Primary NK/T cell lymphoma nasal type of the stomach with skin involvement: a case report

Since nasal NK/T cell lymphoma and NK/T cell lymphoma nasal type are rare diseases, gastric involvement has seldom been seen. We report a unique case of a patient with a primary NK/T cell lymphoma nasal type of the stomach with skin involvement. The patient had no history of malignant diseases and was diagnosed with hematemesis and intense bleeding from his gastric primary site. Shortly after this event, exanthemic skin lesions appeared with concordant histology to the primary site. Despite chemotherapy, the patient died one month after the first symptomatic appearance of disease

Venetoclax resistance induced by activated T cells can be counteracted by sphingosine kinase inhibitors in chronic lymphocytic leukemia

The treatment of chronic lymphocytic leukemia (CLL) patients with venetoclax-based regimens has demonstrated efficacy and a safety profile, but the emergence of resistant cells and disease progression is a current complication. Therapeutic target of sphingosine kinases (SPHK) 1 and 2 has opened new opportunities in the treatment combinations of cancer patients. We previously reported that the dual SPHK1/2 inhibitor, SKI-II enhanced the in vitro cell death triggered by fludarabine, bendamustine or ibrutinib and reduced the activation and proliferation of chronic lymphocytic leukemia (CLL) cells. Since we previously showed that autologous activated T cells from CLL patients favor the activation of CLL cells and the generation of venetoclax resistance due to the upregulation of BCL-XL and MCL-1, we here aim to determine whether SPHK inhibitors affect this process. To this aim we employed the dual SPHK1/2 inhibitor SKI-II and opaganib, a SPHK2 inhibitor that is being studied in clinical trials. We found that SPHK inhibitors reduce the activation of CLL cells and the generation of venetoclax resistance induced by activated T cells mainly due to a reduced upregulation of BCL-XL. We also found that SPHK2 expression was enhanced in CLL cells by activated T cells of the same patient and the presence of venetoclax selects resistant cells with high levels of SPHK2. Of note, SPHK inhibitors were able to re-sensitize already resistant CLL cells to a second venetoclax treatment. Our results highlight the therapeutic potential of SPHK inhibitors in combination with venetoclax as a promising treatment option for the patients

Regulación inmunoneuroendócrina de la respuesta inmune. estudios en pacientes tuberculosos con distinto grado de afectación pulmonar

La Tuberculosis representa la principal causa de muerte producida por un agente infeccioso, transformándose en uno de los principales problemas en salud pública. Existe evidencia que demuestra que el tipo de RI que el huesped desarrolla, condicionar{ia el estadio clínico y curso de la TB. Asimismo, se conoce que productos del SI son capaces de desencadenar respuestas neuroendócrinas, las cuales podr¡an modular la RI en curso. Con el fin de explorar el rol de las interacciones entre ambos sistemas en el contexto de esta patología, en pacientes de diferente severidad se estudiaron: los efectos in vitro de cortisol y DHEA sobre la linfoproliferación y la producción de citoquinas; el perfil endócrino y de citoquinas plasmáticas y la capacidad de sobrenadantes de cultivos de células periféricas mononucleares basales y estimulados con Tso (sonicado de M.tuberculosis) para modificar la esteroidogénesis adrenal. In vitro se observó un efecto dosis dependiente supresor de cortisol tanto sobre la blastogénesis como sobre la producción de la mayoría de las citoquinas determinadas; particularmente cuanto mayor fue la capacidad de respuesta al antígeno Tso. La DHEA mostró efectos inmunoestimulantes en forma aislada o cuando se la combinó con GC, pero fue incapaz de revertir totalmente la inhibición mediada por cortisol. Existieron diferencias entre pacientes y controles. El perfil endócrino y de citoquinas arrojó diferencias significativas con los controles y así como entre subgrupos de severidad de la enfermedad. A medida que aumentaba la misma, el perfil hormonal tendió a favorecer respuestas humorales, ineficaces para enfrentar al MTB. Pudo demostrarse asimismo, que productos de la RI específica frente a MTB son capaces de afectar directamente la esteroidogénesis adrenal, generando una disminución en la producción de DHEA proporcional a la severidad de la TB. En base a lo observado puede concluirse que la interacción entre ambos sistemas influenciaría en buena medida el curso de la TB pulmonar en el huésped.Fil:Mahuad, Carolina V. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Doctorado en Ciencias Biomédicas. Rosario; Argentin

Primary NK/T cell lymphoma nasal type of the colon

Since nasal NK/T-cell lymphoma and NK/T-cell lymphoma nasal type are rare diseases, colonic involvement has seldom been seen. We report a case of a patient with a primary NK/T-cell lymphoma nasal type of the colon. The patient had no history of malignant diseases and was diagnosed after exhaustive study in the context of fever of unknown origin. The first therapeutic approach followed the DAEPOCH-protocol: etoposide, prednisone, doxor-rubicin, vincristine and cyclophosphamide. The persistence of constitutional symptoms after the first treatment course motivated the switch to a second line following the SMILE-protocol: dexamethasone, metotrexate, ifosfamide, <em>E.coli</em> L-asparaginase, and etoposide. Despite intensive chemotherapy, the patient died 2 months after the diagnose of an extranodal NK/T-cell lymphoma of the colon and 4 months after the first symptomatic appearance of disease

Cellular therapy in lymphoma

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has had a dramatic impact on the natural history and survival of patients with high-risk B-cell non-Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T-cell therapy, written by an International community of lymphoma experts, who also happen to be women.</p