Clinical features of myeloproliferative neoplasms with portal hypertension as the main manifestation / 临床肝胆病杂志

Objective To investigate the clinical features, liver histological features, and diagnostic and treatment methods for patients with myeloproliferative neoplasms (MPN) with portal hypertension as the main manifestation. Methods A retrospective analysis was performed for related data of the patients who attended the hospital due to portal hypertension and were finally diagnosed with MPN in Liver Research Center, Beijing Friendship Hospital, from January 2019 to February 2022, including clinical manifestation, liver pathological features, treatment, and follow-up results. Results Nine patients were included in this study, and all the patients had splenomegaly and esophageal and gastric varices, while portal vein thrombosis was observed in eight patients. All patients had normal or slightly abnormal liver function and routine blood test results. Six patients underwent liver biopsy, without the formation of fibrous septum and pseudolobule, and hepatic extramedullary hematopoiesis was observed in two patients. All nine patients underwent bone marrow biopsy and genetic testing, among whom six had essential thrombocythemia and three had primary myelofibrosis, and genetic testing revealed JAK - 2V617F gene mutation in seven patients and CALR gene mutation in two patients. Conclusion MPN is one of the rare causes of portal hypertension and has the clinical manifestations of esophageal and gastric varices, splenomegaly, and even megalosplenia, without the manifestations of hypersplenism such as leukopenia and thrombocytopenia. Detection of the JAK - 2V617F and CALR genes can improve the diagnostic rate of MPN.

Liver and spleen stiffness measurements in patients with BCR-ABL-negative myeloproliferative neoplasms and their clinical significance / 中国基层医药

Objective:To measure liver and spleen stiffness in patients with BCR-ABL-negative myeloproliferative neoplasms and analyze their clinical significance.Methods:Fifteen healthy volunteers and 27 patients with BCR-ABL-negative myeloproliferative neoplasms underwent liver and spleen thickness measurements using FibroScan 502 Touch medical device between June 2018 and June 2020 in Hebei Petro China Central Hospital and they were included in this study. Liver and spleen stiffness was correlated with clinical laboraty indicators.Results:Liver stiffness, spleen stiffness, and the difference between spleen stiffness and liver stiffness in patients with BCR-ABL-negative myeloproliferative neoplasms were significantly greater than those in healthy controls [(6.34 ± 2.22) kPa vs. (5.07 ± 1.27) kPa; (26.00 ± 10.66) kPa vs. (13.61 ± 5.64) kPa; (19.65 ± 10.37) kPa vs. (8.54 ± 5.33) kPa, t = -2.01, -4.30, -4.06, all P < 0.05]. Platelet count was negatively correlated with liver and spleen stiffness ( r = -0.39, -0.42). White blood cell count was negatively correlated with the difference between spleen stiffness and liver stiffness ( r = -0.40, P < 0.05). The uric acid level was negatively correlated with liver stiffness ( r = -0.54, P < 0.05), but it was positively correlated with spleen thickness ( r = 0.41, P < 0.05). The percentage of B lymphocytes among lymphocytes was negatively correlated with spleen stiffness and the difference between spleen stiffness and liver stiffness ( r= -0.56, -0.56, both P < 0.05). The percentage of diseased megakaryocytes was positively correlated with spleen stiffness ( r = 0.40, P < 0.05). The percentage of sideroblasts was negatively correlated with liver stiffness ( r = -0.44, P < 0.05). Conclusion:Spleen stiffness and liver stiffness are closely related to clinical indicators in patients with BCR-ABL-negative myeloproliferative neoplasms, including white blood cell count, platelet count, uric acid level, percentage of B lymphocytes, diseased megakaryocytes and sideroblasts. Dynamic monitoring of liver and spleen stiffnesses or in combination with bone marrow examination in future can help evaluate the condition of patients with BCR-ABL-negative myeloproliferative neoplasms.

