Prise en charge des hémopathies malignes au centre national d'oncologie médicale et de radiothérapie Alassane Ouattara d'Abidjan / Managem ent of hem atologic neoplasm sat the Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara ofAbidjan

Introduction. Les hémopathies malignes sont des proliférations anormales et anarchiques de cellules hématopoïétiques à point de départ médullaire ou périphérique. Notre étude qui avait pour objectif de faire le bilan de la prise en charge des hémopathies malignes au Centre national d'oncologie médical et de radiothérapie Alassane Ouattara. Méthodes. Il s'agissait d'une étude rétrospective descriptive d'une durée de 2 ans 3 mois allant du 1er janvier 2018 au 31 Mars 2020 portant sur 80 dossiers de malades porteurs d'hémopathies malignes et prise en charge dans le centre. Résultats. Notre étude a permis de recenser 2,2% d'hémopathies malignes sur les 3650 cas de pathologies cancéreuses recensées au CNRAO, soit une incidence 26,66 cas/an avec un sex-ratio 1,2. Les syndromes lymphoprolifératifs (SLP) sont les plus fréquents (96,25 %), sous trois principales formes: lymphomes malins non hodgkiniens (LMNH) non Burkitt (51,25%), leucémie myéloïde chronique (20%) et le myélome multiple (16,25%). Les LMNH représentent 51,25% des HM recensées avec 41,46 % de lymphomes de haut grade de malignité. La chimiothérapie était de mise chez tous nos patients. Ainsi sur 41 cas de LMNH, seulement 12 (29,27%) ont bénéficié du protocole R-CHOP. On notait 46,34% de réponse complète. Dans notre étude, le LH représentait 8,75% il était traité à 71,43% avec le protocole ABVD avec une réponse complète chez 6 patients. 37,5% des patients porteurs de leucémie myéloïde chronique ont reçu le Rituximab; ils ont été traités par les protocoles COP (31,25%), CHOP (31,25%), RCVP (12,5%) et R-CHOP (25%). La réponse thérapeutique était complète à 68,75%. Le protocole utilisé dans le traitement du myélome multiple a été le VMCD-REV à 76,92% avec pour réponse thérapeutique complète chez 6 patients, 3 réponses partielles et 4 en cours de traitement. Conclusion. Les SLP qui sont les plus fréquents des HM avec trois principales formes: LMNH non Burkitt, leucémie myéloïde chronique et myélome multiple. Nous avons cependant des difficultés quant à la mise en route de la chimiothérapie.

Introduction. Hematologic neoplasms are abnormal and anarchic proliferations of hematopoietic cells with a medullary or peripheral starting point. Our study aimed to report the management of hematological malignancies at the Centre National d'Oncologie Médicale et de Radiothérapie Alassane Ouattara (CNRAO). Methods. This was a descriptive retrospective study lasting 2 years 3 months from January 1st, 2018 to March 31st, 2020 concerning 80 patients with hematologic neoplasms who were managed in the CNRAO. Results. Hematologic neoplasms represented 2.2% of cancers (80/3650) at CNRAO, giving an annual incidence of 26.66 cases. The sex ratio was 1.2. Lymphoproliferative syndromes were the most common subgroups (96.25%). These were mainly non-Burkitt non Hodgkin lymphoma (51.25%), high grade lymphomas (41.46%), chronic lymphocytic lymphoma (20%) and multiple myeloma (16.25%). Chemotherapy was administered to all patients. Among 41 cases of non-Hodgkin lymphoma, 12 (29.27%) benefited from the R-CHOP protocol and full response was observed in 46.34% of them. We found 7 patients with Hodgkin lymphoma (8.75%) and the ABVD protocol was used for 6 cases (71.43%). Six out of these seven patients were in complete response. Among the 16 patients with chronic lymphocytic leukemia, 6 (37.5%) received Rituximab. The distribution of the patients with chronic lymphocytic leukemia was as follows: COP 31.25%, CHOP 31.25%, RCVP 12.5% and R-CHOP 25% and 68.75% had full response. The most common treatment protocol for multiple myeloma was VMCD-REV (76.92%). Six patients had complete response, 3 had partial response and 4 were in the course of treatment. Conclusion. In our practice, hematologic neoplasms are mainly lymphoproliferative syndromes and the most common varieties are non-Burkitt non Hodgkin lymphoma, high grade lymphomas, chronic lymphocytic lymphoma and multiple myeloma. We have difficulties in getting chemotherapy started.

