Ibrutinib combined with CAR-T cells in the treatment of del (17p) chronic lymphocytic leukemia with BCL-2 inhibitor resistance: a case report and literature review / 中华血液学杂志

Objective: To improve the knowledge and experience of ibrutinib combined with CAR-T cells in the treatment of high-risk chronic lymphoblastic leukemia (CLL) patients or small lymphocytic lymphoma (SLL) with TP53 gene aberration. Methods: One case of del (17p) CLL patients with BCL-2 inhibitor resistance was treated with ibrutinib combined with CAR-T cells, successfully bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT) , and the relative literatures were reviewed. Results: The patient was a young female with superficial lymph node enlarging at the beginning of the onset. Lymph node biopsy was confirmed as small lymphocytic lymphoma (SLL) without del (17p) . The disease progressed rapidly to CLL/SLL with del (17p) and bone marrow hematopoietic failure 2 years later. Firstly, the patient was treated with BCL-2 inhibitor (Venetoclax) , and the enlarged lymph nodes shrank significantly 2 months later. After 3 months, the disease progressed rapidly. The spleen was enlarged to 16 cm below the ribs, the neck lymph nodes was rapidly enlarged, and the superior vena cava syndrome appeared, which were mainly attributed to venetoclax resistance; so BTK inhibitor (ibrutinib) was used continuously after venetoclax discontinuation. Partial remission (PR) was achieved without lymphocytosis after 2 months, then ibrutinib was combined with CAR-T cells targeting CD19 antigen. Grade 1 of cytokine release syndrome (CRS) appeared after CAR-T cells infusion, and the complete remission (CR) was achieved after 1 month both in bone marrow and peripheral blood, with minimal residual disease (MRD) negative, then bridging allo-HSCT after 2 months of combined therapy. Conclusion: CLL/SLL patients with TP53 aberration have poor prognosis because of rapid progression, drug resistance, etc. Ibrutinib combined with CAR-T cell therapy can quickly achieved complete remission.

Diagnosis and treatment of chronic lymphocytic leukemia: recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia

ABSTRACT Chronic lymphocytic leukemia is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+, CD5+ and CD23+. The lymphocytes usually infiltrate the bone marrow, peripheral blood, lymph nodes, and spleen. The diagnosis is established by immunophenotyping circulating B-lymphocytes, and prognosis is defined by two staging systems (Rai and Binet) established by physical examination and blood counts, as well as by several biological and genetic markers. In this update, we present the recommendations from the Brazilian Group of Chronic Lymphocytic Leukemia for the diagnosis and treatment of chronic lymphocytic leukemia. The following recommendations are based on an extensive literature review with the aim of contributing to more uniform patient care in Brazil and possibly in other countries with a similar social-economic profile.

Recent advances in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) was largely considered to be a disease of slow progression, standard treatment with Chlorambucil and having almost similar prognosis. With the introduction of molecular methods for understanding the disease pathophysiology in CLL there has been a remarkable change in the approach towards the disease. The variation in B-cell receptor response and immunoglobulin heavy chain variable region (IGHV) mutation, genetic aberration and defect in apoptosis and proliferation has had an impact on therapy initiation and prognosis. Early diagnosis of molecular variant is therefore necessary in CLL.

Aspectos epidemiológicos, biotipologia e evolução do tratamento da leucemia linfocítica aguda na infância e adolescência no Rio Grande do Sul / Epidemiologic aspects, biotypology and evolution of acute lymphocytic leukemia in childhood and adolescence in Rio Grande do Sul

A leucemia linfocítica aguda na infância e adolescência é umaneoplasia de precursores linfoides de natureza heterogênea. NoBrasil, os estudos cooperativos foram iniciados em 1980. Nasequência destes estudos foram observadas sobrevidas livre deeventos de 50%, 58% e 70% nos protocolos 80, 82 e 85 respectivamente.Neste trabalho foram avaliados 1.472 pacientes comLLA, 56,59% masculinos e 43,41% femininos, com idades entre 0e 20 anos, média de 7,40 anos, no período de 1980 a 2008 provenientesdo RS. Os dados foram colhidos dos prontuários dos pacientesdas principais instituições hospitalares que assistemneoplasias hematológicas pediátricas. Neste estudo, 487 pacientes(39,40%) foram registrados nos protocolos do GBTLI; 678(54,85%) receberam tratamento baseados nos regimes do grupoBFM e 71 (5,75%) por outros regimes. A sobrevida livre de eventosdos pacientes protocolados foi significativamente superiorcomparada aos não protocolados, 62,41% ± 2,43% e 53,86% ±2,04% respectivamente, em cinco anos. Pacientes com idade de 15a 19 anos tiveram um índice de SLE de 37,98% ± 4,72% em cincoanos, inferior quando comparado aos de 0 a 4 anos e 5 a 9 anosrespectivamente: 62,78% ± 2,28% e 62,43% ± 2,84%. Foi observada,na população estudada, uma SG de 63,73% ± 1,49% e SLEde 57,27% ± 1,57%. A incidência da LLA com progenitores Bseguiu o padrão observado em países desenvolvidos com um picode frequência absoluta entre as idades de 2 a 4 anos. Houve diferençasignificativa entre a população da região urbana ou rural:SLE em cinco anos de 61,76% ± 1,76% e 49,81% ± 4,28% respectivamente.A SLE e a SG em lactentes e portadores de síndrome deDown foi inferior aos resultados obtidos em instituições dos paísesdesenvolvidos.

