Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

Radioterapia en pacientes pediátricos con leucemia linfocítica aguda: experiencia de 9 años

Objetivo: Describir las características epidemiológicas y clínicas de los pacientes con leucemia linfocítica aguda atendidos en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", que recibieron radioterapia externa, durante el periodo de enero de 2009 a diciembre de 2017. Métodos: Estudio observacional, descriptivo. Se revisaron retrospectivamente los expedientes clínicos de pacientes pediátricos (0-13 años) con leucemia linfocítica aguda, que recibieron radioterapia externa en el periodo mencionado. Se aplicó un análisis estadístico descriptivo de las variables cualitativas y cuantitativas. Resultados: Se analizó un total de 58 pacientes, de estos el 79,3% fueron hombres. La edad promedio fue de 7,3 años. El 84,2% fueron clasificados como L1, 84,2% con inmunofenotipo B común y el 56,9% eran grupo de alto riesgo al diagnóstico. La principal indicación de radioterapia fue recaída (67,7%). Aproximadamente la mitad se irradió a sistema nervioso central y la otra mitad a testículos. Los principales efectos adversos fueron cutáneos. Conclusiones: Los resultados obtenidos fueron comparables con los reportados en la literatura. La radioterapia es importante en el tratamiento de leucemias, especialmente en pacientes de recaída y de alto riesgo.

Aim: To describe the epidemiological and clinical characteristics of patients with acute lymphocytic leukemia, attended at the National Children´s Hospital "Dr. Carlos Sáenz Herrera" that received external radiation therapy between January 2009 and December 2017. Methods: It is an observational, descriptive study. Clinical records of pediatric patients (0-13 years) with acute lymphoblastic leukemia that received external radiotherapy in the study period were retrospectively reviewed. A descriptive statistical analysis of the qualitative and quantitative variables was applied. Results: 58 patients were studied, 79,3% were males. The mean age was 7,3 years. 84,2% were classified as L1, 84,2% had common B immunophenotype and 56,9% were in the high risk group at diagnosis. The main indication for radiotherapy was relapse (67,7%). About half the patients received radiotherapy to central nervous system and the other half to testicles. The main side effects were cutaneous. Conclusions: The results obtained were comparable to those seen in literature. Radiotherapy is important in leukemia treatment, particularly in relapse and high risk patients.

Leucemia linfocítica aguda con infiltración en la piel. Presentación de un caso y revisión de la literatura

RESUMEN La leucemia cutánea es una patología muy poco frecuente y se puede presentar en diferentes tipos de leucemias asociadas o no a síndromes genéticos. Es una forma muy poco común de presentación inicial de malignidad. Por sus lesiones inespecíficas en la piel y la similitud con diversas patologías cutáneas representa un gran desafío diagnóstico para el dermatólogo pediátrico. Se presenta el caso de un niño de 5 años con antecedentes de leucemia linfocítica aguda con lesiones papulosas descamativas de aspecto liquenoide diseminadas en tegumento cutáneo. Se realizó una biopsia bajo la sospecha de infiltración a piel o leucemia cutis. Se discutió el caso para llegar a la confirmación diagnóstica de leucemia cutánea. Se inició el tratamiento en el Servicio de Hematología. Esta enfermedad hematológica se manifiesta ocasionalmente en la piel y cuando lo hace es necesario reconocerla para completar su diagnóstico y tratamiento y salvar la vida del paciente afectado como en este caso. El interés de esta presentación radica en que la aparición de lesiones cutáneas, aunque sean inespecíficas, en un paciente con leucemia, debe alertar al equipo médico tratante para su rápido estudio y así orientar la conducta terapéutica y por su baja incidencia de presentación.

ABSTRACT Cutaneous leukemia is a very rare pathology and can occur in different types of leukemia associated or not with genetic syndromes. It is a very uncommon form of initial presentation of malignancy. Due to its non-specific skin lesions and the similarity with various skin pathologies, it represents a great diagnostic challenge for the pediatric dermatologist. We present the case of a 5-year-old boy with a history of acute lymphocytic leukemia with scaly papular lesions of a lichenoid appearance disseminated in the cutaneous integument. A skin biopsy was performed on suspicion of skin infiltration or leukemia cutis. The case was discussed to reach diagnostic confirmation of cutaneous leukemia. Treatment was started in the Hematology Service. This hematological disease occasionally manifests itself on the skin and when it does, it is necessary to recognize it to complete its diagnosis and treatment and save the life of the affected patient, as in this case. The interest of this presentation lies in the fact that the appearance of skin lesions, even if they are non-specific, in a patient with leukemia, should alert the treating medical team for their rapid study and thus guide therapeutic behavior and due to their low incidence of presentation.

Impacto orçamentário da incorporação do rituximabe para o tratamento de leucemia linfocítica crônica no SUS / Budget impact of the incorporation of rituximab for the treatment of chronic lymphocytic leukemia in Brazil

Objetivo: O presente estudo objetiva desenvolver um modelo de análise de impacto orçamentário (AIO) relacionada à incorporação do rituximabe no tratamento de primeira linha da leucemia linfocítica crônica (LLC) no Sistema Único de Saúde (SUS). Métodos: A elaboração da AIO foi realizada de acordo com as recomendações metodológicas das diretrizes brasileiras, considerando a perspectiva do SUS, horizonte temporal de cinco anos, população a ser tratada, diferentes cenários de market share do rituximabe e custos diretos envolvidos no tratamento atual e no tratamento proposto, e também foi executada uma análise de sensibilidade para avaliar possíveis incertezas futuras. Resultados: A cada ano e ao final do horizonte temporal de cinco anos, a incorporação do rituximabe promoverá aumento dos custos, quando comparado com o valor de ressarcimento do SUS para o tratamento de primeira linha da LLC. No cenário de maior participação de mercado do rituximabe, os custos totais foram menores em relação ao cenário de menor market share. Dado que a estimativa da AIO é para gastos futuros, incertezas relacionadas como a possível elevação do custo do medicamento foi o fator que promoveu o cenário de maiores gastos. Conclusões: A projeção de custos estimados pela AIO demonstrou menores gastos financeiros no cenário de maior difusão do medicamento, o que pode ter correlação com o atraso da progressão da doença ao utilizar o rituximabe, e consequentemente menos pacientes irão requerer segunda linha de tratamento, que tem custo mais elevado.

