Clinical Analysis of SET-NUP214 Fusion Gene Positive Patients with Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene.@*METHODS@#The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively.@*RESULTS@#Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive.@*CONCLUSION@#The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.

Características clínicas y pronóstico de los pacientes con linfoma leucemia de células t del adulto / Clinical characteristics and prognosis of patients with adult T-cell leukemia lymphoma

Introducción: El objetivo del presente estudio fue determinar las características clínicas y pronóstico de los pacientes con Leucemia/Linfoma de Células T del Adulto (ATL) en el Instituto Nacional de Enfermedades Neoplásicas (INEN) de Perú. Metodología: Se realizó un estudio transversal, que incluyó por Se revisaron 188 historias clínicas y estudio patológico de pacientes con infección por HTLV-1 diagnosticados en el INEN durante 10 años, de quienes 150 tuvieron ATL. Resultados: 62% de los pacientes tuvieron el subtipo ATL linfoma, 37% subtipo agudo y 1% crónico. La mediana de edad fue 53 años (20-89); 51% fueron mujeres. Dentro de las características clínicas: ECOG ≥ 2 (56%); estadio clínico III-IV (80%), síntomas B (58%); incremento de la deshidrogenasa láctica, LDH, (74%); leucocitosis (50%); hipercalcemia (46%) y anemia (36%). 122 pacientes (81,3%) recibieron tratamiento, 79% con quimioterapia (QT) y 4,6% radioterapia complementaria (RT); CHOP fue el esquema de QT más frecuente (89%). De los pacientes con QT tuvieron 18% RC, 32% RP, 7% EE y 13% PE. Conclusión: En este reporte en pacientes con ATL, la forma linfoma es el subtipo más frecuente, existe alta prevalencia de inmunofenotipo atípico y pobre respuesta al CHOP.

Introduction: The objective of this study was to determine the clinical characteristics and progno-sis of patients with adult T-cell leukemia/lymphoma (ATL) at the National Institute of Neoplastic Diseases (INEN) of Peru. Methodology: A cross-sectional study was carried out, which included 188 clinical histories and a pathological study of patients diagnosed with HTLV-1 infection diagnosed at the INEN for ten years, of whom 150 had ATL. Results: Sixty-two percent of the patients had the ATL lymphoma subtype, 37% had the acute sub-type, and 1% had the chronic subtype. The median age was 53 (20-89); 51% were women. Within the clinical characteristics: ECOG ≥ 2 (56%); clinical stage III-IV (80%), symptoms B (58%); increased lactic dehydrogenase, LDH, (74%); leukocytosis (50%); hypercalcemia (46%) and anemia (36%). A total of 122 patients (81.3%) received treatment, 79% with chemotherapy (CT) and 4.6% with complementary radiotherapy (RT); CHOP was the most frequent QT regimen (89%). Of the patients with QT, 18% had CR, 32% PR, 7% EE, and 13% PE. Conclusion: In this report, in patients with ATL, the lymphoma form was the most frequent subtype, and there was a high prevalence of atypical immunophenotype and poor response to CHOP.

Leucemia asociada al virus linfotrópico T humano tipo 1 (HTLV-1) y transmisión intrafamiliar de la infección en Santiago del Estero / Leukemia associated to human T cell lymphotropic virus type 1 (HTLV-1) infection and intrafamily transmission in Santiago del Estero

Resumen La leucemia/linfoma a células T del adulto (ATLL) es una enfermedad hematológica causada por el virus linfotrópico T humano tipo 1 (HTLV-1) que se desarrolla luego de 20 años de incubación, preferencialmente cuando la infección se adquiere por transmisión vertical. Este tiempo se reduce de 3 meses a 3 años cuando la transmisión del virus es por transfusión o trasplante de órganos. La ATLL aguda es de difícil diagnóstico por ser inusual y tener una rápida progresión a la muerte. En el Noroeste argentino, donde el virus es endémico, la ATLL es más frecuente, sin embargo, también se la detecta continuamente en el resto del país. El tratamiento de elección, en primera instancia, es el uso combinado de antivirales. Presentamos un caso de ATLL aguda desarrollada en un hombre de 59 años de Santiago del Estero a partir del cual se identificó transmisión intrafamiliar de la infección por HTLV-1.

