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1.
Haematologica ; 109(1): 245-255, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37439329

RESUMO

In the ELOQUENT-3 trial, the combination of elotuzumab, pomalidomide and dexamethasone (EloPd) proved to have a superior clinical benefit over pomalidomide and dexamethasone with a manageable toxicity profile, leading to its approval for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor. We report here a real-world experience of 200 cases of RRMM treated with EloPd in 35 Italian centers outside of clinical trials. In our dataset, the median number of prior lines of therapy was two, with 51% of cases undergoing autologous stem cell transplant and 73% having been exposed to daratumumab. After a median follow-up of 9 months, 126 patients had stopped EloPd, most of them (88.9%) because of disease progression. The overall response rate was 55.4%, a finding in line with the pivotal trial results. Regarding adverse events, the toxicity profile in our cohort was similar to that in the ELOQUENT-3 trial, with no significant differences between younger (<70 years) and older patients. The median progression-free survival was 7 months, which was shorter than that observed in ELOQUENT-3, probably because of the different clinical characteristics of the two cohorts. Interestingly, International Staging System stage III disease was associated with worse progression-free survival (hazard ratio=2.55). Finally, the median overall survival of our series was shorter than that observed in the ELOQUENT-3 trial (17.5 vs. 29.8 months). In conclusion, our real-world study confirms that EloPd is a safe and possible therapeutic choice for patients with RRMM who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.


Assuntos
Mieloma Múltiplo , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/uso terapêutico , Lenalidomida/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/etiologia , Inibidores de Proteassoma/uso terapêutico , Estudos Retrospectivos , Ensaios Clínicos Controlados como Assunto
2.
Hematol Oncol ; 42(4): e3290, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38818978

RESUMO

The ELOQUENT-3 trial demonstrated the superiority of the combination of elotuzumab, pomalidomide, and dexamethasone (EloPd) in terms of efficacy and safety, compared to Pd in relapsed/refractory multiple myeloma (RRMM), who had received at least two prior therapies, including lenalidomide and a proteasome inhibitor. The present study is an 18-month follow-up update of a previously published Italian real-life RRMM cohort of patients treated with EloPd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow-up of 17.7 months, 213 patients (66.4%) experienced disease progression or died. Median progression-free survival (PFS) and overall survival (OS) were 7.5 and 19.2 months, respectively. The updated multivariate analysis showed a significant reduction of PFS benefit magnitude both in advanced International Staging System (ISS) (II and III) stages and previous exposure to daratumumab cases. Instead, advanced ISS (II and III) stages and more than 2 previous lines of therapy maintained an independent prognostic impact on OS. Major adverse events included grade three-fourths neutropenia (24.9%), anemia (13.4%), lymphocytopenia (15.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 19.3% and 8.7%, respectively. A slight increase in the incidence of neutropenia and lymphocytopenia was registered with longer follow-up. In conclusion, our real-world study still confirms that EloPd is a safe and possible therapeutic choice for RRMM. Nevertheless, novel strategies are desirable for those patients exposed to daratumumab.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Talidomida , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Masculino , Feminino , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Pessoa de Meia-Idade , Talidomida/análogos & derivados , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Talidomida/uso terapêutico , Estudos Retrospectivos , Seguimentos , Idoso de 80 Anos ou mais , Adulto , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Resistencia a Medicamentos Antineoplásicos , Taxa de Sobrevida
3.
Haematologica ; 103(7): 1209-1217, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29674504

RESUMO

We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adenina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Biomarcadores Tumorais , Humanos , Itália , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Pessoa de Meia-Idade , Piperidinas , Prognóstico , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Retratamento , Rituximab/administração & dosagem , Terapia de Salvação , Análise de Sobrevida , Resultado do Tratamento , Reino Unido
4.
Blood ; 119(10): 2219-27, 2012 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-22262773

RESUMO

Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2(V617F) mutations were present in 47.5% of ST and in no HT. The MPL(S505A) mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches.