Objective: This study aims to develop a budget impact analysis (BIA) model related to the incorporation of rituximab in the first-line treatment of chronic lymphocytic leukemia (CLL) in the Unified Health System (SUS). Methods: The preparation of the BIA was carried out in accordance with the methodological recommendations of the Brazilian guidelines, considering the perspective of the SUS, a time horizon of five years, population to be treated, different market share scenarios for rituximab and direct costs involved in the current treatment and treatment proposed, a sensitivity analysis was also performed to assess possible future uncertainties. Results: Each year and at the end of the five-year time horizon, the incorporation of rituximab will increase costs, when compared to the SUS reimbursement value for the first-line treatment of CLL. In the scenario of higher market share for rituximab, total costs were lower compared to the scenario of lower market share. Given that the BIA estimate is for future expenses, uncertainties related to the possible increase in the cost of the drug were the factor that promoted the scenario of higher expenses. Conclusions: The projection of costs estimated by the BIA showed lower financial expenses in the scenario of greater diffusion of the drug, which may be correlated with the delay in the progression of the disease when using rituximab and, consequently, fewer patients will require second-line treatment, which has a higher cost.

Blinatumomabe em pacientes pediátricos com leucemia linfoblástica aguda B em primeira recidiva de alto risco: um estudo de custo-efetividade / Blinatumomab in high-risk first relapse pediatric patients with acute lymphoblastic leukemia: a cost-effectiveness analysis

Objetivo: Estimar a custo-efetividade do blinatumomabe como novo padrão no tratamento de consolidação de pacientes pediátricos com leucemia linfoblástica aguda de células precursoras B (LLA-B) em primeira recidiva de alto risco. Métodos: Um modelo de sobrevida particionado com horizonte lifetime e ciclo de quatro semanas foi construído na perspectiva do Sistema Único de Saúde (SUS). Sobrevida livre de eventos e sobrevida global foram extrapoladas com base no ensaio clínico 20120215, usando funções paramétricas. A taxa de desconto foi de 5%. O impacto de variações em pressupostos foi explorado em análises de cenário. Resultados: O custo lifetime com desconto para o caso base foi de R$ 351.615 para blinatumomabe contra R$ 97.770 para HC3 (grupo controle de quimioterapia-padrão), com ganho de 9,96 e 6,74 anos de vida ajustados para qualidade (QALYs), respectivamente. A razão de custo-efetividade incremental (RCEI) foi de R$ 78.873/QALY. Considerando um cenário sem descontos, a RCEI foi de R$ 33.731/QALY ganho. Os outros cenários com maior impacto na RCEI foram a exclusão do desperdício de blinatumomabe (isto é, considerando que a sobra em frasco-ampola de um paciente seria reaproveitada para outro paciente: R$ 35.751) e a alteração do tempo de infusão (troca de bolsa em 48 ou 96 horas em vez de 24 horas: R$ 35.515). A probabilidade de o blinatumomabe ser custo-efetivo foi de 65,7% na análise probabilística, considerando um limiar de R$ 95.501. Conclusões: Blinatumomabe é custo-efetivo para pacientes pediátricos com LLA-B derivada em primeira recidiva de alto risco na perspectiva do SUS.

Objective: To estimate the cost-effectiveness of blinatumomab as the new standard treatment of consolidation in high-risk first relapse pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL). Methods: A partitioned survival model with a lifetime horizon and a 4-week cycle was developed from the Brazilian public healthcare payer's perspective (SUS). Event-free survival and overall survival were extrapolated based on data from the 20120215 clinical trial using parametric functions. A 5% discount rate was used, and the impact of variations in model parameters and assumptions were explored in scenario analyses. Results: The discounted base case lifetime cost was R$ 351,615 for blinatumomab vs. R$ 97,770 for standard chemotherapy control group (HC3), with 9.96 QALYs gained with blinatumomab vs. 6.74 QALYs gained with HC3. The incremental costeffectiveness ratio (ICER) was R$ 78,873/QALY. Considering an undiscounted scenario, the ICER was.

Análise de custo do sequenciamento dos novos agentes para o tratamento de leucemia linfocítica crônica sob a perspectiva do sistema de saúde suplementar brasileiro / Cost analysis of sequencing new agents for the treatment of chronic lymphocytic leukemia from the perspective of the Brazilian supplementary health system

Objetivo: Estimar o custo do sequenciamento de tratamentos e por desfecho dos novos agentes disponíveis para o tratamento de pacientes com leucemia linfocítica crônica (LLC) em primeira linha (1L) e segunda linha (2L) em um horizonte temporal de 15 anos sob a perspectiva do sistema de saúde suplementar brasileiro. Métodos: Foi desenvolvido um modelo de sobrevida particionada com quatro transições de estados de saúde (sem progressão em 1L, sem progressão em 2L, pós-progressão e morte), considerando os seguintes regimes: venetoclax + obinutuzumabe (VenO), venetoclax + rituximabe (VenR), ibrutinibe (Ibru) e acalabrutinibe (Acala). Foram consideradas na análise as posologias em bula e as curvas de sobrevida livre de progressão (SLP) dos respectivos estudos pivotais em cada uma das linhas terapêuticas. O custo total de cada sequência considerou a soma dos custos dos regimes utilizados em 1L e 2L, baseado no preço fábrica de cada medicamento. Resultados: As sequências de tratamento iniciadas com VenO apresentaram menores custos, especialmente o regime VenO>VenR (R$ 982.447), que apontou redução de aproximadamente R$ 3 milhões em 15 anos, quando comparada às sequências de Ibru>VenR ou Acala>VenR. Na análise de custo por desfecho, a sequência VenO>VenR apresentou o menor custo por ano de SLP (R$ 104.437), até 76% inferior em relação ao sequenciamento com maior custo por ano de SLP (Ibru>VenR). Conclusões: Os resultados desta análise demonstram o impacto significativo que a 1L de tratamento possui na jornada do paciente com LLC. Adicionalmente, o presente estudo aponta o menor custo de tratamento acumulado para o sequenciamento dos regimes VenO>VenR, sugerindo que os regimes de tratamento à base de venetoclax podem contribuir de maneira substancial em uma maior eficiência na alocação de recursos pelo gestor do sistema de saúde suplementar brasileiro.

