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1.
Eur J Haematol ; 104(6): 581-587, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32107795

RESUMO

OBJECTIVE AND METHODS: In order to assess the efficacy of brentuximab vedotin (Bv) in combination with bendamustine (B) in multiple relapsed or refractory (RR) classic Hodgkin lymphoma (cHL), medical records of 47 patients treated with BvB in second relapse or beyond were reviewed. RESULTS: The median number of previous treatments was 2 (1-4). Bv was given at 1.8 mg/kg on day 1 and bendamustine at 90 mg/m2 on days 1 and 2 of a 21-day cycle. The median number of BvB cycles was 4 (2-7), and all patients were evaluable for efficacy. The CR and OR rates were 49% and 79%, respectively; 67% of responding patients and 2 in stable disease proceeded to a SCT procedure. After a median follow-up of 19 months (5-47), median PFS was 18 months (95%CI: 23-29), and the 2-year OS was 72%. Significantly longer PFS and OS were observed in patients attaining a major clinical response to treatment and in those who received consolidation with SCT. Fifteen (32%) patients experienced severe (G > 2) toxicity. The main toxicities were neutropenia (23%), gastrointestinal (10%), peripheral sensory neuropathy (11%), and infection (4%). CONCLUSION: Our real-world results suggest that BvB is an effective third-line rescue and bridge-to-transplant regimen for RR-cHL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Brentuximab Vedotin/administração & dosagem , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Recidiva , Resultado do Tratamento , Adulto Jovem
2.
Haematologica ; 109(7): 2297-2302, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38497158
3.
Br J Haematol ; 183(5): 755-765, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30407629

RESUMO

Splenectomy in addition to immunotherapy with rituximab can provide quick and sometimes durable disease control in patients with splenic marginal zone lymphoma (SMZL). However, systemic chemotherapy is ultimately required in many cases. The BRISMA (Bendamustine-rituximab as first-line treatment of splenic marginal zone lymphoma)/IELSG (International Extranodal Lymphoma Study Group)36 trial is an open-label, single arm phase II study designed by the IELSG in cooperation with the Fondazione Italiana Linfomi and the lymphoma Study Association according to Simon's two-stage method. The primary endpoint was complete response rate. Fifty-six patients with SMZL diagnosis confirmed on central revision were treated with bendamustine (90 mg/m2  days 1, 2) and rituximab (375 mg/m2  day 1) every 28 days for six cycles (B-R). The overall response and CR rates were 91% and 73%, respectively. Duration of response, progression-free survival and overall survival at 3 years were 93% (95% confidence interval [CI] 81-98), 90% (95% CI 77-96) and 96% (95% CI 84-98), respectively. Toxicity was mostly haematological. Neutropenia grade ≥3 was recorded in 43% of patients; infections and febrile neutropenia in 5·4% and 3·6%. Overall, 14 patients (25%) experienced serious adverse events. Five patients (9%) went off-study because of toxicity and one patient died from infection. In conclusion, B-R resulted in a very effective first-line regimen for SMZL. Based on the results achieved in the BRISMA trial, B-R should be considered when a chemotherapy combination with rituximab is deemed necessary for symptomatic SMZL patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Esplênicas/tratamento farmacológico , Adulto , Idoso , Cloridrato de Bendamustina/administração & dosagem , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/administração & dosagem , Esplenectomia , Resultado do Tratamento
4.
Blood ; 123(12): 1836-49, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24452203

