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1.
Oncologist ; 29(6): e789-e795, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339976

RESUMO

INTRODUCTION: Intensive treatment approaches are required for adult patients with Burkitt lymphoma (BL), although an univocal standard of care still does not exist. The use of frontline autologous stem cells transplantation (ASCT) is debated. PATIENTS AND METHODS: Between 2004 and 2020, 50 patients with BL were treated with the Berlin-Frankfurt-Münster (BFM). Treatment plan consisted of 3 blocks, A (ifosfamide, vincristine, methotrexate, etoposide, and cytarabine), B (vincristine, cyclophosphamide, methotrexate, and doxorubicin), and C (vindesine, methotrexate, etoposide, and cytarabine), each repeated twice, every 28 days. Rituximab was given at day 1 each block. Intrathecal prophylaxis was given once per each block. ASCT was scheduled at the end of the 6 blocks after conditioning. RESULTS: Median age at onset was 38 years (range 16-72); stages III-IV disease was observed in 82% of cases; bulky disease occurred in 44% of the patients, with B-symptoms in 38%. Stem cell harvest was performed in 72% of patients, who all received a subsequent ASCT. The full 6 blocks treatment was completed in 70% of the patients. The overall response rate was 74%, with a complete response rate of 60%. Ten-year overall survival and progression-free survival were 83.7% and 76.0%, respectively, without reaching the median. Ten-year disease-free survival was 80.3%. Grades 3-4 neutropenia, thrombocytopenia, anemia, and mucositis were seen in 96%, 60%, 32%, and 24% of patients. Infections occurred in 60% of patients. CONCLUSION: Intensive treatment according to BFM protocol, with rituximab and ASCT, appears feasible, safe, and highly effective in adult patients with BL, as confirmed by long-term survival rates reflecting response maintenance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Burkitt , Transplante de Células-Tronco Hematopoéticas , Rituximab , Transplante Autólogo , Humanos , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/terapia , Linfoma de Burkitt/mortalidade , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Rituximab/farmacologia , Adulto , Masculino , Feminino , Transplante Autólogo/métodos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adolescente , Adulto Jovem , Idoso , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Etoposídeo/uso terapêutico , Etoposídeo/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/administração & dosagem , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico
2.
Ann Hematol ; 103(3): 803-811, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37950052

RESUMO

The COVID-19 pandemic posed a major challenge in cancer care worldwide which might have an impact on the management of diffuse large B-cell lymphoma (DLBCL). We conducted a retrospective study comparing characteristics, management, and outcomes of DLBCL patients diagnosed during the first year of the COVID-19 pandemic (1/3/2020-28/2/2021) to those diagnosed in the previous year (1/3/2019-28/2/2020) in two tertiary centers in Italy and Israel. 182 patients were diagnosed with DLBCL during the study period. More patients were diagnosed during the pandemic compared to the year before: 60 vs. 29 and 54 vs. 39 in Italy and in Israel, respectively. Trends towards older age and higher transformation rates were shown during the pandemic. The interval between the initiation of symptoms and diagnosis was longer during the pandemic. Five and four patients were diagnosed with COVID-19 during treatment in Italy and in Israel, respectively. there was no difference in dose density and intensity of treatment, before and during the pandemic. The median follow-up during and before the pandemic was 15.2 and 25.5 months, respectively. Progression-free survival (PFS) was slightly shorter during the pandemic compared to the year before (64.9% vs. 70.6%; p = 0.0499). In multivariate analysis, older age and transformed disease were independently related to PFS, while diagnosis of DLBCL during the pandemic was not. Despite the challenges caused by COVID-19 pandemic, the management of DLBCL patients remained unchanged including dose density and intensity. Nevertheless, a shorter PFS during the outbreak might be attributed to differences in patients' characteristics.


Assuntos
COVID-19 , Linfoma Difuso de Grandes Células B , Humanos , Israel/epidemiologia , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico , Rituximab/uso terapêutico
3.
Ann Hematol ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695872