Objective: To estimate the cost of treatment sequencing and per outcome of the new agents available for the treatment of patients with chronic lymphocytic leukemia (CLL) in 1st line (1L) and 2nd line (2L) in a 15-years time horizon from the perspective of the Brazilian supplementary health system. Methods: A partitioned survival model including four health state transitions (no progression in 1L, no progression in 2L, post-progression and death) was developed, considering the following regimens: venetoclax + obinutuzumab (VenO), venetoclax + rituximab (VenR), ibrutinib (Ibru) and acalabrutinib (Acala). The package insert dosages and progression-free survival (PFS) curves of the respective pivotal studies in each of the therapeutic lines were considered in the analysis. The total cost of each sequence considered the sum of the costs of the regimens used in 1L and 2L, based on the factory price of each drug. Results: Lower costs were observed when treatment sequences were initiated with VenO, especially the VenO>VenR regimen (R$ 982,447), which showed a reduction of approximately R$ 3 million in 15 years when compared to the Ibru>VenR or Acala>VenR sequences. In the cost per outcome analysis, the sequence VenO>VenR had the lowest cost per year of PFS (R$ 104,437), up to 76% lower than the sequencing with the highest cost per year of PFS (Ibru>VenR). Conclusions: Results show the significant impact that 1L treatment has on the CLL patient's journey. Additionally, the present study points to the lowest accumulated treatment cost for the sequencing of VenO>VenR regimens, suggesting that venetoclax-based treatment regimens can substantially contribute to greater efficiency in the allocation of resources by the manager of the Brazilian supplementary health system.

Leucemia linfocítica crônica associada a melanoma metastático em homem de 53 anos / Metastatic melanoma in a 53-year-old male with relapsed chronic lymphocytic leukemia

Introdução: A associação de leucemia linfocítica crônica (LLC) e melanoma tem sido estudada nos últimos anos. Acredita-se que a imunossupressão causada pelo tratamento da doença seja o fator de risco mais importante para o aumento da susceptibilidade ao desenvolvimento e disseminação do câncer de pele. Relato de Caso: Este relato de caso descreve homem de 53 anos, em tratamento de leucemia linfocítica crônica desde 2018, já submetido a diversos ciclos de quimioterapia com fludarabina. Apresentou histórico de exérese de melanoma nodular epitelioide no couro cabeludo em 2019, removido com margens livres. Um ano após a cirurgia, paciente evoluiu com piora do estado geral com necessidade de hospitalização. Investigação adicional revelou focos de metástase em pulmões, fígado, rins, estômago, sistema nervoso central e linfonodos. Análise histopatológica foi positiva para melanoma. A possibilidade de tratamento foi descartada pela equipe de oncologia, que sugeriu cuidados paliativos. Discussão: Um dos mecanismos mais discutidos para explicar esta associação de neoplasias é a imunossupressão resultante do tratamento da LLC, que deixa o paciente suscetível ao desenvolvimento e à disseminação do melanoma. Além disso, a fludarabina, quimioterápico geralmente usado para remissão da LLC, é conhecida por depletar células T-helper e tem sido descrita como cofator deste processo. A associação de leucemia e melanoma cutâneo têm sido descrita nos últimos anos, porém não há nenhum protocolo de tratamento para esta condição.

BACKGROUND: The association of Chronic Lymphocytic Leukemia (CLL) and melanoma have been studied in the last years. The immunosuppression caused by the treatment of CLL seems to be the major factor of increasing patients' susceptibility to the development and spread of skin cancer. CASE REPORT: This case report describes a 53-year-old male patient, in CLL treatment since 2018, already submitted to many cycles of chemotherapy with fludarabine. History of an exeresis of epithelioid nodular melanoma of the scalp in 2019, which was removed with a clear margin. One year later, he presented with a poor general condition with hospitalization indication. Additional investigation revealed metastatic lesions in lungs, liver, kidneys, stomach, central nervous system, and lymph nodes. Histopathologic analysis positive for melanoma. The possibility of treatment was discarded by the Oncology team, which suggested palliative care. DISCUSSION: One of the most discussed mechanisms to explain this cancer association is the immunosuppression developed during the treatment of CLL, increasing patients' susceptibility to the development and spread of melanoma. In addition, the use of fludarabine, a chemotherapy commonly used in relapsed CLL, is known to deplete T-helper cells and has been described as a cofactor of this process. The association of leukemia and cutaneous melanoma has been reported in the last years, yet there is no surveillance protocol.

Leucemia linfocítica crónica y deleción del gen TP53: reporte de un caso y revisión de la literatura / Chronic lymphocytic Leukemia and deletion of the TP53 gene: Case report and literature review

RESUMEN Las alteraciones genéticas en el gen TP53 están presentes entre el 5 al 8 % de los pacientes de leucemia linfocítica crónica (LLC) en el momento del diagnóstico. Estos casos se relacionan con un mal pronóstico debido a su resistencia al tratamiento estándar. Presentamos el caso de un paciente masculino de 52 años diagnosticado con LLC, expresión del marcador CD38 y una deleción en el gen TP53 (17p13.1). Tras la evaluación posterior del tratamiento, se observó enfermedad mínima residual lo que llevó a un trasplante haploidéntico de progenitores hematopoyéticos. Debido al alto riesgo de recaída, su edad y la ausencia de comorbilidades, era la única opción curativa hasta la fecha para la LLC. El objetivo de este trabajo es realizar una revisión de la literatura que sirva como base para analizar el caso clínico presentado, en el marco de las implicaciones clínicas, pronóstico y respuesta al tratamiento en los individuos con LLC que presentan alteraciones en el gen TP53.

