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This article analyzes the limitations of traditional medical theory teaching, and proposes the strategies for cultivating medical students' autonomous learning ability, i.e., informatization-based flipped classroom, problem-oriented teaching, mind mapping training, semi-open book examination, exploitation of the clinical and scientific thinking, and practice activities of medical humanities. The strategies of "problem oriented teaching" and "mind mapping training" were integrated into the practice teaching of hematology. Compared with the traditional medical teaching mode, students' feedback after class showed that the teaching mode incorporating new cultivation strategies was more conducive to the improvement of students' self-learning ability ( P = 0.008), and their satisfaction with teaching mode, learning interest, and self-learning ability were all improved. Thus, the appropriate application of the above strategies can help improve students' autonomous learning ability and optimize the effect of medical theory teaching.
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Objective:To evaluate the efficiency and safety of modified endoscopic anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease (rGERD) with moderate hiatus hernia.Methods:A total of 30 patients with rGERD with moderate hiatus hernia (3-5 cm) diagnosed at the Department of Gastroenterology of Northern Jiangsu People's Hospital from June 2017 to June 2020 were randomly divided into 2/3 circumferential mucosal resection group ( n=15) and 3/4 circumferential mucosal resection group ( n=15) using random number table method, and received modified ARMS of the corresponding mucosal resection range. The GERD symptoms, esophagitis under endoscopy, 24 h pH results, and lower esophageal sphincter (LES) resting pressure were compared before and after the procedure. The therapeutic effect and complications of the two groups were analyzed. Results:In 2/3 resection group, the GERD questionnaire scores (9.53±0.36 VS 11.93±0.57, t=6.874, P<0.001), acid exposure time (19.81%±1.72% VS 31.45%±2.78%, t=8.020, P<0.001) and the DeMeester score based on 24 h esophageal pH monitoring (40.98±4.55 VS 55.33±5.65, t=6.408, P<0.001) at 6 months after the treatment showed a significant reduction compared with those before. In 3/4 resection group, the GERD questionnaire scores (9.0±0.57 VS 12.47±0.68, t=8.650, P<0.001), acid exposure time (20.07%±2.19% VS 29.96%±3.00%, t=7.444, P<0.001) and the DeMeester score (33.67±3.47 VS 51.17±6.03, t=4.973, P<0.001) at 6 months after the treatment were lower than those before. There was no significant difference in the GERD questionnaire scores ( t=0.790, P=0.436), acid exposure time ( t=0.093, P=0.926) or the DeMeester score ( t=1.278, P=0.212) between the two groups at 6 months after treatment. In the two groups, there was no significant difference in the ratio of esophagitis grade C and D (10/15 VS 5/15, χ2=3.894, P=0.063; 8/15 VS 4/15, χ2=2.778, P=0.125) or LES resting pressure [3.29 (2.66,8.29) mmHg VS 3.98 (3.67,9.43) mmHg, P=0.334;5.78 (1.9,8.46) mmHg VS 5.88 (3.28,8.99) mmHg, P=0.125] before and after the treatment. No postoperative delayed bleeding or perforation was observed. The incidence of postoperative esophageal stenosis of 2/3 resection group was lower than that of the other group (1/15 VS 6/15, χ2=4.658, P=0.021). Conclusion:Modified ARMS is effective for controlling reflux symptoms and esophageal acid exposure in rGRED patients with moderate hiatus hernia (3-5 cm), but cannot significantly increase the postoperative resting pressure of LES. Compared with 3/4 circumferential mucosal resection, 2/3 circumferential mucosal resection can reduce the incidence of postoperative esophageal stenosis.