Abstract Adult T-cell leukemia/lymphoma (ATLL) is an hematological disease caused by human T-cell lymphotropic virus type 1 (HTLV-1) that develops after 20 years of incubation preferentially when the infection is acquired by vertical transmission. In cases of transmission by transfusion or organ transplant, this time is reduced from 3 months to 3 years. Acute ATLL is difficult to diagnose because it is unusual and has a rapid progression to death. In the Argentine Northwest, where the virus is endemic, ATLL is more frequent, however it is also detected continuously in the rest of the country. The treatment of choice, in the first instance, is the combined use of antivirals. We present a case of acute ATLL developed in a 59-year-old man from Santiago del Estero from which intrafamilial transmission of HTLV-1 infection was identified.

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.

Leucemia/linfoma T del adulto tipo linfomatoso por HTLV-1 en una mujer joven / Adult T cell lymphoblastic leukemia/lymphoma by HTLV-1 in a young woman

Resumen La leucemia/linfoma T del adulto (LLTA) de tipo linfomatoso es un subtipo del linfoma de las células T, causado por la infección del virus linfotrópico de células T humanas tipo 1 (HTLV-1); el cual genera una integración proviral en el ADN del hospedero y expansión clonal de linfocitos T. Presentamos el caso de una mujer de 20 años que desarrolló linfadenopatías múltiples, hepatoesplenomegalia y fiebre, con serología positiva para HTLV-1 y reacción de polimerasa en cadena (RPC) con la integración proviral en el ADN del hospedero. La inmunohistoquímica en un ganglio linfático fue positiva para células T CD4+ y CD8+. La LLTA ha sido descrito en todas las áreas endémicas del HTLV-1; sin embargo, existen diferencias en la edad de presentación según la región: 40 a 50 años en América del Sur y 60 años en Japón. Presentamos uno de los pocos casos reportados de LLTA de tipo linfomatoso en adultos jóvenes.

Adult T cell lymphocyte leukemia/lymphoma (ATLL) is a subtype of T-cell lymphoma caused by infection of the human T-cell lymphotropic virus type 1 (HTLV-1); which generates a pro-viral integration into the host DNA, resulting in a clonal expansion of T lymphocytes. We present the case of a 20-year-old woman who developed multiple lymphadenopathies, hepatosplenomegaly and fever, serum positivity for HTLV-1 and proviral integration in the host DNA, demonstrated by polymerase chain reaction (PCR). Immunohistochemistry of lymphoid node was positive to CD4+ and CD8+ T cells. ATLL has been described in all HTLV-1 endemic areas, however, there are differences in the mean age of its presentation in such areas: 40 to 50 years in South America, 60 years in Japan. We showed one of few reported cases of the lymphoma type of ATLL in young adults.