SUMMARY Genetic alterations in the TP53 gene are present in 5 to 8% of chronic lymphocytic leukemia (CLL) cases at the time of diagnosis. These cases are typically associated with poor prognosis due to their resistance against standard CLL treatment. In our report a 52-yearold male patient was diagnosed with CLL, CD38 expression and a deletion in the TP53 gene (17p13.1). Upon evaluation post-treatment, minimal residual disease (MDR) was observed, and a haploidentical stem cell transplant was performed. Because of the high risk of relapse, his age, and the absence of comorbidities it was the only curative option to date for CLL. The purpose of this article is to complete a literature review that will give a basis to analyze the clinical case presented, within the framework of the clinical implications, prognosis, and response to treatment in patients with CLL who present with aberrations of the TP53 gene.

Injuria subendocárdica sin evidencia de aterosclerosis relacionada con infusión de obinutuzumab / Subendocardial injury with no evidence of atherosclerosis associated with obinutuzumab infusión

Resumen El obinutuzumab es un anticuerpo monoclonal completamente humanizado contra CD20, empleado en el tratamiento de leucemia linfocítica crónica. Los eventos cardiovasculares fatales han sido des critos, pero solo en pacientes con antecedentes cardiovasculares conocidos. Presentamos el caso de un hombre adulto con diagnóstico de leucemia linfocítica crónica de alto riesgo que desarrolló injuria subendocárdica, sin evidencia de aterosclerosis coronaria, durante la primera infusión de obinutuzumab.

Abstract Obinutuzumab is a fully humanized monoclonal antibody against CD20 used in the treat ment of chronic lymphocytic leukemia. Fatal cardiovascular events have been described, but only in patients with known cardiovascular records. We report the case of an adult male with a high-risk chronic lymphocytic leukemia who developed subendocardial injury, with no evidence of coronary atherosclerosis, during the first administration of obinutuzumab.

Alterações retinianas em pacientes com leucemia linfocítica aguda (lla): discussão de tema a partir de relato de caso / Retinal changes in patients with acute lymphocytic leukemia (all): discussion of topic from a case report

RESUMO A Leucemia Linfocitica Aguda (LLA) é uma doença caracterizada por uma alta taxa de sobrevida, porém o número absoluto de crianças que morrem por ela representa uma grande parcela dos casos de óbitos infantis por câncer. A morbidade decorrente de seu tratamento pode deixar sequelas em pessoas com grande expectativa de vida, tornando-se extremamente necessário o entendimento da patogênese desta doença, possibilitando o desenvolvimento de novos tratamentos e diminuição de sequelas provocadas pela doença. O diagnóstico precoce é importante para se evitar complicações oculares que possam levar a baixa de acuidade visual em longo prazo e para avaliação de recaídas de tratamento sendo determinante no direcionamento de condutas.

ABSTRACT The Acute Lymphocytic Leukemia (ALL) is a disease characterized by a high survival rate, but the absolute number of children who die from it represents a large proportion of cases of infant deaths from cancer. The morbidity resulting from its treatment can leave sequelae in people with high life expectancy, making it extremely necessary to understand the pathogenesis of this disease, enabling the development of new treatments and reduction of sequelae caused by the disease. This early diagnosis is important to avoid ocular complications that may lead to low long-term visual acuity and to evaluate treatment relapses and determine the conducts.

Leucemias crónicas y SARS-CoV-2 / Chronic leukemias and SARS-CoV-2

Resumen El 30 de enero del año 2020, la Organización Mundial de la Salud declaró emergencia internacional de Salud Pública la pandemia causada por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2). Al inicio surgieron muchas dudas relacionadas con los ajustes al tratamiento y el seguimiento de los pacientes con leucemias crónicas y diversas asociaciones internacionales emitieron recomendaciones. El uso de la telemedicina y la selección de estrategias de tratamiento que permitan un menor acercamiento de los pacientes a los centros hospitalarios ha sido una de las principales técnicas de protección de los pacientes con leucemias crónicas. La experiencia internacional nos describe que al parecer los pacientes con leucemia mieloide crónica son menos susceptibles a contraer la infección y a morir, al contrario de los pacientes con leucemia linfocítica crónica.

Abstract On January 30 of the 2020 year, the World Health Organization declared an international public health emergency the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially, many doubts arose regarding treatment adjustments and follow-up of patients with chronic leukemias, and various international associations issued recommendations. The use of telemedicine and the selection of treatment strategies that allow care without patients going to hospital centers, has been one of the main techniques for protecting patients with chronic leukemias. International experience describes that it seems that patients with chronic myeloid leukemia are less susceptible to infection and death, unlike patients with chronic lymphocytic leukemia.

Linfoma linfocítico de células pequeñas de anexos oculares. Presentación de un caso / Small cell lymphocytic lymphoma of eye annexes. Case presentation

RESUMEN Los linfomas son enfermedades malignas que se originan en las células del sistema inmune y se manifiestan predominantemente por linfoadenopatías; en ocasiones la presentación es en sitios extranodales. El ojo y sus anexos pueden ser afectados por un grupo heterogéneo de linfomas primarios o, secundariamente, por la extensión de linfomas originados en ganglios linfáticos o en otros sitios extranodales. Se reporta el caso de un paciente que acudió a consulta por ptosis palpebral izquierda y al examen físico se detectó afectación bilateral, con presencia de tumores en la conjuntiva bulbar inferior en ojo derecho y en la conjuntiva bulbar superior en ojo izquierdo. Mediante biopsia de conjuntiva se diagnosticó linfoma no Hodgkin linfocítico de células pequeñas B. El paciente fue considerado un estadio IIIAE de Ann Arbor y tratado con seis ciclos de ciclofosfamida, vincristina, doxorrubicina y prednisona, más el anticuerpo monoclonal cubano anti-CD20 CIMABior®. Se alcanzó la respuesta completa, estado en el cual se mantiene hasta el momento.

