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1.
Blood ; 142(17): 1438-1447, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37418685

RESUMO

Treatment of diffuse large B-cell lymphoma (DLBCL) in older patients is challenging, especially for those who are not eligible for anthracycline-containing regimens. Fondazione Italiana Linfomi (FIL) started the FIL_ReRi study, a 2-stage single-arm trial to investigate the activity and safety of the chemo-free combination of rituximab and lenalidomide (R2) in ≥70-year-old untreated frail patients with DLBCL. Frailty was prospectively defined using a simplified geriatric assessment tool. Patients were administered a maximum of 6 28-day cycles of 20 mg oral lenalidomide from days 2 to 22 and IV rituximab 375 mg/m2 on day 1, with response assessment after cycles 4 and 6. Patients with partial response or complete response (CR) at cycle 6 were administered lenalidomide 10 mg/d from days 1 to 21 for every 28 cycles for a total of 12 cycles or until progression or unacceptable toxicity. The primary end point was the overall response rate (ORR) after cycle 6; the coprimary end point was the rate of grade 3 or 4 extrahematological toxicity. The ORR was 50.8%, with 27.7% CR. After a median follow-up of 24 months, the median progression-free survival was 14 months, and the 2-year duration of response was 64%. Thirty-four patients experienced extrahematological toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events grade ≥3. The activity of the R2 combination was observed in a significant proportion of subjects, warranting further exploration of a chemo-free approach in frail older patients with DLBCL. This trial was registered at EudraCT as #2015-003371-29 and clinicaltrials.gov as #NCT02955823.


Assuntos
Idoso Fragilizado , Linfoma Difuso de Grandes Células B , Humanos , Idoso , Rituximab/uso terapêutico , Lenalidomida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma Difuso de Grandes Células B/patologia , Resultado do Tratamento
2.
Br J Haematol ; 205(1): 166-174, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38532575

RESUMO

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of haematological cancers with generally poor clinical outcomes. However, a subset of patients experience durable disease control, and little is known regarding long-term outcomes. The International T-cell Lymphoma Project (ITCLP) is the largest prospectively collected cohort of patients with PTCLs, providing insight into clinical outcomes at academic medical centres globally. We performed a long-term outcome analysis on patients from the ITCLP with available 10-year follow-up data (n = 735). The overall response rate to first-line therapy was 68%, while 5- and 10-year overall survival estimates were 49% and 40% respectively. Most deaths occurred prior to 5 years, and for patients alive at 5 years, the chance of surviving to 10 years was 84%. However, lymphoma remained the leading cause of death in the 5- to 10-year period (67%). Low-risk International Prognostic Index and Prognostic Index for T-cell lymphoma scores both identified patients with improved survival, while in multivariate analysis, age >60 years and Eastern Cooperative Oncology Group performance status 2-4 were associated with inferior outcomes. The favourable survival seen in patients achieving durable initial disease control emphasizes the unmet need for optimal front-line therapeutic approaches in PTCLs.


Assuntos
Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/mortalidade , Linfoma de Células T Periférico/terapia , Linfoma de Células T Periférico/tratamento farmacológico , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Seguimentos , Adulto , Estudos Prospectivos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Prognóstico , Adulto Jovem , Adolescente
3.
Haematologica ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385243

RESUMO

The IELSG38 trial was conducted to investigate the effects of subcutaneous (SC) rituximab on the complete remission (CR) rate and the benefits of SC maintenance in patients with extranodal marginal zone lymphoma (MZL) who received frontline treatment with chlorambucil plus rituximab. Study treatment comprised an induction phase with chlorambucil 6 mg/m2/day orally on weeks 1-6, 9-10, 13-14, 17-18, and 21-22, and rituximab 375 mg/m2 intravenously on day 1 of weeks 1-4, and 1400 mg SC on weeks 9, 13, 17, and 21. Then, a maintenance phase followed with rituximab administered at 1400 mg SC every two months for two years. Of the 112 patients enrolled, 109 were evaluated for efficacy. The CR rates increased from 52% at the end of the induction phase to 70% upon completion of the maintenance phase. With a median follow-up of 5.8 years, the 5-year event-free, progression-free, and overall survival rates were 87% (95% CI, 78-92), 84% (95% CI, 75-89), and 93% (95% CI, 86-96), respectively. The most common grade ≥3 toxicities were neutropenia (33%) and lymphocytopenia (16%). Six patients experienced treatment-related serious adverse events, including fever of unknown origin, sepsis, pneumonia, respiratory failure, severe cerebellar ataxia, and fatal acute myeloid leukemia. The trial showed that subcutaneous rituximab did not improve the complete remission rate at the conclusion of the induction phase, which was the main endpoint. Nevertheless, SC maintenance might have facilitated long-term disease control, potentially contributing to enhanced event-free and progression-free survival.