Expression Level and Clinical Value of PTEN Gene in Patients with Acute T Lymphocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To study the PTEN gene expression level and its clinical significance in patients with acute T lymphoblastic leukemia.@*METHODS@#One hundred and twenty-four patients with T-ALL treated in our hospital from January 2014 to May 2018 were selected, and 120 healthy people were selected as control group. The bone marrow of the patients were collected, and mononuclear cells were separated out. PTEN gene expression level was detected by RT-PCR, PTEN protein expression level was detected by Western blot, Kaplan-Meier was used to analyze the survival rate of patients with T-ALL, Cox multivariate regression analyzed was used to analyze the independent influencing factors of patients, and the correlation between PTEN level and clinical characteristics of patients with T-ALL and its prognostic value were analyzed.@*RESULTS@#The relative level of PTEN gene in patients with T-ALL was 0.19±0.06, which was significantly lower than that in control groups (P<0.05). There was significantly positive correlation of the expression level of PTEN gene with white blood cell count （r=0.993）and peripheral blood immature cells （r=0.996） in patients with T-ALL. There was no correlation between PTEN gene expression level and sex, age, LDH level, Hb level, platelet count in patients with T-ALL. And it was found that expression levels PTEN protein in the middle-risk group, the standard-risk group and the high-risk group were significant lower than those in the control group (P<0.05), while those in the high-risk group were significantly lower than those in other groups (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in PTEN gene high expression group were higher than those in PTEN low expression group (P<0.05). Cox multivariate regression analysis showed that white blood cell count and PTEN gene were independent influencing factors of OS (P<0.05); platelet count and PTEN gene were independent influencing factors of DFS (P<0.05).@*CONCLUSION@#PTEN gene level relates to the prognosis of patients with T-ALL. Patients with better prognosis show a higher PTEN gene level, which provides reference for clinical treatment of patients with T-ALL.

Falla hepática aguda fulminante como manifestación de leucemia de células T del adulto en paciente con infección por HTLV-1 / Acute Liver Failure as Presentation of Adult T-cell Leukemia in an HTLV-1 Patient

La falla hepática aguda es el desarrollo de injuria hepática severa con deterioro de la función de síntesis y encefalopatía. Dentro de la variedad de causas, las infiltraciones neoplásicas representan menos del 0,5%. Presentamos el caso de un paciente varón HTLV1 positivo que debuta con una clínica de hepatitis aguda, siendo posteriormente diagnosticado con diseminación de linfoma/leucemia de células T del adulto. Desafortunadamente el paciente presentó deterioro rápido y progresivo de la función hepática, falleciendo a los pocos días de la hospitalización

Acute liver failure is the development of severe hepatic injury with deterioration of liver synthesis function and encephalopathy. Among all the variety of causes, neoplastic infiltration represents less than 0.5%. We present the case of a male patient with a past medical history of HTLV-1 infection, who reports symptoms of acute hepatitis, being diagnosed with Adult T-cell leukemia/ lymphoma. Unfortunately, the patient had a rapid deterioration and passed away a few days after admission

Case for diagnosis. Infective dermatitis associated with HTLV-1: differential diagnosis of atopic dermatitis

Abstract: Infective dermatitis associated with HTLV-1 (IDH) is the main cutaneous marker of HTLV-1 infection. This disease occurs primarily in children and should be differentiated from other eczemas, especially from atopic dermatitis. The largest series of IDH are from Jamaica and Brazil. There are an estimated 15 to 20 million infected people in the world, and Brazil is one of the endemic regions. Studies suggest that IDH in children may be a marker for the development of T-cell leukemia/lymphoma (ATL) or myelopathy associated with HTLV-1/tropical spastic paraparesis (HAM / TSP) in adulthood.

Un caso de leucemia/linfoma T del adulto en Uruguay / Adult T-cell leukemia/lymphoma. Report of a case in Uruguay

La leucemia/linfoma T del adulto pertenece al grupo de neoplasias T maduras y constituye una entidad clínica de baja incidencia. Su etiopatogenia se asocia a la infección por el virus linfotrópico humano 1. En Uruguay se registra una incidencia muy baja de infección por este virus y no se ha comunicado a la fecha ningún caso de leucemia/linfoma T del adulto. Presentamos el caso de una inmigrante de Perú, quien se presentó con linfocitosis sostenida, múltiples parasitosis intestinales y compromiso cutáneo. El diagnóstico fue tardío y la paciente falleció antes de iniciar tratamiento oncoespecífico. Destacamos la importancia de la sospecha clínica de esta entidad y el estudio de la serología para el virus, en particular en casos, como el nuestro, procedentes de área endémica.

