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We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD-DI) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD-DI without uneven late toxicities.
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No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type-1 (mDC1), type-2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow-cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra-nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6-fold for mDC1, 2·4-fold for mDC2, 4·5-fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais , Células Dendríticas , Citometria de Fluxo , Adulto , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Bleomicina/administração & dosagem , Contagem de Células Sanguíneas , Dacarbazina/administração & dosagem , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Doxorrubicina/administração & dosagem , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Vimblastina/administração & dosagemRESUMO
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 JovemRESUMO
Specific trials on adult Burkitt lymphoma (BL) and 'unclassifiable' lymphomas with features intermediate between BL and diffuse large B-cell lymphoma (BL/DLBCL) are advocated which include substantial numbers of older patients, to improve treatment feasibility, while countering risks of systemic and central nervous system (CNS) recurrences. We prospectively evaluated a modified CODOX-M/IVAC (CODOX-M: cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate; IVAC: ifosfamide, etoposide and high-dose cytarabine) regimen by the addition of rituximab (R) and liposome-encapsulated cytarabine (D) to increase antitumour activity and halve the number of intrathecal treatments. Thirty adults (40% >60years) with BL (n=15) and BL/DLBCL (n=15) were accrued. Primary endpoints were progression-free survival (PFS), CNS recurrence, and liposomal cytarabine-associated toxicity. Eighty percent of patients received the whole treatment programme, the remaining cases received at least three full courses. Application of the RD-CODOX-M/IVAC regimen resulted in remarkable 4-year PFS (78%) and complete remission (CR) rates (93%). However, PFS was significantly lower in patients older than 60years as compared to younger ones (49%vs 93%, P=0·03; median, 36months), despite high actual dose-intensity, CR rate and tolerability. Reduced-intensity intratechal prophylaxis through liposomal cytarabine was effective because the CNS failure rate was low (3·4%) and without severe neurological toxicities. The RD-CODOX-M/IVAC strategy is feasible and highly effective, but improving outcomes in elderly patients remains a priority.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Linfoma de Burkitt/patologia , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Injeções Espinhais , Lipossomos/administração & dosagem , Linfoma de Células B/patologia , Masculino , Pessoa de Meia-Idade , RituximabRESUMO
Few data are available regarding the effectiveness of anti-SARS-CoV-2 vaccine in immunocompromised patients. Vaccination may have a suboptimal efficacy in this population, in particular if patients are exposed to anti-B-cell therapy. We report the virological and clinical characteristics of a patient with follicle center lymphoma under bimonthly maintenance therapy with obinutuzumab, an anti-CD20 monoclonal antibody. Despite three doses of BNT162b2 vaccine, the patient was infected by the SARS-CoV-2 Omicron variant. After an initial period of clinical and molecular remission due to early therapy with sotrovimab, the patient experienced a fatal relapse sustained by the same viral strain.