Acute lymphocytic leukemia (ALL) in childhood andadolescence is a neoplastic disease of varied lymphoid precursors.In Brazil, cooperative studies on the treatment of ALL started in1980. According to these studies, the event free survival (EFS)was 50%, 58% and 70% in the protocols of 1980, 1982 and 1985,respectively. In this work, 1472 ALL patients were evaluated;56.59% were male and 43.41% were female with ages that rangedbetween 0 and 20 years old (mean age of 7.4 years old). Data wascollected from the records of patients with hematologic neoplasiasin medical institutions that offered treatment for pediatricneoplasias in the period from 1980 to 2008. In this study, 487patients (39.40%) were registered in the GBTLI protocol; 678(54.85%) received treatment based on the BFM group regimenand 71 (5.75%) were treated according to other regimens. TheEFS at five years of the patients on the GBTLI protocol wassignificantly higher than those who were not on this protocol(62.41% ± 2.43% and 53.86% ± 2.04%, respectively). In respectto the age range, the patients who were between 15 and 20 yearsold had an EFS of 37.98% ± 4.72% at five years, which is lowerthan the rate for 0 to 4-year-old and 5 to 9-year-old patients(62.78% ± 2.28% and 62.543± 2.84%, respectively). An overallsurvival of 63.73% ± 1.49% and EFS of 57.27% ± 1.57% wereobserved in the studied population. Epidemiologically, theincidence of ALL in B progenitors followed the pattern observedin developed countries with an absolute frequency peak in the agerange of 2 to 4 year olds. The outcome was better for patientsfrom urban areas compared to those from rural areas. EFS andoverall survival in infant and Down syndrome patients were worsethan the results obtained in developed countries.

Consenso Colombiano sobre el tratamiento de la Leucemia linfocítica crónica / Colombian consensus for the treatment of chronic lymphocytic leukemia

Introducción: El Consenso Colombiano de Hematología Oncológica (CC CCHO) es un proyecto apoyado por el Instituto Nacional de Cancerología, E.S.E y por la Sociedad Colombiana de Hematología y Oncología. Su propósito es mejorar los resultados de las intervenciones realizadas en los pacientes con cáncer, ayudando a los profesionales en salud a suministrar la mejor evidencia disponible; a fin de optimizar las decisiones clínicas y promover el uso racional de los recursos. La actividad del CCHO permite desarrollar pautas para la práctica clínica, siguiendo la metodología del grupo nominal; los informes resultantes representan la síntesis de las recomendaciones extraídas de la información recolectada por medio de búsquedas sistemáticas de la literatura médica. La aprobación de las recomendaciones por parte de los miembros del CCHO no significa necesariamente que deba ser adoptada como política;depende del lector.Métodos: Se revisaron las bases Medline (1966-2005), Cochrane Library (Issue 2, 2005), Embase (1974-2005), Biosis (1992-2005), Lilacs (1989-2005) y otras bases de datos relevantes. Los artículos publicados fueron seleccionados y revisados por el comité central del CCHO. Este documento ha sido revisado y aprobada por todos los miembros del Consenso, que incluyó: hematólogos, oncólogos, epidemiólogos, hematopatólogos, un especialista en políticas de salud y un miembro de la comunidad. Tres hematólogos internacionales, de manera independiente, hicieron la revisión externa del documento de resumen. El documento final del consenso requirió un proceso formal de estandarización. Será obligatoria la revisión periódica y continua de la literatura científica y,cuando se considere apropiado, se integrará la nueva información relevante al consenso original.Población: El ámbito del consenso son los pacientes adultos con diagnóstico de leucemia linfocítica crónica (LLC). Los estudios realizados hasta el momento, o el diseño y desarrollo de nuevos experimentos clínicos fa...