Hémopathies malignes de l'adulte à Kinshasa: analyse documentaire d'une série des cas de 2011 à 2021 / Hematological malignancies in adults in Kinshasa: retrospective serial cases from 2011 to 2021

Contexte et objectif. Les hémopathies malignes (HM) constituent un problème majeur de santé publique en Afrique sub-saharienne où les moyens de prise en charge sont limités. L'objectif de l'étude était de décrire les aspects diagnostiques, thérapeutiques et évolutifs observées dans la prise en charge des HM en milieu hospitalier de Kinshasa. Méthodes. Etude observationnelle historique de type suivi des cas d'HM hospitalisés, dans formations sanitaires de Kinshasa entre les 1er janvier 2011 et 31 décembre 2021. Seuls les patients âgés de plus de 18 ans ont été inclus. Les paramètres d'intérêt étaient englobés les données sociodémographiques, cliniques, biologiques, d'imagerie, du myélogramme, de l'analyse histopathologique des pièces biopsiques ganglionnaires ou extra ganglionnaires, le type de chimiothérapie et de la survie à 6 mois. Les tests de chi-carré et de Student ont comparé respectivement les proportions et les moyennes. L'analyse de Kaplan Meier et la régression de Cox ont respectivement décrit la survie et recherché les facteurs associés à la mortalité à 6 mois. Résultats.Sur 2678 patients suspects d'HM, seuls de 250 patients (9,3%, âge moyen 47,6 ± 15,8 ans, 62,4% d'hommes) ont eu un bilan de confirmation. Les adénopathies périphériques (54 %), la fièvre au long cours (48 %) et la poly transfusion (29 %) étaient les principaux motifs de consultation. Les perturbations hématologiques rencontrées étaient l'anémie (72 %), la thrombopénie (50 %), l'hyperleucocytose ( 0 %) et la leucopénie ( 0 %). Les syndromes lymphoproliferatif (68 %) étaient plus fréquents et répartis en lymphomes non hodgkiniens (50 %), Lymphome hodgkinien (27%) et myélome multiple (15 %). Les leucémies aigues venaient en deuxième position (12 %) suivi des syndromes myélodysplasiques (11 %) et des syndromes myéloprolifératifs (8 %). 61 % des patients ont bénéficié de la chimiothérapie. Durant les 6 premiers mois de prise en charge, la létalité globale était de 58,4 %. Conclusion. En milieu hospitalier de Kinshasa, très peu de patients suspects d'HM bénéficient d'une mise au point complète et de la chimiothérapie. Les adultes jeunes, surtout les hommes, sont très affectés et plus de la moitié d'entre eux décèdent endéans 6 mois. L'amélioration de l'accessibilité à la chimiothérapie et du plateau technique permettra une réduction de la létalité.

Cytogenetic abnormalities in patients with hematological malignancies in Lahore city, Pakistan / Anormalidades citogenéticas em pacientes com neoplasias hematológicas na cidade de Lahore, Paquistão

Abstract Hematological and hematopoietic cells malignancies of the genes and hematopoietic cells are associated with the genetic mutation, often at the chromosomal level. The standard cytogenetic study is widely accepted as one of the main diagnostics and prognostic determinants in patients. Therefore, the current descriptive and cross-sectional study sought to determine the cytogenetic analysis of frequent hematological malignancies in Pakistan. A total of 202 peripheral bone marrow or blood samples from patients with benign and malignant hematological malignancy were taken using a conventional G-banding technique. Among enrolled patients, the mean age was 21.5 years ± 23.4, and gender-wise distribution showed a marked predominance of the male 147 (73%) population compared to the female 55 (27%). Patients in the age group (2-10 years) had the highest frequency, 48 (24%), of hematological neoplasms, followed by age (11-20 years) with 40 (20%). Normal karyotypes (46, XX/46, XY) was found in 51% (n=103) patients. Furthermore, the frequency of complex karyotype was 30 (15%), while normal was seen in 171 (85%) patients. Pre-B Acute Lymphoblastic Leukemia (Pre-B ALL) was the most prevalent malignancy of 66 (33%), followed by Chronic Myelogenous Leukemia (CML) of 41 (20%) and Acute Lymphocytic Leukemia of 29 (14%). Translocation was the most prevalent 50 (25%), followed by hypotriploidy 14 (7%) and monosomy 8 (4%) on chromosome aberration analysis. In addition, t(9:22) translocation was found to be 20 (10%) in CML, with the majority in the age group (31-40 years). This study recommends that karyotyping should be tested frequently in hematological conditions because it may provide insight into the relative chromosomal changes associated with particular malignancies.

