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Copyright of Acta Medica Colombiana is the property of Acta Medica Colombiana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Splenic infarction is a rare cause of acute abdomen. The two main causes are thromboembolic diseases and infiltrative hematological disorders. The splenic abscess is the result of a hematogenous seeding, whose causes are trauma, splenic artery embolization, endocarditis, and immunocompromised states. Clinical case: 48-year-old male patient with a history of chronic myelomonocytic leukemia on mercaptopurine-based treatment, who presented intermittent asthenia, adynamia, and abdominal distension for 2 months; a computed tomography of the abdomen with intravenous contrast was performed, reporting areas of infarction and an image suggestive of a splenic abscess in the upper pole, for which an open splenectomy was performed with adequate clinical evolution. A documentary review of the disease and of the therapeutic options was carried out, with an emphasis on surgical management. Conclusion: The main cause of morbidity and mortality in the case presented was splenic infarction, which is aggravated by the presence of hematological diseases; therefore, the identification of those patients at risk of complications will allow in a timely manner a diagnostic and therapeutic approach, and the detection of those who require urgent surgical management. [ABSTRACT FROM AUTHOR]

Introduction: Rectus sheath hematoma is a rare entity. This report presents a clinical case of a rectus sheath hematoma in a patient with COVID-19 pneumonia and chronic myeloid leukemia, along with a review of the literature. Case Report: A 55-year-old male patient, hospitalized for COVID-19 pneumonia and chronic myeloid leukemia, presents with tachycardia and hypotension. Computed tomography shows a rectus sheath hematoma. Surgical management was performed to control bleeding and drainage of the hematoma. There were no postoperative complications or need for reoperation. Discussion: Hemorrhagic complications in patients with COVID-19 are seldomly reported. Bleeding is a possible complication in patients with chronic myeloid leukemia. It is important to take into account rectus sheath hematoma in patients with COVID-19 and/or chronic myeloid leukemia who present with abdominal pain, for early management by a multidisciplinary team. Conclusion: Active surveillance and a high index of suspicion are key to identifying potential bleeding complications in patients with COVID-19 and/or chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

Descobertas recentes sobre a atividade do gene quimérico BCR/ABL têm auxiliado na elucidação de diversos mecanismos envolvidos na gênese e progressão da leucemia mieloide crônica (LMC). Apesar de a LMC ser ainda, uma doença incurável para os pacientes que não podem submeter-se a um transplante alogênico de medula óssea, a sobrevida geral tem aumentado progressivamente, devido especialmente a medidas capazes de prolongar a fase crônica. A técnica de reação da polimerase em cadeia (PCR) para a detecção do gene quimérico BCR/ABL tem sido um teste bastante valioso para a identificação de casos Philadelphia negativos que apresentam o rearranjo genético ao nível molecular e para a detecção de doença residual mínima, especialmente em indivíduos transplantados. Novas formas de tratamento devem traduzir-se em maior sobrevida nos próximos anos quando utilizadas em estágios precoces da doença: transplante autólogo de células-tronco com células mobilizadas e coletadas após quimioterapia em altas doses, o uso de interferon e a terapia gênica. O interferon já é a droga de escolha para o tratamento da maioria dos pacientes. O transplante autólogo é um procedimento promissor que tem sido aplicado por vários centros como uma alternativa ao transplante alogênico. Os resultados de diferentes estratégias de terapia gênica têm sido desapontadores até o momento, mas a melhoria tecnológica neste campo do conhecimento será extremamente interessante para o tratamento da LMC, considerando-se o papel biológico central do gene BCR/ABL nas células malignas.

Copyright of Health Sciences Journal / Revista Ciências em Saúde is the property of Hospital de Clinicas de Itajuba - Associacao de Integracao Social de Itajuba and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objetivo: A Leucemia Mielóide Crônica (LMC) é um distúrbio clonal de células progenitoras hematopoiéticas, caracterizada por uma translocação recíproca entre os cromossomos 9 e 22, que resulta no gene híbrido BCR-ABL1.Mesmo com o progresso no tratamento da doença permitido pelos inibidores de tirosina quinase, mutações pontuais no domínio desse gene são as principais causas de resistência terapêutica, principalmente ao mesilato de imatinibe. O objetivo desse estudo foi analisar as mutações pontuais de alta resistência em paciente com LMC e sua possível correlação com a resposta ao tratamento. Métodos: Estudo transversal com 58 pacientes com LMC em tratamento com imatinibe e com resposta subótima à terapia. As amostras de sangue foram analisadas por PCR em tempo real usando a química TaqMan® para avaliar as seguintes mutações pontuais: T315I, E255V e Y253H. Resultados: Nenhum dos 58 pacientes apresentou alguma das mutações investigadas. Houve uso irregular da medicação em 16% (n = 9), dos quais 44% (n = 4) relataram uso descontínuo e interrupção por conta própria, e 56% (n = 5) apresentaram intolerância ao tratamento e trocaram de fármaco. Conclusão: A ausência das mutações pontuais nos pacientes portadores de LMC analisados neste estudo demonstrou que a falha na terapia não tem correlação molecular com as mutações analisadas e pode estar relacionada à menores taxas de adesão ao tratamento. Estes achados foram demonstrados em um número considerável de pacientes avaliados, apontando a necessidade da edução sobre a importância de seguir as recomendações sobre seu tratamento para evitar complicações futuras.

Se presenta el caso de un paciente con antecedente de Leucemia Mieloide Crónica (LMC) llevado a trasplante alogénico de precursores hematopoyéticos, en el día 10 postoperatorio refiere dificultad respiratoria y empeoramiento de clase funcional además de picos febriles de 38.9, al examen físico presencia de soplo holosistólico en focos de la base, realizan hemocultivos con reporte positivo de S. choleraesuisen 4 de 4, se toma ecocardiograma transesofágico donde se evidencia vegetación en válvula aórtica -valva semilunar posterior (no coronaria) de 12 mm filiforme sin condicionamiento de fracción de eyección -, por estabilidad clínica del paciente sin evidencia de compromiso hemodinámico se decide manejo médico con quinolonas por 4 semanas, logrando desaparición de la vegetación y del soplo a la semana de tratamiento médico y negativización de hemocultivos posteriores.

