RESUMO
OBJECTIVE@#To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation, and establish a systematic evaluation system to verify the success of model construction.@*METHODS@#The bone marrow c-kit+ cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit+ cells were sorted after incubation with CD117 magnetic beads. The method of constructing mouse primary mutant cells is as follows: A gene mutation vector with a GFP tag was constructed by the retroviral system, and the retroviral vector was packaged into the Platinum-E cells to obtain the virus supernatant, and then used it to infect the c-kit+ cells of mice. The MPN mouse model was constructed as follows: the mouse primary c-kit+ cells containing the mutant genes were collected after infection, and then transplanted them via the tail vein into the female recipient mice of the same species which were irradiated with a lethal dose of gamma rays (8.0 Gy). The MPN mouse model was evaluated as follows: After transplantation, the peripheral blood of the mice was regularly collected from the tail vein to perform the complete blood count test, and the size of spleen and the degree of bone marrow fibrosis were estimated.@*RESULTS@#The mouse c-kit+ cells with the mutant genes were successfully obtained from the bone marrow. MPN mouse model was successfully constructed: The peripheral blood cells of the MPN-transplanted mice carried exogenous implanted GFP-positive cells, and the white blood cells (WBC), platelet (PLT) and hematocrit (HCT) were all increased; the body weight loss, and the water and food intake were reduced in the transplanted mice; further pathological analysis showed that the transplanted mice displayed splenomegaly and bone marrow fibrosis. These results suggested that the MPN mouse model was successfully constructed. According to the common and different characteristics of the three MPN mouse model, a preliminary evaluation system for judging the success of MPN mouse model construction was summarized, which mainly included the following indicators, for example, the proportion of GFP-positive cells in the peripheral blood of mice; WBC, PLT and HCT; the degree of spleen enlargement and the bone marrow fibrosis.@*CONCLUSION@#The MPN mouse model with JAK2-V617F, MPLW515L or CALR-Type I gene mutation is successfully established by retroviral system, which can provide an important experimental animal model for the research of MPN pathogenesis and drug-targeted therapy.
Assuntos
Feminino , Camundongos , Animais , Mielofibrose Primária , Transtornos Mieloproliferativos/genética , Medula Óssea/patologia , Mutação , Modelos Animais de Doenças , Neoplasias , Janus Quinase 2/genéticaRESUMO
Primary myelofibrosis (PMF) is easily confused with cirrhosis, due to its main clinical manifestations of splenomegaly and the blood cytopenia. This review focuses on clinical studies to identify primary myelofibrosis and cirrhosis related portal hypertension, to analyze the differences between the two diseases, in order to distinguish PMF and cirrhosis from the pathogenesis, clinical manifestations, laboratory examinations and treatment principles, and simultaneously improve clinicians' understanding of PMF, which is a reference for exploring the early screening or diagnostic indicators of PMF, also provides a clinical basis for the application of new targeted drugs such as ruxolitinib.