RESUMO

Splenic marginal zone lymphoma (SMZL) is a mature B-cell neoplasm characterized by rather indolent clinical course. However, nearly one third of patients experience a rapidly progressive disease with a dismal outcome. Despite the characterization of clone genetics and the recognition of deregulated immunologic stimulation in the pathogenesis of SMZL, little is known about microenvironment dynamics and their potential biological influence on disease outcome. Here we investigate the effect of stroma-intrinsic features on SMZL disease progression by focusing on the microenvironment of the bone marrow (BM), which represents an elective disease localization endorsing diagnostic and prognostic relevance. We show that the quality of the BM stromal meshwork of SMZL infiltrates correlates with time to progression. In particular, we describe the unfavorable prognostic influence of dense CD40 expression by BM stromal cells, which involves the contribution of CD40 ligand (CD40L)-expressing bystander mast cells infiltrating SMZL BM aggregates. The CD40/CD40L-assisted crosstalk between mesenchymal stromal cells and mast cells populating the SMZL microenvironment finds correlation in p53(-/-) mice developing SMZL and contributes to the engendering of detrimental proinflammatory conditions. Our study highlights a dynamic interaction, playing between nonneoplastic elements within the SMZL niche, toward disease progression.


Assuntos
Antígenos CD40/metabolismo , Linfoma de Zona Marginal Tipo Células B/imunologia , Linfoma de Zona Marginal Tipo Células B/patologia , Mastócitos/imunologia , Mastócitos/patologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Linfócitos B/imunologia , Linfócitos B/patologia , Ligante de CD40/metabolismo , Diferenciação Celular , Proliferação de Células , Citocinas/biossíntese , Progressão da Doença , Intervalo Livre de Doença , Feminino , Genes p53 , Humanos , Mediadores da Inflamação/metabolismo , Linfoma de Zona Marginal Tipo Células B/etiologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Pessoa de Meia-Idade , Prognóstico , Microambiente Tumoral/imunologia
5.
Br J Haematol ; 160(2): 207-15, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23167437

RESUMO

The management of patients with Hodgkin lymphoma (HL) recurring after stem cell transplantation (SCT) and multiply relapsed disease remains challenging. We report on 41 such patients who received bendamustine hydrochloride, a bifunctional mechlorethamine derivative mechanistically unrelated to traditional alkylators, after a median of four prior chemotherapy lines, including SCT in 85% of cases. Bendamustine was given at doses of 90-120 mg/m(2) every 21 or 28 d. At first assessment (2-4 cycles), the overall response rate (ORR) was 78% with 12 (29%) complete (CR) and 20 (49%) partial responses (PR). Upon treatment prolongation to 6-8 courses, 40% of PRs progressed, yielding a final ORR of 58% with 31% of CRs. Eight patients (two CRs, six PRs) were subsequently allotransplanted. Median progression-free and overall survival exceeded 11 and 21 months respectively; complete responders displayed a median disease-free survival above 9 months with a relapse rate of only 30%. Outcomes were independent of disease chemosensitivity, previous transplant and bendamustine dose-intensity. No life-threatening or unexpected adverse events occurred. Within the limits of a retrospective analysis and schedule heterogeneity, these results appear very encouraging and prompt prospective trials to confirm bendamustine as a valuable option in the palliative setting and in cytoreductive strategies before allotransplantation.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Terapia de Salvação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cloridrato de Bendamustina , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Terapia Combinada , Reparo do DNA/efeitos dos fármacos , Intervalo Livre de Doença , Avaliação de Medicamentos , Feminino , Doenças Hematológicas/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/patologia , Doença de Hodgkin/radioterapia , Doença de Hodgkin/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Mostarda Nitrogenada/efeitos adversos , Compostos de Mostarda Nitrogenada/farmacologia , Uso Off-Label , Recidiva , Estudos Retrospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
6.
Blood ; 117(9): 2585-95, 2011 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-21119113

RESUMO

The incidental finding of an isolated splenomegaly during clinical assessment of patients evaluated for unrelated causes has become increasingly frequent because of the widespread use of imaging. Therefore, the challenging approach to the differential diagnosis of spleen disorders has emerged as a rather common issue of clinical practice. A true diagnostic dilemma hides in distinguishing pathologic conditions primarily involving the spleen from those in which splenomegaly presents as an epiphenomenon of hepatic or systemic diseases. Among the causes of isolated splenomegaly, lymphoid malignancies account for a relevant, yet probably underestimated, number of cases. Splenic lymphomas constitute a wide and heterogeneous array of diseases, whose clinical behavior spans from indolent to highly aggressive. Such a clinical heterogeneity is paralleled by the high degree of biologic variation in the lymphoid populations from which they originate. Nevertheless, the presenting clinical, laboratory, and pathologic features of these diseases often display significant overlaps. In this manuscript, we present our approach to the diagnosis and treatment of these rare lymphomas, whose complexity has been so far determined by the lack of prospectively validated prognostic systems, treatment strategies, and response criteria.