Assuntos
Policitemia/tratamento farmacológico , Trombocitemia Essencial/tratamento farmacológico , Trombocitose/tratamento farmacológico , Adolescente , Substituição de Aminoácidos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Janus Quinase 2/genética , Masculino , Mutação , Policitemia/complicações , Policitemia/genética , Gravidez , Complicações Hematológicas na Gravidez , Resultado da Gravidez , Receptores de Trombopoetina/genética , Estudos Retrospectivos , Trombocitemia Essencial/complicações , Trombocitemia Essencial/genética , Trombocitose/complicações , Trombocitose/genética , Resultado do Tratamento , Adulto Jovem
5.
Target Oncol ; 18(6): 885-892, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37747623

RESUMO

BACKGROUND: Daratumumab, an anti-CD38 monoclonal antibody, is used for treatment of multiple myeloma (MM) and light chain amyloidosis at an intravenous dosage of 16 mg/kg or at a subcutaneous fixed dose of 1800 mg. However, the subcutaneous formulation has only recently been approved in Europe, and real-life data on its safety are still few. OBJECTIVE: In this multicenter retrospective real-life experience, we provided evidence for the safety of subcutaneous daratumumab in plasma cell disorders. PATIENTS AND METHODS: A total of 189 patients diagnosed with MM or light chain amyloidosis were included in this retrospective study, and all subjects were daratumumab-naïve. Primary endpoint was safety of subcutaneous daratumumab, especially for infusion-related reaction (IRR) incidence and severity. All patients received premedication with dexamethasone, paracetamol, and antihistamine, with montelukast usage in 85% of cases. RESULTS: Eight patients (4%) experienced IRRs, mainly of grade I-II, and other frequent toxicities were: hematological (thrombocytopenia, 4%; neutropenia, 5%; lymphopenia, 6%) and non-hematological (pneumonia, 4%; diarrhea, 2%; and cytomegalovirus reactivation, 0.5%). In our multicenter retrospective real-life experience, subcutaneous daratumumab was well-tolerated with an excellent safety profile with a very low (4%) IRR incidence, even in frailer MM patients with severe renal impairment or increased body weight. CONCLUSIONS: Subcutaneous daratumumab was safe in a real-life setting including patients with severe renal failure and advanced disease. However, further studies on larger and prospective cohorts are required to confirm our real-life observations.


Assuntos
Amiloidose , Antineoplásicos , Mieloma Múltiplo , Humanos , Estudos Retrospectivos , Plasmócitos , Estudos Prospectivos , Antineoplásicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Amiloidose/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
6.
Eur J Haematol ; 88(6): 526-34, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22381133

RESUMO

Infection is a significant cause of death in patients with aplastic anaemia (AA). However, few studies have examined the characteristics of infections in patients with AA, especially in children. The aim of this retrospective study was to evaluate the incidence and types of infections in a large cohort of paediatric patients with AA referred to eight AIEOP (Italian Association of Paediatric Oncology and Haematology) centres in Italy. The study included 78 patients, 45 boys and 33 girls, median age 9.29 yrs (1st-3rd quartile 3.59-13.09) diagnosed with AA. During the study period, 111 infectious episodes were observed in 42 (54%) patients. Fifty-one (46%) episodes were fever of unknown origin and 60 (54%) were documented infections (DI). In this group, microbiologically documented infection (MDI) with bacteremia accounted for 23 (38%) episodes, MDI without bacteremia for 7 (12%), clinically documented infection for 25 (42%) and invasive fungal diseases for 5 (8%). The rate (episodes/1000 d at risk) was similar in severe aplastic anemia and very severe aplastic anemia both before and after day 120. During the first 120 d from diagnosis, the cumulative risk of a DI was 21% (95% CI 12-29) with the last episode at day 117, but the 50% of episodes were observed in the first 24 d. After day 120, the cumulative risk of DI was again 21% (95% CI 12-29), with the last episode at day 445 of follow-up, with 50% of episodes observed in the first 120 d of observation (240 d from the diagnosis of AA). We found a statistically significant association between the grade of aplasia at diagnosis and the incidence of IEs (P = 0.0002). No association was found between gender, age at diagnosis, response at day +120 and at day +180, use of G-CSF and occurrence of IEs. The actuarial overall survival at 5 yrs was 90% ± 3.6. The mortality rate attributable to infection complication was 9%. This is a large paediatric cohort study reporting the epidemiology of infectious complications in children with AA and that allow us to compare the epidemiological data in this diseases with that of the most recent studies in neutropenic children with cancer. Our findings confirm that infections represent the main cause of death in patients with AA and they are important for the design of management strategies of febrile neutropenia in these patients.


