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1.
Am J Case Rep ; 21: e927812, 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33009361

RESUMO

BACKGROUND This is a case report of an immunocompromised patient with a history of non-Hodgkin lymphoma and persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who was seronegative and successfully treated with convalescent plasma. CASE REPORT A 63-year-old woman with a past medical history of non-Hodgkin lymphoma in remission while on maintenance therapy with the anti-CD20 monoclonal antibody, obinutuzumab, tested positive for SARS-CoV-2 via nasopharyngeal reverse transcription polymerase chain reaction (RT-PCR) testing over 12 weeks and persistently tested seronegative for immunoglobulin G (IgG) antibodies using SARS-CoV-2 IgG chemiluminescent microparticle immunoassay technology. During this time, the patient experienced waxing and waning of symptoms, which included fever, myalgia, and non-productive cough, but never acquired severe respiratory distress. She was admitted to our hospital on illness day 88, and her symptoms resolved after the administration of convalescent plasma. CONCLUSIONS As the understanding of the pathogenesis of SARS-CoV-2 continues to evolve, we can currently only speculate about the occurrence of chronic infection vs. reinfection. The protective role of antibodies and their longevity against SARS-CoV-2 remain unclear. Since humoral immunity has an integral role in SARS-CoV-2 infection, various phase 3 vaccine trials are underway. In the context of this pandemic, the present case demonstrates the challenges in our understanding of testing and treating immunocompromised patients.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Hospedeiro Imunocomprometido , Linfoma não Hodgkin/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Antineoplásicos Imunológicos/administração & dosagem , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/terapia , Feminino , Seguimentos , Humanos , Imunização Passiva/métodos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Pandemias , Reação em Cadeia da Polimerase em Tempo Real/métodos , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Resultado do Tratamento
2.
Ann Hematol ; 99(10): 2367-2375, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32816079

RESUMO

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/terapia , Quimiorradioterapia , Irradiação Craniana , Linfoma não Hodgkin/terapia , Temozolomida/uso terapêutico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Quimioterapia Adjuvante , Transtornos Cognitivos/induzido quimicamente , Quimioterapia de Consolidação , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Dose Máxima Tolerável , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Neoplasia Residual , Intervalo Livre de Progressão , Estudos Prospectivos , Temozolomida/efeitos adversos , Adulto Jovem
3.
J Comput Assist Tomogr ; 44(4): 619-626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32558769

RESUMO

OBJECTIVE: The aim of the study was to study clinical, imaging findings, response patterns, and immune-related adverse events in classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma (NHL) patients treated with immune checkpoint inhibitors (ICIs). METHODS: A retrospective search was performed to identify patients with relapsed/refractory cHL and NHL treated with ICIs from 2015 to 2019. Clinical and laboratory data were collected. Imaging studies were reviewed for treatment response and immune-related adverse events. RESULTS: Ten patients with relapsed/refractory cHL (median age, 41 years) and 14 patients with relapsed/refractory NHL (median age, 61 years) were identified. Overall response rate was 70% for cHL patients. None of the NHL patients demonstrated complete or partial response. One case of hyperprogression and one case with atypical response were radiologically detected in cHL patients. Hypothyroidism requiring treatment occurred in 2 (20%) of 10 cHL patients, one of which had imaging correlate. Of 14 NHL patients, 1 (7%) had radiologic evidence of pneumonitis and 1 (7%) had colitis. CONCLUSIONS: This single-institution observational study demonstrated that overall response rate was higher in patients with cHL undergoing ICI. Immune checkpoint inhibitor therapy has unique response patterns and toxicities in both cHL and NHL patients that radiologists should keep in mind.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Colite/epidemiologia , Doença de Hodgkin/tratamento farmacológico , Hipotireoidismo/epidemiologia , Linfoma não Hodgkin/tratamento farmacológico , Pneumonia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Colite/induzido quimicamente , Feminino , Doença de Hodgkin/diagnóstico por imagem , Humanos , Hipotireoidismo/induzido quimicamente , Linfoma não Hodgkin/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Pneumonia/induzido quimicamente , Interpretação de Imagem Radiográfica Assistida por Computador , Estudos Retrospectivos , Análise de Sobrevida , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
4.
Medicine (Baltimore) ; 99(18): e20030, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358382

