Infective dermatitis associated with human T-cell lymphotropic virus type-1, an underdiagnosed disease.

Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.

High Ratio of Human T Cell Lymphotropic Virus Transmission and Prevalence of Human T Cell Lymphotropic Virus Type 1-Associated Diseases in Brazilian Family Groups Followed Up by the GIPH Cohort.

A silent spread of human T cell lymphotropic virus type 1 (HTLV-1) has been occurring for thousands of years, with a high prevalence in some regions due to the sexual and vertical transmission and formation of family clusters. The time from HTLV-1 infection until the onset of virus-associated diseases is extremely long, approximately one to three decades. In this study, we evaluated intrafamilial HTLV-1 transmission and associated diseases in 1,204 individuals enrolled and followed up by the GIPH cohort between 1997 and 2017. The family groups (n = 43) were composed of 279 individuals who were tested for HTLV-1/human T cell lymphotropic virus type 2 (HTLV-2) and were classified as two groups according to the index case: blood donor (blood donors referred to the GIPH cohort) and nondonor (individuals referred to the GIPH cohort by other health services). The observed rates of HTLV-1 transmission and associated diseases among the relatives were high. Of 236 family members and sexual partners tested for HTLV, 104 (44.1%) were confirmed as having HTLV infection, with 36.7% of relatives whose index case was blood donors and 56.9% of relatives with nondonor index cases. At least one case of HTLV-1-associated myelopathy was observed in 42.9% of the families with intrafamilial transmission of HTLV-1. Brazil is an endemic area for HTLV-1/2 and has implemented mandatory universal screening of blood donors for HTLV-1/2 since 1993. However, the lack of public health services offer diagnosis for HTLV to the general population and pregnant women in the country makes it difficult to identify infected people, and contributes to the silent spread of the virus.

Leucemia aguda bilineal Monocítica/B BCR ABL positivo. Presentación de un caso / Bilinear Acute Monocytic Leukemia/B BCR ABL positive. presentation of a case

RESUMEN Introducción: Las leucemias de fenotipo ambigüo, se clasifican en leucemias indiferenciadas y de fenotipo mixto, éstas a su vez pueden dividirse en bilineales o bifenotípicas y suelen asociarse a mal pronóstico, sobre todo si se acompañan de translocaciones agresivas como la del cromosoma Filadelfia. Reporte de caso Presentamos el caso de una paciente adulta mayor que presentó una leucemia aguda bilineal con la presencia de una población de precursores de linaje monoblástico y otra linfoide B, evaluados por estudios de citometría de flujo, quien además presentó el transcrito BCR-ABL, detectado por estudios de PCR en tiempo real. La paciente cursó con mala evolución y falleció a los 11 días de su diagnóstico. Conclusión: Las leucemias de fenotipo mixto son de mal pronóstico y requieren un diagnóstico precoz por citometría de flujo y Biología molecular para brindar un tratamiento oportuno.

ABSTRACT Background: Leukemias with an ambiguous phenotype are classified as undifferentiated leukemias and mixed phenotypes, these in turn can be divided into bilinear or biphenotypic and are usually associated with a poor prognosis, especially if they are accompanied by aggressive translocations such as the Philadelphia chromosome. Case report: We present the case of an elderly adult patient who presented acute bilinear leukemia with the presence of a population of monoblastic lineage precursors and another, B lymphoid, evaluated by flow cytometry studies, who also presented the BCR-ABL transcript. , detected by real-time PCR studies. The patient had a poor evolution and died 11 days after her diagnosis. Conclusion: Mixed phenotype leukemias have a poor prognosis and require early diagnosis by flow cytometry and molecular biology to provide timely treatment.

Distribución geográfica y tipo de infección del virus linfotrópico T humano en pacientes peruanos 2019-2021 / Geographic distribution and type of human T-lymphotropic virus (HTLV) infection in Peruvian patients 2019-2021

En el presente estudio describimos y caracterizamos la distribución geográfica de los casos positivos confirmados a HTLV-1 y 2 de pacientes peruanos con diagnóstico presuntivo entre 2019 y 2021. De un total de 555 muestras positivas confirmadas, 546 (98,4%) fueron HTLV-1 y 9 (1,6%) HTLV-2. Además, 22 de 24 departamentos del Perú presentaron casos de HTLV-1, siendo los principales motivos de solicitud de confirmación diagnóstica: aspirante a donar sangre con prueba de tamizaje reactivo, sospecha de leucemia/linfoma y paraparesia espástica tropical. Los resultados reflejan que la identificación de los puntos críticos constituye una brecha persistente respecto al diagnóstico, siendo cruciales para reducir el número de nuevos casos en Perú.

In the present study we describe and characterize the geographic distribution of HTLV-1 and 2 positive cases from Peruvian patients with presumptive diagnosis 2019 - 2021. Of a total of 555 confirmed positive samples, 546 (98.4%) were HTLV-1 and 9 (1.6%) HTLV-2. In addition, 22 of 24 departments of Peru presented cases of HTLV-1. The main reasons for requesting a confirmatory diagnosis being: aspiring to donate blood with a reactive screening test, suspicion of leukemia/ lymphoma and tropical spastic paraparesis. The results reflect that the identification of critical points constitutes a persistent gap regarding the diagnosis, being crucial to reduce the number of new cases in Peru.