RESUMO

Poor literature report actual and detailed costs of chimeric antigen receptor (CAR) T-cell pathway in a real-life setting. We retrospectively collect data for all patients with relapsed/refractory aggressive large B-cell lymphoma who underwent leukapheresis between August 2019 and August 2022. All costs and medical resource consumption accountability were calculated on an intention-to-treat (ITT) basis, starting from leukapheresis to the time when the patient (infused or not) exited the CAR T-cell pathway for any reason. Eighty patients were addressed to leukapheresis and 59 were finally infused. After excluding CAR-T product cost, the main driver of higher costs were hospitalizations followed by the examinations/procedures and other drugs, respectively 43.9%, 26.3% and 25.4% of the total. Regarding costs of drugs and medications other than CAR T products, the most expensive items are those referred to AEs, both infective and extra-infective within 30 days from infusion, that account for 63% of the total. Density plot of cost analyses did not show any statistically significant difference with respect to the years of leukapheresis or infusion. To achieve finally 59/80 infused patients the per capita patients without CAR-T products results 74,000 euros. This analysis covers a growing concern on health systems, the burden of expenses related to CAR T-cell therapy, which appears to provide significant clinical benefit despite its high cost, thus making economic evaluations highly relevant. The relevance of this study should be also viewed in light of continuously evolving indications for this therapy.

4.
Chemotherapy ; 69(1): 23-26, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37913761

RESUMO

INTRODUCTION: For primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT), there are no uniform recommendations for second-line treatment in case of relapse. CASE PRESENTATION: Here, we present the case of an elderly relapsed/refractory PCDLBCL-LT patient who obtained a prolonged clinical complete remission with lenalidomide. CONCLUSION: Lenalidomide as single agent led to an unexpected long complete response with manageable toxicity.


Assuntos
Perna (Membro) , Linfoma Difuso de Grandes Células B , Humanos , Idoso , Lenalidomida/uso terapêutico , Perna (Membro)/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Resposta Patológica Completa , Resultado do Tratamento
5.
Hematol Oncol ; 40(1): 57-62, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34653277

RESUMO

BRAFV600E mutation is the pathogenic driver of hairy cell leukemia (HCL) found in the vast majority of cases both at onset and during recurrences. The identification of the mutated allele in blood and marrow correlates with the presence of neoplastic cells and can be considered a marker of active disease. Likewise, the absence of the mutation after treatment may indicate a state of deep response. The BRAFV600E burden was measured by droplet digital polymerase chain reaction (ddPCR) and expressed as fractional abundance in 35 HCL patients at different stages of disease (onset, relapse, complete response [CR] after treatment, long-term remission) in peripheral blood and/or bone marrow (when available). Mean values of fractional abundance for patients at diagnosis, relapse and response, respectively, were 12.26%, 16.52% and 0.02% in peripheral blood and 23.51%, 13.96% and 0.26% in bone marrow. Four patients out of 6 evaluated at response were molecularly negative for BRAFV600E in peripheral blood. Mean fractional abundance in peripheral blood tested in 14 patients with long lasting CR was 0.05%, and 10 patients were BRAFV600E negative. These preliminary results suggest that ddPCR permits to assess the active tumor burden in HCL at different disease phases and support the hypothesis that some patients in CR qualify for a molecular CR.


Assuntos
Biomarcadores Tumorais/genética , Leucemia de Células Pilosas/patologia , Mutação , Recidiva Local de Neoplasia/patologia , Reação em Cadeia da Polimerase/métodos , Proteínas Proto-Oncogênicas B-raf/genética , Humanos , Leucemia de Células Pilosas/genética , Recidiva Local de Neoplasia/genética , Prognóstico
6.
Chemotherapy ; 67(4): 253-255, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35537403

RESUMO

Hepatosplenic T-cell lymphoma is a very difficult lymphoma to deal with, almost impossible to cure. "Tandem" consolidation therapy with auto-stem cell transplant and allo-stem cell transplant can induce a long-lasting response and potentially cure this disease.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin , Humanos , Transplante Homólogo , Transplante Autólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfoma não Hodgkin/terapia , Linfócitos T
7.
Ann Hematol ; 100(9): 2261-2268, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33305333

RESUMO

Primary mediastinal B cell lymphoma is a rare entity and often should be promptly treated as a hematological emergency: The initial treatment decision is crucial for the management of this disease. An observational retrospective study was conducted with the aim to improve information on treatment and outcomes of primary mediastinal B cell lymphoma in real practice. After 12 cycles of MACOP-B regimen (methotrexate, doxorubicin, cyclophosphamide, vincristine, bleomycin , and prednisone) with or without rituximab, 120 patients out of 151 (79.5%) achieved a complete response and 12 (7.9%) a partial response leading to a global response of 87.4%. The 21-year overall survival is 82.6%; progression-free and disease-free survivals are 69.3% and 86.4%, respectively. Regarding the role of radiotherapy (RT), patients with a negative PET scan after MACOP-B did not undergo RT: One out of these 48 (2.1%) showed a relapse at 11 months. All relapsed/refractory patients who achieved a response with checkpoint inhibitors are still in continuous complete response with a median follow-up of 14 months. Data that we have gathered over a 30-year experience in the treatment of primary mediastinal B cell lymphoma patients clearly indicate that a third-generation chemotherapy regimen such as MACOP-B is feasible and easily deliverable on an outpatient basis. Regarding the unmet medical need of relapsed/refractory patients, new encouraging results occurred with the advent of the checkpoint inhibitors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Leucovorina/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
8.
Am J Hematol ; 96(10): 1204-1210, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34245477