RESUMO

INTRODUCTION: Complications such as severe infection may occur during the chemotherapy of malignant lymphoma. Phlegmonous gastritis (PG) is a rare acute bacterial infection associated with high mortality, requiring early diagnosis, and prompt management. In addition, Guillain-Barré syndrome (GBS) occasionally requires early treatment and intensive care management due to the occurrence of severe neuropathy and respiratory failure. PATIENT CONCERNS: A 70-year-old male was diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) after the detection of several polypoid tumors with ulcers. The patient underwent chemotherapy for DLBCL and exhibited adverse effects (i.e., fever, vomiting, epigastric pain, and neutropenia). Computed tomography indicated widespread thickening in the gastric wall. Furthermore, approximately 2 weeks later, the patient presented with gradual symmetric lower extremity weakness and respiratory failure due to paralysis of the respiratory muscle. DIAGNOSES: DLBCL was diagnosed through a gastric tumor biopsy. On the basis of the computed tomography findings, a culture of gastric juice, nerve conduction studies, and clinical symptoms, this case of gastric lymphoma was complicated with PG and GBS. INTERVENTIONS: The patient was treated with antimicrobial therapy and administration of granulocyte colony-stimulating factor for PG, and with intravenous immunoglobulin and intensive care management for GBS. OUTCOMES: Despite the aggressive progress of the condition, the patient improved without relapse of DLBCL. CONCLUSION: PG was regarded as a precedent infection of GBS. In this article, we present the first reported case of gastric lymphoma complicated with PG and GBS.


Assuntos
Gastrite/complicações , Síndrome de Guillain-Barré/complicações , Linfoma não Hodgkin/complicações , Infecções por Pseudomonas/complicações , Neoplasias Gástricas/complicações , Idoso , Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Gastrite/tratamento farmacológico , Gastrite/microbiologia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia , Masculino , Condução Nervosa , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
5.
J Cancer Res Ther ; 16(1): 13-17, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32362603

RESUMO

Objective: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin lymphoma. This study attempts to delineate the clinicopathological and radiological profile of PCNSL cases at our center. Materials and Methods: All the pathologically confirmed PCNSL cases between January 2007 and July 2016 were analyzed retrospectively. The influence of potential prognostic parameters and therapeutic strategies on survival was investigated by log-rank test and Cox regression analysis. Results: Of the 53 PCNSL patients, 34 (64%) patients were males. Median age at diagnosis was 44 years (range 22-65 years). The most common location in the brain was the cerebral hemispheres in 32 patients (60%), and 16 patients (30%) had multiple intracranial lesions. Histologically, all patients were diffuse large B-cell lymphomas, except one case of anaplastic large-cell lymphoma. The median survival of the patients received whole-brain radiation alone ( n = 6), standard CHOP chemotherapy + radiation ( n = 14), and DeAngelis protocol ( n = 31) was 8 months, 13 months, and 23 months, respectively. Among the 31 patients treated with DeAngelis protocol, Memorial Sloan Kettering Cancer Center Class 1 ( n = 23) and Class 2 ( n = 8) patients had a median overall survival (OS) of 25 months and 13 months, respectively. The incidence of treatment-related neurotoxicity was significantly higher with DeAngelis protocol, in comparison to CHOP + whole-brain radiation therapy (26% vs. 14%, P < 0.05). Conclusion: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate-based chemotherapy combined with radiation was the only factor, which had a significant impact on survival (log-rank P = 0.000) but at the cost of increased neurotoxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Quimiorradioterapia/mortalidade , Irradiação Craniana/métodos , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/radioterapia , Relação Dose-Resposta a Droga , Feminino , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/radioterapia , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida , Temozolomida/administração & dosagem , Adulto Jovem
6.
Crit Rev Oncol Hematol ; 150: 102945, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32353704