Avaliação da eficácia e segurança de pegaspargase, em comparação à L-asparaginase, e sua viabilidade econômica no tratamento de leucemia linfoblástica aguda / Evaluation of the efficacy and safety of pegaspargase, compared to L-asparaginase, and its economic viability in the treatment of acute lymphoblastic leucemia

Introdução: O tratamento da leucemia linfoblástica aguda (LLA) é relacionado a eventos adversos (EA) e mortalidade por toxicidade dos medicamentos utilizados. Protocolos com L-asparaginase (L-Asp) têm demonstrado melhor prognóstico, porém podem causar hipersensibilidade e desenvolvimento de anticorpos neutralizantes por ser produzida a partir da Escherichia coli. A conjugação de E. coli L-Asp com monometoxipolietilenoglicol resulta na PEG-Asp, com menor imunogenicidade e maior meia-vida. Objetivo: Avaliar eficácia e segurança da PEG-Asp, em comparação à L-Asp, no tratamento de LLA, e sua viabilidade econômica para subsidiar a tomada de decisão quanto à sua incorporação. Material e Métodos: Estudo descritivo de síntese de evidências e avaliação econômica. Busca de evidências foi realizada no MEDLINE, Cochrane Library, Embase, Epistemonikos, e agências de avaliação de tecnologias em saúde. Foram considerados elegíveis revisões sistemáticas, ensaios clínicos e estudos observacionais, publicados em inglês, espanhol e português, independente da data. Viabilidade econômica foi calculada a partir do custo do uso da PEG-Asp no protocolo GRAALL ­ 2003 frente ao valor faturado via Autorização de Procedimentos de Alta Complexidade. Resultados: As evidências demonstraram eficácia semelhante entre PEG-Asp e L-Asp para maioria dos desfechos de interesse, com superioridade na prevenção de leucemia no sistema nervoso central em adultos e comodidade posológica. PEG-Asp demonstrou maior frequência de EA em adultos recém diagnosticados, e ausência de diferença na toxicidade e mortalidade nos recidivados. A incorporação da PEG-Asp se mostrou economicamente viável para pacientes adultos, e desvantajosa naqueles com 18 e 19 anos incompletos, considerando superfície corpórea média de 1,7m². Conclusão: Recomendou-se a incorporação de PEG-Asp para tratamento de LLA em pacientes acima de 18 anos e naqueles com 18 a 19 anos incompletos, deve-se avaliar a viabilidade econômica em função da superfície corpórea. Além do perfil de eficácia e segurança da PEG-Asp, não há medicamentos dessa classe terapêutica com registro para adultos na Agência Nacional de Vigilância Sanitária.

Introduction: Treatment of acute lymphoblastic leukemia (ALL) is associated with adverse events (AEs) and mortality due to toxicity of drugs used. Protocols with L-asparaginase (L-Asp) have shown improved prognosis, but can cause hypersensitivity and development of neutralizing antibodies, as L-Asp is produced from Escherichia coli. The conjugation of E. coli L-Asp with monomethoxypolyethylene glycol results in PEG-Asp, with lower immunogenicity and longer half-life. Objective: To evaluate the efficacy and safety of PEG-Asp, compared to L-Asp, in ALL treatment, and its economic viability in order to subsidize decision making regarding its incorporation. Material and Methods: Descriptive study of evidence synthesis and economic evaluation. Evidence was searched in MEDLINE, Cochrane Library, Embase, Epistemonikos, and Health technology assessment agencies. Systematic reviews, clinical trials and observational studies published in English, Spanish and Portuguese, regardless of date, were considered eligible. Economic viability was calculated based on the cost of using PEG-Asp in GRAALL - 2003 protocol compared to the amount billed via High-complexity Procedures Authorization. Results: Evidence showed similar efficacy between PEG-Asp and L-Asp for most of the outcomes of interest, with superiority in prevention of Central Nervous System leukemia in adults and in dosage convenience. PEG-Asp showed a higher frequency of AEs in newly diagnosed adults, and no difference in toxicity and mortality in relapsed adults. The incorporation of PEG-Asp proved to be economically viable for adult patients, and disadvantageous for patients between 18 and 19 years of age, considering a mean body surface area of 1.7m². Conclusion: Incorporation of PEG-Asp for the treatment of ALL in patients over 18 years was recommended, and in those aged 18 to 19 years incomplete, the economic viability should be assessed according to body surface area. In addition to the efficacy and safety profile of PEG-Asp, there are no drugs in this therapeutic class for adults registered within ANVISA.

Myeloid/lymphoid neoplasm with eosinophilia and BCR/FGFR1 rearrangement with transformation to cortical T-lymphoblastic lymphoma and erythroid precursors: a case report.

