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1.
Br J Haematol ; 189(4): 625-634, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32150650

RESUMO

The combined incidence of classical Philadelphia-negative myeloproliferative neoplasm (MPN) is 6-9/100 000 with a peak frequency between 50 and 70 years. MPN is less frequent in women of reproductive age. However, for essential thrombocythaemia (ET) in particular there is a second peak in women of reproductive age and 15% of polycythaemia vera (PV) patients are less than 40 years of age at the time of diagnosis. Thus these diseases are encountered in women of reproductive potential and may be diagnosed in pregnancy or in women being investigated for recurrent pregnancy loss. The incidence of MPN pregnancies is 3·2/100 000 maternities per year in the UK. The majority of data regarding Philadelphia-negative MPNs relates to patients with ET, for which the literature suggests significant maternal morbidity and poor fetal outcome; specifically maternal thrombosis and haemorrhage, miscarriage, pre-eclampsia, intrauterine growth restriction (IUGR), stillbirth and premature delivery as summarised in the recent systematic review and meta-analysis in Blood, 2018, 132, 3046. The literature for PV is more sparse but increasing and is concordant with ET pregnancy outcomes. The literature regarding primary myelofibrosis (PMF) is even more scarce. Treatment options include aspirin, venesection, low molecular weight heparin (LMWH) and cytoreductive therapy. Data and management recommendations are often extrapolated from other pro-thrombotic conditions or from ET to PV and PMF. Women of reproductive age with a diagnosis of MPN should receive information and assurance regarding management and outcome of future pregnancies. From pre-conceptual planning to the post-partum period, women should have access to joint care from an obstetrician with experience of high-risk pregnancies and a haematologist in a multidisciplinary setting. This paper provides an update with regards to Philadelphia-negative MPN in pregnancy, details local practise in an internationally recognised centre for patients with MPN and outlines a future research strategy.


Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Transtornos Mieloproliferativos/terapia , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez
2.
Rev. cuba. hematol. inmunol. hemoter ; 36(1): e1043, ene.-mar. 2020.
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1126546

RESUMO

Introducción: La leucemia mieloide crónica es un desorden clonal maligno de células madres hematopoyéticas pluripotentes que se caracteriza por la presencia del cromosoma Filadelfia, consecuencia de la traslocación cromosómica recíproca entre los brazos largos de los cromosomas 9 y 22. El resultado de esta alteración cromosómica es un gen de fusión que contiene las uniones b2a2 (e13a2) o b3a2 (e14a2). En la mayor parte de los casos, las células de la leucemia mieloide crónica expresan uno de los dos transcritos (b2a2 o b3a2); sin embargo, el 5 por ciento de los pacientes tienen ambos tipos de ARNm como resultado de empalmes alternativos. Se han encontrado otros transcriptos como e19a2, e2a2, e1a3, e6a2, e13a3(b2a3), y e14a3(b3a3), que ocurren con menos frecuencia. Objetivo: Describir el comportamiento de dos pacientes con leucemia mieloide crónica que presentan un trascripto BCR/ABL atípico. Casos clínicos: En el estudio molecular por reacción en cadena de la polimerasa cualitativo realizado a los dos pacientes, se observó un punto de ruptura del gen de fusión BCR/ABL poco frecuente, el cual se correspondía al transcripto e14a3 (b3a3). Estos pacientes iniciaron tratamiento con mesilato de imatinib a dosis de 400 mg diarios. Al primer paciente a los dos meses de tratamiento se le detectó crisis blástica, por lo que se le cambió el tratamiento a nilotinib 400 mg diarios que mantiene hasta la actualidad. La segunda paciente mantuvo igual tratamiento, aunque en ocasiones ha sido necesario incorporar tratamiento citorreductor con hidroxiurea por presentar leucocitosis. Conclusiones: Los pacientes con BCR/ABL a3 presentan un curso más benigno de la enfermedad. Aunque en los pacientes estudiados no se observó una respuesta satisfactoria al tratamiento pues presentaron diversas complicaciones(AU)