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This Phase II study assessed feasibility and efficacy of a biweekly R-COMP-14 regimen (rituximab, cyclophosphamide, non-pegylated liposome-encapsulated doxorubicin, vincristine and prednisone) in untreated elderly patients with poor-risk diffuse large B-cell lymphoma (DLBCL) and moderate to high 'life threat' impact NIA/NCI cardiac comorbidity. A total of 208 courses were delivered, with close cardiac monitoring, to 41 patients (median age: 73years, range: 62-82; 37% >75years) at a median interval of 15·6 (range, 13-29) days; 67% completed all six scheduled courses. Response rate was 73%, with 68% complete responses (CR); 4-year disease-free survival (DFS) and time to treatment failure (TTF) were 72% and 49%, respectively. Failures were due to early death (n=3), therapy discontinuations (no-response n=2; toxicity n=6), relapse (n=6) and death in CR (n=3). Incidence of cardiac grade 3-5 adverse events was 7/41 (17%; 95% confidence interval: 8-31%). Time to progression and overall survival at 4-years were 77% and 67%, respectively. The Age-adjusted Charlson Comorbidity Index (aaCCI) correlated with failures (P=0·007) with patients scoring ≤7 having a longer TTF (66% vs. 29%; P=0·009). R-COMP-14 is feasible and ensures a substantial DFS to poor-risk DLBCL patients who would have been denied anthracycline-based treatment due to cardiac morbidity. The aaCCI predicted both treatment discontinuation rate and TTF.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cardiopatias/tratamento farmacológico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/administração & dosagem , Comorbidade , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/análogos & derivados , Feminino , Cardiopatias/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/complicações , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prednisona/administração & dosagem , Prognóstico , Risco , Rituximab , Análise de Sobrevida , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
Patients with recurring T-cell non-Hodgkin lymphoma (T-NHL) are incurable and candidate for investigational agents. Here, we report on five patients with T-NHL refractory to multiple chemotherapy lines, including in all cases alkylators and gemcitabine, who received the third-generation chloroethylnitrosourea fotemustine at a dose of 120 mg/m(2) every 21 d, up to eight courses. Median actual dose intensity was 79%; toxicity was manageable and mainly hematological. One complete remission, one partial remission, two protracted disease stabilization, and one transient, minor response were achieved. Time to progression ranged from 48 to 240+ d. This is the first evidence ever reporting the activity of fotemustine in end-stage T-NHL. Formal studies with this agent are warranted in T-cell malignancies.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Linfoma de Células T/tratamento farmacológico , Compostos de Nitrosoureia/uso terapêutico , Compostos Organofosforados/uso terapêutico , Idoso , Antineoplásicos Alquilantes/efeitos adversos , Humanos , Pessoa de Meia-Idade , Compostos de Nitrosoureia/efeitos adversos , Compostos Organofosforados/efeitos adversosAssuntos
Neoplasias do Sistema Nervoso Central/prevenção & controle , Neoplasias do Sistema Nervoso Central/secundário , Genes abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Pirimidinas/uso terapêutico , Tiazóis/uso terapêutico , Antineoplásicos/uso terapêutico , Dasatinibe , Genes abl/fisiologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Recidiva , Falha de TratamentoAssuntos
Antineoplásicos/efeitos adversos , Doença de Hodgkin/patologia , Recidiva Local de Neoplasia/patologia , Talidomida/análogos & derivados , Adulto , Anti-Inflamatórios/uso terapêutico , Ensaios de Uso Compassivo , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Lenalidomida , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Talidomida/efeitos adversos , Adulto JovemRESUMO
INTRODUCTION: Hyperhomocysteinemia is a known risk factor for myocardial infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma homocysteine levels have been demonstrated in patients with recurrent episodes or a single episode of thrombosis. Here we describe the development of cardiovascular disease as a complication of a surgical intervention in a patient with colorectal cancer and hyperhomocysteinemia. CASE PRESENTATION: A 65-year-old Caucasian man complained of pain and constipation, attributed to previously diagnosed adenocarcinoma (stage IIB) of the hepatic flexure. An anamnestic investigation showed that he had undergone two surgical interventions. During both, he suffered thrombotic postoperative complications, a deep vein thrombosis of the upper extremity after the first operation and retinal vein occlusion after the second. He was diagnosed with hyperhomocysteinemia associated with a homozygous C677T mutation of the gene encoding the enzyme methylenetetrahydrofolate reductase. Our patient was initially treated with folic acid and high-dose B vitamins. On day 7 he underwent a right hemicolectomy. Anesthesia was performed with sevoflurane in 40% O2 and without the use of nitrous oxide. Postoperatively, our patient remained on folic acid and B vitamins and was without immediate or subsequent complications. CONCLUSIONS: Neoplastic disease and related surgery followed by the administration of chemotherapeutic drugs alter the hemostatic balance in cancer patients. Those suspected of also having a thrombophilic disease require a thorough laboratory diagnostic workup, including a molecular analysis aimed at identifying the genetic mutation responsible for the hyperhomocysteinemia, as indicated. The case described in this report highlights the importance of a multidisciplinary approach that includes expertise in peri-operative anesthesia, surgery, oncology, and hematology.
