Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

Objective:The effect and safety of etoposide combined with G-CSF were compared with those of cyclophosphamide combined with G-CSF in autologous peripheral blood mobilization in patients with multiple myeloma (MM) .Methods:Patients with MM who received autologous peripheral blood stem cell mobilization and collection in the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 1, 2020 to July 31, 2023 were included. A total of 134 patients were screened by propensity score matching technology according to a 1∶1 ratio. A total of 67 cases were each treated with ETO combined with G-CSF mobilization scheme (ETO group) and CTX combined with G-CSF mobilization scheme (CTX group). Their clinical data were retrospectively analyzed.Results:①Collection results: the ETO and CTX groups [2 (1-3) d vs 2 (1-5) d; P<0.001] and CD34 + cells [7.62×10 6 (2.26×10 6-37.20×10 6) /kg vs 2.73×10 6 (0.53×10 6-9.85×10 6) /kg; P<0.001] were collected. The success rate of collection was 100.0% (67/67) versus 76.1% (51/67) ( P<0.001). Excellent rate of collection was 82.1% (55/67) versus 20.9% (14/67; P<0.001). Two patients in the ETO group switched protocols after 1 day of collection, and 11 patients in the CTX group switched protocols after 1-2 days of collection. ②Adverse reactions: granular deficiency with fever (21.5%[14/65] vs. 10.7%[6/56]; P=0.110), requiring platelet transfusion [10.7% (7/65) vs 1.8% (1/56) ; P=0.047]. ③Until the end of follow-up, 63 cases in the ETO group and 54 cases in the CTX group have undergone autologous transplantation. The median number of CD34 + cells infused in the two groups was 4.62×10 6 (2.14×10 6-19.89×10 6) /kg versus 2.62×10 6 (1.12×10 6-5.31×10 6) /kg ( P<0.001), neutrophil implantation time was 11 (9-14) d versus 11 (10-14) d ( P=0.049), and platelet implantation time was 11 (0-19) d vs. 12 (0-34) d ( P=0.035). One case in the CTX group experienced delayed platelet implantation. Conclusion:The mobilization scheme of etoposide combined with G-CSF requires relatively platelet transfusion, but the collection days are shortened. The collection success rate, excellent rate, and the number of CD34 + cells obtained are high, and the neutrophil and platelet engraftment is accelerated after transplantation.

Objective:To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents.Methods:The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors.Results:Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor ( HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy ( HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better ( HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions:In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Objective:To investigate the clinical features and prognosis of multiple myeloma(MM)patients who resisted to the combination of bortezomib,lenalidomide and dexamethasone(VRD). Methods:The clinical features and prognosis of 150 patients with newly diagnosed MM in Beijing Chaoyang Hospital who were treated with VRD from January 2015 to January 2020 were retrospectively analyzed by SPSS software. Results:Among a total of 150 MM patients,21 patients resisted to VRD,including 14 patients with primary refractory to VRD and 7 patients with early relapse.In the VRD-resistant group(n=21),the median age of patients was 58 years(37-70 years),and female patients were more common(61.9％);Durie-Salmon stage:17 patients were DS stage Ⅲ,4 patients were DS stage Ⅱ;44.4％of those patients were cytogenetic high risk.CD20 positive rate was higher in the VRD-resistant group(P=0.014).The overall survival(OS)of MM patients in the VRD-resistant group was significantly lower than that in the VRD-nonresistant group(34 months vs not achieved,P＜0.001).In the VRD-resistant group,the median OS of MM patients receiving autologous hematopoietic stem cell transplantation was significantly longer than that of non-transplant patients(34 months vs 16 months,P=0.038).Drug resistance and non-autologous transplantation are independent adverse prognostic factors for newly diagnosed MM patients receiving VRD induction chemotherapy.COX multivariate analysis showed that age＞65,cytogenetic high risk and non-autologous stem cell transplantation may be adverse prognostic factors for VRD-resistant MM patients. Conclusion:Positive CD20 was more common in MM patients with VRD resistence,which may indicate more aggressive biological characteristics in VRD-resistent MM patients.The VRD-resistent MM patients had poor prognosis,they can obtain disease remission from salvage chemotherapy including daratumumab,and the survival of them also can be improved after autologous stem cell transplantation.

