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.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Blast Crisis/drug therapy* ; Primary Myelofibrosis/genetics* ; Prognosis ; Splenomegaly ; Retrospective Studies ; Myeloproliferative Disorders/genetics* ; Mutation ; Leukemia, Myeloid, Acute ; Janus Kinase 2/genetics*

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.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/pathology* ; Exons ; Humans ; Janus Kinase 2/genetics* ; Middle Aged ; Mutation ; Mutation, Missense ; Polycythemia Vera/genetics* ; Young Adult

OBJECTIVE: To evaluate the performance of 3.0T magnetic resonance imaging examination (MRI) for the local detecting of muscle invasive bladder cancer following transurethral resection of bladder tumor (TURBT). METHODS: Retrospective study identified 55 patients with pathology-proven bladder cancer who underwent transurethral resection of bladder tumor followed by 3.0T magnetic resonance imaging between September 2012 and April 2019 in our hospital. Two radiologists reviewed pelvic magnetic resonance imaging together and judged muscle invasive bladder cancer. Sensitivity, specificity and accuracy were calculated for the presence of muscle invasion by T2 weighted imaging (T2WI) only, diffusion-weighted imaging (DWI) only and T2WI+DWI compared with the findings at radical cystectomy as the reference standard. RESULTS: Of the 55 patients with pathological results from radical cystectomy, 3.64% (2/55) had no residual disease; 29.09% (16/55) were non-muscle invasive bladder cancer on pathology, including 13 cases in T1 and 3 cases in Ta; 34.55% (19/55) were in stage T2 depending on pathology, 25.45% (14/55) in T3, and 7.27% (4/55) in T4. The average age was 60.76 years, ranging from 42 to 82 years. There were 48 males and 7 females in our study. Before pelvic MRI examination, all the patients received transurethral resection of bladder tumor, including 16 cases taking the operation in our hospital and 39 cases in other hospitals. The interval between the pelvic MRI examination and transurethral resection of bladder tumor was more than 2 weeks in all the patients. They all underwent radical cystectomy within 1 month after the pelvic MRI examination, and no patient underwent radiotherapy or chemotherapy in our study during the interval between the MRI examination and radical cystectomy. T2WI only, DWI only, and T2WI+DWI of 3.0T magnetic resonance imaging for readers were with sensitivity: 94.59%, 83.78%, 91.89%; with specificity: 66.67%, 77.78%, 72.22% and with accuracy: 85.45%, 81.82%, 85.45%, respectively. CONCLUSION 3.0T MRI may have a role in diagnosing muscle invasive bladder cancer following TURBT. T2WI has the advantage of detecting the location of bladder tumor, and DWI has the advantage of differentiating between the benign and malignant lesion. 3.0T MRI T2WI+DWI has a good utility in the detection of muscle invasive bladder cancer following TURBT with satisfied accuracy.
Adult ; Aged ; Aged, 80 and over ; Cystectomy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neoplasm Staging ; Retrospective Studies ; Urinary Bladder Neoplasms/diagnostic imaging*

Objective: To explore the prognostic effects of mean corpuscular volume (MCV) in patients with myelodysplastic syndromes (MDS) . Methods: 321 newly diagnosed, untransfused primary MDS patients who administered from December 2009 to December 2017 were enrolled. The association of MCV with prognosis and several clinical features and genetic mutations were analyzed. Results: Patients were divided into MCV≤100 fl (n=148) and MCV>100 fl (n=173) cohorts. Median overall survival of patients with MCV≤100 fl was shorter than their counterparts (27 months vs 72 months, P<0.001) . In subgroup analysis, MCV≤100 fl patients had worse survivals in bone marrow blast <5% cohort (34 months vs not reached, P=0.002) , but not so in ≥5 % cohort (17 months vs 20 months, P=0.078) . MCV≤100 fl was still an independent adverse variable (HR=1.890, 95%CI 1.007-3.548, P=0.048) after adjusting for clinical and laboratory variables and mutation topography in bone marrow blasts<5% cohort. In bone marrow blasts<5% cohort, patients with MCV≤100 fl had higher hemoglobin levels [90 (42-153) g/L vs 78.5 (28-146) g/L, P=0.015].The proportions of Revised International Prognostic Scoring System (IPSS-R) high/very high risks and poor/very poor IPSS-R karyotypes were higher in MCV≤100 fl cohort (28.8% vs 10.8%, P=0.003; 24.7% vs 12.9%, P=0.049) . MCV≤100 fl cohort had more genetic mutations than those with MCV>100 fl though without significance (0.988 vs 0.769, P=0.064) . Mutated SF3B1 was less frequently in MCV≤100 fl cohort (4.7% vs 15.4%, P=0.018) . Conclusion: MCV≤100 fl was an independent adverse variable after adjusting for clinical and laboratory variables and mutation topography in MDS patients with bone marrow blasts<5%.
Bone Marrow ; Erythrocyte Indices ; Humans ; Karyotyping ; Myelodysplastic Syndromes ; Prognosis

