Analysis of 7 cases of pediatric acute myeloid leukemia with DEK-NUP214 fusion gene / 中华儿科杂志

Objective: To investigate the clinical features, treatment regime, and outcome of pediatric acute myeloid leukemia (AML) with DEK-NUP214 fusion gene. Methods: The clinical data, genetic and molecular results, treatment process and survival status of 7 cases of DEK-NUP214 fusion gene positive AML children admitted to the Pediatric Blood Diseases Center of Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2015 to February 2022 were analyzed retrospectively. Results: DEK-NUP214 fusion gene positive AML accounted for 1.02% (7/683) of pediatric AML diagnosed in the same period, with 4 males and 3 females. The age of disease onset was 8.2 (7.5, 9.5) years. The blast percentage in bone marrow was 0.275 (0.225, 0.480), and 6 cases were M5 by FAB classification. Pathological hematopoiesis was observed in all cases except for one whose bone marrow morphology was unknown. Three cases carried FLT3-ITD mutations, 4 cases carried NRAS mutations, and 2 cases carried KRAS mutations. After diagnosis, 4 cases received IAE induction regimen (idarubicin, cytarabine and etoposide), 1 case received MAE induction regimen (mitoxantrone, cytarabine and etoposide), 1 case received DAH induction regimen (daunorubicin, cytarabine and homoharringtonine) and 1 case received DAE induction regimen (daunorubicin, cytarabine and etoposide). Complete remission was achieved in 3 cases after one course of induction. Four cases who did not achieved complete remission received CAG (aclarubicin, cytarabine and granulocyte colony-stimulating factor), IAH (idarubicin, cytarabine and homoharringtonine), CAG combined with cladribine, and HAG (homoharringtonine, cytarabine and granulocyte colony-stimulating factor) combined with cladribine reinduction therapy, respectively, all 4 cases reached complete remission. Six patients received hematopoietic stem cell transplantation (HSCT) after 1-2 sessions of intensive consolidation treatment, except that one case was lost to follow-up after complete remission. The time from diagnosis to HSCT was 143 (121, 174) days. Before HSCT, one case was positive for flow cytometry minimal residual disease and 3 cases were positive for DEK-NUP214 fusion gene. Three cases accepted haploid donors, 2 cases accepted unrelated cord blood donors, and 1 case accepted matched sibling donor. The follow-up time was 20.4 (12.9, 53.1) months, the overall survival and event free survival rates were all 100%. Conclusions: Pediatric AML with DEK-NUP214 fusion gene is a unique and rare subtype, often diagnosed in relatively older children. The disease is characterized with a low blast percentage in bone marrow, significant pathological hematopoiesis and a high mutation rate in FLT3-ITD and RAS genes. Low remission rate by chemotherapy only and very high recurrence rate indicate its high malignancy and poor prognosis. Early HSCT after the first complete remission can improve its prognosis.

Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study / 中华血液学杂志

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

Current treatment preferences in acute myeloid leukemia: a survey in Brazil

ABSTRACT Introduction:: Most adults with acute myeloid leukemia (AML) will eventually relapse from their disease. The combination of 7-day cytarabine and an anthracycline on days 1-3 (the so called "7 + 3" regimen) can be considered standard of care of younger patients with AML. However, the treatment of the elderly ineligible for intensive chemotherapy remains a challenge. Low-dose of subcutaneous cytarabine or hypomethylating agents (HMA) have been studied this group. There are no studies investigating physician practice variation in treating AML in Brazil. Methods:: We developed a survey with ten questions in order to explore the approach to AML in Brazil. Results:: The sample size comprised 100 hematologists. Most reported regular (63%) or occasional (29%) treatment of AML patients. Karyotype analysis and polymerase chain reaction were available in 88% and 71% of institutions, respectively. Next generation sequencing analysis was used in 7% of instituitions. Younger patients receive the "7 + 3" protocol with continuous infusion of cytarabine and anthracycline in 98% of cases. The preferred anthracycline is daunorubicin (64%), followed by idarubicin (34%). The most prescribed daunorubicin dose was 60 mg/m2 (56%). Consolidation after CR with high cytarabine doses (HIDAC) was indicated by 84% of hematologists and 70% use 3 g/m2 twice a day for 3 days. Elderly and unfit patients received HMA (47%) as the preferred treatment. Conclusion:: We showed that the most prevalent AML treatments were according to current guidelines. There is room to improve on the availability of diagnostic tools and the capacity to perform bone marrow transplantation.