Introduction: Chronic myeloid leukemia is a malignant clonal disorder of pluripotent hematopoietic stem cells and characterized by the presence of the Philadelphia chromosome, which is the product of a reciprocal translocation between the long arms of chromosomes 9 and 22. The result of this chromosomal alteration is a fusion gene that contains the e13a2 (b2a2) and e14a2 (b3a2) junctions. In most cases, chronic myeloid leukemia cells express one of the two transcripts (b2a2 or b3a2); however, 5 percent of patients have both types of mRNA, as a result of alternative junctions. Other transcripts have been identified, such as e19a2, e2a2, e1a3, e6a2, e13a3 (b2a3), and e14a3 (b3a3), which occur less frequently. Objective: To describe the behavior of two patients with chronic myeloid leukemia who have an atypical BCR-ABL transcript. Clinical cases: In a qualitative molecular study of polymerase chain reaction carried out with two patients, a BCR-ABL fusion gene breakpoint was observed, which corresponded to the e14a3 (b3a3) transcript. These patients started treatment with imatinib mesylate at a dose of 400mg/d. At two months, the first patient had a diagnose of blast crisis, so the treatment was changed to nilotinib at a dose of 400mg/d, which the patient maintained to date. The second patient maintained the same treatment, although it was sometimes necessary to incorporate cytoreductive treatment with hydroxyurea due to leukocytosis. Conclusions: Patients with BCR-ABL a3 present a more benign evolution of the disease. However, a satisfactory response to treatment was not observed in the patients studied, as long as they presented various complications(AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Cuba
4.
Rinsho Ketsueki ; 61(2): 128-130, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32147612

RESUMO

A 64-year-old male presented with a rapidly growing anterior mediastinal mass during the clinical course of atypical chronic myeloid leukemia. A needle biopsy performed for suspected myeloid sarcoma revealed the presence of Aspergillus abscess. Early diagnosis of mediastinal abscesses, which are associated with a high mortality rate, can prevent the progression of severity. Infectious abscesses should be considered for prompt qualitative diagnosis in patients with mediastinal masses. Thymoma, germ cell tumor, and malignant lymphoma are the most common anterior mediastinal tumors, whereas infectious abscesses should also be considered when myeloid sarcoma is suspected in patients with an underlying myeloid tumor.


Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Neoplasias do Mediastino , Timoma , Neoplasias do Timo , Abscesso , Aspergillus , Humanos , Masculino , Pessoa de Meia-Idade
5.
Intern Med ; 59(12): 1549-1553, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32188810

RESUMO

Patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) are often asymptomatic and thus can remain undiagnosed until they become symptomatic due to progression to the accelerated phase (AP) or transformation to acute leukemia (leukemic transformation; LT). We herein report the case of a previously healthy 38-year-old man who had hyperleukocytosis with dysplastic myeloid precursor cells and severe disseminated intravascular coagulation. Hematopoietic recovery with features of atypical chronic myeloid leukemia (aCML) after induction chemotherapy was a diagnostic clue. Although rare, this case highlights the limitation of the diagnostic approach for aCML with AP or LT at the initial presentation.


Assuntos
Coagulação Intravascular Disseminada/complicações , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/complicações , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Adulto , Antineoplásicos/uso terapêutico , Humanos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Leucocitose/complicações , Masculino
7.
Rinsho Ketsueki ; 60(11): 1538-1543, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31839631

