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1.
BMC Neurol ; 24(1): 250, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039441

RESUMO

BACKGROUND: Diagnosis of primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) is challenging and often delayed. MRI imaging, CSF cytology and flow cytometry have a low sensitivity and even brain biopsies can be misleading. We report three cases of PCNSL with various clinical presentation and radiological findings where the diagnosis was suggested by novel CSF biomarkers and subsequently confirmed by brain biopsy or autopsy. CASE PRESENTATIONS: The first case is a 79-year-old man with severe neurocognitive dysfunction and static ataxia evolving over 5 months. Brain MRI revealed a nodular ventriculitis. An open brain biopsy was inconclusive. The second case is a 60-year-old woman with progressive sensory symptoms in all four limbs, evolving over 1 year. Brain and spinal MRI revealed asymmetric T2 hyperintensities of the corpus callosum, corona radiata and corticospinal tracts. The third case is a 72-year-old man recently diagnosed with primary vitreoretinal lymphoma of the right eye. A follow-up brain MRI performed 4 months after symptom onset revealed a T2 hyperintense fronto-sagittal lesion, with gadolinium uptake and perilesional edema. In all three cases, CSF flow cytometry and cytology were negative. Mutation analysis on the CSF (either by digital PCR or by next generation sequencing) identified the MYD88 L265P hotspot mutation in all three cases. A B-cell clonality study, performed in case 1 and 2, identified a monoclonal rearrangement of the immunoglobulin light chain lambda (IGL) and kappa (IGK) gene. CSF CXCL-13 and IL-10 levels were high in all three cases, and IL-10/IL-6 ratio was high in two. Diagnosis of PCNSL was later confirmed by autopsy in case 1, and by brain biopsy in case 2 and 3. CONCLUSIONS: Taken together, 5 CSF biomarkers (IL-10, IL-10/IL-6 ratio, CXCL13, MYD88 mutation and monoclonal IG gene rearrangements) were strongly indicative of a PCNSL. Using innovative CSF biomarkers can be sensitive and complementary to traditional CSF analysis and brain biopsy in the diagnosis of PCNSL, potentially allowing for earlier diagnosis and treatment.


Assuntos
Linfoma Difuso de Grandes Células B , Humanos , Masculino , Idoso , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Pessoa de Meia-Idade , Feminino , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Biomarcadores Tumorais/líquido cefalorraquidiano , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética
2.
Blood ; 143(12): 1198, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512259
3.
Rev Med Suisse ; 19(850): 2175-2181, 2023 Nov 15.
Artigo em Francês | MEDLINE | ID: mdl-37966150

RESUMO

Tyrosine kinase inhibitors (TKI) have emerged as a paradigm-shifting therapeutic approach for the treatment of chronic myeloid leukemia (CML) following their regulatory approval in 2001. These agents have revolutionized the management of CML by significantly improving patient outcomes and enabling them to achieve near-normal life expectancies. Consequently, the utilization of TKI has become increasingly prevalent, accompanied by the recognition and management of their associated adverse effects. Given the expanding patient population receiving TKI therapy, it is imperative that hematologists, as well as general practitioners, assume the responsibility of closely and meticulously monitoring patients' treatment progress while effectively addressing the occurrence of any untoward effects.


Les inhibiteurs de tyrosine kinase (ITK) ont révolutionné la prise en charge de la leucémie myéloïde chronique (LMC) depuis leur autorisation de mise sur le marché en 2001, permettant aux patients d'obtenir une survie comparable à celle de la population générale. À ce jour, plusieurs générations d'ITK sont apparues, avec leurs effets secondaires respectifs. Leur prescription nécessite donc un suivi rapproché et pluridisciplinaire entre l'hématologue et l'interniste hospitalier, mais également le médecin généraliste, qui peut aussi être confronté à ces effets indésirables.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Terapia de Alvo Molecular , Personalidade
8.
Haematologica ; 105(4): 987-9998, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31289201

RESUMO

Targeting chemoresistant malignant cells is one of the current major challenges in oncology. Therefore, it is mandatory to refine the characteristics of these cells to monitor their survival and develop adapted therapies. This is of particular interest in acute myeloid leukemia (AML), for which the 5-year survival rate only reaches 30%, regardless of the prognosis. The role of the microenvironment is increasingly reported to be a key regulator for blast survival. In this context, we demonstrate that contact with mesenchymal stromal cells promotes a better survival of blasts in culture in the presence of anthracycline through the activation of ABC transporters. Stroma-dependent ABC transporter activation leads to the induction of a Side Population (SP) phenotype in a subpopulation of primary leukemia blasts through alpha (α)4 engagement. The stroma-promoting effect is reversible and is observed with stromal cells isolated from either healthy donors or leukemia patients. Blasts expressing an SP phenotype are mostly quiescent and are chemoresistant in vitro and in vivo in patient-derived xenograft mouse models. At the transcriptomic level, blasts from the SP are specifically enriched in the drug metabolism program. This detoxification signature engaged in contact with mesenchymal stromal cells represents promising ways to target stroma-induced chemoresistance of AML cells.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Camundongos , Células Estromais , Microambiente Tumoral
10.
Ann Hematol ; 94(11): 1859-63, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26280395

RESUMO

In recent years, the outcome of Burkitt leukemia/lymphoma (BL) has improved significantly. Central nervous system (CNS) involvement continues to be a poor prognostic indicator. High doses of intravenous polychemotherapy, intrathecal chemotherapy, and cranio-spinal radiation therapy are used by numerous groups. Majority of patients are cured after this strategy. The next challenge is to decrease toxicities of treatment, including long-term toxicities secondary to cranio-spinal radiation therapy observed in these cured patients. Liposomal cytarabine could be a good alternative to cranio-spinal radiation therapy as already reported in acute lymphoblastic leukemia. We report here eleven patients treated in our center for BL, with liposomal cytarabine instead of cranio-spinal radiation therapy as prophylactic or curative treatment for CNS involvement. Treatment was safe with no short-term grade >3 adverse events. Moreover, no long-term side effects and no impact on outcome were observed. We conclude that LC could be a good option to decrease short/long-term side effects of cranio-spinal radiation therapy in BL and could be evaluated in a future clinical trial.


Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Linfoma de Burkitt/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/prevenção & controle , Citarabina/administração & dosagem , Adolescente , Adulto , Antimetabólitos Antineoplásicos/efeitos adversos , Linfoma de Burkitt/patologia , Linfoma de Burkitt/radioterapia , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/secundário , Quimioprevenção/efeitos adversos , Quimioprevenção/métodos , Irradiação Craniana , Citarabina/efeitos adversos , Feminino , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
Ann Biol Clin (Paris) ; 70(5): 617-21, 2012 Oct 01.
Artigo em Francês | MEDLINE | ID: mdl-23047909

RESUMO

We describe a case of a patient hospitalized in haematology unit for treatment to blastic plasmacytoid dendritic cell neoplasm. Apart skin lesions found at diagnosis in 83% of patients, few elements suggest the diagnosis. Cytology is not characteristic and no cytogenetic abnormality is specific to the LpDC, the karyotype shows generally at least three cytogenetic abnormalities. Definitive diagnosis rests to identification of a blastic population with immunophenotype CD4+ CD56+. This leukemia is chemosensitive but the relapse rate is important and the survival time is 16 months.


Assuntos
Células Dendríticas/patologia , Leucemia/diagnóstico , Leucemia/patologia , Doença Aguda , Idoso , Dorso , Células da Medula Óssea/patologia , Feminino , Humanos , Infiltração Leucêmica/diagnóstico , Infiltração Leucêmica/patologia , Pele/patologia , Tórax
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