Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.

Objective:To investigate the efficacy of using a pediatric-inspired regimen for adolescents and young adults (AYA) with Philadelphia chromosome-negative (Ph -) acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) at a single center in China. Methods:Clinical data of 71 consecutive newly diagnosed AYA patients with Ph - ALL/LBL on a pediatric-inspired regimen in Peking Union Medical College Hospital from January 2012 to November 2018 were retrospectively analyzed. Results:Median age at diagnosis was 20 years (range: 15-38) , and 46 patients (64.8%) were male. Forty-nine (69.0%) had B-ALL/LBL. Among 62 ALL patients, 22 (35.5%) were high-risk. Complete remission rate was 93.0%. At follow-up with a median time of 44 months, the estimated 5-year disease-free survival (DFS) and overall survival (OS) was 56.3% and 64.3%, respectively. There was no significant difference in 5-year OS between allogeneic hematopoietic stem cell transplantation group and the continuous chemotherapy group after completion of 4 courses of chemotherapy. The 5-year DFS and OS for the non-high-risk group was 63.1% and 73.7%, respectively, which were significantly higher than 32.0% and 44.4% for the high-risk group, respectively ( P<0.001) . Conclusions:The use of pediatric-inspired regimen for AYAs with Ph - ALL/LBL was feasible and effective.

Objective To evaluate the safety and efficacy of lenalidomide plus rituximab in treatment of the patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL). Methods The clinical data of the patients with relapsed/refractory B-NHL after the varieties of treatment methods in Peking Union Medical College Hospital between January 2015 and December 2017 were retrospectively analyzed. All the patients were treated with R2 regimen: oral lenalidomide (25 mg/d for day 1-day 21) and rituximab (375 mg/m2 of intravenous infusion on day 1, 28-day of each cycle); the efficacy was evaluated after three cycles. After this induction phase, the patients achieving complete response (CR), partial response (PR), or stable disease (SD) were given R2 regimen until the end of 8 cycles. The major end point was overall response rate (ORR) defined as CR + PR. Secondary end point included 1-year progression free survival (PFS), 1-year overall survival (OS) and grade 3-4 adverse events. T cell and B cell subsets of 7 patients at baseline were measured, and T cell and B cell subsets of 13 patients with good efficacy were dynamically observed. Results A total of 49 patients who received 1-4 chemotherapy regimens were included. The ORR after the R2 treatment for 3 courses was 65% (32/49). Thirty-six patients (9 cases of CR, 22 cases of PR, 5 cases of SD) were enrolled in R2 maintenance treatment. The median follow-up time was 13 months, 1-year PFS rate was 61% and 1-year OS rate was 84% . The most common adverse event was bone marrow suppression, including grade 3-4 neutropenia (27% ), grade 3-4 thrombocytopenia (6% ) and grade 4 anemia (4% ), most of which could be controlled by prolonging interval cycles or reduced lenalidomide dosage. The decreased number of CD19+B cell after treatment could be seen in 13 patients who obtained good efficacy under the dynamic observation. Conclusion Lenalidomide plus rituximab is well tolerated and highly active in the treatment of relapsed/refractory B-NHL.

Objective: To investigate the predictors of death after endovascular mechanical thrombectomy (EMT) in patients with acute vertebrobasilar occlusive stroke (VBOS). Methods: Patients with acute VBOS treated with EMT in Wuhan No. 1 Hospital were enrolled retrospectively. The demographic and clinical data were collected. According to whether the patients died at 90 d after procedure, they were divided into survival group and death group. The demographic and clinical data were compared between the two groups. Multivariate logistic regression analysis was used to determine the independent risk factors for death at 90 d after EMT. Results: A total of 47 patients were enrolled. The median age was 62 years, 34 were males (72.3%), the median baseline National Institutes of Health Stroke Scale (NIHSS) score was 16, 42 patients (89.4%) had recanalization (modified Thrombolysis in Cerebral Infarction[mTICI] 2b/3 grade), and 12 (25.5%) died within 90 d after procedure. Univariate analysis showed that the baseline NIHSS score (26 [21-28]vs. 12 [5-23]; Z=-3.165, P=0.002), percentage of neutrophil (81.61% ±11.82% vs. 72.20% ±12.09%; t=-2.137, P=0.033), neutrophil/lymphocyte ratio (10.54±7.17 vs. 4.98±3.57; t=-2.393, P=0.017), and incidence of sICH (25.0% vs. 2.9%; χ²=5.627, P=0.018) in the death group were significantly higher than those in the survival group, while the percentage of lymphocyte (12.00%±9.04% vs. 20.67%±10.39%; t=-2.429, P=0.015) was significantly lower than that of the survival group. Multivariate logistic regression analysis showed that high baseline NIHSS score (odds ratio [OR] 1.243, 95% confidence interval [CI] 1.046-1.318; P=0.038), high neutrophil/lymphocyte ratio (OR 1.278, 95% CI 1.002-1.630; P=0.049) and symptomatic intracranial hemorrhage (OR 5.088, 95% CI 1.065-38.718; P=0.046) were the independent predictors for death. Conclusion High baseline NIHSS score, high neutrophil/lymphocyte ratio and symptomatic intracranial hemorrhage are the independent predictors for death within 90 d after EMT in patients with acute VBOS.

