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.
Biomarkers ; Humans ; Hydroxyurea/therapeutic use* ; Interferon Regulatory Factors/genetics* ; Janus Kinase 2/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Phenotype ; Primary Myelofibrosis/genetics* ; Thrombocythemia, Essential/genetics*

Humans ; Nails ; Hydroxyurea/adverse effects* ; Alopecia/chemically induced*

OBJECTIVE: To evaluate the efficacy and safety of ruxolitinib in patients with polycythemia vera (PV). METHODS: The clinical data of patients with PV treated with ruxolitinib in Peking Union Medical College Hospital from January 1, 2013 to December 31, 2019 were retrospectively analyzed. The starting dose of oral ruxolitinib was 10 mg twice daily and could be increased after 3 months of treatment if hematocrit (HCT) control was not achieved. HCT control was defined as HCT<45% in the absence of phlebotomy. RESULTS: Thirty-three patients (17 males and 16 females) were treated with ruxolitinib at a median age of 50 (21-72) years. JAK2V617F and JAK2exon12 alleles were detected in 31 and 2 patients, respectively. Before treatment, median hemoglobin level was 187 (166-208) g/L, median white blood cell and platelet level was 10.4 (5.0-15.8)×10⁹/L and 457(237-677)×10⁹/L, respectively. Totally 17 patients (51.5%) who were resistant to or intolerant of hydroxyurea were treated with ruxolitinib as second-line therapy, and 16 patients (48.5%) were treated with ruxolitinib as first-line therapy voluntarily. The median time since PV diagnosis to treatment of ruxolitinib was 47 (3-188) months. By December 31, 2019, all the patients continued to receive ruxolitinib. The median duration of ruxolitinib exposure was 19 (2-91) months. Both in the first-line therapy group and second-line therapy group, 15 cases (accounting for 93.8% and 88.2%, respecitvely) achieved HCT control. The median time from start of therapy to HCT control was 2.2 (0.8-11.6) months. One patient (3.0%) had disease progression after HCT control. The most common hematologic adverse events included anemia and thrombocytopenia, according to CTCAE classification, including 1 case of grade 1 anemia (3.0%) and 1 case of grade 2 thrombocytopenia (3.0%). There was no thromboembolic event occurred during the therapy of ruxolitinib. CONCLUSION The remission rate of HCT in PV patients treated with ruxolitinib is high, and adverse reactions are rare. Ruxolitinib is effective in HCT control and generally well tolerated in patients with PV.
Adult ; Aged ; Anemia ; Female ; Hemoglobins/therapeutic use* ; Humans ; Hydroxyurea/therapeutic use* ; Male ; Middle Aged ; Nitriles ; Polycythemia Vera/drug therapy* ; Pyrazoles ; Pyrimidines ; Retrospective Studies ; Thrombocytopenia ; Young Adult

β-thalassaemias are inherited hemoglobin disorders caused by defects in the β-globin gene. In recent years, researches have re-mentioned the therapeutic significance of drug-induced fetal hemoglobin (HbF), which can reduce the imbalance of α and β chains and improve the severity of anemia by increasing the expression of γ chain. Drug trials, such as hydroxyurea, thalidomide and desitabine have shown elevated hemoglobin, decreased blood transfusion dependence, and reduced symptoms other than anemia after treatment. In addition, in vitro experiments suggested that HbF can also induce by other drugs, which providing important clues for safe and effective HbF inducers. Therefore, this article reviews the current research progress so as to expect beneficial to clinical treatment.
Blood Transfusion ; Fetal Hemoglobin ; Humans ; Hydroxyurea ; beta-Globins ; beta-Thalassemia

OBJECTIVE: To explore the symptomatic burden of patients with essential thrombocythemia (ET) and its relation with clinical characteristics including the mutation status, therapeutic protocols and sex. METHODS: Total of 173 Chinese ET patients were selected and grouped on the basis of disease characteristics (mutation status, therapeutic pro to- cols, and sex). RESULTS: All the groups showed low-to-high symptom burden, with the highest in the Hu (hydroxyurea)-group (total symptom score [TSS], 14.7; range, 7.6-14.7). In the JAK2V617F-positive, Hu-treated, and female groups TSS and independent symptom scores were higher than those in the control group. The CALR-positive and IFN-α-treated groups had lower overall and individual scores as compared with groups lacking the corresponding characteristics. As the number of characteristics (JAK2V617F-positive, Hu-treated, and female) increases, the severity of symptoms gradually increased. CONCLUSION The different characteristics have various effects on symptom burden in ET patients. The accumulation of certain characteristics will lead to more severe symptom burden, thus the patient＇s symptom burden should be considered comprehensively when making up the treatment schemes and prognosis.
Asian Continental Ancestry Group ; Calreticulin ; Female ; Humans ; Hydroxyurea ; Janus Kinase 2 ; Mutation ; Thrombocythemia, Essential

Three aged dogs, all over 15 years old, with multiple seizure events and various neurologic signs such as head turn and ataxia were brought to the referring hospital. Two cases were tentatively diagnosed with intracranial meningioma based on magnetic resonance imaging, and one case was histopathologically confirmed as meningioma at necropsy. All dogs improved after initiation of pulsed high-dose hydroxyurea (HU) treatment. Clinical sign relapses were managed by repeating high-dose HU without obvious side effects. Pulsed high-dose HU can be applied when clinical signs are refractory to the traditionally recommended dosage for intracranial meningioma in dogs.
Animals ; Ataxia ; Brain Neoplasms ; Dogs ; Drug Therapy ; Head ; Hydroxyurea ; Magnetic Resonance Imaging ; Meningioma ; Neurologic Manifestations ; Recurrence ; Seizures

