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1.
Lancet Haematol ; 7(11): e838-e850, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33091357

RESUMO

The integration of rituximab (R) into cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) by Coiffier and colleagues was the first, and last, successful modification of this backbone regimen, which has endured now for almost 20 years. Countless attempts to redefine R-CHOP for patients with diffuse large B-cell lymphoma (DLBCL) have migrated from a focus on dose-intense and dose-dense regimens, to the use of maintenance therapies, and most recently the addition of novel agents. To date, none have changed the basic formula. Although there are many reasons for the absence of success, the incredible molecular heterogeneity of DLBCL is likely to be a major complicating factor. It is clear that as the scientific field's understanding of the genetic heterogeneity of DLBCL deepens, a precision medicine approach should be accounted for and might be one of several paths that could lead to improved outcomes. The rapid identification of poor prognostic groups within the evolving diverse molecular landscape of DLBCL will create new opportunities to produce the next generation of studies with targeted agents against specific pathological drivers. It is conceivable that targeting these driver pathways will require more than one agent, and of course, splitting the pool of patients with DLBCL into smaller groups on the basis of molecular characteristics, will reduce the number of eligible patients for clinical trial investigation. The integration of immunological agents might afford new opportunities to develop treatments agnostic to the complex molecular diversity, while adding minimal toxicity to the regimen. With each of these iterations, the hope is to ultimately shift away from a one-size-fits-all chemotherapy mentality to one predicated on an individualised approach, whether that be through the use of a targeted small molecule or a biological drug. In this Viewpoint, we explore the history of the collective efforts to improve upon R-CHOP, and underscore those lessons that might help to reshape our future plans.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/administração & dosagem , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Heterogeneidade Genética , Humanos , Lenalidomida/administração & dosagem , Linfoma Difuso de Grandes Células B/patologia , Medicina de Precisão , Prednisona/uso terapêutico , Prognóstico , Vincristina/uso terapêutico
2.
Medicine (Baltimore) ; 99(38): e22238, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957367

RESUMO

BACKGROUND: Systematic evaluation of the effectiveness and safety of combined procarbazine, lomustine, and vincristine for treating recurrent high-grade glioma. METHODS: Electronic databases including PubMed, MEDLINE, EMBASE, Cochrane Library Central Register of Controlled Trials, WanFang, and China National Knowledge Infrastructure (CNKI) were used to search for studies related to the utilization of combined procarbazine, lomustine, and vincristine as a therapeutic method for recurrent high-grade glioma. Literature screening, extraction of data, and evaluation of high standard studies were conducted by 2 independent researchers. The robustness and strength of the effectiveness and safety of combined procarbazine, lomustine, and vincristine as a therapeutic methodology for recurrent high-grade glioma was assessed based on the odds ratio (OR), mean differences (MDs), and 95% confidence interval (CI). RevMan 5.3 software was used for carrying out the statistical analysis. RESULTS: These results obtained in this study will be published in a peer-reviewed journal. CONCLUSION: Evidently, the conclusion of this study will provide an assessment on whether combined procarbazine, lomustine, and vincristine provides an effective and safe form of treatment for recurrent high-grade glioma. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202080078.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Metanálise como Assunto , Recidiva Local de Neoplasia/tratamento farmacológico , Revisões Sistemáticas como Assunto , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Lomustina/efeitos adversos , Lomustina/uso terapêutico , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Procarbazina/efeitos adversos , Procarbazina/uso terapêutico , Vincristina/efeitos adversos , Vincristina/uso terapêutico , Adulto Jovem
3.
PLoS One ; 15(9): e0238807, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960887