Adult T-cell leukemia/lymphoma belongs to the group of mature T-cell malignancies according to the WHO classification. It constitutes a rare entity and has a strong association with infection by human T-lymphotropic virus 1. In Uruguay, this viral infection is very infrequent and, to our knowledge, no case of adult T-cell leukemia/lymphoma has been previously reported. We describe the case of a woman, immigrant from Peru, who presented with persistent lymphocytosis, intestinal parasitic diseases, and skin involvement. The diagnosis was delayed and the patient died before initiating oncological treatment. We therefore emphasize the relevance of an early clinical suspicion and serology for this virus, especially in patients coming from endemic countries like Peru.

Linfoma duodenal asociado a infección por Strongyloides stercoralis. Dos manifestaciones de la infección por HTLV-1 / Duodenal Lynphoma associated to Strongyloides stercoralis infection. Two types of HTLV-1 infection

La infección por el virus linfotrópico de células T humanas tipo 1 (HTLV-1), es causante de la leucemia/linfoma de células T del Adulto (ATLL), siendo la afectación duodenal poco usual. La coinfección de HTLV-1 con Strongyloides stercolaris es común en los pacientes con HTLV- 1 debido a la inadecuada respuesta TH2 que presentan estos sujetos. Describimos a una paciente mujer de 48 años de edad, natural y procedente de la selva del Perú con historia familiar de infección por HTLV- 1 quien acude con diarrea crónica y baja de peso. Se le diagnosticó infección por HTLV-1 así como ATLL duodenal y estrongiloidiasis. Se inició tratamiento con ivermectina y quimioterapia, siendo estabilizada y dada de alta. Reportamos el presente caso debido a la poca frecuencia de coexistencia en duodeno de ATLL y estrongiloidiasis.

Infection by the Human T- Lymphotropic virus I (HTLV-1) causes Adult T cell Leukemia-lymphoma (ATLL), being the duodenal involvement rare. Commonly, patients co-infected with HTLV-1 and Strongyloides stercoralis are seen due to the lack of TH2 response found on these patients. We describe a 48-year-old woman, from the jungle of Peru, with a family history of HTLV-1 infection, who presented with a History of chronic diarrhea and weight loss. HTLV-1 infection with ATLL and strongyloidiasis were diagnosed. Ivermectin treatment and chemotherapy were initiated, being stabilized, and discharged. We report this case because of the unusual coexistence in the duodenum of ATLL and strongyloidiasis.

Adult T-cell leukemia/lymphoma treatment in Bahia, Brazil

Abstract Background: Adult T-cell leukemia/lymphoma is a peripheral disease associated with human T-cell lymphotropic virus type 1. Treatment is carried out according to clinical type with watchful waiting being recommended for less aggressive types. Aggressive adult T-cell leukemia/lymphoma is generally treated with chemotherapy and/or antivirals. The objective of this study was to correlate the survival of patients diagnosed in Bahia, Brazil, with the therapeutic approaches employed and to evaluate what issues existed in their treatment processes. Methods: Eighty-three adult T-cell leukemia/lymphoma patients (26 smoldering, 23 chronic, 16 acute, 13 lymphoma and five primary cutaneous tumoral) with available data were included in this study. Results: Complete response was achieved in seven smoldering patients with symptomatic treatment, in two with chronic disease using antivirals/chemotherapy, in one with acute disease using antivirals and in one lymphoma using the LSG15 regimen [vincristine, cyclophosphamide, doxorubicin, and prednisolone (VCAP); doxorubicin, ranimustine, and prednisolone (AMP); and vindesine, etoposide, carboplatin, and prednisolone (VECP)]. Smoldering patients who received symptomatic treatment presented longer survival. Favorable chronic patients treated with antivirals presented longer survival compared to the unfavorable subtype. However, for the acute form, first-line chemotherapy was better, albeit without significance, than antivirals. Only one of the patients with lymphoma and primary cutaneous tumors responded. Conclusions: Watchful waiting associated with phototherapy represents the best option for smoldering adult T-cell leukemia/lymphoma with survival in Bahia being superior to that described in Japan. There was a trend of better results with zidovudine/interferon-alpha in favorable chronic disease. Excellent results were achieved in the lymphoma type treated with the LSG15 protocol. Patients are diagnosed late probably due to lack of knowledge of adult T-cell leukemia/lymphoma by primary healthcare doctors and a Brazilian treatment protocol needs to be established.

