[Clinical analysis of seven cases of primary hyperoxaluria type 1].

We retrospectively analyzed the clinical data of seven patients (four men and three women) with primary hyperoxaluria (PH) type 1 (PH1) in the Department of Nephrology of Zhongda Hospital, Southeast University from January 2018 to October 2023. The mean age at disease onset was 32.1 (range: 26-42) years. The mean age at diagnosis was 40.6 (range: 28-51) years. All patients initially had kidney stones, and three patients were found to have renal insufficiency at the time of disease onset. Among them, two patients underwent hemodialysis immediately. Symptoms at the first visit included bone pain (n=7), joint pain or deformity (n=5), fatigue (n=5), hypotension (n=3), and subcutaneous nodules (n=2). Four patients had a family history of PH. All patients had varying degrees of anemia (60-114 g/L), significant hypoalbuminemia (16.5-32.1 g/L), and hypercoagulable state (D-dimer: 2 230-12 781 µg/L). Seven patients received maintenance hemodialysis; their mean age was 37.7 (range: 26-50) years. The mean duration from disease onset to hemodialysis was 5.6 (range: 0-20) years. Five patients repeatedly experienced dialysis access dysfunction. Three patients underwent kidney transplantation before a diagnosis was made, and all transplanted kidneys lost function due to oxalate deposition. The mean follow-up duration was 14.43 (range: 4-38) months. Unfortunately, one patient died. All seven patients underwent computed tomography of the abdomen. All patients suffered skeletal abnormalities, bilateral nephrolithiasis, and nephrocalcinosis. Six patients carried AGXT gene mutations, including four compound heterozygous mutations and two pure homozygous mutations.The mutation sites included: c.823-824dup.AG (p.S275Rfs*38)(exon 8), c.815-816ins.GA (p.S275Rfs*38)(exon 8), c.595G>A (p.G199S) (exon 5), c.32C>G (p.P11R) (exon 1), and c.638C>T (p.A213V)(exon 6). According to the American College of Medical Genetics and Genomics guidelines, two loci were identified as likely pathogenic variants, seven were identified as pathogenic variants, and one locus was identified as having uncertain significance. In addition, patients 1 and 4 underwent skin biopsy, patient 2 underwent renal transplant biopsy, and patient 3 underwent bone marrow biopsy. Interestingly, significant oxalate deposition was found in the tissues. Therefore, PH1 is a rare autosomal recessive inherited disease. This study not only enhanced the understanding of the clinical characteristics of PH1 patients but also had great significance in early diagnosis and treatment of the disease.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Pulmonary nuclear protein of the testis midline carcinoma:a case report].

Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare malignant epithelial tumor that typically occurs in the midline regions such as the head, neck, and mediastinum. This tumor is characterized by rapid development, aggressive growth, and strong invasiveness. Due to its short duration, most patients are diagnosed at advanced stages, often leading to rapid mortality. Although reports on pulmonary NUT carcinoma are uncommon, this article presents a case of pulmonary NUT carcinoma in which the patient repeatedly expectorated bronchial casts and tumor tissue. Additionally, a comprehensive review of relevant literature from recent years is provided to enhance understanding of this disease.

[Application and clinical significance of intercellular proximity labeling technique in chronic myelogenous leukemia].

Objective: This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) . Methods: Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed. Results: Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3(+) T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4(+) T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8(+) T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7(-)CD45RA(-) effector memory T cells and CCR7(-)CD45RA(+) effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion: The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.

[Exploration and expectation of magnetic resonance imaging in the evaluation of prostate cancer].

With the progress of imaging technology, magnetic resonance imaging (MRI) has become the preferred imaging method for prostate cancer due to its excellent soft tissue resolution and the capability of multiparametric and multi-planar imaging. This paper briefly describes the current application and research progress of MRI in the preoperative qualitative diagnosis, staging assessment and postoperative recurrence monitoring of prostate cancer. The purpose is to deepen the understanding of clinicians and radiologists on the value of MRI in prostate cancer, and to promote the exploration of MRI in the management of prostate cancer.

[Diagnostic value of multiparametric MRI-based models in the assessment of extra-prostatic extension of prostate cancer].