Estudio de mutaciones en neoplasias mieloproliferativas Philadelphia negativas en un hospital público chileno / Search for mutations in patients with Philadelphia negative myeloproliferative neoplasms in a public hospital in Chile

BACKGROUND: Philadelphia negative myeloproliferative neoplasms (Ph-MPN) are clonal disorders whose pathogenesis has been elucidated in recent years, creating diagnostic and prognostic algorithms. AIM: To study JAK2, CALR y MPL gene mutations in patients with Ph-MPN. MATERIALS AND METHODS: Descriptive cross-sectional observational study of patients with MPN (2015-2019), reviewing clinical, demographic and laboratory data. JAK2, CALR and MPL gene mutations were analyzed by RT-PCR. Results: We studied 72 patients. Fifty percent had essential thrombocythemia (ET), 26.4% had polycythemia vera (PV) and 23.6% had primary myelofibrosis (PM). Bone marrow biopsy was available in 76.5%. At diagnosis, the mean age was 65.5 years and 61% were symptomatic. A thrombotic event was the most frequent problem in 20% and 25% had splenomegaly. There were statistically significant differences in hematological parameters between the different MPNs. JAK2 V617F mutation was detected in 61.1%. Only 19 JAK2 V617F negative patients were available for CALR and MPL mutation studies, identifying 10 triple negative cases. Kaplan Meier curves showed a median survival of 88 months, being similar in the three MPNs. Causes of death in 20 patients were thrombotic complications in 30%, disease progression in 25%, infection in 20%, other neoplasms in 15% and other causes in 10%. CONCLUSIONS: The presentation and frequency of JAK2 V617F, CALR and MPL mutations in our cohort was similar to those reported in other studies for ET and PM. JAK2 V617F mutation was lower for PV. No significant differences between the three MPNs were observed for overall survival. We could not assess the prognostic value of the mutations.

Clinical Correlation of Lactate Dehydrogenase Activity with JAK2V617F and FLT3 Mutations in Myeloproliferative Disorders and Acute Myeloid Leukemia: Indian Population

Background: Lactate dehydrogenase (LDH) play main role in the cell damage.Previous study has shown elevated level in acute leukemia and myeloproliferative disorders. Molecular markers specifically for JAK2V617F mutation in myeloproliferative disorders (MPDs) and FLT3 mutations in acute myeloid leukemia patients (AML) are well known for clinical practice. But, still only few reports have shown the correlation of LDH activity with molecular markers in Hematological Malignancy. Therefore, aim of study is to correlate LDH activity with established specific molecular markers in MPDs and AML. Methods:10 healthy individuals, 50 patients with MPDs and 50 patients with AML were included for the study. Serum LDH was performed by autoanalyser. The JAK2V617F mutations is analyse from blood by Real time PCR and FLT3 ITD/D835 mutations are analysed from blood by PCR-RFLP respectively. Statistical analysis was done by SPSS statistical software. Results: LDH Activity were higher in MPDs and AML as compared with healthy individual. Mean LDH activity was higher in FLT3 ITD/D835 positive mutation and JAK2V617F positive mutation in AML and MPDs respectively was observed. Conclusion: High LDH activity with Positive frequency of FLT3 ITD/D835 mutation in Acute Myeloid Leukemia and Positive frequency of JAK2V617F mutation in Myeloproliferative Disorders were observed.

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.

Clinical Spectrum of Primary Polycythaemia and Its Complications -Experience from a Single Center in Karnataka.

Awareness and diagnosis of Philadelphia Negative Chronic Myeloproliferative Disorders has now improved and there is a need for more epidemiological data from India. MethodsThis is a retrospective study of patients of polycythaemia conducted at clinical haematology services, BMCRI, Bengaluru from 2010 to 2017. Results88 patients of polycythaemia were retrospectively studied. 84.1% were male and 15.9% were female. Their ages ranged from 19 to 79 years. 75 (85.23%) had Polycythaemia Rubra Vera (PRV). JAK-2 (V617F) mutation was positive in 33.33%. The commonest presentation was with unexplained erythrocytosis in 50 (66.66%), thrombosis in 20 (26.66%) and with bleeding in 2 (2.66%). 22 thrombotic events occurred in 20 PRV patients. Cortical sinus thrombosis was seen in 27.3%, cerebrovascular accidents in 22.8%, portal vein thrombosis in 13.6%, pulmonary embolism in 9.1%, central retinal artery occlusion in 13.6%, myocardial infarction in 4.5% and digital infarction in 9.1% patients. 3 cases of PRV presented with diplopia. No other definitive cause for ocular palsy could be found. The JAK 2 positive group was slightly older than the negative group and had higher frequency of splenomegaly (p<0.05) and higher values for haemoglobin (p<0.001) and neutrophil counts (p<0.001) and platelet counts (p<0.05). ConclusionsPatients with thrombosis, erythrocytosis, thrombocytosis and haemorrhage should be suspected to have myeloproliferative disorders like PRV and investigated. Ophthalmoplegia is a rare presentation and should raise the suspicion for polycythaemia. There is a higher probability of splenomegaly and higher values for haemoglobin and neutrophil counts and platelet counts in JAK 2 positive group.