RESUMO

Autoimmune disorders are a spectrum of diseases caused by impaired self-tolerance of the immune system. Previous studies underscored the association between autoimmune disorders and lymphomas. However, only a few papers studied the exact mechanisms of this association. The effect of IL-2, IL-5, IL-6, IL-10 and TNF-α, contribution of NOTCH, FAS and MHC receptor families, the interplay of various immune cells, and the relation of immunosuppressive agents and development of autoimmune disorders are the proposed mechanisms for this association. Each individual autoimmune disorder associates with particular types of lymphomas and their common pathways are not necessarily similar to other pairs of autoimmune disorder-lymphomas. Thus, the lymphomas susceptibility in various autoimmune disorders could not be investigated through a single pathway. In this review, we demonstrate the association between each pair of autoimmune disorder-lymphoma and the underlying pathways. By clarifying these associations, follow-up plans could be made leading to early diagnosis of lymphomas.


Assuntos
Doenças Autoimunes/complicações , Imunossupressores/uso terapêutico , Linfoma não Hodgkin/complicações , Linfoma/etiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/patologia
7.
Anticancer Res ; 40(4): 2373-2377, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234940

RESUMO

BACKGROUND/AIM: The clinical significance of surgery for secondary small intestinal non-Hodgkin's lymphomas (NHL) remains unknown. This study aimed to investigate the efficacy of resection for both primary and secondary small intestinal NHL. PATIENTS AND METHODS: Twenty patients with small intestinal lymphoma who underwent surgical resection at our Institute between 2009 and 2017 were retrospectively evaluated. The clinicopathological and surgery-related factors were reviewed. We also analyzed their surgical outcomes such as postoperative complications, perforation rate, and overall survival (OS). RESULTS: In total, 13 (65%) and 7 (35%) patients had primary and secondary lymphomas, respectively. A total of 70% of patients were diagnosed with aggressive-type lymphomas. A total of 15 (75%) patients had Lugano system stage IV. Only one (5%) patient experienced postoperative grade II deep vein thrombosis and pulmonary embolism. The 3-year OS rate after surgery was 59.6%. CONCLUSION: Surgical resection prior to chemotherapy is a feasible and safe therapeutic strategy for small intestinal NHL.


Assuntos
Intestino Delgado/cirurgia , Linfoma não Hodgkin/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/patologia , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
Pediatr Blood Cancer ; 67(6): e28197, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32207557

RESUMO

Fibrin sheath formation around long-term indwelling central venous catheters is common and usually benign. Fibrin sheath can persist after catheter removal and rarely leads to complications. This is a report of three pediatric oncology patients that required cardiac surgery for cardiac embolization of a "ghost" catheter several years after catheter removal. One case required tricuspid valve replacement for complete tricuspid valve destruction and two had erosion through the atrial wall. The severity of these rare complications mandates follow-up of "ghost" catheters in pediatric oncology patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/métodos , Cateteres de Demora/efeitos adversos , Embolia/cirurgia , Átrios do Coração/cirurgia , Linfoma não Hodgkin/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Embolia/etiologia , Embolia/patologia , Átrios do Coração/patologia , Humanos , Linfoma não Hodgkin/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico
9.
PLoS One ; 15(3): e0229973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163477