BACKGROUND: Myeloproliferative neoplasms are a group of diseases with diverse biological and clinical characteristics. As a provisional separate entity, myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangement have been described, which may present an initial clinical behavior of myeloproliferation and be characterized by varied genetic rearrangements. One of these entities is associated with FGFR1 rearrangements, characterized by its low prevalence and few treatment options. CASE PRESENTATION: We present the case of a 53-year-old Mestizo male patient of Hispanic origin who initially presented weight loss and fatigue, with a complete blood count showing leukocytosis and eosinophilia, with an initial diagnosis of nonspecific myeloproliferative disorder. In a next-generation sequencing study, BCR::FGFR1 rearrangement was documented, a diagnosis of myeloid/lymphoid neoplasia with eosinophilia and BCR::FGFR1 rearrangement was made, and hydroxyurea therapy was initiated. Subsequently, transformation to cortical T-lymphoblastic leukemia/lymphoma and erythroid precursors was documented, requiring management with chemotherapy. CONCLUSIONS: Myeloid/lymphoid neoplasms with eosinophilia and genetic rearrangements constitute a group of deeply heterogeneous diseases with variable clinical and diagnostic characteristics and whose treatment is not clearly defined.

COVID-19 infection during blinatumomab therapy: Is safety a dilemma?

Patients with acute lymphoblastic leukemia may be particularly vulnerable to SARS-CoV-2 infection and severe illness. The mainstay of current treatment is the use of blinatumomab in patients with refractory or relapsed B-cell precursor acute lymphoblastic leukemia. We discuss the case of a patient with relapsed acute lymphoblastic leukemia who became positive for SARS-CoV-2 during blinatumomab therapy. There are no formal recommendations on the decision to continue, withhold, or delay blinatumomab treatment in these patients. More studies exploring this issue are warranted, as SARS-CoV-2 is expected to be here to stay.

Htlv-1 na leucemia/linfoma de células-t e abordagem social sobre a infecção / Htlv-1 in t-cell leukemia/lymphoma and social approach to the infection / Htlv-1 en la leucemia/linfoma de células t y el enfoque social de la infección

A Leucemia/Linfoma de Células-T do Adulto (LLCT) é um tipo agressivo de doença linfoproliferativa causada pelo Vírus Linfotrópico de Células-T Humano (HTLV-1), classificada em cinco tipos: indolente, tumoral primária de pele, crônico, linfomatoso e agudo. O HTLV pertence à família Retroviridae, gênero Deltaretrovirus, subfamília Oncovirinae, de três genes estruturais (Gag, Pol e Env) e sua transmissão ocorre por contato sexual, transfusão de sangue ou inoculação por materiais perfuro- cortantes contaminados e aleitamento materno. Esta revisão narrativa tem como objetivo apresentar uma síntese sobre a relação do HTLV-1 na LLCT, seu processo patogênico e uma abordagem social. O vírus infecta, principalmente, células T CD4+, desregulando o sistema imunológico do hospedeiro, podendo ocasionar neoplasia de células-T a partir de uma única célula que teve expansão clonal, constituindo uma população monoclonal em que todas as células contêm o DNA proviral do HTLV-1. O prognóstico é ruim, a maioria dos pacientes que desenvolvem LLCT apresenta doença de progressão rápida e o óbito em curto período, mesmo com quimioterapia agressiva. Não há política nacional específica para o HTLV, não faz parte da lista de doenças de notificação compulsória e pouco se debate publicamente, gerando desconhecimento por parte da população e por parte de profissionais de saúde, sendo uma infecção negligenciada. Conclui-se que a infecção pelo HTLV é um tema que precisa ser popularizado, havendo urgência na implantação de políticas públicas específicas e de pesquisas contínuas, devido à grande incidência no Brasil e associação a doenças graves como a LLCT.

Adult T-Cell Leukemia/Lymphoma (TCLL) is an aggressive type of lymphoproliferative disease caused by the Human T-Cell Lymphotropic Virus (HTLV- 1), classified into five types: indolent, primary skin tumor, chronic, lymphomatous and sharp. HTLV belongs to the Retroviridae family, Deltaretrovirus genus, Oncovirinae subfamily, with three structural genes (Gag, Pol and Env) and its transmission occurs through sexual contact, blood transfusion or inoculation with contaminated sharps and material and breastfeeding. This narrative review aims to present a synthesis about the relationship of HTLV-1 in CLL, its pathogenic process and a social approach. The virus mainly infects CD4+ T cells, disrupting the host's immune system, and may cause T-cell neoplasia from a single cell that underwent clonal expansion, constituting a monoclonal population in which all cells contain the HTLV proviral DNA -1. Prognosis is poor, most patients who develop TCLL have rapidly progressive disease and death within a short period, even with aggressive chemotherapy. There is no specific national policy for HTLV, it is not part of the list of notifiable diseases and little is discussed publicly, generating ignorance on the part of the population and on the part of health professionals, being a neglected infection. It is concluded that HTLV infection is a topic that needs to be popularized, with urgency in the implementation of specific public policies and continuous research, due to the high incidence in Brazil and association with serious diseases such as TCLL.