Prolonged lymphocytosis as the first manifestation of Hodgkin-like adult T-cell leukemia/lymphoma

Abstract Hodgkin-like ATLL is a rare variant of adult T-cell leukemia/lymphoma (ATLL), a disease caused by human T-cell lymphotropic virus type-1 (HTLV-1). At admission, a 46-year-old female presented with lymphadenomegaly, lymphocytosis, slight elevation of LDH blood level, and acid-alcohol resistant bacilli in sputum and was being treated for pulmonary tuberculosis (Tb). She had lymphocytosis in the previous 20 months. Serology for HTLV-1 was positive. Lymph node was infiltrated by medium-sized lymphocytes with scattered Hodgkin and Reed-Sternberg-like cells CD30+, CS1-4+, and CD79a+. Background cells were CD4+ and CD25+. A clinical diagnosis of favorable chronic ATLL was given. She was treated with chemotherapy but later progressed to acute ATLL and ultimately died. Hodgkin-like ATLL should be considered in the histological differential diagnosis with Hodgkin lymphoma since treatment and prognosis of these diseases are distinct. It is also important to search for HTLV-1 infection in patients with unexplained prolonged lymphocytosis.

Comorbidity between HTLV-1-associated adult T-cell lymphoma/leukemia and verrucous carcinoma: a case report / Comorbilidad entre carcinoma verrugoso y linfoma/leucemia de células T del adulto asociado con HTLV-1: un reporte de caso

Abstract Background: Adult T-cell Leukemia/Lymphoma (ATLL) is classified as a peripheral CD4+ T-cell neoplasm caused by the human T-cell lymphotropic virus type 1 (HTLV-1). Typical symptoms are associated with leukemic infiltration; however, atypical and exaggerated manifestations of verrucous carcinoma have also been described. Case report: We present here the case of a patient with multiple skin lesions, ischemic necrosis in the hallux and lymphadenopathies. Biopsies were taken, which showed verrucous epidermal carcinoma and cutaneous lymphoma. Splenomegaly and adenopathy in mesentery, retro peritoneum and lymph node chains in the limbs were observed. Bone marrow examination showed findings compatible with T-cell leukemia/lymphoma; and it was ELISA positive for HTLV-1/2. Treatment and outcome: The patient had a good initial response to a CHOP scheme (cyclophosphamide, doxorubicin, vincristine and prednisone) with filgrastim. However, the patient had a relapse and died before the second cycle. Clinical relevance: Comorbidity could lead to the associated risk factors model. According to this model, secondary immunodeficiency caused by HTLV-1 may induce the development of verrucous carcinomas; alternatively, the disease could be due to a correlation between HTLV-1 and the human papillomavirus (HPV).

Resumen Antecedentes: La leucemia/linfoma de células T del adulto se clasifica como una neoplasia de células T CD4+ periféricas desencadenada por el virus linfotrópico de células T humanas tipo 1 (HTLV-1). Los síntomas típicos se asocian a la infiltración leucémica; sin embargo, también se ha descrito la manifestación atípica y exagerada de carcinomas verrugosos. Caso clínico: Se presenta el caso de una paciente con lesiones múltiples en piel, necrosis isquemica del hallux y linfadenopatías. se realizaron biopsias que reportaron carcinoma epidermoide verrugoso y linfoma cutáneo. Se detectó esplenomegalia y adenopatías en mesenterio, región retroperitoneal, y cadenas ganglionares de las extremidades. la medula ósea presentó hallazgos compatibles con leucemia/linfoma de células T y ELISA positivo para HTLV-1/2. Tratamiento y resultado: La paciente presentó buena respuesta inicial al esquema CHOP (ciclofosfamida, doxorrubicina, vincristina, prednisona) con filgrastim. Sin embargo, presentó recaída de la enfermedad antes del segundo ciclo y falleció Relevancia clinica: La comorbilidad podría conducir al modelo de factores de riesgo asociados. De acuerdo con este modelo, la inmunodeficiencia secundaria causada por HTLV-1 puede inducir el desarrollo de carcinomas verrugosos; Alternativamente, la enfermedad podría deberse a una correlación entre el HTLV-1 y el virus del papiloma humano (VPH).