RESUMO

PURPOSE: To describe patterns of utilization, survival and infectious events in patients treated with rituximab at the University Hospital of Siena (UHS) to explore the feasibility of combining routinely collected administrative and hospital-pharmacy data for examining the real-world use of intravenous antineoplastic drugs. METHODS: A retrospective, longitudinal cohort study was conducted using data from the Hospital Pharmacy of Siena (HPS) and the Regional Administrative Database of Tuscany (RAD). Patients aged ≥18 years with ≥1 rituximab administration recorded between January 2012 and June 2016 were identified in the HPS database. Anonymized patient-level data were linked to RAD. Rituximab utilization during the first year of treatment was described using HPS. Hospital diagnoses of adverse infectious events that occurred during the first year of follow-up and four-year survival were observed using RAD. RESULTS: A total of 311 new users of rituximab were identified: 264 patients received rituximab for non-Hodgkin's lymphoma (NHL) and 47 were treated for chronic lymphocytic leukemia (CLL). Among new users with one complete year of follow-up (n = 203) over 95% received rituximab as the first-line treatment, and approximately 70% of them received 5-8 doses. No patient in the CLL group received >8 administrations. Four-year survival was approximately 70% in both CLL and NHL patients. Sepsis was the most frequent infectious event observed (5.1%). CONCLUSION: HPS and RAD provided complementary information on rituximab utilization, demonstrating their potential for future pharmacoepidemiological studies on antineoplastic medications administered in the Italian hospital setting. Overall, this general description of the real-world utilization of rituximab in patients treated for NHL and CLL at UHS was in line with treatment guidelines and current knowledge on the rituximab safety profile.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Infecções/epidemiologia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Rituximab/administração & dosagem , Administração Intravenosa , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Infecções/induzido quimicamente , Infecções/imunologia , Itália/epidemiologia , Estimativa de Kaplan-Meier , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/mortalidade , Estudos Longitudinais , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/mortalidade , Masculino , Pessoa de Meia-Idade , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Estudos Retrospectivos , Rituximab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
10.
Adv Clin Exp Med ; 29(2): 197-202, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32154678

RESUMO

BACKGROUND: Post-transplantation lymphoproliferative disorder (PTLD) is a complication of organ transplantation and a life-threatening condition. Children who underwent organ transplantation are at risk of developing lymphoproliferative disorders and, among them, non-Hodgkin lymphoma (NHL) is the most serious. OBJECTIVES: The objective of this study was to describe the clinical course of NHL after liver and kidney transplantation. MATERIAL AND METHODS: Retrospective analysis of medical records of children who underwent liver/kidney transplantation and developed NHL. RESULTS: Nine children were identified, all girls, 6 after liver and 3 after kidney transplantations. Age at transplantation ranged from 1 year to 13 years (median: 4 years), while age at lymphoma diagnosis from 4 to 17 years (median: 12 years). Time from transplantation to lymphoma diagnosis ranged from 7 months to 12 years (median: 9 years). All but 1 patient developed mature B-cell lymphoma, 4 children - diffuse large B-cell lymphoma (DLBCL), 2 children - Burkitt's lymphoma, 1 child - mature B-cell leukemia, 1 child - Burkitt-like lymphoma, while 1 patient was diagnosed with T-cell lymphoblastic lymphoma. High levels of Epstein-Barr virus (EBV) DNA were found in blood of 3 patients, and EBV in tissue samples was detected in 4 patients. Six patients presented with stage III and 2 with stage IV disease. Two patients had graft involvement. Three children received chemotherapy according to R-CHOP, 3 LMB protocol (2 with addition of rituximab), while 1 received CHOP and 5 courses of COP. T-cell lymphoma patient was treated with Euro-LB protocol. Six out of 8 treated patients are alive with a median follow-up of 6 years. Two children died from disease progression during treatment and 1 from cerebral herniation before starting therapy. All patients experienced at least 1 toxic episode of grade 3 and 4 according to Common Toxicity Criteria Adverse Event (CTCAE). Complications of chemotherapy were manageable and there were no transplanted organ failures. CONCLUSIONS: Our study provides further data on the treatment and outcome of monomorphic PTLD and indicates that it is feasible to treat solid organ recipients with multiagent chemotherapy.


Assuntos
Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Linfoma não Hodgkin/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Linfoma não Hodgkin/tratamento farmacológico , Estudos Retrospectivos
11.
PLoS One ; 15(3): e0230526, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32187209