4.
Br J Haematol ; 201(4): 653-662, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36733229

RESUMO

Up to 10%-15% of diffuse large B-cell lymphoma (DLBCL) are related to hepatitis C virus (HCV) infection, in particular in elderly patients. The Fondazione Italiana Linfomi has recently published a multicentre prospective observational study, the 'Elderly Project', on the outcome of DLBCL in patients aged ≥65 years, evaluated using a simplified comprehensive geriatric assessment. The aim of this study was to compare biological and clinical features of HCV positive (HCV+) with HCV negative (HCV-) cases. A total of 89 HCV+ patients were identified out of 1095 evaluated for HCV serology (8.1%). The HCV+ patients were older, less fit, and had frequent extranodal involvement. The cell-of-origin determination by Nanostring showed that HCV+ cases less frequently had an activated B-cell profile compared to HCV- patients (18% vs. 43%). In all, 86% of HCV+ patients received rituximab-cyclophosphamide, doxorubicin, vincristine (Oncovin) and prednisone (R-CHOP)-like immunochemotherapy. Grade 3-4 liver toxicity occurred in 3% of cases. Among centrally reviewed cases confirmed as DLBCL, the 3-year overall survival of HCV+ patients was very similar to HCV- (63% vs. 61%, p = 0.926). In all, 20 HCV+ patients were treated with direct-acting antiviral agents (DAAs), with good tolerance and sustained virological response in all cases. The 3-year progression-free survival for this subgroup was excellent (77%), suggesting DAAs' possible role in reducing the risk of relapse by eliminating the viral trigger.


Assuntos
Hepatite C Crônica , Hepatite C , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Hepacivirus/genética , Antivirais/uso terapêutico , Estudos Prospectivos , Hepatite C Crônica/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Rituximab/uso terapêutico , Doxorrubicina/uso terapêutico , Vincristina/uso terapêutico , Ciclofosfamida/uso terapêutico , Prednisona/uso terapêutico
5.
Haematologica ; 108(4): 1083-1091, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36384247

RESUMO

Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians [LO]) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.


Assuntos
Linfoma Difuso de Grandes Células B , Octogenários , Idoso , Idoso de 80 Anos ou mais , Humanos , Rituximab , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antraciclinas/uso terapêutico , Linfoma Difuso de Grandes Células B/patologia , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Vincristina/uso terapêutico , Estudos Retrospectivos
6.
Hematol Oncol ; 41(1): 78-87, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36177902

RESUMO

The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index and has been validated to predict overall survival in older patients with diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3 months were available. Three main treatment groups were identified based on the anthracycline amount administered: cases receiving >70% of the theoretical anthracyclines dose (Full Dose [FD] group), ≤70% (Reduced Dose [RD]) and palliative therapy (PT; no anthracyclines). The primary endpoint was early mortality rate, defined as death for any cause occurring within 90 days from diagnosis. We identified 1150 patients with a median age of 76 years (range 65-94). Overall, 69 early deaths were observed, accounting for 19% of all reported deaths. The cumulative rate of early mortality at 90 days was 6.0%. Comparing early with delayed deaths, we observed a lower frequency of deaths due to lymphoma progression (42% vs. 75%; p < 0.001) and a higher frequency due to toxicity and infections (22% vs. 4%, p < 0.001, and 22% vs. 3%, p < 0.001, respectively) for early events. A multivariable logistic analysis on 931 patients (excluding PT) confirmed an independent association of high-risk EPI (odds ratio [OR] 3.60; 95% confidence interval [CI] 1.15-11.2) and bulky disease (OR 2.08; 95% CI 1.09-3.97) with the risk of early mortality. The cumulative incidence of early mortality for older patients with DLBCL is not negligible and is mainly associated with non-lymphoma related events. For patients receiving anthracyclines, high-risk EPI and bulky disease are associated with a higher probability of early mortality.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Humanos , Idoso , Idoso de 80 Anos ou mais , Prognóstico , Rituximab , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antibióticos Antineoplásicos/uso terapêutico , Antraciclinas , Linfoma Difuso de Grandes Células B/patologia
7.
Oncologist ; 26(2): e336-e337, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33044758

RESUMO

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.