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Objective:To investigate the distribution of pathogenic bacteria of bloodstream infection after chemotherapy in patients with acute leukemia (AL), to analyze the risk factors for the occurrence of adverse events and to construct a nomogram model to predict the occurrence of adverse events.Methods:The clinical data of 313 AL patients with bloodstream infection who were admitted to the First Hospital of Jilin University from January 2018 to December 2020 were retrospectively analyzed, and the incidence, fatality and distribution characteristics of pathogenic bacteria after chemotherapy in AL patients were analyzed; the occurrence of adverse events (death or infectious shock) in patients with different clinicopathological characteristics were compared. Unconditional logistic binary regression model multifactor analysis was used to screen independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy; the nomogram model for predicting the occurrence of adverse events was developed by using R software; the Hosmer-Lemeshow test was used to verify the predictive effect of the model.Results:Of the 313 AL patients, the overall fatality rate was 4.2% (13/313), the all-cause fatality rate of bloodstream infection was 3.5% (11/313). Of the 313 cases, 254 cases (81.1%) were Gram-negative bacteria infection, mainly including 115 cases (45.3%) of Escherichia coli, 80 cases (31.5%) of Klebsiella pneumoniae, and 29 cases (11.4%) of Pseudomonas aeruginosa, and 10 cases (3.9%) died; 51 cases (16.3%) were Gram-positive cocci infection, mainly including 22 cases (43.1%) of Streptococcus spp., 20 cases (39.2%) of Staphylococcus spp., 7 cases (13.7%) of Enterococcus faecalis, and 0 case died; 8 cases (2.6%) were fungal infection, including 4 cases (1.3%) of Candida tropicalis, 2 cases (0.6%) of Candida subsmoothis, 1 case (0.3%) of Candida smooth, 1 case (0.3%) of new Cryptococcus, and 3 cases (37.5%) died. The differences in the occurrence rates of adverse events were statistically significant when comparing different treatment stage, risk stratification, timing of sensitive antibiotic use, total duration of fever, and glucocorticoid use in chemotherapy regimen, infecting bacteria carbapenem resistance, and leukemia remission (all P < 0.05). The results of logistic binary regression analysis showed that the use of glucocorticoid in chemotherapy regimen, the total duration of fever ≥7 d, the timing of sensitive antibiotic use ≥24 h, and carbapenem resistance of the infecting bacteria were independent risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy (all P < 0.05). A nomogram prediction model for the occurrence of adverse events in AL patients with bloodstream infection was established, and the nomogram model was calibrated and validated with good calibration and discrimination. Conclusions:The pathogenic bacteria of bloodstream infection after chemotherapy in AL patients is mainly Gram-negative bacteria, and the presence of glucocorticoid in chemotherapy regimen, long total duration of fever, poor timing of sensitive antibiotics, and infecting bacteria carbapenem resistance are risk factors for the occurrence of adverse events in AL patients with bloodstream infection after chemotherapy, and the nomogram prediction model based on these factors has a reliable predictive ability for the occurrence of adverse events.
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Objective:To investigate the clinical effect of CAG stimulating regimen for refractory adult early T cell precursor acute lymphoblastic leukemia (ETP-ALL) complicated with fusarium infection and the clinical features as well as antifungal strategy of cutaneous fusarium infection.Methods:The diagnosis and treatment of 1 adult patient diagnosed as ETP-ALL complicated with cutaneous fusarium infection in the First Hospital of Jilin University in September 2020 were retrospectively analyzed, and related literatures were reviewed.Results:VICP chemotherapy regimen showed no effectiveness in this patient who was presented with persistent agranulocytosis complicated with cutaneous fusariosis infection. After amphotericin B therapy for infection, he achieved the stable disease and successfully underwent CAG stimulating regimen salvage treatment. The minimal residual disease turned into negative after consolidation chemotherapy based on the myeloid regimen. Finally this patient survived from haploid allogeneic hematopoietic stem cell transplantation after consolidation chemotherapy and fusarium was under the control by using posaconazole as secondary prevention therapy.Conclusions:CAG stimulating regimen can be recommended as reinduction therapy for relapsed/refractory ETP-ALL. Sequential therapy of amphotericin B followed by posaconazole can be a useful antifungal strategy for fusarium infection.