RESUMO

Relapse of chronic lymphocytic leukaemia and non-Hodgkin's lymphoma after standard of care treatment is common and new therapies are needed. The targeted alpha therapy with 212Pb-NNV003 presented in this study combines cytotoxic α-particles from 212Pb, with the anti-CD37 antibody NNV003, targeting B-cell malignancies. The goal of this study was to explore 212Pb-NNV003 for treatment of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma in preclinical mouse models.An anti-proliferative effect of 212Pb-NNV003 was observed in both chronic lymphocytic leukaemia (MEC-2) and Burkitt's lymphoma (Daudi) cells in vitro. In biodistribution experiments, accumulation of 212Pb-NNV003 was 23%ID/g and 16%ID/g in Daudi and MEC-2 tumours 24 h post injection. In two intravenous animal models 90% of the mice treated with a single injection of 212Pb-NNV003 were alive 28 weeks post cell injection. Median survival times of control groups were 5-9 weeks. There was no significant difference between different specific activities of 212Pb-NNV003 with regards to therapeutic effect or toxicity. For therapeutically effective activities, a transient haematological toxicity was observed. This study shows that 212Pb-NNV003 is effective and safe in preclinical models of CD37 positive chronic lymphocytic leukaemia and non-Hodgkin's lymphoma, warranting future clinical testing.


Assuntos
Radioisótopos de Chumbo/uso terapêutico , Leucemia Linfoide/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Animais , Antígenos de Neoplasias , Antineoplásicos Imunológicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cetuximab/uso terapêutico , Feminino , Humanos , Leucemia Linfoide/metabolismo , Linfoma não Hodgkin/metabolismo , Camundongos , Camundongos SCID , Radiometria , Tetraspaninas/antagonistas & inibidores
12.
Lancet Haematol ; 7(4): e295-e308, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32135128

RESUMO

BACKGROUND: Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen. METHODS: We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3-4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex. FINDINGS: Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5-52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3-4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81-2·93; heterogeneity test Q=326·21; τ2=0·0042; I2=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25-7·65; heterogeneity test Q=527·33; τ2=0·0384; I2=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82-2·65) to 11·72% (3·00-24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting. INTERPRETATION: The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages. FUNDING: None.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças Cardiovasculares/etiologia , Linfoma não Hodgkin/tratamento farmacológico , Rituximab/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças Cardiovasculares/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Humanos , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Rituximab/efeitos adversos , Índice de Gravidade de Doença , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
13.
Expert Opin Pharmacother ; 21(8): 917-929, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32162560

RESUMO

INTRODUCTION: PI3K inhibition with idelalisib (at that time CAL-101) was at the forefront of the development of molecularly targeted therapies in Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) and follicular lymphoma. However, after initial approval, subsequent trials identified specific immune-mediated and infectious toxicity that led to a reduced use and stopped the further development of this agent. PI3K inhibition as a treatment paradigm fell out of favor compared to other developments such as BTK or BCL2 inhibitors. AREAS COVERED: This review provides an overview of the experience with approved PI3Ki, including long-term experience, and highlights the current PI3Ki developments in CLL, B-cell and T-Cell Non-Hodgkin's Lymphoma. EXPERT OPINION: With careful monitoring and prophylaxis usage of the first-generation PI3K inhibitor, idelalisib, in the approved indications, it is safe and remains an option in higher line therapy after the failure of other novel agents and/or chemoimmunotherapy. New developments with next-generation PI3K inhibitors of improved tolerability and sustained efficacy reignited the treatment principle and already led to newly approved therapeutic options for patients. Certainly, the authors here believe that PI3K inhibitors as a monotherapy and in combination with other agents is currently a rapidly evolving field in cancer treatment.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Leucemia Linfocítica Crônica de Células B/enzimologia , Linfoma não Hodgkin/enzimologia , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Lancet Oncol ; 21(4): 541-550, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32192573