Tyrosine kinase inhibitors, used as the first line for treating chronic myeloid leukemia (CML)-Philadelphia chromosome positive, have been associated with the development of cutaneous adverse effects, where lesions compatible with psoriasis have been described. We present the case of a 55-year-old man with a history of CML-Philadelphia chromosome positive, with no personal or family history of psoriasis. However, he developed plaque psoriasis 2 years after starting treatment with this group of medications (imatinib and dasatinib). A narrative review of the literature on psoriasis triggered by tyrosine kinase inhibitors was conducted, and other cutaneous adverse effects probably caused by these drugs are described. [ABSTRACT FROM AUTHOR]

Copyright of Gaceta Médica de Caracas is the property of Academia Nacional de Medicina and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Latinoamericana de Hipertension is the property of Revista Latinoamericana de Hipertension and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: Chronic myeloid leukemia is a myeloproliferative disease; the most effective drugs in the treatment of this disease are imatinib, nilotinib and dasatinib. Those drugs are available at the ISSSTE. OBJECTIVES: To know the number of chronic myeloid leukemia cases, to identify the clinical characteristics and to measure the degree of response to tyrosine kinase inhibitors and the survival. MATERIAL AND METHOD: A retrospective, cross-sectional, observational and explanatory study was done from 2005 to 2016, including patients over 18 years of age, with a diagnosis of chronic myeloid leukemia; with any of the three phases of the disease and treatment with any of the tyrosine kinase inhibitors. RESULTS: There were included 31 cases (55.2% women); the median age was 62 years; 72.4% were in chronic phase, 27.6% in accelerated phase and none in the blast phase. The haematological response was of 94.1%, 90% and 96%; the complete cytogenetic response at 12 months was of 69.2%, 60% and 57% and the mayor molecular response was of 62.9%, 68.6%, 69.1% of the patients treated with imatinib, nilotinib or dasatinib, respectively. Disease-free survival at 5 years was of 83% and global survival at 5 years was of 94%. CONCLUSION: Independently of the inhibitor prescribed, the hematologic response is achieved in more than 90%, the complete cytogenetics around 60% at 12 months and major molecular almost 60% in a ISSSTE hospital. [ABSTRACT FROM AUTHOR]

Background: The HLA complex is involved in the pathogenesis of leukemia. Objectives: The presence of class II HLA alleles DRB1 *, DQB1 *, DPA1 *, and DPB1 * was evaluated in 47 patients with acute lymphoblastic leukemia (ALL) and 48 with chronic myeloid leukemia (CML) for comparison with 48 healthy volunteers in Zulia, Venezuela, and to evaluate potential associations of HLA with leukemia. Methods: Low- and high-resolution PCR-SSP was used for class II HLA regions DRB1 *, DQB1 *, DPA1 *, and DPB1 * following the instructions of KIT Olerup SSP Genovision. Results: Alleles HLA-DRB1*14, especially DRB1*14:21, -DPA1*1:06, -DPA1*01:03,-DPA1*02:01, and the haplotypes HLA-DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*99:01, -DRB1*14-DPA1*01:03, -DRB1*15-DPA1*01:03 were associated with CML (RR > 3); alleles HLA-DRB1*13, -DQB1*02, -DPA1*01:05, -DPA1*01:09 and the haplotypes HLA-DPA1*01:09-DPB1*02:01, DPA1*01:09-DPB1*04:01 were protective (RR < 1). Alleles HLA-DQB1*04, -DQB1*05, -DPA1*1:06, -DPA1*01:07, -DPA1*1:08 had a positive association with ALL. Alleles HLA-DPA1*01:09, -DPA1*02:01, -DPB1*02:01, -DPB1*03:01 and the haplotypes HLA-DPA1*01:03-DPB1*04:02, -DPA1*01:09-DPB1*02:01, -DPA1*01:09-DPB1*04:01, -DPA1*02:01-DPB1*04:02 were negatively associated. Conclusions: The absence of associations with HLA-DRB1 * region in ALL and other association patterns identified suggest marked differences in the pathogenesis of leukemia, which suggests possible deficiencies in antigen presentation for ALL or potential effects of molecular mimicry in CML.

Background: A possible interaction between a specific HLA type and Adenovirus has been postulated as a promoter in leukemia clonal evolution. The HLA-DRB1*14, specifically DRB1*14:21, 14:22, 14:45, 14:26, 14:33, 14:51, 14:35 subtypes was the most frequent in CML venezuelan patients. Objectives: It is interesting to evaluate the molecular mimicry between the Adenovirus and the DRB1*14 subtypes which exhibit the same change in the amino acid position of the DR53 epitope. This mimicked segment has been identified as a LLERRRA polypeptide. Material and methods: Experimental research conducted in the IHO Venezuela, in peripheral blood samples of patients with ALL, CML and healthy controls. Mixed culture, serology, lymphocyte proliferation and cytofluorometry were performed. Results: DRB1*14 patient’s lymphocytes reacted in 48 hours mixed culture against DRB1*14 promoters lymphocytes exhibiting increased CD8+T lymphocytes. CML patients show a different serological profile against Adenovirus. Only CML patients reacted to LLERRRA peptide, increasing CD8+ T cells. Conclusion: It is established that the relationship CML, HLA-DRB1*14, autoreactive CD8+ T memory cell and CD8+T specific response from Adenovirus could be at the origin of the CML in venezuelan.

Introducción: la leucemia mieloide crónica (LMC) se caracteriza por la presencia del cromosoma Filadelfia (Ph) que resulta de la translocación recíproca balanceada t(9;22)(q34;q11); este marcador cromosómico se encuentra con menor frecuencia en pacientes con leucemia linfoide aguda (LLA). Objetivo: determinar la frecuencia de las fusiones génicas BCR-ABL, que codifican para los transcriptos p210BCR-ABL y p190 BCR-ABL en pacientes colombianos con diagnóstico de LMC, en diferentes fases de la enfermedad o de su tratamiento. Materiales y métodos: estudio descriptivo de corte transversal de 31 pacientes con LMC (15-78 años). El análisis se hizo a partir de muestras de sangre periférica con la técnica PCR anidada cualitativa para las isoformas P210 BCR-ABL (b3a2 e b2a2) y P190 BCR-ABL (e1a2). Resultados: se detectó el transcripto p210BCR-ABL en 29 de los 31 casos (93,6%). En ellos se identificaron las fusiones génicas b2a2 (16/29; 55,2%), b3a2 (10/29; 34,5%) y la coexpresión b3a2 y b2a2 (3/29; 10,3%). Conclusión: la fusión génica b2a2 fue la más frecuente en esta población con LMC.