Assuntos
Linfoma/diagnóstico , Linfoma/terapia , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/terapia , Medula Óssea/patologia , Diagnóstico por Imagem , Humanos , Linfoma/sangue , Linfoma/cirurgia , Esplenectomia , Neoplasias Esplênicas/sangue , Neoplasias Esplênicas/cirurgia
7.
Am J Hematol ; 88(7): 539-44, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23553682

RESUMO

Total body computed tomography (TB-CT) scan is not mandatory in the diagnostic/staging algorithm of chronic lymphocytic leukemia (CLL). The aim of this study was to determine the value and prognostic significance of TB-CT scan in early stage CLL patients. Baseline TB-CT scan was performed in 240 Binet stage A CLL patients (179 Rai low- and 61 Rai intermediate-risk) included in a prospective multicenter observational study (clinicaltrial.gov ID:NCT00917549). The cohort included 69 clinical monoclonal B lymphocytosis (cMBLs). Patients were restaged considering only radiological data. Following TB-CT scans, 20% of cases reclassified as radiologic Binet (r-Binet) stage B. r-Binet B patients showed a higher incidence of unfavorable cytogenetic abnormalities (P = 0.027), as well as a shorter PFS (P = 0.001). At multivariate analysis, r-Binet stage [HR = 2.48; P = 0.004] and IGHV mutational status [HR = 3.01; P = 0.002] retained an independent predictive value for PFS. Among 179 Rai low-risk cases, 100 were redefined as r-Rai intermediate-risk based upon TB-CT scan data, showing a higher rate of cases with higher ZAP-70 (P = 0.033) and CD38 expression (P = 0.029) and ß2-microglobulin levels (P < 0.0001), as well as a shorter PFS than those with r-Rai low-risk (P = 0.008). r-Rai stage [HR = 2.78; P = 0.046] and IGHV mutational status [HR = 4.25; P = 0.009] retained a significant predictive value for PFS at multivariate analysis. Forty-two percent of cMBL patients were reclassified as r-small lymphocytic lymphomas (r-SLLs) by TB-CT scan. TB-CT scan appears to provide relevant information in early stage CLL related to the potential and the timing of patients to progress towards the more advanced disease stages.


Assuntos
Leucemia Linfocítica Crônica de Células B/diagnóstico , Linfocitose/diagnóstico , ADP-Ribosil Ciclase 1/genética , Adulto , Idoso , Linfócitos B/metabolismo , Linfócitos B/patologia , Aberrações Cromossômicas , Progressão da Doença , Feminino , Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico por imagem , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/patologia , Linfocitose/diagnóstico por imagem , Linfocitose/genética , Linfocitose/patologia , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Proteína-Tirosina Quinase ZAP-70/genética , Microglobulina beta-2/genética
8.
Front Immunol ; 14: 1207959, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680642

RESUMO

We have established a pseudotemporal ordering for the transcriptional signatures of distinct microregions within reactive lymphoid tissues, namely germinal center dark zones (DZ), germinal center light zones (LZ), and peri-follicular areas (Peri). By utilizing this pseudotime trajectory derived from the functional microenvironments of DZ, LZ, and Peri, we have ordered the transcriptomes of Diffuse Large B-cell Lymphoma cases. The apex of the resulting pseudotemporal trajectory, which is characterized by enrichment of molecular programs fronted by TNFR signaling and inhibitory immune checkpoint overexpression, intercepts a discrete peri-follicular biology. This observation is associated with DLBCL cases that are enriched in the Unclassified/type-3 COO category, raising questions about the potential extra-GC microenvironment imprint of this peculiar group of cases. This report offers a thought-provoking perspective on the relationship between transcriptional profiling of functional lymphoid tissue microenvironments and the evolving concept of the cell of origin in Diffuse Large B-cell Lymphomas.