RESUMO

BACKGROUND: Immune checkpoint inhibitors targeting PD-1 have shown clinical benefit in adults with cancer, but data on these drugs in children are scarce. We did a phase 1-2 study of nivolumab, a PD-1 blocking monoclonal antibody, to determine its safety, pharmacokinetics, and antitumour activity in children and young adults with recurrent or refractory non-CNS solid tumours or lymphoma. METHODS: We did a multicentre, open-label, single-arm, dose-confirmation and dose-expansion, phase 1-2 trial in 23 hospitals in the USA. Eligible patients for part A (dose-confirmation phase) of the study were aged 1-18 years with solid tumours with measurable or evaluable disease (by Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1) regardless of histology. Eligible patients for part B (dose-expansion phase) were aged 1-30 years with measurable disease (by RECIST criteria) in the following disease cohorts: rhabdomyosarcoma, Ewing sarcoma, osteosarcoma, neuroblastoma, Hodgkin lymphoma, non-Hodgkin lymphoma, and melanoma. Patients in part A and were given nivolumab 3 mg/kg intravenously over 60 min on days 1 and 15 of a 28-day cycle in a rolling 6 study design with de-escalation upon dose-limiting toxicities to establish the recommended phase 2 dose. Patients in part B were given the recommended phase 2 dose. The primary outcomes were the tolerability, systemic exposure, maximum tolerated dose, and the antitumour activity of nivolumab at the adult recommended dose in children and young adults. This trial is registered with ClinicalTrials.gov, NCT02304458, with follow-up ongoing and is closed to new participants. FINDINGS: 85 patients were enrolled between Feb 22, 2015, and Dec 31, 2018, and 75 patients were fully evaluable for toxicity. Median follow-up was 30 days (IQR 27-83). In part A, 13 patients were enrolled and 12 were evaluable for toxicity. There were no dose de-escalations or dose-limiting toxicities and nivolumab 3 mg/kg was confirmed as the paediatric recommended phase 2. 72 patients were enrolled in part B and 63 were evaluable for toxicity. Five (7%) patients in part B had dose-limiting toxicities. The most common overall toxicity was anaemia (35 [47%] of 75 patients; five patients had grade 3 or grade 4) and non-haematological toxicity was fatigue (28 [37%] patients; none had grade 3 or grade 4). Responses were observed in patients with lymphoma (three [30%] of ten with Hodgkin lymphoma and one [10%] of ten with non-Hodgkin lymphoma; all responders had PD-L1 expression). Objective responses were not observed in other tumour types. INTERPRETATION: Nivolumab was safe and well tolerated in children and young adults and showed clinical activity in lymphoma. Nivolumab showed no significant single-agent activity in the common paediatric solid tumours. This study defines the recommended phase 2 dose and establishes a favourable safety profile for nivolumab in children and young adults, which can serve as the basis for its potential study in combinatorial regimens for childhood cancer. FUNDING: Bristol-Myers Squibb, Children's Oncology Group, National Institutes of Health, Cookies for Kids Cancer Foundation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias/tratamento farmacológico , Nivolumabe/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Critérios de Avaliação de Resposta em Tumores Sólidos , Adulto Jovem
15.
Anticancer Res ; 40(2): 795-805, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32014922

RESUMO

BACKGROUND/AIM: We previously have described the "3+1" tumors cure approach consisting of individual time schedule of cyclophosphamide and dsDNA preparation administrations. The aim of the study was to adapt the "3+1" approach based on eradication of cancer stem cells to the model of murine ascitic cyclophosphamide-resistant lymphosarcoma (RLS). MATERIALS AND METHODS: Adaptation of the "3+1" approach includes the identification of the timing to disrupt the tumorigenic potential of a certain tumor. RESULTS: The proposed therapeutic scheme allowed complete reduction of primary RLS ascites in experimental animals. However, reduction of primary ascites due to the complementary action of cyclophosphamide and dsDNA was inevitably followed by the development of a secondary one, most likely arising from a solid carcinomatous formation in the peritoneal wall. CONCLUSION: The "3+1" approach resulted in the elimination of cancer stem cells, and, as a consequence, in the complete reduction of RLS ascites.