Pioderma gangrenoso paraneoplásico en una paciente con recaída de leucemia mieloide aguda / Paraneoplastic bullous pyoderma gangrenosum occurring in a patient with a relapse of an acute myeloid leukemia

Resumen El pioderma gangrenoso ampolloso fue descrito por primera vez en 1972. Se presenta el caso de una paciente con pioderma gangrenoso asociado a una recaída de leucemia mieloide aguda y se hace una revisión de la literatura sobre el tema.

Abstract Bullous pyoderma gangrenosum was first described by Perry in 1972. We present a case of a patient with paraneoplastic pyoderma gangrenosum associated to relapse of an acute myelogenous leukemia and we review the literature on pyoderma gangrenosum.

CD47 expression is decreased in hematopoietic progenitor cells in patients with myelofibrosis

Myelofibrosis (MF) is characterized by increased circulating hematopoietic progenitor cells (HPCs), abnormal cytokine levels, and the survival advantage of neoplastic progenitors over their normal counterparts, which leads to progressive disappearance of polyclonal hematopoiesis. CD47 is a surface glycoprotein with many functions, such as acting as a phagocytosis inhibitor of the expressing cell, that is increased in normal hematopoietic stem and progenitor cells mobilized into the blood and several human cancer-initiating cells, such as in acute myeloid leukemia. We compared CD47 expression in hematopoietic stem and progenitor cells of patients with MF and controls and found it to be decreased in progenitors of MF. Exposure of control HPCs to the cytokines transforming growth factor β and stromal-derived factor 1, which are important regulators of hematopoietic stem cell cycling and are overexpressed in patients with MF, did not modulate CD47 expression.

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.

Mutational profile of myeloproliferative neoplasms detected by a customized NGS-based gene panel / 中华检验医学杂志

Objective By a sequencing panel consisting of 50 targeted genes, aiming at depicting the molecular landscape of ET, PV, and PMF, which are three major subtypes of MPN, to provide valuable information in the diagnosis and prognosis of MPN.Methods A retrospective study was conducted of 53 patients from Huashan hospital and Changhai hospital. All patients were diagnosed in accordance with the 2016 WHO diagnostic criteria for MPN, including 31 cases of ET(11 males, 20 females, median age 55 years), 17 cases of PV(12 males, 5 females, median age 65 years), and 5 cases of PMF(4 males, 1 females, median age 67 years), and underwent next-generation of DNA sequencing of their bone marrow or blood samples. The genetic analyses were performed on bone marrow or peripheral blood. Referring to COSMIC, dbSNP, Clinvar and other public databases, we analyzed the sequencing data, and elucidated the mutation profile of MPN patients, combining with their clinic information. Results In addition to the typical JAK2, CALR, and MPL mutations, pathogenic mutations in other 11 genes were detected, as well as 4 SNPs that confer individual susceptibility to MPNs (rs4858647, rs9376092, rs58270997, rs621940). The average rate of mutated genes was 2.3 genes per patient. In all patients (53 cases), the mutated genes detected were TET2, EZH2, ASXL1, MIR662, SF3B1, BARD1, DNMT3A, KIT, RUNX1, TP53, NRAS according to their mutational frequency. Conclusions Applying next-generation sequencing technology, multi-gene sequencing of a bunch of typical BCR-ABL-negative MPN patients can be performed at one time within 2 working days, and pathogenic mutations other than JAK2, CALR, MPL can be found, which has a bright prospection in clinic.

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.

Pigmented purpura and cutaneous vascular occlusion syndromes

Abstract: Purpura is defined as a visible hemorrhage in the skin or mucosa, which is not evanescent upon pressure. Proper classification allows a better patient approach due to its multiple diagnoses. Purpuras can be categorized by size, morphology, and other characteristics. The course varies according to the etiology, as do the diagnostic approach and treatment. This review discusses pigmented purpuras and some cutaneous vascular occlusion syndromes.