Objective: To explore the utility and safety of leadless intracardiac transcatheter pacing system. Methods: The study was a prospective observational study. Patients underwent Micra transcatheter pacing system in Beijing Anzhen hospital from December 2019 to January 2020 were enrolled. The baseline characteristics, platelet count, hemoglobin, anticoagulation and/or antiplatelet therapy, mean procedural time, average fluoroscopy time, number of deployment and electrical parameters (threshold, R-wave amplitude, impedance) were recorded. Ultrasonography of bilateral femoral and iliac veins was performed in all patients. Patients were followed including access site complication, adverse event and device evaluation at implant, hospital discharge, 1 and 3 months post-implant. R-wave≥5 mV, impedance between 400 and 1 500 Ω and threshold increase≤1.5 V than implant is considered a stable parameter. Femoral access site complications included hematoma, hemorrhage, pseudoaneurysm, and arteriovenous fistula. Adverse events included dislodgement, cardiac effusion/perforation and infection. Left ventricular end diastolic diameter and ejection fraction before and at 1 month after implant were reported. Results: Five patients were enrolled and pacemaker implantation was successful in all 5 patients. Patients were all males and the average age was (78.4±8.4) years. 2 patients received aspirin and clopidogrel therapy, 1 patient suffered from anemia and thrombocytopenia occurred in 1 patient. No stenosis, occlusion and vascular malformation of bilateral femoral and iliac veins was observed. The mean implant time was (39.6±1.7) minutes. The average fluoroscopy time was (9.2±1.3) minutes and the number of deployment was (1.40±0.55). Electrical parameters(threshold, R-Wave amplitude and impedance) were as follows: (0.40±0.10) V/0.24 ms, (10.80±3.72) mV and (822.00±162.23) Ω at implant; (0.45±0.07) V/0.24 ms, (13.04±2.41) mV, and (748.0±91.5) Ω at discharge, (0.40±0.06) V/0.24 ms, (14.26±4.11) mV, and (700.0±91.7) Ω at 1 month post-implant and (0.39±0.05) V/0.24 ms, 14.40±3.97 mV, and (682.0±96.0) Ω at 3 months post-implant, respectively. Threshold increase was ≤1.5 V compared to that during implantation, electrical parameters were acceptable and stable. There was no difference in LVEDD [(44.00±5.24) mm vs. (44.00±5.34) mm,P=1.000] and EF [(62.00±3.39)% vs. (62.20±3.56)%, P=0.861] before and 1 month post-implant. No incidence of access site complications, cardiac effusion/perforation, dislodgment or infections occurred during the 3 months. Conclusions: The leadless transcatheter pacemaker implantation performed in our study archived a high implant success rate and favorable safety profile as well as associated with low and stable pacing thresholds. The long-term safety and benefit of leadless pacemaker need to be evaluated in future clinical studies.
Aged ; Aged, 80 and over ; Equipment Design ; Follow-Up Studies ; Humans ; Male ; Pacemaker, Artificial ; Prospective Studies ; Treatment Outcome