Objective: To evaluate the diagnostic value of multiparametric magnetic resonance imaging (mpMRI) based models in the assessment of extra-prostatic extension (EPE) of prostate cancer. Methods: This retrospective study included 168 consecutive men with prostate cancers [aged 48 to 82 (66.6±6.8) years] who underwent radical prostatectomy and preoperative mpMRI examinations at the First Medical Center of the PLA General Hospital from January 2021 to February 2022. According to European Society of Urogenital Radiology (ESUR) score, EPE grade and mEPE score, all cases were independently evaluated by two radiologists, with disagreement reviewed by a senior radiologist as the final result. The diagnostic performance of each MRI-based model for pathologic EPE prediction was assessed using receiver operating characteristic curve (ROC), and the differences between the corresponding area under the curve (AUC) were compared using the DeLong test. The weighted Kappa test was used to evaluate the inter-reader agreement of each MRI-based model. Results: A total of 62 (36.9%) prostate cancer patients had pathologic confirmed EPE after radical prostatectomy. The AUC of ESUR score, EPE grade and mEPE score for predicting pathologic EPE were 0.836 (95%CI: 0.771-0.888), 0.834 (95%CI: 0.769-0.887) and 0.785 (95%CI: 0.715-0.844), respectively. The AUC of ESUR score and EPE grade were both superior to that of mEPE score with significant differences (all P<0.05), while there was no significant difference between the ESUR score and EPE grade models (P=0.900). EPE grading and mEPE score had good inter-reader consistency, with weighted Kappa values of 0.65 (95%CI: 0.56-0.74) and 0.74 (95%CI: 0.64-0.84), respectively. The inter-reader consistency of ESUR score was moderate, and the weighted Kappa value was 0.52 (95%CI: 0.40-0.63). Conclusion: All MRI-based models showed good preoperative diagnostic value in predicting EPE, among which the EPE grade resulted in more reliable performance with substantial inter-reader agreement.

Retraction Note: MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK.

The article "MicroRNA-375 accelerates the invasion and migration of colorectal cancer through targeting RECK", by L.-J. Wei, D.-M. Bai, Z.-Y. Wang, B.-C. Liu, published in Eur Rev Med Pharmacol Sci 2019; 23 (11): 4738-4745-DOI: 10.26355/eurrev_201906_18055-PMID: 31210300 has been retracted by the authors for the following reasons: This paper has been questioned on PubPeer (https://pubpeer.com/publications/0E5B55962B277F3D0ABBC0451DAAB3). In particular, concerns were raised about Figure 3 and Table I. Unfortunately, the authors are not able to confirm nor deny this concern as they did not find the primary data for figures. The authors decided to study this experiment again to deliver more precise results. After consultation among the authors, in line with the rigorous attitude towards scientific research, authors agreed that it was necessary to withdraw the article and make further research and improvement. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18055.

[Value of clear cell likelihood score in differentiation between renal oncocytoma and clear cell renal cell carcinoma].

Objective: To evaluate the value of clear cell likelihood score (ccLS) in identifying renal oncocytoma (RO) and clear cell renal cell carcinoma (ccRCC). Methods: Retrospective data of pathologically confirmed 43 RO patients [24 men and 19 women, aged 22-77 (54±14) years] between February 2008 and September 2021 and 43 ccRCC patients [30 men and 13 women, aged 29-78 (56±12) years] between May and July 2021 were consecutively included in the department of radiology, Chinese PLA General Hospital. Two radiologists used ccLS to assess each case independently, and disagreements were resolved by consensus. The ability of ccLS to identify RO and ccRCC was examined by the receiver operating characteristic (ROC) curve which identified the best optimal diagnostic cut-off values, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value. Results: The mean tumor diameter was 3.8 cm in RO patients and 3.7 cm in ccRCC patients. Central scar and segmental enhancement inversion (SEI) were more frequently observed in the RO group compared to the ccRCC group [53.5% (23∶43) versus 11.6% (5∶43) and 41.9% (18∶43) versus 7.0% (3∶43), respectively], with statistical differences (P<0.001). The ccLS scores in the RO group ranged from 1 to 4, while 79.0% of the cases were 3. The ccLS scores in the ccRCC group ranged from 2 to 5, while 72% of the cases were 4. The scores of the two groups were statistically different (P<0.001). The ccLS showed the best performance when the threshold was 4 according to the ROC curve. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of ccLS for distinguishing RO from ccRCC were 83.7%, 90.7%, 87.2%, 90.0%, and 84.8%, respectively, and the area under the ROC curve value was 0.879. Conclusion: The ccLS has credible sensitivity and specificity in differentiating renal oncocytoma from clear cell carcinoma, which may be helpful for the preoperative diagnosis.