Assuntos
COVID-19/prevenção & controle , Tumor do Seio Endodérmico/terapia , Transplante de Células-Tronco Hematopoéticas/normas , Doença de Hodgkin/terapia , Controle de Infecções/normas , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/transmissão , Teste para COVID-19/normas , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/imunologia , Humanos , Masculino , Pandemias/prevenção & controle , Roupa de Proteção/normas , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/normas , Transplante Autólogo/normas , Resultado do Tratamento
8.
Oncologist ; 24(9): 1246-1252, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30940746

RESUMO

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma subtype, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis with currently available treatments. Lenalidomide is available in Italy for patients with rrDLBCL based on a local disposition of the Italian Drug Agency. SUBJECTS, MATERIALS, AND METHODS: An observational retrospective study was conducted in 24 Italian hematology centers with the aim to improve information on effectiveness and safety of lenalidomide use for rrDLBCL in real practice. RESULTS: One hundred fifty-three patients received lenalidomide for 21/28 days with a median of four cycles. At the end of therapy, there were 36 complete responses (23.5%) and 9 partial responses with an overall response rate (ORR) of 29.4%. In the elderly (>65 years) subset, the ORR was 33.6%. With a median follow-up of 36 months, median overall survival was reached at 12 months and median disease-free survival was not reached at 62 months. At the latest available follow-up, 29 patients are still in response out of therapy. Median progression-free survivals differ significantly according to age (2.5 months vs. 9.5 in the younger vs. elderly group, respectively) and to disease status at the latest previous therapy (15 months for relapsed patients vs. 3.5 for refractory subjects). Toxicities were manageable, even if 30 of them led to an early drug discontinuation. CONCLUSION: Lenalidomide therapy for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients. IMPLICATIONS FOR PRACTICE: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and approximately 50% of the patients are >60 years of age. Patients with relapsed/refractory (rr) disease have a poor prognosis, reflected by the remarkably short life expectancy of 12 months with currently available treatments. The rrDLBCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for patients with rrDLBCL is effective and tolerable even in a real-life context, especially for elderly patients.


Assuntos
Lenalidomida/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Itália/epidemiologia , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Indução de Remissão , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Resultado do Tratamento
9.
Oncologist ; 24(8): e720-e729, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30552159

RESUMO

BACKGROUND: International guidelines suggest hepatitis C virus (HCV) eradication by direct-acting antivirals (DAAs) after first-line immunochemotherapy (I-CT) in patients with HCV-positive diffuse large B-cell lymphoma (DLBCL), although limited experiences substantiate this recommendation. Moreover, only a few data concerning concurrent administration of DAAs with I-CT have been reported. SUBJECTS, MATERIALS, AND METHODS: We analyzed hematological and virological outcome and survival of 47 consecutive patients with HCV-positive DLBCL treated at 23 Italian and French centers with DAAs either concurrently (concurrent cohort [ConC]: n = 9) or subsequently (sequential cohort [SeqC]: n = 38) to first-line I-CT (mainly rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]-like). RESULTS: Median age was 61 years, 89% of patients had stage III/IV, and 25% presented evidence of cirrhosis. Genotype was 1 in 56% and 2 in 34% of cases. Overall, 46 of 47 patients obtained complete response to I-CT. All patients received appropriate DAAs according to genotype, mainly sofosbuvir-based regimens (n = 45). Overall, 45 patients (96%) achieved sustained virological response, 8 of 9 in ConC and 37 of 38 in SeqC. DAAs were well tolerated, with only 11 patients experiencing grade 1-2 adverse events. Twenty-three patients experienced hepatic toxicity (grade 3-4 in seven) following I-CT in SeqC, compared to only one patient in ConC. At a median follow-up of 2.8 years, two patients died (2-year overall survival, 97.4%) and three progressed (2-year progression-free survival, 93.1%). CONCLUSION: Excellent outcome of this cohort of HCV-positive DLBCL suggests benefit of HCV eradication by DAAs either after or during I-CT. Moreover, concurrent DAAs and R-CHOP administration appeared feasible, effective, and ideally preferable to deferred administration of DAAs for the prevention of hepatic toxicity. IMPLICATIONS FOR PRACTICE: Hepatitis C virus (HCV)-associated diffuse large B-cell lymphomas (DLBCLs) represent a great therapeutic challenge, especially in terms of hepatic toxicity during immune-chemotherapy (I-CT) and long-term hepatic complications. The advent of highly effective and toxicity-free direct-acting antivirals (DAAs) created an exciting opportunity to easily eradicate HCV shortly after or in concomitance with first-line immunochemotherapy (usually R-CHOP). This retrospective international study reports the real-life use of the combination of these two therapeutic modalities either in the concurrent or sequential approach (DAAs after I-CT) in 47 patients. The favorable reported results on long-term outcome seem to support the eradication of HCV with DAAs in all patients with HCV-positive DLBCL. Moreover, the results from the concurrent approach were effective and safe and displayed an advantage in preventing hepatic toxicity during I-CT.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Incidência , Itália/epidemiologia , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Vincristina/administração & dosagem
10.
Biol Blood Marrow Transplant ; 24(9): 1814-1822, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29857196

