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1.
Ann Oncol ; 34(2): 186-199, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36402300

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Humanos , Fosfatidilinositol 3-Quinases/genética , Linfoma Difuso de Grandes Células B/patologia , Mutação , Complexo Repressor Polycomb 2/genética , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia
2.
Ann Hematol ; 102(5): 1159-1169, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36991231

RESUMO

Primary central nervous system lymphomas (PCNSLs) classically remain confined within the CNS throughout their evolution for unknown reasons. Our objective was to analyse the rare extracerebral relapses of PCNSL in a nationwide population-based study. We retrospectively selected PCNSL patients who experienced extracerebral relapse during their follow-up from the French LOC database. Of the 1968 PCNSL included in the database from 2011, 30 (1.5%, median age 71 years, median KPS 70) presented an extracerebral relapse, either pure (n = 20) or mixed (both extracerebral and in the CNS) (n = 10), with a histological confirmation in 20 cases. The median delay between initial diagnosis and systemic relapse was 15.5 months [2-121 months]. We found visceral (n = 23, 77%), including testis in 5 (28%) men and breast in 3 (27%) women, lymph node (n = 12, 40%), and peripheral nervous system (PNS) (n = 7, 23%) involvement. Twenty-seven patients were treated with chemotherapy, either with only systemic targets (n = 7) or mixed systemic and CNS targets (n = 20), 4 were consolidated by HCT-ASCT. After systemic relapse, the median progression-free survival and overall survival (OS) were 7 and 12 months, respectively. KPS > 70 and pure systemic relapses were significantly associated with higher OS. Extracerebral PCNSL relapses are rare, mainly extranodal, and frequently involve the testis, breast, and PNS. The prognosis was worse in mixed relapses. Early relapses raise the question of misdiagnosed occult extracerebral lymphoma at diagnostic workup that should systematically include a PET-CT. Paired tumour analysis at diagnosis/relapse would provide a better understanding of the underlying molecular mechanisms.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Masculino , Humanos , Feminino , Idoso , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/terapia , Prognóstico , Neoplasias do Sistema Nervoso Central/terapia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica
3.
Rev Neurol (Paris) ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38042665

RESUMO

BACKGROUND: Primary central nervous system lymphoma (PCNSL) accounts for less than 5% of primary brain tumors. Epileptic seizures are a common manifestation of brain tumors; however, literature on the prevalence, characteristics, and oncological implications of seizures in patients with PCNSL is limited, and the management of antiepileptic drugs (AEDs) is unclear. This review aimed to summarize the existing knowledge on seizures in PCNSL, their potential association with surgery, oncological treatment, survival rates, and management of AEDs. METHODS: A systematic review was performed according to the PRISMA recommendations and included articles published between 1953 and 2023 describing seizures in patients with PCNSL. RESULTS: The search identified 282 studies, of which 21 were included. Up to 33% of patients with PCNSL developed seizures, mostly at the initial presentation. Little information was found on changes in seizure incidence through the course of the disease, and no details were found on seizure frequency, the percentage of treatment-resistant patients, or the evolution of seizures at remission. Younger age, cortical location, and immunodeficiency have been identified as potential risk factors for seizures, but evidence is very limited. The growing use of vigorous treatments including intensive chemotherapy with autologous stem cell transplantation and immunotherapy with CAR-T cells is associated with a higher incidence of seizures. The association between seizure development and patient mortality in PCNSL remains unknown. There are no data on AED prophylaxis or the use of specific AEDs in PCNSL. CONCLUSIONS: Further studies are needed to investigate seizures in larger cohorts of PCNSL, to clarify their prevalence, better characterize them, identify risk factors, analyze survival rates, and make recommendations on AED management. We recommend following general practice guidelines for seizures symptomatic of brain tumors and not to prescribe AED prophylaxis in PCNSL.

4.
Ann Oncol ; 30(4): 621-628, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698644

RESUMO

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R2) in DLBCL-PCNSL. PATIENTS AND METHODS: Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R2 (rituximab 375/m2 i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%). RESULTS: Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 ≥ 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03). CONCLUSIONS: The R2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL. CLINICAL TRIALS NUMBER: NCT01956695.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma Intraocular/tratamento farmacológico , Lenalidomida/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/mortalidade , Esquema de Medicação , Feminino , Seguimentos , França/epidemiologia , Humanos , Análise de Intenção de Tratamento , Linfoma Intraocular/mortalidade , Lenalidomida/efeitos adversos , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Estudo de Prova de Conceito , Estudos Prospectivos , Indução de Remissão/métodos , Rituximab/efeitos adversos
5.
Ann Hematol ; 98(4): 915-922, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30535802