Assuntos
Anemia Aplástica/complicações , Infecções/epidemiologia , Infecções/etiologia , Adolescente , Bacteriemia/complicações , Bacteriemia/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Febre de Causa Desconhecida/complicações , Febre de Causa Desconhecida/epidemiologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco
7.
Front Immunol ; 13: 892331, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003404

RESUMO

Introduction: In immunocompromised patients, SARS-CoV-2 mRNA vaccine has been used in Italy from the beginning of the vaccination campaign, but several studies have shown that the serological response of onco-hematological patients was reduced compared to healthy subjects, due to the state of immunosuppression because of both underlying disease and administered therapy. Methods: We evaluated the association of anti-SARS-CoV-2 spike IgG titers in 215 hematological patients with clinical and demographic variables to verify if it was possible to identify predictive parameters of serological response, as well as using a control group, consisting of healthy health workers of San Carlo Hospital in Potenza. Anti-SARS-CoV2 IgG titers were evaluated after 30-45 days post second dose vaccine using chemiluminescent microparticle immunoassay technology. Results: Patients with hematological malignancies, compared with the control arm, had both a mean concentration of anti-SARS-CoV-2 IgG significantly lower and a seroconversion rate numerically lower. All chronic lymphatic leukemia patients showed levels of antibody titer below the mean concentration, also in only clinical surveillance patients. Comparing serological response in hematological malignancies, only acute leukemia patients who were off therapy had the highest seroconversion rate among the patients' cohorts and a mean antibody concentration greater than the control arm. Patients treated with steroids and rituximab showed a lower level of anti-SARS-CoV-2 spike IgG. Differences in anti-spike IgG levels among chronic myeloid leukemia patients stratified according to tyrosine kinase inhibitor therapy and molecular response were observed, and they could have interesting implications on the evaluation of the effects of these drugs on the immune system, but having not reached statistical significance at the moment. The cohort of patients who received a stem cell transplant was very heterogeneous because it included different hematological malignancies and different types of transplant; however, a mean concentration of anti-SARS-CoV2 IgG greater than the control arm was reported. Indeed, among patients who performed a transplant for over 6 months only one had a spike IgG concentration below the cutoff. Conclusions: Our data confirm reduced serological response in hematological patients after anti-SARS-CoV-2 vaccination. However, we found a great diversity of SARS-CoV-2 antibody response according to types of pathologies and therapies.


Assuntos
COVID-19 , Neoplasias Hematológicas , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulina G , RNA Mensageiro , SARS-CoV-2 , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
8.
Blood ; 113(17): 4094-100, 2009 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-19179465

RESUMO

In paroxysmal nocturnal hemoglobinuria (PNH) hemolytic anemia is due mainly to deficiency of the complement regulator CD59 on the surface of red blood cells (RBCs). Eculizumab, an antibody that targets complement fraction 5 (C5), has proven highly effective in abolishing complement-mediated intravascular hemolysis in PNH; however, the hematologic benefit varies considerably among patients. In the aim to understand the basis for this variable response, we have investigated by flow cytometry the binding of complement fraction 3 (C3) on RBCs from PNH patients before and during eculizumab treatment. There was no evidence of C3 on RBCs of untreated PNH patients; by contrast, in all patients on eculizumab (n = 41) a substantial fraction of RBCs had C3 bound on their surface, and this was entirely restricted to RBCs with the PNH phenotype (CD59(-)). The proportion of C3(+) RBCs correlated significantly with the reticulocyte count and with the hematologic response to eculizumab. In 3 patients in whom (51)Cr labeling of RBCs was carried out while on eculizumab, we have demonstrated reduced RBC half-life in vivo, with excess (51)Cr uptake in spleen and in liver. Binding of C3 by PNH RBCs may constitute an additional disease mechanism in PNH, strongly enhanced by eculizumab treatment and producing a variable degree of extravascular hemolysis.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Complemento C3/metabolismo , Eritrócitos/metabolismo , Hemoglobinúria Paroxística/metabolismo , Hemoglobinúria Paroxística/terapia , Imunoterapia , Anticorpos Monoclonais Humanizados , Sobrevivência Celular , Eritrócitos/patologia , Feminino , Citometria de Fluxo , Hemoglobinúria Paroxística/imunologia , Humanos , Masculino
9.
Br J Haematol ; 144(5): 726-31, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19133977

