1.Dynamic changes and prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients
Zhi YAN ; Xingyue WU ; Weiqin YAO ; Lingzhi YAN ; Song JIN ; Jingjing SHANG ; Xiaolan SHI ; Depei WU ; Chengcheng FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(7):807-814
Objective·To detect immunoglobulin(Ig)expression levels in newly diagnosed multiple myeloma(MM)patients before and after induction therapy,and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy,infection occurrence,and prognosis.Methods·Clinical data from 142 MM patients treated at the Department of Hematology,The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed.Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone(VRD)regimen were assessed.Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal.Patients were stratified by immunoparesis severity(mild,moderate,severe,extremely severe).ANOVA,rank-sum tests,and x2 tests were used to analyze correlations with baseline characteristics.The relationship between the improvement in immunoparesis and the induction efficacy,infection occurrence,and prognosis was analyzed based on the dynamic changes in immunoparesis.Results·Normal Igs were severely reduced in newly diagnosed MM patients.Immunoparesis was present in 128 patients(90.1%),with severe or extremely severe immunoparesis accounting for 76.1%.Patients with extensive immunoparesis(all uninvolved Ig levels below the lower normal limit)were more likely to have severe immunoparesis(P<0.05).There were no statistically significant differences in age,gender,presence of severe renal insufficiency,and high-risk cytogenetics among MM patients with different degrees of immunoparesis(P>0.05),but there were statistically significant differences in MM staging(P=0.008)and typing(P=0.010).Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System(R-ISS)and were of the IgG type.At diagnosis,the levels of the involved Ig or light chain were negatively correlated with normal Ig levels(P<0.05).Improvement in immunoparesis after induction therapy was positively correlated with treatment response(P=0.006).The infection rate was high(26.8%),but no significant correlation was found between immunoparesis and infection occurrence(P>0.05).After induction therapy,patients showing improvement in immunoparesis had significantly longer progression-free survival(PFS)(median PFS:not reached vs 38 months,P=0.025),but no significant impact on overall survival(OS)was observed(P=0.450).Conclusion·Immunoparesis is common and severe in newly diagnosed MM patients,with severity correlating with disease stage and subtype.VRD therapy can partially reverse immunoparesis,and improvement is positively associated with treatment response and PFS benefit.Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies.Humoral immune deficiency may serve as a prognostic indicator in MM,but its impact on OS requires further investigation.
2.Clinical observation on the effect of RIC-PTCY on allogeneic hematopoietic stem cell transplantation in patients with hematologic malignancies
Yanting LI ; Yujie LIU ; Yang XU ; Depei WU
Chinese Journal of Organ Transplantation 2025;46(11):741-748
Objective:To evaluate the efficacy and safety of reduced intensity conditioning (RIC) combined with posttransplant high-dose cyclophosphamide (PTCY) in the treatment of high-risk and relapsed/refractory malignant hematological diseases through allogeneic hematopoietic stem cell transplantation (allo-HSCT).Method:A retrospective analysis was conducted on clinical data of 42 recipients with high-risk or relapsed/refractory malignant hematological diseases who underwent allo-HSCT using the RIC-PTCY regimen at the First Affiliated Hospital of Soochow University from December 2014 to August 2023. Data were collected on engraftment rate, incidence of graft-versus-host disease (GVHD), infections, relapse, and survival outcomes.Result:The median age of the 42 recipients was 52.5 years (range, 20-75 years). Among them, 23 were classified as high-risk and 19 as relapsed/refractory. Three recipients experienced graft failure, and one recipient died of infection early after transplantation. The remaining 38 recipients achieved complete donor chimerism at a median of 21 days (range, 9-52 days). The median time to neutrophil and platelet engraftment was 14 days (range, 9-27 days) and 15 days (range, 7-51 days), respectively. The cumulative incidence (CI) of grade I-II and grade III-IV acute GVHD (aGVHD) at 100 days post-transplantation was 23.7% and 18.4%, respectively. The 2-year CI of chronic GVHD (cGVHD) was 30.1%, with no moderate-to-severe cGVHD observed. The CI of pulmonary and bloodstream infections was 45.2%. The CI of infections with cytomegalovirus (CMV), Epstein-Barr virus (EBV), and BK virus (BKV) was 21.1%, 2.9%, and 7.9%, respectively. The CI of grade I-II hemorrhagic cystitis was 15.8%. The median follow-up duration was 11.2 months (range, 0.4-106.9 months). At the last follow-up, the overall survival (OS) and disease-free survival (DFS) rates were 40.7% and 38.5%, respectively. The cumulative incidence of relapse and non-relapse mortality (NRM) was 44.9% and 19.5%, respectively.Conclusion:The RIC-PTCY regimen may improve early post-transplant outcomes and broaden donor availability. recipients with high-risk or relapsed/refractory malignant hematologic diseases may benefit from this transplantation strategy.