[Comparison of the efficacy of IA and HAD induction regimens in the treatment of patients with newly diagnosed acute myeloid leukemia: a single-center study].

Objective: To compare the efficacy of two induction regimens, namely, idarubicin combined with cytarabine (IA) versus the combination of homoharringtonine, daunorubicin, and cytarabine (HAD) , in adult patients with newly diagnosed de novo acute myeloid leukemia (AML) . Methods: From May 2014 to November 2019, 199 patients diagnosed with AML receiving either the IA or HAD regimens were assessed for overall survival (OS) , relapse-free survival (RFS) , as well as the CR rate and the MRD negative rate after induction therapy. The differences in prognosis between the two induction therapy groups was assessed according to factors, including age, white blood cell (WBC) count, NPM1 mutation, FLT3-ITD mutation, 2017 ELN risk stratification, CR(1) transplantation, and the use of high-dose cytarabine during consolidation therapy, etc. Results: Among the 199 patients, there were 104 males and 95 females, with a median age of 37 (15-61) years. Ninety patients received the IA regimen, and 109 received the HAD regimen. Comparing the efficacy of the IA and HAD regimens, the CR rates after the first induction therapy were 71.1% and 63.3%, respectively (P=0.245) , and the MRD negative rates after the first induction therapy were 53.3% and 48.6%, respectively (P=0.509) . One patient in the IA group and two in the HAD group died within 60 days after induction. The two-year OS was 61.5% and 70.6%, respectively (P=0.835) , and the two-year RFS was 51.6% and 57.8%, respectively (P=0.291) . There were no statistically significant differences between the two groups. Multivariate analysis showed that the ELN risk stratification was an independent risk factor in both induction groups; CR(1) HSCT was an independent prognostic factor for OS and RFS in the IA patients and for RFS in the HAD patients but not for OS in the HAD patients. Age, WBC level, NPM1 mutation, and FLT3-ITD mutation had no independent prognostic significance. Conclusion: The IA and HAD regimens were both effective induction regimens for AML patients.

[Efficacy and safety of IAC regimen for relapse/refractory acute myeloid leukemia: a prospective randomized controlled study].