RESUMO

The treatment of hairy cell leukemia (HCL) has considerably changed over years. Purine analogues, namely cladribine, now represent the treatment of choice. One hundred and eighty-four patients were followed between 1986 and 2018 and treated according to era-specific guidelines. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received. Patients treated first line responded in 86% of cases, with complete response (CR) in 44% of cases. Response rates remained high throughout the first four lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively). One hundred and twenty-two patients received cladribine as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and three patients at more than 20 years. Median time-to-next treatment (TTNT) for frontline cladribine-treated patients was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years vs median not reached at 25.8 years, p < 0.001). Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogues allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting treatment-free intervals after one course of cladribine.


Assuntos
Antineoplásicos/uso terapêutico , Cladribina/uso terapêutico , Leucemia de Células Pilosas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Leucemia de Células Pilosas/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
9.
Haematologica ; 105(6): 1604-1612, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31537689

RESUMO

In recent years, the outcome of mantle cell lymphoma (MCL) has improved, especially in younger patients, receiving cytarabine-containing chemoimmunotherapy and autologous stem cell transplantation. Nevertheless, a proportion of MCL patients still experience early failure. To identify biomarkers anticipating failure of intensive chemotherapy in MCL, we performed target resequencing and DNA profiling of purified tumor samples collected from patients enrolled in the prospective FIL-MCL0208 phase 3 trial (high-dose chemoimmunotherapy followed by autologous transplantation and randomized lenalidomide maintenance). Mutations of KMT2D and disruption of TP53 by deletion or mutation associated with an increased risk of progression and death, both in univariate and multivariate analysis. By adding KMT2D mutations and TP53 disruption to the MIPI-c backbone, we derived a new prognostic index, the "MIPI-genetic" ("MIPI- g"). The "MIPI-g" improved the model discrimination ability compared to the MIPI-c alone, defining three risk groups: i) low-risk patients (4-year progression free survival and overall survival of 72.0% and 94.5%); ii) inter-mediate-risk patients (4-year progression free survival and overall survival of 42.2% and 65.8%) and iii) high-risk patients (4-year progression free survival and overall survival of 11.5% and 44.9%). Our results: i) confirm that TP53 disruption identifies a high-risk population characterized by poor sensitivity to conventional or intensified chemotherapy; ii) provide the pivotal evidence that patients harboring KMT2D mutations share the same poor outcome as patients harboring TP53 disruption; and iii) allow to develop a tool for the identification of high-risk MCL patients for whom novel therapeutic strategies need to be investigated. (Trial registered at clinicaltrials.gov identifier: NCT02354313).


Assuntos
Proteínas de Ligação a DNA/genética , Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto , Proteínas de Neoplasias/genética , Proteína Supressora de Tumor p53/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Mutação , Prognóstico , Estudos Prospectivos , Transplante Autólogo
10.
Hematol Oncol ; 38(5): 737-741, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32905626

RESUMO

In recent years, novel drugs are available for the patients with relapsed/refractory Hodgkin lymphoma (HL), like immune checkpoint inhibitors (CPi). These drugs have been able to rescue a cohort of patients who subsequently could receive an allogeneic stem-cell transplant (SCT). No data were reported for subsequent autologous SCT (ASCT) after CPi. Here, we report our real-life experience in heavily pretreated HL patients undergoing ASCT as consolidation approach after CPi treatment. A retrospective observational study was conducted. Patients had CPi therapy in the context of clinical trials (n = 6) or in the named patient program (n = 7) between July 2014 and November 2019: 9 out of 13 received pembrolizumab and the remaining four underwent nivolumab. A median of 12 cycles (range, 3-16) of CPi therapy were infused. Thirteen patients underwent ASCT after CPi: 11 (84.6%) patients obtained a complete response (CR) and 2 had progression of disease, with an overall response rate of 84.6%. With a median follow-up of 3.3 years (range, 1.1-5.5), only one CR patient had disease relapse after 3.9 months from ASCT, leading to an estimated disease-free survival of 87.5% at 56.9 months. The estimated 5-year progression-free survival was 73.4% and overall survival was 92.3% at 4.8 years, respectively. No unexpected or cumulative toxicity was observed. Our results indicated that ASCT may represent a further effective therapeutic option as consolidation in HL after CPi treatment that today represents the last conventionally recognized therapeutic line.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Adulto , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hodgkin/patologia , Humanos , Masculino , Terapia de Alvo Molecular , Prognóstico , Recidiva , Indução de Remissão , Retratamento , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
11.
Hematol Oncol ; 38(4): 487-492, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32594531