O artigo analisa as experiências de enfermidade de pacientes com leucemia mieloide crônica (LMC), centrando nas dimensões que apontam a chegada da doença como uma ruptura biográfica. Este estudo qualitativo baseou-se na análise das narrativas de seis pacientes, com idades entre 23 e 62 anos, usuários do Sistema Único de Saúde (SUS) e pacientes de um hospital – centro de referência em atenção hematológica na cidade de Salvador, Bahia, Brasil. Nos resultados apresenta-se a experiência de ruptura com base em três categorias (1) os significados da doença e a LMC como ameaça; (2) rupturas físicas, sociais e as experiências estigmatizantes; (3) a percepção de um “antes” e um “depois” da LMC, apontando para as mudanças no self, nas relações sociais e na vida cotidiana. Concluiu-se que os impactos biográficos, sociais e dos sistemas de saúde (considerando o custo das medicações) atualizam e ampliam questões como o acesso a tratamentos, assim como o enfrentamento do certo e do incerto, em que o “conhecido” da LMC encontra-se pouco acessível ao estoque de conhecimento da vida cotidiana.

Introduction: Chronic myelogenous leukemia (CML) is characterized by the presence of the Philadelphia chromosome (Ph), resulting from the balanced reciprocal translocation t(9;22)(q34;q11). This marker chromosome is found less frequently in patients suffering from acute lymphoblastic leukemia. Objective: To determine the frequency of BCR-ABL gene fusions encoding the p210BCR-ABL y p190 BCR-ABL transcripts in Colombian patients diagnosed with CML in different stages of the disease and/or its treatment. Materials and methods: Cross sectional, descriptive study of thirty one CML patients (aged 15-78). Analysis was carried out through qualitative nested PCR for the isoforms P210 BCR-ABL (b3a2 e b2a2) and P190 BCR-ABL (e1a2), and based on peripheral blood samples. Results: In 29 of the 31 patients (93.6%) transcript p210BCR-ABL was detected; b2a2 and b3a2 gene fusions and the coexpression b3a2 y b2a2 were identified in 55.2% (16/29), 34.5% (10/29) and 10.3% (3/29) of the cases, respectively. Conclusion: b2a2 gene fusion was the most frequent in this CML population.

Copyright of Medicina (Buenos Aires) is the property of Medicina (Buenos Aires) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Evolución clonal en la leucemia mieloide crónica se denomina a la presencia de alteraciones cromosómicas adicionales al cromosoma Filadelfia. Ocurre aproximadamente en el 30 % de los pacientes en fase acelerada y en el 80 % de los pacientes en crisis blástica. Es considerada un criterio de la fase acelerada de la enfermedad. Aunque se plantea que su presencia implica peor pronóstico, su significado es controversial y está en dependencia de la alteración citogenética específica, su frecuencia en el cariotipo, la asociación con otras alteraciones citogenéticas y clínicas de progresión, relación con el tiempo en que aparece en la evolución de la enfermedad y los tratamientos empleados.Clonal evolution in chronic myeloid leukemia is defined as the presence of a variety of additional, nonrandom chromosomal abnormalities besides the Philadelfia chromosome. It occurs in approximately 30 % of patients in accelerated phase and 80 % of patients in blastic phase. It is considered a criterion for accelerated phase. Although it is associated with a poor prognosis, its significance is controversial. It depends on the specific cytogenetic abnormality, its frequency in karyotype study, the association with other progression clinical and cytogenetic alterations, its relationship with the time of appearance during the course of the disease and the therapy used.

Según el mito universal, cuando se acercaba su fin el ave fénix construía un nido donde se incineraba para después renacer de sus cenizas. Esta leyenda puede aplicarse metafóricamente a lo sucedido en los últimos años con el interferón (IFN) en el tratamiento de la leucemia mieloide crónica (LMC), donde fue sustituido por los inhibidores de la actividad tirosina cinasa. Antes de la introducción del imatinib, la regla de oro para el tratamiento de la LMC en fase crónica eran los protocolos basados en el INF-a, pero los resultados obtenidos con dicho medicamento favorecieron que este inhibidor de la tirosina cinasa fuera aceptado como el mejor tratamiento inicial para la LMC recién diagnosticada. Sin embargo, la experiencia acumulada con los inhibidores de la tirosina cinasa ha evidenciado que generalmente hay cierto número de enfermos en que este tratamiento no es totalmente eficaz. Ante este hecho más la profundización de los conocimientos sobre los mecanismos de acción del INF-a, se pensó en su reincorporación al tratamiento de la LMC, pues pudiera complementar y coadyuvar a los inhibidores de la actividad tirosina cinasa. Esta idea promovió el interés de asociar el INF-a, que había sido prácticamente eliminado del escenario terapéutico de la LMC, con los inhibidores de la actividad tirosina cinasa. Los resultados que se han logrado con su asociación al imatinib son incuestionables y muy promisorios, lo que hizo que el INF-a, cual ave fénix, surgiera de sus cenizas con nuevos bríos. Aunque los resultados son significativos, se considera necesaria la ampliación de los estudios con esa combinación terapéutica para poder precisar mejor sus efectos, fundamentalmente a largo plazo.According to the universal myth, as its end approaches the phoenix built a nest where it cremated itself and then rose from its ashes. This legend can be metaphorically applied to what happened in recent years with interferon (IFN) in the treatment of chronic myeloid leukemia (CML), which was replaced by tyrosine kinase activity inhibitors. Before the introduction of imatinib, the gold standard for the treatment of CML chronic phase was based on INF-alpha protocols, but the results obtained with the drug favored tyrosine kinase inhibitors to be accepted as the best initial treatment for newly diagnosed CML. However, the experience with the tyrosine kinase inhibitors has shown that this treatment is usually not completely effective in a number of patients. Given this fact plus deepening the understanding of IFN-alpha action mechanisms, its reinstating in CML treatment was considered, since it might be a complement and contribute to inhibitors of tyrosine kinase activity. This idea promoted the interest of associating INF-alpha, which had been virtually eliminated from CML therapy, with inhibitors of tyrosine kinase activity. The results achieved with its association with imatinib are unquestionable and very promising, which made INF-alpha a phoenix arising from its ashes with renewed spirit. Although the results are significant, the extension of studies of that combination therapy is considered necessary to better clarify its effects, mainly in long terms.

