RESUMO
Systemic mastocytosis (SM) is a myeloproliferative neoplasm displaying abnormal mast cell proliferation. It is subdivided into different forms, including aggressive systemic mastocytosis (ASM) and systemic mastocytosis with an associated hematologic neoplasm (SM-AHN). Oncogenic genetic alterations include point mutations, mainly the KIT D816V, conferring poor prognosis and therapy resistance, and fusion genes, with those involving PDGFRA/PDGFRB as the most recurrent events. We here describe an ASM case negative to the KIT D816V and JAK2 V617F alterations but showing a RUNX1 frameshift heterozygous mutation and the co-occurrence of three fusion transcripts. The first one, PRKG2::PDGFRB, was generated by a balanced t(4;5)(q24;q32) translocation as the sole abnormality. Other two novel chimeras, KAT6A::NCOA2 and RXRA::NOTCH1, originated from cryptic intra-chromosomal abnormalities. The patient rapidly evolved towards SM-AHN, characterized by the persistence of the PRKG2::PDGFRB chimera, due to the presence of an extra copy of the der(5)t(4;5)(q24;q34) chromosome and an increase in the RUNX1 mutation allelic frequency. The results indicated that the transcriptional landscape and the mutational profile of SM deserve attention to predict the evolution and prognosis of this complex disease, whose classification criteria are still a matter of debate.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Mutação da Fase de Leitura , Mastocitose Sistêmica , Proteínas de Fusão Oncogênica , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Mastocitose Sistêmica/genética , Proteínas de Fusão Oncogênica/genética , Receptor Notch1/genética , Coativador 2 de Receptor Nuclear/genética , Masculino , Heterozigoto , Feminino , Pessoa de Meia-Idade , Histona AcetiltransferasesRESUMO
OBJECTIVE: To determine the incremental cost-effectiveness ratios (ICERs) of two therapeutic regimens of infliximab for ankylosing spondylitis (AS). METHODS: 230 patients with active AS who were participating in a randomised controlled trial comparing two infliximab infusion modalities-every 6 weeks (Q6) and on demand (DEM)-were included in an economic evaluation within the trial. Data were collected by phone every 3 months for 1 year. Direct and indirect costs were calculated from a payer perspective. Health-related quality of life was assessed with a general health rating scale. ICERs were calculated for one 20% improvement (ASAS20), for one partial remission and for one quality-adjusted life year (QALY) gained. RESULTS: The Q6 regimen was significantly more efficacious than the DEM regimen but also more costly (euro22 388 vs euro17 596; p<0.001), because it required significantly more infliximab infusions per patient (8.4 vs 6.2). The ICERs of the Q6 to DEM regimen were euro15 841 for one ASAS20 response, euro23 296 for one partial remission and euro50 760 for one QALY gained. CONCLUSION: The administration of infliximab every 6 weeks is cost effective as compared with a DEM regimen; however, the ICER is close to the acceptability threshold of euro50 000 for one QALY gained. TRIAL REGISTRATION NUMBER: NCT 00439283.
Assuntos
Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Adulto , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/economia , Antirreumáticos/uso terapêutico , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Esquema de Medicação , Custos de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença , Espondilite Anquilosante/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To evaluate the clinical characteristics and outcome of NK/T-cell lymphoma 'nasal type' developed in Italian patients. PATIENTS: Between 1997 and 2004, 26 new cases of NK/T-cell lymphoma 'nasal type' were diagnosed in 10 Italian Hematology institutions. RESULTS: All patients were Caucasian, male/female ratio was 19/7, with a median age of 50 years (range 20-80). In 23 cases presentation at the onset was in the nasal cavity or adjacent structures, in two cases the lymphoma onset with skin lesions was followed successively by rhynopharyngeal dissemination, while the remaining case had bone marrow and lymph node involvement followed by oro-pharyngeal involvement. Regarding the stage of disease: 12 patients were in stage I; six in stage II; eight in stage IV. Diagnosis was based on the finding of a NK/T-cell phenotype at the histological and immunophenotypic examination of oropharyngeal or cutaneous lesions. All patients but one were treated with chemotherapy, alone in nine cases or associated to radiotherapy in 14 cases; two patients had chemotherapy, radiotherapy and surgery, while one patient underwent only surgery. Chemotherapy was anthracycline-based in 17 out of 25 cases. In those patients in whom radiotherapy was performed, radiation dosages ranged between 36 Gy and 47.5 Gy, with a median dosage of 40 Gy. Nine patients (34%) were responsive to the treatments: six patients obtained a complete remission and other three a partial remission. The remaining 17 patients resulted refractory or presented a limited response to therapy. The median disease-free survival was 14 months and the median overall survival time was 9 months. CONCLUSION: The results of this retrospective survey confirmed that NK/T-cell lymphoma 'nasal type' is a very rare lymphoma in the Italian population, and it is characterized by a very bad prognosis. Due to the rarity of this disease, a standardized therapeutic approach is lacking. More data are needed to know the epidemiology of this kind of lymphoma in Europe.