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.
Humans ; Primary Myelofibrosis ; Prognosis ; Retrospective Studies ; Thrombocytopenia

Objective: To evaluate the efficacy and tolerability of ruxolitinib combined with prednisone, thalidomide and danazol for treatment of in myelofibrosis (MF). Methods: Patients of MF according to the WHO 2016 criteria, received ruxolitinib (RUX) combined with prednisone, thalidomide and danazol (PTD). The response, changes of blood counts and adverse events were evaluated. Results: Six PMF and one post-ET MF patients were enrolled. Four patients presented JAK2V617F mutation, one CALR mutation, one MPL mutation, one triple-negative. Responses per IWG-MRT criteria were clinical improvement in 5 patients, stable disease in 2 ones, spleen response in 6 ones. All of 7 patients were symptomatic responses, four patients achieved at least 50% improvement from baseline on MPN-SAF TSS. Three patients initially treated with RUX alone, all of 3 patients experienced treatment-associated anemia and thrombocytopenia. Then these 3 patients received RUX combined with PTD, both hemoglobin and platelet increased significantly. Four patients initially treated with RUX combined with PTD. Increased levels of hemoglobin and platelet were seen in all of 7 patients received RUX combined with PTD with maximum increased hemoglobin of 30(18-54) g/L and maximum increased platelets of 116(13-369)×10(9)/L, respectively from baseline. The treatment dose of RUX increased due to improved platelet count in 3 patients. The frequent non-hematologic adverse events grade 1-2 were constipation, abdominal distension, crura edema and increased ALT. Conclusions: RUX combined with PTD for treatment of MF may modulate initial hematologic toxicity observed when RUX alone, and may increase response due to improved levels of hemoglobin or platelet.
Danazol ; Drug Combinations ; Humans ; Nitriles ; Pilot Projects ; Prednisone ; Primary Myelofibrosis/drug therapy* ; Pyrazoles/therapeutic use* ; Pyrimidines ; Thalidomide/therapeutic use* ; Treatment Outcome

Objective: To explore the clinical implications and prognostic value of TP53 gene mutation and deletion in patients with myelodysplastic syndromes (MDS) . Methods: 112-gene targeted sequencing and interphase fluorescence in situ hybridization (FISH) were used to detect TP53 mutation and deletion in 584 patients with newly diagnosed primary MDS who were admitted from October 2009 to December 2017. The association of TP53 mutation and deletion with several clinical features and their prognostic significance were analyzed. Results: Alterations in TP53 were found in 42 (7.2%) cases. Of these, 31 (5.3%) cases showed TP53 mutation only, 8 (1.4%) cases in TP53 deletion only, 3 (0.5%) cases harboring both mutation and deletion. A total of 37 mutations were detected in 34 patients, most of them (94.6%) were located in the DNA binding domain (exon5-8) , the remaining 2 were located in exon 10 and splice site respectively. Patients with TP53 alterations harbored significantly more mutations than whom without alterations (z=-2.418, P=0.016) . The median age of patients with TP53 alterations was higher than their counterparts[60 (21-78) years old vs 52 (14-83) years old, z=-2.188, P=0.029]. TP53 alterations correlated with complex karyotype and International prognostic scoring system intermediate-2/high significantly (P<0.001) . Median overall survival of patients with TP53 alterations was shorter than the others[13 (95%CI 7.57-18.43) months vs not reached, χ(2)=12.342, P<0.001], while the significance was lost during complex karyotype adjusted analysis in multivariable model. Conclusion: TP53 mutation was more common than deletion in MDS patients. The majority of mutations were located in the DNA binding domain. TP53 alterations were strongly associated with complex karyotype and always coexisted with other gene mutations. TP53 alteration was no longer an independent prognostic factor when complex karyotype were occurred in MDS.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Genes, p53 ; Humans ; In Situ Hybridization, Fluorescence ; Middle Aged ; Mutation ; Myelodysplastic Syndromes/genetics* ; Prognosis ; Tumor Suppressor Protein p53 ; Young Adult

