JAK2, CALR, and MPL Mutation Profiles in Colombian patients with BCR-ABL Negative Myeloproliferative Neoplasms

Background: Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway. Objective: This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms. Methods: The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia. Results: The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Conclusion: Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Antecedentes: Entre las neoplasias mieloproliferativas crónicas no asociadas con mutaciones BCR-ABL se encuentran la policitemia vera, la mielofibrosis primaria y la trombocitemia esencial. Estas enfermedades están causadas por mutaciones en genes, como los genes JAK2, MPL y CALR, que participan en la regulación de la vía de señalización JAK-STAT. Objetivo: Establecer las frecuencias de mutaciones en los genes JAK2, MPL y CALR en un grupo de pacientes colombianos con diagnóstico clínico negativo de NMP BCR-ABL. Metodos: Se analizaron las mutaciones y deleciones o inserciones JAK2 V617F y MPL W515K en el exón 9 del gen CALR en 52 pacientes colombianos con policitemia vera, mielofibrosis primaria y trombocitemia esencial. Resultados: La mutación JAK2V617F la portaban el 51.9% de los pacientes, la mutación CALR el 23.0% y la mutación MPL el 3.8%; El 23.0% fueron triple negativos para las mutaciones analizadas. En estas neoplasias se identificaron seis tipos de mutación en CALR, uno de los cuales no ha sido reportado previamente. Además, un paciente presentó una doble mutación tanto en el gen CALR como en el JAK2. En cuanto a los resultados hematológicos para las mutaciones, se encontraron diferencias significativas en el nivel de hemoglobina, el nivel de hematocrito y el recuento de plaquetas entre las tres neoplasias. Conclusiones: Así, este estudio demuestra la importancia de la caracterización molecular de las mutaciones JAK2, CALR y MPL en pacientes colombianos (cuyo contexto genético aún no está claro en las neoplasias antes mencionadas) para lograr un diagnóstico certero, un buen pronóstico, un manejo adecuado y una mejoría del paciente. supervivencia.

Oclusión intestinal por policitemia vera en una anciana / Intestinal occlusion due to polycythemia vera in an old woman

Se describe el caso clínico de una paciente de 67 años de edad con varias comorbilidades, entre ellas la policitemia vera, quien acudió al Cuerpo de Guardia del Hospital Clinicoquirúrgico Universitario Dr. Ambrosio Grillo Portuondo de Santiago de Cuba por presentar síntomas y signos de un síndrome de abdomen agudo oclusivo. Se indicó intervención quirúrgica de urgencia, que permitió confirmar el diagnóstico presuntivo de afección vascular mesentérica de tipo trombótica. La inmediatez del tratamiento quirúrgico, la reversibilidad del daño vascular sin necesidad de procedimiento de resección intestinal y la administración efectiva de anticoagulantes permitieron una evolución favorable y sin complicaciones.

The case report of a 67 years patient with several comorbidities is described, among them polycythemia vera, who went to the emergency room of Ambrosio Grillo Portuondo University Clinical Surgical Hospital in Santiago de Cuba due to symptoms and signs of a syndrome of occlusive acute abdomen. An emergency surgical intervention was indicated, that confirmed the presumptive diagnosis of mesenteric vascular thrombosis. The immediacy of the surgical treatment, the reversibility of the vascular damage without necessity of intestinal resection procedure and the effective use of anticoagulants allowed a favorable clinical course without complications.

Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms / 南方医科大学学报

OBJECTIVE@#To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN).@*METHODS@#We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment.@*RESULTS@#After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P < 0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86%) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42%) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed.@*CONCLUSION@#For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon- α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients.

Clinical and laboratory features compared between JAK2 exon12 and JAK2 V617F mutated polycythemia vera / 中华血液学杂志

Objective: To compare clinical and laboratory features between JAK2 exon12 and JAK2 V617F mutated polycythemia vera (PV) . Method: We collected data from 570 consecutive newly-diagnosed subjects with PV and JAK2 mutation, and compared clinical and laboratory features between patients with JAK2 exon12 and JAK2 V617F mutation. Results: 543 (95.3%) subjects harboured JAK2 V617F mutation (JAK2 V617F cohort) , 24 (4.2%) harboured JAK2 exon12 mutations (JAK2 exon12 cohort) , and 3 (0.5%) harboured JAK2 exon12 and JAK2 V617F mutations. The mutations in JAK2 exon12 including deletion (n=10, 37.0%) , deletion accompanied insertion (n=10, 37.0%) , and missense mutations (n=7, 25.9%) . Comparing with JAK2 V617F cohort, subjects in JAK2 exon12 cohort were younger [median age 50 (20-73) years versus 59 (25-91) years, P=0.040], had higher RBC counts [8.19 (5.88-10.94) ×10(12)/L versus 7.14 (4.11-10.64) ×10(12)/L, P<0.001] and hematocrit [64.1% (53.7-79.0%) versus 59.6% (47.2%-77.1%) , P=0.001], but lower WBC counts [8.29 (3.2-18.99) ×10(9)/L versus 12.91 (3.24-38.3) ×10(9)/L, P<0.001], platelet counts [313 (83-1433) ×10(9)/L versus 470 (61-2169) ×10(9)/L, P<0.001] and epoetin [0.70 (0.06-3.27) versus 1.14 (0.01-10.16) IU/L, P=0.002] levels. We reviewed bone marrow histology at diagnosis in 20 subjects with each type of mutation matched for age and sex. Subjects with JAK2 exon12 mutations had fewer loose megakaryocyte cluster (40% versus 80%, P=0.022) compared with subjects with JAK2 V617F. The median follow-ups were 30 months (range 4-83) and 37 months (range 1-84) for cohorts with JAK2 V617F and JAK2 exon12, respectively. There was no difference in overall survival (P=0.422) and thrombosis-free survival (P=0.900) . Conclusions: Compared with patients with JAK2 V617F mutation, patients with JAK2 exon12 mutation were younger, and had more obvious erythrocytosis and less loose cluster of megakaryocytes.