RESUMO

PURPOSE: The optimal treatment for primary gastric diffuse large B-cell lymphoma (PG-DLBCL) is still unknown. We evaluated unfavorable prognostic factors and pattern of failure in PG-DLBCL to determine the optimal treatment strategy. METHODS: Between April 2001 and November 2018, 120 patients with complete remission following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy were retrospectively reviewed. According to the Lugano staging system, 80 patients (66.7%) had localized disease and 40 patients (33.3%) had advanced disease. A total of 93 (77.5%) patients had single gastric lesion and 27 (22.5%) patients had multiple gastric lesions. Ninety patients (75%) were treated with R-CHOP chemotherapy alone and 30 patients (25%) received R-CHOP chemotherapy with additional local treatment for gastric lesions. RESULTS: The 5-year locoregional failure-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) rates in patients treated with R-CHOP chemotherapy with local treatment were 100%, 100%, and 100%, respectively, whereas the LRFS, PFS, and OS rates in patients treated with R-CHOP chemotherapy alone were 86.3%, 78.2%, and 87.4%, respectively (p = 0.031, p = 0.095, and p = 0.025, respectively). During the follow-up period, 17 patients (14.2%) had disease recurrence. Only 3 of the 17 patients had relapse in a completely new site without relapse in the initial involved site. All, except 2, cases of local recurrence included gastric failure. In the multivariate analysis, performance status and number of gastric lesions were independent prognostic factors for treatment outcome. CONCLUSIONS: Patients with complete remission following R-CHOP chemotherapy showed a good prognosis. The main pattern of failure in patients with PG-DLBCL was local recurrence, especially in the stomach. Patients who received local treatment for gastric lesions showed improved gastric control. Therefore, in patients with unfavorable prognostic factors, we recommend R-CHOP chemotherapy with additional local treatment for gastric lesions.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/secundário , Taxa de Sobrevida , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
4.
Anticancer Res ; 40(9): 5237-5243, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878812

RESUMO

BACKGROUND/AIM: Adult T-cell leukemia/lymphoma (ATLL) is a relatively refractory CD4-positive peripheral T-cell lymphoma. VCAP-AMP-VECP (mLSG15) is one of the standard chemotherapeutic regimens for patients with aggressive ATLL. Mogamulizumab (moga), a monoclonal antibody for C-C chemokine receptor 4 antigen expressed on the cell surface, has recently been poised for use as monotherapy and in combination with chemotherapy. However, to date, a significant survival benefit has not been obtained with the combination of moga + mLSG15 therapy. PATIENTS AND METHODS: We retrospectively analyzed 77 patients diagnosed with aggressive ATLL. Of them, 22 were treated with moga + a chemotherapy regimen comprised of etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisolone (EPOCH), 16 with moga + mLSG15, and 39 with chemotherapy alone. RESULTS: A risk reduction of approximately 30% was obtained with moga + EPOCH compared with moga + mLSG15. CONCLUSION: The addition of moga to chemotherapy did not result in a survival benefit compared with chemotherapy alone. However, a statistically significant overall survival benefit was observed in patients with moga-induced skin disorders.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma de Células T do Adulto/diagnóstico , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Leucemia-Linfoma de Células T do Adulto/mortalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prognóstico , Modelos de Riscos Proporcionais , Retratamento , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
5.
Lancet Haematol ; 7(10): e765-e771, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976753

RESUMO

Over the past 30 years, the scientific community has made little progress in changing the natural history of peripheral T-cell lymphomas. Of the haematological malignancies, T-cell lymphomas have an extremely poor prognosis. One reason for this poor outcome has been that no treatment programme has ever been developed specifically for the broader category of the disease-peripheral T-cell lymphoma-let alone any of the specific subtypes, except advances made for patients with CD30-positive anaplastic large cell lymphoma. Decades of effort have focused on retrofitting chemotherapy programmes used for other diseases, such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for diffuse large B-cell lymphoma, which have not been associated with much progress, and have universally produced far more toxicity than benefit. A remarkable heterogeneity, a paucity of cases, and the absence of peripheral T-cell lymphoma-specific drugs, until recently at least, have limited the field's ability to make substantive and innovative advances. Over the past few years, however, it appears the field is beginning to make progress. Lineage and disease-specific novel-to-novel platforms are producing, although perhaps not unsurprisingly, compelling results suggesting that the path to a cure for this rare orphan disease might be heading in a different direction.