Evaluation of the role of TAX, HBZ, and HTLV-1 proviral load on the survival of ATLL patients

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy with very poor prognosis and short survival, caused by the human T-lymphotropic virus type-1 (HTLV-1). The HTLV-1 biomarkers trans-activator x (TAX) and HTLV-1 basic leucine zipper factor (HBZ) are main oncogenes and life-threatening elements. This study aimed to assess the role of the TAX and HBZ genes and HTLV-1 proviral load (PVL) in the survival of patients with ATLL. METHODS: Forty-three HTLV-1-infected individuals, including 18 asymptomatic carriers (AC) and 25 ATLL patients (ATLL), were evaluated between 2011 and 2015. The mRNA expression of TAX and HBZ and the HTLV-1 PVL were measured by quantitative PCR. RESULTS: Significant differences in the mean expression levels of TAX and HBZ were observed between the two study groups (ATLL and AC, P=0.014 and P=0.000, respectively). In addition, the ATLL group showed a significantly higher PVL than AC (P=0.000). There was a significant negative relationship between PVL and survival among all study groups (P=0.047). CONCLUSION: The HTLV-1 PVL and expression of TAX and HBZ were higher in the ATLL group than in the AC group. Moreover, a higher PVL was associated with shorter survival time among all ATLL subjects. Therefore, measurement of PVL, TAX, and HBZ may be beneficial for monitoring and predicting HTLV-1-infection outcomes, and PVL may be useful for prognosis assessment of ATLL patients. This research demonstrates the possible correlation between these virological markers and survival in ATLL patients.

Adult T-cell leukemia/lymphoma / Leucemia/linfoma de células T do adulto

Summary Adult T-cell leukemia/lymphoma (ATL) is a malignancy of mature CD4+ T-cells caused by human T-cell lymphotropic virus type 1 (HTLV-1). Twenty million people are believed to be infected throughout the world, mostly in Japan, Africa, the Caribbean, and South America, particularly in Brazil and Peru. ATL affects about 5% of infected individuals and is classified in the following clinical forms: acute, lymphoma, primary cutaneous tumoral, chronic (favorable and unfavorable), and smoldering (leukemic and non-leukemic). Although it is considered an aggressive disease, there are cases with a long progression. We emphasize the importance of clinical classification as an indispensable element for evaluating prognosis and appropriate therapeutic approach. Since several cases have been published in Brazil and this disease is still poorly known, we decided to make a review paper for dissemination of clinical, hematological and pathological aspects, diagnosis, and therapy. The best way to reduce the occurrence of ATL would be halting the transmission of the virus through breastfeeding.

Resumo A leucemia/linfoma de células T do adulto (LLcTA) é uma neoplasia de células T maduras CD4+ causada pelo vírus linfotrópico para células T humanas tipo 1 (HTLV-1). Acredita-se que existem cerca de 20 milhões de pessoas infectadas em todo o mundo, principalmente no Japão, na África, no Caribe e na América do Sul, particularmen te no Brasil e no Peru. A LLcTA acomete cerca de 5% dos indivíduos infectados e classifica-se nas seguintes formas clínicas: aguda, linfomatosa, tumoral primária de pele, crônica (favorável e desfavorável) e indolente (leucêmica e não leucêmica). Embora seja considerada uma doença agressiva, há casos com longa evolução. Salientamos a importância da classificação clínica como elemento im prescindível para avaliação do prognóstico e conduta terapêutica adequada. Como já foram publicados vários casos no Brasil e essa doença ainda é pouco conhecida, decidimos fazer um trabalho de revisão para divulgar os seus aspectos clínicos, hematológicos, anatomopatológi cos, diagnósticos e terapêuticos. O melhor meio de redu zir a ocorrência de LLcTA seria sustando a transmissão vertical do vírus pela amamentação.