Objective To evaluate the safety and efficacy of Hyper-CVAD intensive chemotherapy regimen in patients with newly diagnosed aggressive T-cell lymphoma. Methods The efficacy, side effects and survival status were retrospectively analyzed in 34 patients with newly diagnosed aggressive T-cell lymphoma who received Hyper-CVAD regimen as induction therapy in Peking Union Medical College Hospital from September 2009 to December 2010. Results Of 34 patients, 28 cases (82.4 ％) showed treatment response, including 10 cases (29.4 ％) of complete response (CR). Eleven patients underwent stem cell transplantation, including 1 case of human leukocyte antigen-identical siblings allogeneic stem cell transplantation. The median follow-up was 16 months (1-82 months), and the overall survival (OS) rate of 1 or 3-year was 70.2 ％ and 41.1 ％ respectively, and progression-free survival (PFS) rate of 1 or 3-year was 49.3 ％ and 31.6 ％ respectively. The major adverse reaction was myelosuppresion, including 18 cases (52.9％) of myelosuppresion with grade Ⅳ. Three patients died of serious infection. Cox regression multifactor analysis showed CR was the only influencing factor for PFS (HR=6.118, 95％CI 1.327-28.206, P=0.020). Marrow involvement (HR= 0.270, 95 ％CI 0.101-0.722, P= 0.009) and CR (HR= 6.669, 95 ％CI 1.754-25.354, P= 0.005) were independent influencing factors for OS. Conclusions Hyper-CVAD regimen has a high response rate for aggressive T-cell lymphoma, but the lasting effectiveness and the short-term efficacy show unfavorable performances. Meanwhile, myelosuppression is serious and infection incidence is high. Autologous hematopoietic stem-cell transplantation after remission may improve the outcome.

Objective: To Evaluate the efficacy and safety of posaconazole as primary prevention of invasive fungal disease (IFD) in patients with severe aplastic anemia (SAA) treated with anti-thymus/lymphocyte immunoglobulin (ATG/ALG) combined with cyclosporine intensive immunosuppressive therapy (IST). Methods: A retrospective analysis of clinical data of 58 SAA patients who received IST of anti-thymocyte immunoglobulin combining cyclosporine and antifungal prophylaxis during April 2013 to May 2017 in Peking Union Medical College Hospital was performed. The patients were divided into posaconazole prophylaxis group and the control group (itraconazole or fluconazole). The disease characteristics, IFD prevention effect and adverse drug reaction, curative effect and prognosis of the two groups were compared. Results: Posaconazole was used to prevent fungal infection in 20 patients. The other 38 patients were used as the control group. Retrospective analysis showed comparable characteristics (gender, age, disease severity, etiology, interval between the onset of disease to treatment, ATG/ALG type) of both groups. The incidence of IFD were 0 and 15.8% in posaconazole prophylaxis group and the control group, respectively (P=0.084). In the control group, there were 6 cases diagnosed as IFD. Of them, 2 were confirmed, 2 suspected and 2 not identified. Five of the 6 cases were pulmonary infection, 1 bloodstream infections. Of the 6 IFD cases, 5 were very severe aplastic anemia (VSAA). There was no obvious adverse reaction in posaconazole prophylaxis group. Conclusion Posaconazole is safe and effective for primary prevention of fungal infection of SAA patients receiving IST, especially for the VSAA.

Objective: To analyze the clinical effects and safety of combination treatment of thalidomide, stanozolol, and prednisone (TSP regimen) in patients with myelofibrosis (MF) who experienced hematological adverse reactions during ruxolitinib treatment. Methods: Ten MF patients with anemia or thrombocytopenia during ruxolitinib treatment from January 2016 to July 2017 in Peking Union Medical College Hospital were retrospectively analyzed. All patients were treated with a combination of low dose of thalidomide (around 75 mg/d), stanozolol (2 mg/time, 3 times per day), and low dose of prednisone (0.5 mg·kg^-1·d^-1). The hematological response and safety were assessed. Results: There were 9 cases of anemia and 7 cases of thrombocytopenia during ruxolitinib treatment. After TSP regimen treatment, there were 5 cases of hemoglobin response including 1 case of complete remission (CR). There were 4 cases of platelet response and all achieved CR. Totally, the hematological overall response was seen in 7 cases. The median time from taking medicine to getting response was 27 d (13-89 d). 3 patients lost efficacy, while the median duration of response didn't reach (28-207 d). Conclusion TSP regimen can improve anemia or thrombocytopenia during ruxolitinib treatment in patients with MF.

Objective: The clinical characteristics and outcomes of patients with chronic myeloid leukemia (CML) who had discontinued tyrosine kinase inhibitors (TKI) therapy were analyzed retrospectively. Methods: Clinical data of 109 cases of chronic CML patients who had discontinued TKI therapy in seven centers were retrospectively analyzed from June 1, 2005 to March 1, 2018. 91 cases with complete clinical data were enrolled in this study. We aimed to observe the status of patients with treatment free remission (TFR) after TKI therapy discontinuation and its prognostic factors. Results: 38 of 91 patients lost MMR after a median follow-up of 9 months and the estimated TFR was 52.6%. 31 of 38 patients who met the definition of molecular relapse resumed TKI treatment immediately and regained the major molecular response (MMR) with a median time of 3 months (range, 1-12 months). No significant difference was found in median course of imatinib therapy between the TFR group and the relapse. Similarly, duration to MMR, age and gender also showed no difference between the two groups. The longer duration of MMR maintenance (more than 24 months), the lower relapse rate was observed (P=0.027). Conclusion TKI might be safely discontinued in part of CML patients.