Análisis causal integrado en la radiosinoviortesis y el tratamiento mielosupresor de la policitemia vera / Integrated causal analysis in radiosynoviorthesis and the myelosupressor treatment of polycythemia vera

Introducción: Con la matriz de riesgo se identifican las medidas de control relevantes. El análisis de modos y efectos de fallo posterga definir la efectividad de las medidas correctivas. El uso de uno solo de estos métodos limita el alcance al evaluar los riesgos y la toma de decisiones. Objetivos: Determinar la contribución individual de las causas básicas de fallo en el riesgo radiológico de la radiosinoviortesis y el tratamiento mielosupresor de la policitemia vera, a partir del modelo de la matriz y los reportes. Métodos: Se adaptó el análisis de la gestión de la calidad en radioterapia a las prácticas en estudio y la selección individual de las causas básicas más contribuyentes al riesgo radiológico. La base internacional de incidentes aportó las causas que completaron el listado de las derivadas de la aplicación del principio de Pareto. Resultados: Los subprocesos más contribuyentes al riesgo fueron, por orden de importancia, la administración del radiofármaco, su preparación y la prescripción clínica. Para estos se identificaron las etapas, modos de fallo y sus causas más importantes. Existieron causas que contribuyeron a varios modos de fallo. El incumplimiento de procedimientos, protocolos o prácticas, la falta de entrenamiento del personal y la fatiga del personal son las causas de los riesgos identificados. Conclusiones: Se caracterizó la efectividad de las medidas correctivas de las causas más contribuyentes, las que se adicionan a las derivadas de la matriz, en el plan de mejora en la radiosinoviortesis y el tratamiento mielosupresor de la policitemia vera en Cuba(AU)

Introduction: The risk matrix identifies the relevant control measures. Failure modes and effects analysis postpones defining the effectiveness of corrective measures. Using just one of these methods limits the scope when assessing risks and making decisions. Objectives: To determine the individual contribution of the basic causes of failure in the radiological risk of radiosynoviorthesis and the myelosupressor treatment of polycythemia vera, based on the matrix model and the reports. Methods: The analysis of quality management in radiotherapy was adapted to the practices under study and the individual selection of the basic causes most contributing to radiological risk. The international incident base provided the causes that completed the list of those derived from the application of the Pareto principle. Results: The sub-processes that contributed the most to risk were, in order of importance, the administration of the radiopharmaceutical, its preparation and the clinical prescription. For these, the most important, stages, failure modes and their causes were identified. There were causes that contributed to various failure modes. Non-compliance with procedures, protocols or practices, lack of staff training and staff fatigue are the causes of the identified risks. Conclusions: The effectiveness of the corrective measures of the most contributing causes, which are added to those derived from the matrix, was characterized in the improvement plan in radiosynoviorthesis and myelosupressor treatment of polycythemia vera in Cuba(AU)

Características clínicas y epidemiológicas de las neoplasias mieloproliferativas Philadelphia negativas en el sistema público de salud de Chile

Background: Philadelphia-negative myeloproliferative neoplasms (Ph-MPN) are chronic hematological disorders characterized by the overproduction of one or more mature myeloid blood cell lineages. Classical Ph-MPN are polycythemia vera (PV), essential thrombocytopenia (ET) and primary myelofibrosis (PMF). Aim: To assess the epidemiological, clinical and diagnostic characteristics of Ph-MPN in Chile. Material and Methods: Retrospective review of medical records of all patients referred as MPN from 2012 to 2017. Patients with (9;21) translocation were excluded. Results: Data of 462 cases with a median age of 69 years from 10 public hospitals was reviewed. ET was the most frequently Ph-MNP found. The incidence of Ph-MPN was 1.5 x 100.000 cases. The JAK2 V617F mutation study was performed in 96% of patients and only 30% had a bone marrow biopsy. Thrombotic events were observed in 29% of patients. Bleeding events were observed in 7%. Five-year overall survival was 87%. Conclusions: ET is the most frequent Ph-MPN. The mean incidence was lower than reported in the literature, in part because of a sub diagnosis.