Resumo As neoplasias hematológicas e de células hematopoiéticas dos genes e as células hematopoiéticas estão associadas à mutação genética, geralmente em nível cromossômico. O estudo citogenético padrão é amplamente aceito como um dos principais determinantes diagnósticos e prognósticos em pacientes. Portanto, o presente estudo descritivo e transversal buscou determinar a análise citogenética de neoplasias hematológicas frequentes no Paquistão. Um total de 202 amostras de medula óssea periférica ou sangue de pacientes com malignidade hematológica benigna e maligna foi coletado usando uma técnica convencional de banda G. Entre os pacientes inscritos, a média de idade foi de 21,5 anos ± 23,4, e a distribuição por gênero mostrou uma marcada predominância da população masculina de 147 (73%) em comparação com a feminina de 55 (27%). Pacientes na faixa etária (2-10 anos) tiveram a maior frequência, 48 (24%), de neoplasias hematológicas, seguida da idade (11-20 anos) com 40 (20%). Cariótipos normais (46, XX / 46, XY) foram encontrados em 51% (n = 103) dos pacientes. Além disso, a frequência de cariótipo complexo foi de 30 (15%), enquanto normal foi observada em 171 (85%) pacientes. Leucemia linfoblástica aguda pré-B (LLA Pré-B) foi a doença maligna mais prevalente de 66 (33%), seguida por leucemia mieloide crônica (LMC) de 41 (20%) e leucemia linfocítica aguda de 29 (14%). A translocação foi o 50 mais prevalente (25%), seguido por hipotriploidia 14 (7%) e monossomia 8 (4%) na análise de aberração cromossômica. Além disso, a translocação t (9:22) encontrada foi de 20 (10%) na LMC, com a maioria na faixa etária (31-40 anos). Este estudo recomenda que o cariótipo deve ser testado com frequência em condições hematológicas porque pode fornecer informações sobre as alterações cromossômicas relativas associadas a doenças malignas específicas.

Aspectos clínicos do câncer durante o período gestacional: desafios diagnósticos e terapêuticos / Clinical aspects of cancer during the gestational period: diagnostic and therapeutic challenges

O câncer é uma das maiores causas de morte em mulheres na idade reprodutiva e ocorre em aproximadamente 0,05% a 0,1% das gestações. Os cânceres ginecológicos, de mama, tireoide e hematológicos são os mais comuns na gravidez. O obstetra é o principal médico para investigar sintomas que podem estar relacionados à malignidade. O diagnóstico pode ser dificultado devido à sobreposição de sintomas da gravidez, como náusea, vômitos, aumento do útero e das mamas, dor abdominal, além da limitação para uso de exames de imagem e alterações comuns em exames laboratoriais. O risco e o benefício do diagnóstico e o tratamento para o bem-estar materno e fetal devem ser avaliados com cuidado pelos profissionais envolvidos. Este artigo tem como objetivo realizar uma revisão sobre quando suspeitar e como investigar os principais cânceres na gestação.(AU)

Cancer is the major cause of death in women on reproductive age and occurs in approximately 0.05% to 0.1% of pregnancies. Gynecological, breast, thyroid and hema- tological cancers are the most common in pregnancy. The obstetrician is the primary physician to investigate symptoms that may be related to malignancy. The diagnosis can be difficult due to the overlap of pregnancy symptoms, such as nausea, vomiting, enlargement of the uterus and breasts, abdominal pain, in addition to the limitation for the use of imaging tests and common changes in laboratory tests. The risk and be- nefit of diagnosis and treatment for maternal and fetal well-being should be carefully assessed by the professionals involved. This article aims to conduct a review on when to suspect and how to investigate the main cancers in pregnancy.(AU)

Aplicación del índice de mortalidad pediátrica 3 y evaluación de falla orgánica secuencial pediátrica en una unidad de cuidados intensivos en México / Implementation of the Pediatric Index of Mortality 3 and the pediatric Sequential Organ Failure Assessment in an intensive care unit in Mexico

Introducción. El objetivo del estudio fue analizar el índice de mortalidad pediátrica 3 (PIM 3) y la evaluación de falla orgánica secuencial pediátrica (pSOFA) para predicción de muerte. Métodos. Estudio observacional prospectivo; se incluyeron pacientes de 1 mes a 17,9 años. La precisión se evaluó con el área bajo la curva (AUC) y se estimó la tasa de mortalidad estandarizada. Resultados. Se estudiaron 244 ingresos; la mediana de edad fue 60 meses. Los diagnósticos principales fueron neoplasias sólidas o hematológicas (26,5 %). La mortalidad por ingresos fue del 18 % (44/244). Para PIM 3 el AUC fue de 0,77 y para pSOFA, de 0,81; ambas escalas mostraron adecuada calibración (p > 0,05). La tasa de mortalidad estandarizada fue de 1,91. Conclusiones. Identificamos que las escalas de evaluación de mortalidad PIM 3 y pSOFA muestran capacidad de discriminación aceptable. En pacientes con neoplasias sólidas o hematológicas, PIM 3 no mostró adecuada calibración.

Introduction. The study objective was to analyze the Pediatric Index of Mortality 3 (PIM 3) and the pediatric Sequential Organ Failure Assessment (pSOFA) for the prediction of mortality. Methods. Observational, prospective study; patients aged 1 month to 17.9 years were included. Assessment of area under the curve (AUC) accuracy and estimation of standardized mortality rate. Results. A total of 244 admissions were studied: median age was 60 months. The main diagnoses were solid or hematologic neoplasms (26.5%). The mortality by admission was 18% (44/244). The AUC was 0.77 for PIM 3 and 0.81 for pSOFA; both scales showed an adequate calibration (p > 0.05). The standardized mortality rate was 1.91. Conclusions. We identified that the PIM 3 and pSOFA have an acceptable discrimination power. The calibration of the PIM 3 was not adequate in patients with solid or hematologic neoplasms.

