Aspectos diagnósticos, evolutivos y terapéuticos de la leucemia mieloide crónica / Diagnostic, evolutive and therapeutic aspects of chronic myeloid leukemia

Introducción: la leucemia mieloide crónica (LMC) es un síndrome mieloproliferativo crónico caracterizado por la presencia de una alteración citogenética en las células proliferantes, el cromosoma Filadelfia (Ph), que da lugar a la formación de un gen híbrido BCR-ABL, fundamental en la patogénesis de la enfermedad. Objetivo: describir el comportamiento de esta enfermedad en los pacientes tratados en el Instituto de Hematología e Inmunología. Métodos: se estudiaron las características de esta enfermedad en sus aspectos diagnósticos, evolutivos y terapéuticos, en los pacientes atendidos desde marzo de 1974 hasta junio de 2012. Resultados: el grupo de edad que predominó para ambos sexos fue de 30 a 39 años. El 21 por ciento de los pacientes se encontraban asintomáticos en el momento del diagnóstico. La esplenomegalia fue el signo predominante en el 64 por ciento de los pacientes. Los hallazgos iniciales más significativos del hemograma consistieron en leucocitosis, basofilia y anemia. El 81 por ciento de los casos se encontraba en fase crónica al inicio de la enfermedad. La mayoría de los pacientes debutaron con niveles de LDH elevados. Se observó el cromosoma Filadelfia en el 68 por ciento de los pacientes a quienes se les realizó estudio citogenético. El estudio del reordenamiento del gen BCR/ABL se realizó en el 70 por ciento de los casos, siendo positivo en su totalidad. La media de supervivencia en relación con el tratamiento fue mayor en los pacientes tratados con mesilato de imatinib desde el momento del diagnóstico (11.7 años). La media de supervivencia global es de 11.44 años y la mediana es de 8.18 años. Conclusiones: todos los parámetros demográficos, clínicos, de laboratorio y terapéuticos coincidieron con lo descrito en la literatura, excepto la edad de aparición de la LMC que evidenció una disminución

Introduction: Chronic myeloid leukemia (CML) is a chronic myeloproliferative syndrome characterized by the presence of a citogenetic alteration in proliferant cells, the Philadelphia chromosome (Ph), giving rise the formation of a hybrid gene BCR-ABL, with a fundamental role in the pathogenesis of the disease. Objective: To describe the clinical behavior of the illness in patients treated at the Institute of Hematology and Immunology. Methods: Characteristics according to diagnose, evolution and therapeutic aspects of the patients treated at from March 1974 to June 2012 were studied. Results: The age group that prevailed for both sexes was 30-39 years; 21 percent of the patients were asintomatic at diagnosis. Splenomegaly was the predominant sign in 64 percent of the patients. The most significant initial discoveries on blood film were leucocytosis, basophillia and anemia; at debut 81 percent of the patients were in chronic phase. Most patients debuted with high levels of LDH. Ph chromosome was observed in 68 percent of individuals with cytogenetc studies. The BCR/ABL gene was detected in every patient with molecular studies. The mean of survival in relation to treatment was higher in patients treated with imatinib mesilate at diagnosis (11.7 years). The mean of global survival was 11.44 years with the median of 8.18 years. Conclusion: All demographic, clinical, laboratory and therapeutic parameters coincided with the literature with the exception of a lower age at onset of CML

Chronic myeloid leukemia in case of Klinefelter syndrome.

Klinefelter syndrome (KS) is a sex chromosome disorder and has been reported to be associated with increased risk for malignancies. We report a 22‑year‑old male patient who was diagnosed to have chronic myeloid leukemia in chronic phase. Bone marrow cytogenetic examination revealed karyotype 47, XXY, t (9; 22)(q34, q11) suggestive of KS with presence of Philadelphia chromosome. The patient was treated with oral imatinib mesylate (400 mg/day). Complete hematological response was achieved after 2 months of therapy. The bcr‑abl/abl transcript percentage measured from peripheral blood at baseline, 1 and 2 years after imatinib were 97%, 1.99%, 0.007%, respectively. He remains in complete hematological and major molecular remission after 2 years of continued imatinib therapy.

Prognostic scoring in patients of chronic myeloid leukemia: correlation between Sokal and Hasford scoring systems

Chronic myeloid leukaemia [CML] is a clonal myeloproliferative disorder of transformed primitive hematopoietic progenitor cells. Chronic myeloid leukaemia is one of the commonest leukemias. Patients of CML are usually subjected to risk stratification according to various prognostic criteria. The Sokal scoring system is popular as a prognostic discriminator for survival in patients treated with chemotherapy. Hasford et al proposed a new CML scoring system referred to as Euro score. Correlation of various prognostic risk groups of Hasford scoring system with comparable prognostic groups of Sokal scoring system in chronic myeloid leukemia. This descriptive study was conducted at department of pathology, Pakistan institute of medical sciences from March 2003 to October 2006. A total of 59 consecutive freshly diagnosed untreated cases of CML were subjected to Sokal and Hasford scoring systems, and the results were correlated with each other. In total of 59 cases of CML age range was from 8 to 70 years with mean +/- SD of 35.39 +/- 17.12 years. Six [10.1%] patients belonged to pediatric age group i.e. <15 years. Male: female ratio was 1.3:1. According to Sokal criteria about half of the patients were found in intermediate risk group; 44% were in high risk group and only 5% in low risk group. Using Hasford scoring system, 44% of patients were placed in intermediate risk, 30.5% in high risk and 15% in low risk groups. Hasford score identifies more patients still in low risk group as compared to Sokal scoring system and prospective studies should be carried out to see overall survival and disease free survival of these risk groups