Objective: To evaluate the efficacy and toxicity profiles of idarubicin, cytarabine, and cyclophosphamide (IAC) in relapse/refractory acute myeloid leukemia (AML) . Methods: This study was a prospective, randomized controlled clinical trial with the registration number NCT02937662. The patients were randomly divided into two groups. The experimental group was treated with an IAC regimen, and the regimen of the control group was selected by doctors according to medication experience. After salvage chemotherapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was conducted as far as possible according to the situation of the patients. We aimed to observe the efficacy, safety, and toxicity of the IAC regimen in relapse/refractory AML and to explore which is the better regimen. Results: Forty-two patients were enrolled in the clinical trial, with a median age of 36 years (IAC group, 22 cases and control groups, 20 cases) . ①The objective response rate was 71.4% in the IAC group and 40.0% in the control group (P=0.062) ; the complete remission (CR) rate was 66.7% in the IAC group and 40.0% in the control group (P=0.121) . The median follow-up time of surviving patients was 10.5 (range:1.7-32.8) months; the median overall survival (OS) was 14.1 (range: 0.6-49.1) months in the IAC group and 9.9 (range: 2.0-53.8) months in the control group (P=0.305) . The 1-year OS was 54.5% (95%CI 33.7%-75.3%) in the IAC group and 48.2% (95%CI 25.9%-70.5%) in the control group (P=0.305) , with no significant difference between these two regimens. ②The main hematologic adverse events (AEs) were anemia, thrombocytopenia, and neutropenia. The incidence of grade 3-4 hematologic AEs in the two groups was 100% (22/22) in the IAC group and 95% (19/20) in the control group. The median time of neutropenia after chemotherapy in the IAC group and control group was 20 (IQR: 8-30) and 14 (IQR: 5-50) days, respectively (P=0.023) . ③The CR rate of the early relapse (relapse within 12 months) group was 46.7% and that of the late relapse (relapse after 12 months) group was 72.7% (P=0.17) . The median OS time of early recurrence was 9.9 (range:1.7-53.8) months, and that of late recurrence patients was 19.3 (range: 0.6-40.8) months (P=0.420) , with no significant differences between the two groups. The 1-year OS rates were 45.3% (95%CI 27.2%-63.3%) and 66.7% (95%CI 40.0%-93.4%) , respectively (P=0.420) . Survival analysis showed that the 1-year OS rates of the hematopoietic stem cell transplantation group and non-hematopoietic stem cell transplantation group were 87.5% (95%CI 71.2%-100%) and 6.3% (95%CI 5.7%-18.3%) , respectively. The OS rate of the hematopoietic stem cell transplantation group was significantly higher than that of the non-hematopoietic stem cell transplantation group (P<0.001) . Conclusion: The IAC regimen is a well-tolerated and effective regimen in relapsed/refractory AML; this regimen had similar efficacy and safety with the regimen selected according to the doctor's experience for treating relapsed/refractory AML. For relapsed/refractory patients with AML, allogeneic hematopoietic stem cell transplantation should be attempted as soon as possible to achieve long-term survival.

[Clinical and genetic characteristics of patients with newly diagnosed acute promyelocytic leukemia: a single-center retrospective of 790 cases].

Objective: To retrospectively analyze the data of Chinese patients with newly diagnosed acute promyelocytic leukemia (APL) to preliminarily discuss the clinical and cytogenetic characteristics. Methods: From February 2004 to June 2020, patients with newly diagnosed APL aged ≥ 15 years who were admitted to the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College were chosen. Clinical and laboratory features were retrospectively analyzed. Results: A total of 790 cases were included, with a male to female ratio of 1.22. The median age of the patients was 41 (15-76) years. Patients aged between 20 and 59 predominated, with 632 patients (80%) of 790 patients classified as low and intermediate risk and 158 patients (20%) of 790 patients classified as high risk. The white blood cell, platelet, and hemoglobin levels at diagnosis were 2.3 (0.1-176.1) ×10(9)/L, 29.5 (2.0-1220.8) ×10(9)/L, and 89 (15-169) g/L, respectively, and 4.8% of patients were complicated with psoriasis. The long-form type of PML-RARα was most commonly seen in APL, accounting for 58%. Both APTT extension (10.3%) and creatinine>14 mg/L (1%) are rarely seen in patients at diagnosis. Cytogenetics was performed in 715 patients with newly diagnosed APL. t (15;17) with additional chromosomal abnormalities were found in 155 patients, accounting for 21.7%; among which, +8 was most frequently seen. A complex karyotype was found in 64 (9.0%) patients. Next-generation sequencing was performed in 178 patients, and 113 mutated genes were discovered; 75 genes had an incidence rate>1%. FLT3 was the most frequently seen, which accounted for 44.9%, and 20.8% of the 178 patients present with FLT3-ITD. Conclusions: Patients aged 20-59 years are the most common group with newly diagnosed APL. No obvious difference was found in the ratio of males to females. In terms of risk stratification, patients divided into low and intermediate risk predominate. t (15;17) with additional chromosomal abnormalities accounted for 21% of 715 patients, in which +8 was most commonly seen. The long-form subtype was most frequently seen in PML-RARα-positive patients, and FLT3 was most commonly seen in the mutation spectrum of APL.

[Observational study of chronic myeloid leukemia Chinese patients who discontinued tyrosine kinase inhibitors in the real-world].

Objective: This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) . Methods: The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed. Results: A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM (P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI (RR=1.827, 95%CI 1.015-3.288, P=0.044) . Conclusion: In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.

[Treatment status of tyrosine kinase inhibitors in Chinese patients with chronic myeloid leukemia in 2020].