RESUMO

First line therapy of patients with marginal zone lymphomas (MZL) is not well established and various regimens with chemo-immunotherapy can be used. Rituximab plus bendamustine (BR) is an effective and manageable treatment option for patients affected by indolent non-Hodgkin lymphoma. The aim of this monocentric retrospective study was to analyze the effectiveness and safety of the use of BR regimen in MZL patients in first line in daily clinical practice. The treatment schedule was rituximab at the dose of 375 mg/m2 on day 1 of each cycle and bendamustine at the dose of 90 mg/m2 on day 2 and 3, every 28 days for a maximum of 6 cycles. We analyzed 65 MZL patients (28 extranodal [EMZL], 23 splenic [SMZL], and 14 nodal [NMZL]) who underwent BR regimen as first line treatment. The median time from diagnosis to therapy was 2.5 months. Final responses were: 38 complete response (CR, 58.5%), 20 partial response and 7 progressive disease, leading to an overall response rate (ORR) of 89.2%. With respect to the histology, the ORR was 89.3% for EMZL, 82.6% for SMZL and 100% for NMZL, respectively (difference not statistically significant). With a median follow-up time of 44.6 months (range, 3.3-175.0 months), 2 (one EMZL after 42 months and one SMZL after 10 months) of 38 (5.2%) CR patients had disease relapse, yielding an estimated disease free survival of 89.2% at 61.1 months. The estimated 6-year progression free survival was 71.8% with 15 relapsed/progressed patients showing lymphoma recurrence within 48 months from end of treatment. The most frequently reported adverse events (any grade) were neutropenia (N = 35, 53.8%), fatigue (N = 15, 23.0%), and nausea (N = 12, 18.4%). All toxicities quickly resolved and no treatment-related death occurred. The BR regimen is effective and feasible in MZL patients inducing prolonged disease control with manageable toxicities.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cloridrato de Bendamustina/administração & dosagem , Feminino , Seguimentos , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida
12.
Eur J Nucl Med Mol Imaging ; 46(8): 1661-1671, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31102000

RESUMO

PURPOSE: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease. METHODS: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference. RESULTS: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67. CONCLUSIONS: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.


Assuntos
Didesoxinucleosídeos , Linfoma/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos , Adulto , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Sensibilidade e Especificidade
13.
Hematol Oncol ; 37(2): 202-204, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30637815

RESUMO

Existing therapies for Sézary syndrome (SS) are limited in efficacy and in disease control, and patients have very poor prognosis. Here, we report a case report of a patient who has a 16-year history of SS and related treatments (both standard and experimental). In particular, two drugs, one conventional (gemcitabine) and one experimental (mogamulizumab), were able to induce long lasting response. Patient refused to undergo allogeneic stem cell transplantation. After eleven lines of therapeutic approaches, the patient is in very good partial response and free of therapy at the latest available follow-up.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Desoxicitidina/análogos & derivados , Síndrome de Sézary/tratamento farmacológico , Adulto , Desoxicitidina/administração & dosagem , Humanos , Masculino , Fatores de Tempo , Gencitabina
14.
Oncologist ; 23(9): 1033-1038, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29674440

