occurred more frequently with S + B. The addition of siltuximab to bortezomib did not appear to improve PFS or OS despite a numerical increase in response rate in patients with relapsed or refractory multiple myeloma.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ácidos Borônicos/uso terapêutico , Interleucina-6/imunologia , Mieloma Múltiplo/tratamento farmacológico , Pirazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/mortalidade , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Recidiva
10.
Ann Med ; 52(3-4): 94-108, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32212941

RESUMO

Aim of the study: To assess serum sclerostin in transfusion-dependent beta-thalassaemia patients versus healthy controls and to examine its associations with bone mineral density, bone metabolism markers and beta thalassaemia alterations.Material and methods: Sixty-two transfusion-dependent beta-thalassaemia (TDßT) patients and 30 healthy controls were evaluated for serum sclerostin, osteocalcin, beta-cross laps, osteoprotegerin and serum level of receptor activator of nuclear factor kappa-Β ligand (sRANKL). Bone mineral density was measured at the lumbar spine and femoral neck. Thalassaemia characteristics were collected from the patients' medical records.Results: A significantly higher sclerostin level (median 565.50 pmol/L) was observed in the transfusion-dependent beta-thalassaemia patients vs. the healthy controls (median 48.65 pmol/L, p < .001). Sclerostin showed significant associations with the Z-scores at the lumbar spine and femoral neck, osteocalcin, beta-cross laps, osteoprotegerin, sRANKL, pretransfusion haemoglobin, liver iron concentration and female gonadal state. Significantly higher levels of sclerostin were observed in splenectomized TDßT patients and in those with fragility fractures. Age, sex, body mass index, disease severity, serum ferritin, cardiac T2* and male gonadal state did not show significant associations with sclerostin.Conclusion: Sclerostin may play a role in the bone pathophysiology of beta-thalassaemia patients and could serve as a marker of severe osteoporosis.KEY MЕSSAGESSerum sclerostin is more than 10-fold higher in adult patients with transfusion-dependent beta-thalassaemia compared to healthy controls.Serum sclerostin is negatively associated with bone mineral density and the bone synthesis markers and positively with the bone resorption indices.Serum sclerostin is significantly associated with pre-transfusion haemoglobin, liver iron concentration, splenectomy status and fragility fracture events in adult patients with transfusion-dependent beta-thalassaemia.Serum sclerostin could serve as a marker of severe osteoporosis in beta-thalassaemia patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Densidade Óssea , Talassemia beta/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/diagnóstico , Osteoporose/etiologia , Fraturas por Osteoporose/sangue , Fraturas por Osteoporose/etiologia , Talassemia beta/complicações
11.
Folia Med (Plovdiv) ; 51(2): 5-11, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19670534

RESUMO

POEMS syndrome (polyneuropathy, organomegaly, M-protein, and skin changes) is a rare plasma cell disease with small tumour mass and multisystem involvement. Since 2003 POEMS syndrome has been a nosological entity with approved diagnostic criteria, though its etiology and pathogenesis are still not clear. Males are more often affected, with peak incidence in the 5th and 6th decades. The major diagnostic problems are difficult detection of plasma cell infiltration in the osteosclerotic lesions and M-gradient most often low concentration IgA (lamda). We present a case of POEMS syndrome in a 47-year-old male patient who initially presented with edema of the lower limbs, moderate lymphadenopathy, hepatosplenomegaly, histological findings of Castleman disease with marked sinusoidal angioproliferation in the lymph nodes and multiple osteosclerotic lesions. Pleural effusion, ascitis, renal failure, progressive lower limbs polyneuropathy with invalidisation of the patient developed later. The attempts to detect lymphoproliferative process by myelogram, trephine biopsy, histological examination of lymph node and the spleen were ineffective and deceptively non-informative, neither did immunoelectrophoresis reveal M-grade. Diagnosis was made after bone biopsy of the largest osteosclerotic lesion and immunofixation (monoclonal IgA, lamda in the serum). The patient underwent treatment with alkylating agents and corticosteroids, radiation of the predominant osteosclerotic lesions and therapy with radioactive strontium. The general condition improved, lymphadenomegaly, skin lesions, pleural effusion and ascitis regressed and renal function was restored. There was a minor improvement of the neurological symptoms. Autollogous stem-cell transplantation is also recommended in literature for patients with generalized bone lesions or progressive and disease-resistant therapy.