Algunas variables clínicas y de laboratorio en pacientes adultos con leucemia mieloide crónica tratados con interferón alfa recombinante + citosina arabinósido / Some clinical and laboratory variables in adult patients with chronic myeloid leukemia treated with recombinant alpha interferon + cytosine arabinoside

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 por ciento de los enfermos presentó un índice pronóstico de Sokal de alto riesgo. Las manifestaciones clínicas más frecuentes al diagnóstico fueron astenia (37 por ciento), esplenomegalia (31 por ciento) y pérdida de peso (28,3 por ciento). La respuesta hematológica parcial y completa fue del 26,8 por ciento y 65,9 por ciento a los 6 meses; la respuesta citogenética y molecular completa de 9,1 por ciento y 16,3 por ciento, respectivamente. Las reacciones adversas más frecuentes fueron fiebre (34,9 por ciento), trombocitopenia (26,2 por ciento) y síndrome general (23,8 por ciento). El 47,8 por ciento de los casos mostraron resistencia o intolerancia al INF?r y el 90,9 por ciento falleció por progresión de la enfermedad. La sobrevida global a los 5 años fue del 63,8 por ciento y la sobrevida libre de eventos a los 3 años fue del 68,9 por ciento. 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 percent), splenomegaly (31 percent) and weigh lost (28.3 percent). The partial and complete hematological response was of 26,8 percent and 65.9 percent after 6 months and the complete cytogenetic and molecular response was of 9.1 percent and 16.3 percent. The most frequent adverse reactions were: fever (34.9 percent), thrombocytopenia (26.3 percent) and general syndrome (23.8 percent). Resistance or intolerance to INF?2 was found in 47.8 percent of the patients and 90.0 percent died due to progression of the disease. The 5 year overall survival was of 63.8 percent and the 3 years free event survival was of 68.9 percent. 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

Studies on biomarkers for oxidative stress in patients with chronic myeloid leukemia

Chronic myeloid leukemia [CML] is a myeloproliferative disorder with a unique genetic rearrrangement, the Philadelphia chromosome. High reactive oxygen species [ROS] levels favor oxidative stress, which could play a vital role in normal processes and various pathophysiologies including neoplasm. Biomarkers of oxidative stress are measured as products of oxidized proteins and lipids. Plasma levels of protein carbonyl [PC], thiobarbituric acid reactive substances [TBARS] and total lipid hydroperoxide [LOOH] were used as biommarkers of oxidative stress in the past. The aim of this study was to evaluate the products of protein oxidation and lipid peroxidation in plasma as biomarkers of oxidative stress in CML patients. The study included 40 CML patients and 20 age- and sex-matched healthy voluntteers. Of 40 CML patients, 28 were in chronic phase [CML-CP] and 12 in accelerated phase [CML-AP]. Plasma levels of PC, TBARS and LOOH as biomarkers of oxidative stress were evaluated by spectrophotometric methods. There were significant differences [P<.05] in plasma levels of PC, TBARS and LOOH in CML, CML-CP and CML-AP patients as compared to controls. PC, TBARS and LOOH might reflect oxidative stress in CML patients and might be used as biomarkers in such patients

Chronic myeloid leukaemia at the University Hospital of the West Indies A 17-year review / Leucemia mieloide crónica en el Hospital Universitario de West Indies un estudio de 17 años

OBJECTIVE: To determine the presenting features and evolution of patients diagnosed with chronic myeloid leukaemia between 1983 and 1999 at the University Hospital of the West Indies. METHODS: Forty-one records were retrospectively analyzed for the patients' demographics, reasons for referral, clinical features, laboratory investigations and the time to blast transformation and death. RESULTS: Seventy-one per cent were males and 29% were females. The male to female ratio was 2.4:1. The median age at presentation was 37 years (range 14-81 years). Seventy-eight per cent of the patients presented in the chronic phase. Weight loss and splenomegaly were the most frequent presenting features being seen in 54 and 83 per cent respectively. The median survival was 36 months. CONCLUSION: In this study, the clinical features and evolution were comparable to existing data. Improved accrual and routine Philadelphia chromosome testing would provide a more accurate reflection of the status of CML in our population.