Assuntos
Humanos , Mielofibrose Primária/tratamento farmacológico , Hipertensão Portal/complicações , Cirrose Hepática/patologia , Esplenomegalia/patologia , AnemiaRESUMO
Objective: To evaluate the clinical characteristics and prognostic factors of patients with Philadelphia-negative myeloproliferative neoplasm-accelerated phase/blast phase (MPN-AP/BP) . Methods: A total of 67 patients with MPN-AP/BP were enrolled from February 2014 to December 2021 at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences. Their clinical features and prognostic factors were analyzed retrospectively. Results: ① Sixty-seven patients with MPN-AP/BP with a median age of 60 (range, 33-75) years, including 31 males (46.3% ) and 36 females (53.7% ) , were analyzed. Forty-eight patients progressed from primary myelofibrosis (PMF) , and 19 progressed from other myeloproliferative neoplasms (MPNs) , which included polycythemia vera, essential thrombocythemia, and MPN unclassifiable. Patients who progressed from PMF had higher lactate dehydrogenase (LDH) levels than those who progressed from other MPNs (925.95 vs. 576.2 U/L, P=0.011) , and there were higher proportions of patients who progressed from PMF with splenomegaly (81.4% vs. 57.9% , P=0.05) , a myelofibrosis grade of ≥2 (93.6% vs. 63.2% , P=0.004) , and a shorter duration from diagnosis to the transformation to AP/BP (28.7 vs. 81 months, P=0.001) . ② JAK2V617F, CALR, and MPLW515 were detected in 41 (61.2% ) , 13 (19.4% ) , and 3 (4.5% ) patients, respectively, whereas 10 (14.9% ) patients did not have any driver mutations (triple-negative) . Other than driver mutations, the most frequently mutated genes were ASXL1 (42.2% , n=27) , SRSF2 (25% , n=16) , SETBP1 (22.6% , n=15) , TET2 (20.3% , n=13) , RUNX1 (20.3% , n=13) , and TP53 (17.2% , n=11) . The ASXL1 mutation was more enriched (51.1% vs. 21.1% , P=0.03) , and the median variant allele fraction (VAF) of the SRSF2 mutation (median VAF, 48.8% vs. 39.6% ; P=0.008) was higher in patients who progressed from PMF than those who progressed from other MPNs. ③ In the multivariate analysis, the complex karyotype (hazard ratio, 2.53; 95% confidence interval, 1.06-6.05; P=0.036) was independently associated with worse overall survival (OS) . Patients who received allogeneic stem cell transplantation (allo-HSCT) (median OS, 21.3 vs. 3 months; P=0.05) or acute myeloid leukemia-like (AML-like) therapy (median OS, 13 vs. 3 months; P=0.011) had significantly better OS than those who received supportive therapy. Conclusion: The proportions of patients with PMF-AP/BP with splenomegaly, myelofibrosis grade ≥2, a higher LDH level, and a shorter duration from diagnosis to the transformation to AP/BP were higher than those of patients with other Philadelphia-negative MPN-AP/BP. The complex karyotype was an independent prognostic factor for OS. Compared with supportive therapy, AML-like therapy and allo-HSCT could prolong the OS of patients with MPN-AP/BP.
Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Crise Blástica/tratamento farmacológico , Mielofibrose Primária/genética , Prognóstico , Esplenomegalia , Estudos Retrospectivos , Transtornos Mieloproliferativos/genética , Mutação , Leucemia Mieloide Aguda , Janus Quinase 2/genéticaAssuntos
Translocação Genética , Cariótipo , Trombocitose , Leucemia Mieloide , Citogenética , Mielofibrose PrimáriaRESUMO
CONTEXTO: Mielofibrose é uma neoplasia maligna rara que pode se desenvolver como doença primária, sendo uma doença mieloproliferativa crônica caracterizada pela falha da medula óssea e proliferação clonal de células mieloides associada com excesso de fibras de reticulina e/ou colágeno, e algum grau de atipia no megacariócito. O quadro clínico pode evoluir com esplenomegalia, anemia, sintomas constitucional (fadiga, sudorese noturna, febre), caquexia, dor óssea, infarto esplênico, prurido, trombose e sangramentos. A incidência na União Europeia e EUA é de 0,3 casos por 100.000 habitantes. Não há dados epidemiológicos robustos no Brasil. Ruxolitinibe é um inibidor seletivo das Janus Quinases associadas (JAKs) JAK1 e JAK2. A desregulação da via JAK-STAT tem sido associada a vários tipos de câncer e aumento da proliferação e sobrevida de células malignas. TECNOLOGIA: Ruxolitinibe. PERGUNTA: O uso de ruxolitinibe no tratamento da mielofibrose risco intermediário-2 ou alto (classificação IPSS), em adultos, com contagem plaquetária acima de 100.000/mm3 é eficaz e seguro quando comprado ao
Assuntos
Humanos , Janus Quinases/antagonistas & inibidores , Mielofibrose Primária/tratamento farmacológico , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economiaRESUMO
OBJECTIVE@#To investigate the clinical characteristics and prognosis of multiple myeloma patients with myelofibrosis.@*METHODS@#The clinical data of 263 patients with multiple myeloma (including 92 patients with myelofibrosis) treated in the department of hematology of our hospital from January 1, 2016 to June 31, 2020 were collected and retrospectively analyzed, the patients were divided into combined group and uncombined group. The MM stage, MM type, genetic characteristics and therapeutic effect of the patients in combined group and uncombined group were observed, and the relationship between the curative effect and the degree of myelofibrosis change of the patients in combined group was analyzed.@*RESULTS@#There was no statistically difference in the MM staging and classification between multiple myeloma patients with or without myelofibrosis (P>0.05). The positive rate of FISH results of the patients in combined group was significantly higher than those in uncombined group, and was significantly correlated to 1q21 amplification, D13S319 deletion, and IgH breakage (P<0.05). After treatment, the effective rate of the patients in uncombined group was significantly higher than those in combined group, and the degree of fibrosis in the effective patients in combined group was significantly reduced.@*CONCLUSION@#The survival rate of the patients with multiple myeloma complicated with myelofibrosis is shorter than that of the patients without myelofibrosis, and the overall prognosis is poor.