Assuntos
Tecido Linfoide , Linfoma Difuso de Grandes Células B , Feminino , Humanos , Linfoma Difuso de Grandes Células B/genética , Centro Germinativo , Folículo Ovariano , Nonoxinol , Microambiente Tumoral/genética
9.
Br J Haematol ; 159(2): 164-71, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22924582

RESUMO

This international retrospective study of 593 Splenic Marginal Zone Lymphoma (SMZL) patients aimed to identify factors that determine treatment initiation and influence lymphoma-specific survival (LSS). Logistic regression was used to identify the factors associated with treatment. A Cox regression was used to analyse LSS in a derivation cohort of 366 patients. This produced a prognostic index (PI) and enabled the identification of three risk groups. The resulting stratification was validated in another cohort of 227 patients and compared with the Interguppo Italiano Linfomi (IIL) score in the group of 450 patients for whom all the required data were available using an extension of the net reclassification improvement. Haemoglobin concentration (Hb), extrahilar lymphadenopathy and hepatitis C virus status were associated with the initiation of treatment. Hb, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy were independently associated with LSS. Three risk groups with significantly different five-year LSS (94%, 78% and 69%, respectively) were identified. This stratification (named HPLL on the basis of determinant factors) had a better discriminative power than the IIL score. This system is useful for stratifying SMZL patients into risk groups and may help in the selection of risk-tailored treatment approaches.


Assuntos
Hemoglobinas/metabolismo , L-Lactato Desidrogenase/sangue , Linfoma de Zona Marginal Tipo Células B , Neoplasias Esplênicas , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfoma de Zona Marginal Tipo Células B/sangue , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/terapia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Retrospectivos , Fatores de Risco , Neoplasias Esplênicas/sangue , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/terapia , Taxa de Sobrevida
10.
Hematol Oncol ; 30(4): 194-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22271092

RESUMO

The purpose of the work was to investigate the factors predicting early resistance to treatment in Hodgkin lymphoma. Many staging parameters, including relative tumour burden (rTB), were analysed in 246 patients with Hodgkin lymphoma in relation to early failure, that is, less than complete remission (i.e. partial response, null response or progression) or occurrence of early relapse, as clinical expressions of resistance to treatment. Patients with early unfavourable disease were 129 and were treated with four to six cycles of ABVD + involved field radiotherapy; 117 patients with advanced stage disease received six cycles of ABVD + optional irradiation to no more than two sites. The rTB was volumetrically measured through the evaluation of staging computed tomography for all the lesions except bone marrow involvement, which was quantified by calculation. The relationship with early resistance was analysed with logistic regressions. The rTB demonstrated to be the best predictor of early failure in both patient subsets, being superior to the multiparameter International Prognostic Score. The rTB showed a significant exponential relationship with the relative risk of early failure, and with inclusion of the extranodal involvement into the model, a single equation became adequate to predict resistance in both early unfavourable and advanced stage patients. The conclusions are that the rTB is the best pretreatment factor related to the risk of resistance to combined ABVD + radiotherapy and that this relationship can be mathematically expressed in an easy way. A simplified assessment of rTB is highly desirable.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Resistencia a Medicamentos Antineoplásicos , Doença de Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Tolerância a Radiação , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação , Adulto , Bleomicina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Doença de Hodgkin/epidemiologia , Doença de Hodgkin/patologia , Humanos , Itália/epidemiologia , Masculino , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Vimblastina/uso terapêutico
11.
Ann Hematol ; 91(7): 1013-22, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22349722