Clinical and molecular profile of a Brazilian cohort of patients with classical BCR-ABL1-negative myeloproliferative neoplasms

ABSTRACT Background: The classical BCR-ABL1-negative myeloproliferative neoplasms (MPNs) are Polycythemia Vera (PV), Essential Thrombocythemia (ET) and Primary Myelofibrosis (PMF). In developing countries, there are few reports that truly reveal the clinical setting of these patients. Therefore, we aimed to characterize a single center MPN population with a special focus on the correct diagnosis based on the recent review of the WHO criteria for the diagnosis of myeloid neoplasms. Methods: This retrospective study analyzed data from medical records of patients with classical BCR-ABL1-negative MPNs diagnosed from January 1997 to October 2017 and followed at the University Hospital of Ribeirão Preto Medical School. Results: A total of 162 patients were assessed, 61 with PV, 50 with ET, and 51 with PMF. The mutational status analysis revealed that 113 (69.3%) harbored the JAK2V617F mutation, 23 (14.1%), the CALR mutation, and 12 (7.4%) had a triple-negative status. None of the patients were found to have mutations on the thrombopoietin receptor gene (MPL), including some ET and PMF patients who were not tested. Among the PV patients, 57 (93.5%) were positive for the JAK2V617F mutation, one (1.6%) presented an in-frame deletion JAK2 exon 12 mutation and one (1.6%) presented a missense JAK2 exon 9 mutation, not previously described. The overall survival was lower in the triple-negative patients with PMF, when compared to the JAK2V617F or CALR-mutated (p= 0.002). Conclusion: The frequency of somatic mutations and survival in our cohort, stratified according to the respective disease, was consistent with the literature data, despite some limitations. Further prospective epidemiological studies of MPN cohorts are encouraged in developing countries.

Vitamin D Deficiency and Janus kinase 2 V617F Mutation Status in Essential Thrombocythemia and Polycythemia Vera

@#Introduction: Vitamin D, which is known for its effects on calcium and bone metabolism, has recently been associated with haematological malignancies. We aimed to investigate the relationship between disease findings and vitamin D deficiency in essential thrombocythemia (ET) and polycythemia vera (PV). Material and Methods: This retrospective cohort study conducted in Turkey included 73 patients diagnosed with PV or ET according to WHO criteria between 2012 and 2018. Vitamin D deficiency was defined as 25-OH vitamin D < 20 ng/mL. Polymerase chain reaction (PCR) was used to detect the Janus kinase 2 (JAK2) V617F mutation. Results: Vitamin D deficiency was found in 66.7% of PV and 74.2% of ET patients. The median follow-up time of ET and PV patients was 48 months and 47 months, respectively. Patients with the JAK2 mutation had a higher prevalence of a history of thrombosis and age older than 65 years. There was a significant relationship between JAK2 positivity and vitamin D deficiency. Conclusion: There was a remarkably higher prevalence of vitamin D deficiency in JAK2 mutation-positive ET and PV patients. These patients should be carefully evaluated for vitamin D deficiency. More studies are required to further investigate the association between JAK2 and vitamin D.

Calidad de vida en pacientes con neoplasias mieloproliferativas crónicas Filadélfia negativas / Quality of life in patients with Philadelphia negative chronic myeloproliferative neoplasms

Resumen Introducción: la carga sintomática de pacientes con neoplasias mieloproliferativas crónicas Filadélfia negativas (NMC-PhN) afecta la calidad de vida (CV). Existen escalas para evaluar la magnitud de los síntomas, una de ellas, MPN-SAF-10. En nuestra región existe escasa información sobre CV de pacientes con NMC-PhN. Objetivos: estimar el puntaje de calidad de vida con la escala MPN-SAF-10 en pacientes con NMC-PhN atendidos en el Hospital de San José (Bogotá, Colombia) y explorar asociaciones entre el tiempo de tratamiento, carga de complicaciones y el efecto en la CV. Material y métodos: estudio de corte transversal analítico para evaluar CV basada en carga sintomática de pacientes con NMC-PhN del Hospital de San José (Bogotá, Colombia). Se realizó análisis descriptivo y estratificado de calidad de vida, tratamiento citorreductor y de diferentes complicaciones, así como pruebas de asociación de los puntajes de riesgo de cada enfermedad con sus respectivos puntajes de CV. Resultados: en 64 pacientes la escala MPN-SAF-10 documentó medianas de puntajes globales de CV de 3 (RIC 1-6), MPN-SAF-10 de 20 (RIC 8-32). Un 49% de los pacientes tuvo algún grado de alteración (30% moderada y 19% severa), sin diferencias entre las tres enfermedades. Los puntajes de CV no variaron entre las NMC-PhN. El tratamiento y duración del mismo no se correlacionaron con la escala de MPN-SAF-10 (hidroxiúrea r: - 0.27; ruxolitinib r: 0.12). Conclusiones: en pacientes con NMC-PhN, la evaluación de CV con la escala MPN-SAF-10 evidencia algún grado de afectación a pesar del tratamiento; ésta es útil para objetivar dicha afectación y debe implementarse en la práctica clínica. (Acta Med Colomb 2019; 44: 82-90).