RESUMO

A 61-year-old man was admitted to our hospital with fever and massive leukocytosis. A bone marrow smear revealed an increased density of myeloid cells in various stages of maturation as well as dysplasia in the neutrophils. There was no proliferation of blasts, eosinophils, or basophils. Genomic analysis of the bone marrow cells revealed no detectable abnormalities associated with myeloproliferative neoplasms, including BCR-ABL1. Therefore, the patient was diagnosed with atypical chronic myeloid leukemia (aCML). Chromosomal analysis revealed the presence of 1-17 double minute chromosomes (dmin) in 20 of 20 tumor cells examined. Multiple MYC signals were detected via interphase fluorescence in situ hybridization, indicating MYC gene amplification in the dmins. Three months after the oral administration of hydroxyurea, leukocytosis reoccurred. Therefore, induction therapy followed with umbilical cord blood transplantation was performed. However, MYC signals remained detectable in the bone marrow sample obtained immediately after neutrophil engraftment, indicating the presence of residual tumor cells. To the best of our knowledge, this is the first case report of aCML with dmin gene amplification, suggesting that the dmin MYC amplification exacerbated the patient's disease.


Assuntos
Amplificação de Genes , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Medula Óssea , Aberrações Cromossômicas , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade
9.
Cancer Genet ; 238: 44-49, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31425925

RESUMO

Emergence of clonal chromosomal abnormalities in Philadelphia chromosome-negative (CCA/Ph-) cells in chronic myeloid leukemia (CML) patients during the treatment with tyrosine kinase inhibitors (TKIs) is an interesting phenomenon. Although previous studies revealed some potential impact of CCA/Ph- on CML patients' outcome, clinical significance of CCA/Ph- in CML patients remains to be further elucidated. We retrospectively reviewed the patients with CML evaluated at Genoptix Medical Laboratory in Carlsbad, California from 2005 to 2015. Twenty-four CML patients with CCA/Ph- cells were identified. These include 18 patients with single chromosomal abnormality, 4 patients with double chromosomal abnormalities, and two patients with complex cytogenetic abnormalities. In addition to trisomy 8 and monosomy 7, we identified that 20q- was also a common abnormality in CCA/Ph- cells. Most of the patients with CCA/Ph- cells demonstrated no significant dysplasia or increased blasts with two exceptions: one patient with persistent 7q- exhibiting mild dysmegakaryopoiesis, suggestive of an early evolving myelodysplastic syndrome, and another patient with complex cytogenetic abnormalities who developed acute myeloid leukemia after gained MLL amplification. One patient with complex cytogenetic abnormalities showed optimal response to TKI treatment, no overt dysplasia, and no disease progression during almost 4-years of follow-up. More interestingly, FISH tests could identify more cases with double chromosomal abnormalities and these cases showed suboptimal responses to TKI treatments. Our observation indicates that 20q- was also a common abnormality in CCA/Ph- cells, further FISH tests revealed additional CCA/Ph-, and the majority of CML patients with two or more chromosomal abnormalities in Ph- cells showed inferior response to TKI treatments. The results of our study suggest that CML cases with CCA/Ph- may represent a group of patients with heterogeneous genetic alterations.


Assuntos
Aberrações Cromossômicas , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Masculino , Pessoa de Meia-Idade
12.
BMC Med Genet ; 20(1): 115, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248375

RESUMO

BACKGROUND: Calreticulin (CALR) gene mutations are currently recommended as biomarkers in diagnosis of patients with myeloproliferative neoplasms (MPN) with Jak2 V617F negative phenotype. Our aim was to establish a rapid, low cost and sensitive assay for identification of CALR gene mutations and to validate the diagnostic performance of the established assay in a patient cohort with different clinical MPN phenotypes. METHODS: One hundred five Philadelphia-negative MPN patients, including polycythemia vera (PV), essential thrombocythaemia (ET), and primary myelofibrosis (PMF) were initially screened for JAK2 mutations by amplification-refractory mutation system (ARMS-PCR) methodology and were further subjected to detection of CALR gene mutations by our in-house assay, a PCR based amplicon length differentiation assay (PCR-ALDA). The PCR-ALDA methodology was compared with real time PCR and Sanger sequencing methods. Furthermore, the analytical sensitivity of the assay was established. RESULTS: PCR - ALDA approach was able to detect and discriminate the pseudo-positive samples containing more than 1% CALR mutant alleles. CALR mutations were not detected in 63 Jak2 V617F positive cases in all three methods. In contrast, amongst 42 Jak2 V617F negative cases, both PCR-ALDA and Sanger sequencing coherently identified 12 CALR mutants compared to 10 CALR mutants detected by real-time PCR method. CONCLUSION: PCR-ALDA can be utilized as an easy-to-use, rapid, low cost and sensitive tool in the detection of CALR mutations in Philadelphia-negative MPN patients.