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Objective:To evaluate the efficiency and safety of endoscopic anti-reflux mucosectomy (ARMS) for refractory gastroesophageal reflux disease (rGERD) in the absence of hiatus hernia (HH).Methods:Among 28 rGERD patients adimitted to Gastrointestinal Medical Center, Subei People's Hospital from Jan 2018 to Jun 2020 16 underwent endoscopic mucosal resection (EMR) and 12 did endoscopic submucosal dissection (ESD), The GERD symptoms, endoscopy, 24-h pH monitoring results, manometry, were compared before and after the procedure.Results:ARMS was successfully performed in all 28 patients. Three months after ARMS, 19 patients discontinued the use of pump inhibitors (PPIs), while 9 patients reduced their PPI dose. The GERD questionnaire scores, the median gastroesophageal flap valve grade, the median DeMeester score and acid exposure time based on 24 h esophageal pH monitoring were significantly lower than those before treatment [6.5±2.5 vs.13.4±3.1, 1(1-2) vs.3(1-3), 14.8(8.2-30) vs.34.6(16.2-60.7), 4.4%(1.3%-7.9%) vs. 8.7%(6.2%-13.9%),all P<0.01]. Esophageal sphincter pressure increased after ARMS, from (9.0±3.2) mmHg to (15.5±5.5) mmHg ( t=0.159, P<0.01). The operation time used in ESD was (66.9±4.5) minutes compared to EMR [(29.1±2.0) minutes]( t=13.911, P<0.001). The treatment cost of ESD was (19.9±1.6) thousand yuan vs. for EMR [(9.0±1.6) thousand yuan]( t=58.411, P<0.001). There were no major complications in both groups. Conclusions:ARMS is safe and effective for treatment of rGERD in the absence of HH, and EMR is less time-consuming and more acceptable technique.
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Objective:To investigate the clinical characteristics and prognosis of acute myeloid leukemia (AML) patients with positive TLS-ERG fusion gene.Methods:The clinical data of 9 AML patients with positive TLS-ERG fusion gene in the First Hospital of Jilin University from June 2013 to August 2020 were retrospectively analyzed, and the relevant literature was reviewed.Results:Among 9 patients with positive TLS-ERG fusion gene, there were 5 males and 4 females, with a median age of 16 years old (6-40 years old). Five patients received chemotherapy alone, 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), and 1 patient did not receive systematic treatment. Among 8 patients with systematic treatment, 1 patient had complete remission after the first induction chemotherapy and 5 patients had complete remission after induction therapy. The median overall survival time of 5 patients with chemotherapy alone was 1.5 months (1-11 months), of which 3 patients did not respond to the first course of treatment and died of infection, and 2 patients died after relapse. The median overall survival time of 3 patients with allo-HSCT was 16 months (13-17 months), of which 2 patients died after relapse and 1 patient had sustained molecular complete remission by the end of follow-up.Conclusions:AML with positive TLS-ERG fusion gene has low incidence rate and poor induction efficacy. Hematopoietic stem cell transplantation may partially improve the survival prognosis of patients, but it cannot overcome the adverse effect of positive TLS-ERG fusion gene on prognosis.
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Chronic myeloid leukemia (CML) is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells. With the improvement of disease awareness and the introduction of new drugs, more than 90% of CML patients can achieve long-term survival. However, a few patients still show drug resistance. This article reviews the mechanism of drug resistance in CML patients treated with tyrosine kinase inhibitor (TKI) and the characteristics of ABL kinase region mutation.
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Objective:To evaluate the efficiency and safety of endoscopic submucosal tunnel dissection (ESTD) on treatment of early esophageal cancer with submucosal fibrosis.Methods:In the Department of Gastroenterology of Northern Jiangsu People′s Hospital from June 2015 to Feburary 2018, data of 87 patients undergoing ESTD or endoscopic submucosal dissection (ESD) for early esophageal cancer or precancerous lesion were collected with inclusion criteria of cancer size less than 1/3 circumference with submucosal fibrosis, which was confirmed by pathology. According to the degree of submucosal fibrosis, 60 patients had mild fibrosis (31 underwent ESTD and 29 underwent ESD), and 27 patients had severe fibrosis (16 underwent ESTD and 11 underwent ESD). The dissection speed, en bloc resection rate, complete resection rate, and the complications (including bleeding, muscularis injury, perforation, neck subcutaneous emphysema and esophageal stenosis) were compared between the two methods of dissection