Assuntos
Linfoma de Células T Periférico/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos como Assunto , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Imunoterapia/métodos , Medicina de Precisão/métodos , Prednisona/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1210-1214, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798400

RESUMO

OBJECTIVE: To analyze the clinical efficacy and safety of rituximab therapy for patients with Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL), and to explore the factors influencing the clinical efficacy. METHODS: According to therapeutic regimen, 66 patients with EBV-positive DLBCL were divided into two groups: CHOP group (32 cases) and R-CHOP group (CHOP+ rituximab, 34 cases). The clinical efficacy and the incidence of complication were compared between two groups. The clinical risk factors for the clinical efficacy in patients with EBV-positive DLBCL were confirmed by multivariate Logistic analysis. RESULTS: Compared with CHOP group, the complete remission rate, partial remission rate and the overall effective rate in R-CHOP group all were high (P<0.05), moreover the disease progression rate in R-CHOP group were low (P<0.05). The occurrences rate of myelotoxicity, hepatic injury and gastrointestinal reaction were not statistically significantly different between two groups (P>0.05). Multivariate Logistic analysis showed that the Ann Arbor staging, IPI risk score and Ki-67 positive rate were independent risk factors for the clinical efficacy in patients with EBV-positive DLBCL (OR=2.689, P=0.038; OR=3.232, P=0.025; OR=2.919, P=0.023). CONCLUSION: The clinical efficacy and safety of the therapy with rituximab on the patients with EBV-positive DLBCL are better. The poor Ann Arbor stage, high IPI risk score and the Ki-67 positive rate are factors affecting the clinical efficacy for the patients with EBV-positive DLBCL.


Assuntos
Herpesvirus Humano 4 , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
7.
PLoS One ; 15(8): e0237509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810157

RESUMO

Limited data are available regarding treatment patterns, healthcare resource utilization (HCRU), treatment costs and clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL) in Japan. This retrospective database study analyzed the Medical Data Vision database for DLBCL patients who received treatment during the identification period from October 1 2008 to December 31 2017. Among 6,965 eligible DLBCL patients, 5,541 patients (79.6%) received first-line (1L) rituximab (R)-based therapy, and then were gradually switched to chemotherapy without R in subsequent lines of therapy. In each treatment regimen, 1L treatment cost was the highest among all lines of therapy. The major cost drivers i.e. total direct medical costs until death or censoring across all regimens and lines of therapy were from the 1L regimen and inpatient costs. During the follow-up period, DLBCL patients who received a 1L R-CHOP regimen achieved the highest survival rate and longest time-to-next-treatment, with a relatively low mean treatment cost due to lower inpatient healthcare resource utilization and fewer lines of therapy compared to other 1L regimens. Our retrospective analysis of clinical practices in Japanese DLBCL patients demonstrated that 1L treatment and inpatient costs were major cost contributors and that the use of 1L R-CHOP was associated with better clinical outcomes at a relatively low mean treatment cost.


Assuntos
Custos de Cuidados de Saúde , Linfoma Difuso de Grandes Células B , Padrões de Prática Médica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Análise Custo-Benefício , Ciclofosfamida/economia , Ciclofosfamida/uso terapêutico , Bases de Dados Factuais , Doxorrubicina/economia , Doxorrubicina/uso terapêutico , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Formulário de Reclamação de Seguro/estatística & dados numéricos , Japão/epidemiologia , Linfoma Difuso de Grandes Células B/economia , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/economia , Terapia Neoadjuvante/estatística & dados numéricos , Padrões de Prática Médica/economia , Padrões de Prática Médica/estatística & dados numéricos , Prednisona/economia , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/administração & dosagem , Rituximab/economia , Rituximab/uso terapêutico , Análise de Sobrevida , Vincristina/economia , Vincristina/uso terapêutico , Adulto Jovem
8.
Ann Hematol ; 99(9): 2119-2124, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676733