RESUMO

Bendamustine is an alkylating agent with a nitrogen mustard group and a purine-like benzimidazole group. The aim of this study was to collect all the Italian experiences with this drug in order to evaluate the results in term of response to therapy and toxicities. We analyzed lymphoma patients treated in 24 Italian haematological centres with bendamustine alone or in combination with anti-CD20 antibody. One hundred seventy-five relapsed or refractory lymphoma patients were enrolled. The median age was 69 years (range 26-87). Seventy-nine patients were relapsed, 35 were refractory and 61 presented a progressive disease after partial response. The diagnoses were 60 indolent non-follicular lymphomas, 34 diffuse large B-cell lymphomas, 48 follicular lymphomas, 30 mantle cell lymphomas and three peripheral T-cell lymphomas. All patients were evaluable for response: 52 (29%) with complete remission, 72 (43%) with partial response with an overall response rate of 71%, and 51 non-responders. With a median observation period of 10 months (1-43), 70% of patients are alive. In summary, this retrospective study shows that treatment with bendamustine alone or in combination with rituximab is a safe and effective regimen in a subset of multi-resistant patients.


Assuntos
Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Compostos de Mostarda Nitrogenada/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina , Quimioterapia Adjuvante , Feminino , Fundações , Humanos , Itália/epidemiologia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Linfoma não Hodgkin/mortalidade , Masculino , Oncologia/organização & administração , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Compostos de Mostarda Nitrogenada/efeitos adversos , Recidiva , Estudos Retrospectivos , Rituximab , Sociedades Médicas , Análise de Sobrevida , Falha de Tratamento
12.
Br J Haematol ; 153(3): 351-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21371003

RESUMO

To retrospectively assess the efficacy of bendamustine alone and with rituximab (R-B), 109 patients with relapsed chronic lymphocytic leukaemia (CLL) were enrolled in 24 Italian centres. The median age was 66 years (range 39-85). Forty-three percent of patients had relapsed and 57% were resistant (median previous therapies = 3; range 1-8). Twenty-two patients received bendamustine alone and 87 patients received R-B (median B dosage: 100 mg/m(2) per day, range 90-130 mg/m(2) per day). The overall response rate was 69·6% (complete response 28·6%; partial response 41%), and was significantly higher in patients treated with R-B (P = 0·014) and in those responsive to the previous treatment (P=0·04). After a median follow-up of 7·9 months (range 1-148), the median progression-free survival was 16 months and the median duration of response was 13 months. Median overall survival (OS) was 16·8 months for the whole cohort; patients not responding to the treatment had a significantly worse outcome than those who attained a response (P = 0·0001). In multivariate analysis, only resistant disease status at start of bendamustine treatment (HR 3·2, 95% CI 1·4-7·3, P = 0·006) had an independent prognostic value for OS. Toxicity was manageable and mostly haematological. In conclusion, in our experience R-B was an effective and well-tolerated treatment for relapsed/refractory CLL patients, producing a remarkable high CR rate and mild toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Compostos de Mostarda Nitrogenada/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina , Avaliação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Mostarda Nitrogenada/administração & dosagem , Compostos de Mostarda Nitrogenada/efeitos adversos , Recidiva , Rituximab , Resultado do Tratamento
13.
Cancer Med ; 9(18): 6565-6575, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32710498

RESUMO

PURPOSE: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. PATIENTS AND METHODS: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). RESULTS: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP  = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. CONCLUSIONS: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/efeitos adversos , Bleomicina/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Dacarbazina/efeitos adversos , Dacarbazina/uso terapêutico , Progressão da Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/etiologia , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Transplante de Células-Tronco , Fatores de Tempo , Transplante Autólogo , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
14.
Haematologica ; 94(1): 127-30, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19029148

RESUMO

CD146(+) bone marrow stromal cells have been recently recognized as clonogenic osteoprogenitors able to organize a complete hematopoietic microenvironment. In this study we used immunohistochemical analysis to investigate the contribution of CD146(+) bone marrow osteoprogenitors to the stromal remodeling occurring in the different stages of primary myelofibrosis. We found that CD146(+) cells sited at the abluminal side of the bone marrow vessels and branching among hematopoietic cells significantly increased in the advanced stages of primary myelofibrosis (p<0.001), paralleling the extent of fibrosis (rho=0.916, p<0.0001) and the microvascular density (r=0.883, p<0.0001). Coherently with a mural cell function, such cells also displayed smooth-muscle actin expression. Our data providing evidence of CD146(+) cell involvement in bone marrow stromal changes occurring in primary myelofibrosis are consistent with the capability of these cells to participate in fiber deposition, angiogenesis, and bone formation. They could also represent rationale for new therapies targeting the bone marrow stroma in primary myelofibrosis.