3.Dynamic changes and prognostic significance of immunoparesis in newly diagnosed multiple myeloma patients
Zhi YAN ; Xingyue WU ; Weiqin YAO ; Lingzhi YAN ; Song JIN ; Jingjing SHANG ; Xiaolan SHI ; Depei WU ; Chengcheng FU
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(7):807-814
Objective·To detect immunoglobulin(Ig)expression levels in newly diagnosed multiple myeloma(MM)patients before and after induction therapy,and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy,infection occurrence,and prognosis.Methods·Clinical data from 142 MM patients treated at the Department of Hematology,The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed.Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone(VRD)regimen were assessed.Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal.Patients were stratified by immunoparesis severity(mild,moderate,severe,extremely severe).ANOVA,rank-sum tests,and x2 tests were used to analyze correlations with baseline characteristics.The relationship between the improvement in immunoparesis and the induction efficacy,infection occurrence,and prognosis was analyzed based on the dynamic changes in immunoparesis.Results·Normal Igs were severely reduced in newly diagnosed MM patients.Immunoparesis was present in 128 patients(90.1%),with severe or extremely severe immunoparesis accounting for 76.1%.Patients with extensive immunoparesis(all uninvolved Ig levels below the lower normal limit)were more likely to have severe immunoparesis(P<0.05).There were no statistically significant differences in age,gender,presence of severe renal insufficiency,and high-risk cytogenetics among MM patients with different degrees of immunoparesis(P>0.05),but there were statistically significant differences in MM staging(P=0.008)and typing(P=0.010).Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System(R-ISS)and were of the IgG type.At diagnosis,the levels of the involved Ig or light chain were negatively correlated with normal Ig levels(P<0.05).Improvement in immunoparesis after induction therapy was positively correlated with treatment response(P=0.006).The infection rate was high(26.8%),but no significant correlation was found between immunoparesis and infection occurrence(P>0.05).After induction therapy,patients showing improvement in immunoparesis had significantly longer progression-free survival(PFS)(median PFS:not reached vs 38 months,P=0.025),but no significant impact on overall survival(OS)was observed(P=0.450).Conclusion·Immunoparesis is common and severe in newly diagnosed MM patients,with severity correlating with disease stage and subtype.VRD therapy can partially reverse immunoparesis,and improvement is positively associated with treatment response and PFS benefit.Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies.Humoral immune deficiency may serve as a prognostic indicator in MM,but its impact on OS requires further investigation.
4.Progress in Application of Evaluation Methods of Treatment Tolerance for Hematological Malignancies
Siman HUANG ; Chaoling WAN ; Depei WU ; Shengli XUE
China Cancer 2025;34(1):73-80
Although standardized diagnosis and treatment procedures and appropriate therapy have been recommended for hematological malignancies under the practice of evidence-based medicine,due to heterogeneity of the disease and individual differences in the population,different patients may get dif-ferent clinical efficacy and treatment-related toxicities under the same therapy.How to predict the toler-ance of an individual with hematological malignancy to a specific regimen accurately is critical.This pa-per reviews the evaluation methods of treatment tolerance in patients with hematological malignancies,assisting clinicians in making scientific evaluation of tolerance for different patients and choosing the most suitable regimen.