Objective: To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia (CML) in China. Methods: From the end of April to mid-May in 2020, a cross-sectional survey, by filling out a survey questionnaire, was conducted to explore the first-line choice of tyrosine kinase inhibitors (TKI) , current medications, drug switch and major molecular responses (MMR) as well as the variables associated with them in patients in China. Results: Data of 2933 respondents with CML from 31 provinces, municipalities, and autonomous regions across the country were included in this study. 1683 respondents (57.4%) were males. Median age was 38 (16-87) years old. 2481 respondents (84.6%) received imatinib as first-line TKI; 1803 (61.5%) , the original new drug (branded drug) . When completing the questionnaire, 1765 respondents (60.2%) were receiving imatinib; 1791 (61.1%) , branded drug. 1185 respondents (40.4%) had experienced TKI switch. With a median follow-up of 45 (3-227) months, 1417 of 1944 (72.9%) respondents with newly diagnosed CML in the chronic phase achieved MMR. Multivariate analysis showed that the respondents with urban household registration (OR=0.6, 95%CI 0.5-0.8, P<0.001) , ≥ bachelor degree (OR=0.5, 95%CI 0.4-0.7, P<0.001) , and in the advanced phase at diagnosis (OR=0.5, 95%CI 0.3-0.8, P=0.001) less preferred Chinese generic TKI, while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region (OR=1.7, 95%CI 1.4-2.0, P<0.001) . Moreover, the respondents in the advanced phase at diagnosis more preferred second-generation TKI (OR=5.4, 95%CI 3.6-8.2, P<0.001) ; those ≥60 years old, less preferred second-generation TKI (OR=0.4, 95%CI 0.2-0.7, P=0.002) . Being in the advanced phase at diagnosis (OR=2.2, 95%CI 1.6-3.2, P<0.001) , first-line choice of imatinib (OR=2.0, 95%CI 1.6-2.6, P<0.001) or Chinese generic drugs (OR=1.3, 95%CI 1.1-1.6, P=0.002) , longer interval from diagnose of CML to starting TKI treatment (OR=1.2, 95%CI 1.1-1.2, P<0.001) and longer duration of TKI therapy (OR=1.1, 95%CI 1.0-1.1, P<0.001) were significantly associated with TKI switch; urban household registration (OR=0.7, 95%CI 0.6-0.8, P<0.001) , ≥MMR (OR=0.6, 95%CI 0.5-0.8, P<0.001) and unknown response (OR=0.7, 95%CI 0.6-0.9, P=0.003) , no TKI switch. Female sex (OR=1.4, 95%CI 1.1-1.7, P=0.003) , urban household registration (OR=1.6, 95%CI 1.3-2.0, P<0.001) , front-line imatinib therapy (OR=1.4, 95%CI 1.1-1.9, P=0.016) and longer duration of TKI treatment (OR=1.2, 95%CI 1.2-1.3, P<0.001) were significantly associated with achieving a MMR or better response; age ≥ 60 years old (OR=0.7, 95%CI 0.4-1.0, P=0.047) and TKI switch (OR=0.6, 95%CI 0.5-0.7, P<0.001) , achieving no MMR. Conclusions: By 2020, the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it. More than half of TKIs were branded drugs. Socio-demographic characteristics and clinical variables affect their TKI choice, drug switch, and treatment response.

[Dasatinib combined with multi-agent chemotherapy regimen in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: a prospective study from a single center].