ABSTRACT Lymphomas are malignant diseases that originate in the immune system cells and are predominantly manifested by lymphadenopathy; sometimes the presentation is in extranodal places. The eye and its annexes may be affected by a heterogeneous group of primary lymphomas or, secondarily, by the extension of lymphomas originated in lymph nodes or other extranodal sites. The case of a patient who went to the consultation due to left palpebral ptosis is reported and physical examination showed bilateral involvement, with tumors in the lower right eye bulbar conjunctiva and in the left eye upper bulbar conjunctiva. A small B cell lymphocytic non-Hodgkin lymphoma was diagnosed by conjunctiva biopsy. The patient was considered a stage IIIAE of Ann Arbor and treated with six cycles of cyclophosphamide, vincristine, doxorubicin and prednisone, plus the Cuban monoclonal antibody anti-CD20 CIMABior®. The complete response was reached, state in which the disease remains so far.

Leucemia linfoide crónica de células B: revisión de sus aspectos etiopatogénicos, moleculares y pronósticos / B-cell chronic lymphoid leukemia: a review of its etiopathogenic, molecular and prognostic aspects

La leucemia linfoide crónica (LLC) es una neoplasia maligna que afecta principalmente a pacientes de mediana edad y ancianos. Se caracteriza por la proliferación de linfocitos morfológicamente maduros pero inmunoincompetentes que se acumulan en sangre periférica, médula ósea y tejido linfático. Presenta gran heterogeneidad clínica. Se describen diversos fenotipos, aunque predomina la expansión clonal de células B CD5+CD23+. Los factores pronósticos en la LLC incluyen el subgrupo citogenético, estado mutacional de inmunoglobulina, la expresión de ZAP-70, CD38 y CD49d. El tratamiento se basa en usar modernos algoritmos terapéuticos aprobados, que produzcan mayores respuestas y menores eventos secundarios, en lograr la remisión clínica completa y mejorar la calidad de vida de estos pacientes(AU)

Chronic lymphocytic leukemia (CLL) is a malignancy that mainly affects middle-aged and elderly patients. It is characterized by the proliferation of morphologically mature but immunoincompetent lymphocytes that accumulate in blood, bone marrow and lymphatic tissue. It presents great clinical heterogeneity. Several phenotypes are described, although the clonal expansion of CD5 + CD23 + B cells predominates. Prognostic factors include the cytogenetic subgroup, immunoglobulin mutational status, expression of ZAP-70, CD38, and CD49d. The treatment is based on using modern approved therapeutic algorithms that produce greater responses and minor secondary events, to achieve complete clinical remission and to improve the quality of life of these patients(AU)

Mutaciones del gen NOTCH1 en la leucemia linfocítica crónica / NOTCH1 gene mutations in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world. The disease has\r\na highly variable clinical course, ranging from very indolent cases to patients with aggressive and rapidly\r\nprogressing outcome. Genetic studies are useful tools in analyzing this pathology, and have been incorporated in international risk classifications. The analysis of genomic rearrangements and the mutational status of immunoglobulin heavy chain variable have allowed risk groups of high prognostic value to be established. More recently, next generation sequencing studies have identified novel somatic mutations that could explain the wide clinical variability of this pathology. Among them, the analysis of NOTCH1 (neurogenic locus notch homolog protein 1) gene mutations are of interest, as deregulation is associated with tumorigenesis. NOTCH11 mutations are mostly located at exon 34 (80% of cases) and 3´UTR (untranslated region). They produce premature stop codons that produce a constitutively active and stable NOTCH1 protein. NOTCH1 mutations are associated with adverse prognosis and refractoriness to treatment. The aim of this study was to analyze NOTCH1 mutations in CLL patients by ASO-PCR and sequencing. Our results found 4.4% of cases with NOTCH1 mutated values concordant with international observations (5%-10%). Including them in the genetic status of CLL patients allows the characterization of risk groups, an aspect of great importance in clinical practice and therapeutic decisions, to be refined.

La leucemia linfocítica crónica (LLC) es la leucemia más frecuente en adultos de Occidente. Presenta\r\nun curso clínico altamente variable, con pacientes que requieren tratamiento inmediato y otros con un curso indolente de la enfermedad. Los estudios genéticos constituyen herramientas de suma utilidad en esta enfermedad, encontrándose incorporados a las clasificaciones de riesgo internacionales. El análisis de los rearreglos genómicos y del estado mutacional de los genes IGHV (immunoglobulin heavy chain variable region) ha hecho factible establecer grupos de riesgo de alto valor pronóstico. Más recientemente, estudios de secuenciación de última generación permitieron la detección de mutaciones\r\nsomáticas previamente desconocidas en esta afección, que podrían explicar la amplia variabilidad clínica\r\nobservada en la LLC. Entre ellas, resultan de interés las observadas en el gen NOTCH1 (neurogenic locus notch homolog protein 1), cuya desregulación se asocia con el desarrollo tumoral. Estas mutaciones se acumulan en mayor medida en el exón 34 (80% de los casos) y en la región 3´UTR (untraslated region), lo que genera codones de terminación prematuros que originan una proteína NOTCH1 constitutivamente activa y más estable, los cuales se asocian con pronóstico adverso y refractariedad al tratamiento. Nuestro objetivo fue evaluar mutaciones de NOTCH1 en nuestros pacientes mediante ASO-PCR y secuenciación. Se detectaron mutaciones en el 4.4% de los casos, valor concordante con los datos internacionales (5% a 10%). Su inclusión en la caracterización genética de los pacientes con LLC permitirá refinar la categorización de los grupos de riesgo, aspecto de suma importancia tanto en el seguimiento clínico como en la toma de decisiones terapéuticas.