Western Blot e PCR em tempo real em pacientes com leucemia/linfoma de células T do adulto associado ao HTLV-1 / Western blot and real-time PCR in patients with HTLV-1-associated adult T-cell leukemia / lymphoma

Contexto: Um dos requisitos para garantir a instituição de um tratamento adequado aos pacientes acometidos por leucemia/linfoma associada ao HTLV-1 é a confirmação diagnóstica da infecção por HTLV-1. Essa confirmação, dá-se hoje por meio de exames laboratoriais, a saber: ELISA, WESTERN BLOT e PCR em tempo real (RT-PCR). O Elisa já se encontra incorporado ao SUS para investigação diagnóstica nesta doença, contudo, por conta de sua baixa acurácia, são necessárias outras provas confirmatórias que permitam um diagnóstico preciso da doença que possibilite que pacientes com possibilidade de tratamento, como é o caso dos pacientes com leucemia/linfoma acometidos pelo HTLV-1, recebam o melhor tratamento. O processo diagnóstico da infecção pelo HTLV se baseia na detecção de anticorpos anti-HTLV circulantes no sangue. Geralmente o processo se inicia através da realização do ELISA. Para confirmação do diagnóstico, é recomendada a realização de um teste complementar em casos com ELISA positivo. Além de confirmar o diagnóstico, os exames complementares também irão diferenciar entre HTLV-I e HTLV-II e descartar casos falso-positivos. As combinações tornam a sensibilidade e especificidade mais confiáveis. Dentre estes testes os mais utilizados são o Western Blot (WB), e o teste de biologia molecular (PCR). Evidências científicas: O Western blot é um teste imunoenzimático para detecção de anticorpos anti-HTLV-1 e HTLV-2, utilizado como teste confirmatório da infecção pelo HTLV após reatividade em teste de triagem e também para diferenciação entre a presença de HTLV-1 e HTLV-2. É o teste mundialmente mais aceito como exame confirmatório para HTLV. Os antígenos utilizados pelos testes mais modernos incluem as proteínas env recombinante GD21, presente nos dois vírus, e rgp46-I e rpg46-II, respectivamente específicas do HTLV-I e HTLV-II. Além das proteínas gag p19, p24, p26, p28, p32, p36, p53. Da mesma forma, a PCR em tempo real surge para melhorar a acurácia dos resultados, abrindo novas perspectivas sobre seu uso na prática clínica. Alguns estudos mostram que a sensibilidade da PCR-RT é de 100% e especificidade de 96,7 a 100%. Estudos que analisaram a sensibilidade comparativamente pelo tipo de vírus demonstram que a PCR-RT apresentou sensibilidade de 84,6% a 94,2% para o HTLV-1 e 76,9% a 90,7% para o HTLV-2. Decisão: Incorporar os procedimentos laboratoriais por técnicas de Western Blot e PCR em tempo real no diagnóstico de leucemia/linfoma de células T do adulto associado ao HTLV-1, no âmbito do Sistema Único de Saúde ­ SUS, dada pela Portaria SCTIE-MS nº 23 publicada no Diário Oficial da União (DOU) nº 106, de 06 de junho de 2016.

Antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV-1 / Antiretroviral zidovudine for use in the treatment of HTLV-1 associated T cell leukemia / lymphoma

INTRODUÇÃO: O HTLV é um retrovírus descoberto em 1981 que possui as mesmas vias de transmissão do HIV e apresenta prevalência variada mundialmente. No Brasil estudos com gestantes e doadores em bancos de sangue refletem uma baixa prevalência do HTLV, segundo própria classificação do vírus em termos de prevalência, na população (entre 0,1-1%). Dos pacientes infectados pelo vírus, 90% permanecerão assintomáticos por toda vida. Em relação à leucemia/linfoma associada aos portadores de HTLV as taxas variam entre 1 a 5%. A medicação AZT encontra-se incorporada no SUS para uso terapêutico de Pessoas vivendo com HIV/Aids (PVHA), a indicação do uso desse medicamento para pacientes acometidos pela leucemia/linfoma associado ao HTLV não está contemplada no SUS. No entanto é constatada demanda de todas as partes do Brasil no que se refere à liberação do AZT para esse fim. Anteriormente não constavam trabalhos científicos que dessem embasamento para o uso do AZT no tratamento da leucemia/linfoma associado ao HTLV. Realizava-se a solicitação da liberação do AZT diretamente para o Ministério da Saúde e a liberação era realizada em formato de parecer individualizado. A leucemia/linfoma associada ao HTLV-1 é um evento raro e de prognóstico reservado, porém no momento atual trabalhos relacionados ao tema mostram que terapia antiviral com zidovudina e alfainterferona é eficaz na forma leucêmica da doença, com aumento significativo na sobrevida livre de progressão quando comparado ao uso da quimioterapia. A forma linfomatosa se beneficia do uso associado da quimioterapia com os antivirais. A demanda para utilização do AZT como tratamento para leucemia/linfoma associada ao HTLV- 1 é baixa, já que o acometimento da doença citada é um evento raro. EVIDÊNCIAS CIENTÍFICAS: Os trabalhos científicos selecionados para dar subsídio à solicitação da incorporação do medicamento AZT para tratamento de leucemia/linfoma associado ao HTLV-1 demonstraram aumento importante na sobrevida dos indivíduos tratados com antirretroviral exclusivamente ou associado à quimioterapia nos casos linfomatosos quando comparados ao tratamento apenas com quimioterapia, mostrando ser essa terapêutica eficaz para todas as formas de leucemias/linfomas associados ao HTLV-1. Em relação à segurança, os trabalhos avaliaram como sendo seguro o uso de AZT para a população em questão. Os estudos selecionados incluem série de casos, estudos retrospectivos e prospectivos. Abaixo segue tabela 1 com referências principais sobre o uso do AZT para tratamento de leucemia/linfoma associado ao HTLV-1. CONCLUSÃO: A solicitação da incorporação da zidovudina para uso no tratamento de leucemia/linfoma associado ao HTLV-1 tem como base trabalhos que demostram diferença no prognóstico dos pacientes que fizeram uso da zidovudina. Na prática clínica a utilização do AZT, nesses casos, encontra barreira burocrática na liberação da medicação pela incompatibilidade entre a indicação e o registro. Nos últimos anos os trabalhos relacionados ao tema surgiram e dão sustentação para a solicitação da incorporação em questão. Com o intuito de atualizar e sincronizar Ministério da Saúde e a prática clínica baseada em evidência, a Secretaria de Vigilância em Saúde (SVS/MS) solicitou a avaliação da incorporação do AZT para esta condição pela CONITEC. Mesmo sendo a leucemia/linfoma associada ao HTLV-1 um evento menos frequente na população, existem brasileiros em tratamento para essa patologia e que, para os quais, a liberação do AZT traz mudança nos seus prognósticos. DELIBERAÇÃO FINAL: Os membros da CONITEC presentes na reunião do plenário do dia 05/08/2015 deliberaram, por unanimidade, recomendar a incorporação do antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV- 1 conforme Protocolo Clínico e Diretrizes Terapêuticas do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 135/2015. DECISÃO: Portaria nº 50, de 29 de setembro de 2015 - Torna pública a decisão de incorporar no âmbito do Sistema Único de Saúde-SUS o antirretroviral zidovudina para uso no tratamento de leucemia/linfoma de células T associado ao HTLV-1, conforme Protocolo do Ministério da Saúde.