Assuntos
Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Antígeno CD146/metabolismo , Mielofibrose Primária/metabolismo , Mielofibrose Primária/patologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proliferação de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
15.
Liver Int ; 29(8): 1171-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19602139

RESUMO

BACKGROUND/AIM: Patients with an occult hepatitis B virus (HBV) infection undergoing deep immunosuppression are potentially at risk of HBV reactivation. In order to assess whether a polymerase chain reaction (PCR) assay for HBV DNA in serum could be used to predict the reactivation of an occult HBV infection, we performed a retrospective study in a cohort of Sicilian patients with oncohaematological diseases. METHODS: We studied by a highly sensitive ad hoc nested PCR for serum HBV DNA 75 HBsAg-negative oncohaematological patients requiring chemotherapy. RESULTS: Thirty-three patients (44%) were HBV seronegative (anti-HBc and anti-HBs negative) and 42 patients (56%) were HBV seropositive (anti-HBc and/or anti-HBs positive). Baseline serum HBV DNA was positive in nine out of 33 HBV-seronegative patients and in nine out of 42 HBV-seropositive patients (27.3 vs. 21.4%; P=NS). HBsAg seroconversion was observed in five out of 33 seronegative vs. six out of 42 seropositive patients (15 vs. 14%, P=0.9), and in five out of 18 HBV DNA-positive vs. six out of 57 HBV DNA-negative patients (27.7 vs. 10.6%P=0.11). Hepatitis C virus infection was found in 18 patients (24.3%), although with no correlation to HBV serological status, presence of serum HBV DNA or frequency of HBsAg seroconversion. CONCLUSIONS: In oncohaematological patients undergoing chemotherapy, highly sensitive serum HBV DNA testing at baseline has a 28% predictive ability to forecast HBsAg seroconversion in HBV DNA-positive patients, and a 90% ability to forecast persistent HBsAg negativity in HBV DNA-negative patients, a better performance than serological tests.


Assuntos
DNA Viral/sangue , Neoplasias Hematológicas/sangue , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Antineoplásicos/uso terapêutico , Estudos de Coortes , Comorbidade , Feminino , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/virologia , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Fatores de Risco , Ativação Viral
16.
Oncol Rep ; 21(4): 1029-35, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19288005

RESUMO

The aim of this study was to evaluate the apoptotic damage to bone marrow cells caused by three chemotherapy regimens for advanced Hodgkin's lymphoma, ABVD, COPPEBVCAD and BEACOPP, which were randomly administered in the HD 2000 GISL trial. Bone marrow mononuclear cells (BMMCs) stained with anti-CD34 antibody and Annexin V, were evaluated by flow cytometry before starting chemotherapy, 30 days after completing chemotherapy and after 6 months. Results are expressed as the percentages of BMMCs positive to anti-CD34, to Annexin V or to both. Fourteen patients treated with ABVD, 11 with COPPEBVCAD and 13 with BEACOPP were evaluated before and 30 days after treatment. Late assessments were made in 6, 7 and 8 of them, respectively. No differences were found among the pretherapeutic flow cytometry findings in relation to the staging characteristics (marrow involvement included). All the regimens increased the apoptotic fraction of the whole mononuclear bone marrow cells (COPPEBVCAD did so significantly) and increased the CD34+ compartment (with significant early differences after ABVD and BEACOPP, tending to late persistence for ABVD, only). All the regimens increased the apoptotic CD34+ cells within the whole BMMC population (significantly after BEACOPP), although with a general trend to decrease in their percentage within the CD34+ compartment over time, even after the most dose-dense regimens. Based on the variations induced in the apoptotic fraction of all mononuclear and CD34+ cells, ABVD was the least toxic regimen and COPPEBVCAD the most toxic one.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Células-Tronco Hematopoéticas/efeitos dos fármacos , Doença de Hodgkin/tratamento farmacológico , Adolescente , Adulto , Idoso , Antígenos CD34/análise , Apoptose/efeitos dos fármacos , Bleomicina/efeitos adversos , Ciclofosfamida/efeitos adversos , Dacarbazina/efeitos adversos , Doxorrubicina/efeitos adversos , Etoposídeo/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Procarbazina/efeitos adversos , Vimblastina/efeitos adversos , Vincristina/efeitos adversos
17.
Clin Lymphoma Myeloma ; 9(2): 138-44, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19406724