RESUMO

Recurrent primary central nervous system lymphomas (PCNSL) have a very poor prognosis. For young and fit patients, intensive chemotherapy followed by autologous stem cell transplantation could be proposed at relapse. In the other cases (unfit or elderly patients), therapeutic options are limited with no consensual regimen. The poly-chemotherapy by (R)-GEMOX is associated with anti-tumor activity in systemic lymphomas and a favorable toxicity profile. Our objective was to evaluate the activity and tolerance of (R)-GEMOX in PCNSL patients enrolled in the French nation-wide LOC cohort. We retrospectively analyzed all refractory or recurrent patients included in the LOC network who benefited from (R)-GEMOX (rituximab 375 mg/m2, gemcitabine 1000 mg/m2, and oxaliplatine 100 mg/m2). Administration, tolerance, and efficacy data were analyzed. Thirteen patients, treated in five different institutions, benefited from the (R)-GEMOX regimen from February 2013 to August 2017. At the initiation of (R)-GEMOX, median age was 71.4 years old (range, 49.5-82.5) and median Karnofsky performance status (KPS) was 60 (range, 40-80). Seven patients were in second line of treatment whereas the six others were in third line or over. All patients had received methotrexate-based polychemotherapy as first-line treatment except one. Overall response rate was 38% with two complete responses and three partial responses. Median progression-free survival was 3.2 months (95%CI: 0.2-6.2), and median overall survival was 8.2 months (95%CI: 0.6-15.8). Toxicity was mainly hematological including grade ¾ neutropenia (38%), lymphopenia (23%), and thrombopenia (23%). Older age (p = 0.046) and low KPS (p = 0.054) tended to be associated with a worse prognosis. (R)-GEMOX is associated with substantial response rate and favorable toxicity profile in unfit patients with recurrent PCNSL. (R)-GEMOX could be considered to be an additional option in patients with recurrent/refractory PCNSL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Desoxicitidina/análogos & derivados , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Rituximab/administração & dosagem , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Sistema Nervoso Central/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Linfoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida
8.
Ann Oncol ; 27(3): 397-408, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26681686

RESUMO

Malignancies represent a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients. The introduction of combined antiretroviral therapy has modified the spectrum of malignancies in HIV infection with a decreased incidence of acquired immunodeficiency syndrome (AIDS) malignancies such as Kaposi's sarcoma and non-Hodgkin's lymphoma due to partial immune recovery and an increase in non-AIDS-defining malignancies due to prolonged survival. Management of HIV-infected patients with cancer requires a multidisciplinary approach, involving both oncologists and HIV physicians to optimally manage both diseases and drug interactions between anticancer and anti-HIV drugs. The French CANCERVIH group presents here a review and an experience of managing non-AIDS malignancies in HIV-infected individuals.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade , Doença de Hodgkin/epidemiologia , Sarcoma de Kaposi/epidemiologia , Consenso , Prova Pericial , Doença de Hodgkin/terapia , Humanos , Prognóstico , Risco , Sarcoma de Kaposi/terapia
9.
Am J Transplant ; 15(4): 1091-100, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25736912

RESUMO

Tailoring treatment by patient strata based on the risk of disease progression and treatment toxicity might improve outcomes of patients with posttransplant lymphoproliferative disorder (PTLD). We analysed the cohort of 70 patients treated in the international, multicenter phase II PTLD-1 trial (NCT01458548) to identify such factors. Of the previously published scoring systems in PTLD, the international prognostic index (IPI), the PTLD prognostic index and the Ghobrial score were predictive for overall survival. None of the scoring systems had a considerable effect on the risk for disease progression. Age and ECOG performance status were the baseline variables with the highest prognostic impact in the different scoring systems. Baseline variables not included in the scoring systems that had an impact on overall survival and disease progression were the type of transplant and the response to rituximab at interim staging. Thoracic organ transplant recipients who did not respond to rituximab monotherapy were at particularly high risk for death from disease progression with subsequent CHOP-based chemotherapy. Patients in complete remission after four courses of rituximab and patients in partial remission with low-risk IPI had a low risk of disease progression. We speculate that chemotherapy might not be necessary in this patient cohort.


Assuntos
Antígenos CD20/imunologia , Linfócitos B/imunologia , Transtornos Linfoproliferativos/tratamento farmacológico , Rituximab/uso terapêutico , Humanos , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/patologia , Pessoa de Meia-Idade , Prognóstico
10.
Am J Transplant ; 14(4): 857-66, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24666832

RESUMO

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5) copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6) copies/mL, patients received one rituximab infusion (375 mg/m(2) ). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p = 0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting.


Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/efeitos adversos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Rejeição de Enxerto/patologia , Rejeição de Enxerto/virologia , Herpesvirus Humano 4/genética , Humanos , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/virologia , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carga Viral , Ativação Viral/efeitos dos fármacos , Adulto Jovem
11.
Am J Transplant ; 13(6): 1512-22, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23721553

RESUMO

We performed a multicenter, International analysis of solid organ transplant (SOT)-related primary central nervous system (PCNS) posttransplant lymphoproliferative disease (PTLD). Among 84 PCNS PTLD patients, median time of SOT-to-PTLD was 54 months, 79% had kidney SOT, histology was monomorphic in 83% and tumor was EBV+ in 94%. Further, 33% had deep brain involvement, 10% had CSF involvement, while none had ocular disease. Immunosuppression was reduced in 93%; additional first-line therapy included high-dose methotrexate (48%), high-dose cytarabine (33%), brain radiation (24%) and/or rituximab (44%). The overall response rate was 60%, while treatment-related mortality was 13%. With 42-month median follow-up, three-year progression-free survival (PFS) and overall survival (OS) were 32% and 43%, respectively. There was a trend on univariable analysis for improved PFS for patients who received rituximab and/or high-dose cytarabine. On multivariable Cox regression, poor performance status predicted inferior PFS (HR 2.61, 95% CI 1.32-5.17, p = 0.006), while increased LDH portended inferior OS (HR 4.16, 95% CI 1.29-13.46, p = 0.02). Moreover, lack of response to first-line therapy was the most dominant prognostic factor on multivariable analysis (HR 8.70, 95% CI 2.56-29.57, p = 0.0005). Altogether, PCNS PTLD appears to represent a distinct clinicopathologic entity within the PTLD spectrum that is associated with renal SOT, occurs late, is monomorphic and retains EBV positivity.


Assuntos
Doenças do Sistema Nervoso Central/epidemiologia , Transtornos Linfoproliferativos/epidemiologia , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Idoso , Doenças do Sistema Nervoso Central/etiologia , Feminino , Seguimentos , Saúde Global , Humanos , Incidência , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Adulto Jovem
12.
Pharmacogenomics J ; 13(6): 507-13, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23069858

RESUMO

Human multidrug resistance-related protein 2 (MRP2, encoded by ABCC2) is involved in the transport of anionic drugs such as methotrexate (MTX). We prospectively investigated the influence of four common ABCC2 genetic variants (rs717620, rs2273697, rs8187694 and rs8187710) on MTX pharmacokinetics parameters. MTX concentrations were monitored in 50 patients with lymphoid malignancy (27 males; mean age: 53±17 years) receiving high-dose MTX (5.13±1.88 g m(-)(2) in a 4-h perfusion). The population pharmacokinetics modelling showed that ABCC2 -24T allele (rs717620) had a combined influence on both MTX elimination and distribution. The MTX clearance and distribution volume were significantly higher in carriers of at least one copy of the -24T allele as compared with noncarriers: 8.6±2.2 vs 6.7± 2.5 l h(-1), P<0.01 and 30.7±7.7 vs 22.1±8.8 l, P<0.001, respectively. Consequently, -24T allele carriers were more prone to reach MTX nontoxic levels, 48 h after administration.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Linfoma/tratamento farmacológico , Metotrexato/farmacocinética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Primers do DNA , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma/classificação , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
13.
ESMO Open ; 7(6): 100650, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36493603