RESUMO

BEAM (carmustine [bis-chloroethylnitrosourea (BCNU)]-etoposide-cytarabine-melphalan) chemotherapy is the standard conditioning regimen for autologous stem cell transplantation (ASCT) in lymphomas. Owing to BCNU shortages, many centers switched to fotemustine-substituted BEAM (FEAM), lacking proof of equivalence. We conducted a retrospective cohort study in 18 Italian centers to compare the safety and efficacy of BEAM and FEAM regimens for ASCT in lymphomas performed from 2008 to 2015. We enrolled 1038 patients (BEAM = 607, FEAM = 431), of which 27% had Hodgkin lymphoma (HL), 14% indolent non-Hodgkin lymphoma (NHL), and 59% aggressive NHL. Baseline characteristics including age, sex, stage, B-symptoms, extranodal involvement, previous treatments, response before ASCT, and overall conditioning intensity were well balanced between BEAM and FEAM; notable exceptions were median ASCT year (BEAM = 2011 versus FEAM = 2013, P < .001), Sorror score ≥3 (BEAM = 15% versus FEAM = 10%, P = .017), and radiotherapy use (BEAM = 18% versus FEAM = 10%, P < .001). FEAM conditioning resulted in higher rates of gastrointestinal and infectious toxicities, including severe oral mucositis grade ≥3 (BEAM = 31% versus FEAM = 44%, P < .001), and sepsis from Gram-negative bacteria (mean isolates/patient: BEAM = .1 versus FEAM = .19, P < .001). Response status at day 100 post-ASCT (overall response: BEAM = 91% versus FEAM = 88%, P = .42), 2-year overall survival (83.9%; 95% confidence interval [CI], 81.5% to 86.1%) and progression-free survival (70.3%; 95% CI, 67.4% to 73.1%) were not different in the two groups. Mortality from infection was higher in the FEAM group (subhazard ratio, 1.99; 95% CI, 1.02 to 3.88; P = .04). BEAM and FEAM do not appear different in terms of survival and disease control. However, due to concerns of higher toxicity, fotemustine substitution in BEAM does not seem justified, if not for easier supply.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Condicionamento Pré-Transplante/métodos , Transplante Autólogo/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carmustina/farmacologia , Carmustina/uso terapêutico , Estudos de Coortes , Citarabina/farmacologia , Citarabina/uso terapêutico , Etoposídeo/farmacologia , Etoposídeo/uso terapêutico , Feminino , Humanos , Itália , Linfoma/patologia , Masculino , Melfalan/farmacologia , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Hematol Oncol ; 36(1): 68-75, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28524259

RESUMO

The purpose of this phase 2, multicenter study was to determine the activity and safety of nonpegylated liposomal doxorubicin as part of "R-COMP" combination in patients with diffuse large B-cell lymphoma and coexisting cardiac disorders. The study was conducted using a Bayesian continuing assessment method using complete remission rate and rate of cardiac events as study endpoints. Between November 2009 and October 2011, 50 evaluable patients were enrolled (median age, 76 years). Median baseline left ventricular ejection fraction (LVEF) was 60%. Ischemic cardiopathy was the most frequent preexisting cardiac disorder (35%), followed by atrial fibrillation (15%), left ventricular hypertrophy (13%), and baseline LVEF <50% (12%). Based on the intent to treat analysis, overall response rate was 72%, including 28 patients in complete remission (complete remission rate, 56%), and 8 in partial remission (16%). At the end of treatment, grades 3 to 4 cardiac events were observed in 6 patients. No significant modifications from baseline values of LVEF were observed during treatment and follow-up. Nonpegylated liposomal doxorubicin instead of doxorubicin in the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen is a feasible option for patients with diffuse large B-cell lymphoma presenting with concomitant cardiac disorders.