RESUMO

PURPOSE: In the pre-positron emission tomography era, the Gruppo Italiano Studio Linfomi (GISL) investigated the feasibility and efficacy of a treatment based on a response-tailored number of doxorubicin/bleomycin/vinblastine/dacarbazine (ABVD) courses in 218 intermediate-stage Hodgkin lymphoma patients. PATIENTS AND METHODS: Patients with stage I/II showing at least one adverse prognostic factor and stage IIIA without adverse prognostic factors were recruited. Treatment included a first step of 3 ABVD courses, followed by an early-restaging. Patients in CR/CRu received 1 additional ABVD cycle, patients in PR received 3 more ABVD, and nonresponder patients went off study. Involved-field radiation therapy (RT) was recommended on chemotherapy completion. RESULTS: The median age was 30 years (range, 15-68 years) and 131 patients (61%) were female. Seven percent of patients were in stage I, 78% in stage II, and 15% in stage III; B-symptoms, bulky tumor and erythrocyte sedimentation rate > 30 were recorded in 20%, 26%, and 43% of cases, respectively. The CR/CRu rate was 62% at early restaging, 72% at the end of chemotherapy, and 95% following RT. With a median follow-up of 74 months (range, 6-193 months), 7-year overall survival, relapse-free survival, and freedom from treatment failure were 91.8% (95% CI, 86%-95.5%), 89.2% (95% CI, 82.8%-93.3%), and 81.8% (95% CI, 75.2%-86.7%), respectively. Patients in CR/CRu on early restaging, receiving 4 ABVD, had an excellent outcome with 7-year RFS and cause-specific survival similar to those of the late responders treated with 6 ABVD (RFS, 87.5% vs. 90.5% and CSS, 96.6% vs. 92.7%, respectively). CONCLUSION: The response-guided ABVD program we report, based on standard clinical staging procedures, proved to be feasible and safe in patients with intermediate-stage Hodgkin lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Terapia Combinada , Dacarbazina/administração & dosagem , Dacarbazina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto Jovem
18.
Crit Rev Oncol Hematol ; 68(3): 264-71, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18684638

RESUMO

Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive neoplasm clinically characterized by sudden onset of constitutional symptoms, lymphadenopathy, hepatosplenomegaly, frequent autoimmune phenomena, particularly hemolytic anemia and thrombocytopenia, and polyclonal hypergammaglobulinemia. The lymph node histological picture is also distinctive, constituted by a polymorphic infiltrate, a marked proliferation of high endothelial venules, and a dense meshwork of dentritic cells. The neoplastic CD4+ T-cells represent a minority of the lymph node cell population; its detection is facilitated by the aberrant expression of CD10. Almost all cases arbor an EBV infected B-cell population. Patients with AITL have a poor prognosis with conventional treatment, with a median overall survival of less than 3 years. Patients achieving a good clinical response seem beneficiate from a consolidation with high-dose therapy and autologous stem cell transplantation. Constitutional symptoms and autoimmune phenomena, and some times also the neoplastic masses may respond to immunosuppressive or immunomodulatory agents such as thalidomide.