Se estudiaron 13 pacientes con leucemia mieloide crónica y anemia hemolítica autoinmune inducida por el interferón alfa, a quienes se les realizó la detección de inmunoproteínas y la caracterización de las subclases de IgG en los hematíes mediante la prueba de antiglobulina directa (PAD) y la técnica de microplacas. Se aplicó además un ELISA para la cuantificación de inmunoglobulinas en los hematíes. Se detectó la presencia de IgG y C3 en el 53,84 % de los casos, IgG sola en el 23,07 % y en el 15,38 % se identificaron autoanticuerpos IgG e IgA. En 11 pacientes se demostró la presencia de IgG1 y en un caso se identificaron además autoanticuerpos de la subclase IgG3. El ELISA detectó autoanticuerpos en concentraciones de 183 moléculas de IgG por hematíe en un paciente con PAD negativa. En los pacientes con hemólisis de alto grado se encontró una concentración de autoanticuerpos entre 1 500 y 3 180 moléculas de IgG por hematíe, mientras que en los casos con hemólisis de bajo grado se comportó entre 183 y 1 000 moléculas. Se observó una correlación negativa entre las cifras de Hb y los valores de haptoglobina plasmática con el número de moléculas de IgG por hematíe y una correlación positiva entre este último con el conteo de reticulocitos.We studied 13 patients with chronic myeloid leukemia and autoimmune hemolytic anemia induced by interferon alfa. They underwent tests for immune protein detection and characterization of IgG subclasses in RBCs by direct antiglobulin test (PAD) and the microplate technique. Also they were applied ELISA test for quantifying immunoglobulins in the red blood cells. It was detected the presence of IgG and C3 in 53.84 % of cases, IgG alone in 23.07 % and in 15.38 % were identified IgG and IgA autoantibodies. In 11 patients the presence of IgG1 was showed and also in one case the subclass IgG3 autoantibodies was identified. The ELISA detected antibodies at concentrations of 183 IgG molecules per erythrocyte in a patient with negative PAD. In high-grade hemolysis patients, it was found a concentration of autoantibodies between 1 500 and 3 180 molecules of IgG per erythrocyte, while in low-grade hemolysis patients it behaved between 183 and 1 000 molecules. There was a negative correlation between Hb and plasma haptoglobin values with the number of IgG molecules per erythrocyte and a positive correlation between the latter with the reticulocyte count.

Introducción: La leucemia mieloide crónica es una enfermedad mieloproliferativa caracterizada por 3 fases evolutivas. La evaluación citogenética de la enfermedad permite confirmar el diagnóstico y establecer el pronóstico. Objetivo: Reportar los resultados del estudio citogenético de 180 pacientes con diagnóstico clínico de leucemia mieloide crónica y correlacionarlos con las 3 fases de dicha neoplasia. Métodos: El análisis cromosómico de las muestras de médula ósea se realizó por las técnicas de bandas G y los cariotipos se clasificaron según los criterios del Sistema Internacional de Nomenclatura Cromosómica. Resultados: El 94 % de los pacientes estudiados presentó la translocación t(9;22), que apareció con mayor frecuencia en los individuos en fase crónica (87,5 %). En contraste, las anomalías cromosómicas secundarias al cromosoma Philadelphia resultaron las más frecuentes en los que estaban en fase acelerada y en crisis blástica (81,5 % y 96 %, respectivamente). Los resultados obtenidos confirman la relación que existe entre las alteraciones cromosómicas y las diferentes fases evolutivas de la leucemia mieloide crónica.Introduction: The chronic myeloid leukemia is a myeloproliferative disease characterized by three progressive phases. Its cytogenetic analysis assessment allows us to verify the diagnosis and to establish the prognosis. Objective: To report the cytogenetic results from 180 patients clinically diagnosed with chronic myeloid leukemia and correlate them with the three phases of such neoplasia. Methods: The chromosomal analysis of bone marrow samples was performed using the techniques of G bands and the karyotypes were classified according to the criteria of the International System of Chromosomal Nomenclature. Results: The 94 % of study patients had the translocation t(9:22) more frequent in subjects in chronic phase (87,5 %). In contrast, the chromosomal anomalies secondary to Philadelphia chromosome were the more frequent ones in those cases in accelerated phase and of blast crisis (81.5 % and 96 %), respectively. Results obtained confirm the relation existing among the chromosomal alterations and the different evolution phases of chronic myeloid leukemia.

Se efectuó un estudio descriptivo y transversal de 94 niños con leucemia, ingresados en el Servicio de Hematología del Hospital Infantil Sur Docente de Santiago de Cuba durante el quinquenio 2006-2010, a fin de describir las características clinicoepidemiológicas de estos pacientes. La enfermedad predominó en el grupo etario de más de 8 años y en los varones, mientras que entre las formas clínicas de presentación sobresalieron el síndrome anémico, las manifestaciones purpuricohemorrágicas y la fiebre. El tipo de leucemia principalmente observada fue la linfoblástica aguda y la de mayor mortalidad, la mieloide crónica; las infecciones y hemorragias resultaron ser las complicaciones más importantes en la serie.A descriptive and cross-sectional study of 94 children with leukemia, admitted in the Hematology Service of the Teaching Southern Children Hospital from Santiago de Cuba was carried out during the five year period 2006-2010, in order to describe the clinical and epidemiological characteristics of these patients. The disease prevailed in the age group of more than 8 years and in males, while among the clinical forms of presentation there were: the anemic syndrome, the purpureal and hemorrhagic manifestations and fever. The type of leukemia mostly observed was the lymphoblastic acute leukemia and that of higher mortality, was the chronic myeloid leukemia. Infections and hemorrhages were the most important complications in the series.