Técnicas de citogenética para el estudio de las leucemias / Cytogenetic techniques for the study of leukemias

Introducción: La leucemia se define como un proceso clonal de células hematopoyéticas, que se origina cuando las células sanguíneas que se producen en la médula ósea, cambian y se multiplican sin control. Esta se caracteriza por su heterogeneidad genética y se explica a través de mecanismos causados por alteraciones cromosómicas utilizados en la práctica clínica diaria como biomarcadores útiles para el diagnóstico, el pronóstico o la predicción de respuesta al tratamiento. Objetivo: Describir las técnicas de citogenética convencional y molecular para el diagnóstico y seguimiento de las leucemias. Métodos: Se realizó una revisión de la literatura en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google Académico, de artículos publicados en los últimos cinco años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: En el transcurso de los años la citogenética ha proporcionado información crucial para el diagnóstico y el pronóstico de las neoplasias hematológicas. Tanto las técnicas de citogenética convencional y molecular, como la hibridación in situ fluorescente, la hibridación in situ fluorescente multicolor, el cariotipo espectral, la hibridación genómica comparada y los microarreglos, participan en el reconocimiento de alteraciones cromosómicas y de genes, así como de interacciones involucradas en el proceso de oncogénesis. Conclusiones: Las técnicas de citogenética contribuyen al diagnóstico, a la estratificación pronóstica y a la aplicación del tratamiento según el tipo o subtipo de leucemia(AU)

Introduction: Leukemia is defined as a clonal process of hematopoietic cells, which occurs when blood cells that are produced in the bone marrow change and multiply uncontrollably. This is characterized by its genetic heterogeneity and is explained through mechanisms caused by chromosomal alterations that are used in daily clinical practice as useful biomarkers for diagnosis, prognosis or prediction of response to treatment. Objective: To describe the conventional and molecular cytogenetic techniques used for the diagnosis and monitoring of leukemias. Methods: A review of the literature in English and in Spanish was carried out, in the PubMed website and using the search engine Google, for articles published in the last five years. We performed analysis and summary of the reviewed bibliography. Analysis and synthesis of information: Cytogenetics over the years has provided crucial information for the diagnosis and prognosis of hematologic malignancies. Both conventional and molecular cytogenetic techniques such as fluorescent in situ hybridization, multicolor fluorescent in situ hybridization, spectral karyotype, comparative genomic hybridization and microarrays, participate in the recognition of chromosomal and gene alterations, as well as interactions involved in the oncogenesis process. Conclusions: These cytogenetic techniques contribute to the diagnosis, prognostic stratification and application of treatment according to the type or subtype of leukemia(AU)

Enfermedad tromboembólica venosa en hemopatías malignas: un enfoque desde la prevención / Venous thromboembolic disease in hematologic malignancies: a preventive approach

Introducción: La enfermedad tromboembólica venosa es una complicación frecuente en las hemopatías malignas, con incidencia similar a la observada en tumores sólidos de alto riesgo trombótico. Objetivo: Describir la influencia de factores de riesgo y biomarcadores de la enfermedad tromboembólica venosa asociada a hemopatías malignas y su aplicación en el diseño de modelos de evaluación de riesgo para la prevención de esta enfermedad. Métodos: Se realizó una revisión exhaustiva en la literatura especializada de artículos publicados sobre la temática a través de las bases de datos: PubMed, SciELO, ScienceDirect, Medline y el motor de búsqueda Google académico. Análisis y síntesis de la información: En pacientes con hemopatías malignas han sido descritos múltiples factores de riesgo para la ocurrencia de eventos tromboembólicos venosos: moleculares, relacionados con el paciente, la enfermedad y el tratamiento, así como biomarcadores de riesgo. Basados en ellos, varias investigaciones han sido desarrolladas para elaborar y validar modelos predictivos de enfermedad tromboembólica venosa que guíen la estratificación del riesgo y el tratamiento profiláctico de esta enfermedad en hemopatías malignas, aunque aún son insuficientes. Enfermedades como los linfomas y el mieloma múltiple tienen más investigaciones en esta área que el resto de las hemopatías malignas. Conclusión: Se necesita diseñar nuevos modelos de riesgo y validar los existentes en un mayor número de casos; así como desarrollar estudios prospectivos en pacientes con riesgo de eventos tromboembólicos y hemopatías malignas, para realizar una estrategia de prevención primaria personalizada con estratificación de la tromboprofilaxis(AU)

