CAR-T cell therapy for patients with hematological malignancies. A systematic review.

Hematological malignancies represent defying clinical conditions, with high levels of morbidity and mortality, particularly considering patients who manifest multiple refractory diseases. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a potential treatment option for relapsed/refractory B cell malignancies, which have motivated the Food and Drug Administration approval of a series of products based on this technique. The objective of this systematic review was to assess the efficacy and safety of CAR-T cell therapy for patients with hematological malignancies. A comprehensive literature search was conducted in the electronic databases (CENTRAL, Embase, LILACS, and MEDLINE), clinical trials register platforms (Clinicaltrials.gov and WHO-ICTRP), and grey literature (OpenGrey). The Cochrane Handbook for Reviews of Interventions was used for developing the review and the PRISMA Statement for manuscript reporting. The protocol was prospectively published in PROSPERO database (CRD42020181047). After the selection process, seven RCTs were included, three of which with available outcome results. The available results are from studies assessing axicabtagene, lisocabtagene, and tisagenlecleucel for patients with B cell lymphoma, and the certainty of evidence ranged from very low to low for survival and progression-related outcome and for safety outcomes. Additionally, four randomized controlled trials comparing CAR-T cell therapy to the standard treatment for various types of relapsed/refractory B cell non-Hodgkin lymphomas and multiple myeloma included in this systematic review still did not have available outcome data. The results of this review may be used to guide clinical practice but evidence concerning the safety and efficacy of CAR-T Cell therapy for hematological malignancies is still immature to recommend its application outside of clinical trials or compassionate use context for advanced and terminal cases. It is expected the results of the referred comparative studies will provide further elements to subsidize the broader application of this immunotherapy.

Hippo pathway deregulation: implications in the pathogenesis of haematological malignancies.

The Hippo pathway participates in the regulation of cell proliferation, differentiation and apoptosis. It is composed by a large array of proteins whose deregulation has been associated with pro-oncogenic and antioncogenic processes. The present review focuses on the Hippo pathway signalling network and discusses its dual role in oncogenesis, particularly in haematological malignancies.

Assessing the Influence of Different Comorbidities Indexes on the Outcomes of Allogeneic Hematopoietic Stem Cell Transplantation in a Developing Country.

Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) has enabled better prediction of transplant-related mortality (TRM) in allogeneic hematopoietic stem cell transplants (AHSCT), data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27), in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM) and peripheral blood stem cells (PBSC) as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18-65 years); HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3) in this Brazilian population might justify these results.

Drepanocitosis y cáncer: un camino hacia nuevas investigaciones / Sickle cell and cancer: a path to new research

La asociación entre drepanocitosis y enfermedades malignas ha sido reportada desde hace mucho tiempo. Entre ellas, se han diagnosticado, tanto tumores sólidos en diferentes sitios del organismo, como enfermedades hematológicas malignas. En la sobrevida ha incidido, no solo la gravedad de la enfermedad neoplásica, sino también el compromiso orgánico crónico de estos pacientes, en los que la fisiopatogenia de la enfermedad hereditaria condiciona con alta frecuencia un desenlace fatal. Se realiza una revisión actualizada de esta asociación para que constituya una alerta, máxime que ya se conoce la relación casi exclusiva de algunas neoplasias y la hemoglobinopatía S(AU)

Association between sickle cell disease and cancer has been reported for a long time. Among them, solid tumors in different locations of the body and hematological malignances have been diagnosed. Not only the severity of the neoplastic disease but also chronic organ involvement have influenced in patients´survival where the physiopathogenesis of the hereditary disease with high frequency determines a fatal outcome. Our goal is to make an updated review on such association as a warning, considering that the almost exclusive relationship of some cancers and hemoglobinopathy S is already known(AU)

Drepanocitosis y cáncer: un camino hacia nuevas investigaciones / Sickle cell and cancer: a path to new research

La asociación entre drepanocitosis y enfermedades malignas ha sido reportada desde hace mucho tiempo. Entre ellas, se han diagnosticado, tanto tumores sólidos en diferentes sitios del organismo, como enfermedades hematológicas malignas. En la sobrevida ha incidido, no solo la gravedad de la enfermedad neoplásica, sino también el compromiso orgánico crónico de estos pacientes, en los que la fisiopatogenia de la enfermedad hereditaria condiciona con alta frecuencia un desenlace fatal. Se realiza una revisión actualizada de esta asociación para que constituya una alerta, máxime que ya se conoce la relación casi exclusiva de algunas neoplasias y la hemoglobinopatía S...