RESUMO

Acute leukemias of ambiguous lineage (ALAL) are rare hematologic malignancies with poor outcomes. Retrospective studies have suggested that acute lymphoblastic leukemia (ALL) regimens are more effective than acute myeloid leukemia (AML) regimens. We retrospectively examined the effectiveness of the widely-used adult ALL regimen hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyperCVAD) as initial therapy in patients with ALAL at five academic institutions. Twenty-five patients were identified, including 23 with mixed phenotype acute leukemia (MPAL) and two with acute undifferentiated leukemia. Five of 8 tested (63%) had FLT3-ITD and 3 of 25 (12%) were Philadelphia chromosome-positive. The complete remission (CR) rate was 76%, with CR with incomplete count recovery (CRi) in an additional 8%, for an overall response rate of 84%. Median number of cycles to CR/CRi was 1. There were no deaths in the first 30 days. Of the 21 patients achieving CR or CRi, 14 (66%) proceeded to allogeneic hematopoietic stem cell transplantation. With a median follow-up time of 31.6 months, median overall survival for the entire cohort was not reached, and the estimated 2-year survival was 63%. HyperCVAD can be considered an effective and tolerable front-line regimen for patients with ALAL, and warrants further prospective study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/tratamento farmacológico , Adulto , Idoso , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Dexametasona/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
9.
Int J Hematol ; 112(3): 369-376, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529585

RESUMO

Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is one of the standard regimens for indolent B-cell non-Hodgkin's lymphoma (NHL). It is unclear whether the prednisolone (PSL) dosage affects the therapeutic effect or the adverse event profile. We retrospectively examined 48 patients with indolent B-cell NHL who were treated with R-CHOP (PSL 50 mg/m2/day for 5 days) at our institute between 2006 and 2016. We compared them with 149 patients with indolent B-cell lymphoma who were treated with R-CHOP (PSL 100 mg for 5 days) in the JCOG 0203 trial. The proportions of patients with bulky disease, extranodal involvement, and increased nodal sites were higher at our institute. Nevertheless, there was no difference in the CR rate, PFS, OS or the frequency of adverse events, except for peripheral neuropathy, between the two treatment groups. In our institute, there was no difference in the CR rate, PFS, OS or adverse event profile between patients who received PSL at 60-80 mg/day and at 81-100 mg/day. Patients who received PSL at 60-80 mg/day included many female and light-weight patients. In conclusion, the PSL dose adjusted based on body surface area appeared to be appropriate in terms of efficacy and safety.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Prednisolona/administração & dosagem , Rituximab/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Superfície Corporal , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Intervalo Livre de Doença , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Linfoma Folicular/mortalidade , Linfoma não Hodgkin/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisolona/efeitos adversos , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
10.
Ann Hematol ; 99(7): 1583-1594, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32506244

RESUMO

Relapsing diffuse large B cell lymphomas (rDLBCL) represent a heterogeneous disease. This heterogeneity should be recognized and reflected, because it can deform the interpretation of clinical trial results. DLBCL patients with the first relapse and without CNS involvement were identified in the Czech Lymphoma Study Group (CLSG) database. Interval-to-therapy (ITT) was defined as the time between the first manifestation of rDLBCL and the start of any treatment. The overall survival (OS) of different ITT cohorts (< 7 vs. 7-21 vs. > 21 days) was compared. In total, 587 rDLBCLs (51.8% males) progressed with a median of 12.8 months (range 1.6 to 152.3) since the initial diagnosis (2000-2017). At the time of relapse, the median age was 67 years (range 22-95). First-line therapy was administered in 99.3% of the patients; CHOP and anti-CD20 were given to 69.2% and 84.7% of the patients, respectively. The salvage immune/chemotherapy was administered in 88.1% of the patients (39.2% platinum-based regimen). The median ITT was 20 days (range 1-851), but 23.2% of patients initiated therapy within 7 days. The 5-year OS was 17.4% (range 10-24.5%) vs. 20.5% (range 13.5-27.4%) vs. 42.2% (range 35.5-48.8%) for ITT < 7 vs. 7-21 vs. > 21 days (p < 0.001). ITT was associated with B symptoms (p 0.004), ECOG (p < 0.001), stage (p 0.002), bulky disease (p 0.005), elevated LDH (p < 0.001), and IPI (p < 0.001). The ITT mirrors the real clinical behavior of rDLBCL. There are patients (ITT < 7 days) with aggressive disease and a poor outcome. Conversely, there are rDLBCLs with ITT ≥ 21 days who survive for a long time.