Primer caso de leucemia mieloide aguda tratado en Cuba con altas dosis de antraciclinas en la inducción / First case of acute myeloid leukemia treated in Cuba using high doses of anthracycline in induction

La leucemia mieloide aguda abarca un heterógeneo espectro de enfermedades, de naturaleza maligna y clonal, que representan un reto formidable para la medicina moderna. Con la excepción de la leucemia promielocítica, los resultados terapéuticos alcanzados continúan siendo desalentadores. Recientemente han surgido datos que demuestran mejores resultados con el uso de altas dosis de antraciclinas en la inducción. Se presentó el primer caso en Cuba, en cuya inducción se utilizó la rubidomicina a 100 mg/m² por 3 d, más el arabinósido de citosina a 100 mg/m² por 7 d, ambos en infusión endovenosa continua. La evolución clínica es satisfactoria hasta el momento. Se revisó brevemente la literatura médica al respecto...

The acute myeloid leukemia includes an heterogeneous spectrum of diseases of malignant and clonal origin representing a challenge of the current medicine. With the exception of the pro-myelocytic, the achieved therapeutical results continue being discouraging. Recently are available data demonstrating better results with the use of high doses of anthracycline in the induction. This is the first case in Cuba where in induction it was used the 100 mg/m² rubidomicin plus 100 mg/m2 for three days plus 100 mg/m² arabinoside for seven days, both in continuous intravenous infusion. The clinical course is satisfactory until now. Authors made a brief review of medical literature in this respect...

A Case of del(16)(q22) in a Patient with Acute Myeloid Leukemia with Complex Karyotype / 대한진단검사의학회지

Inversion of chromosome 16 [inv(16)(p13.1q22)] and t(16;16)(p13.1;q22) are associated with acute myelomonocytic leukemia (AMML) with eosinophilia and a favorable prognosis. On the other hand, patients with del(16)(q22) usually present with MDS or chronic myelomonocytic leukemia (CMML), which can evolve to AMML without eosinophilia, and this chromosomal aberration is associated with older age, a complex karyotype, and a poor prognosis. We report a case of AML with del(16)(q22) which showed a complex karyotype, absence of eosinophilia in bone marrow study and a poor response to chemotherapy.

Relationship between In Vitro Chemosensitivity assessed with MTT Assay and Clinical Outcomes in 103 Patients with Acute Leukemia / 대한진단검사의학회지

BACKGROUND: Cellular drug resistance is supposed to play a major role in chemotherapy failure or relapse. The purpose of this study was to analyze the relationship between in vitro chemosensitivity test results using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clinical response on chemotherapy, and to find the possibility of optimizing the treatment protocol for individual patients according to their actual drug resistance. METHODS: For MTT assay, we obtained bone marrow aspirates from 103 patients with acute leukemia at the time of initial diagnosis or relapse. The following drugs were tested: cytarabine, vincristine, methotrexate, daunorubicin, dexamethasone, L-asparaginase, and mitoxantrone. To evaluate clinical responses after induction chemotherapy, we followed up on their bone marrow study. RESULTS: In our study, in vitro chemosensitivity test with the MTT assay significantly predicted whether patients with AML remained continuous complete remission or went into relapse. It also predicted whether or not child patients with ALL would acquire complete remission after induction chemotherapy. CONCLUSIONS: Although it does not provide the insight into the mechanisms that cause drug resistance, the MTT assay may be a useful tool in individually optimizing the chemotherapy of patients with acute leukemia.