Assuntos
Células Matadoras Naturais/patologia , Linfoma de Células T/patologia , Cavidade Nasal/patologia , Estadiamento de Neoplasias , Neoplasias Nasais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/terapia , Prognóstico , Dosagem Radioterapêutica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: To assess the incidence of infusion reactions in patients with rheumatoid arthritis (RA) receiving infliximab treatment with and without betamethasone premedication. To determine whether patients with an atopic diathesis had a better response to corticosteroid pretreatment than those without, and the course of patients' functional capacity and quality of life. PATIENTS AND METHODS: A prospective, multicentre, randomised, double blind phase 4 study of 355 patients with RA in two groups: group A received betamethasone and group B placebo, before a 36 week infusion treatment with infliximab. Incidence and severity of infusion reactions from infliximab treatment were assessed. RESULTS: The incidence of reactions to infliximab infusion was <5%. More infusion reactions occurred with betamethasone pretreatment than with placebo. Response to infliximab of patients with atopic backgrounds did not differ in the presence or absence of betamethasone from that of non-atopic patients. Mean Health Assessment Questionnaire score improved by 47% at week 24, quality of life assessed by Short Form-36 improved in mental and physical component subscales. CONCLUSIONS: Incidence of infusion reactions with infliximab was low and their severity generally mild, but betamethasone pretreatment did not decrease the incidence and severity of infusion reactions. Betamethasone, therefore, is not recommended as a systematic prophylactic measure, even in atopic patients.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Betametasona/uso terapêutico , Adulto , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/patologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Indicadores Básicos de Saúde , Humanos , Infliximab , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
In this paper we analysed clinical, laboratory characteristics and outcome of patients with haematological diseases who developed an Aspergillus niger infection, in a multicentre study involving 14 Italian Haematological Divisions during a 10-year period. The study recorded 194 consecutive microbiologically documented aspergilloses, eight of which (4%) were due to A. niger, and were observed only in five of the participating centres. The primary localization of infection was lung in seven cases and paranasal sinus in one case. Seven patients died at the end of follow-up. The death was mainly attributable to A. niger progression in six of them. Our study that collected the largest number of cases of A. niger infection in haematological malignancies confirms that this infrequent complication is characterized by a high mortality rate.
Assuntos
Anemia Aplástica/complicações , Aspergilose , Aspergillus niger , Leucemia/complicações , Pneumopatias Fúngicas , Linfoma/complicações , Adulto , Idoso , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/mortalidade , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/isolamento & purificação , Líquido da Lavagem Broncoalveolar/microbiologia , Evolução Fatal , Feminino , Humanos , Leucemia/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Linfoma/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Escarro/microbiologia , Resultado do TratamentoRESUMO
In the bone marrow transplant setting, several authors hypothesized that severely overweight patients are at increased risk of transplant-related toxicity, but different definitions of obesity, different body weight groupings and heterogeneous samples of patients were analyzed. To overcome these limitations, we retrospectively considered a homogeneous group of 54 patients (median age 36.5 years), with a diagnosis of de novo acute myeloid leukemia (AML), autografted in first complete remission (CR) with the Bu-Cy2 conditioning regimen, dosed on actual body weight. Patients were classified into three groups (obese, non-obese, underweight) using body mass index (BMI = kg/m(2)); for each group we analyzed transplant-related toxicity and mortality, overall survival and disease-free survival (OS/DFS). In spite of the relatively small number of patients, in our results high BMI appears a predictive factor for an increase of treatment-related toxicity and mortality. Moreover, 30 (55%) patients are currently alive in continuous CR, and after a median follow-up of 76.5 months (range 14-137) statistically significant differences in OS and DFS were detected between obese and non-obese groups (P = 0.012 and 0.021, respectively). Our study suggests that obesity may represent an independent risk factor for autograft in AML and further investigations are warranted.