Assuntos
Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/terapia , Tempo para o Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Ciclofosfamida/uso terapêutico , República Tcheca/epidemiologia , Bases de Dados Factuais , Progressão da Doença , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Prednisona/uso terapêutico , Prognóstico , Recidiva , Estudos Retrospectivos , Rituximab/administração & dosagem , Tempo para o Tratamento/estatística & dados numéricos , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
11.
Medicine (Baltimore) ; 99(21): e20048, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481271

RESUMO

RATIONALE: Ustekinumab is a biological agent that inhibits interleukin 12 and 23 and has been approved for the treatment of moderate and severe plaque psoriasis. There have been case reports that raise concerns about its oncogenic potential. We are the first authors to report a case of Hodgkin lymphoma in a psoriatic patient receiving ustekinumab. PATIENT CONCERNS: A 22-year-old asymptomatic female patient presented to our department to investigate an enlarged cervical lymph node. Her past history was unremarkable, except for psoriasis since age 13. Two months before presentation the decision to administer Ustekinumab was taken and the patient had already received 3 doses. DIAGNOSES: During workup a Stage IV Hodgkin lymphoma was discovered. INTERVENTIONS: Ustekinumab administration was discontinued. The patient received treatment with the ABVD regimen. OUTCOMES: The patient's disease was refractory to the above-mentioned treatment. Therefore, a more aggressive regimen (BEACOPP escalated) was administered. LESSONS: Growing postmarketing surveillance data and case reports indicate that further research is warranted in order to elucidate a potential association between Ustekinumab and malignancy.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Doença de Hodgkin/induzido quimicamente , Psoríase/tratamento farmacológico , Ustekinumab/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Prednisona/uso terapêutico , Procarbazina/uso terapêutico , Ustekinumab/administração & dosagem , Vincristina/uso terapêutico , Adulto Jovem
12.
Leuk Res ; 95: 106391, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32559556

RESUMO

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare type of aggressive large B - cell non-Hodgkin Lymphoma (NHL) which was initially described in HIV positive individuals and later was also described in immune-competent individuals. It was included as a distinct entity in the WHO lymphoma classification in 2008. METHODS: The clinical features, HIV status, treatment details, and outcomes of patients diagnosed with plasmablastic lymphoma from January 2012 to December 2018 were retrospectively collected from the patient records and analyzed. The survival analysis was done by Kaplan Meier analysis and the comparison was done by the Log Rank test. RESULTS: The median age of 25 patients, included in the study was 41 years (Range 13-71 years). Males constituted 76 %. HIV positivity was 72 %. Stage IV disease was present in 76 %. Extranodal involvement was seen in 96 %. Out of 25 patients, seven did not receive any treatment and three received metronomic oral chemotherapy due to poor performance status at presentation. Fifteen patients received chemotherapy on a curative intent. Infusional EPOCH chemotherapy was given in 13 patients. CHOP and CHOEP chemotherapy was given in one patient each. The median number of cycles was 6 (Range: 3-8). The overall response rate of patients treated on a curative intent was 80 % (Complete response and partial response in 8 and 4 respectively). Three patients underwent high dose chemotherapy with autologous stem cell rescue at first remission. The median event-free survival (EFS) and median overall survival (OS) of the whole study population was 5.9 and 12.4 months respectively, with a median follow of 26.9 months. The median EFS was 13.8 months and the median OS was not reached in the curative-intent group. The factors adversely influencing the EFS and OS were Age > 40 years, high IPI, and non-curative intent of treatment. CONCLUSION: Plasmablastic lymphoma commonly presents as stage 4 disease with extranodal involvement and is more common in immune-deficient individuals. Infusional EPOCH chemotherapy is a promising option that induces long term remission.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Plasmablástico/tratamento farmacológico , Adolescente , Adulto , Idoso , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linfoma Plasmablástico/mortalidade , Prednisona/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Vincristina/uso terapêutico , Adulto Jovem
13.
Ann Hematol ; 99(9): 2149-2157, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32390113

RESUMO

Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.