Esquemas de quimioterapia y bacteriemias en pacientes adultos con leucemia aguda / Chemotherapy schedules and bacteremias in adult patients with acute leukemia

En un estudio efectuado para evaluar la utilidad de la profilaxis con fluoroquinolonas en pacientes neutropénicos afebriles, se encontró una asociación inesperada entre el esquema de poliquimioterapia utilizado y la posterior documentación de bacteriemias durante los episodios de neutropenia y fiebre. Se analizaron 25 episodios de neutropenia febril secundaria a quimioterapia antileucémica. Los pacientes recibieron etoposide y mitoxantrona o bien citarabina - en dosis estándar, intermedia o alta - asociada a daunomicina o mitoxantrona. El análisis de los datos microbiológicos demostró una mayor incidência de bacteriemias con el uso combinado de antraciclinas y citarabina en dosis intermedia o alta en comparación con la administración de etoposide y mitoxantrona (p = 0,000387). Ambos grupos de pacientes desarrollaron una neutropenia igualmente veloz y severa con una mucositis digestiva equivalente. El esquema de poliquimioterapia fue el único dato que se asoció con la aparición o no de bacteriemias en el episodio de neutropenia febril subsiguiente. Se concluye en que otros efectos - además de la aplasia medular y la mucositis digestiva - podrían ser relevantes en la susceptibilidad a las infecciones que originan los citostáticos.

O câncer infantil: caracterizaçäo da populaçäo atendida em um hospital-escola como subsídio para a assistência de enfermagem / Cancer in children: characterization of an university-hospital population as an AID to the nursing care

O presente estudo tem por objetivo descrever algumas características biológicas e clínicas de uma determinada populaçäo infantil afetada por neoplasias, a fim de subsidiar a assistência de enfermagem. Através da coleta de dados empíricos, realizada em um hospital-escola do município de Ribeiräo Preto-SP, evidenciamos que o câncer acomete mais frequentemente crianças menores de 10 anos de idade (84,5 por cento); a maioria (71,3 por cento) so sexo masculino; o diagnóstico mais frequente (56,3 por cento) foi leucemia; a terapêutica mais utilizada foi a quimioterapia , em associaçäo ou näo e os diagnósticos secundários foram os infecciosos, destacando-se a pneumonia, infecçäo de vias aéreas superiores, otite média aguda, amidalite e septicemia

Leucemía mieloide aguda en niños del Hospital Universitario de Caracas (Período 1979-1989) / Acute myeloid leukemia in children at the University Hospital of Caracas (period 1979-1989)

En el Hospital Universitario de Caracas 52 nuevos casos de Laucemia Mieloblástica aguda (LMA) fueron tratados en dos series consecutivas entre 1979-1989. Concomitantemente se intentó correlacionar los hallazgos clínicos y de laboratorio al ingreso, y la respuesta al tratamiento, con los subtipos morfológicos (FAB) de LMA. Serie I (1979-1985): comprendió 37 niños que recibieron principalmente la terapia de inducción con Citosina Arabinosa 100 mg/m2/día, en una infusión continua por 7 días, además de Daunomicina 45 mg/m2/día, en los 3 primeros días del tratamiento. La serie II incluyó solo 15 pacientes tratados en igual forma, excepto por la Citosina Arabinosa que se administró durante 10 días. Los pacientes que alcanzaron remisión en ambas series recibieron luego 5 ciclos con el esquema de COAP como terapia de consolidación. Posteriormente, fueron a un tratamiento de mantenimiento semanal con 6-Thioguanima por 4 días más Citosina Arabinosa el 5to. día durante 24 meses en remisión contínua. el tratamineto de inducción se realizó en 44 niños, dado que 7 murieron durante la fase de inducción en aplasia y otro caso se descartó por Síndrome de Down. La remisión completa fue de 64 por ciento (21/33) en la Serie I y de 36 por ciento (4/11) en la Serie II; observandose en ambas series un 42 por ciento de LMA con un componente monocítico, la mayoría del tipo M4 y 80 por ciento (20/25) de los casos que alcanzaron remisión, presentaban diferenciación mieloide FAB M1-M4. La duración de la remisión fué corta, lo que sugiere fallas en el tratamiento citotócico recayendo el 60 por ciento en los primeros 6 meses. La sobrevida libre de enfermedad fue menor de 20 por ciento al año y de sólo 6 por ciento a los 30 meses, sin diferencias estadísticas significativas en las 2 Series. Se estima que la problemática asistencial crónica de nuestro hospital pudo haber influido en la alta tasa de mortalidad temprana. Esta es la primera casuística de niños con LMA reportada en Venezuela