Assuntos
Humanos , Aberrações Cromossômicas , Mieloma Múltiplo/complicações , Mielofibrose Primária/complicações , Prognóstico , Estudos RetrospectivosRESUMO
Objective: To analyze the influencing factors of iron metabolism assessment in patients with myelodysplastic syndrome. Methods: MRI and/or DECT were used to detect liver and cardiac iron content in 181 patients with MDS, among whom, 41 received regular iron chelation therapy during two examinations. The adjusted ferritin (ASF) , erythropoietin (EPO) , cardiac function, liver transaminase, hepatitis antibody, and peripheral blood T cell polarization were detected and the results of myelofibrosis, splenomegaly, and cyclosporine were collected and comparative analyzed in patients. Results: We observed a positive correlation between liver iron concentration and ASF both in the MRI group and DECT groups (r=0.512 and 0.606, respectively, P<0.001) , only a weak correlation between the heart iron concentration and ASF in the MRI group (r=0.303, P<0.001) , and no significant correlation between cardiac iron concentration and ASF in the DECT group (r=0.231, P=0.053) . Moreover, transfusion dependence in liver and cardiac [MRI group was significantly associated with the concentration of iron in: LIC: (28.370±10.706) mg/g vs (7.593±3.508) mg/g, t=24.30, P<0.001; MIC: 1.81 vs 0.95, z=2.625, P<0.05; DECT group: liver VIC: (4.269±1.258) g/L vs (1.078±0.383) g/L, t=23.14, P<0.001: cardiac VIC: 1.69 vs 0.68, z=3.142, P<0.05]. The concentration of EPO in the severe iron overload group was significantly higher than that in the mild to moderate iron overload group and normal group (P<0.001) . Compared to the low-risk MDS group, the liver iron concentration in patients with MDS with cyclic sideroblasts (MDS-RS) was significantly elevated [DECT group: 3.80 (1.97, 5.51) g/L vs 1.66 (0.67, 2.94) g/L, P=0.004; MRI group: 13.7 (8.1,29.1) mg/g vs 11.6 (7.1,21.1) mg/g, P=0.032]. Factors including age, bone marrow fibrosis, splenomegaly, T cell polarization, use of cyclosporine A, liver aminotransferase, and hepatitis antibody positive had no obvious effect on iron metabolism. Conclusion: There was a positive correlation between liver iron concentration and ASF in patients with MDS, whereas there was no significant correlation between cardiac iron concentration and ASF. Iron metabolism was affected by transfusion dependence, EPO concentration, and RS.
Assuntos
Humanos , Ferritinas , Ferro , Sobrecarga de Ferro , Fígado/metabolismo , Síndromes Mielodisplásicas/terapia , Mielofibrose Primária , Estudos Retrospectivos , EsplenomegaliaRESUMO
Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.
Assuntos
Humanos , Mutação , Nitrilas , Mielofibrose Primária/genética , Pirazóis , Pirimidinas , Estudos Retrospectivos , Tecnologia , Fatores de Transcrição/genéticaRESUMO
The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.