La leucemia/linfoma de células T del adulto (LLCT) es un tipo agresivo de enfermedad linfoproliferativa causada por el virus linfotrópico de células T humanas (HTLV-1), clasificada en cinco tipos: indolente, tumor primario de piel, crónica, linfomatosa y aguda. El HTLV pertenece a la familia Retroviridae, género Deltaretrovirus, subfamilia Oncovirinae, con tres genes estructurales (Gag, Pol y Env) y su transmisión se da por contacto sexual, transfusión de sangre o inoculación con material cortopunzante contaminado y lactancia materna. Esta revisión narrativa tiene como objetivo presentar una síntesis sobre la relación del HTLV-1 en la LLC, su proceso patogénico y un abordaje social. El virus infecta principalmente a los linfocitos T CD4+, alterando el sistema inmunitario del huésped y puede causar neoplasia de linfocitos T a partir de una sola célula que experimentó expansión clonal, constituyendo una población monoclonal en la que todas las células contienen el ADN proviral -1 del HTLV. El pronóstico es malo, la mayoría de los pacientes que desarrollan LLCT tienen una enfermedad rápidamente progresiva y mueren en un período corto, incluso con quimioterapia agresiva. No existe una política nacional específica para el HTLV, no forma parte de la lista de enfermedades de notificación obligatoria y poco se discute públicamente, generando desconocimiento por parte de la población y por parte de los profesionales de la salud, siendo una infección desatendida. Se concluye que la infección por HTLV es un tema que necesita ser popularizado, con urgencia en la implementación de políticas públicas específicas y de investigación continua, debido a la alta incidencia en Brasil y la asociación con enfermedades graves como la LLCT.

Cytopathological diagnosis of herpes simplex virus infection causing oral aphthous ulcers in a patient with acute lymphocytic leukemia: case report / Diagnóstico citopatológico de infecção pelo vírus herpes simples causando úlceras aftosas orais em paciente com leucemia linfocítica aguda: relato de caso

Aim:This paper aims to report an atypical oral HSV infection diagnosed by cytopathological examination in a patient with acute lymphocytic leukemia. Case report: A nine-year-old white female was admitted with acute lymphocytic leukemia, presenting ulcers covered with pseudomembrane and spontaneous bleeding on the left soft palate, measuring approximately 2 cm, as well as other ulcers measuring 1 cm on the left lateral border of the tongue. Exfoliative cytopathology revealed neutrophils and cytopathic effects of HSV in the keratinocytes in a fibrin background. Based on the exfoliative examination, the diagnosis of HSV infection was obtained. Conclusion: Oral HSV infection can be atypical in immunocompromised patients and can cause high morbidity and mortality. Healthcare professionals, especially those working in a hospital environment, should be aware of the possibility of HSV infection in atypical lesions in these patients and evaluate the need to include antiviral prophylactic therapy.

Objetivo:Este trabalho tem como objetivo relatar uma infecção oral atípica por HSV diagnosticada por exame citopatológico em um paciente com leucemia linfocítica aguda. Relato de caso:Paciente do sexo feminino, nove anos, branca, portadora de leucemia linfocítica aguda, apresentando úlceras recobertas por pseudomembrana e sangramento espontâneo em palato mole esquerdo medindo aproximadamente 2 cm, além de outras úlceras medindo 1 cm na borda lateral esquerda da língua. A citopatologia esfoliativa revelou neutrófilos e efeitos citopáticos do HSV nos ceratinócitos em um fundo de fibrina. Com base no exame esfoliativo, foi obtido o diagnóstico de infecção por HSV. Conclusão: A infecção oral por HSV pode ser atípica em pacientes imunocomprometidos e pode causar alta morbidade e mortalidade. Os profissionais de saúde, principalmente os que atuam em ambiente hospitalar, devem estar atentos à possibilidade de infecção pelo HSV em lesões atípicas nesses pacientes e avaliar a necessidade de inclusão de terapia antiviral profilática.

Basic zipper protein (HBZ): biomarcador diagnóstico y de seguimiento de leucemia/linfoma T del adulto / Basic zipper protein ( HBZ ) : diagnostic and follow - up biomarker of adult T - cell leukemia/lymphoma

Introducción: El virus linfotrópico de células T humanas tipo 1 es el retrovirus causal de la leucemia-linfoma de células T. Su escaso diagnóstico en fases agudas hace que encontrar un biomarcador acertado para conocer el desarrollo de la leucemia sea de interés clínico y científico. Objetivo: Presentar la proteína basic zipper protein como marcador diagnóstico y de seguimiento al tratamiento de la leucemia-linfoma de células T. Métodos: Se consultó material académico en diferentes bases de datos científicas tales como PubMed, Springerlink, Proquest y Sciencedirect. Se tuvieron en cuenta criterios como datos, efectividad en la identificación y amplificación de basic zipper protein, reconocimiento de las fases del virus linfotrópico de células T, epidemiología y mecanismos moleculares en la patogenia del virus. Análisis y síntesis de la información: La basic zipper protein es una proteína del virus linfotrópico de células T indispensable para el proceso de leucemogénesis, capaz de interactuar con factores endógenos del huésped, lo que la convierte en marcador de la enfermedad. Conclusiones: La basic zipper protein cuenta con características que la perfilan para ser el biomarcador con mayor predicción de la enfermedad por su estabilidad e importancia en la leucemogénesis. Además, el nivel de ARNm de la basic zipper protein es mayor en leucemia-linfoma de células T.