Assuntos
Calreticulina/genética , Mutação , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Reação em Cadeia da Polimerase em Tempo Real , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Biomarcadores Tumorais , Análise Custo-Benefício , Feminino , Técnicas de Genotipagem/métodos , Humanos , Janus Quinase 2/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Masculino , Pessoa de Meia-Idade , Fenótipo , Policitemia Vera , Mielofibrose Primária , Reação em Cadeia da Polimerase em Tempo Real/economia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Trombocitemia Essencial , Adulto Jovem
13.
Hematol Oncol ; 37(3): 291-295, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31050810

RESUMO

There have been some reports on a possible role of azacytidine (AZA) in the treatment of accelerated/blastic phase evolved from Philadelphia-negative myeloproliferative neoplasms (MPN-AP/BP), but results are conflicting. In this study, we analyzed a cohort of 39 patients with MPN-AP/BP treated frontline with AZA at the standard dosage (75 mg/m2 ). Median time from diagnosis to AP/BP evolution was 92.3 months (IR 29.9-180.1). All patients were evaluable for hematologic response: two patients (5.2%) died early after AZA initiation, 13 patients (33.3%) had a progressive or stable disease, nine (23.1%) had a hematologic improvement (HI), seven (17.9%) achieved a partial response (PR), and eight (20.5%) a complete response (CR). Overall, 24 patients achieved a clinical hematologic response (HI + PR + CR), with an overall response rate of 61.5%. Median overall survival (OS) from AZA start of the whole cohort was 13.5 months (95% CI, 8.2-18.7). There was no difference in median OS among patients with HI, PR, or CR (P = .908). These three subgroups as "responders" having been considered, a significantly better OS was observed in responder compared with nonresponder patients, with a median OS of 17.6 months (95% CI, 10.1-25.0) versus 4.1 months (95% CI, 0.4-10.0) (P = .001) Only female gender was significant for both achievement of response (.010) and OS duration (P = .002). In conclusion, AZA is useful for the management of MPN-AP/BP, with an overall response rate (HI + PR + CR) of 61.5% and a longer OS in responders.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Crise Blástica/tratamento farmacológico , Transtornos Mieloproliferativos/tratamento farmacológico , Idoso , Crise Blástica/diagnóstico , Feminino , Humanos , Hidroxiureia/uso terapêutico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Masculino , Melfalan/uso terapêutico , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/diagnóstico , Pipobromano/uso terapêutico , Policitemia Vera/diagnóstico , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/diagnóstico , Mielofibrose Primária/tratamento farmacológico , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Resultado do Tratamento
16.
Blood Rev ; 33: 74-81, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30078497

RESUMO

Atypical chronic myeloid leukemia (aCML) is a BCR-ABL1 negative myelodysplastic (MDS)/myeloproliferative (MPN) neoplasm with poor overall survival. The current 2016 WHO classification of myeloid neoplasms allows clinicians to more accurately differentiate aCML from its similar MDS/MPN overlap and MPN counterparts. In addition, the advent of next-generation sequencing has expanded our understanding of the molecular pathogenesis of aCML and its therapeutic potential. Hematopoietic stem cell transplant (HSCT) remains the first consideration in the treatment algorithm for aCML, however, with the advances in mutational analysis, opportunities for targeted therapy have expanded. In this review, we highlight the current classification, diagnostic criteria, and molecular pathogenesis of aCML. We also discuss the therapeutic implications of the heterogeneous molecular fingerprint of aCML focusing on emerging targeted therapies, specifically ruxolitinib, dasatinib, and trametinib. Future disease management will rely on clinical trial development focused on new mutational drug targets, combination therapies, and signaling pathway dysregulation.