Assuntos
Humanos , Biomarcadores , Hidroxiureia/uso terapêutico , Fatores Reguladores de Interferon/genética , Janus Quinase 2/genética , Leucemia Mieloide Aguda/genética , Mutação , Fenótipo , Mielofibrose Primária/genética , Trombocitemia Essencial/genéticaRESUMO
La panmielosis aguda con mielofibrosis (PMAF) es un raro desorden hematológico, definido como un subtipo de leucemia aguda. Se reporta un paciente masculino de 31 años de edad con historia de decaimiento marcado, fiebre vespertina y gingivorragia. El examen físico muestra palidez cutáneo mucosas, esplenomegalia ligera y en exámenes complementarios pancitopenia con 5 por ciento de blastos. En el medulograma no se obtuvo material y la impronta sugiere leucemia mieloide aguda no promielocítica. El estudio de inmunofenotipo por citometría de flujo confirma incremento de mieloblastos positivo para (CD34, CD13, CD17, CD117, CD38) y disminuidos en (CD11c y HLA-DR), con una mielofibrosis marcada en biopsia de medula ósea sin la presencia de blastos. Recibe tratamiento de inducción con esquema 3 + 7 (Citosar + Rubidomicina) después del cual el paciente se encuentra en remisión hematológica con persistencia de la fibrosis medular. Posteriormente inicia tratamiento con lenalidomida, Bifosfonatos (Ácido Zoledronico) y se encuentra en remisión hematológica 11 meses después del diagnóstico, hasta marzo 2020. Se realizan estudios de histocompatibilidad (HLA) para trasplante alogénico(AU)
Acute panmyelosis with myelofibrosis (PMAF) is a rare hematologic disorder, defined as a subtype of acute leukemia. A 31-year-old male patient with a history of marked decay, evening fever, and gingivorrhagia is reported. The physical examination showed mucous skin paleness, slight splenomegaly and the complementary examinations showed pancytopenia with 5 percent blasts. In the medullogram no material was obtained and the imprint suggests non-promyelocytic acute myeloid leukemia. Immunophenotype study by flow cytometry confirmed an increase in myeloblasts positive for (CD34, CD13, CD17, CD117, CD38) and decreased in (CD11c and HLA-DR), with marked myelofibrosis in bone marrow biopsy without the presence of blasts. He received induction treatment with a 3 + 7 scheme (Citosar + Rubidomycin) after which the patient was in hematological remission with persistence of spinal fibrosis. Later, he started treatment with lenalidomide, bisphosphonates (Zoledronic Acid) and was in hematological remission 11 months after diagnosis, until March 2020. Histocompatibility studies (HLA) were performed for allogeneic transplantation(AU)
Assuntos
Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Doenças Mieloproliferativas-Mielodisplásicas/diagnóstico , Mielofibrose PrimáriaRESUMO
Abstract Background and objective: in the global scientific literature, the frequency of JAK2 is highly heterogenous in chronic myeloproliferative neoplasms. The objective of this study was to analyze the prevalence of the JAK2 mutation in primary myelofibrosis (PMF) and compare it according to the detection method used, from 2007-2018. Materials and methods: a systematic review with meta-analysis, using 21 searches in three multidisciplinary databases. The PRISMA guideline phases of identification, screening, selection and inclusion were applied. Reproducibility and evaluation of the methodological quality were ensured. The analyses were based on frequencies and meta-analysis for the prevalence of the mutation with its 95% confidence interval. Results: twenty-nine studies with 744 patients were included, mainly from Korea, Brazil and China. The most commonly used technique was AS-PCR, and the prevalence of JAK2 with this technique ranged from 33.3 to 71.4%; with real-time PCR ranging from 42.9 to 77.3%, sequencing from 14.3-57.4%, and ARMS from 36.4-83.3%. The prevalence of JAK2 showed no statistically significant differences according to the type of diagnostic test used. Conclusion: high frequencies of the JAK2V617F mutation are seen in PMF, which shows that this entity should not be diagnosed solely based on clinical and hematological characteristics, but also on the patients' genetic screening.