Introduction: Human T-cell lymphotropic virus type 1 is the retrovirus that causes T-cell leukemia-lymphoma. Its scarce diagnosis in acute phases means that finding an accurate biomarker to determine the development of leukemia is of clinical and scientific interest. Objective: To present the basic zipper protein as a diagnostic and follow-up marker for treatment of T-cell leukemia-lymphoma. Methods: Academic material was consulted in different scientific databases such as PubMed, Springerlink, Proquest and Sciencedirect. Criteria such as: data, effectiveness in the identification and amplification of basic zipper protein, recognition of the phases of the T-cell lymphotropic virus, epidemiology and molecular mechanisms in the pathogenesis of the virus were taken into account. Analysis and synthesis of the information: The basic zipper protein is a protein of the T-cell lymphotropic virus essential for the leukemogenesis process, capable of interacting with endogenous factors of the host, which makes it a marker of the disease. Conclusions: The Basic zipper protein has characteristics that outline it to be the biomarker with the highest prediction of the disease due to its stability and importance in leukemogenesis. In addition, the mRNA level of the basic zipper protein is higher in T-cell leukemia-lymphoma.

Immunophenotypic characterization of acute leukemias in Bahia, Brazil

ABSTRACT Objective To characterize the immunophenotypic profile of acute leukemias in the population of the state of Bahia, Brazil. Methods This is a descriptive, retrospective study. From 2014 to 2018, 796 new cases of acute leukemia were evaluated. The data were obtained from analysis of reports and records of tests performed by flow cytometry immunophenotyping. All individuals of all age groups diagnosed as acute lymphoblastic leukemia or acute myeloid leukemia were included in the study. Demographic variables and expression of leukemia antigens were evaluated. Results Most cases were diagnosed as acute myeloid leukemia and 42.7% as acute lymphoblastic leukemia. Significant differences were found in expression of markers in acute leukemias when age groups were compared, as well as in demographic characteristics. B-cell acute lymphoblastic leukemia was more prevalent than cases of T-cell origin. Assessing the aberrant markers in acute myeloid leukemias, the non-acute promyelocytic leukemia group presented expression of CD7 and CD56 as the most frequent ones. In B-cell acute lymphoblastic leukemia, the most frequent aberrant markers were CD66c, CD13 and CD33. Conclusion Significant differences were found as to several antigens when comparing adults and children, and these findings may contribute to future studies correlating the phenotypic profile to genetic characteristics and therapeutic response, including specific antigen therapies, which may be better targeted.

Predictive Factors and Outcomes after Allogeneic Stem Cell Transplantation for Adults with Acute Lymphoblastic Leukemia in Brazil.

Allogeneic stem cell transplantation (HSCT) remains a potentially curative approach for acute lymphoblastic leukemia (ALL), especially for high-risk patients and those with relapsed/refractory disease, although its efficacy is offset by a not-negligible toxicity. Adult patients with ALL fare worse in developing countries, with little data about the HSCT in this setting. In this study, we aimed to describe outcomes and examine risk factors for overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD) after HSCT for ALL in Brazilian centers. This retrospective registry study included patients with ALL or ambiguous lineage leukemia age >16 years who underwent a first HSCT at 5 Brazilian centers between January 2007 and December 2017. A total of 275 patients were included, with a median age of 31 years (range, 16 to 65 years). Thirty-five percent were Philadelphia chromosome-positive. A matched sibling donor was used in 53%, a matched unrelated donor (MUD) in 19%, a mismatched unrelated donor in 9%, a haploidentical donor in 19%, and umbilical cord blood in 5%. The engraftment failure rate was 1.5%. The 5-year cumulative incidence of acute grade II-IV was 54.2%, and that of chronic GVHD was 26.2%. Five-year CIR and NRM were 28.1% and 34.1%, respectively. Central nervous system involvement at diagnosis (hazard ratio [HR], 2.2) and disease status (HR, 1.8 for second or later complete response and 7.9 for refractory) were associated with increased relapse incidence, whereas the use of peripheral blood graft (HR, .51) and a haploidentical donor (HR, .4) significantly decreased relapse incidence. Five-year OS and LFS were 40.7% (95% confidence interval [CI], 35.1-47.1) and 37.8% (95% CI, 32.3-44.1), respectively. Patient age, donor age, and disease status were independently associated with OS and LFS. Pre-HSCT positivity of minimal residual disease (>.01%) was associated with worse LFS (HR, 1.47) in available cases. This is the largest series of adults with ALL undergoing HSCT from Brazil reported to date. Although OS and LFS were similar to data reported in the literature, NRM was higher. Patient age and donor age outweighed donor type or graft source in our analysis. Interestingly, haploidentical HSCT was associated with lower CIR, whereas the use of MUDs was associated with higher NRM and GVHD rates. These results impact donor selection strategy in Brazil with the aim of offering timely HSCT for high-risk ALL patients in our setting.