Assuntos
Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/etiologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Suscetibilidade a Doenças , Humanos , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/terapia , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/terapia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptores de Fator Estimulador de Colônias/genética , Receptores de Fator Estimulador de Colônias/metabolismo
17.
Lima; IETSI; 2019.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1014985

RESUMO

INTRODUCCIÓN: El presente dictamen expone la evaluación de la eficacia y seguridad de blinatumomab; comparado con quimioterapia de rescate (metotrexato, vincristina, etopósido) para el tratamiento de pacientes con diagnóstico de leucemia linfoblástica aguda de precursores de células B, Philadelphia negativo, que hayan recaído o cuya enfermedad haya sido refractaria al tratamiento. La leucemia linfoblástica aguda (LLA) es una neoplasia maligna con proliferación de células precursoras linfoides. Solo el 20 % de las LLA se presentan en adultos. En pacientes de 25 a 59 años de edad, la sobrevida es, aproximadamente, 40 % y en adultos mayores es menor al 20 %. Pueden identificarse tres tipos de LLA: de linaje ambiguo, de células B (LLA-B) y de células T. La LLA-B es el tipo más frecuente (80-85 % de los casos). El pronóstico de los pacientes con LLA-B empeora con la presencia de alteraciones genéticas, como la translocación BCR/ABL; también llamado: cromosoma Philadelphia (Ph) y en los casos recurrentes y/o refractarios (R/R). Estos pacientes requieren de tratamientos más agresivos para lograr la remisión. No obstante, la curación y la sobrevida libre de enfermedad a largo plazo es posible en menos del 25 % de los casos y las remisiones son de corta duración. TECNOLOGÍA SANITARIA DE INTERÉS: Blinatumomab es un anticuerpo bi-específico de células T desarrollado para el tratamiento de neoplasias hematológicas originadas en el linaje de células B, especialmente en casos de LLA-B y linfoma no Hodgkin (Sanford M. 2015) . Aunque al momento de su aparición blinatumomab fue considerado un medicamento revolucionario, se advierte el riesgo de complicaciones potencialmente fatales, como: neutropenia, infecciones, síndrome de liberación de citoquinas o toxicidad neurológica. OBJETIVO: Evaluar la eficacia y seguridad del uso de blinatumomab, en comparación con quimioterapia de rescate en pacientes con LLA-B, Ph(-) en recaída y/o refractario. METODOLOGÍA: Se llevó a cabo una búsqueda sistemática de la literatura con respecto a la eficacia y seguridad de blinatumomab en el tratamiento de pacientes con diagnóstico de leucemia linfoblástica aguda de precursores de células B, Philadelphia negativo, en recaída y/o refractario. Se realizó tanto una búsqueda sistemática como una búsqueda manual en las páginas web de grupos dedicados a la investigación y educación en salud que elaboran guías de práctica clínica (GPC) y evaluaciones de tecnologías sanitarias (ETS). RESULTADOS: La presente evaluación de tecnología sanitaria muestra la evidencia encontrada luego de una búsqueda sistemática, con respecto a la eficacia (sobrevida global, remisión completa de enfermedad, y calidad de vida) y seguridad (incidencia de eventos adversos) de blinatumomab, comparado con quimioterapia de rescate en pacientes adultos con LLA-B, Ph(-) R/R. Al respecto, se identificaron dos guías de práctica clínica (GPC) elaboradas por la European Society for Medical Oncology (ESMO) en 2016 y la National Comprehensive Cancer Network (NCCN) en 2019; tres evaluaciones de tecnologías sanitarias (ETS) elaboradas por la Canadian Agency for Drugs and Technologies in Health (CADTH) en 2016, el Scottish Medicines Consortium (SMC) en 2016 y el National Institute for Health and Care Excellence (NICE) 2017; y, tres publicaciones de los años 2017 y 2018 del ensayo clínico aleatorizado (ECA) fase III TOWER; los cuales responden directamente a la PICO establecida en el presente dictamen. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se presenta la evidencia recabada sobre la eficacia y seguridad blinatumomab en comparación con la quimioterapia de rescate en pacientes adultos con LLA-B, Ph(-), R/R. Se recolectó la evidencia de dos GPC, tres ETS y un ECA fase III. Aunque las GPC y las ETS recomiendan blinatumomab para el tratamiento de pacientes adultos con LLA-B, Ph(-), R/R, la confianza en la evidencia utilizada para formular esta recomendación está limitada por: i) la poca cantidad de evidencia primaria disponible: dos ECA fase II (MT 103-211 y MT 103-206) y un ECA fase III (TOWER), ii) los detalles de las recomendaciones de las GPC y ETS difieren entre sí a pesar de provenir prácticamente de la misma evidencia, iii) El ECA TOWER (principal estudio para responder la pregunta PICO) presenta varias limitaciones que afectan la validez de sus resultados, y, iv) la incertidumbre en la evidencia disponible solo logra que blinatumomab sea considerado por las ETS solo como una alternativa de tratamiento (por debajo de la participación de EC de nuevos medicamentos) sujeta a acuerdos económicos (para el caso de las ETS) que mejoren su costo-efectividad. Con respecto a lo expuesto previamente, el equipo técnico del IETSI valoró los siguientes aspectos: i) La LLA-B es una enfermedad de mal pronóstico cuando se presenta en adultos y empeora en los casos R/R, ii) La evidencia disponible no asegura que la magnitud de la eficacia de blinatumomab se traduzca en un cambio clínicamente relevante, iii) Toda vez que blinatumomab ha sido recomendado por las ETS, es bajo la condición de reducir del precio de compra blinatumomab a niveles de costo-efectividad aceptables, y, iv) No es posible asumir un perfil de costo-oportunidad favorable para sistemas públicos de servicios de salud como el nuestro porque no se ha encontrado que blinatumomab sea más eficaz o seguro que otros esquemas de quimioterapia de rescate disponibles en EsSalud. Se queda a la espera de futuras publicaciones con mayor tiempo de seguimiento y que superen las limitaciones presentes en la evidencia disponible hasta la fecha. El Instituto de Evaluación de Tecnologías en Salud e Investigación - IETSI, no aprueba el uso de blinatumomab para el tratamiento de pacientes adultos con LLA-B, Ph(-), R/R.