Abstract Introduction: the symptomatic burden of patients with Philadelphia negative chronic myelopro liferative neoplasms (NMC-PhN) affects the quality of life (QL). There are scales to evaluate the magnitude of the symptoms; one of them, MPN-SAF-10. In our region there is scarce information on QL of patients with NMC-PhN. Objectives: To estimate the quality of life score with the MPN-SAF-10 scale in patients with NMC-PhN treated at Hospital de San José (Bogotá, Colombia) and to explore associations between treatment time, complication load and the effect on the QL. Material and methods: Analytical cross-sectional study to evaluate QL based on symptomatic load of patients with NMC-PhN from Hospital de San José (Bogotá, Colombia). A descriptive and stratified analysis of quality of life, cytoreductive treatment and different complications was carried out, as well as association tests of the risk scores of each disease with their respective QL scores. Results: in 64 patients the MPN-SAF-10 scale documented medians of global QL scores of 3 (RIC 1-6), MPN-SAF-10 of 20 (RIC 8-32). 49% of the patients had some degree of alteration (30% moderate and 19% severe), without differences between the three diseases. The QL scores did not vary between the NMC-PhN. The treatment and its duration did not correlate with the MPN-SAF-10 scale (Hydroxyurea r: - 0.27, Ruxolitinib r: 0.12). Conclusions: in patients with NMC-PhN, the evaluation of QL with the MPN-SAF-10 scale shows some degree of affectation despite the treatment; this is useful to objectify this affectation and should be implemented in clinical practice. (Acta Med Colomb 2019; 44: 82-90).

Evaluación del riesgo radiológico en la radiosinoviortesis y el tratamiento mielosupresor de la policitemia vera / Radiological risk assessment in radiosynoviorthesis and the myelosupressor treatment of polycythemia vera

Introducción: La aplicación del método de la matriz de riesgo para la evaluación del riesgo radiológico en la medicina permite identificar de manera proactiva debilidades en las etapas del proceso y hacer un plan de acciones de mejora para la seguridad y calidad. Objetivo: Evaluar los riesgos radiológicos de la radiosinoviortesis y el tratamiento mielosupresor con Fósforo-32 de la policitemia vera. Método: Se utilizó el método de matriz de riesgo y se realizó el análisis y tratamiento de los riesgos radiológicos por medio del código cubano SECURE-MR-FMEA 3.0. Resultados: El 17 por ciento del riesgo alto se eliminó con las medidas adicionales adoptadas; predominaron las consecuencias medias para los trabajadores y el público, 30 por ciento y el 14 por ciento, respectivamente. Las defensas más importantes fueron: levantamiento radiológico inicial de las áreas del departamento; revisión independiente del proyecto con las regulaciones de seguridad aplicables; inspección de trabajos de construcción civil y montaje de equipos antes de iniciar la operación del departamento; capacitación de los médicos nucleares en los tratamientos; existencia de protocolos de tratamiento; análisis de lecciones aprendidas de incidentes radiológicos; levantamiento radiológico periódico de las áreas del servicio y procedimiento de emergencia para reducir la dosis en órganos críticos en caso de administración errónea de radiofármacos. Se creó una base de datos de incidentes utilizada como referencia para el modelo utilizado. El factor humano fue la causa mayor de los sucesos radiológicos analizados (88 por ciento). Conclusiones: Estos resultados facilitan la toma de decisiones para el mejor desempeño de la radiosinoviortesis y el tratamiento de la policitemia vera con Fósforo-32 en Cuba. Se sugiere elaborar el plan de mejora de la seguridad con especial atención a las operaciones de administración del radiofármaco en ambos casos.(AU)

Introduction: The application of risk matrix for ionizing radiation medicine allow identify in proactive way the weakness of the process' step, which implies in the design of safety and quality improvement plan for this. Method: Risk matrix method applied for radiosynoviorthesis and the myelosupressor treatment with Phosphorus-32 of polycythemia vera. The Cuban code SECURE-MR-FMEA 3.0 is used. Results: It was eliminated the 17 percent of the high risk with additional measures, and the medium consequences for workers and public are 30 percent and 14 percent, respectively. The most important identified safety measures were the initial radiological monitoring from different nuclear medicine department areas; the project revision based on the applicable safety regulations; a survey of civil construction works and equipment assembly before work began; training of nuclear medicine doctors in related aspects of nuclear medicine treatments; existence of treatment protocols; the analysis of learned lessons from radiological incidents; the periodical radiological monitoring from different services areas and the emergency procedure for the cases of mistake in the radiopharmaceuticals administration. Human factor was the major cause in analyzed radiological events (88 percent). Conclusions: These results facilitate taking decisions for the best performance of radiosynoviorthesis and the myelosupressor treatment with Phosphorus-32 of polycythemia vera in Cuba. It is recommended to elaborate the safety improvement plan from these and focussing in the radiopharmaceutical administration operations in both cases.(AU)