Rhodotorula fungemia in a patient with acute lymphoblastic leukemia / Fungemia de Rhodotorula em paciente com leucemia linfoblástica aguda / Fungemia por Rhodotorula en un paciente con leucemia linfoblástica aguda

Objectives: Rhodotorula is an environmental yeast that belongs to Basidiomycota Phylum. Rhodotorula species are ubiquitous in nature, can be found in soil and freshwater. Immunocompromised patients can develop Rhodotorulosis due to wide-ranging exposure to Rhodotorula in the hospital environment. Case Discussion: The patient was a 3-year-old male with a diagnosis of Pro B-Acute Lymphoblastic Leukemia (ALL). He was admitted to the hospital with complaints of malaise, fatigue, weight loss, and diarrhea between courses of chemotherapy. Rhodotorula was isolated from the patient's blood culture obtained during the elevation of temperature. After 14 days of amphotericin B treatment, clinical situation of the patient was improved and he was discharged. Conclusion: Rhodotorula spp. as a rare yet emerging pathogen, often presents as fever of unknown etiology resistant to antibacterial treatment and can be associated with fungemia and other severe complications.(AU)

Objetivos: Rhodotorula é uma levedura ambiental que pertence ao filo Basidiomycota. As espécies de Rhodotorula são onipresentes na natureza, podem ser encontradas no solo e na água doce. Pacientes imunocomprometidos podem desenvolver rodotorulose devido à ampla exposição a Rhodotorula no ambiente hospitalar. Descrição do caso: O paciente era uma criança de 3 anos de idade com diagnóstico de Leucemia Linfoblástica Aguda Pro B (LLA). O paciente deu entrada no hospital com queixas de mal-estar, cansaço, perda de peso e diarreia entre os ciclos de quimioterapia. A Rhodotorula foi isolada da hemocultura do paciente obtida durante a elevação da temperatura. Após 14 dias de tratamento com anfotericina B, a situação clínica do paciente melhorou e o paciente recebeu alta. Conclusão: Rhodotorula spp. como um patógeno raro, porém emergente, frequentemente se apresenta como febre de etiologia desconhecida resistente ao tratamento antibacteriano e pode estar associada a fungemia e outras complicações graves.(AU)

Objetivos: Rhodotorula es una levadura ambiental que pertenece al filo Basidiomycota. Las especies de Rhodotorula son ubicuas en la naturaleza, se pueden encontrar en el suelo y en agua dulce. Los pacientes inmunodeprimidos pueden desarrollar Rhodotorulosis debido a una amplia exposición a Rhodotorula en el entorno hospitalario. Descripción del caso: El paciente era un niño de 3 años con diagnóstico de leucemia linfoblástica aguda Pro B (LLA). El paciente ingresó en el hospital con quejas de malestar, fatiga, pérdida de peso y diarrea entre ciclos de quimioterapia. Se aisló Rhodotorula del hemocultivo del paciente que se obtuvo durante la elevación de la temperatura. Después de 14 días de tratamiento con anfotericina B, la situación clínica del paciente mejoró y fue dado de alta. Conclusión: Rhodotorula spp. como patógeno poco común pero emergente, a menudo se presenta como fiebre de etiología desconocida resistente al tratamiento antibacteriano y puede asociarse con fungemia y otras complicaciones graves.(AU)

Induction-related mortality in adolescents and young adults with acute lymphoblastic leukemia in a resource-limited setting: do treatment-related complications create more impact than disease biology?

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a malignant clonal bone marrow disorder with a high mortality rate during the initial therapy. This retrospective study aimed to describe and analyze the risk factors and causes of induction-related mortality (IRM) in an adolescent and adult ALL population treated in a low- and middle-income country. METHODS: From 2009 to 2016, a total of 167 patients were included, of which 50.9% were male with a median age of 28 years. B-immunophenotype represented 97.6%, and high-risk cytogenetics were present in 23.3%. During induction therapy, 91% had at least 1 complication, most of which were infectious, with an IRM of 12%. RESULTS: Factors associated with increased mortality rate were central nervous system (CNS) status [CNS-3: hazard ratio (HR) 3.029; 95% confidence interval (CI), 0.79‒11.49; P =0.103 and CNS-2: HR, 9.98; 95% CI, 2.65‒37.65; P =0.001] and dialysis requirement (HR, 9.15; 95% CI, 2.44‒34.34; P =0.001). CONCLUSION: Our study confirms that ALL patients treated in resource-constrained settings have high rates of IRM, mainly attributed to advanced disease and high tumor burden at diagnosis.

Silencioso e negligenciado: o que se sabe após quatro décadas do descobrimento do HTLV-1? / Silent and neglected: what is known after four decades of the discovery of the HTLV-1? / Silencioso y descuidado: ¿qué se sabe después de cuatro décadas del descubrimiento del HTLV-1?