Assuntos
Doxorrubicina/análogos & derivados , Cardiopatias/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Comorbidade , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Cardiopatias/mortalidade , Humanos , Itália , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Resultado do Tratamento
15.
Cancers (Basel) ; 16(4)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38398082

RESUMO

Kaposi's sarcoma (KS) is a rare angioproliferative tumor classified in four different clinical-epidemiological forms. The diagnosis is based on histopathological and immunohistochemical analyses. The treatment is heterogeneous and includes several local and systemic therapeutic strategies. Methods: This is a retrospective cohort study including 86 KS patients treated between 1993 and 2022 at the University Hospital of Padua (AOPD) and at the Veneto Institute of Oncology (IOV). The data were extracted from an electronic database. Survival curves were generated using the Kaplan-Meier method, and Cox regression models were employed to explore associations with overall and disease-free survival. The male sex (89.53%), classical variant (43.02%), and cutaneous involvement (77.9%) were predominant. More than 61.6% of patients received a single treatment. Surgery, antiretroviral therapy, and chemotherapy were the mostly adopted approaches. A persistent response was observed in approximately 65% of patients, with a 22% relapse rate (at least 2 years). The overall survival ranges from 90 to 70% at 2 to 10 years after the diagnosis. Iatrogenic KS demonstrated a higher mortality (52.9%). This study reflects our experience in the management of KS. Comorbidities are very frequent, and treatments are heterogeneous. A multidisciplinary approach involving multiple referral specialists is essential for the appropriate management of this disease during diagnosis, treatment, and follow-up.

16.
Blood Adv ; 7(15): 4160-4169, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37276080

RESUMO

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most commonly used regimen for the upfront treatment of diffuse large B-cell lymphoma (DLBCL). However, it is associated with cardiotoxicity, especially in older patients. Substituting doxorubicin with non-PEGylated liposomal doxorubicin (R-COMP) may reduce the risk of cardiac events, but its efficacy has never been demonstrated in prospective trials. We describe the characteristics and outcome of patients with DLBCL aged ≥65 years prospectively enrolled in the Elderly Project by the Fondazione Italiana Linfomi and treated with full doses of R-CHOP or R-COMP per local practice. Starting from 1163 patients, 383 (55%) were treated with R-CHOP and 308 (45%) with R-COMP. Patients treated with R-COMP were older (median age, 76 vs 71 years), less frequently fit at simplified geriatric assessment (61% vs 88%; P < .001), and had a more frequent baseline cardiac disorders (grade >1, 32% vs 8%; P < .001). Three-year progression-free survival (PFS) was similar between R-CHOP and R-COMP (70% and 64%); 3-year overall survival was 77%, and 71% respectively. R-CHOP was associated with better PFS vs R-COMP only in the Elderly Prognostic Index (EPI) low-risk group. The two groups had similar rates of treatment interruptions due to toxicities or of cardiac events (P = 1.00). We suggest R-COMP is a potentially curative treatment for older patients with intermediate- or high-risk EPI, even in the presence of a baseline cardiopathy. R-CHOP is confirmed as the standard therapy for low risk patients.


Assuntos
Cardiopatias , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Rituximab/efeitos adversos , Vincristina/efeitos adversos , Estudos de Coortes , Estudos Prospectivos , Prednisona/efeitos adversos , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/patologia , Doxorrubicina/efeitos adversos , Cardiopatias/etiologia , Ciclofosfamida/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
17.
Crit Rev Oncol Hematol ; 169: 103568, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34890801

RESUMO

BACKGROUND: Evidence for the choice of second line, standard vs high dose chemotherapy, (SDCT, HDCT) for patients with relapsed germ cell tumors (GCTs) comes mainly from retrospective studies. MATERIAL AND METHODS: relevant literature was reviewed, considering as endpoints both survival and long term quality of life (QoL). Patients with metastatic GCT progressing after first-line treatment at our Institution were retrospectively evaluated. RESULTS: HDCT seems to achieve a higher rate of long-term remissions. QoL data for this group of patients are lacking. Our experience on 29 patients was in line with these results. Two-year OS for the 18 patients treated with one or two HDCT/PBSCT procedures was 47.5 %, while 2-year PFS was 44 %. For the 11 receiving SDCT 2-year OS was 36.4 %, and 2-year PFS was 32.7 %. CONCLUSIONS: HDCT/PBSCT confirmed to be effective in treating patients with relapsed GCT, but prospective studies are needed.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias Embrionárias de Células Germinativas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Terapia de Salvação , Transplante de Células-Tronco , Transplante Autólogo
18.
Cancers (Basel) ; 14(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35053500