in the groups with same degree of submucosal fibrosis.Results:For patients with mild submucosal fibrosis, ESTD had a higher en bloc resection rate (96.8%, 30/31) and complete resection rate (96.8%, 30/31), and lower muscularis injury rate (6.5%, 2/31) than those of ESD [82.8% (24/29), 75.9% (22/29), and 17.2% (5/29), respectively, all P<0.05]. There was no difference in the dissection speed, incidence of intraoperative bleeding, perforation and postoperative esophageal stenosis between the two methods (all P>0.05), and no postoperative delayed bleeding or neck subcutaneous emphysema occurred. For patients with severe submucosal fibrosis, ESTD had a higher dissection speed (12.3±2.8 mm 2/min), and lower incidence of intraoperative bleeding (12.5%, 2/16), muscularis injury (18.8%, 3/16), perforation (6.3%, 1/16) and neck subcutaneous emphysema (6.3%, 1/16) than those of ESD [7.1±3.2 mm 2/min, 54.5% (6/11), 54.5% (6/11), 27.3% (3/11), and 27.3% (3/11)]. There was no difference in en bloc resection rate, complete resection rate, and the incidence of postoperative esophageal stenosis between the two methods, and no postoperative delayed bleeding occurred. Cancer recurred locally in 2 patients undergoing ESD and 1 patient undergoing ESTD at 12 months after the operation, and 1 patient undergoing ESTD developed metachronous cancer at 24 months after the operation. Conclusion:ESTD is safe and effective for endoscopic management of early esophageal cancer or precancerous lesion with submucosal fibrosis. Compared with standard ESD, the advantage of ESTD is more efficient for patients with mild submucosal fibrosis, and is safer for patients with severe submucosal fibrosis.
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Objective:To explore immune cell reconstitution after allogeneic hematopoietic stem cell transplantation(allo-HSCT)by using mathematical function models.Methods:From June 2011 to May 2015, 65 patients with malignant hematological disorders were retrospectively analyzed. Immune cell frequencies and absolute counts were detected at day 14/28/42 and month 2/3/6/9/12/18/24 post-allo-HSCT. The immune cells included CD3 + T, CD4 + helper T, CD8 + effector T, regulatory T, CD19 + B, CD3 -CD56 + NK and CD3 + CD56 + NKT. Kinetic curve models and mathematical equations were established by utilizing curve model estimation. Results:Cubic curve models were observed for the changes of immune cell frequencies. Except for CD3 + T, CD8 + T and NK cells, the changes of absolute counts of immune cells conformed to cubic curve models. The reconstructed kinetic models of CD8 + T and NK cells after allo-HSCT were associated with relapse. Conclusions:Immune cell reconstitution after allo-HSCT conforms to certain mathematical function curve models. It may provide a new strategy for in-depth studies of immune reconstitution after allo-HSCT.
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Objective:To explore the incidence rates, clinical features, risk factors and its impacts on survival of central nervous system complications (CNSC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:From June 2011 to October 2018, 237 consecutive patients undergoing allo-HSCT were retrospectively analyzed.Results:The incidence of CNSC was 10.5%(25/237) and the median time 82(-4 - 810) days post-transplantation. The most common instances of CNSC were drug-associated encephalopathy (n=6), CNS infection (n=5), unexplained convulsions (n=4), metabolic encephalopathy (n=3), immune-related encephalopathy (n=3), primary central relapse (n=3) and cerebrovasculopathy (n=1). The most common clinical symptom was epileptic seizure (n=11). CsA-related encephalopathy was manifested mainly as posterior reversible encephalopathy syndrome on brain MRI. Metabolic encephalopathy is mostly demyelination. Most hippocampal lesions were caused by immune-related encephalopathy or CNS infection. Analysis of risk factors indicated that umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation were high risk factors for post-transplantation occurrence of CNSC. Survival analysis suggested that non-relapse mortality rate (42.9%, 9/21) in group with CNSC of malignant hemoblastosis was higher than that in group without CNSC (15.3%, 27/176) and inter-group difference was statistically significant ( χ2=9.511, P=0.005). The 1/3-year OS rates in group with CNSC were lower than those in group without CNSC (56.6% vs 77.8%; 37.1% vs 65.7%). And the difference was statistically significant ( P=0.022). Conclusions:With a complex etiology, CNSC is one of serious complications after allo-HSCT and it significantly reduces the overall survival rate of patients. Umbilical cord blood transplantation, HLA incompatible transplantation and delayed platelet implantation are high-risk groups for CNSC.