O vírus linfotrópico T humano tipo 1 (HTLV-1) foi o primeiro retrovírus humano descoberto, descrito pela primeira vez há 41 anos. Esse retrovírus está associado ao desenvolvimento de duas doenças graves: a leucemia/linfoma de células T do adulto (ATLL) e a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP). Este trabalho teve como objetivo analisar as atualizações sobre o HTLV-1, destacando os aspectos clínicos, os avanços e as limitações no tratamento e na prevenção da infecção pelo HTLV-1. Para isso, foi realizada uma revisão integrativa, por meio de coleta de dados nas plataformas PubMed, LILACS e SciELO, entre março e abril de 2021. Foram incluídos 61 artigos de diferentes países. O Brasil foi o país com maior número de publicações na área: 12. Os resultados obtidos mostram que existem avanços importantes no que diz respeito ao tratamento e à prevenção da infecção pelo HTLV-1. No entanto, a falta de estudos específicos sobre o vírus, que abordem os aspectos clínicos da infecção, foi um fator limitante para este estudo, o que reforça a necessidade de investimento em novas pesquisas sobre o tema.

The Human T-lymphotropic Virus 1 (HTLV-1) was the first human retrovirus discovered, described for the first time 41 years ago. This retrovirus is associated with the development of two serious diseases: adult T-cell leukemia/lymphoma (ATLL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (HAM/TSP). This study aimed to analyze the updates about HTLV-1, highlighting the clinical aspects, advances, and limitations in the treatment and prevention of HTVL-1 infection. To this end, an integrative review was carried out, with data collection on PubMed, LILACS, and SciELO platforms, between March and April 2021. A total of 61 articles from different countries were included. Brazil was the country with the largest number of publications in the area: 12. The results showed effective advances regarding treating and preventing HTLV-1 infection. However, the lack of specific studies about the virus, which address the clinical aspects of the infection, was a limiting factor for this study, which reinforces the need for investment in new research about this topic.

El virus linfotrópico T tipo 1 humano (HTLV-1) fue el primer retrovirus humano descubierto y se describió por primera vez hace 41 años. Este retrovirus está asociado con el desarrollo de dos enfermedades graves: leucemia/linfoma de células T del adulto (ATLL) e mielopatía asociada a HTLV-1/paraparesia espástica tropical (HAM/TSP). Este estudio tuvo como objetivo analizar las actualizaciones sobre HTLV-1, destacando los aspectos clínicos, los avances y limitaciones en el tratamiento y prevención de la infección por HTLV-1. Para ello, se realizó una revisión integradora, a través de la recolección de datos en las plataformas PubMed, LILACS y SciELO entre marzo y abril de 2021. Se incluyeron 61 artículos de diferentes países. Brasil fue el país con mayor número de publicaciones en el área: 12. Los resultados obtenidos muestran que existen avances efectivos en cuanto al tratamiento y prevención de la infección por HTLV-1. Sin embargo, la falta de estudios específicos sobre el virus que aborden los aspectos clínicos de la infección fue un factor limitante para el presente estudio, lo que refuerza la necesidad de invertir en nuevas investigaciones sobre este virus.

Diagnosis, prevention and treatment of central nervous system involvement in peripheral t-cell lymphomas.

Non-Hodgkin lymphomas with T-cell immunophenotype encompass a heterogeneous group of infrequent neoplasms that follow variable clinical courses but prevalently include aggressive behavior and high mortality rates. The involvement of the central nervous system (CNS) is an uncommon event in T-cell lymphomas, with wide variability among the different disease entities. CNS can be affected either at initial diagnosis or at recurrence, and both forms are considered "secondary CNS T-cell lymphoma". Given the low incidence of secondary CNS T-cell lymphoma, related literature is sparse, contradictory, and primarily constituted by small case series and single case reports. However, reported studies uniformly suggest high mortality rates related to this event. Therefore, to improve our ability to identify high-risk patients and offer them successful CNS prophylaxis or timely and effective treatment once the event has occurred may prevent CNS-related T-cell lymphomas deaths. For example, some entities like aggressive adult T-cell leukemia/lymphoma, extranodal natural killer/T-cell lymphoma, and other peripheral T-cell lymphomas with involvement of two or more extranodal organs are prone to CNS dissemination and should be considered for personalized CNS prophylaxis. The level of evidence suggesting an increased risk of CNS recurrence for other T-cell lymphomas and for other risk factors is lower. Published case series show that, following the example of aggressive B-cell lymphomas, patients with T-cell lymphomas and putative increased CNS risk receive different forms of prophylaxis, mostly methotrexate and cytarabine delivered by intrathecal and/or intravenous routes, with varied success. To date, achievements in the treatment of CNS involvement in patients with aggressive B-cell lymphoma were not replicated in secondary CNS T-cell lymphomas, and identification of effective therapies remains an urgent research target. This review is focused on clinical findings, diagnosis, treatment, and prognosis of patients with T-cell lymphoma experiencing CNS dissemination either at presentation or relapse. It aims to provide logical and, oftentimes, evidence-based answers to the most common questions on the most probable risk factors to CNS involvement in patients with T-cell lymphoma, the indications and strategies to prevent this life-threating event, and the management of patients with CNS disease.