La leucemia mieloide crónica del adulto es la hemopatía maligna más frecuente dentro de los síndromes mieloproliferativos. En un estudio retrospectivo longitudinal realizado entre enero de 1985 y diciembre de 2009, se evaluaron 46 pacientes en fase crónica atendidos en el Instituto de Hematología e Inmunología. Todos recibieron tratamiento inicial citorreductor y posteriormente interferón ? recombinante (INF?r) + citosina arabinósido. El 41,0 % de los enfermos presentó un índice pronóstico de Sokal de alto riesgo. Las manifestaciones clínicas más frecuentes al diagnóstico fueron astenia (37 %), esplenomegalia (31 %) y pérdida de peso (28,3 %). La respuesta hematológica parcial y completa fue del 26,8 % y 65,9 % a los 6 meses; la respuesta citogenética y molecular completa de 9,1 % y 16,3 %, respectivamente. Las reacciones adversas más frecuentes fueron fiebre (34,9 %), trombocitopenia (26,2 %) y síndrome general (23,8 %). El 47,8 % de los casos mostraron resistencia o intolerancia al INF?r y el 90,9 % falleció por progresión de la enfermedad. La sobrevida global a los 5 años fue del 63,8 % y la sobrevida libre de eventos a los 3 años fue del 68,9 %. Según el índice pronóstico de Sokal, la sobrevida global mostró diferencia significativa entre los 3 grupos (p= 0,005), no así para la sobrevida libre de eventos (p= 0,165). El tratamiento con INF?r mostró resultados superiores a los de algunos países desarrollados y constituye una opción terapéutica eficaz en Cuba.Chronic myeloid leukemia is the most frequent myeloproliferative syndrome in adults. In a longitudinal retrospective study performed between January 1985 - December 2009, 46 patients in chronic phase diagnosed at the Institute of Hematology and Immunology were evaluated. They received cytoreductor agent as first treatment followed by interferon ?2 + cytosar. Forty one percent showed high risk Sokal prognosis score. The most frequent clinical manifestations at diagnosis were asthenia (37 %), splenomegaly (31 %) and weigh lost (28.3 %). The partial and complete hematological response was of 26,8 % and 65.9 % after 6 months and the complete cytogenetic and molecular response was of 9.1 % and 16.3 %. The most frequent adverse reactions were: fever (34.9 %), thrombocytopenia (26.3 %) and general syndrome (23.8 %). Resistance or intolerance to INF?2 was found in 47.8 % of the patients and 90.0 % died due to progression of the disease. The 5 year overall survival was of 63.8 % and the 3 years free event survival was of 68.9 %. According to Sokal prognosis score the overall survival showed significant difference between groups (p= 0.005) but there was no significant difference for free event survival (p= 0.165). The INF?2 treatment in our patients showed better results than those obtained in different developed countries and is an effective therapeutic option in Cuba.

Se presenta un paciente con leucemia mieloide crónica (LMC) y un transcripto BCR-ABL atípico. Mediante el análisis cualitativo de los productos de la reacción en cadena de la polimerasa, y por comparación con los pesos moleculares del producto de amplificación de muestras de pacientes positivos a los puntos de ruptura más frecuentes e13a2 (b2a2) y e14a2 (b3a2), se determinó que el gen quimérico BCR-ABL de este paciente debe corresponder al transcripto e13a3 (b2a3) que aparece con muy poca frecuencia en la LMC. El paciente se encuentra en tratamiento con imatinib (400 mg diarios) desde el inicio de la enfermedad. A los 6 meses no se detectó presencia del gen quimérico BCR-ABL; 2 estudios moleculares posteriores, al año y a los 2 años de tratamiento, resultaron positivos, pero esto no implicó modificación del tratamiento. La evolución favorable del paciente, a pesar de la recaÍda molecular, concuerda con lo esperado descrito en la literatura en relación con la presencia del transcripto b2a3 en la LMC.The case of a patient with chronic myeloid leukemia and atypical BCR-ABL transcript was presented. By using the qualitative analysis of the polymerase chain reaction products and the comparison with the molecular weights of the amplification product from the samples taken from those patients positive to the most frequent rupture points e13a2 (b2a2) and e14a2 (b3a2), it was determined that chimeric gen BCR-ABL of this patient should correspond to transcript e13a3 (b2a3) that rarely occurs in CML. The patient is being treated with Imatinib (400 mg daily) since the onset of his disease. After six months, the chimeric gen BCR-ABL was not detected. Two molecular studies carried out one year and two years after the treatment yielded positive results, but this did not imply any change to the treatment. Despite the molecular relapse, the favorable recovery of the patient agreed with the expected result described in the literature in terms of the presence of transcript b2a3 in CML.

Chronic Myeloid Leukemia (CML) is a myeloproliferative disease characterized by the presence of the Philadelphia chromosome (translocation between chromosomes 9 and 22), resulting in the formation of the hybrid BCR-ABL protein. Currently, the treatment of CML patients is performed with imatinib mesylate (IM), which promotes the elimination of leukemic cells by inhibiting the kinase activity of BCR-ABL. This study evaluated the effectiveness of IM by monitoring 22 CML patients in a chronic phase treated at the CEPON/SC with IM for a minimum follow-up period of two years. Cytogenetic Response (CR) and bone marrow biopsies (BMB) were evaluated before and after IM treatment. BMB were evaluated by detection of reticulin degree and vascularization. The results were correlated to the CR. Mean time to achieve CR was 9 months and was attained by 77.27% of the patients. The results from the initial BMB analysis showed that 59.09% presented reticulin of between 2+ and 4+ whereas after treatment, only 27.17% presented this degree. With regard to vascularization of the initial sample, 90.91% were graded between II and IV, whereas after treatment, 40.91% had this degree. The results suggest a positive correlation of degree of reticulin and vascularization with CR.A Leucemia Mielóide Crônica (LMC) é uma doença mieloproliferativa caracterizada pela presença do cromossomo Filadélfia (translocação entre os cromossomos 9 e 22), que resulta na formação da proteína híbrida BCR-ABL. Atualmente o tratamento de pacientes com LMC é realizado com mesilato de imatinibe (MI), o qual promove a eliminação das células leucêmicas pela inibição da atividade quinase de BCR-ABL. O presente estudo avaliou a eficácia do MI por meio do acompanhamento de pacientes portadores de LMC em fase crônica, atendidos no CEPON/SC tratados com MI pelo tempo mínimo de dois anos. Foram avaliadas a Resposta Citogenética (RC) e as biópsias de medula óssea (BMO) antes e após o tratamento com MI. As BMO foram avaliadas quanto ao grau de reticulina e vascularização. Os resultados correlacionaram-se com a RC cujo tempo médio para obtenção da RC foi de 9 meses, sendo atingida por 77.27% dos pacientes. Na primeira BMO, 59.09% dos pacientes apresentaram grau de reticulina entre 2+ e 4+ e após o tratamento, apenas 27.17% apresentaram esta graduação. Quanto à vascularização da primeira amostra, 90.91% foram graduadas entre II e IV e após o tratamento, 40.91% apresentaram esta graduação. Os resultados sugerem uma correlação diretamente proporcional entre os graus de reticulina e vascularização com a RC.