Assuntos
Regulação Neoplásica da Expressão Gênica , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/terapia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-myc/genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-myc/biossíntese , Estudos Retrospectivos , Fatores de Risco , Transplante Autólogo/métodos , Vincristina/uso terapêutico , Adulto Jovem
14.
Intern Med ; 59(14): 1745-1748, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32296003

RESUMO

A 67-year-old woman received induction chemotherapy comprising vincristine, daunorubicin, cyclophosphamide, L-asparaginase and prednisolone for acute lymphoblastic leukemia with a common B-cell phenotype. The administration of L-asparaginase at 3,000 U/m2 for 6 days was planned. Before the fourth administration on day 16, left parotid swelling was identified along with increased serum amylase (991 U/L; 94% derived from salivary glands). An enlarged left parotid gland was apparent on computed tomography. The symptoms resolved after cessation of L-asparaginase, with serum amylase normalizing by day 20. This rare adverse event should be recognized as improving within a week after ceasing L-asparaginase.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/efeitos adversos , Asparaginase/uso terapêutico , Parotidite/induzido quimicamente , Parotidite/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Idoso , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Daunorrubicina/efeitos adversos , Daunorrubicina/uso terapêutico , Feminino , Humanos , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Resultado do Tratamento , Vincristina/efeitos adversos , Vincristina/uso terapêutico
15.
BMJ Case Rep ; 13(4)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32303524

RESUMO

A 62-year-old man presented to our institute with diarrhoea and dysuria on a background of subtotal colectomy and end ileostomy and biological therapy for Crohn's disease. He was diagnosed with urinary tract infection and acute kidney injury (AKI). Renal ultrasound suggested left hydronephrosis, with renal protocol computed tomography (CT) showing a large pelvic mass. Magnetic resonance imaging (MRI) of the pelvis demonstrated a rectal tumour invading the bladder and compressing both ureters. He underwent cystoscopy, flexible sigmoidoscopy and positron emission tomography-CT and was diagnosed with stage IV non-Hodgkin's diffuse large B-cell lymphoma. He was treated primarily with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin and prednisolone chemotherapy regimen. He had ongoing urosepsis before admission for pelvic exenteration. He underwent cystoprostatectomy, excision of rectal stump and formation of ileal conduit. Histology showed no signs of residual malignancy. One year later, the patient was admitted to the intensive care unit with aspiration pneumonia, urosepsis and AKI. Despite maximal therapy, he developed multiorgan failure and passed away.


Assuntos
Terapia Biológica/efeitos adversos , Doença de Crohn/terapia , Linfoma Difuso de Grandes Células B/complicações , Neoplasias Retais/complicações , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Diagnóstico Diferencial , Doxorrubicina/uso terapêutico , Evolução Fatal , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Rituximab/uso terapêutico , Vincristina/uso terapêutico
16.
Am J Clin Pathol ; 153(5): 672-685, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112707

RESUMO

OBJECTIVES: To better characterize the clinicopathologic presentation and outcomes of follicular lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and triple-hit follicular lymphoma), we present three cases from our institution and perform a literature review of 37 published cases. METHODS: Cases were identified using institutional SoftPath software and the MEDLINE database via the PubMed search engine. Clinical and pathologic data were collected with subsequent stratification by histologic grade and treatment for comparison. RESULTS: Similar to classic follicular lymphoma, patients presented most often with low-grade (1-2) but high-stage (III-IV) disease with absence of B symptoms; however, overall survival was worse than that of traditional follicular lymphoma. In a small sample size, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) achieved better outcomes than a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Specific pathologic features that might prompt testing for MYC rearrangement include elevated proliferation index out of proportion to cytology and aggressive features such as angioinvasion. CONCLUSIONS: Double-hit and triple-hit follicular lymphoma may be better classified as a distinct entity from classical follicular lymphoma with a worse prognosis. Aggressive therapy with a treatment regimen used for high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements might be beneficial, but more evidence is needed to justify aggressive treatment as standard of care.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Folicular/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Rearranjo Gênico , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Rituximab/uso terapêutico , Resultado do Tratamento , Vincristina/uso terapêutico
17.
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
18.
Tohoku J Exp Med ; 250(2): 129-135, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32115495