Introduction: Venous thromboembolic disease is a frequent complication in hematologic malignancies with incidence similar to that observed in solid tumors with high thrombotic risk. Objective: To describe the influence of risk factors and biomarkers of venous thromboembolic disease associated with hematologic malignancies and their application in the design of risk assessment models for the prevention of this disease. Methods: An exhaustive review was carried out in the specialized literature of articles published on the subject using the following databases: PubMed, SciELO, ScienceDirect, Medline and the academic Google search engine. Analysis and synthesis of the information: Multiple risk factors for the occurrence of venous thromboembolism have been described in patients with hematologic malignancies: patient-related, disease-related, treatment-related and molecular, as well as biomarkers of risk. Based on these, several investigations have been developed to elaborate and validate predictive venous thromboembolism models to guide risk stratification and prophylactic treatment of venous thromboembolic disease in hematologic malignancies, although they are still insufficient. Lymphomas and multiple myeloma have more research in this area than other hematologic malignancies. Conclusion: There is a need to design new risk models and validate existing ones in a larger number of cases, as well as to develop prospective studies in patients at risk of thromboembolic events and hematologic malignancies, to carry out a personalized primary prevention strategy with thromboprophylaxis stratification(AU)

Proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic: A systematic review and meta-analysis

Introduction The coronavirus disease-2019 (COVID-19) has emerged as a novel infection which has spread rapidly across the globe and currently presents a grave threat to the health of the cancer patient. Objective The aim of this meta-analysis was to evaluate the proportion of hematological cancer patients with the SARS-CoV-2 infection during the COVID-19 pandemic. Method A comprehensive literature review was performed on PubMed, Web of Science, Scopus, EKB SciELO, SID, CNKI and Wanfang databases to retrieve all relevant publications up to January 31, 2021. Observational studies, consecutive case-series and case-control studies were included. The proportion for hematological cancer patients with COVID-19 was estimated using the odds ratios (ORs) and 95% confidence interval (95% CIs). Results Fourteen studies with a total of 3,770 infected cancer patients and 685 hematological cancer cases with COVID-19 were selected. Combined data revealed that the overall proportion of hematological cancer patients with COVID-19 was 16.5% (95% CI 0.130 - 0.208, p ≤ 0.001). The stratified analysis by ethnicity showed that the proportion was 18.8% and 12.4% in Caucasian and Asian hematological cancer patients with COVID-19, respectively. Moreover, subgroup analysis by country of origin showed that its proportion was the highest in the United Kingdom (22.5%), followed by France (17.1%) and China (8.2%). Conclusion This meta-analysis result indicated that the proportion of hematological cancer patients with SARS-CoV-2 infection during the COVID-19 pandemic was 16.5%. Further larger sample sizes and multicenter studies among different ethnic groups are necessary to get a better assessment of the proportion.

Can SARS-CoV-2 induce hematologic malignancies in predisposed individuals? A case series and review of the literature

Abstract Introduction Coronavirus disease 2019 (COVID-19) may present with extrapulmonary manifestations, including hematologic changes. Previous studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) can interact with the renin-angiotensin system, ultimately causing increased production of angiotensin II. By reporting the cases of previously healthy young adults diagnosed with a hematologic malignancy after experiencing COVID-19, we raise the hypothesis that the SARS-Cov-2 infection could act as a trigger for leukemogenesis in predisposed individuals. Methods This was a case series performed through extraction of relevant clinical information from the medical records of three patients admitted to our Hematology unit between August 2020 and September 2020. Main Results Considering the relatively rapid development of cytopenias following recovery from COVID-19, it cannot be ruled out that SARS-Cov-2 played a role in leukemogenesis in those patients. Based on previous in vitro studies, the renin-angiotensin system imbalance induced by SARS-CoV-2 could potentially promote in vivo leukemogenesis through several mechanisms. Conclusion Despite the advances in pathophysiological and clinical characterization of COVID-19, the consequences of the pandemic to the incidence of hematologic diseases are still to be elucidated. In this context, future dissection of the status of the local bone marrow renin-angiotensin system in leukemogenesis is a clinically relevant basic research area.

Gestão do cuidado ao paciente com doença hemato-oncológica sob a perspectiva do SUS: análise de hospitalizações e avaliação econômica do daratumumabe no tratamento do mieloma múltiplo / Health care manegement for patients with hematologic malignances from the perspective of the Brazilian Public Health System: analysis of hospitalizations and economic evaluation of daratumumab in the treatment of multiple myeloma