Uso de la quimioterapia alterno secuencial con Epidoxorubicina en la inducción de los linfomas No Hodgkin / Use of alternate sequencial chemoterapy with Epidoxorubicin in the induction of Non Hodgkin lymphomas

Entre Octubre 85 y Julio 87, 30 pacientes consecutivos con Linfoma No Hodgkin avanzado (estadíos III y IV) y de histología desfavorable fueron tratados con 2 regímenes de QT diferentes y sucesivos. Ninguno de los pacientes había recibido tratamiento previo y luego de administrarles 8 ciclos de inducción con el régimen CHOP-epidoxorubicina; a aquellos con RC se les consolidó con un esquema de poliquimioterapia con Ara C, VP16, vinblastina, BCNU prednisona. El objetivo era incrementar el porcentaje de RC y cura, alternando 2 esquemas consecutivos sin resistencia cruzada entre ellos. Un total de 28 pacientes son considerados aptos para evaluar la respuesta al tratamiento. Un estadiaje cuidadoso fué requerido para demostrar la respuesta. Con el régimen CHOP-epidoxo se obtuvieron 25 respuestas (89 por ciento) en total; de las cuales 19 fueron RC y 6 RP. La sobrevida promedio para aquellos que han cpmpletado la consolidación es de 38 meses post-QT de inducción y sólo 5 de 17 han presentado recurrencia. Mielotoxicidad importante fué observada en la fase de consolidación, presentándose un caso fatal se sepsis asociada a neutropenia. Un paciente tuvo que ser retirado de protocolo por cardiotoxicidad en la inducción y las náuseas y vómitos, así como la alopecía, fueron equiparables en ambas etapas del tratamiento

Las infecciones durante el tratamiento de inducción en la leucemia linfoide aguda (LLA): importancia de las medidas profilácticas / Infections during induction treatment in acute lymphoid leukemia (ALL): importance of prophylactic measures

Se realizó un estudio acerca de la importancia de las medidas generales en la prevención de las infecciones en el período de inducción de la remisión, en 82 niños con LLA. En 42 pacientes se utilizó el protocolo 1-LLA-79 que no incluía medidas generales profilácticas, y en 40 el esquema 1-LLA-84, en el que se administraron trimetropin-sulfamethoxazol, miconazol y medidas de aislamiento simple. Se demostró que las infecciones bacterianas, virales y, sobre todo, las micóticas, fueron menores en este último grupo. Se destaca la labor de la enfermera en el cumplimiento de estas medidas

Leucemia mielóide aguda complicando gestaçäo: relato de um caso / Acute myeloid leukemia pregnancy: a case repost

Os autores relatam o caso de uma paciente branca, de 23 anos, que foi internada na Clínica Obstétrica do Hospital Universitário Antonio Pedro com gestaçäo de 23 semanas, complicada com febre, tosse produtiva, petéquias, sangramento vaginal e palidez. Encaminhada à Hematologia Clínica, foi feito o diagnóstico de leucemia mielóide aguda, forma M3 (Promielocítica). A paciente foi tratada com Daunomicina, Arabinoside da Citosina, Prednisona, 6-Tioguanina, além de terapêutica suporte. Houve boa tolerância da paciente e do feto à quimioterapia. A evoluçäo fetal foi acompanhada por ultra-sonografia e tococardiografia. A leucemia näo remiu completamente, mas a evoluçäo clínica da doente era boa quando entrou em trabalho de parto entre a 32ª e 33ª semanas de gestaçäo, após ser submetida a procedimento obstétrico desnecessário. Deu a luz a um feto de sexo masculino que desenvolveu síndrome de angústia respiratória 40 minutos após o nascimento, que veio a falecer com 26 horas de vida. A necrópsia näo revelou anomalias congênitas macro ou microscópicas ou ainda lesöes atribuíveis ao uso dos quimioterápicos. A mäe faleceu no 12§ dia de pós-parto com sepse e graves manifestaçöes hemorrágicas conseqüentes ao recrudescimento de sua doença básica