Objective:To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM).Methods:A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1.Results:Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR=0.644, 95 %CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS ( HR=0.646, 95 %CI 0.457-0.913, P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR=0.705, 95 %CI 0.497-0.998, P=0.049), but OS was not affected ( P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion:These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

Objective:To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients.Methods:A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1∶1 scale, 64 in each group, and correlation analysis was performed.Results:A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients ( P=0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P=0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P=0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS ( HR=0.448, 95% CI 0.260-0.771, P=0.004) and PFS ( HR=0.446, 95% CI 0.280-0.778, P=0.003) . Conclusion:These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.

Objective: To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients. Methods: 8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed. Results: Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last. Conclusions Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.

Objective To explore the application effect of case method combined with role play in clinical nursing teaching on hematologic diseases.Methods Totals of 100 nursing students from School of Nursing in Capital Medical University were selected, with the 50 enrolled in 2015 as the experimental group, and the other 50 in 2014 as the control group. Traditional teaching method was conducted to the control group, while students in the experimental group were taught with case method combined with role play. After the class, nursing students in the two groups took a theoretical examination on completion of the course and an evaluation on their writing on nursing plans, and were also evaluated by Active learning state (ALS).Results Compared with the control group, scores of students in the experimental group were higher in terms of theoretical examination and evaluation on their writing on nursing plans (P<0.05); total scores of ALS evaluation and scores in its individual items in the experimental group were higher than that in the control group (P<0.05). Conclusions In clinical nursing teaching on hematologic diseases, by circulating the teaching through combining case method and role play, a standardized handbook was formed, which can quickly and effectively improve the students' clinical nursing practice skills.

Objective To explore the application effects of continuous nursing based on multi-disciplinary cooperation in patients with multiple myeloma.MethodsA total of 108 patients with multiple myeloma hospitalized in Beijing Chao-Yang Hospital Affiliated to Capital Medical University from January 2015 to June 2016 were included and randomly divided into two groups, 54 cases respectively. In the control group, patients received the routine oral and written discharge guidance. The continuous nursing based onmulti-disciplinary cooperation was performed in the intervention group. Self-care ability, bone pain related health knowledge,pain relief and satisfaction of patients before and 6 months after the intervention were compared between two groups.ResultsBefore the intervention, there were no significant differences in self-care knowledge, self concept, self-care skills, self-care responsibility, the score of bone pain control health knowledge, patient numbers of bone pain relief and percentage of bone pain relief between two groups(t/χ2/Z=0.518,0.361,1.587,0.325,0.475,0.609,0.905;P>0.05). At 6 months after the intervention, the score of self-care knowledge(44.5±7.0), self concept(17.6±5.1), self-care skills(23.1±6.1), self-care responsibility (14.7±4.2), the score of bone pain control health knowledge(93.0±7.0), patient numbers of bone pain relief and percentage of bone pain relief(88.9%)in the intervention group were significantly better than those in the control group(t/χ2/Z=6.582,3.973,4.548,3.606,9.973,7.542,5.655;P<0.05). Nursing satisfaction in guidance, non-specialized service support, convenient service channels and available health service resources. Conclusions Extended nursing specially designed for empty nesters should be equipped with extended psychological nursing, daily nursing and other nursing services, and personalized services should be provided to empty nesters in effective forms of extended nursing. Meanwhile, community hospitals' functions as well as cooperation between hospitals and communities should be strengthened to improve extended nursing services.

Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase which belongs to the Tec kinase family and plays an important role in B cell receptor signaling.Nowadays,BTK has been a nove] target for treating some B cell malignancies.Recently,some studies have confirmed that BTK inhibitor,PCI-32765 (ibrutinib),can effectively treat chronic lymphocytic leukemia,mantle cell lymphoma and so on.This review will discuss the preclinical and clinical development of this BTK inhibitor in B cell malignancies.