Com o objetivo de contribuir para a gestão do Sistema único de Saúde (SUS) no que se refere às neoplasias hematológicas (NH), este trabalho apresenta a elaboração de dois estudos: (a) analise de custos por hospitalização por NH, e (b) avaliação de custo-efetividade da adição de daratumumabe ao esquema de tratamento do Mieloma Múltiplo (MM) em pacientes não elegíveis para transplante autológico de células tronco hematopoiéticas (TCTH). Por meio da extração de dados do sistema de internações hospitalares do SUS, desenvolveu-se uma análise retrospectiva descritiva de frequências e custos das internações por NH de acordo com sua distribuição temporal, espacial (por estados e regiões), e por patologia, na década compreendida entre os anos de 2010 e 2019. Foram também calculados custo médio pro procedimento e taxa de acesso. Foi observado que houve uma tendência de crescimento estável das frequências e dos custos ao longo do período analisado. Além disso, contatou-se uma significativa discrepância na frequência dos procedimentos entre as regiões Norte e Sudeste, que registraram o menor e o maior número de procedimentos, respectivamente. Observou-se também eu a frequência das internações por patologia não refletiu a incidência estimada pela literatura no país para cada uma das patologias avaliadas. Para o estudo de custo-efetividade, foi desenvolvido um modelo de simulação de sobrevida particionado para a adição do daratumumabe ao esquema de tratamento composto por bortezomibe, melfalano e prednisona (VMP). O horizonte temporal de 30 anos e a perspectiva de análise do SUS, foram usados. Com base nos dados da literatura foi possível observar que a adição deste medicamento ao VMP no tratamento desses pacientes pode aumentar a sobrevida global e a sobrevida livre de progressão. Considerados os custos relacionados a esta tecnologia e ao manejo do paciente no cenário brasileiro, no entanto, a inclusão do daratumumabe está aparentemente acima do limiar de aceitabilidade adotado pelo SUS. Para que esta estratégia seja custo-efetiva no cenário observado, a tecnologia precisaria sofrer uma redução de quase 50% no custo. O estudo, portanto, não recomenda a adição do daratumumabe ao VMP no tratamento do MM em pacientes não elegíveis para TCTH.

Aiming to contribute to the management of the Brazilian Public Health System (SUS) regarding hematologic malignances (NH), this work presents the development of two studies: (a) cost analysis per hospitalization for NH, and (b) cost-effectiveness evaluation of adding daratumumab to the treatment scheme for Multiple Myeloma (MM) in patients not eligible for autologous hematopoietic stem cell transplantation (TCTH). By extracting data from the SUS hospital admissions system, we developed a retrospective descriptive analysis of frequencies and costs of NH admissions according to their temporal, spatial distribution (by states and regions), and by pathology, in the decade between the years 2010 and 2019. Average cost per procedure and access rate were also estimated. It was observed that there was a stable growth trend in frequencies and costs over the analyzed period. Furthermore, a significant discrepancy in the procedure frequency was found between the North and Southeast regions, which recorded the lowest and highest number of procedures, respectively. It was also observed that the frequency of hospitalizations per pathology did not reflect the incidence estimated by the literature in the country for each of the pathologies evaluated. For the cost-effectiveness study, a partitioned survival simulation model was developed for the inclusion of daratumumab in the treatment scheme consisting of bortezomib, melphalan, and prednisone (VMP). A 30-year time horizon and the perspective of the SUS were used for the analysis. Based on literature data, it was possible to observe that the inclusion of this drug to VMP in the treatment of these patients can increase overall survival and progression-free survival. Considering the costs related to this technology and patient management in the Brazilian scenario, however, the inclusion of daratumumab is seemingly above the threshold of acceptability adopted by SUS. For this strategy to be cost-effective in the observed scenario, the technology would require a cost reduction of almost 50%. The study, therefore, does not recommend the inclusion of daratumumab to VMP in the treatment of MM in patients not eligible for TCTH.

Perfil Demográfico e Clínico de Casos de Neoplasias Hematológicas em Crianças e Adolescentes / Demographic and Clinical Profile of Cases of Hematological Neoplasms in Children and Adolescents / Perfil Demográfico y Clínico de Casos de Neoplasias Hematológicas en Niños y Adolescentes

Introdução: As neoplasias hematológicas são importantes causas de morte na infância e adolescência. Objetivo: Caracterizar o perfil demográfico e clínico de casos notificados de neoplasias hematológicas em crianças e adolescentes em um hospital de referência do município de São Luís, Maranhão, Brasil. Método: Estudo observacional retrospectivo com dados coletados de prontuários médicos de casos de neoplasias hematológicas em pacientes com idade até 19 anos registrados em um hospital público de referência para tratamento oncológico, no período de 2005 a 2015. Foram coletados dados de caracterização geral dos pacientes e dados do seguimento do tratamento. Os testes qui-quadrado e exato de Fisher foram utilizados na análise estatística. O nível de significância adotado foi de 5% (p<0,05). Resultados: Os casos de óbito foram mais elevados nos pacientes diagnosticados com linfoma não Hodgkin. A maioria dos pacientes com leucemia linfoide era do sexo masculino com idade até 5 anos, e a frequência de óbito nos pacientes com leucemia linfoide foi mais baixa nos casos confirmados de leucemia linfoblástica de células precursoras tipo B em comparação a outras categorias. Conclusão: Os achados sugerem que a maioria dos pacientes com até 19 anos diagnosticados com leucemia linfoide era do sexo masculino e com idade até 5 anos