RESUMO

Five cases of persistent polyclonal B-cell lymphocytosis (PPBL) with progressive splenomegaly are reported; three were splenectomized. BCL2/IGH rearrangements were found in three cases; HLA-DRB1*07 in all. Bone marrow (BM) trephines showed a moderate lymphoid infiltrate with intrasinusoidal distribution resembling a splenic marginal-zone lymphoma. Splenic white pulp revealed an enlargement of the marginal-zone area; red pulp was infiltrated by the same lymphocytes engulfing the sinuses. Splenic and BM B-lymphocytes were CD79a(+)/CD20(+)/IgM(+)/IgD(+)/bcl-2(+)/CD27(+)/DBA.44(-)/CD31(-) and polyclonal by immunophenotype/polymerase chain reaction. PPBL features an expansion of splenic marginal-zone B-lymphocytes, which infiltrate BM sinusoids and circulate in the blood with no evidence of clonality, even in cases with progressive splenomegaly.


Assuntos
Linfócitos B/imunologia , Linfocitose/imunologia , Fumar/imunologia , Baço/imunologia , Esplenomegalia/imunologia , Adolescente , Adulto , Medula Óssea/imunologia , Feminino , Seguimentos , Rearranjo Gênico , Antígenos HLA-DR/análise , Cadeias HLA-DRB1 , Humanos , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/imunologia , Imunofenotipagem , Contagem de Linfócitos , Linfocitose/cirurgia , Masculino , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Esplenectomia , Adulto Jovem
10.
Leuk Lymphoma ; 47(2): 333-6, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16321867

RESUMO

This study hereby reports the case of a 19-year old boy with a gamma-delta hepatosplenic T-cell lymphoma (HSTCL). Initial therapy consisted of four cycles of the IEV (Ifosphamide, Epirubicin and Etoposide) scheme. Further treatment strategy was then adapted according to minimal residual disease monitoring by immunophenotypic and T-cell receptor gamma chain gene evaluation. The patient remains in complete clinical, immunological and molecular remission and in good clinical conditions 48 months after diagnosis and 40 months after stopping therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/biossíntese , Adulto , Citometria de Fluxo , Seguimentos , Hepatomegalia/etiologia , Humanos , Imunofenotipagem , Linfoma de Células T/diagnóstico , Masculino , Neoplasia Residual , Indução de Remissão , Sensibilidade e Especificidade , Esplenomegalia/etiologia , Resultado do Tratamento
12.
J Nucl Med ; 44(8): 1253-62, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12902415

RESUMO

UNLABELLED: Gaucher's disease is a lysosomal storage disorder due to a genetically transmitted deficiency of the enzyme glucocerebrosidase. In the most common form of the disease (type 1), accumulation of glucosylceramide in the reticuloendothelial cells of liver, spleen, and bone marrow leads to visceromegaly, anemia, thrombocytopenia, and osteopenia. Skeletal manifestations secondary to infiltration of the bone marrow by Gaucher's cells are detectable by radiography only in advanced stages. Imaging of bone marrow involvement can be performed indirectly by magnetic resonance techniques or by bone marrow scintigraphy with radiocolloids. However, both procedures lack specificity because the normal bone marrow, rather than the pathologic process, is imaged. The aim of this study was to assess the reliability of (99m)Tc-sestamibi scintigraphy for direct evaluation of bone marrow involvement. METHODS: Seventy-two patients with type 1 and 2 patients with type 3 Gaucher's disease (35 males, 39 females) were enrolled in the study. The mean age +/- SD was 31.9 +/- 16.5 y (range, 3-76 y), and the average duration of the disease manifestations when performing scintigraphy was 12.95 y (median, 10.5 y; range, 0-44 y). Forty-three of 74 patients had never received enzyme replacement therapy (ERT), whereas 31 patients were already being treated with ERT. (99m)Tc-Sestamibi was injected intravenously (6-8 MBq/kg of body weight) and imaging was recorded at the lower limbs 30 min after injection, at the plateau of tracer accumulation in the involved bone marrow. The scans were evaluated visually, assigning a semiquantitative score based on the extension and intensity of uptake in the bone marrow of the lower limbs (0 = no uptake; 8 = maximum uptake). The scintigraphic score was entered into complex statistical analysis, which included a series of clinical and blood chemistry parameters defining overall severity of the disease. RESULTS: (99m)Tc-Sestamibi scintigraphy showed that 71 of 74 patients had some degree of bone marrow involvement. The scintigraphic score was highly correlated with an overall clinical severity score index (SSI) and with various parameters contributing to the SSI, either positively or negatively. The highest correlation of the scintigraphic score was found with an overall biochemical marker of disease severity (serum chitotriosidase). ERT-naive patients showed high correlation of the scintigraphic score with the clinical SSI, with a radiographically based score, and with serum chitotriosidase. In the ERT-treated patients, the scintigraphic score was correlated with the clinical SSI, with hepatomegaly, and with hemoglobin. CONCLUSION: (99m)Tc-Sestamibi uptake reliably identifies bone marrow infiltration by Gaucher's cells. The scintigraphic score is helpful for defining the severity of bone marrow involvement and for comparing patients. (99m)Tc-Sestamibi scintigraphy, which provides topographic information about the sites involved by the disease, is highly correlated with other parameters of disease severity and appears to correlate with response to ERT.