Symptom load assessment of Ph chromosome/BCR-ABL fusion gene negative myeloproliferative tumor patients at different efficacy evaluation periods / 国际肿瘤学杂志

Objective@#To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN).@*Methods@#A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People′s Hospital of Longhua District of Shenzhen were selected, and were divided into polycythemia vera (PV) group, essential thrombocyhemia (ET) group, and myelofibrosis (PMF) group according to their subtypes, with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides, the scores of the scale (myeloproliferative neoplasm symptom assessment form total symptom score, MPN-SAF-TSS) in different treatment periods (at the time of the visit, when the disease progressed, when the disease was stable, when the clinical improvement was made, when the partial remission was completed, at the time of remission and recurrence) were also compared.@*Results@#At the time of initial diagnosis, there were significant differences in the incidences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ2=6.095, P=0.047), abdominal discomfort (χ2=7.342, P=0.025), poor mobility (χ2=13.029, P=0.001), inattention (χ2=6.099, P=0.047), pruritus (χ2=6.956, P=0.031), bone pain (χ2=7.807, P=0.020), fever (χ2=8.000, P=0.018) and weight loss (χ2=27.340, P<0.001). The incidences of poor mobility (85.71%, 24/28), inattention (67.86%, 19/28) and weight loss (82.14%, 23/28) in PMF group were significantly higher than those in PV group [42.86% (12/28), 39.29% (11/28), 35.71% (10/28)] and ET group [46.43% (13/28), 39.29% (11/28), 14.29% (4/28)] (all P<0.05). The incidences of abdominal discomfort (75.00%, 21/28) and bone pain (60.71%, 17/28) in PMF group were higher than those in PV group [39.29% (11/28), 25.00% (7/28)] (both P<0.05). The incidences of abdominal fullness (89.29%, 25/28) and fever (42.86%, 12/28) in PMF group were higher than those in ET group [60.71% (17/28), 10.71% (3/28)] (both P<0.05). The incidence of pruritus in PV group (71.43%, 20/28) was higher than that in ET group (42.86%, 12/28) and PMF group (39.29%, 11/28) (both P<0.05). Symptom load scores of patients with fatigue (χ2=368.594, P<0.001), abdominal fullness (χ2=261.312, P<0.001), abdominal discomfort (χ2=195.629, P<0.001), poor mobility (χ2=217.862, P<0.001), lack of concentration (χ2=280.664, P<0.001), night sweats (χ2=239.650, P<0.001), pruritus (χ2=254.418, P<0.001), bone pain (χ2=180.291, P<0.001), fever (χ2=231.613, P<0.001) and weight loss (χ2=227.831, P<0.001) were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P<0.05), and the symptom score of abdominal fullness was lower than that at the time of visit (P<0.05). Symptom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P<0.05). When the clinical improvement was made, symptom load scores of weakness, abdominal discomfort, inattention, night sweats, weight loss were lower than those when the disease was stable (all P<0.05). Symptom load scores of abdominal fullness, poor mobility, inattention, night sweats and pruritus in partial remission period decreased compared to temporary improvement period (all P<0.05). Compared to the partial remission period, the symptom load scores of weakness, abdominal fullness, night sweats, pruritus, bone pain and weight loss in complete remission period were lower (all P<0.05). At last, symptom load scores of weakness, abdominal fullness, abdominal discomfort, poor mobility, inattention, night sweats, pruritus, bone pain, fever and weight loss in recurrence period were higher than those in complete remission period (all P<0.05).@*Conclusion@#There are several differences in the main clinical symptoms among patients with different MPN subtypes, and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

Red blood cell lifespan detected by endogenous carbon monoxide breath test in patients with polycythemia vera / 中华内科杂志

Objective@#To detect the red blood cell lifespan in patients with polycythemia vera (PV), and explore the influencing factors.@*Methods@#From February 2017 to December 2018, 27 patients with PV at Blood Diseases Hospital, Chinese Academy of Medical Science and 18 normal controls were recruited. Red blood cell lifespan was detected by endogenous carbon monoxide (CO) breath test. The related factors were analyzed.@*Results@#The average red blood cell lifespan of 27 PV patients was 80 (range, 35-120) days (d), which was significantly shorter than that of the normal controls [110.5(69-166) d, P<0.05], namely 35.3 d shorter. The red blood cell lifespan of ten newly diagnosed patients and 17 patients who were treated with hydroxyurea and/or interferon were 98 (35-117) d and 69 (45-120) d, respectively, which were both shorter than that of the normal control (P=0.010, 0.000). Correlation analysis showed that red blood cell lifespan of patients with newly diagnosed PV was associated with JAK2 mutation allele burden (r=0.900, P=0.037), peripheral blood lymphocyte count (r=-0.742, P=0.014) and the level of serum vitamin B12 (r=-0.821, P=0.023).@*Conclusion@#The lifespan of red blood cells in patients with PV is about one-third shorter than normal, and is related to JAK2 mutation allele burden, absolute lymphocyte count, and serum vitamin B12 level.