Epidemiologia, tratamento e profilaxia das infecções na leucemia linfóide crônica / Epidemiology, treatment and prophylaxis of infections in chronic lymphocytic leukemia

Infecção é uma freqüente complicação em pacientes com leucemia linfocítica crônica (LLC). O risco de infecção é maior à medida que a doença avança, e guarda estreita correlação com a dosagem de imunoglobulinas no sangue. Embora o defeito imune primário na LLC seja deficiência de imunoglobulinas, as diversas modalidades de tratamento comprometem outros elementos do sistema imune, ampliando o espectro de agentes infecciosos. Este texto sumariza o conhecimento atual sobre os riscos de infecção com as diversas modalidades de tratamento e apresenta recomendações para o manejo destas infecções, seja na prevenção seja no tratamento. Tais recomendações são colocadas em graus de evidência tanto do ponto de vista de sua força quanto da qualidade da evidência.

Infection is a frequent complication in patients with chronic lymphocytic leukemia (CLL). The risk of infection is greater with advanced disease and with lower serum immunoglobulin levels. In newly diagnosed patients, the main immunodeficiency is hypogamaglobulinemia, but with different regimens of treatment, other immunodeficiencies occur and contribute to changing the spectrum and increasing the incidence of infection. This paper reviews the current knowledge of the risks and epidemiology of infection according to the different regimens given in the treatment of CLL, and presents recommendations for prophylaxis and treatment of these infections. Such recommendations are rated according to standard scoring schema used in other guidelines to illustrate the strength of the supporting evidence and the quality of the data.

Leucemia linfoblástica aguda en niños: resultados del tratamiento en 24 años / Acute lymphoblastic leukemia in children: result of treatment in twenty four years

Se realiza un estudio de 186 niños diagnósticados de leucemia linfoblástica aguda (LLA) de 1972 a 1995 y tratados con distintos esquemas terapéuticos, casi todos incluidos en los protocolos del grupo Latinoamericano de Tratamiento de Hemopatías Malignas (GLATHEM). Los pacientes se clasificaron en 5 grupos. El grupo está constituido por 20 niños tratados antes de iniciarse en nuestro centro los estudios del GLATHEM; el grupo 2 corresponde a 94 pacientes tratados con los protocolos clásicos de la década de los 70 grupos 3,4 y 5 fueron tratados con esquemas agresivos tipo BFM a partir de 1982. En los grupos 4 y 5 se incluyó el Methotrexate Endovenoso en altas dosis. Independientemente de que se había utilizado distintos parámetros para la clasificación por grupos pronósticos en los protócolos del GLATHEM, con vistas a lograr uniformidad en este trabajo se clasificaron a todos los pacientes retrospectivamente en 3 grupos: bueno, intermedio y malo, en base a la edad y la cifra de leucocitos. Se obtuvo remisión completa en el 92 por ciento de los pacientes incluidos en el GLATHEM sin diferencias significativas entre los distintos protócolos. La sobrevida global se elevó desde un 15 por ciento a los 5 años en el grupo 1 hasta un 70 por ciento en los grupos 4 y 5. La sobrevida libre de eventos (SLE) se eleva de 31 por ciento en el grupo 2 a 67 por ciento en los grupos 4 y 5 en conjunto. El grupo 5 considerado aisladamente tiene un 88 por ciento de sobrevida global y un 72 por ciento de SLE a los 3 años de evolución. Se encontró una diferencia significativa en los porcentajes sobrevida entre los grupos bueno, intermedio y malo en los protocolos de la década de los 70, mientras en los esquemas tipo BFM se borran las diferencias entre bueno e intermedio, persistiendo una sobrevida significativamente menor en el grupo de pronóstico malo. Los porcentajes de sobrevida de 5 años para estos esquemas fueron de 81 por ciento, 78 por ciento y 26 por ciento para los grupos de riesgo bueno, intermedio y malo respectivamente. Los factores pronósticos analizados en forma aislada que tuvieron importancia significativa en los porcentajes de sobrevida fueron: la edad, la esplenomegalia y la cifra de leucocitos superior a 50x10 a la 9/l

Leucemia linfoblástica aguda e envolvimento ocular / Leukemia lymphoblastic acute and ocular envolvement

Os autores relatam 3 casos de Leucemia Linfoblástica Aguda com envolvimento ocular, discorrem a respeito dos modos pelos quais o globo ocular e órbita podem ser envolvidos, seja em consequência das alteraçöes hematológicas inerentes às leucemias ou pela infiltraçäo neoplásica. Comentam acerca do globo ocular como santuário das leucemias e relatam complicaçöes terapêuticas que com evoluçäo da oftalmologia podem ser manejadas com o objetivo de melhorar a qualidade de vida destes pacientes