Resumen Antecedentes y objetivo: en la literatura científica mundial la frecuencia de JAK2 presenta una alta heterogeneidad en las neoplasias mieloproliferativas crónicas. El objetivo de esta investigación fue analizar la prevalencia de la mutación JAK2 en mielofibrosis Primaria (MFP) y compararla según la técnica de detección en los años 2007-2018. Material y métodos: revisión sistemática con metaanálisis, usando 21 búsquedas en tres bases de datos multidisciplinarias. Se aplicaron las fases de identificación, tamización, elección e inclusión de la guía PRISMA. Se garantizó reproducibilidad y evaluación de la calidad metodológica. Los análisis se basaron en frecuencias y metaanálisis para la prevalencia de la mutación con su intervalo de confianza de 95%. Resultados: se incluyeron 29 estudios con 744 pacientes, los cuales provienen principalmente de Corea, Brasil y China. La técnica más empleada fue AS-PCR, las prevalencias de JAK2 con esta técnica oscilaron entre 33.3 y 71.4%; con PCR en tiempo real entre 42.9 y 77.3%, con secuenciación de 14.3-57.4% y en ARMS de 36.4-83.3%. La prevalencia de JAK2 no presentó diferencias estadísticamente significativas según el tipo de prueba diagnóstica utilizada. Conclusión: se evidencian altas frecuencias de la mutación JAK2V617F en MFP, lo que evidencia que el diagnóstico de esta entidad no debe realizarse únicamente por características clínicas y hematológicas sino también por la tamización genética de los pacientes.
Assuntos
Humanos , Masculino , Feminino , Metanálise , Pacientes , Testes Genéticos , Prevalência , Janus Quinase 2 , Mielofibrose Primária , MutaçãoRESUMO
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.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Policitemia Vera , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa , Mielofibrose Primária , Trombocitemia Essencial , Transtornos MieloproliferativosRESUMO
Abstract Introduction Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. Methods JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. Results All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n = 20). Serious AEs were reported in 62.5% of patients (n = 65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. Conclusion Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Tratamento Farmacológico , Mielofibrose Primária/terapia , Policitemia , Esplenomegalia , Trombocitose , BrasilRESUMO
OBJECTIVE@#To investigate the clinical characteristics of essential thrombocytopenia (ET) patients with positive mutations including JAK2, CALR, MPL, or negative mutations.@*METHODS@#A total of 66 newly diagnosed ET cases from January 2016 to December 2018 in Department of Hematology, Huaian No.1 People's Hospital affiliated to Nanjing Medical University were analyzed. Statistical analysis data included the patient's sex, age, symptoms, thrombosis and embolism events, spleen omegaly, platelet count (Plt), leukocyte (WBC) count, hemoglobin (Hb), fibrinogen (FIB), thrombus elastic diagram (TEG), serum potassium, blood glucose (GLU), lactate dehydrogenase (LDH), JAK2, CALR and MPL mutations, treatment options, and efficacy.@*RESULTS@#All the patients were not MPL-positive, and divided in three groups: JAK2 mutation (46 cases, 69.7%), CALR mutation (9 cases, 13.6%) and gene negative mutation (11 cases, 16.7%) group. The average age of patients in the JAK2 mutation group was 63.2 years old, and significantly higher than that in the CALR mutation group (51.8 year) and gene negative group (50.2 year) (P<0.05). Compared with the JAK2 mutation group and gene negative group, the CALR mutation group had lower WBC count (6.3×10/L vs 13.79×10/L) (P=0.003) (6.3×10/L vs 9.70×10/L) (P=0.009). Also the Hb level of patients in CALR mutation group was lower than the JAK2 mutation group (121.22 g/L vs 136.2 g/L) (P=0.036). However, there was higher tumor burden in the CALR mutation group, compared with the gene negative mutation group (300.11 U/L vs 227.4 U/L) (P=0. 033). There was no significant difference among the three groups, such as the Plt counts, serum potassium level, GLU level and FIB level (P>0.05). In addition, thrombus and embolism appeared in 30.3% (20/66) cases. 18.2% (12/66) cases were complicated with hyperkalemia, which significantly correlated with Plt counts (r=0.518). TEG was performed in 34 patients, of which 41.2% (14/34) had abnormal TEG and 55.9% (19/34) were accompanied by Plt count > 1 000 ×10/L, but there was no significant correlation between them (r=0.134). After routine clinical treatment, all the 66 cases achieved partial or complete hematological remission, but the disease usually repeated. Until now 4.5% (3/66) cases had been converted to myelofibrosis (MF) all with JAK2 mutation, but without advancing to acute myeloid leukemia.@*CONCLUSION@#ET patients with JAK2 mutation have higher incidence, moreover were in older age. However, the patients with CALR mutations display lower WBC count and Hb level, but higher tumor burden. In short, the multiple gene mutations of ET showed different clinical features closely relates with the prognosis, thus providing guidance for the clinical diagnosis and treatment.