Red blood cell lifespan detected by endogenous carbon monoxide breath test in patients with polycythemia vera / 中华内科杂志

Objective To detect the red blood cell lifespan in patients with polycythemia vera (PV), and explore the influencing factors. Methods From February 2017 to December 2018, 27 patients with PV at Blood Diseases Hospital, Chinese Academy of Medical Science and 18 normal controls were recruited. Red blood cell lifespan was detected by endogenous carbon monoxide (CO) breath test. The related factors were analyzed. Results The average red blood cell lifespan of 27 PV patients was 80 (range, 35-120) days (d), which was significantly shorter than that of the normal controls [110.5(69-166) d, P<0.05], namely 35.3 d shorter. The red blood cell lifespan of ten newly diagnosed patients and 17 patients who were treated with hydroxyurea and/or interferon were 98 (35-117) d and 69 (45-120) d, respectively, which were both shorter than that of the normal control (P=0.010, 0.000). Correlation analysis showed that red blood cell lifespan of patients with newly diagnosed PV was associated with JAK2 mutation allele burden (r=0.900, P=0.037), peripheral blood lymphocyte count (r=-0.742, P=0.014) and the level of serum vitamin B12 (r=-0.821, P=0.023). Conclusion The lifespan of red blood cells in patients with PV is about one?third shorter than normal, and is related to JAK2 mutation allele burden, absolute lymphocyte count, and serum vitamin B12 level.

Risk factors for recurrent thrombosis in patients with polycythemia vera and essential thrombocythemia / 中华血液学杂志

Objective@#To analyze the clinical characteristics of recurrent thrombosis in patients with polycythemia vera (PV) and essential thrombocythemia (ET) to probe the risk factors for recurrent thrombosis in patients with ET and PV.@*Methods@#The clinical data of 104 ET and PV patients with thrombosis in Beijing Anzhen Hospital from February 2001 to November 2016 were retrospectively analyzed. Thrombosis reoccurred in 38 patients. Statistical analyses were performed by multivariate logistic regression for risk factors of recurrent thrombosis in ET and PV patients.@*Results@#Recurrent thrombosis occurred in 36.5% of patients with ET/PV, the total incidence rate in ET and PV patients was 9.8% patient-years, 12.3% patient-years and 5.7% patient-years in ET and PV respectively. There were a total of 56 re-thrombotic events, and 42.1% of events occurred within 1 year after the first thrombosis. The arterial re-thrombosis was 97.4% (most of acute coronary syndrome, ACS), and venous events was 2.6%. The most common cases of re-thrombosis were ACS in ET patients (18 cases, 64.3%), and cerebral infarction in PV patients (7 cases, 70.0%). The number of PV patients with 2 times or more re-thrombotic events was significantly higher than that of ET patients (9 cases, 90.0% vs 7 cases, 25.0%). The proportion of the patients with WBC>12.5×109/L or Hct>45%, and thrombosis history or splenomegaly and high risk thrombotic events were higher than those with a single thrombus (52.6% vs 31.8%; 50.0% vs 30.0%; 86.8% vs 13.6%; 84.2% vs 33.3%; 52.6% vs 15.2%; 94.7% vs 53.0%; P values were 0.036,0.046, <0.001, <0.001, <0.001 and <0.001, respectively). Logistic regression analysis showed that thrombosis history (OR=13.697, P=0.025), splenomegaly (OR=13.301, P=0.034) and high risk stratification of thrombotic events (OR=44.618, P=0.025) were independent risk factors for recurrent thrombotic events.@*Conclusions@#ET and PV patients had a higher risk of re-thrombosis. The incidence of re-thrombosis in ET was higher than in PV, ACS was more common cases of re-thrombotic events; but PV patients were more susceptible to multiple re-thromboses than ET ones, also with more cerebral infarction. Previous thrombus history, splenomegaly and high risk stratification of thrombotic events were independent risk predictors for re-thrombosis of ET and PV patients.

Myeloproliferative neoplasms and coronary artery disease / 中国实用内科杂志

Myeloproliferative neoplasms(MPN) are high risk factors of atherosclerosis and arterial thromboembolism. This article gives a review on the incidence, pathogenesis, clinical features and treatment of MPN with coronary artery disease, emphasizing the importance of knowing MPN as possible causes of acute cardiovascular events in patients, in order to help clinicians to learn about the disease and make a proper diagnosis and treatment.

Research status of polycythemia vera in China / 中国实用内科杂志

Polycythemia vera is a clonal malignant hematopoietic disorder that results from genetic alterations in hematopoietic stem cells, which is characterized by two or three-line blood cells increase, and mainly by erythrocytosis. This article reviews research situation of PV in China, including pathogenesis, clinical features, disease progression and therapeutic options, which helps clinical specialists to carry out precise diagnosis and treatment.