Caracterización y síntomas de pacientes colombianos con neoplasias mieloproliferativas crónicas / Characterization and Symptoms of Patients in Colombia with Chronic Myeloproliferative Neoplasm / Caracterização e sintomas de pacientes colombianos com neoplasias mieloproliferativas

Resumen Objetivo: describir las características sociodemográflcas y los síntomas en pacientes colombianos con neoplasias mieloproliferativas crónicas. Métodos: los autores utilizaron la información contenida en el ejercicio de validación de la escala de síntomas MPN-SAF TSS -myeloproliferative neoplasm symptom assessment form total symptom score-, la cual, a través de una metodología de encuesta en 62 pacientes diagnosticados con estas neoplasias a nivel nacional, aportó el insumo de análisis para alcanzar el objetivo de este estudio. Resultados: dentro de las características sociodemográflcas, la variable edad concentró el 59% de los pacientes incluidos en el estudio por encima de los 60 años con una media de 58,8 (DS 15,53). Se identifica una mayor frecuencia y severidad de los síntomas en pacientes con diagnóstico de policitemia vera, seguido de trombocitemia esencial y, por último, en pacientes con diagnóstico de mielofibrosis. La "fatiga" se manifestó en el 98,3% de los pacientes, siendo el principal síntoma registrado en la escala utilizada en este estudio. Conclusión: los pacientes en estudio presentaron una edad promedio de 59 años con una mayor proporción de mujeres (58%) y una escolaridad baja (40%). El total de síntomas referidos en la escala se presentaron en más del 70% de los pacientes, siendo los más frecuentes fatiga, saciedad temprana y problemas de concentración.

Abstract Objective: To describe the sociodemographic characteristics and symptoms in Colombian patients with chronic myeloproliferative neoplasms. Methods: The authors used the information contained in the validation exercise symptom scale MPN-SAF TSS -myeloproliferative neoplasm symptom assessment form the total symptom score-, which, through a survey methodology in 62 patients diagnosed with these malignancies level in Colombia, provided the input analysis to achieve the objective of this study. Results: Among the socio-demographic characteristics, the age variable accounted for 59% of the patients included in the study over 60 years, with a mean of 58.8 (SD 15.53). Increased frequency and severity of symptoms in patients diagnosed with polycythemia vera were identified, followed by essential thrombocythemia and finally in patients diagnosed with myelofibrosis. "Fatigue" was expressed in 98% of patients to be the main symptom registered on the scale used in this study. Conclusion: The patients in the study had a mean age of 59 years with a higher proportion of women by 58% and a low level of schooling of 40%. The total number of symptoms referred to in the scale occurred in more than 70% of the patients, being the most frequent fatigue, early satiety and concentration problems.

Resumo Objetivo: descrever as características sócio demográficas e os sintomas em pacientes colombianos com neoplasia mieloproliferativa crónica. Métodos: os autores utilizaram a informação contida no exercício de validação da escala de sintomas MPN-SAF TSS -myeloproliferative neoplasm symptom assessment form total symptom score-, a qual, através de uma metodologia de questionário em 62 pacientes diagnosticados com estas neoplasias a nível país, aportaram o insumo de análise para alcançar o objetivo deste estudo. Resultados: dentro das características sócio demográficas, a variável idade concentrou o 59% dos pacientes incluídos no estudo por cima dos 60 anos com uma média de 58,8 (DS 15,53); se identifica uma maior frequência e severidade dos sintomas, em pacientes com diagnóstico de policitemia vera, seguido de trombocitemia essencial e por último em pacientes com diagnósticos de mielofibrose. A "fatiga" se manifestou no 98,3% dos pacientes sendo o principal sintoma registrado na escala utilizada neste estudo. Conclusão: os pacientes em estudo apresentaram uma idade média de 59 anos com uma maior proporção de mulheres 58% e uma escolaridade baixa do 40; o total de sintomas referidos na escala se apresentaram em mais do 70% dos pacientes, sendo os mais frequentes a fatiga, saciedade precoce e problemas de concentração.