Assuntos
Humanos , Anticorpos Antideltaretrovirus/uso terapêutico , Leucemia Aguda Bifenotípica/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Análise Custo-Eficiência
18.
Zhonghua Xue Ye Xue Za Zhi ; 40(7): 547-553, 2019 Jul 14.
Artigo em Chinês | MEDLINE | ID: mdl-32397016

RESUMO

Objective: To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph(-) MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph(+) CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph(-)) during tyrosine kinase inhibtor (TKI) - therapy. Methods: We retrospectively analyzed Ph(+) CML patients who developed CCA/Ph(-) during TKI-therapy from May 2001 to December 2017. Results: Data of CCA/Ph(-) 63 patients, including 7 progressing to Ph(-) MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph(-)MDS/AML had lower hemoglobin (P=0.007) and platelet (P=0.006) counts, and higher proportion of peripheral blasts (P<0.001) when the first time CCA/Ph(-) was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed; meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph(-) MDS/AML were poor. However, most of those with CCA/Ph(-) and stable disease had optimal response on TKI-therapy. Conclusions: A few patients with Ph(+) CML developed CCA/Ph(-) during TKI-therapy, most of them had stable disease, but very few patients developed Ph(-) MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/tratamento farmacológico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/fisiopatologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Humanos , Cromossomo Filadélfia , Estudos Retrospectivos
19.
Leuk Res ; 75: 50-57, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30458320