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Objective To explore the efficacy and prognostic factors of chemotherapy regimens including decitabine in treatment of elderly patients newly diagnosed with acute myeloid leukemia (AML). Methods The clinical data of 47 elderly patients newly diagnosed with AML (except M3) who received chemotherapy regimens including decitabine in the First Hospital of Jilin University from February 2013 to November 2017 were retrospectively analyzed, including 11 patients treated with single decitabine and 36 patients treated with decitabine combined with low_dose chemotherapy group. The treatment outcome and the impact of different factors on the prognosis were also analyzed. Results Of 47 patients, there were 15 males and 32 females, and the median age was 65 years old (60-83 years old). The overall response rate of decitabine plus low_dose chemotherapy group for 1 course was higher than that of single decitabine group [80.6% (26/36) vs. 27.3% (3/11), χ 2 ＝ 8.693, P＝ 0.003], and the former showed less courses to acquire remission than the latter (u＝ 3.133, P＝ 0.002); however, there was no significant difference in the median overall survival (OS) time between the two groups (14 months vs. 12 months, P＝ 0.950). Univariate analysis indicated that the median OS time in the complete remission (CR) group was longer than that in the non_CR group (17 months vs. 5 months, P <0.01). The median OS time of the elderly patients with primary AML was longer than that of the patients with secondary AML (16 months vs. 6 months, P＝ 0.01). Cox multifactor analysis showed that failing to achieve CR was identified as an independent adverse influencing factor ( HR＝0.180, 95% CI 0.085-0.382, P< 0.01). The incidence of neutropenia with fever in the patients treated with decitabine plus low_dose chemotherapy group was higher than that in single decitabine group [69.4% (25/36) vs. 36.4% (4/11), χ2＝3.902, P＝0.048]. Conclusion For newly elderly AML patients, chemotherapy regimens including decitabine are safe and effective.
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Objectives@#To evaluate the clinical characteristics and prognosis of high risk cytogenetic abnormalities (HRCA) and various combinations of cytogenetic abnormality in patients with newly-diagnosed multiple myeloma (NDMM) .@*Methods@#This retrospective study collected 182 NDMM patients in the First Affiliated Hospital of Jilin University between Nov. 2009 and May 2018. HRCA included 1q+, del (17p) , t (4;14) , and t (14;16) detected by FISH, and non-HRCA included del (13q) , t (11;14) detected by FISH. The clinical characteristics among three groups, including cases who carrying a single HRCA, 1 HRCA in combination with non-HRCA and cases carrying two or more HRCAs (double/triple-hit) were observed. Kaplan-Meier curve was used to analyze both progression-free survival (PFS) and overall survival (OS) for the three groups.@*Results@#The survivals of patients with 1 HRCA in combination with non-HRCA were similar to those with two or more HRCAs (double/triple-hit) , the median PFS (mPFS) was 19.1 m vs 12.1 m (P=0.248) and median OS (mOS) was 29.6 m vs 29.3 m (P=0.774) . Furthermore, the prognosis of these two groups were both inferior to patients with a single HRCA, respectively. (mPFS: 32.2 m, P=0.040, P=0.001; mOS: 42.3 m, P=0.021, P=0.041) . Strikingly, both the mPFS and the mOS of patients with 1 HRCA in combination with non-HRCA (regardless of high risk or not) were significantly shorter than that of cases with a single HRCA (mPFS: 15.1 m vs 32.2 m, HR=2.126, 95%CI 1.176-3.843, P=0.005; mOS: 29.3 m vs 42.3 m, HR=1.442, 95%CI 0.705-2.950, P=0.011) .@*Conclusion@#It is of prognostic significance value for detecting double/triple-hit based on FISH cytogenetics in NDMM.
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Objective@#To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) .@*Methods@#A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc.@*Results@#①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD-) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD- rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD- status. ②The 2-year PFS rate of patients with MRD- status was significantly higher than that of MRD+ status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD+) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD- status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD-status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD- status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD- duration (median MRD- duratio: 25 months vs 10 months, P=0.034) .@*Conclusion@#Our findings supported MRD+ status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD- status also played a significant role in evaluation of prognosis, while loss of MRD-status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.
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Objective@#To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients.@*Methods@#A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform.@*Results@#① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle.@*Conclusions@#1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.