Association between sickle cell disease and cancer has been reported for a long time. Among them, solid tumors in different locations of the body and hematological malignances have been diagnosed. Not only the severity of the neoplastic disease but also chronic organ involvement have influenced in patients´survival where the physiopathogenesis of the hereditary disease with high frequency determines a fatal outcome. Our goal is to make an updated review on such association as a warning, considering that the almost exclusive relationship of some cancers and hemoglobinopathy S is already known...

[Donor lymphocyte infusions as adoptive immunotherapy in patients with relapsed hematologic neoplasms post-allogenic transplant of hematopoietic progenitor cells]. / Infusiones de linfocitos de dador como inmunoterapia adoptiva en pacientes con neoplasias hematológicas recaídos post trasplante alogénico de células progenitoras hematopoyéticas.

An increasing body of literature has documented the usefulness of donor lymphocyte infusions in inducing remissions in patients relapsing post allogeneic hematopoietic progenitor cell transplantation. Efficacy was shown to depend on the disease entity; the best results have been reported in chronic myeloid leukemia in chronic phase, where the remission rate varied between 60 and 80%. In acute myeloid leukemia and myelodysplastic syndromes the remission rate ranged between 20 and 40% and in multiple myeloma the response rate was approximately 40%. In contrast, results have been poor in acute lymphoid leukemia with only 10-20% and even lower reported responses. Considering the efficacy of donor lymphocyte infusions in inducing responses in several hematologic neoplasias post allogeneic transplantation, as will be described in detail in this review, it is justified to anticipate an increasing role for this modality of treatment in relapsed non transplanted patients and as maintenance of the responses achieved with chemotherapy at conventional or high doses.

Infusiones de linfocitos de dador como imunoterapia adoptiva en pacientes con neoplasias hamatologicas recaidos post transplante alogenico de celulas progenitoras hematopoyeticas / Donor lymphocyte infusions for the treatment of relapse after allogeneic hematopoietic stem cell transplantation

Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis. (AU)

Infusiones de linfocitos de dador como imunoterapia adoptiva en pacientes con neoplasias hamatologicas recaidos post transplante alogenico de celulas progenitoras hematopoyeticas / Donor lymphocyte infusions for the treatment of relapse after allogeneic hematopoietic stem cell transplantation

Un número creciente de publicaciones ha demostrado claramente que la infusión de infusión de linfocitos provenientes del dador original es capaz de reinducir remisiones en pacientes con recaídas luego de un trasplante alogénico de células precursoras hematopoyéticas. También se ha comunicado que la efectividad de la misma varía en las distintas patologías en la que se ha utilizado. Los mejores resultados se obtuvieron en leucemia mieloide crónica, con un rango de remisiones entre 60 y 80 por ciento, mientras que los pacientes con leucemia aguda mieloblástica o síndromes melodisplásicos mostraron porcentajes de remisiones del orden del 20 a 40 por ciento y y pacientes con mieloma múltiple un nível de respuestas próximo a 40 por ciento. En cambio en leucemia aguda linfoblástica los resultados han sido por lo general desalentadores, con un rango de respuestas de apenas 10-20 por ciento y aun inferiores en algunas series. Dada la eficacia de las ILD en ciertas recaidas hematológicas post trasplante alogénico como se expondrá en detalle en esta revisión, es justificado anticipar la extensión de su indicación a pacientes recaídos no trasplantados y como terapia de mantenimiento de la remision obtenida por quimioterapia convencional o a altas dosis.

Anormalidades cromossômicas em neoplasias hematológicas e exposiçäo ocupacional a agrocitoquímicos / Chromosoic abnormalities in haematological neoplasias and occupational exposure to agrotoxic chemicals

A vagotomia subdiafragmática seletiva interfere com a homeostasia glicêmica no modelo experimental animal estudado. Verificou-se que a interrupçäo do ramo vagal anterior (hepático) ou posterior (pancreático) determina elevaçäo da glicemia tanto em ratos avaliados agudamente (15 dias de pós-operatório) quanto cronicamente (60 dias de pós-operatório). Adicionalmente, observou-se que a vagotomia posterior exerce um efeito anterior na fase aguda, evidência que desaparece no grupo crônico. Entretanto, ocorre uma tendência de reduçäo da glicemia nos ratos avaliados cronicamente (60 dias de pós-operatório) em relaçäo aos animais do experimento agudo (15 dias de pós-operatório)