El imatinib es un inhibidor sintético de la tirosina cinasa usado en el tratamiento de la leucemia mieloide crónica (LMC) y considerado como la droga de primera línea para el tratamiento de la enfermedad. Los efectos adversos más comunes son: náuseas, dolores musculoesqueléticos, diarrea, erupción cutánea, fatiga y mielosupresión, a expensas, fundamentalmente, de la línea granulopoyética. Se realizó un estudio en 43 pacientes adultos (23 femeninos y 20 masculinos) con LMC Ph+ en fase crónica, atendidos en el Instituto de Hematología e Inmunología y en otros servicios de hematología del país. Todos los casos presentaron resistencia o intolerancia al tratamiento con interferón alfa recombinante (INFα) y recibieron terapia con imatinib (400mg/día) en el período comprendido entre abril del 2003 hasta julio del 2008. El 48,8 % de los pacientes no tuvieron reacciones adversas. Dentro de los efectos adversos no hematológicos, los más frecuentes fueron: 23,3 % dolores óseos, musculares o ambos; 23,3 % edemas; 20,9 % hipopigmentación de la piel; y 11,6 % nódulos subcutáneos. Dentro de las reacciones hematológicas, en el 14 % se diagnosticó la anemia hemolítica inmune por droga; en el 11,6 % la trombocitopenia inmune por droga; y en el 9,3 % bicitopenia.Imatinib is a synthetic inhibitor of kinase-tyrosine used in the treatment of chronic myeloid leukemia (CML) and also is considered as the first-line drug for the treatment of this entity. The commonest side effects include: nausea, musculoskeletal pains, diarrhea, cutaneous eruption, fatigue and myelosuppression mainly at the expense of granulopoiesis line. A study was conducted in 43 adult patients (23 females and 20 males) presenting with CML pH+ in chronic phase, seen in the Hematology and Immunology Institute and in other Hematology services in our country. All cases showed resistance and intolerance to treatment with recombinant Alfa-Interferon (INFα) and Imatinib therapy (400 mg/day) from April, 2003 to July, 2008. The 48,8% of patients have not adverse reactions. The more frequent non-hematologic side effects include bone, muscular or both pain (23%), edema (23,3%); skin hypopigmentation (20,9%), and subcutaneous nodules (11,6%). In hematological reactions are included the drug-hemolytic anemia (14%) drug-immune anemia, drug immune thrombocytopenia (11,6%) and bicitopenia ( 9,3%).

Chronic myeloid leukemia (CML) is a malignant myeloproliferative disorder that originates from a pluripotent stem cell characterized by abnormal release of the expanded, malignant stem cell clone from the bone marrow into the bloodstream. The vast majority of patients with CML present Bcr-Abl transcripts. Lactate dehydrogenase (LDH) is considered a biochemical marker common for tumor growth, anaerobic glycolysis and has been considered a poor prognostic factor for acute myeloid leukemia. Therefore, this study aimed to evaluate the concentration of LDH in plasma and the detection of the Bcr-Abl transcripts in patients with CML and healthy donors. We analyzed 22 patients demonstrably diagnosed with CML and 56 healthy donors. LDH concentration in plasma was higher in patients with CML. All patients with CML in this study were under treatment, but even so four patients had the Bcr-Abl (b3a2) transcript in peripheral blood. Two out of the four patients with b3a2 showed higher LDH (486 U L-1 and 589 U L-1). Thus, although the study was conducted with small numbers of samples, it is possible to suggest therapy alteration for two patients who presented transcript b3a2 in the peripheral blood samples and whose LDH concentration was high, in order to improve the disease. Leucemia mieloide crônica (LMC) é uma desordem mieloproliferativa maligna que é originada de célula-tronco pluripotente caracterizada por expansão anormal, maligna de clones de células tronco da medula óssea na circulação. A grande maioria dos pacientes com LMC apresentam transcritos Bcr-Abl. Lactato desidrogenase (LDH),considerado um marcador bioquímico para crescimento tumoral, glicólise anaeróbica, e tem sido considerado um fator de pior prognóstico da LMC. Portanto, este estudo visa avaliar a concentraçãode LDH no plasma e a detecção do transcrito Bcr-Abl em 22 pacientes com LMC e 56 indivíduos saudáveis. Foram avaliados 22 pacientes com LMC e 56 doadores saudáveis. A concentração de LDH no plasma foi maior nos pacientes com LMC. Todos pacientes com LMC neste estudoestavam em tratamento, mesmo assim quatro pacientes apresentavam o transcrito Bcr-Abl (b3a2) no sangue periférico. Dois dos quatro pacientes com o transcrito b3a2 apresentavam LDH elevado (486 U L-1 e 589 U L-1). Embora o estudo tenha sido realizado com um pequeno número de amostras, é possível sugerir alteração de terapia para os dois pacientes que apresentam o transcrito b3a2 na amostra de sangue periférico com concentração de LDH elevada.