RESUMO

BACKGROUND: Consumption of herbs, food used as medicine and dietary supplements (HFDSs) is common in cancer patients. Herbs and food-drug interactions (HFDIs) can lead to serious adverse effects and can be prevented. We previously reviewed cytochrome P-450 (CYP)-mediated HFDI for 261 HFDSs and we classified the risk of CYP inhibition and induction on a level of evidence scale from 1 (high evidence, supported by several clinical studies) to 5 (low evidence, only limited preclinical data). PATIENTS AND METHODS: We conducted a prospective, non-interventional study (NCT04128865) to assess whether self-assessment of patients could detect HFDI classified as 'probable' (i.e. level 1, 2 or 3 of the scale) in a population of cancer patients. Patients were invited through a tablet application to report their consumption of herbs, regular CYP-interacting food consumption and dietary supplements, as well as some clinical data and cancer treatments. The patient's completion of the survey could be supervised by a health care professional or not. A prespecified threshold of 5% of HFDIs classified as 'probable' detected with the application was deemed relevant. RESULTS: Between 29 March 2018 and 22 June 2018, 143 patients completed the survey. Ninety-five patients (66%) reported at least one current systemic cancer treatment and were included in the analyses. Seventy-four patients reported an intake of at least one HFDS (77.9%), while 21 patients reported no HFDS (22.1%). Twenty-two HFDIs classified as 'probable' were found in 16 patients (16.8%) with the application, which was significantly superior to the prespecified threshold (P = 0.02). The interactions were reported with food (n = 19, 86%) more frequently than with herbs (n = 3, 14%) or with dietary supplements (no interaction reported). CONCLUSIONS: Self-assessment of HFDS interaction with cancer treatment with an application is feasible and should be considered in daily routine. Prospective interventional studies should be conducted to better assess the clinical benefits of this approach.


Assuntos
Interações Alimento-Droga , Neoplasias , Humanos , Estudos Prospectivos , Interações Ervas-Drogas , Sistema Enzimático do Citocromo P-450 , Neoplasias/tratamento farmacológico
16.
Rev Neurol (Paris) ; 166(1): 66-75, 2010 Jan.
Artigo em Francês | MEDLINE | ID: mdl-19403149

RESUMO

INTRODUCTION: The most frequent neurological complication of Waldenström's macroglobulinemia is IgM-mediated polyneuropathy. Direct tumor cell infiltration of the nervous system is very rare and better known as the "Bing and Neel syndrome". This syndrome relates usually to a meningeal or meningo-myelo-cerebral tumor infiltration. OBSERVATION: A 54-year-old man developed a terminal cauda equina syndrome over several years. MRI disclosed lumbar roots infiltration and lumbar puncture the presence of lymphocytic meningitis with intrathecal synthesis of monoclonal IgM identical to that found in the blood. The bone biopsy revealed a lymphoplasmocytic infiltration consistent with the diagnosis of Waldenström's macroglobulinemia. The final diagnosis was meningeal and lumbar roots infiltration revealing Waldenström's macroglobulinemia. Partial remission was obtained after polychemotherapy with CHOP, rituximab and methotrexate. At the end of the treatment, the patient improved his bladder's control and was able to walk with a stick. DISCUSSION: We reviewed the 35 cases of "Bing and Neel syndrome" we have identified by a PubMed research. The present case report is original by the initial neurological presentation of the disease three years before diagnosis and the successful use of rituximab in the polychemotherapy regimen.


Assuntos
Doenças do Sistema Nervoso Central/sangue , Neoplasias do Sistema Nervoso/complicações , Macroglobulinemia de Waldenstrom/sangue , Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Osso e Ossos/patologia , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Terapia Combinada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningite/complicações , Meningite/patologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Neoplasias do Sistema Nervoso/sangue , Neoplasias do Sistema Nervoso/tratamento farmacológico , Polirradiculopatia/complicações , Polirradiculopatia/patologia , Prednisona/uso terapêutico , Rituximab , Raízes Nervosas Espinhais/patologia , Síndrome , Vincristina/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico
17.
Eur J Cancer ; 117: 121-130, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31279304

RESUMO

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal centre B-cell subtype, with unmet medical needs. This study aimed to evaluate the efficacy and toxicity of ibrutinib in DLBCL-PCNSL PATIENTS AND METHODS: This prospective, multicentre, phase II study involved patients with relapse or refractory(R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma. The treatment consisted of ibrutinib (560 mg/day) until disease progression or unacceptable toxicity occurred. The primary outcome was the disease control (DC) rate after two months of treatment (P0 < 10%; P1 > 30%). RESULTS: Fifty-two patients were recruited. Forty-four patients were evaluable for response. After 2 months of treatment, the DC was 70% in evaluable patients and 62% in the intent-to-treat analysis, including 10 complete responses (19%), 17 partial responses (33%) and 5 stable diseases (10%). With a median follow-up of 25.7 months (range, 0.7-30.5), the median progression-free and overall survivals were 4.8 months (95% confidence interval [CI]; 2.8-12.7) and 19.2 months (95% CI; 7.2-NR), respectively. Thirteen patients received ibrutinib for more than 12 months. Two patients experienced pulmonary aspergillosis with a favourable (n = 1) or fatal outcome (n = 1). Ibrutinib was detectable in the cerebrospinal fluid (CSF). The clinical response to ibrutinib seemed independent of the gene mutations in the BCR pathway. CONCLUSION: Ibrutinib showed clinical activity in the brain, the CSF and the intraocular compartment and was tolerated in R/R PCNSL. The addition of ibrutinib to standard methotrexate-base induction chemotherapy will be further evaluated in the first-line treatment. CLINICAL TRIAL NUMBER: NCT02542514.