Quimioterapia intensiva asociada a imatinib en leucemia linfoblástica aguda del adulto, Philadelphia positivo. Experiencia en un hospital público / Intensive chemotherapy with tyrosine kinase inhibitors in philadelphia-positive acute lymphoblastic leukemia

Background: Before the advent of tyrosine kinase inhibitors (TKIs), patients with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ALL) had a poor prognosis. The association of TKIs to intensive chemotherapy (CT) improved outcome. Aim: To evaluate results of an intensive CT protocol including TKI in a public hospital in Santiago, Chile. Material and Methods: All patients with Ph+ALL diagnosed between January 2010 and February 2019, and who met inclusion criteria for intensive CT, received the Ph+ALL national protocol in association with imatinib and were included in this analysis. Results: Thirty-five patients aged 15 to 59 years received treatment. Complete response (CR) was obtained in 97%. Measurable residual disease (MRD) was negative in 61% (19/31 evaluable cases) during follow-up, and 55% (16/29) were MRD (-) before three months. Relapse was observed in 13 cases. Three patients underwent allogeneic hematopoietic stem cell transplant (HSCT), two in CR1. The overall survival (OS) and event-free survival (EFS) at three years were 52 and 34%, respectively. In patients who achieved MRD negativity before three months, no statistically significant differences in OS (64 and 42% respectively, p = 0.15) or EFS (35 and 32% respectively, p = 0.37) were observed. Conclusions: The prognosis of Ph+ALL improved with the association of imatinib to intensive CT. MRD-negative status before three months in this series was not significantly associated with better outcomes. Our series suggests that the Ph+ALL national protocol associated to TKI is a therapeutic alternative with high CR and aceptable MRD (-) rates.

HTLV-1 infection in acute t- lymphocytic leukemia/lymphoma.

Adult T- lymphocyte leukemia/ lymphoma (ATLL), described by Uchiyama et al. in 1977, is a distinct neoplasia of peripheral T-lymphocytes caused by human T-cell lymphotropic virus type 1 (HTLV-1). The authors describe the case of a 75-year-old female patient who presented with fever, chills, and altered mental status. The peripheral blood morphology showed large atypical lymphocytes with multilobed nuclei and flow cytometry consistent with ATLL. The authors discuss the pathophysiology, differential diagnosis, and subtypes of ATLL in addition to the diagnostic approach using flow cytometry when bone marrow biopsy is not available and modalities of treatment.

Raoultella ornithinolytica urinary tract infection in a pediatric patient with T-cell precursor acute lymphoblastic leukemia / Infección de vías urinarias por Raoultella ornithinolytica en un paciente pediátrico con leucemia linfoblástica aguda de células T

Abstract Background: Currently, Raoultella ornithinolytica is considered an emerging pathogen of community- and hospital-acquired infection, particularly in patients with immunodeficiencies, malignancies, anatomical abnormalities, or after invasive procedures. Pediatric infections with R. ornithinolytica are exceedingly rare, with only six previously reported cases, of which only two were reported as a urinary tract infection. Case report: Here, we describe a polymicrobial urinary tract infection (R. ornithinolytica and Enterococcus faecalis) in a pediatric patient with T-cell precursor acute lymphoblastic leukemia, which was successfully treated with ampicillin-sulbactam. Conclusions: To the extent of our knowledge, we report the seventh case in a pediatric patient and only the third case of a urinary tract infection in this age group caused by R. ornithinolytica.

Resumen Introducción: Actualmente Raoultella ornithinolytica es considerado un patógeno emergente involucrado en infecciones adquiridas en la comunidad y en el hospital, en particular en pacientes con algún tipo de inmunodeficiencia, malignidad, alteraciones anatómicas o sometidos a procedimientos invasivos. Las infecciones pediátricas causadas por R. ornithinolytica son sumamente raras, con solo seis casos publicados, de los cuales nada más dos se presentaron como infección de vías urinarias. Caso clínico: Se describe una infección de vías urinarias polimicrobiana (R. ornithinolytica y Enterococcus faecalis) en un paciente pediátrico con leucemia linfoblástica aguda de células T, que fue tratado satisfactoriamente con ampicilina-sulbactam. Conclusiones: Con base en lo que se sabe hasta el momento, se reporta el séptimo caso en un paciente pediátrico y el tercer caso de infección de vías urinarias causada por R. ornithinolytica en este grupo de edad.

Raoultella ornithinolytica urinary tract infection in a pediatric patient with T-cell precursor acute lymphoblastic leukemia.

BACKGROUND: Currently, Raoultella ornithinolytica is considered an emerging pathogen of community- and hospital-acquired infection, particularly in patients with immunodeficiencies, malignancies, anatomical abnormalities, or after invasive procedures. Pediatric infections with R. ornithinolytica are exceedingly rare, with only six previously reported cases, of which only two were reported as a urinary tract infection. CASE REPORT: Here, we describe a polymicrobial urinary tract infection (R. ornithinolytica and Enterococcus faecalis) in a pediatric patient with T-cell precursor acute lymphoblastic leukemia, which was successfully treated with ampicillin-sulbactam. CONCLUSIONS: To the extent of our knowledge, we report the seventh case in a pediatric patient and only the third case of a urinary tract infection in this age group caused by R. ornithinolytica.