Major Changes to the 2017 Revision of the World Health Organization Classification of Myeloproliferative Neoplasms / 대한내과학회지

The World Health Organization (WHO) Classification of Tumors of Haematopoietic and Lymphoid Tissues was recently published in a revised fourth edition. The categories of myeloproliferative neoplasms (MPNs) have not significantly changed since the 2008 fourth edition of the classification; however, newly discovered mutations including CALR and CSF3R and improved characterizations and standardizations of morphological features of some entities, particularly BCR-ABL1-negative MPNs, have impacted the diagnostic criteria of disease entities, increasing the reliability and reproducibility of diagnoses. The 2017 revised edition attempts to incorporate new clinical, prognostic, morphologic, and genetic data that have emerged since the last edition. This article reviews the major changes in the classification and their rationale for MPN classification within the revised 2017 WHO system.

Acute leukemia transformed from myeloproliferative neoplasms with Philadelphia chromosome-negative: report of eight cases and review of literature / 白血病·淋巴瘤

Objective@#To analyze the disease progression of acute leukemia (AL) transformed from myeloproliferative neoplasms (MPN) with Philadelphia chromosome-negative (Ph-), and to investigate its mechanism and clinical treatments.@*Methods@#The pre-transformation and post-transformation data of 8 AL patients with Ph- MPN from July 2013 to December 2017 in Ruijin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The literature was also reviewed.@*Results@#All 8 cases transformed into acute myelogenous leukemia (AML). The median conversion time was 47.5 months (2-180 months), and the median survival time after transformation was 2 months (1-17 months). Three of 4 patients who undergone AML-related molecular biology after transformation had new mutant genes. One refractory patient achieved stable disease after oral treatment with ruxolitinib.@*Conclusions@#AML patients transformed from MPN have poor clinical outcomes and short survival time. Allogeneic hematopoietic stem cell transplantation is the only known potential curative treatment strategy and JAK2 inhibitor may be effective.

A Concomitant Hemato-Oncologic Disorder of Patient with Down Syndrome

A patient with Down syndrome has hematologic and oncologic disorders of medical complication. Down syndrome shows that characteristic hematologic and oncologic abnormalities and developments of disorders are different at ages. Many hematologic disorders were related to Down syndrome. There are diseases of red blood cells, white blood cell disorders, platelet and bleeding disorders, aplastic anemia, and transient myeloproliferative disease. Acute myeloid leukemia, acute lymphoblastic leukemia, and rarely solid tumors (Neuroblastoma, Wilm's tumor, Hodgkin's lymphoma) are also associated with Down syndrome. We checked clinical manifestations of each disorder and we should make standard hematologic index of different age groups. In addition, the relations between chromosome 21 and hemato-oncologic disorders should be found. We need to investigate potential therapeutic interventions that can improve quality of life and life expectancy in patients with Down syndrome.

Descripción de las caracteristicas clínicas de las neoplasias mieloproliferativas crónicas (NMPC). Primer informe del registro colombiano de NMPC / Description of the clinical characteristics of chronic myeloproliferative neoplasms (MPNs). First report of the colombian registry of MPNs

Resumen Introducción y objetivos: las neoplasias mieloproliferativas crónicas (NMPC) son relativamente raras, con incidencias que varían entre 0.47-1.03/100 000 habitantes. Se presenta el primer informe del trabajo del registro colombiano de NMPC, cuyo objetivo es describir las características clínicas de estos pacientes en nuestro país. Material y métodos: estudio descriptivo observacional, multicéntrico, retrospectivo y prospectivo en ocho centros del país, de abril de 2013 a diciembre de 2014. Las variables cualitativas se presentan con frecuencias absolutas y relativas; y las cuantitativas se resumen en medidas de tendencia central y dispersión. Resultados: once centros fueron aprobados, ocho ingresaron pacientes. En los primeros 179 casos reportados, 50% eran hombres, la edad promedio al diagnóstico 58.7 años (rango 19-92). Noventa y tres muestran trombocitemia esencial (TE); 55, policitemia vera (PV); y 31, mielofibrosis (MF). El 41% tenía esplenomegalia al diagnóstico; el 20% tuvo complicaciones trombóticas; y 12.85%, sangrado. Sólo en 57.5% se realizó JAK; de ellos, en 53.5% fue positivo, en especial sólo 60% de las PV. El 8% de los casos no tenía estudio de médula ósea, el 29.3% tiene algún grado de fibrosis. El hallazgo más frecuente fue hiperplasia megacariocítica en 59.78%. Más de 50% de pacientes estaban sintomáticos al diagnóstico. Sólo el 11% no recibió tratamiento farmacológico; los más frecuentes fueron hidroxiurea en 149 casos y ASA en 79. Con promedio de seguimiento de 52.6 meses; el 97.21% de los pacientes están vivos. Conclusiones: los hallazgos sugieren que algunas características de las NMPC podrían ser diferentes a lo reportado en otras series, lo que valida la importancia del esfuerzo de recoger información local.