Assuntos
Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Linfoma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Neoplasias da Retina/tratamento farmacológico , Terapia de Salvação , Adenina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Seguimentos , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Piperidinas , Prognóstico , Estudos Prospectivos , Neoplasias da Retina/patologia , Taxa de Sobrevida
18.
Rev Med Interne ; 38(9): 619-622, 2017 Sep.
Artigo em Francês | MEDLINE | ID: mdl-28196699

RESUMO

INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder of unknown cause. Apparition or flare of previously diagnosed sarcoidosis following hematopoietic stem cell transplantation (HSCT) has rarely been reported. OBSERVATION: We report a 62-year-old woman who presented a radiological flare of sarcoidosis post-autologous stem cell transplantation for a POEMS syndrome. Imaging findings and lymph node histology, which revealed non-caseating granuloma, were consistent with the sarcoidosis diagnosis. The patient was asymptomatic and was kept free of treatment. CONCLUSION: Sarcoidosis must be considered ahead of compatible clinicoradiological presentation occurring after HSCT. Sarcoidosis can mimic metastatic cancer or lymphatic relapse. Tissue biopsies and exclusion of differential diagnosis of granuloma diseases are warranted to confirm sarcoidosis diagnosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Sarcoidose/etiologia , Sarcoidose/imunologia , Imunologia de Transplantes/fisiologia , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome POEMS/imunologia , Síndrome POEMS/terapia , Sarcoidose/diagnóstico , Transplante Autólogo
19.
Bone Marrow Transplant ; 52(8): 1113-1119, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28436974

RESUMO

In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT. Fifteen patients (28.8%) received HDT-ASCT as first-line treatment and 37 (71.2%) received it as second or subsequent line. Remission status before HDT-ASCT was: CR 34.6%, PR 51.9%, stable disease 3.8% and progressive disease 9.6%. Following completion of HDT-ASCT, 36 patients (69.2%) achieved CR (21.2% first-line setting and 48.1% second or subsequent line setting) and 9 (17.3%) PR (5.8% first-line setting and 11.5% second or subsequent line setting). With a median follow-up of 22 months after HDT-ASCT, median PFS and OS were reached after 51.1 and 122.3 months, respectively. The 2-year PFS and OS rates were 62.0% and 70.8%, respectively. We observed two HDT-ASCT-associated deaths (3.8%). In selected elderly PCNSL patients, HDT-ASCT, using thiotepa-based conditioning regimes, is feasible and effective. Further prospective and comparative studies are warranted to further evaluate the role of HDT-ASCT in elderly PCNSL patients.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Tiotepa/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Alquilantes/administração & dosagem , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Europa (Continente) , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Indução de Remissão , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/mortalidade , Transplante Autólogo
20.
Leukemia ; 19(10): 1831-4, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16121217

RESUMO

Fludarabine (FDR) therapy gives a response rate of about 30% in previously treated patients with Waldenström's macroglobulinemia (WM). The combination of FDR and cyclophosphamide (Cy) has been shown to be effective in chronic lymphoproliferative disorders. We administered the combination of FDR (30 mg/m2 i.v. D1-D3) and Cy (300 mg/m2 i.v. D1-D3) to 49 patients. Median age was 64 years. The median hemoglobin, albumin, beta 2 microglobulin and immunoglobulin M (IgM) levels were 9.9 g/100 ml, 39.6 g/l, 3 mg/l and 24.7 g/l, respectively. In all, 14 patients (29%) had not previously been treated. FDR/Cy was administered every 4 weeks for a median of four cycles. In all, 38 patients (77.6%) had partial responses, nine had stable disease and two had progressive disease. After a median of follow-up of 25 months, six patients relapsed and two patients developed large-cell lymphoma. The median time to treatment failure was 27 months. The main toxicity was hematological. In all, 12 patients died, four from progression, one from large-cell lymphoma, three from infection and four from a second malignancy. Two factors negatively influenced overall and event-free survival, age >65 years and IgM <40 g/l. The FDR/Cy combination, therefore, gives a high response rate in WM, even in previously treated patients with factors of poor prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Macroglobulinemia de Waldenstrom/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Progressão da Doença , Feminino , Hemoglobinas/metabolismo , Humanos , Imunoglobulina M/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
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