Symptom load assessment of Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative tumor patients at different efficacy evaluation periods / 国际肿瘤学杂志

Objective To observe the disease type and the changes of symptom load during treatment of patients with Ph chromosome/ BCR-ABL fusion gene negative myeloproliferative neoplasm (MPN). Methods A total of 84 patients with MPN diagnosed from May 2017 to January 2019 in People's Hospital of Longhua Dis-trict of Shenzhen were selected,and were divided into polycythemia vera (PV)group,essential thrombocy-hemia (ET)group,and myelofibrosis (PMF)group according to their subtypes,with 28 cases in each group. The scores of MPN-SAF-TSS were compared among the three groups. Besides,the scores of the scale (myelo-proliferative neoplasm symptom assessment form total symptom score,MPN-SAF-TSS)in different treatment periods (at the time of the visit,when the disease progressed,when the disease was stable,when the clinical improvement was made,when the partial remission was completed,at the time of remission and recurrence) were also compared. Results At the time of initial diagnosis,there were significant differences in the inci-dences of symptom burdens among the three groups of MPN patients with abdominal fullness (χ2 = 6. 095,P =0. 047),abdominal discomfort (χ2 = 7. 342,P = 0. 025),poor mobility (χ2 = 13. 029,P = 0. 001),inatten-tion (χ2 = 6. 099,P = 0. 047),pruritus (χ2 = 6. 956,P = 0. 031),bone pain (χ2 = 7. 807,P = 0. 020),fever (χ2 = 8. 000,P = 0. 018)and weight loss (χ2 = 27. 340,P < 0. 001). The incidences of poor mobility (85. 71％,24 / 28),inattention (67. 86％,19 / 28)and weight loss (82. 14％,23 / 28)in PMF group were significantly higher than those in PV group [42. 86％ (12 / 28),39. 29％ (11 / 28),35. 71％ (10 / 28)]and ET group [46. 43％ (13 / 28),39. 29％ (11 / 28),14. 29％ (4 / 28)](all P < 0. 05). The incidences of abdominal discomfort (75. 00％,21 / 28)and bone pain (60. 71％,17 / 28)in PMF group were higher than those in PV group [39. 29％ (11 / 28),25. 00％ (7 / 28)](both P < 0. 05). The incidences of abdominal fullness (89. 29％,25 / 28)and fever (42. 86％,12 / 28)in PMF group were higher than those in ET group [60. 71％ (17 / 28),10. 71％ (3 / 28)](both P < 0. 05). The incidence of pruritus in PV group (71. 43％, 20 / 28)was higher than that in ET group (42. 86％,12 / 28)and PMF group (39. 29％,11 / 28)(both P <0. 05). Symptom load scores of patients with fatigue (χ2 = 368. 594,P < 0. 001),abdominal fullness (χ2 =261. 312,P < 0. 001),abdominal discomfort (χ2 = 195. 629,P < 0. 001),poor mobility (χ2 = 217. 862,P <0. 001),lack of concentration (χ2 = 280. 664,P < 0. 001),night sweats (χ2 = 239. 650,P < 0. 001),pruri-tus (χ2 = 254. 418,P < 0. 001),bone pain (χ2 = 180. 291,P < 0. 001),fever (χ2 = 231. 613,P < 0. 001) and weight loss (χ2 = 227. 831,P < 0. 001)were significantly different during different therapeutic periods. The fatigue symptom load score was higher when the disease progressed than that at the time of the visit (P <0. 05),and the symptom score of abdominal fullness was lower than that at the time of visit (P < 0. 05). Symp-tom load scores of weakness and pruritus when the condition was stable was lower than those when the disease progressed (both P < 0. 05). When the clinical improvement was made,symptom load scores of weakness, abdominal discomfort,inattention,night sweats,weight loss were lower than those when the disease was stable (all P < 0. 05). Symptom load scores of abdominal fullness,poor mobility,inattention,night sweats and pruri-tus in partial remission period decreased compared to temporary improvement period (all P < 0. 05). Compared to the partial remission period,the symptom load scores of weakness,abdominal fullness,night sweats,pruri-tus,bone pain and weight loss in complete remission period were lower (all P < 0. 05). At last,symptom load scores of weakness,abdominal fullness,abdominal discomfort,poor mobility,inattention,night sweats,pruri-tus,bone pain,fever and weight loss in recurrence period were higher than those in complete remission period (all P < 0. 05). Conclusion There are several differences in the main clinical symptoms among patients with different MPN subtypes,and there are significant changes in the main clinical symptoms as the disease progresses or turns around.