RESUMO

BACKGROUND: Mantle cell lymphoma (MCL) has the worst prognosis of B-cell subtypes owing to its aggressive clinical disease course and incurability with standard chemo-immunotherapy. Options for relapsed MCL are limited, although several single agents have been studied. Lenalidomide is available in Italy for patients with MCL 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 in real practice. RESULTS: Seventy patients received lenalidomide for 21/28 days with a median of eight cycles. At the end of therapy, there were 22 complete responses (31.4%), 11 partial responses, 6 stable diseases, and 31 progressions, with an overall response rate of 47.1%. Eighteen patients (22.9%) received lenalidomide in combination with either dexamethasone (n = 13) or rituximab (n = 5). Median overall survival (OS) was reached at 33 months and median disease-free survival (DFS) at 20 months: 14/22 patients are in continuous complete response with a median of 26 months. Patients who received lenalidomide alone were compared with patients who received lenalidomide in combination: OS and DFS did not differ. Progression-free survivals are significantly different: at 56 months, 36% in the combination group versus 13% in patients who received lenalidomide alone. Toxicities were manageable, even if 17 of them led to an early drug discontinuation. CONCLUSION: Lenalidomide therapy for relapsed MCL patients is effective and tolerable even in a real-life context. IMPLICATION FOR PRACTICE: Several factors influence treatment choice in relapsed/refractory mantle cell lymphoma (rrMCL), and the therapeutic scenario is continuously evolving. In fact, rrMCL became the first lymphoma for which four novel agents have been approved: temsirolimus, lenalidomide, ibrutinib, and bortezomib. The rrMCL therapeutic algorithm is not so well established because data in the everyday clinical practice are still poor. Lenalidomide for rrMCL patients is effective and tolerable even in a real-life context.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Lenalidomida/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Inibidores da Angiogênese/farmacologia , Humanos , Itália , Lenalidomida/farmacologia , Linfoma de Célula do Manto/patologia , Estudos Retrospectivos , Resultado do Tratamento
15.
BMC Cancer ; 18(1): 645, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29879938

RESUMO

BACKGROUND: No standard of care is established for plasmablastic lymphoma (PBL) and prognosis remains extremely poor, given that patients relapse early after chemotherapy and display resistance to commonly applied cytostatic drugs. CASE PRESENTATION: We report a case of nodal, HIV-unrelated PBL in a patient who achieved and maintained a very long lasting complete remission after an intensive therapy consisting consisting of thalidomide plus dexamethasone followed by a consolidation with double autologous stem cell transplantation. Our approach was based on the full application of a standard multiple myeloma treatment and, to the best of our knowledge, it represents the only reported experience so far. This treatment was overall well tolerated. CONCLUSIONS: Multiple myeloma-like treatment may represent a possible alternative to intensive lymphoma-directed therapies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Quimioterapia de Indução/métodos , Linfoma Plasmablástico/terapia , Dexametasona/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Talidomida/administração & dosagem , Transplante Autólogo , Resultado do Tratamento
16.
Hematol Oncol ; 36(1): 136-143, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28332724

RESUMO

Epoetin biosimilars are an alternative to originator erythropoietic agents in the treatment of chemotherapy-induced anaemia; however, their effects in patients with lymphoproliferative disorders remain unclear. This analysis examined the response of patients with lymphoproliferative disorders experiencing chemotherapy-induced anaemia to 4- or 8-week treatment with the biosimilar epoetin alpha. Treatment was initiated at first occurrence of haemoglobin (Hb) < 10 g/dL during chemotherapy and was stopped when Hb was >11 g/dL, when chemotherapy was completed, or in case of transfusion dependency. Response to epoetin alpha was defined as an increase in Hb of >1 g/dL or as an Hb > 11 g/dL. Stability was defined as change in Hb of ±1 g/dL, and no response was indicated by a decrease in Hb of >1 g/dL or acquired transfusion dependence. Overall, 65 patients were enrolled (median age 69 years; 47.7% ≥ 70 years old). Mean Hb levels at the initiation of epoetin alpha was 9.3 ± 0.5 g/dL. Mean Hb levels reached 10.7 ± 1.4 and 10.6 ± 1.5 g/dL at weeks 4 and 8, respectively, in patients on first-line chemotherapy and 11.4 ± 1.6 and 9.7 ± 1.3 g/dL in those on a second- or higher-line regimen. Overall, 70.8% of patients responded, 26.1% had stable Hb, and 3.1% did not respond. Delays or interruption of any chemotherapy cycle due to anaemia occurred in 18 patients. The biosimilar epoetin alpha was well tolerated and allowed patients with non-Hodgkin lymphoma or chronic lymphoproliferative disorders to continue their course of chemotherapy by effectively increasing and maintaining adequate concentrations of Hb.