RESUMO

The identification of prognostic factors for aggressive B-cell lymphomas still represents an unmet clinical need. We used forward phase protein arrays (FFPA) to identify proteins associated with overall survival (OS) from diagnostic formalin-fixed paraffin-embedded material of diffuse large B-cell lymphoma (DLBCL) patients (n = 47). Univariate Cox regression analysis identified numerous proteins, including immune check-point molecules (PDCD1, PDCD2 and PD1L2) and BCL2 to be significantly associated with OS. However, only ETV6 and PIM2 proteins persisted following multivariate Cox analysis. Independent validation studies by immunohistochemistry and analysis of public gene expression profiles of DLBCL confirmed a prognostic role for high ETV6 and ETV6/PIM2 ratios in DLBCL. ETV6 is a recurrently mutated/deleted gene in DLBCL for which its function in this disease entity is currently unknown. We find that ETV6 is upregulated during oncogenic transformation of germinal center B-cells and that it regulates DLBCL survival, as its acute loss results in marked apoptosis. Fluctuations in survivin (BIRC5) expression levels were associated with this phenomenon. Furthermore, an inverse correlation between ETV6 and BIRC5 expression levels was found and correlated with a response to the BIRC5 inhibitor, YM155. In conclusion, we present evidence for an oncogenic function of ETV6 in DLBCL.

19.
Patient Prefer Adherence ; 16: 353-362, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35173420

RESUMO

PURPOSE: The SARS-CoV-2 spread has impacted Healthcare systems. COVID-19 pandemic has had consequences for patients with cancer, being associated with delays in diagnosis, in treatment And follow-up care, increase in overall infection rates and higher mortality. A survey on COVID-19 and a vaccination-questionnaire were developed at different times of the outbreak, to evaluate cancer patient-reported experience measures (PREMs) on the policies implemented to reduce the infection from SARS-CoV-2 and on the timing and methods of COVID-19 vaccination. PATIENTS AND METHODS: The survey was distributed to all patients accessing the Institute during the "first-wave" Of the pandemic, evaluating patients' concerns about the pandemic, the pandemics' consequences on their cancer care, and their perception Of the measures adopted to limit the infection spread. The vaccination-questionnaire was proposed to 10% of the first 5297 cancer patients vaccinated with two doses of the Pfizer-BioNTechCOVID-19 vaccine. This questionnaire aimed at assessing the degree Of satisfaction with the Institutional vaccination campaign and vaccination-related adverse events. RESULTS: From May 18th 2020 to June 15th 2020 the survey was completed by 3238 patients. Most of the responders expressed concern on the pandemic yet acknowledging their oncological disease as a priority. Measures implemented were appreciated by patients. Telemedicine was positively evaluated and the absence of the caregiver during the visit did not determine discomfort for two thirds of patients. From March 6th 2021 to May 8th 2021 the vaccination-questionnaire was completed by 357 patients. The 98.8% were satisfied with the vaccination campaign. No serious vaccination-correlated adverse events were reported. No patient had to delay/discontinue chemotherapy due to vaccination. CONCLUSION: PREMs during COVID-19 pandemic and related vaccination can provide important information to help reorganization of the health care systems for cancer care. Patients' feedback on the organizational changes implemented in the emergency period are essential for healthcare improvement and to help informed choices that are consistent with patients' needs.

20.
Virchows Arch ; 480(2): 459-465, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33830333

RESUMO

Incidental lymphomas (ILs) are rare and challenging lesions with poorly characterized clinical-epidemiological and histological features. The present study addressed the open issues concerning these tumors, by assessing the clinical-pathological features of 28 consecutive ILs, diagnosed over a 10-year period at a tertiary center for surgical pathology. ILs were more frequently documented in elderly males (mean age at surgery 70.8 years; M/F ratio 3.3), with sharp prevalence of gastrointestinal and urinary tract involvement (22/28 [78.6%] cases). Low-grade B-cell lymphomas outnumbered all other entities, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) was the most common subtype (18/28 [64.3%] cases). Compared to other ILs, CLL/SLL occurred at older age and was the sole lymphoid neoplasm affecting the urinary tract. In conclusion, ILs are rare lesions, mostly affecting the gastrointestinal and urinary tract of elderly males. The diagnosis of IL is based on a high degree of suspicion and on careful morphological/phenotypic characterization.


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma , Patologia Clínica , Idoso , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma/diagnóstico , Masculino
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