Introduction: Hematological cancersare important causes of death in childhood and adolescence. Objective: To design the demographic and clinical profile of cases of hematological cancer reported for children and adolescents in a referral hospital in the city of São Luís, Maranhão, Brazil. Method: A retrospective observational study with secondary data collected from medical records of bone marrow tumor cases in patients aged up to 19 years registered in a public referral hospital for cancer treatment from 2005 to 2015. Patient's profile was collected in addition to follow-up data. The chi-square and Fisher's exact test were used in the statistical analysis. The significance level was 5% (p<0.05). Results: Cases of death were higher in patients diagnosed with non-Hodgkin's lymphoma. Most patients with lymphoid leukemia were males aged up to 5 years, and the frequency of death in patients with lymphoid leukemia was lower in confirmed cases of type B lymphoblastic precursor cell leukemia when compared to the other categories. Conclusion: The findings suggest that most patients aged up to 19 years diagnosed with lymphoid leukemia were males and aged up to 5 years old

Introducción: Las neoplasias hematológicas son causas importantes de muerte en la niñez y la adolescencia. Objetivo: Caracterizar el perfil demográfico y clínico de los casos notificados de neoplasias hematológicas en niños y adolescentes en un hospital de referencia de la ciudad de São Luís, Maranhão, Brasil. Método: estudio observacional retrospectivo con datos secundarios recolectados de registros médicos de casos de tumores de médula ósea en pacientes de hasta 19 años registrados en un hospital público de referencia para tratamiento de cáncer de 2005 a 2015. Se recolectaron datos de caracterización. Datos generales de pacientes y seguimiento -up datos. En el análisis estadístico se utilizaron las pruebas de chi-cuadrado y exacta de Fisher. El nivel de significancia adoptado fue del 5% (p<0,05). Resultados:Los casos de muerte fueron mayores en pacientes con diagnóstico de linfoma no Hodgkin. La mayoría de los pacientes con leucemia linfoide eran varones de hasta 5 años, y la frecuencia de muerte en pacientes con leucemia linfoide fue menor en los casos confirmados de leucemia de células precursoras linfoblásticas tipo B en comparación con las otras categorías. Conclusión:Los hallazgos sugieren que la mayoría de los pacientes de hasta 19 años diagnosticados con leucemia linfoide eran hombres y tenían hasta 5 años

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success? / 医学前沿

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

Fanconi anemia gene-associated germline predisposition in aplastic anemia and hematologic malignancies / 医学前沿

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.

Impact of Coronavirus Disease 2019 on Prognosis and Treatment Strategies in Patients with Hematological Malignancy--Review / 中国实验血液学杂志

Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since outbreak in December 2019, and become a global public health crisis. Patients with hematological malignancy concurrently infected with COVID-19 are often associated with severe even fatal complications, due to low basic immune function, high intensity of chemotherapy and radiotherapy, and slow immune reconstruction post hematopoietic stem cell transplantation, and their treatment strategies, such as anti-infective therapy, blood transfusion, and the use of granulocyte colony stimulating factor need to be adjusted. The characteristics of patients, chemotherapy, hematopoietic stem cell transplantation, and other clinical factors may affect the prognosis of patients with hematological malignancy concurrently infected with COVID-19. Herein, the latest research progress is reviewed.

The Prognostic Value of Prognostic Nutritional Index in Patients with Lymphoma--Review / 中国实验血液学杂志

The morbidity and mortality of hematological tumors have shown a rising tendency in recent years and become one of the major diseases which affect public health. The nutritional and inflammation status of the body has been proved to play an important role in the occurrence, development and prognosis of the blood system disease. The prognostic nutritional index (PNI) is an important index to reflect the nutritional and inflammation status of the body, and it can be calculated by serum albumin level and peripheral blood lymphocyte count. A large number of studies have reported that PNI can effectively predict the prognosis of several hematological tumors, including lymphoma. In this review, the prognostic value of PNI in patients with lymphoma was summarized briefly.

Research Progress of Intercellular Mitochondrial Transfer in the Development of Hematological Malignant Tumors --Review / 中国实验血液学杂志

In recent years, studies have found that mitochondrial transfer between leukemic cells and different types of cells in their bone marrow microenvironment, especially mesenchymal stem cells, plays a key role in the occurrence, development and drug resistance of hematological malignant tumors. This paper mainly introduces the role and latest research progress of mitochondrial transfer in acute and chronic myeloid leukemia, acute lymphoblastic leukemia and multiple myeloma, and briefly describes the mechanism of drug resistance caused by mitochondrial transfer in leukemic cells during chemotherapy. The aim is to provide a new idea and theoretical basis for using intercellular mitochondrial transfer as a potential therapeutic target.

Chinese Medicine Regulates DNA Methylation to Treat Haematological Malignancies: A New Paradigm of "State-Target Medicine" / 中国结合医学杂志

Aberrant regulation of DNA methylation plays a crucial causative role in haematological malignancies (HMs). Targeted therapy, aiming for DNA methylation, is an effective mainstay of modern medicine; however, many issues remain to be addressed. The progress of epigenetic studies and the proposed theory of "state-target medicine" have provided conditions to form a new treatment paradigm that combines the "body state adjustment" of CM with targeted therapy. We discussed the correlation between Chinese medicine (CM) syndromes/states and DNA methylation in this paper. Additionally, the latest research findings on the intervention and regulation of DNA methylation in HMs, including the core targets, therapy status, CM compounds and active components of the Chinese materia medica were concisely summarized to establish a theoretical foundation of "state-target synchronous conditioning" pattern of integrative medicine for HMs, simultaneously leading a new perspective in clinical diagnosis and therapy.