A leucemia mieloide crônica (LMC) é uma doença clonal da medula óssea caracterizada pela presença do cromossomo Philadelphia (Ph), resultante da translocação entre os cromossomos 9 e 22. O gene híbrido assim formado, BCR-ABL codifica proteínas com atividade de tirosinoquinases que regulam o crescimento celular. A partir da década de 80, o transplante alogênico de células-tronco hematopoéticas (TCTH) se tornou tratamento de escolha para pacientes com idade menor que 55 anos de idade e doador compatível. Não obstante, a partir do advento dos inibidores de tirosinoquinases, drogas de alta eficácia e baixa toxicidade, houve uma mudança no algoritmo de tratamento da LMC. As indicações do TCTH foram restritas em decorrência da mortalidade relacionada a este procedimento e o mesilato de imatinibe tornou-se o novo tratamento de escolha para esta enfermidade. No Brasil e possivelmente em outros países em desenvolvimento, as condições socioeconômicas fazem com que o TCTH ainda seja considerado como primeira linha de tratamento em algumas situações. O TCTH permanece indicado nas doenças (ou neoplasias) mieloproliferativas, como a mielofibrose primária em situações de alto risco e pacientes portadores de policitemia vera ou trombocitose essencial que tenham evoluído para mielofibrose com características de alto risco.Chronic myeloid leukemia (CML) is a clonal disease of the bone marrow characterized by the presence of Philadelphia chromosome (Ph) which results from translocation between chromosome nine and 22. The hybrid gene, BCR-ABL, encodes proteins with tyrosine kinase activity that regulate cell growth. From the 80´s allogeneic hematopoietic stem cell transplantation (HSCT) has become the treatment of choice for patients younger than 55 years of age and donor. However, from the advent of tyrosine kinase inhibitors, drugs of high efficacy and low toxicity, there was a change in the treatment algorithm of CML. The indications of HSCT have been restricted as a result of mortality related to this procedure and imatinib mesylate has become the new treatment of choice for this disease. In Brazil and possibly in other developing countries, socio-economic conditions make HSCT still feasible as first-line treatment in some situations. The HSCT remains indicated for Ph negative myeloproliferative disorders such as high risk myelofibrosis or patients with polycythemia vera or essential thrombocytosis that have evolved to myelofibrosis with high-risk features.

Se evaluaron 43 pacientes adultos con leucemia mieloide crónica, Philadelphia positivo, que recibieron tratamiento con mesilato de imatinib como droga de segunda línea por resistencia o intolerancia al interferón alfa recombinante. La manifestación más frecuente al inicio de la enfermedad fue la esplenomegalia. El tratamiento con mesilato de imatinib se inició por resistencia (33; 76,7 %) o intolerancia grado 3 o 4 (10; 23,3 %). El mayor porcentaje de respuesta citogenética mayor (22; 91,7 %) y completa (11; 61,1 %) se alcanzó a los 18 y 24 meses de evolución. El 74,3 % no mostró respuesta molecular y el 5,1 % ya presentaba respuesta molecular antes del tratamiento; 9 (26,5 %) mostraron pérdida de la remisión hematológica completa, de ellos, 7 fallecieron por progresión de la enfermedad. La sobrevida global fue de 90,7 %, 83,3 %, 82,6 % y 78,9 % a los 5, 6, 7 y 8 años de evolución, respectivamente. La sobrevida global y libre de eventos a los 3 años de iniciado el mesilato de imatinib fue de 92,3 % y 81,8 %, respectivamente. Se encontró diferencia significativa entre la sobrevida libre de eventos y el índice pronóstico de Sokal. Las reacciones clínicas secundarias más frecuentes fueron dolores óseos, musculares o ambos; y las hematológicas: anemia hemolítica autoinmune y trombocitopenia.Forty three patients presenting with chronic positive-Philadelphia myeloid leukemia were assessed treated with Imatinib Mesilate as a second line drug by resistance or intolerance to recombinant alpha Interferon. At onset, the more frequent manifestation of this condition was the splenomegalia. Imatinib Mesilate treatment was started by resistance (33; 7.6 %) or 3 or 4 degree intolerance (10; 23.3 %). The greater percentage of cytogenetic response (22; 91.7 %) and complete (11; 61.1 %) was achieved at 18 and 24 course months. The 74.3 % hadn't "molecular response and the 5.1 % yet had it before treatment; 9 (26.5 %) showed a loss of complete hematologic remission, from them, 7 deceased from disease progression. Global survival was of 90.7 %, 83.3 %, 82.6 % and 78.9 % at 5, 6, 7 and 8 course years, respectively. Global survival and free of events at three years of Imatinib Mesilate appearance was of 92.3 % and 81.8 %, respectively. There was a significant difference between survival free of events and the Sokal prognostic rate. The more frequent secondary clinical reactions were the bone and/or muscular pain and the hematologic ones were the autoimmune hemolytic anemia and the thrombocytopenia.