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Objective To analyze the effect of haploidentical hematopoietic stem cell transplantation (HID-HSCT) on high-risk acute lymphoblastic leukemia (ALL),and to explore the influence of minimal residual disease (MRD) before transplant on the outcomes.Methods A retrospective analysis was performed on 39 high risk ALL patients receiving HID-HSCT in our hospital from Jan.2013 to Jan.2018.The clinical features,stem cell engraftment,complications,survival and recurrence were compared between patients with pretransplant MRD + and MRD-.Results All the 39 patients presented with successful engraftment.The overall survival (OS) was 54.67％;the disease free survival (DFS) was 40.96％;the incidence rate of acute graft versus host disease (aGVHD) was 53.8％,including 23.1％ Ⅱ-Ⅳ degree aGVHD and 2.6％ Ⅲ-Ⅳ degree aGVHD.There was no significant difference in stem cell engraftment,GVHD,cytomegalovirus infection and hemorrhagic cystitis between MRD + and MRD-patients.DFS and OS in MRD + patients were significantly lower than those in MRD-patients;the cumulative RR rate increased significantly,and there was no significant difference in cumulative TRM.Conclusion HID-HSCT was an effective method to treat high-risk ALL,but MRD + patients had high recurrence rate and poor prognosis.Strategy adjustment should be considered to reduce tumor residual and the transplantation strategy should be optimized for these kinds of high risk patients,so as to improve long-term outcomes.
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Objective To study the immune re-constitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies.Methods From June 2011 to May 2015,65 patients with hematological malignancies were analyzed retrospectively.Lymphocyte subsets were determined by flow cytometry (FCM),including total T lymphocytes (CD3+),helper T cells (CD3+ CD4+),cytotoxic T cells (CD3+ CD8+),CD4/CD8 ratio,nature killer (NK) cells (CD3-CD56+),NKT cells (CD3+ CD56+),B lymphocytes (CD19+),naive T cells (CD3+ HLA-DR+),static T cells (CD3+ HLA-DR-),and regulatory T cells (CD4+ CD25high Foxp3+) on the day 14,28 and 42,and on the month 2,3,6,9,12,15,18 and 24 after allo-HSCT.Results The percentage of CD3+ T cells located normal range after hematological recovery,and its absolute number recovered to normal range at + 15 months.The percentage of CD3+ CD4+ T cells recovered to normal range at + 24 months.However,the absolute number of CD3+ CD4+ T cells did not recover to normal range until 24 months after allo-HSCT.The percentage of CD3+ CD8+ T cells was higher than normal range at + 42 day,and its absolute number was greater than normal range at + 3 months.Hence,low CD4/CD8 ratio was observed for a long period.The re-constitution time points of the percentage and absolute number of CD3+ HLA-DR+ T cells were + 3 months and + 24 months respectively.The re-constitution time points of the percentage and absolute number of CD3 + HLA-DR-T cells were + 2 months and + 15 months respectively.The re-constitution time points of the percentage and absolute number of regulatory T cells were + 12 months and + 15 months respectively.The percentage of NKT cells located in normal range after hematological recovery,and its absolute number retumed to normal range at + 12 months.The re-constitution time points of the percentage and absolute number of B cells were + 9 months and + 18 months respectively.The percentage of NK cells located in normal range after hematological recovery,and its absolute number returned nearly to normal range at + 3 months.Conditioning regimen containing ATG,source of stem cells,CD34+ cell number,GVHD,and CMV reactivation were all associated with immune re-constitution after allo-HSCT.Conclusion Different immune cells showed different re-constitution models after allo-HSCT,and the percentage recovered faster than absolute number for a certain kind of immune cells.Studying immune re-constitution and its associated factors may offer beneficial information for insight into transplantation immunology and improve the management of allo-HSCT.