Analysis of Agranulocytosis Time and Its Influencing Factors in Patients with Hematological Malignancies Treated with rhIL-11 combined rhG-CSF / 中国实验血液学杂志

OBJECTIVE@#To explore the intervention effect of recombinant human interleukin-11 (rhIL-11) and recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the duration and severity of agranulocytosis in patients with hematological malignancies after chemotherapy, and to analyze the influencing factors.@*METHODS@#The data of hematological malignancy patients treated with rhIL-11 and rhG-CSF after chemotherapy in the hematology department of The First Hospital of Lanzhou University from July 2017 to July 2020 were collected retrospectively. The duration and differences of agranulocytosis in differeent groups were compared by univariate analysis, and the influencing factors of agranulocytosis duration were further analyzed by multiple regression analysis.@*RESULTS@#The duration of agranulocytosis in 97 patients was 6.47±2.93 days. The results of univariate analysis showed that there were no statistical differences in the duration of agranulocytosis among patients with different sex, age, height, weight, body surface area, body mass index (BMI), dose of rhG-CSF, dose of rhIL-11, spontaneous bleeding after administration of rhG-CSF and rhIL-11, and the duration of agranulocytosis in patients with different red blood cell count (RBC), hemoglobin(HGB) level, platelet count (PLT) and absolute neutrophil count (ANC), before administration of rhG-CSF and rhIL-11. There were significant differences in agranulocytosis time among patients with different disease types, chemotherapy cycle, fever after rhG-CSF and rhIL-11 administration, and different white blood cell count (WBC) baseline level before rhG-CSF and rhIL-11 administration (P＜0.05). Compared with patients with acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), patients with acute myeloid leukemia (AML) had the longest duration of agranulocytosis, which was 7.07±3.05 d. Compared with patients with chemotherapy cycles of 4－6 and ≥7, patients with total chemotherapy cycle of 1－3 had the shortest duration of agranulocytosis, which was 5.25±2.48 d. Compared with patients without fever, patients with fever within 1 day after administration of cytokines and patients with fever within 2-5 days after administration of cytokines, the duration of agranulocytosis was the longest in patients with fever 6 days after administration of cytokines, which was 8.85±2.85 d. Compared with patients with WBC baseline <1.0×109/L, (1.0－1.9)×109/L and (2.0－3.9)×109/L, patients with WBC baseline ≥4.0×109/L had the shortest duration of agranulocytosis, which was 4.50±2.56 d. Multiple linear regression analysis showed that chemotherapy cycle, different fever after administration of rhG-CSF and rhIL-11, diagnosis of ALL and NHL, and WBC baseline level before administration of rhG-CSF and rhIL-11 were the influencing factors of the duration of agranulocytosis (P＜0.001).@*CONCLUSION@#The risk of prolonged agranulocytosis is higher in patients diagnosed with AML, with more chemotherapy cycles, lower WBC baseline before cytokines administration and fever later after cytokines administration, which should be paid more attention to.

Clinical Characteristics and Prognosis of Patients with Hematological Malignancies Superimposed with Solid Tumors / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical characteristics and prognosis of hematological malignancies superimposed patients with solid tumors.@*METHODS@#The clinical data of 30 patients with more than two kinds of malignancy (the second is hematological malignancy) from October 2011 to October 2020 in Department of Hematology, Jiangning Hospital Affiliated to Nanjing Medical University were collected and analyzed retrospectively. The overall survival time was used as the prognostic evaluation standard, and the survival of patients were analyzed by KaplanMeier method. Logrank test and Cox regression model were used to carry out univariate and multivariate retrospective analysis on clinical and laboratory parameters of 30 patients.@*RESULTS@#Among 30 cases, 20 were male, 10 were female, the median age of onset of the second tumor was 70 years old. The common types of the secondary hematological malignancies to solid tumors are myelodysplastic syndrome, acute myeloid leukemia, multiple myeloma. Univariate analysis showed that patients' gender, age, type of solid tumors, the onset of interval between two kinds of tumor, chromosome karyotype were not related to do with the patients' overall survival time. Type of hematologic disease, ECOG score were associated with patients' overall survival time, and the multivariate analysis showed that the type of hematologic disease and ECOG score were independent risk factors for patients with poor prognosis.@*CONCLUSION@#Patients superimposed with solid tumors complicated with myelodysplastic syndrome or acute leukemia and ECOG score ≥3 have poor prognosis and shorter overall survival time, which are independent risk factors influencing the prognosis. Bone marrow injury, immune dysfunction and genetic susceptibility after chemoradiotherapy may be the main causes of these diseases.