Assuntos
Idoso , Humanos , Pessoa de Meia-Idade , Calreticulina , Genética , Janus Quinase 2 , Genética , Mutação , Mielofibrose Primária , Trombocitemia Essencial , TrombocitopeniaRESUMO
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).
Assuntos
Humanos , Masculino , Feminino , Adulto , Doenças Mieloproliferativas-Mielodisplásicas , Policitemia Vera , Qualidade de Vida , Mielofibrose Primária , Trombocitemia EssencialRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Células-Tronco Hematopoéticas/metabolismo , Antígeno CD47/metabolismo , Mielofibrose Primária/metabolismo , Estudos de Casos e Controles , Fator de Crescimento Transformador beta/metabolismo , Quimiocina CXCL12/metabolismo , Mielofibrose Primária/genéticaRESUMO
No abstract available.
Assuntos
Dasatinibe , Leucemia Mielogênica Crônica BCR-ABL Positiva , Mielofibrose PrimáriaRESUMO
No abstract available.
Assuntos
Herpesvirus Humano 4 , Transtornos Linfoproliferativos , Mielofibrose PrimáriaRESUMO
Objective: To evaluate clinical characteristics and prognosis of primary myelofibrosis (PMF) patients with thrombocytopenia in varied degrees. Methods: Clinical features and survival data of 1 305 Chinese patients with PMF were retrospectively analyzed. The prognostic value of thrombocytopenia in patients with PMF was evaluated. Results: 320 subjects (47%) presented severe thrombocytopenia (PLT<50×10(9)/L), 198 ones (15.2%) mild thrombocytopenia [PLT (50-99)×10(9)/L] and 787 ones (60.3%) without thrombocytopenia (PLT ≥ 100×10(9)/L). The more severe the thrombocytopenia, the higher the proportions of HGB<100 g/L, WBC<4×10(9)/L, circulating blasts ≥ 3%, abnormal karyotype and unfavourable cytogenetics (P<0.001, P<0.001, P=0.004, P<0.001 and P<0.001, respectively) were observed in this cohort of patients. The more severe the thrombocytopenia, the lower the proportion of JAK2V617F positive (P<0.001) was also noticed. Platelet count was positively correlated with splenomegaly, HGB and WBC (P<0.001, correlation coefficients were 0.131, 0.445 and 0.156, respectively). Platelet count was negative correlated with constitutional symptoms and circulating blasts (P=0.009, P=0.045, respectively; correlation coefficients were -0.096 and -0.056, respectively). The median survival of patients with severe thrombocytopenia, mild thrombocytopenia and without thrombocytopenia were 32, 67 and 89 months, respectively (P<0.001). Multivariate analysis identified thrombocytopenia in varied degrees (HR=1.693, 95%CI 1.320-2.173, P<0.001) and Dynamic Internation Prognostic Scoring System(DIPSS) prognostic model (HR=2.051, 95%CI 1.511-2.784, P<0.001) as independent risk factors for survival. Conclusion: PMF patients with severe thrombocytopenia frequently displayed anemia, leucopenia, circulating blasts and short survival, so active treatment measures should be taken especially in these patients.