Assuntos
Anemia/induzido quimicamente , Epoetina alfa/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Epoetina alfa/farmacologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
17.
Int Ophthalmol ; 38(1): 353-361, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28039672

RESUMO

PURPOSE: To report two cases of primary vitreoretinal lymphoma (PVRL), which presented as intermediate and posterior uveitis. METHODS: Combined clinical assessment, multimodal imaging with spectral-domain optical coherence tomography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, brain magnetic resonance imaging and vitreous and retinal biopsy. Case 1 was a 48-year-old woman who complained of visual loss in her right eye secondary to a diffuse vitreous opacification and multiple chorioretinal lesions. Case 2, a 74-year-old man, presented with low vision in his right eye due to a wide chorioretinal lesion at the posterior pole, vitreous opacification and posterior uveitis in both eyes. RESULTS: Diffuse large B cell lymphoma was histologically diagnosed in the cerebellum in the first case and in chorioretinal tissue in the second patient. Atypical lymphoid cells were detected and allowed to make a diagnosis of primary central nervous system lymphoma in case 1 and PVRL in case 2. CONCLUSION: PVRL often masquerades ad intermediate or posterior uveitis. The management of the patients needed a team of pathologists, haematologists and ophthalmologists to achieve the correct diagnosis and choose the more appropriate therapy. Some peculiar characteristics on multimodal imaging, even in atypical cases of PVRL, should raise suspicious for PVRL and lead to a diagnostic vitrectomy and/or retinal biopsy.


Assuntos
Angiofluoresceinografia/métodos , Linfoma Difuso de Grandes Células B/diagnóstico , Imagem Multimodal/métodos , Retina/patologia , Neoplasias da Retina/diagnóstico , Uveíte Posterior/etiologia , Corpo Vítreo/patologia , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Seguimentos , Fundo de Olho , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias da Retina/complicações , Neoplasias da Retina/cirurgia , Tomografia de Coerência Óptica , Uveíte Posterior/diagnóstico , Uveíte Posterior/cirurgia , Acuidade Visual , Vitrectomia
18.
Haematologica ; 102(11): 1931-1935, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28775121

RESUMO

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged <30 years at first infusion. The treatment was well tolerated even in this real-life context and no deaths were linked to drug toxicity. Brentuximab vedotin induces clinical responses quite rapidly, i.e. within the first four cycles of treatment in most responders, thus enabling timely use of transplantation. For patients ineligible for transplant or for those in whom a transplant procedure failed, brentuximab vedotin may represent a feasible effective therapeutic option in everyday clinical practice.


Assuntos
Antineoplásicos/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Brentuximab Vedotin , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Imunoconjugados/administração & dosagem , Imunoconjugados/efeitos adversos , Linfoma Anaplásico de Células Grandes/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Recidiva , Retratamento , Resultado do Tratamento , Adulto Jovem
19.
BMC Cancer ; 17(1): 276, 2017 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-28415982

RESUMO

BACKGROUND: The purpose of this study is to investigate the most suitable first-line approach and the best combination treatment for primary mediastinal large B-cell lymphoma (PMLBCL) as they have been matter of debate for at least two decades. METHODS: Our single centre experience in the treatment of 98 de novo PMLBCL patients over the last 20 years is reviewed. All patients received MACOP-B chemotherapy. Thirty-seven received both rituximab and mediastinal radiotherapy; 30 were irradiated after chemotherapy, although not receiving rituximab and 20 received rituximab without radiotherapy consolidation. Eleven patients received chemotherapy only. RESULTS: Sixty-one (62.2%) patients achieved a complete response after MACOP-B (with or without rituximab); among the 27 (27.6%) partial responders, 21 obtained a complete response after radiotherapy. At the end of their scheduled treatment, 82 patients (83.7%) had a complete and 6 a partial response (6.1%). Eleven patients relapsed within the first 2 years of follow-up. The 17-year overall survival is 72.0% (15 patients died); progression-free and disease-free survival are 67.6% and 88.4%, respectively. A statistically significant difference in overall and progression-free survival was noted among treatment groups, although no disease-free survival difference was documented. CONCLUSIONS: Our data indicate that a third-generation regimen like MACOP-B could be considered a suitable first-line treatment. Mediastinal consolidation radiotherapy impacts on survival and complete response rates and remains a good strategy to convert partial into complete responses. Data suggest that radiotherapy may be avoided in patients obtaining a complete response after (immuno)chemotherapy, but this requires confirmation with further ad hoc studies.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/terapia , Neoplasias do Mediastino/terapia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Humanos , Imunoterapia , Leucovorina/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/radioterapia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prednisona/administração & dosagem , Estudos Retrospectivos , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Vincristina/administração & dosagem , Adulto Jovem
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