Objective: This study evaluates the efficacy and safety of dasatinib combined with a multi-agent chemotherapy regimen of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients. Methods: This prospective, single-arm, and open clinical study enrolled 30 adult Ph(+) ALL patients who were newly diagnosed and treated from January 2016 to April 2018 in the center of this study. Standard induction chemotherapy was given for 4 weeks. However, dasatinib (100 mg/d) was continuously administered from day 8 until the end of the whole therapy in the induction therapy. Patients who are available for allogeneic or autologous stem cell transplantation (SCT) received transplantation when the disease was evaluated as complete remission. Results: All 30 patients achieved hematological complete remission (HCR) after the induction chemotherapy, and 70.0% (21/30) of them achieved the accumulated molecular complete remission (MCR) . The patients were followed up with a median follow-up time of 37.8 months (32.0-46.6) . The 3 year overall survival (OS) and 3 year hematological relapse-free survival (HRFS) were 68.1% and 61.6%, respectively. Moreover, 63.3% and 43.3% of the patients achieved molecular major remission and MCR, respectively. Consequently, 60.0% of the patients achieved MCR until 6 months. The patients who achieved MCR within 6 months had superior OS (P=0.004) , HRFS (P=0.049) , and event-free survival (EFS; P=0.001) . Fifteen patients (50.0%) received SCT at the first HCR. However, HRFS (P=0.030) and EFS (P=0.010) in the SCT group were better than those in the chemotherapy group. Conclusions: The regimen of dasatinib combined with a multi-agent chemotherapy was proven safe and effective in the treatment of newly diagnosed adult Ph(+) ALL patients. Clinical trial registration: ClinicalTrials.gov, NCT02523976.

[Effect of imatinib on the height of children with chronic myeloid leukemia in the chronic phase].

Objective: To evaluate the effect of imatinib on growth impairment in children with chronic myeloid leukemia (CML-CP) in the chronic phase. Methods: From July 2018 to July 2019, questionnaires were distributed to CML children aged <18 years at the time of diagnosis who were receiving imatinib for at least 3 months or to their parents in China. The height-for-age standard deviation score (HtSDS) and the difference of standard deviation integral (△HtSDS) were used to explore the change in height with imatinib therapy. Results: The data of 238 respondents were included; 138 (58.0% ) respondents were men. The median age at the first diagnosis of CML was 11.0 years (range, 1.4-17.9 years) , and 93 (39.0% ) respondents were at the prepuberty stage. At the time of completing the questionnaires, the median age was 15.0 years (range, 2.0-34.0 years) . The median duration of imatinib therapy was 28 months (range, 3-213 months) . Among all the respondents, the mean HtSDS when completing the questionnaires (-0.063±1.361) was significantly lower than that at the time of starting imatinib treatment (0.391±1.244) (P<0.001) . Total 71.0% respondents showed growth impairment that was more common in those starting imatinib therapy at prepubertal age than in those starting at pubertal age. Multivariate analysis showed that younger at the start of imatinib therapy (P<0.001) and longer duration of imatinib therapy (P<0.001) were significantly associated with severe growth impairment on imatinib therapy. Conclusions: Imatinib induced growth impairment in children with CML-CP. Younger the age of initiation and longer the duration of imatinib therapy, more obvious the effect of imatinib on growth impairment.

[Rituximab combined with short-course and intensive regimen for Burkitt leukemia: efficacy and safety analysis].

Objective: This study aimed to explore the efficacy and safety of rituximab combined with short-course and intensive regimens in the treatment of adult patients with Burkitt leukemia. Methods: The clinical data of 11 Burkitt leukemia patients in our hospital from January 30, 2006, to September 12, 2018, were collected. The clinical details, complete remission (CR) rate, overall survival (OS) , relapse-free survival (RFS) , and adverse events were evaluated. Results: The median age of 11 patients was 34 (15-54) years, of which six were males and five were females (M∶F, 1.2∶1) . The median white blood cell (WBC) count was 12.28 (2.21-48.46) ×10(9)/L, and the median blast percent of peripheral blood and bone marrow were 40% (3%-76%) and 84.0% (29.5%-94.5%) , respectively. Ten patients were administered with rituximab combined with a short-course and intensive regimens, and two patients underwent autologous hematopoietic stem cell transplantation following consolidation chemotherapy. The CR rate after one cycle of induction therapy was 100%, the four-year OS was 90%, and RFS was 90%. Out of the ten treated patients, only one patient suffered from tumor lysis syndrome during the induction chemotherapy. Consequently, renal function recovered after hemodialysis and other treatments. The regimen is safe with no treatment-related deaths. Conclusions: Rituximab combined with short-course and intensive chemotherapy regimens is effective and well-tolerated in adult Burkitt leukemia.

[Analysis of risk factors for necrosis of femoral head after internal fixation surgery in young and mid-aged patients with femoral neck fracture].