Abstract Introduction and objectives: chronic MPNs are relatively rare, with incidences varying between 0.47-1.03 / 100 000 inhabitants. The first report of the work of the Colombian registry of chronic MPNs, whose objective is to describe the clinical characteristics of these patients in our country, is presented. Materials and methods: descriptive observational, multicenter, retrospective and prospective study in eight centers of the country, from April 2013 to December 2014. Qualitative variables are presented with absolute and relative frequencies, and the quantitative ones are summarized in measures of central tendency and dispersion. Results: eleven centers were approved; 8 admitted patients. In the first 179 cases reported, 50% were men; the average age at diagnosis was 58.7 years (range 19-92). Ninety-three present essential thrombocythemia (ET); 55, polycythemia vera (PV); and 31, myelofibrosis (MF). 41% had splenomegaly at diagnosis; 20% had thrombotic complications, and 12.85%, bleeding. JAK was performed in only 57.5%. Of them, in 53.5% was positive, especially in only 60% of the PV. 8% of the cases had no bone marrow study; 29.3% had some degree of fibrosis. The most frequent finding was megakaryocytic hyperplasia in 59.78%. More than 50% of patients were symptomatic at diagnosis. Only 11% did not receive pharmacological treatment, being the most frequent hydroxyurea in 149 cases and ASA in 79, with an average follow-up of 52.6 months. 97.21% of patients are alive. Conclusions: the findings suggest that some characteristics of chronic MPNs could be different from those reported in other series, which validates the importance of the effort to collect local information.

Validación de la escala abreviada de síntomas en pacientes con neoplasias mieloproliferativas (MPN-SAF-TSS): evaluación en pacientes colombianos / Validation of the Abbreviated Symptom Scale for Patients with Myeloproliferative Neoplasm (MPN-SAF-TSS): Evaluation for Colombian Patients / Validação da Escala Abreviada de Sintomas em Pacientes com Neoplasias Mieloproliferativas (MPN-SAF-TSS): Avaliação em Pacientes Colombianos

Resumen Objetivo: Validar en Colombia la escala abreviada de síntomas representativos de neoplasias mieloproliferativas para su posterior uso en investigación y aplicación en el ámbito clínico. Materiales y métodos: Se realizó la adaptación transcultural de la escala MPN-SAF-TSS (por sus siglas en inglés: Mieloproliferative Neoplasm Symptom Assesment Form-Total Sympton Score) a español y al contexto colombiano, con análisis estadísticos de validez y confiabilidad con un tamaño de muestra determinado para cada propiedad psicométrica. Resultados: Con base en las propiedades psicométricas se logró verificar la confiabilidad y la estructura interna de la escala con alfa de Cronbach de 0,8552, lo que denota una buena consistencia interna; se obtuvo un coeficiente de correlación de concordancia de Lin de 0,765 que muestra una buena confiabilidad. El análisis factorial mostró múltiples valores de coeficiente de correlación por encima de 0,3, lo que indica que las variables de la escala miden factores comunes; la validez de criterio concurrente determina que la escala mide lo que debe medir con un adecuado coeficiente de correlación de Spearman de -0,71 y -0,73 al confrontarla con las escalas FACIT-Fatigue y Fact-Lym respectivamente. Conclusión: La escala MPN-SAF-TSS adaptada a español y al contexto colombiano es un instrumento válido para la evaluación de síntomas en pacientes con neoplasias mieloproliferativas y puede ser utilizado en la práctica clínica o en estudios clínicos por sus adecuadas propiedades psicométricas.