Assuntos
Linfoma não Hodgkin/tratamento farmacológico , Células-Tronco Neoplásicas/metabolismo , Animais , Linfoma não Hodgkin/patologia , Camundongos
16.
Zhonghua Nei Ke Za Zhi ; 59(2): 165-168, 2020 Feb 01.
Artigo em Chinês | MEDLINE | ID: mdl-32074694

RESUMO

A 47-year-old female patient presented nausea and vomiting for half a year and elevated serum creatinine for 3 days. Proximal renal tubular acidosis (RTA) complicated with anemiawas confirmed after admission. Secondary factors, such as autoimmune disease, drugs, poison, monoclonal gammopathy, were excluded. Renal biopsy revealed acute interstitial nephritis. The patient was administrated with daily prednisone 50 mg, sodium bicarbonate 4 g, 3 times per day, erythropoietin 3 000 U, 2 times per week, combined with potassium, calcium, and calcitriol tablets. Serum creatinine reduced to 90 µmol/L. However nausea and vomiting deteriorated with lactic acidosis. Bone marrow biopsy indicated the diagnosis of non-Hodgkin lymphoma, therefore the patient was treated with chemotherapy. Although metabolic acidosis improved gradually after chemotherapy, severe pneumocystis carinii pneumonia developed two weeks later. The patient refused further treatment and was discharged.


Assuntos
Acidose Láctica/complicações , Acidose Tubular Renal/patologia , Anemia/complicações , Linfoma não Hodgkin/patologia , Pneumonia por Pneumocystis/diagnóstico , Insuficiência Renal/complicações , Acidose Láctica/sangue , Antineoplásicos/administração & dosagem , Biópsia , Creatinina/sangue , Eritropoetina/administração & dosagem , Feminino , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Pessoa de Meia-Idade , Náusea , Pneumonia por Pneumocystis/complicações , Prednisona/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Recusa do Paciente ao Tratamento , Vômito
17.
Ann Hematol ; 99(4): 819-828, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32025840

RESUMO

Autologous stem cell transplant (ASCT) is an effective treatment for non-Hodgkin lymphoma (NHL). However, recent supply issues and toxicity of carmustine have necessitated a new conditioning regimen. We conducted a multicenter, phase II study of BEB (busulfan, etoposide, and bendamustine) conditioning regimen for ASCT in patients with NHL. Thirty-one patients were enrolled and underwent ASCT with the BEB conditioning regimen. The most common subtype was diffuse large B-cell lymphoma (n = 23, 74.2%). Nine patients (29.0%) had a history of relapse, and 18 patients (58.1%) received more than 2 lines of chemotherapy before ASCT. A median number of 6.05 × 106/kg CD34 cells were infused, and all patients engrafted after a median period of 11 days. Thirteen patients (41.9%) experienced neutropenic fever, and 16 patients (51.6%) had grade 3 or 4 toxicities during ASCT. No one had a documented infection, veno-occlusive disease, or treatment-related death. Three-month complete remission rate was 81.8%. Median follow-up period of 15 months showed 6 patients (19.4%) relapsed or progressed and 3 patients died. The estimated 2-year progression-free survival and overall survival rate were 73.0% and 89.8%, respectively. Our results show that BEB conditioning regimens for ASCT are feasible with tolerable toxicity in patients with NHL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/tratamento farmacológico , Condicionamento Pré-Transplante/métodos , Adulto , Antifúngicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Terapia Combinada , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Neutropenia Febril/induzido quimicamente , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Pré-Medicação , Intervalo Livre de Progressão , Estudos Prospectivos , Indução de Remissão , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Adulto Jovem
18.
Medicine (Baltimore) ; 99(4): e18807, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977874

RESUMO

RATIONALE: Primary lymphoma of the bones (PLB) is a rare extranodal non-Hodgkin lymphoma (NHL) that is particularly rare in children. The clinical presentation and radiological features of PLB are often nonspecific, making clinical diagnosis challenging and misdiagnosis frequent. Here, we report 2 children with PLB focusing on clinical presentation, differential diagnosis, and treatment outcomes. PATIENTS CONCERNS: A 9-year-old boy presented with left knee swelling and pain for 4 months after a fall. He was previously misdiagnosed with traumatic soft tissue injury. The second patient was an 11-year-old boy with a 6-month history of intermittent left knee pain. He was previously misdiagnosed with bone tuberculosis and chronic osteomyelitis. DIAGNOSES: A 9-year-old boy showed an abnormal signal of the left tibia metaphysis, diaphysis, and epiphysis, and tibia with periosteal reactions and surrounding soft tissue swelling. Tumor biopsy and immunohistochemistry confirmed a diagnosis of B-cell lymphoblastic lymphoma.An 11-year-old boy showed a permeative lesion in the metaphysis and diaphysis of the left proximal tibia. Tumor biopsy and immunohistochemistry confirmed the diagnosis of diffuse large B-cell lymphoma. INTERVENTIONS: Both patients were treated with 6 courses of NHL-Berlin-Frankfurt-Münster-95. OUTCOMES: Both patients are in complete clinical remission with a follow-up of 27 and 18months after treatment, respectively. LESSONS: PLB is a rare malignancy that is difficult to diagnose, particularly in children. Clinicians should increase the awareness of the disease and consider a differential diagnosis of bone lesions. Chemotherapy combined with radiotherapy is a favorable treatment for children with PLB. Early diagnosis and active treatment can improve patient prognosis.