Assuntos
Síndrome POEMS/diagnóstico , Criança , Humanos , Masculino , Síndrome POEMS/complicações , Síndrome POEMS/terapia
12.
Folia Med (Plovdiv) ; 51(4): 53-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20232660

RESUMO

In recent years, the incidence of osteonecrosis of the jaw (ONJ) as an unknown complication in patients receiving bisphosphonates (BP) has been on the increase. According to literature data it is in the range of 0.83% to 11.9%. ONJ has been mostly reported in patients with malignancies--mainly in multiple myeloma (MM) patients, followed by patients with bone metastases from breast and prostatic cancer. The view that is supported by a growing body of researchers in the discussion on the etiopathogenetic relationship between ONJ and BPs is that ONJ seems to be a class-specific side effect rather than a result of the use of a specific drug. The major risk factor for development of ONJ is not the BP type, but the time of their administration and accumulation in the bone structures. More than 70% of the ONJ patients report preceding dental problems. The immunosuppressive effects of chemo- and radiotherapy, the impaired bone remodeling resulting from corticoid therapy, the antiangiogenetic properties of thalidomide slow down the reparative processes in the oral cavity and appear as a predisposing factor for the development of ONJ. Possibilities for successful treatment are limited; conservative approaches and least surgery, if larger areas are involved, are recommended. Dental prophylaxis is of particular importance. We present a 66-year-old man with multiple myeloma, IgG, BJ(k), II A KC (after Durie and Salmon staging system). ONJ was diagnosed one year after the disease onset, during which the patient received chemotherapy and was administered concurrently 14 cycles of BPs (pamidronate/zolendronate). The diagnosis was based on clinical, radiologic and histological evidence. Surgical removal of the necrotic sequesters and antibiotic treatment produced a clinical improvement. This rare, refractory complication requires the joint efforts of hematologists, oncologists, and maxillofacial surgeons to diagnose, manage prophylactically and treat.


Assuntos
Difosfonatos/efeitos adversos , Doenças Maxilomandibulares/induzido quimicamente , Mieloma Múltiplo/complicações , Osteonecrose/induzido quimicamente , Idoso , Antibacterianos/uso terapêutico , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Desbridamento/métodos , Diagnóstico Diferencial , Difosfonatos/uso terapêutico , Seguimentos , Humanos , Doenças Maxilomandibulares/diagnóstico , Doenças Maxilomandibulares/terapia , Masculino , Mieloma Múltiplo/diagnóstico , Osteólise/tratamento farmacológico , Osteonecrose/diagnóstico , Osteonecrose/terapia
13.
Acta Clin Croat ; 56(2): 262-269, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29485793

RESUMO

There is a small but well recognized group of patients with multiple myeloma (MM), characterized by multiple bone lesions and low tumor burden, the so-called macrofocal form of MM (MF-MM). The aim of the study was to analyze the incidence, clinical manifestation, therapeutic outcome and prognosis of patients with MF-MM treated with bortezomib-based therapy and radiotherapy, in comparison to classic MM. There were 148 MM patients treated with bortezomibbased regimens, with 15 (10.1%) of them meeting the criteria for MF-MM. Comparative analysis involved disease- and therapy-related variables and markers of bone metabolism in MF-MM and classic MM groups. Event-free survival (EFS) and median survival (MS) were analyzed. Patients in MF-MM and classic MM groups had similar mean age and sex distribution. Patients with MF-MM had advanced myeloma bone disease (MBD), significantly lower clonal plasma cell infiltration in bone marrow, and lower paraprotein level. These patients were predominantly in an early International Staging System stage, showed non-secretory and light-chain variants, and significant association with extramedullary plasmacytomas. EFS was 20 months in MF-MM group versus 13 months in classic MM group (nonsignificant difference). MS was 42 months in both MF-MM and classic MM groups. MF-MM presents with imbalance of the minimal tumor burden and massive bone involvement. Along with advanced skeletal manifestations, these patients showed features of preserved bone marrow and no end-organ damages. Following bortezomib-based therapy and radiotherapy, the EFS and MS did not differ between MF-MM and classic MM groups.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Bortezomib/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/radioterapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/radioterapia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
15.
Acta Clin Croat ; 50(2): 273-9, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22263396

RESUMO

A severe complication of the administration of bisphosphonate-containing medications is known as bisphosphonate-associated osteonecrosis of the jaws (BONJ). A case series of three patients affected by BONJ is presented. These patients currently represent the only described cases of BONJ in Bulgaria. Exposed necrotic bone of the mandible was observed in two patients and the maxilla was affected in the third case. Two of the patients had been treated with zoledronate for metastatic prostate cancer and one patient for metastatic endometrioid cancer. All three patients underwent surgical treatment. One of the patients received conservative surgical debridement, i.e. removal of necrotic bone only, and primary wound closure. Conservative surgical debridement and application of local medications without wound closure were used in the other two patients. All three patients received systemic antibiotic treatment. No evidence of disease progression was observed during the follow-up period of 3 to 12 months. The surgical approach utilized in the present study is discussed in the light of the etiopathogenesis, prevention and treatment of BONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Imidazóis/efeitos adversos , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Difosfonatos/administração & dosagem , Feminino , Humanos , Imidazóis/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Ácido Zoledrônico
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