As síndromes mieloproliferativas crônicas, atualmente denominadas neoplasias mieloproliferativas (NMP), de acordo com a 4ª. edição da classificação da Organização Mundial da Saúde (OMS), são doenças clonais de célula-tronco hematopoética, nas quais há a proliferação aumentada de uma ou mais das séries mieloides (granulocítica, eritrocítica, megacariocítica ou mastocítica) com maturação eficaz. A progressão de todas é caracterizada por fibrose medular ou transformação leucêmica. Pela classificação da OMS, as NMP incluem: leucemia mieloide crônica (LMC), policitemia vera (PV), mielofibrose idiopática crônica (MF), trombocitemia essencial (TE), leucemia neutrofílica crônica (LNC), leucemia eosinofílica crônica não especificada(LEC), mastocitose (M) e neoplasia mieloproliferativa inclassificável (NMI). É interessante notar que tanto a LMC (BCR/ABL1) como PV, MF e TE (JAK2 V617F e éxon 12, MPLW515L/K) e M (KITD816V) tiveram suas bases moleculares desvendadas e apresentam em comum a ativação constitutiva de tirosino-quinase graças às mutações adquiridas pela célula-tronco hematopoética. A mutação JAK2 V617F é observada em mais de 90% dos casos de PV, mas também em cerca de 50%-60% das MF e TE, levando ao questionamento de como uma única lesão molecular desencadeia três manifestações clínicas diversas. Já há evidências de que eventos genéticos e epigenéticos adicionais contribuem para a patogênese, tais como MPLW515L e MPLW515K. No presente manuscrito são apresentados os aspectos clínicos, a fisiopatologia e os critérios diagnósticos das diferentes NMP.Chronic myeloproliferative disorders, currently called myeloproliferative neoplasms (MPN), according to the 4th edition of the World Health Organization (WHO) classification are clonal diseases of hematopoietic stem cells, in which there is increased proliferation of the myeloid series (granulocytic, erythrocytic, megakaryocytic series or mast cells) with effective maturation. The progression of all is characterized by marrow fibrosis or leukemic transformation. According to the WHO classification, the MPNs include: chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), idiopathic myelofibrosis (IM), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia not otherwise categorized (CEL-NC), mastocytosis (M) and myeloproliferative neoplasm unclassifiable (MPNU). It is worth noting that the molecular basis of CML (BCR/ABL1), as well as PV,ET, IM (JAK2V617F and exon 12, MPL W515L/K) and M (KITD816V) have been identified and have, in common, constitutive activation of tyrosine kinase due to acquired hematopoietic stem cell defects. The JAK2V617F mutation is observed in around 90% of PV cases and in around 50-60% of IM and ET leading to the question why a single molecular lesion induces three different clinical manifestations. There is already evidence that additional genetic and epigenetic events contribute to the pathogenesis, including MPL W515L/K mutation. Some clinical aspects, the pathophysiology and diagnostic criteria of MPNs are presented in this paper.

Impressive response rates and the good tolerability have allowed imatinib to become the gold standard frontline therapy for all CML patients in the early chronic phase. Optimal outcomes are attained with more than two thirds of the CML cases treated with standard dose imatinib (400 mg daily). Criteria to establish failure and suboptimal responses to imatinib have been defined. Treatment guidelines have also suggested imatinib dose escalation based on clinical assessments of disease response. However, despite all the effort to optimize therapy with imatinib, cases of real resistance exist. For imatinib resistant and intolerant cases, second generation powerful tyrosine kinase inhibitors (TKIs) have been developed and registered. Sequential kinase inhibitor therapy is used to overcome resistance however, a future strategy might be a combination therapy with different ABL kinase inhibitors in the same therapeutic scheme, used sequentially or simultaneousl.Respostas impressionantes e boa tolerância transformaram o imatinibe no "padrão ouro" de tratamento de primeira linha na LMC em fase crônica precoce. Evolução favorável em mais de 2/3 dos pacientes com LMC é obtida com dose standard de 400 mg por dia. Critérios para estabelecer falha de tratamento e resposta "sub-ótima" têm sido definidos. Guidelines têm sugerido que o escalonamento da dose do imatinibe possa melhorar a resposta em subgrupo de pacientes. Entretanto, a despeito de todos os esforços para otimizar a resposta ao imatinibe, casos de resistência realmente existem. Para os casos de intolerância ou resistência ao imatinibe, inibidores potentes de segunda geração foram desenvolvidos e registrados (nilotinibe e dasatinibe). Além disto, terapêutica sequencial de inibidores podem ultrapassar a resistência, e a terapia combinada usada sequencialmente ou simultaneamente pode ser usada como estratégia futura.

O mesilato de imatinibe, como terapia alvo, se revelou altamente eficiente na leucemia mielóide crônica. Um desafio é a resistência primária ou secundária, principalmente nas fases avançadas da doença. Na secundária, as mutações pontuais no domínio quinase ABL são o mecanismo mais frequente. Estudou-se no período de outubro de 2000 a dezembro de 2005, 112 pacientes no Serviço de Hematologia e Hemoterapia da Santa Casa de São Paulo. O objetivo foi caracterizar o perfil dos resistentes e pesquisar a presença de mutação. Encontrou-se maior porcentagem de resistentes nas fases mais avançadas. Foram fatores de risco para resistência na fase crônica o número de plaquetas superior a 450.000/mm³ pré-imatinibe ou plaquetas inferior a 50.000/mm³ durante o tratamento. A taxa de resposta hematológica completa e o tempo para obtenção foram semelhantes entre os resistentes e não resistentes. Observou-se menor sobrevida global nos resistentes. Destacaram-se dez pacientes resistentes com resposta citogenética completa pós 12 meses, "responsivos tardios", cuja freqüência de resposta hematológica e citogenética foi semelhante aos não resistentes (100%). A sobrevida livre de progressão foi similar até aos 40 meses e a sobrevida global até aos 70 meses. A sobrevida global e as respostas foram superiores aos demais resistentes. Referente à pesquisa de mutação, analisou-se 22 resistentes, dos quais oito apresentaram mutação (36,4%). Caracterizou-se maior risco para a condição de mutação, a presença de blastos no sangue periférico ao diagnóstico nos pacientes em fase crônica.Imatinib mesylate, as target therapy, is highly efficient in chronic myelogenous leukemia. A challenge is primary and secondary resistance, particularly in the advanced phases of the disease. In secondary resistance, point mutations in the ABL dominion are the most common mechanism. From October 2000 to December 2005, 112 patients were investigated in the Hematology and Hemotherapy Service of Santa Casa of Sao Paulo. The aim was to characterize the profile of resistance and study the presence of the mutation. The majority of resistant patients were in the most advanced phases of the disease. Risk factors for resistance in the chronic phase were a platelet count higher than 450,000/mm3 before imatinib treatment or less than 50,000/mm3 during treatment. The total hematological response rate and the time to achieve this were similar between resistant and non-resistant patients. Lower overall survival was observed with resistance. It was notable that ten resistant patients had complete cytogenetic responses after 12 months (late responses) with both hematological and cytogenetic response rates similar to non-resistant patients (100%). Survival free from progression was similar up to 40 months and the overall survival rate was comparable up to 70 months. The overall survival and response to treatment were better than for the other resistant patients. In respect to the investigation of mutations, 22 resistant patients were investigated with eight presenting with the mutation (36.4%) The presence of blast cells in the peripheral blood at diagnosis of patients in the chronic phase was characterized as a higher risk factor for this mutation.