Histoplasmosis diseminada como manifestación inicial del linfoma linfocítico de células pequeñas / Disseminated histoplasmosis as a first clinical manifestation in a patient with small lymphocytic lymphoma: A case report

RESUMEN El linfoma linfocítico de células pequeñas es una neoplasia de células B maduras con un amplio espectro de presentaciones clínicas. Las infecciones por gérmenes oportunistas no asociadas con el tratamiento, incluso en estadios avanzados de la enfermedad, tienen baja incidencia. Se han reportado muy pocos casos de pacientes con linfoma linfocítico de células pequeñas asociado a histoplasmosis diseminada que no habían recibido quimioterapia en el momento del diagnóstico. Se presenta el caso de una paciente de 82 años que fue hospitalizada por presentar tos seca intermitente, astenia y adinamia de un mes de evolución. Se le practicaron múltiples estudios para detectar infecciones o compromiso inmunológico o reumático, y se diagnosticó un síndrome adenopático extenso con compromiso cervical, torácico y retroperitoneal. En la citometría de flujo y en la biopsia de ganglio linfático cervical, se reportaron los fenotipos CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg y CD10neg, con restricción de la cadena ligera kappa, lo cual confirmó un linfoma linfocítico de células pequeñas. En la histopatología del ganglio, se observaron granulomas epitelioides sin necrosis, pero las coloraciones especiales no mostraron la presencia de microorganismos, en tanto que el cultivo del ganglio fue positivo para Histoplasma capsulatum. Se inició el tratamiento antifúngico con anfotericina B e itraconazol, y la paciente tuvo una adecuada evolución. Dado que no se cumplían los criterios para el tratamiento oncológico, se continuó con su observación mediante controles periódicos. Las infecciones oportunistas pueden ser la manifestación clínica inicial en pacientes con síndromes linfoproliferativos de bajo grado. Este caso demuestra que pueden desarrollarse, incluso, en ausencia de quimioterapia.

ABSTRACT The small lymphocytic lymphoma is a mature B cell neoplasm with a broad spectrum of clinical presentations. Opportunistic infections that are not related to the treatment, even in advanced stages, have a low incidence rate. There are few case reports in the medical literature of patients who have not received immunosuppressive therapy and present with small lymphocytic lymphoma associated with disseminated histoplasmosis at diagnosis. A female 82-year-old patient was admitted due to an intermittent dry cough, asthenia, and adynamia that had persisted for one month. Multiple studies to detect infections and immuno-rheumatic conditions were performed and an extensive cervical, thoracic and peritoneal adenopathic syndrome was diagnosed. A flow cytometry and a cervical lymph node biopsy were performed reporting CD19+, CD20dim, CD5+, CD45+, CD23+, CD43neg, and CD10neg phenotypes with restriction in the light kappa chain compatible with a small lymphocytic lymphoma. Epithelioid granulomas without necrosis were observed in the lymph node histopathology and special colorations showed no microorganisms. The culture from the lymph node was positive for Histoplasma capsulatum. We initiated treatment with amphotericin B and itraconazole with an adequate response. In the absence of compliance with oncology treatment criteria, the patient was managed on a "watch and wait" basis. Opportunistic infections could be the initial clinical manifestation in patients with low-grade lymphoproliferative syndromes. This case report shows that they can develop even in the absence of chemotherapy.

Pancreatitis aguda como efecto adverso de L-asparginasa en el tratamiento de la leucemia linfocítica aguda / Acute pancreatitis as an adverse side effect of L-asparaginase in the treatment of acute lymphoblastic leukemia

Resumen La leucemia linfocítica aguda es la enfermedad oncológica con mayor incidencia en la población pediátrica, tanto a nivel mundial como en Costa Rica. Para su tratamiento requiere protocolos de quimioterapia complejos, lo que representa un reto constante para los médicos, ya que deben equilibrar los riesgos y beneficios del manejo. Es necesario tomar en cuenta los factores de riesgo de cada paciente, el grado de severidad de la enfermedad y los potenciales efectos adversos del tratamiento. A continuación, se reporta un caso de pancreatitis aguda edematosa no biliar, secundaria al uso de L-asparginasa, en un paciente con diagnóstico de leucemia linfocítica aguda, atendido en el Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera". El paciente, quien se encontraba cumpliendo el régimen poliquimioterapeútico AHOPCA 2008, presentó clínica sugestiva de pancreatitis aguda en el día 50 de este, por lo que se decidió no colocar la quimioterapia indicada e inmediatamente se trasladó al Servicio de Emergencias. El cuadro clínico estaba asociado a laboratorios y ultrasonido anormales, por lo que fue tratado interdisciplinariamente y su pronóstico fue favorable; actualmente continúa con tratamiendo quimioterapeútico, como fue indicado.

Abstract The acute lymphocytic leukemia is the oncological disease with the highest incidence in the pediatric population both worldwide and in Costa Rica. It requires complex chemotherapy protocols, which confers a constant challenge on physicians to balance the risks and benefits of management. Therefore, it is necessary to take into account the risk factors of each patient, the degree of severity of the disease and the potential adverse effects of the treatment. A case report is presented with an acute non-biliary edematous pancreatitis, secondary to the use of L-asparaginase in a patient diagnosed with acute lymphocytic leukemia, seen at the National Children's Hospital "Dr. Carlos Sáenz Herrera". The patient who was started on the AHOPCA 2008 polychemotherapy regimen presented symptoms suggestive of acute pancreatitis on the day 50 of the same, so it was decided not to apply the indicated chemotherapy and transfer the patient to the Emergency Room. The clinical picture was associated with abnormal laboratories and ultrasound, so it was immediately treated interdisciplinarily, which is why its prognosis was favorable and currently he continues with chemotherapy treatment as indicated.