OBJETIVO: Determinar los rasgos presentes y la evolución de los pacientes diagnosticados con leucemia mieloide crónica entre 1983 y 1999 en el Hospital Universitario de West Indies. MÉTODOS: Cuarenta historias clínicas fueron analizadas respectivamente en busca de los datos demográficos de los pacientes, las razones para la remisión de casos, las características clínicas, las investigaciones de laboratorio y el tiempo hasta la transformación blástica y la muerte. RESULTADOS: El setenta y uno por ciento eran varones y el 29% eran hembras. La proporción varones-hembras fue 2.4:1. La mediana de la edad en el momento de la presentación fue de 37 años (rango 14-81 años). Setenta y ocho por ciento de los pacientes se presentaron en la fase crónica. Pérdida de peso y esplenomegalia fueron las características más frecuentemente observadas en el 54 y el 83 por ciento respectivamente. La mediana de la supervivencia fue 36 meses. CONCLUSIÓN: En este estudio, las características clínicas y la evolución fueron comparables con los datos existentes. El mejoramiento de la acumulación y las pruebas de rutina para identificar el cromosoma Filadelfia, reflejarían con mayor precisión el estatus de la LMC en nuestra población.

Grading of marrow fibrosis in chronic myeloid leukemia--a comprehensive approach.

In the course of Chronic myeloid leukemia (CML), appearance of increased number of blasts may herald evolution of accelerated phase as well as onset of marrow fibrosis (MF) thereby necessitating the need to perform trephine biopsy for correct diagnosis and appropriate treatment. In the existing grading systems of MF, a comprehensive view has not been taken of the variability of density and area occupied by reticulin and collagen fibres. To overcome this shortcoming, we quantitated the reticulin and collagen content of marrow, its pattern of distribution and percentage area occupied by each type of fibres in every individual case. We performed 50 bone marrow (BM) trephine biopsies in patients of CML in order to assess the incidence and degree of MF. Various grades of MF were correlated with peripheral smear including blast count, bone marrow aspirate and LAP score of the case. A positive correlation was found between increasing grades of MF and number of megakaryocytes in the BM.

Clinicoepidemiological features of adult leukemias in Pakistan

A total of 113 patients of leukemia, over 15 years of age, were seen in three different institutions from July, 1992 to June, 1994. There was an almost equal distribution of acute myeloid leukemia [AML] and acute lymphoblastic leukemia [ALL] [44 vs 43 cases respectively]. Chronic lymphocytic leukemia [CLL] was the least common, accounting for 5% of all cases. Mean age in CLL was 59 years. Chronic myeloid leukemia [CML] was three times commoner than CLL with a younger age distribution [median age was 34 years]. We conclude that the clinicoepidemiological features of adult leukemias differ considerably from that seen in the developed world. However, recruitment of patients needs to continue in order to define these features based on a larger patient population

Chronic myeloid leukemia (CML): prognostic factors and survival analysis

The prognostic value of different factors upon diagnosis of CML was analysed in 45 Philadelphia (Ph1)-positive patients. The median survival was 48 months. Univariate analysis showed 5 poor prognostic factors (male sex, under 45 years-old, bone marrow blasts greater than or equal to 10 percent, blood basophils greater than or equal to 6 percent and blood eosinophilis greater than or equal to 6 percent) which provided for the development of a clinical staging system: Stage I whith none or one factor and a two-year survival rate of 100 percent; Stage II with two or three factors and two-year survival of 72.2 percent; and Stage III with four or five factors and two-year survival of 0 percent (p=0.00016). Multivariate survival analysis showed that combination of blood basophilia and bone marrow blasts had the strongest predective relationship to survival time. We conclude that a combination of pretreatment factors identifies different risk subcategories in CML patients and is helpful in assessing the overall prognosis and the treatment approach.

Incidence estimation of leukemia among Koreans

This study was undertaken in order to estimate the incidence of leukemia among Koreans. Medical records were studied of patients with diagnoses of either ICD-9 038 (septicemia), or 204-208 (leukemias), or 284 (aplastic anemia), or 289 (other diseases of the blood and blood-forming organs) in the claims sent in by medical care institutions throughout the country to the Korea Medical Insurance Corporation (KMIC) during the period from January 1, 1986 to December 31, 1987. These records were abstracted in order to identify and confirm new cases of leukemia among the beneficiaries of KMIC, which covers about 10% of the whole Korean population. Using these data from the KMIC, the incidence rates of leukemia among Koreans were estimated as of July 1st, 1986 to June 30, 1987. The crude incidence rate of all types of leukemia among Koreans is estimated to be 3.45 (95% CI; 0.77-9.55) and 2.29 (95% CI; 0.28-7.81) per 100,000 in males and females, respectively. The cumulative rate for the age span 0-64 is 0.25% in males and 0.18% in females, and for the age span 0-74, 0.35% in males and 0.23% in females. The adjusted rates for the standard world population are 3.90 and 2.48 per 100,000 in males and females, respectively. The relative frequencies by type are 51.5% for AML, 21.6% for ALL, 20.2% for CML, and only 1.5% for CLL. The incidence patterns of various types of leukemia, of which this is the first report in Korea, are analyzed and presented.(ABSTRACT TRUNCATED AT 250 WORDS)