Assuntos
Linfoma Difuso de Grandes Células B/patologia , Linfoma não Hodgkin/patologia , Tíbia/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Criança , Ciclofosfamida/uso terapêutico , Citarabina/uso terapêutico , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma não Hodgkin/tratamento farmacológico , Imagem por Ressonância Magnética , Masculino , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Indução de Remissão , Tioguanina/uso terapêutico , Tíbia/diagnóstico por imagem , Vincristina/uso terapêutico
19.
Support Care Cancer ; 28(1): 113-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30993450

RESUMO

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/economia , Neutropenia Febril Induzida por Quimioterapia/terapia , Custos de Cuidados de Saúde , Neoplasias Pulmonares/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/economia , Neoplasias da Mama/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Custos e Análise de Custo , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Serviços de Saúde para Idosos/economia , Serviços de Saúde para Idosos/estatística & dados numéricos , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/epidemiologia , Linfoma não Hodgkin/economia , Linfoma não Hodgkin/epidemiologia , Masculino , Medicare/economia , Estudos Retrospectivos , Estados Unidos/epidemiologia
20.
J Oncol Pharm Pract ; 26(1): 99-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30924740

RESUMO

OBJECTIVE: This study was conducted with the aim of making the contribution to a decision for treatment and determination of the modalities in patients diagnosed with non-Hodgkin lymphoma which increasingly become widespread in the geriatric population. MATERIALS AND METHODS: Ninety-one patients aged over 65 years diagnosed with lymphoma and treated in Bezmialem Vakif University Medical Faculty Hospital and Haseki Training and Research Hospital between 2008 and 2013 were retrospectively evaluated. Finally, 63 patients for whom data could be reached were included in the study. RESULTS: Examining the results, histological diagnoses of our patients were as follows: diffuse large B-cell lymphoma (50.8%), follicular lymphoma (23.8%), marginal zone lymphoma (12.7%), mantle cell lymphoma (4.8%), T-cell lymphoma (4.8%), lymphoplasmacytic lymphoma (1.6%) and small lymphocytic lymphoma (1.6%). Stages at the time of diagnosis were early stage by 33.3% and late stage by 66.7%. Of the patients, 36.5% had a low-intermediate and 63.5% a high-intermediate International Prognostic Index score. According to the Eastern Cooperative Oncology Group scoring, 34.9% of the patients have an Eastern Cooperative Oncology Group score of 2-4. Activities of daily living score of 33.3% patients was under 5. Looking at the responses to treatment, the complete response was found in 50.8%, partial response in 4.8%, stable disease in 1.6% and progressive disease in 9.5% of the patients. The mean follow-up duration of patients was found as 25.2 months and disease-free survival after remission as 20.2 months. CONCLUSION: We found that we have achieved a complete remission in more than half of our patients (50.8%). Based on this, treatment should aim remission in elderly patients.


Assuntos
Atividades Cotidianas , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma Folicular/diagnóstico , Linfoma Folicular/tratamento farmacológico , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma de Célula do Manto/diagnóstico , Linfoma de Célula do Manto/tratamento farmacológico , Masculino , Indução de Remissão/métodos , Estudos Retrospectivos
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