Pénfigo paraneoplásico asociado a leucemia linfocítica crónica / PARANEOPLASTIC PENPHIGUS ASSOCIATED TO CHRONIC LYMPHOCYTIC LEUKEMIA

El pénfigo paraneoplásico es una dermatosis ampollar autoimmune asociada a un proceso neoplásico, conocido previamente o no. Se presenta con mayor frecuencia en hombres, entre los 45 y 70 años, pero también puede manifestarse en niños. La clínica es polimorfa. Existen 5 variantes posibles: pénfigo símil, penfigoide ampollar símil, eritema multiforme símil, enfermedad de injerto contra huésped símil y liquen plano símil. Todas ellas comparten una característica en común: la estomatitis severa, dolorosa, progresiva y refractaria a los tratamientos convencionales, que obliga a descartar esta enfermedad. Si bien los antígenos involucrados en su fisiopatogenia son múltiples, la detección de anticuerpos Ig G anti envoplaquina y anti periplaquina constituye el método de diagnóstico más específico. En la actualidad se utilizan los criterios de diagnóstico de Camisa y Helm, que se basan en hallazgos clínicos (erupción mucocutánea polimorfa), histológicos (acantolisis) e inmunohistoquímicos (inmunofluorescencia directa, indirecta e inmunoprecipitación positivas). El abordaje de esta enfermedad debe considerar dos aspectos: el tratamiento del pénfigo en sí y el de la neoplasia asociada, que puede ser benigna (raro) o maligna (con mayor frecuencia). El pronóstico es severo (mortalidad del 75-90%) y en la mayoría de los casos la causa de muerte depende de las complicaciones de la enfermedad, como sepsis y bronquiolitis obliterante. Se presenta un paciente varón de 67 años con PPN asociado a Leucemia Linfocítica Crónica que respondió satisfactoriamente al tratamiento instaurado (meprednisona + quimioterapia con fludarabina, ciclofosfamida y rituximab) y no presentó recidiva a más de 2 años de seguimiento interdisciplinario.

Paraneoplastic pemphigus is an autoimmune blistering disease associated with neoplasms, previously known or not. It occurs most often in men, between 45-70 years, but can also manifest in children. The clinic is polymorphic. There are 5 possible variants: pemphigus-like, bullous pemphigoid-like, erythema multiforme-like, graft versus host disease-like and lichen planus-like. All of them share a common characteristic: a severe, painful, progressive and refractory to conventional treatments stomatitis, which forces us to rule out this disease. Although the antigens involved in its physiopathogenesis are multiple, the detection of anti-envoplakin and anti-periplakin IgG antibodies constitutes the most specific diagnostic method. At present, the diagnostic criteria of Camisa and Helm are used, which are based on clinical (polymorphic mucocutaneous eruption), histological (acantholysis) and immunohistochemical findings (direct and indirect immunofluorescence and immunoprecipitation positive). The approach to this disease must consider two aspects: treatment of the pemphigus as well as the associated neoplasm, which can be benign (rare) or malignant (more frequently). The prognosis is severe (mortality of 75-90%) and in most cases the cause of death depends on the complications of the disease, such as sepsis and bronchiolitis obliterans. We present a 67-year-old male patient with PPN associated with Chronic Lymphocytic Leukemia who responded satisfactorily to the established therapy (meprednisone + chemotherapy with fludarabine, cyclophosphamide and rituximab) and did not present recurrence after more than two years of interdisciplinary follow-up.

Leucemia linfocítica crónica con infiltración ocular / Chronic lymphocytic leukemia with eye infiltration

La incidencia de la leucemia linfocítica crónica (LLC) aumenta progresivamente con la edad; aproximadamente el 75 por ciento de los casos presentan 60 años o más. Este tipo de leucemia es más frecuente en varones y se desconoce su causa, existen casos que son de origen hereditario. Se presenta el caso de un paciente con el diagnóstico de LLC con infiltración ocular. Paciente blanco, masculino de 76 años de edad con antecedentes de salud de haber sido diagnosticado con LLC desde hace 5 años que se trata con Leukeran (Clorambucil) (2mg) 2 tabletas en el almuerzo y 3 tab en la comida, así como de prednisona (5mg) 1 cada 8 horas solo cuando está descompensado. Hace alrededor de 3 días comenzó con astenia, anorexia, mareos, dolor e inflamación del párpado superior derecho. El examen físico, la biopsia del párpado superior y el frotis de sangre revelaron la presencia de una recaída hematológica de la LLC con infiltración ocular(AU)

The incidence of chronic lymphocytic leukemia (CLL) increases progressively with age, approximately 75 percent of cases present 60 years or more. This type of leukemia is more frequent in men and its cause is unknown, there are cases that are of hereditary origin. A clinical case of a patient with the diagnosis of Chronic Lymphocytic Leukemia with ocular infiltration is presented. A 76-year-old white male patient with a health history of having been diagnosed with a Chronic Lymphocytic Leukemia for 5 years who is treated with Leukeran (Chlorambucil) ( 2mg) 2 tab at lunch and 3 at night; and prednisone (5mg) 1 tab every 8 hours. About 3 days ago begins with asthenia, anorexia, dizziness, pain and swelling of the upper right eyelid. Physical examination, upper eyelid biopsy and blood smears reveal the presence of a hematological relapse with ocular infiltration(AU)

Seguridad y efecto del uso compasivo del anticuerpo monoclonal anti-CD20 CIMABior® / Safety and response to treatment of compassionate use of an anti-CD20 monoclonal antibody CIMABior®

Introducción: el uso de anticuerpos monoclonales transformó el tratamiento de los linfomas no hodgkinianos. El Centro de Inmunología Molecular generó un anticuerpo anti-CD20 (CIMABior®) biosimilar del rituximab, que se ha caracterizado desde el punto de vista biológico, pero la seguridad y eficacia aún están en estudio. Objetivo: evaluar la seguridad y la respuesta al tratamiento con CIMABior ®, en pacientes con síndromes linfoproliferativos de células B tratados con intención compasiva. Métodos: estudio multicéntrico, exploratorio, con dos grupos de tratamiento (monoterapia o combinado con quimioterapia) no controlado, ni aleatorizado. Se incluyeron adultos con linfomas no hodgkinianos y leucemia linfocítica crónica, no elegibles para el ensayo clínico en ejecución con este producto. Se determinó la frecuencia de eventos adversos y se caracterizaron. La respuesta al tratamiento se definió como: remisión completa, remisión parcial, enfermedad estable o en progresión. Se calculó la tasa de respuesta objetiva (remisión completa más remisión parcial) con el intervalo de confianza al 95 por ciento, se evaluó la relación de algunas variables con la respuesta y se estimó la razón de Odss. Como medida de balance beneficio-riesgo se estimó el factor de Bayes. Resultados: los eventos adversos más frecuentes fueron: temblor (12,8 por ciento) y fiebre (10,3 por ciento). Los relacionados con el producto (43,4 por ciento) fueron leves o moderados y evolucionaron hacia la recuperación. No se informó muerte asociada directamente al tratamiento. Se constató respuesta objetiva global de 71,2 por ciento (59,6 por ciento de remisiones completas y 11,5 por ciento, parciales). La respuesta objetiva en el grupo de monoterapia fue de 66,7 por ciento y de 73,0 por ciento en el grupo de CIMABior® más quimioterapia, con remisiones completas de 46,7 por ciento y 64,9 por ciento, respectivamente. Conclusiones: el AcM CIMABior® es seguro, bien tolerado y se demostraron evidencias de efecto. El tratamiento aportó un beneficio clínico superior al riesgo de desarrollar algún evento adverso grave(AU)