Assuntos
Imunossupressores/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Transplante de Células-Tronco , Talidomida/uso terapêutico , Linfócitos B/metabolismo , Linfócitos B/patologia , Linfócitos B/virologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/patologia , Proliferação de Células , Células Dendríticas/metabolismo , Células Dendríticas/patologia , Infecções por Vírus Epstein-Barr/metabolismo , Infecções por Vírus Epstein-Barr/mortalidade , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Herpesvirus Humano 4 , Humanos , Linfonodos/metabolismo , Linfonodos/patologia , Linfoma de Células T/metabolismo , Linfoma de Células T/mortalidade , Linfoma de Células T/patologia , Masculino , Neprilisina/metabolismo , Taxa de Sobrevida , Transplante Autólogo
19.
Hematol Rep ; 10(1): 7523, 2018 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-29721255

RESUMO

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somatic mutation in PIG-A gene that results in the absence of CD55 and CD59, two important complement regulatory proteins. In this paper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms is described, together with an adequate follow- up over a 7-years treatment period. In this case, the not specificity and the limited clinical relevance of the symptoms led to a delay in diagnosis. After thrombosis, Eculizumab therapy has been shown to be effective, and during seven years of followup no events have occurred that put the patient's life at risk. A multidisciplinary approach is crucial in cases like this, in order to allow early diagnosis and minimize the risks for the patients.

20.
Clin Cancer Res ; 12(2): 529-35, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16428496

RESUMO

PURPOSE: MOPPEBVCAD (mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine) chemotherapy with limited radiotherapy was devised in 1987 to reduce late toxicity and second tumor incidence while trying to improve effectiveness through increases of dose intensity and dose density. Late results, toxicity, and second tumor incidence were reviewed in all the patients treated. EXPERIMENTAL DESIGN: The drugs of three previous alternating regimens [CAD (lomustine, melphalan, and vindesine), MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), and ABV (doxorubicin, bleomycin, and vinblastine)] were intensified and hybridized, the cumulative dose of mechlorethamine was lowered, and irradiation was delivered to no more than two sites either bulky or partially responding to chemotherapy. RESULTS: A total of 307 previously untreated advanced-stage patients underwent MOPPEBVCAD chemotherapy. Radiotherapy was delivered to 118 of 307 patients (38%). Remission was complete in 290 patients (94%). With a median follow-up of 114 months, 10-year overall, disease-free, and failure-free survival rates were 79%, 84%, and 71%, respectively. Forty-two patients relapsed and 60 died. The causes of death were Hodgkin's lymphoma in 36 patients, second neoplasms in 12, cardiorespiratory diseases in 4, pulmonary diseases in 2, and unknown in 6. Sixteen second tumors (of which nine were myelodysplasia and/or acute leukemia) were diagnosed in all. Outside this series of 307 patients, MOPPEBVCAD obtained complete responses in 12 of 15 relapsed and 9 of 9 refractory patients who had previously been treated with other regimens. CONCLUSIONS: Clinical response and long-term results are very satisfactory, whereas the second tumor incidence was lower than would have been expected with MOPP analogues. Given its response/late toxicity balance, MOPPEBVCAD does not undermine the leading role of ABVD as first-line regimen but can be indicated as a very effective second-line conventional therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Segunda Neoplasia Primária/etiologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Bleomicina/administração & dosagem , Bleomicina/toxicidade , Terapia Combinada , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epirubicina/administração & dosagem , Epirubicina/toxicidade , Feminino , Doença de Hodgkin/mortalidade , Humanos , Lomustina/administração & dosagem , Lomustina/toxicidade , Masculino , Mecloretamina/administração & dosagem , Mecloretamina/toxicidade , Pessoa de Meia-Idade , Projetos Piloto , Prednisona/administração & dosagem , Prednisona/toxicidade , Procarbazina/administração & dosagem , Procarbazina/toxicidade , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/toxicidade , Vincristina/administração & dosagem , Vincristina/toxicidade , Vindesina/administração & dosagem , Vindesina/toxicidade
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