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Objective To explore the outcome and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Methods Forty-nine newly diagnosed adult patients with Ph+ALL were analyzed retrospectively, and the treatment effect and the impact of different factors on prognosis were explored. Results In 49 patients, there were 24 males and 25 females;the median age was 38 years (range 15-77 years). Hematologic complete remission (CR), major molecular response (MMR) and complete molecular remission (CMR) rate in patients received tyrosine kinase inhibitors (TKI) plus chemotherapy were higher than those in patients received chemotherapy only (96.8 % vs. 72.2 %, χ2= 4.308, P= 0.038; 64.5% vs. 16.7 %, χ2=10.468, P= 0.001; 25.8 % vs. 11.1 %, χ2=4.250, P=0.039). With a median overall survival (OS) of 24 months (3-70 months), the 3-year OS and relapse-free survival (RFS) rates were 32.7 % and 21.4 %, respectively. The 3-year OS rate and 1-year RFS rate in TKI plus chemotherapy group were 40.3 % and 67.8 % respectively, which were higher than those in chemotherapy group (11.1 % and 11.1 %) (χ2= 12.725, χ2= 17.401, both P< 0.001). The 3-year OS and RFS rates in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group were higher than those in the group without allo-HSCT(62.5 % vs.25.7 %,χ2= 6.196,P= 0.013; 41.7 % vs. 15.0 %,χ 2= 8.032, P=0.005).The 3-year OS and RFS rates in patients achieved MMR after 2 circles treatment were higher than those in the others (45.1 % vs. 17.6 %,χ2= 5.446,P= 0.020; 28.9 % vs. 11.7 %,χ 2= 6.484,P= 0.011). Multivariate analysis showed that received TKI (HR= 0.227, 95 % CI 0.094-0.550, P= 0.001) was an independent prognostic factor for OS; received TKI (HR= 0.225, 95 % CI 0.082-0.618, P= 0.004) and allo-HSCT (HR=0.275, 95 % CI 0.077-0.983, P=0.047) were independent prognostic factors for RFS. Conclusions TKI can increase CR,MMR and CMR rates,improve outcome,and give more chance to receive HSCT.In TKI era,allo-HSCT is still the important treatment for Ph+ALL,especially for patients without MMR.
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Objective To explore the outcome and prognostic factors of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Methods Forty-nine newly diagnosed adult patients with Ph+ALL were analyzed retrospectively, and the treatment effect and the impact of different factors on prognosis were explored. Results In 49 patients, there were 24 males and 25 females;the median age was 38 years (range 15-77 years). Hematologic complete remission (CR), major molecular response (MMR) and complete molecular remission (CMR) rate in patients received tyrosine kinase inhibitors (TKI) plus chemotherapy were higher than those in patients received chemotherapy only (96.8 % vs. 72.2 %, χ2= 4.308, P= 0.038; 64.5% vs. 16.7 %, χ2=10.468, P= 0.001; 25.8 % vs. 11.1 %, χ2=4.250, P=0.039). With a median overall survival (OS) of 24 months (3-70 months), the 3-year OS and relapse-free survival (RFS) rates were 32.7 % and 21.4 %, respectively. The 3-year OS rate and 1-year RFS rate in TKI plus chemotherapy group were 40.3 % and 67.8 % respectively, which were higher than those in chemotherapy group (11.1 % and 11.1 %) (χ2= 12.725, χ2= 17.401, both P< 0.001). The 3-year OS and RFS rates in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group were higher than those in the group without allo-HSCT(62.5 % vs.25.7 %,χ2= 6.196,P= 0.013; 41.7 % vs. 15.0 %,χ 2= 8.032, P=0.005).The 3-year OS and RFS rates in patients achieved MMR after 2 circles treatment were higher than those in the others (45.1 % vs. 17.6 %,χ2= 5.446,P= 0.020; 28.9 % vs. 11.7 %,χ 2= 6.484,P= 0.011). Multivariate analysis showed that received TKI (HR= 0.227, 95 % CI 0.094-0.550, P= 0.001) was an independent prognostic factor for OS; received TKI (HR= 0.225, 95 % CI 0.082-0.618, P= 0.004) and allo-HSCT (HR=0.275, 95 % CI 0.077-0.983, P=0.047) were independent prognostic factors for RFS. Conclusions TKI can increase CR,MMR and CMR rates,improve outcome,and give more chance to receive HSCT.In TKI era,allo-HSCT is still the important treatment for Ph+ALL,especially for patients without MMR.