Introduction : The use of monoclonal antibodies transformed the treatment of non-Hodgkin lymphomas. The Center of Molecular Immunology created an anti-CD20 monoclonal antibody (CIMABior®), biosimilar of rituximab, which has been characterized from a biological point of view, but the safety and effectiveness are still being studied. Objective: Evaluate the safety and response to treatment, in patients with B-cell malignancies with compassionate use of CIMABior®. Methods : A multicenter, exploratory, non-controlled, non-randomized study was conducted with two variants of treatments (monotherapy or combined with chemotherapy). Adults with non-Hodgkin lymphomas and chronic lymphocytic leukemia not eligible for clinical trial with this product were included. Frequency of adverse events was calculated and those were characterized. The response to treatment was defined as: complete response, partial response, stable disease or progressive disease. Overall response rate (complete plus partial remission) was calculated with 95 percent confidence interval. The relation of some variables with response was estimated per Odss ratio. As a measure of the benefit-risk balance, the Bayes factor was estimated. Results : The more frequent adverse events were: tremors (12.8 percent) and fever (10.3 percent). Those related to the product (43.4 percent) were minor and evolved to recovery. There were no deaths in reference to the treatment. An overall response of 71.2 percent was confirmed (59.6 percent complete remissions and 11.5 percent partial remission). The monotherapy group objective response was 66.7 percent and 73.0 percent in the CIMABior® plus chemotherapy group, with complete remissions of 46.7 percent and 64.9 percent respectively. Conclusions: The monoclonal antibodies CIMABor® is safe, well tolerated and evidences of its effectiveness was demonstrated. The treatment provided a superior clinical benefit to the risk of developing a severe adverse event(AU)

Obinutuzumabe no tratamento de pacientes com leucemia linfoide crônica, não elegíveis à dose completa de fludarabina: análise de impacto orçamentário baseado no tempo para a próxima terapia / Obinutuzumab for the treatment of unfit patients with chronic lymphocytic leukemia: budget impact analysis based on time to next treatment

Objetivo: Comparar o impacto orçamentário de obinutuzumabe + clorambucila (GClb), rituximabe + clorambucila (RClb), ofatumumabe + clorambucila (OClb) ou clorambucila (Clb) na primeira linha de tratamento (1L) e suas respectivas opções de segunda linha (2L) recomendadas por consenso brasileiro e internacional para adultos com leucemia linfoide crônica (LLC) não tratados previamente e inelegíveis à dose completa de fludarabina (slow-go). Métodos: A análise foi conduzida a partir do desfecho de tempo para próxima terapia (TPPT) na perspectiva do Sistema de Saúde Suplementar (SSS). Apenas custos de aquisição de medicamentos foram considerados, incluindo posologia de bulas registradas. Regimes de tratamento de 2L considerados foram RClb ou ibrutinibe. As curvas de TPPT foram obtidas do estudo CLL11 e COMPLEMENT 1. Resultados: Em horizonte temporal de cinco anos, GClb demonstrou benefício econômico, quando comparado com RClb, OClb e Clb, sendo o potencial de savings por paciente de R$ 80 mil, R$ 149 mil e R$ 284 mil, respectivamente. Adicionalmente, em cinco anos, verificou-se que a adoção de GClb na 1L para pacientes com LLC pode promover economia de R$32 milhões para SSS quando comparado com RClb e Clb, uma vez que seu intervalo livre de tratamento é mais longo do que o das tecnologias comparadas, o que posterga o início do tratamento de 2L. Conclusões: Apesar de o preço unitário de obinutuzumabe e o custo de tratamento inicial de GClb serem superiores aos de RClb, OClb e Clb, o tratamento de 1L com GClb pode promover benefícios econômicos em longo prazo, consequentes dos resultados clínicos favoráveis da associação de GClb no tratamento da LLC.

Objective: To compare the budget impact of obinutuzumab + chlorambucil (GClb), rituximab + chlorambucil (RClb), ofatumumabe + chlorambucil (OClb) or chlorambucil (Clb) in first line treatment (1L) and their respective therapeutic options in second line (2L), recommended by a Brazilian and international consensus for adults with chronic lymphocytic leukemia (CLL), with no previous treatment and classified as ineligible to full dose fludarabine treatment (slow-go). Methods: The analysis was conducted based on the outcome time to next treatment (TPPT) under the perspective of the Brazilian Private Healthcare System (SSS). Only drug acquisition costs were considered, including dosage from registered labels. RClb and ibrutinib were considered as 2L treatment regimens. The TPPT curves were obtained from the CLL11 and COMPLEMENT 1 studies. Results: Considering a five-year time horizon, GClb demonstrated economic benefit when compared to RClb, OClb and Clb, with potential savings per patient of R$ 80 thousand, R$ 149 thousand and R$ 284 thousand, respectively. Additionally, in five years, the adoption of GClb as 1L for patients with CLL can promote an economy of R$ 32 million to the SSS when compared to RClb and Clb, since the GClb treatment free interval is longer than the compared technologies, which delays the beginning of the more costly 2L treatment. Conclusions: Although the unitary obinutuzumab price and the cost of initial GClb treatment are greater than RClb, OClb and Clb, 1L treatment with GClb can promote economic benefits in the long term, resulting from the favorable clinical results of GClb association in CLL treatment.