Assuntos
Medula Óssea/diagnóstico por imagem , Medula Óssea/metabolismo , Doença de Gaucher/diagnóstico por imagem , Doença de Gaucher/metabolismo , Tecnécio Tc 99m Sestamibi/farmacocinética , Adolescente , Adulto , Idoso , Medula Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Doença de Gaucher/complicações , Doença de Gaucher/tratamento farmacológico , Glucosilceramidase/uso terapêutico , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/metabolismo , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
13.
Diabetes Educ ; 36(5): 774-83, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20584997

RESUMO

PURPOSE: The purpose of this study was to examine measures of chronic disease severity and treatment according to insurance status in a clinical trial setting. METHODS: Baseline insurance status of 776 patients with type 2 diabetes and stable coronary artery disease (CAD) enrolled in the United States in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial was analyzed with regard to measures of metabolic and cardiovascular risk factor control. RESULTS: Compared with patients with private or public insurance, the uninsured were younger, more often female, and less often white non-Hispanic. Uninsured patients had the greatest burden of CAD. Patients with public insurance were treated with the greatest number of medications, had the greatest self-reported functional status, and the lowest mean glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol values. Overall, for 5 measured risk factor targets, the mean number above goal was 2.49 ± 1.18. After adjustment for demographic and clinical variables, insurance status was not associated with a difference in risk factor control. CONCLUSIONS: In the BARI 2D trial, we did not observe a difference in baseline cardiovascular risk factor control according to insurance status. An important observation, however, was that risk factor control overall was suboptimal, which highlights the difficulty in treating type 2 diabetes and CAD irrespective of insurance status.


Assuntos
Doença das Coronárias/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Seguro Saúde/estatística & dados numéricos , Idoso , Ponte de Artéria Coronária , Doença das Coronárias/economia , Doença das Coronárias/cirurgia , Angiopatias Diabéticas/economia , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/cirurgia , Pessoas com Deficiência , Emprego , Etnicidade , Feminino , Nível de Saúde , Humanos , Masculino , Medicare , Pessoa de Meia-Idade , Grupos Raciais , Aposentadoria , Estados Unidos
14.
J Clin Oncol ; 25(9): 1048-53, 2007 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-17369568

RESUMO

PURPOSE: Polycythemia vera (PV) and essential thrombocythemia (ET) can present in pediatric age as sporadic or familial diseases. To define the biologic profile of childhood PV and ET, we evaluated specific markers in a cohort of pediatric patients affected by PV and ET, including cases with familial occurrence. PATIENTS AND METHODS: Thirty-eight children with PV and ET were investigated. The control group included 58 adults with PV and ET. Endogenous erythroid colonies, qualitative reverse transcriptase polymerase chain reaction for polycythemia rubra vera-1 (PRV-1) RNA expression, human androgen receptor assay and allele specific polymerase chain reaction for JAK2 V617F mutation were undertaken in all patients. Thrombopoietin, thrombopoietin receptor (c-mpl), and erythropoietin receptor mutation analysis was performed by direct sequencing in familial cases. RESULTS: The JAK2 V617F mutation in children with PV was significantly less frequent than in adult PV. The most common myeloproliferative marker found in these patients was PRV-1 RNA overexpression. Children and adults with sporadic ET showed a similar proportion of patients with PRV-1 RNA overexpression, JAK2 V617F mutation, and clonality, while none of the familial ET showed JAK2 V617F mutation and clonality. Also, PRV-1 RNA overexpression was significantly less common. Furthermore, most patients with familial ET exhibited the dominant-positive activating mutation of c-mpl. Finally, children with PV and ET had a significant lower incidence of thrombosis than adults. CONCLUSION: This study demonstrates that familial and sporadic ET recognize different pathogenetic mechanisms. Myeloproliferative markers are specific tests for the diagnosis of ET in children with sporadic forms, while a significant proportion of children with PV can prove negative.