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Objective@#To investigate the efficacy and safety of IA regimen which contains idarubicin (IDA) 8 mg/m2, 10 mg/m2 or 12 mg/m2 as induction chemotherapy for adult patients with de-novo acute myeloid leukemia (AML) .@*Methods@#A total of 1 215 newly diagnosed adult AML patients, ranging from May 2011 to March 2015 in the First Affiliated Hospital of Soochow University and other 36 clinical blood centers in China were enrolled in the multicenter, single-blind, non-randomized, clinical controlled study. To compare the response rate of complete remission (CR) , adverse events between different dose idarubicin combined with cytarabine (100 mg/m2) as induction chemotherapy in newly diagnosed patients of adult AML.@*Results@#Of 1 207 evaluable AML patients were assigned to this analysis of CR rate. The CR rates of IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 73.6% (215/292) , 84.1% (662/787) and 86.7% (111/128) , respectively (P<0.001) . After adjusted for age, blast ratio of bone marrow, FAB classification and risk stratification, the odds ratios (95% CI) of IDA 10 mg/m2 group and IDA 12 mg/m2 group were 0.49 (0.34-0.70) and 0.36 (0.18-0.71) , as compared with the IDA 8 mg/m2 group (P<0.001, P=0.003) . In the intermediate and favorable groups, CR rates was 76.5% (163/213) , 86.9% (506/582) and 86.1% (68/79) in different doses of IDA (P=0.007) . Interestingly, IA regimen with IDA 10 mg/m2 was the only beneficial factor affecting CR in this group after adjusted for age, blast ratio of bone marrow and FAB classification[OR=0.47 (95% CI 0.31-0.71) , P<0.001]. CR rates in adverse group was 50.0% (18/36) , 60.6% (43/71) and 81.8% (18/22) respectively (P=0.089) . However, the odds ratios (95% CI) of IDA 12 mg/m2 when compared with the IDA 8 mg/m2 was 0.22 (0.06-0.80) , after adjusted for age, blast ratio of bone marrow and FAB classification. The median time (days) of neutrophil count less than 0.5×109/L in IDA 8 mg/m2 group, IDA 10 mg/m2 group and IDA 12 mg/m2 group were 14 (11-18) , 15 (11-20) and 18 (14-22) , respectively (P=0.012) and of platelet count lower than 20×109/L were 14 (7-17) , 15 (11-20) and 17 (15-21) , respectively (P=0.001) . The incidences of lung infection in the three groups were 9.8%, 13.5% and 25.2%, respectively (P<0.001) .@*Conclusions@#For young adult patients (aged 18-60 years) with AML in China, intensifying induction therapy with idarubicin 10 mg/m2 is clinically superior to IDA 8 mg/m2 and IDA 12 mg/m2 in favorable intermediate AML subgroup. However, idarubicin 12 mg/m2 is more suitable to adverse AML subgroup.
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Objective@#To evaluate efficacy of the BiRd regimen, a combination of clarithromycin, lenalidomide, and dexamethasone, in the treatment of patients with relapsed/refractory multiple myeloma (RRMM) .@*Methods@#Patients with RRMM treated with BiRd between September 11, 2013 and August 1, 2016 at six centers were included to evaluate overall survival rate (ORR) , clinical benefit rate (CBR) , progression-free survival (PFS) , overall survival (OS) , as well as adverse events.@*Results@#Of 30 patients with RRMM, 27 patients were evaluable, and ORR and CBR were 51.9% (14/27) and 66.7% (18/27) respectively, including 1 sCR (3.7%) , 3 CR (11.1%) , 3 VGPR (11.1%) , and 7 PR (25.6%) . In 13 patients with prior Rd, ORR and CBR were 38.5% (5/13) and 61.5% (8/13) respectively, of which 5 patients with ≥MR carried high-risk cytogenetic[ (e.g.17p- or t (4;14) ] together with at least one of other adverse-prognostic cytogenetic (e.g.13q- and/or 1q21+) . In 24 patients with prior bortezomib-based therapy, ORR and CBR were 45.8 and 62.5%, respectively. With a median follow-up time of 14.9 (range 1.0-33.8) months, the median PFS and OS were 12.0 (95%CI 11.6-12.4) and 27.6 (95%CI 15.1-40.1) months, respectively. The BiRd regimen was well tolerated.@*Conclusion@#The BiRd regimen is an effective and safety protocol for RRMM, including those carrying high-risk cytogenetic markers.