Policitemia vera: Presentación clínica, diagnóstico y nuevos abordajes teraPéuticos / Polycythemia Vera: clinical presentation, diagnosis and new therapeutic approaches

Introducción: los desórdenes mieloproliferativos como la Policitemia vera (PV) pertenecientes al grupo clásico filadelfia negativo, son un área de la hematología que requiere un acercamiento de mayor profundidad, de modo que sea posible ofrecer un abordaje clínico, diagnóstico y terapéutico de carácter amplio, pertinente y actualizado.Así será factible ofrecer alternativas a individuos que no responden a un tratamiento convencional. Objetivo: recoger los elementos clínicos característicos o de mayor importancia de la Policitemia vera y realizar una contextualización sobre las opciones terapéuticas existentes o disponibles y las nuevas alternativas en desarrollo, desde diferentes disciplinas médicas básicas como la biología molecular y el área de la inmunología. Materiales y métodos: se realizó durante el segundo semestre de 2017 y el primer trimestre de 2018 una revisión exhaustiva de material bibliográfico existente sobre la Policitemia vera, su fisiopatología, enfoque terapéutico actual y las nuevas alternativas médicas disponibles para su tratamiento, todo lo anterior en la base de datos de la Universidad Pontificia Bolivariana, utilizando motores de búsqueda como lo son PubMed, Clinical Key, SciELO y Science Direct. Conclusión: es de vital importancia el estudio y la comprensión de la fisiopatología de la Policitemia vera para llegar, en un futuro, a la instauración de nuevas alternativas terapéuticas para los pacientes que la padecen y no responden a terapias tradicionales, pues aún no existe cura para esta condición hematológica y actualmente su enfoque terapéutico se centra principalmente, en controlar, mitigar y prevenir las complicaciones asociadas a la misma..(AU)

Introduction: myeloproliferative disorders such as Polycythemia vera (PV) belonging to the classic Philadelphian negative group, are an area of internal medicine and hematology that requires a closer look, in order to offer a clinical, diagnostic and therapeutic approach of a broad, pertinent and updated nature. Thus it would be feasibleto offer alternatives to individuals who do not respond or do not have an indication to apply a conventional treatment. Objective: to collect the characteristic or most important clinical elements of the Polycythemia Vera and to contextualize the existing or available therapeutic options and the new alternatives in development, from different basic medical disciplines such as molecular biology and the area of immunology. Materials and methods: an exhaustive review of existing bibliographic material on Polycythemia Vera, its physiopathology, current therapeutic approach and the new medical alternatives available for its treatment, was carried out during the second semester of 2017 and the first quarter of 2018. This was made under the license of Universidad Pontificia Bolivarina database, using search engines such as PubMed, Clinical Key, SciELO and Science Direct. Conclusion: the study and understanding of the pathophysiology of Polycythemia Vera is of vital importance to reach the establishment of new therapeutic alternatives for patients who suffer it and do not respond to traditional therapies, as there is still no cure for this hematological condition and currently, its therapeutic approach is mainly focused on controlling, mitigating and preventing complications associated with it..(AU)

Trombosis espleno-portal no cirrótica, no tumoral y policitemia vera: una asociación poco frecuente / Non-cirrhotic Splenic-portal Thrombosis, non-tumoral Polycitemia Vera: an Infrequent Association

La policitemia vera se incluye dentro del grupo de las neoplasias mieloproliferativas crónicas. Tiene una incidencia inferior a 2,5 de cada 100 000 personas. Las formas trombóticas de presentación representan solo entre el 10-15 % de casos. La trombosis del eje espleno-portal no asociada a cirrosis o neoplasias tiene una prevalencia inferior a 5 por cada 10000 habitantes, entre el 17-53 % se asocian a algún tipo de síndrome mieloproliferativo primario. Se presenta el caso de una paciente de 70 años de edad que acudió debido a dolor abdominal de 15 días de evolución. El ultrasonido abdominal mostró en el hígado un marcado aumento de la ecogenicidad hacia las paredes de las estructuras vasculares, compatible con extensas áreas de trombosis del eje espleno-portal, corroborado luego por tomografía por contraste. La biopsia de médula ósea concluyó una hiperplasia de las tres series, la determinación de la mutación JAK2V617F resultó positiva. La baja incidencia de la policitemia vera y la forma inusual de mostrarse como una trombosis del sistema espleno-portal motivó a la presentación de este caso.

Polycitemia vera is included in the group chronic mieloproliferative neoplasias. It has an incidence below 2.5 every 100 000 people. The thrombotic forms represent only between 10.15 % of the cases. Splenic-portal thrombosis not associated to cirrhosis or neoplasias have an incidence below 5 every 10000 inhabitants, between 17-53 % are associated to any type of primary mieloproliferative syndrome. A case of a 70 year old patient who came to the doctor complainig of an abdominal pain of 15 day duration. Abdominal ultrasound showed a markedly ecogenic liver towards vascular structures, compatible with extensive thrombotic areas of the splenic-portal axis, corroborated later by contrast tomography. Bone morrow biopsy concluded a three series hyperplasia, the determination of JAK2V617F mutation was positive. The low incidence of polycitemia vera and its unusual way of presenting as thromobosis of splenic-portal system motivated the presentation of this case.