Assuntos
Biomarcadores/sangue , Policitemia Vera/sangue , Policitemia Vera/genética , Trombocitemia Essencial/sangue , Trombocitemia Essencial/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Células Precursoras Eritroides/patologia , Feminino , Seguimentos , Proteínas Ligadas por GPI , Humanos , Incidência , Isoantígenos/sangue , Isoantígenos/genética , Janus Quinase 2/sangue , Janus Quinase 2/genética , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/genética , Linhagem , Policitemia Vera/complicações , Policitemia Vera/patologia , RNA Mensageiro/sangue , Receptores Androgênicos/sangue , Receptores Androgênicos/genética , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/genética , Receptores da Eritropoetina/sangue , Receptores da Eritropoetina/genética , Receptores de Trombopoetina/sangue , Receptores de Trombopoetina/genética , Cidade de Roma/epidemiologia , Trombocitemia Essencial/complicações , Trombocitemia Essencial/patologia , Trombopoetina/sangue , Trombopoetina/genética , Trombose/epidemiologia , Trombose/etiologia , Fatores de Tempo
15.
Blood ; 110(9): 3384-6, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17644735

RESUMO

In the proposed revised World Health Organization (WHO) criteria for the diagnosis of BCR-ABL(-) myeloproliferative diseases (MPDs), exclusion criteria have been replaced by the presence of JAK2 mutations. We applied these criteria to 45 children with MPDs: 13 with polycythemia vera (PV) and 32 with essential thrombocythemia (ET). Among these 45 patients, 12 with ET and 5 with PV had a familial history of MPD, and had been investigated for hereditary mutations of the erythropoietin receptor, thrombopoietin, or MPL genes. We found that the JAK2(V617F) mutation in children occurs less frequently than in adults, and that exon 12 JAK2 mutations are absent. On the basis of the revised WHO criteria, a significant proportion of childhood PVs were misdiagnosed. Furthermore, all familial ET, including patients carrying the hereditary MPL(Ser505Asn) activating mutation, were erroneously diagnosed as MPDs. Our observations suggest that childhood MPDs require a set of specific diagnostic criteria.


Assuntos
Testes Genéticos/métodos , Transtornos Mieloproliferativos/diagnóstico , Cromossomo Filadélfia , Policitemia Vera/diagnóstico , Trombocitemia Essencial/diagnóstico , Organização Mundial da Saúde , Criança , Humanos , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Policitemia Vera/genética , Receptores da Eritropoetina/genética , Receptores de Trombopoetina/genética , Trombocitemia Essencial/genética , Trombopoetina/genética
16.
Blood ; 109(4): 1401-7, 2007 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-17077333

RESUMO

In idiopathic thrombocytopenic purpura (ITP), corticosteroids have been widely recognized as the most appropriate first-line treatment, even if the best therapeutic approach is still a matter of debate. Recently, a single high-dose dexamethasone (HD-DXM) course was administered as first-line therapy in adult patients with ITP. In this paper we show the results of 2 prospective pilot studies (monocentric and multicentric, respectively) concerning the use of repeated pulses of HD-DXM in untreated ITP patients. In the monocenter study, 37 patients with severe ITP, age at least 20 years and no more than 65 years, were enrolled. HD-DXM was given in 4-day pulses every 28 days, for 6 cycles. Response rate was 89.2%; relapse-free survival (RFS) was 90% at 15 months; long-term responses, lasting for a median time of 26 months (range 6-77 months) were 25 of 37 (67.6%). In the multicenter study, 95 patients with severe ITP, age at least 2 years and no more than 70 years, were enrolled. HD-DXM was given in 4-day pulses every 14 days, for 4 cycles; 90 patients completed 4 cycles. Response rate (85.6%) was similar in patients classified by age (<18 years, 36 of 42=85.7%; >or=18 years, 41 of 48=85.4%, P=not significant), with a statistically significant difference between the second and third cycle (75.8% vs 89%, P=.018). RFS at 15 months 81%; long-term responses, lasting for a median time of 8 months (range 4-24 months) were 67 of 90 (74.4%). In both studies, therapy was well tolerated. A schedule of 3 cycles of HD-DXM pulses will be compared with standard prednisone therapy (eg, 1 mg/kg per day) in the next randomized Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) trial.


Assuntos
Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Indução de Remissão
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