Abstract Objective: To validate in Colombia the abbreviated scale of representative symptoms of myeloproliferative neoplasms, for further use in research and for application in the clinical setting. Materials and methods: A cross-cultural adaptation of the MPN-SAF TSS-scale (mieloproliferative neoplasm symptom assessment form total symptom score) to Colombian Spanish using statistical validity and reliability analysis with a specific sample size for each psychometric property. Results. Based on the psychometric properties, the verification of reliability and internal structure with a Cronbach's alpha scale of 0.8552 was achieved, denoting good internal consistency. A Lin's concordance correlation coefficient of 0.765 was obtained, showing good reliability; factor analysis showed multiple correlation coefficient values above 0.3, indicating that the scale variables measure common factors. Concurrent validity determines that the scale measures what it should measure with an adequate Spearman correlation coefficient of -0.71 and -0.73 when confronted with the FACIT-Fatigue and Fact-Lym scales, respectively. Conclusion: The MPN-SAF-TSS scale adapted to Colombian Spanish is a valid assessment instrument for symptoms in patients with myeloproliferative neoplasms and can be used in clinical practice or trials due to its adequate psychometric properties.

Resumo Objetivo: Validar na Colômbia, a escala abreviada de sintomas representativos de neoplasias mielo-proliferativas, para u seu posterior uso em investigação e a sua aplicação no âmbito clínico. Materiais e métodos: Realizou-se a adaptação transcultural da escala MPN-SAF-TSS (pelas suas siglas em inglês mieloproliferative neoplasm symptom assesment form total sympton score) ao espanhol colombiano, com análises estadísticas de validez e confiabilidade com um tamanho de amostra determinado para cada propriedade psicométrica. Resultados: Com base nas propriedades psicomé-tricas conseguiu-se verificar a confiabilidade e a estrutura interna da escala com alfa de Cronbach de 0,8552, o que denota uma boa consistência interna; se obteve um coeficiente de correlação de concordância de Lin de 0,765 mostrando uma boa confiabilidade; a análise fatorial mostrou múltiplos valores de coeficiente de correlação por acima de 0.3 indicando que as variáveis da escala medem fatores comuns, a validez de critério concorrente determina que a escala mede o que deve medir, com um adequado coeficiente de correlação de Spearman de -0,71 e -0,73 ao confrontá-la com as escalas FACIT-Fatigue e Fact-Lym respectivamente. Conclusão: A escala MPN-SAF TSS adaptada ao espanhol colombiano, é um instrumento válido para a avaliação de sintomas em pacientes com neoplasias mieloproliferativas e pode ser utilizado na prática clínica ou em estudos clínicos pelas suas adequadas propriedades psicométricas.

Analysis of gene mutation and risk factors of thrombosis in patients with bcr-abl negative myeloproliferative neoplasms / 白血病·淋巴瘤

Objective To explore the relationship between gene mutation of JAK2 V617F, JAK2 (exon12), CALR, MPL and clinical features of patients with bcr-abl negative myeloproliferative neoplasms (MPN), and to analyze the risk factors of thrombosis. Methods Clinical features and laboratory tests of 115 patients with bcr-abl negative MPN were analyzed retrospectively. 34 patients with thrombosis were treated as the observation group, and 81 patients without thrombosis were treated as the control group. Results Among 71 primary thrombocythemia cases, the white blood cell count (WBC) and hemoglobin level of JAK2 V617F positive group and CALR positive group was higher than that of 4 gene mutations in negative group (F= 5.835, P= 0.005; F= 3.405, P= 0.039). The incidence of splenomegaly in JAK2 V617F positive group and CALR positive group was higher than that of 4 gene mutations in negative group (χ2=16.902, P=0.0002; χ2= 12.658, P= 0.001). The patients'proportion of JAK2 V617F positive, high hemoglobin level (male ≥160 g/L, female ≥150 g/L), hypertension and over 60 years old in the observation group was higher than that in the control group (χ2= 5.585, P= 0.025; χ2= 4.909, P= 0.043; χ2= 8.891, P= 0.004; χ2=15.933, P=0.023). Conclusion The detection of JAK2 V617F, JAK2 (exon12), CALR and MPL gene mutations is helpful to the diagnosis of bcr-abl negative MPN; JAK2 V617F positive, high hemoglobin level, hypertension, and elderly age are risk factors of thrombosis.