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Anestesia/métodos , Neoplasias Colorretais/cirurgia , Homocistinúria/complicações , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Espasticidade Muscular/complicações , Idoso , Anestesia por Inalação , Homocistinúria/cirurgia , Humanos , Masculino , Éteres Metílicos , Espasticidade Muscular/cirurgia , Óxido Nitroso , Transtornos Psicóticos/complicações , Transtornos Psicóticos/cirurgia , SevofluranoRESUMO
PURPOSE: We report on a multicenter phase II trial of (90)yttrium-ibritumomab-tiuxetan ((90)YIT) as first-line stand-alone therapy for patients with follicular lymphoma (FL). PATIENTS AND METHODS: Fifty-nine patients with CD20(+) FL grade 1 to 3a in stages II, III, or IV, age 50 years old or older requiring therapy were enrolled. They received (90)YIT according to standard procedure. If complete response (CR) or unconfirmed complete response (CRu) without evidence for minimal residual disease (MRD) 6 months after application of (90)YIT was achieved, patients were observed without further intervention. The same applied to patients with partial response (PR) or with stable disease (SD). Patients with CR but with persisting MRD were to receive a consolidation treatment with rituximab. Primary end point was the clinical and molecular response rate. Secondary end points were time to progression, safety, and tolerability. RESULTS: Six months after treatment with (90)YIT, 56% of the patients showed a CR or CRu and 31% achieved a PR. After a median follow-up of 30.6 months, the progression-free survival (PFS) was 26 months. There was a trend for shorter PFS in patients with increased lactate dehydrogenase (LDH). Of the 26 patients who had CR 12 months after (90)YIT, only three had relapsed. Median time to next treatment has not been reached. The most common toxicities were transient thrombocytopenia and leukocytopenia. Nonhematologic toxicities never exceeded grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE v2.0). CONCLUSION: (90)YIT is well tolerated and achieves high response rates. Patients with increased LDH tend to relapse earlier, and individuals in remission 1 year after (90)YIT appear to have long- lasting responses.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Folicular/radioterapia , Radioimunoterapia/métodos , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Folicular/mortalidade , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Modelos de Riscos Proporcionais , Fatores de TempoRESUMO
PURPOSE: To determine the efficacy and safety of the combination of gemcitabine plus oxaliplatin, with and without rituximab, in patients with relapsed/refractory B-cell lymphoma unsuitable for high dose therapy. METHODS: Patients were prospectively enrolled in two subsequent trials, GEMOX [gemcitabine (1200 mg/m(2), days 1 and 8) and oxaliplatin (120 mg/m(2), day 2), three-weekly] and R-GEMOX [rituximab (375 mg/m(2), day 1), gemcitabine (1200 mg/m(2), day 1) and oxaliplatin (120 mg/m(2), day 2), bi-weekly], up to six courses. RESULTS: Sixty-two patients were enrolled: GEMOX [n = 30; median age, 66 years (range, 46-85); previous chemotherapy > or =2, 70%; PS ECOG > or = 2, 57%]; R-GEMOX [n = 32; median age, 65 years (range 32-79); previous chemotherapy > or =2, 75%; PS ECOG > or = 2, 47%]. Overall and complete response rates were 57 and 30% (95% CI, 15-49) for GEMOX and 78 and 50% (95% CI, 32-68) in R-GEMOX, respectively. Grade 3/4 neutropenia occurred in 57 and 47% of cycles and grade 3/4 thrombocytopenia in 26 and 17% of courses for GEMOX and R-GEMOX, respectively. At 42 months, the failure-free survival (FFS) was 7% (95% CI, 0-16) for GEMOX and 28% (95% CI, 9-47) for R-GEMOX (P = 0.014), with overall survivals of 7 (95% CI, 0-16) and 37% (95% CI, 20-55), respectively (P = 0.016). CONCLUSIONS: Both regimes showed good tolerability and appealing response rates. FFS was more prolonged in R-GEMOX, but patients continuously relapsed without a clear plateau on survival curves.