RESUMO

Atypical chronic myeloid leukemia (aCML) and chronic neutrophilic leukemia (CNL) are rare BCR-ABL1 fusion gene-negative myeloid neoplasms with a predominance of neutrophils. Since no standard therapeutic strategy currently exists for these diseases, we retrospectively evaluated the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for aCML and CNL. Data from 14 aCML and 5 CNL patients as their diagnoses were collected using a nationwide survey. Allo-HSCT was performed between 2003 and 2014. Preconditioning regimens included myeloablative (n = 15), reduced-intensity (n = 3), and non-myeloablative (n = 1) regimens. Transplanted stem cells were obtained from HLA-matched related donors (n = 5) and alternative donors (n = 14). Neutrophil engraftment was successfully achieved in 17 patients. One-year overall survival rates (OS) were 54.4% (95% confidence interval [CI], 24.8 to 76.7%) and 40.0% (95% CI, 5.2 to 75.3%) in patients with aCML and CNL, respectively. Among aCML patients, 1-year OS were 76.2% (95% CI, 33.2 to 93.5%) and 20.0% (95% CI, 0.8 to 58.2%) in patients with <5% myeloblasts (n = 9) and ≥5% myeloblasts (n = 5) in peripheral blood before allo-HSCT, respectively. These results suggest that allo-HSCT achieves long-term survival in patients with aCML and CNL. Better pre-transplant management is required to improve the outcomes of aCML patients with ≥5% blasts in peripheral blood.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/terapia , Leucemia Neutrofílica Crônica/terapia , Adolescente , Adulto , Idoso , Criança , Intervalo Livre de Doença , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/mortalidade , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/patologia , Leucemia Neutrofílica Crônica/mortalidade , Leucemia Neutrofílica Crônica/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
20.
Indian J Pathol Microbiol ; 61(3): 371-374, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30004057

RESUMO

Background: : It is still a matter of debate regarding the association of JAK2V617F mutation with thrombosis in BCR-ABL negative CMPN patients. The role of JAK2V617F mutation in increasing the thrombotic risk in CMPNs is yet unequivocal. Aims: : To clarify the contribution of JAK2V617F mutation in thrombosis in CMPN patients. Settings and Design: This retrospective study was done to evaluate role of JAK2V617F mutation in thrombosis in CMPNs. Materials and Methods: 65 CMPN patients (PV, ET and PMF) were analyzed for JAK2V617F mutation using ARMS-PCR and detailed history of thrombosis was recorded in these patients. Statistical Analysis: P values were 2 tailed, and statistical significance was set at P < 0.05. Results: : 46/65 were males and 19/65 were females [M: F: 2.4:1] with median age 46 years [range, 14-80 years]. Patients had median Hb 15.6 g/dl [range, 5.1-20.3], median TLC 10.7 × 109/l [range 2.4-216] and platelet count 360 × 109/l [range, 20-1859]. 32 were JAK2V617F positive and 33 were negative for this mutation. On comparing the prevalence of thrombosis in JAK2V617F positive patients with JAK2V617F negative patients, we observed that 20/32 (62.5%) JAK2V617F positive patients had thrombosis as compared to 16/33 (48%) in JAK2V617F negative patients (P = 0.04). We observed significant association of JAK2V617F mutation with thrombosis, however no association of this mutation with thrombosis was observed among the JAK2V617F negative patients. Conclusion: Our study suggests that JAK2V617F mutation may increase the risk of thrombosis in CMPNs. This finding could lead to risk stratification, setting up the treatment strategy in CMPNs.


Assuntos
Estudos de Associação Genética , Janus Quinase 2/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Mutação , Trombose/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Índia/epidemiologia , Janus Quinase 2/sangue , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/sangue , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/genética , Estudos Retrospectivos , Trombose/epidemiologia , Adulto Jovem
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