OBJECTIVE: To retrospectively analyze the risk factors of avascular necrosis of femoral head (ANFH) after internal fixation in young and mid-aged adults. METHODS: From January 2007 to December 2017, femoral neck fracture patients (18-60 years old) treated by reduction and internal fixation were retrospectively studied in Peking University Third Hospital. We recorded their gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) grade, reason of injury, fracture side, interval between injury and surgery, location of fracture line, Garden classification, Pauwels classification, reduction method (open or closed), internal fixation and reduction quality. The diagnosis of ANFH was confirmed based on X-ray and MRI images during the follow-up. The internal fixation method included cannulated compression screw (CCS) or dynamic hip screw (DHS, with or without anti-rotation screw). χ2 test and Logistic regression analysis were used to analyze the relationship between the various factors and postoperative ANFH. RESULTS: A total of 113 patients were included in this study, including 63 males and 50 females with an average age of (43.17 ± 12.34) years. They were followed up by (25.08 ± 16.17) months. ASA grade included grade I (21 cases), grade II (55 cases) and grade III (37 cases). The reasons of injury included low-energy trauma (76 cases) and high-energy (37 cases). The fracture line included subcapital type (37 cases), transverse type (74 cases) and basal type (2 cases). Garden classification included type I (3 cases), type II (46 cases), type III (39 cases) and type IV (25 cases). Pauwels classification included type I (21 cases), type II (55 cases) and type III (37 cases). Interval between injury and surgery was (3.88 ± 3.66) days, 108 patients and 5 patients performed closed and open reduction respectively. 63 patients performed CCS, and 50 patients performed DHS. The reduction quality included grade A (91 cases), grade B (18 cases) and grade C (4 cases). 18 patients developed ANFH after surgery, the incidence rate was 15.93% (18/113). The result of χ2 test showed the reason of injury (OR=0.19, P < 0.01), Garden classification (OR=0.13, P < 0.01), Pauwels classification (OR=0.12, P = 0.02), internal fixation method (OR=3.29, P = 0.04) and reduction quality (OR=0.33, P < 0.01) were significantly associated with ANFH. These five factors were further included into the Logistic regression analysis, and its results showed that the reason of injury (OR=4.11, P = 0.03) and Garden classification (OR=4.85, P = 0.04) were statistically significant. CONCLUSION: The reason of injury, Garden classification, Pauwels classification, internal fixation and reduction quality may increase the risk of ANFH after surgery, and the reason of injury and Garden classification were much more significant.

Upregulated lncRNA CACNA1G-AS1 aggravates the progression of colorectal cancer by downregulating p53.

OBJECTIVE: To investigate the role of long non-coding RNA (lncRNA) CACNA1G-AS1 in regulating proliferative and invasive abilities of colorectal cancer (CRC) cells by mediating p53, thus influencing the progression of CRC. PATIENTS AND METHODS: CACNA1G-AS1 level in CRC tissues and adjacent normal tissues was first determined. Its level in CRC patients with different tumor stages was detected as well. Changes in proliferative and invasive abilities of HCT116 and SW480 cells influenced by CACNA1G-AS1 were evaluated. Subcellular distribution of CACNA1G-AS1 was analyzed. Through Western blot, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assay, the interaction between CACNA1G-AS1 and EZH2 was assessed. The biological function of the target gene of CACNA1G-AS1 was finally explored. RESULTS: CACNA1G-AS1 was upregulated in CRC tissues compared to adjacent normal ones. Its level remained higher in CRC patients with stage III-IV compared to those with stage I-II. Knockdown of CACNA1G-AS1 reduced proliferative and invasive abilities of HTC116 and SW480 cells. CACNA1G-AS1 was mainly distributed in the nucleus. Moreover, CACNA1G-AS1 was verified to interact with EZH2. Knockdown of CACNA1G-AS1 or EZH2 upregulated p53 level and decreased the recruitment ability of EZH2 on p53. Finally, p53 knockdown could partially reverse the regulatory effect of CACNA1G-AS1 on the proliferative ability of HCT116 cells. CONCLUSIONS: CACNA1G-AS1 downregulates p53 level by forming a carcinogenic complex with EZH2, thereby enhancing the proliferative and invasive abilities of CRC cells.