RESUMO

Pulmonary lymphoma is rare, accounting for < 1% of primary lung cancers. Most primary pulmonary lymphomas (PPL) are low-grade mucosa-associated lymphoid tissue (MALT)-type, and among PPL, diffuse large B-cell lymphoma (DLBCL) is extremely rare. In contrast, there has been an increase in the incidence of DLBCL among patients with autoimmune disorders and recurrent or chronic bacterial infection. A subset of DLBCL has been reported to develop through transformation of preexisting or concurrent MALT. The respiratory symptoms are non-specific, and the chest X-ray findings demonstrate the presence of interstitial and mixed alveolar infiltrates, nodular lesions, and localized homogeneous consolidations; the diagnosis of pulmonary DLBCL is thus challenging and often leads to a misdiagnosis or delayed diagnosis. We herein report a case of DLBCL which was assumed to have arisen from the lesion of chronic atelectasis that was successfully diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). A 74-year-old woman with diffuse bronchiectasis and chronic atelectasis of the left lower lobe suffered from productive cough and high fever. Increased airway filling with mucoid secretion was repeatedly observed within the area of atelectasis with bronchiectasis, and left lower lobe atelectasis developed. Subsequently, the hilar and mediastinal lymph nodes gradually became enlarged, and DLBCL was pathologically confirmed. In the present case, DLBCL was considered to have arisen in the lesion of chronic atelectasis. Physicians should recognize that DLBCL may develop at the site of chronic atelectasis during disease course of diffuse bronchiectasis, and thus DLBCL may be misdiagnosed as superimposed infection of chronic atelectasis.


Assuntos
Neoplasias Pulmonares/patologia , Linfoma de Células B/patologia , Atelectasia Pulmonar/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/análogos & derivados , Doxorrubicina/uso terapêutico , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Linfoma de Células B/diagnóstico por imagem , Linfoma de Células B/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Prednisolona/uso terapêutico , Atelectasia Pulmonar/diagnóstico por imagem , Atelectasia Pulmonar/tratamento farmacológico , Tomografia Computadorizada por Raios X , Vincristina/uso terapêutico
19.
Leuk Res ; 91: 106335, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32114372

RESUMO

We performed a retrospective study comparing treatment patterns and overall survival (OS) in chronic lymphocytic leukemia (CLL) patients with the advent of ibrutinib to provide current real-world data. METHODS: Using a provincial population-based database, we analyzed CLL patients who received upfront treatment in British Columbia before ibrutinib availability (1984-2014), during ibrutinib access for: relapse only (2014-2015) and for upfront treatment of patients (with 17p deletion or unfit for chemotherapy) (2015-2016). Analysis included up to third-line treatment. RESULTS: Of 1729 patients meeting inclusion criteria (median age, 66 years; 1466, period 1; 140, period 2; 123, period 3), FR was the most common first-line therapy (35.8 %, 54.3 % and 40.7 %, periods 1-3, respectively) and 18.7 % received ibrutinib upfront in period 3. The most common therapies in relapse were chemoimmunotherapy (36.1 % and 55.6 %, periods 1 and 2, second-line; 29.2 %, period 1, third-line) and ibrutinib (69.8 %, period 3, second-line; 46.4 % and 70.3 %, periods 2 and 3, third-line). OS improved for patients treated in periods 2-3 over period 1 (median OS not reached vs. 11.9 years, p < 0.001; no difference in OS for periods 2-3, p = 0.385). CONCLUSION: Ibrutinib has replaced chemoimmunotherapy as the preferred therapy in relapse. Overall survival has improved over time with access to ibrutinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfocítica Crônica de Células B/terapia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Síndrome de Smith-Magenis/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica , Deleção Cromossômica , Cromossomos Humanos Par 17/genética , Ciclofosfamida/uso terapêutico , Gerenciamento Clínico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Prednisona/uso terapêutico , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Síndrome de Smith-Magenis/diagnóstico , Síndrome de Smith-Magenis/genética , Síndrome de Smith-Magenis/mortalidade , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Vincristina/uso terapêutico
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