No abstract available.
Dermoscopy ; Hydroxyurea

BACKGROUND/AIMS: Renal complications related to BCR-ABL1-negative myeloproliferative neoplasms (MPNs) have not been examined fully in Asian populations. METHODS: We analyzed estimated glomerular filtration rate (eGFR) and its changes with time retrospectively in patients with BCR-ABL1-negative MPN from 2005 to 2015. RESULTS: The prevalence of chronic kidney disease (CKD) was 11% (6.6% having stage 3 and 4.4% having stage 4). In a linear regression analysis of eGFR versus time (years), overall, patients showed increased eGFR (mL/min/1.73 m2) by 0.51 (95% confidence interval [CI], –0.30 to 1.33; p = 0.22). Patients with polycythemia vera (PV), and those treated with hydroxyurea, showed statistically significant increases in eGFR (1.59; 95% CI, 0.28 to 2.90; p = 0.22 in PV; and 1.55; 95% CI, 0.56 to 2.54; p = 0.22 in treatment with hydroxyurea). In total, 17 patients (20.5%) showed rapid loss of eGFR (<–3 mL/min/1.73 m2per year). This rapid loss in eGFR was associated with a higher incidence of kidney disease (23.5% vs. 6.1%, p= 0.05) and a higher percentage of patients with high neutrophil (>7.0 × 109 /L) and high monocyte (> 0.7 × 109 /L) counts (76.5% vs. 50%, p=0.05; 52.9% vs. 28.8%, p= 0.06, respectively). More patients had high serum lactate dehydrogenase (> 500 U/L) levels (52.9% vs. 25.8%, p = 0.03) at diagnosis. CONCLUSIONS: CKD is prevalent in patients with BCR-ABL1-negative MPN. Active cytoreductive therapy has the potential to improve kidney function in BCR-ABL1-negative MPN.
Asian Continental Ancestry Group ; Diagnosis ; Glomerular Filtration Rate ; Humans ; Hydroxyurea ; Incidence ; Kidney ; Kidney Diseases ; L-Lactate Dehydrogenase ; Linear Models ; Monocytes ; Neutrophils ; Polycythemia Vera ; Prevalence ; Renal Insufficiency, Chronic* ; Retrospective Studies*

We report a case that a 68-year-old man taking hydroxyurea for essential thrombocythemia produced milky urine during propofol infusion. Under microscopic analysis, the cloudy urine sample was revealed to comprise uric acid crystals. Postoperatively, kidney function such as urine output and blood urea nitrogen to creatinine ratio showed no abnormality. We suggest that the cloudy urine may be due to the increased excretion of uric acid after administration of propofol. Although this rare case of cloudy milky urine is resolved on its own, we need to consider the possibility of such urine color changes. It is particularly important to understand that medication, preoperative serum uric acid level, urine pH, and the hypothermal operating room can change the color of urine through the presence of uric acid crystals.
Aged ; Anesthesia, Intravenous* ; Blood Urea Nitrogen ; Creatinine ; Humans ; Hydrogen-Ion Concentration ; Hydroxyurea* ; Kidney ; Operating Rooms ; Propofol* ; Thrombocythemia, Essential ; Uric Acid

BACKGROUND: The aim of this study is to investigate the clinical results of adjuvant chemotherapy with hydroxyurea and to compare those with the results of postoperative radiotherapy after incomplete resection of atypical meningiomas (ATMNGs). METHODS: We retrospectively reviewed the medical records of 84 patients with ATMNGs diagnosed in the period from January 2000 to December 2014. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy or hydroxyurea chemotherapy, duration of follow-up, and progression. In terms of the extent of surgical resection, incomplete resection was defined as Simpson grade II–V. RESULTS: Among the 85 patients, 55 (65.5%) patients underwent incomplete resection; 24 (43.6%) were treated with adjuvant hydroxyurea (group A), and 20 (36.4%) with postoperative radiotherapy (group B), and 11 (20.0%) underwent conservative treatment after surgery (group C). Twenty-five (45.5%) patients experienced the progression of tumors during the follow-up period (mean 47.7 months, range 12.4-132.1 months); 8 of 24 (33.3%) patients in group A, 7 of 20 (35.0%) patients in group B, and 10 of 11 (90.9%) patients in group C. The mean progression-free survival (PFS) was 30.9 months (range 6.4-62.3 months); 46.2 months in group A, 40.4 months in group B, and 11.9 months in group C (p=0.041). Multivariate analysis showed that Simpson grade (p=0.040), adjuvant treatment after surgery (p<0.001), increased Ki67 (p=0.017), mitotic index (p=0.034), and overexpression of p53 (p=0.026) predicted longer PFS. CONCLUSION: This investigation suggested that adjuvant treatment after incomplete resection of ATMNGs are associated with longer PFS than conservative treatment, and that there is no difference of PFS between hydroxyurea chemotherapy and radiotherapy after surgery. Therefore, hydroxyurea chemotherapy can be considered as another adjuvant tool for the ATMNGs if the postoperative adjuvant radiotherapy cannot be applicable.
Chemotherapy, Adjuvant ; Diagnosis ; Disease Progression ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Hydroxyurea* ; Medical Records ; Meningioma* ; Mitotic Index ; Multivariate Analysis ; Neurosurgery ; Radiotherapy ; Radiotherapy, Adjuvant ; Retrospective Studies