Objective: To observe the clinical characteristics, treatment responses and prognosis of patients with myelodysplastic syndrome (MDS) -del (5q) syndrome who met WHO (2016) diagnostic typing criteria. Methods: A total of 77 patients with del (5q) syndrome, according to WHO (2016) classification, were retrospectively analyzed between January 2008 and April 2018 in the Blood Diseases Hospital, Chinese Academy of Medical Sciences. Clinical characteristics, lenalidomide (LEN) efficacy and survivals were compared between the patients with del (5q) alone and those with one additional cytogenetic abnormality (ACA) with the exception of monosomy 7 or del (7q) . Treatment response and overall survival (OS) were compared between patients who were treated with LEN and traditional non-LEN drugs. Results: Of 77 patients, 64 were isolated del (5q) and 13 were del (5q) with ACA. There were significant differences of the median age and percentage of patients who had small megakaryocytes in bone marrow smear by immunohistochemistry (CD41) between the patients with isolated del (5q) and the patients with del (5q) + ACA[58 (29-64) years old vs 63 (31-82) years old, z=2.164, P=0.030; and 91.7%vs 60.0%, P=0.046, respectively]. The overall hematological response rate (78.9%vs 80.0%) , complete hematological remission (CR) rate (57.9% vs 60.0%) , cytogenetic response (CyR) rate[69.2% (9/13) vs 66.7% (4/6) ] and complete cytogenetic response (CCyR) rate [61.5% (8/13) vs 33.3% (2/6) ] of LEN were similar between the patients with isolated del (5q) (n=19) and with del (5q) + ACA (n=10) , as well as the median Overall survival (OS) between these two groups of patients (62 months vs 78 months, P=0.388) . The hematological response rate (79.3% vs 36.0%) , CR rate (58.6% vs 8.0%) , CyR rate [68.4% (13/19) vs 11.1% (1/9) ] and CCyR rate [52.6% (10/19) vs 0 (0/9) ] were higher among patients treated with LEN (n=29) than those treated with non-LEN therapy (n=25) . There was no statistically significant difference in OS between the patients with LEN or non-LEN therapy (78 months vs 62 months, P=0.297) . Conclusion: Comparing del (5q) syndrome patients with isolated del (5q) or with del (5q) + ACA, two groups of patients had similar clinical characteristics, median OS and LEN efficacy. LEN showed better treatment response than traditional drugs in patients with del (5q) syndrome.
Adult ; Aged ; Aged, 80 and over ; Anemia, Macrocytic ; Humans ; Lenalidomide ; Middle Aged ; Myelodysplastic Syndromes ; Retrospective Studies ; Thalidomide

Objective To compare the approaches used for the assessment of disability adjust life years (DALYs) for advanced schistosomiasis japonica, so as to provide scientific evidence for accurate assessment of the burden of advanced schistosomiasis japonica. Methods The patients with advanced schistosomiasis japonica receiving treatment and assistance programs in Hunan Province in 2017 were enrolled, and the years lived with disability (YLD) for the patients with advanced schistosomiasis japonica was calculated using the common global burden of disease (GBD) estimation method, the modified GBD method with addition of common syndromes of advanced schistosomiasis japonica, and the quality of life assessment method. Results The YLDs of patients with advanced schistosomiasis japonica, the mean YLDs per capita, and the percentages of YLD were 673.94, 728.77 person-years and 1 761.99 person-years; 0.181, 0.196 person-years and 0.474 person-years; and 10.61, 11.48 person-years per 100 thousand persons and 27.75 person-years per 100 thousand persons with the common GBD method, modified GBD method and the quality of life method, respectively. The YLDs of the patients with advanced schistosomiasis japonica in Hunan Province estimated with the modified GBD method and the quality of life method were 8.14% and 2.61 times higher than that with the common GBD method. Of the major symptoms included in the calculation, the 5 symptoms with the greatest contribution to the burden of advanced schistosomiasis japonica included ascites, moderate anemia, severe anemia, diarrhea and hematochezia. Conclusion The quality of life method may more comprehensively assess the YLDs in patients with advanced schistosomiasis japonica than the common and modified GBD methods.