5.Diagnostic PICALM::MLLT10 fusion by transcriptome sequencing in acute myeloid leukemia and its clinical characteristics
Jing XIA ; Xiaohui HU ; Ye ZHAO ; Xiao MA ; Depei WU ; Suning CHEN ; Feng CHEN
Chinese Journal of Internal Medicine 2025;64(3):234-238
A retrospective analysis of clinical data of 8 patients with PICALM::MLLT10 (P/M) fusion gene-positive acute myeloid leukemia (AML) diagnosed by transcriptome sequencing (RNA-seq) at the First Affiliated Hospital of Soochow University from June 2017 to March 2023 was performed. Laboratory findings and treatment status were analyzed, and survival analysis was performed using the Kaplan-Meier method. The 8 patients included 5 males and 3 females, aged 16-35 years, with a median age of 27 years. The platelet count of patients was normal, and 3 patients had mild to moderate anemia. Extramedullary infiltration was present in all patients with clinical manifestations, including 5 patients with mediastinal masses, 2 patients with hepatosplenomegaly, 1 patient with central nervous system leukemia, and 1 patient with cervical lymph node enlargement. Karyotypical analysis revealed 7 patients with an abnormal karyotype, including 6 cases of complex karyotypes. Of these, 4 patients harbored the t(10;11) translocation. The complete remission rate of induction chemotherapy in the patients was 7/8, and 2 patients experienced early recurrence. All patients subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), The follow-up period ranged from 86 to 812 days, with a median of 330 days. Among the 8 patients, 3 survived and 5 died due to recurrence. Relapse and death only occurred in the P/M fusion gene-positive patients after transplantation. The overall survival rate at 1 year after transplantation was 37.5%. P/M +AML has the characteristics of young age at onset, normal platelet count, high incidence of extramedullary infiltration, and high proportion of complex karyotype. RNA-seq can significantly improve the detection rate of this disease type. Allo-HSCT can partially improve the prognosis of P/M +AML, and P/M positivity after transplantation can be a warning sign of recurrence, which is an important factor affecting survival.
6.The effect of cytomegalovirus and EB virus activation on hematopoietic reconstitution after intensive immunosuppressive therapy for severe aplastic anemia
Qian ZHANG ; Hong WANG ; Xiaoli LI ; Miao MIAO ; Hongxia MA ; Yaoyao SHEN ; Nan WEI ; Kai ZOU ; Wanxiu SU ; Jingqiu YU ; Depei WU ; Limin LIU
Chinese Journal of Internal Medicine 2025;64(6):514-521
Objective:To investigate the infection rate of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in patients with severe aplastic anemia (SAA) after intensive immunosuppressive therapy in combination with a thrombopoietin receptor agonist (lST+TPO-RA) as well as assess the clinical impact of treatment.Methods:A retrospective, case series study was undertaken involving patients with SAA who were admitted to Soochow Hopes Hematonosis Hospital, The First Affiliated Hospital of Soochow University, and Zhengzhou Third People′s Hospital from June 2022 to February 2025. Thirty patients with complete CMV and EBV monitoring data after IST+TPO-RA treatment were enrolled. The first activation time of CMV and EBV, the maximum viral load, the first negative conversion time, and blood routine tests within 3 days before CMV and EBV positivity, during the positive period, and within 3 days after turning negative were recorded. The patients were followed up for 9 months after the completion of IST. One-way analysis of variance was used to compare the changes of blood routine before and after virus positivity and after turning negative. The χ2 test was used to compare the viral infection rate and the therapeutic effect of IST between the two groups. Results:The 30 SAA patients comprised 15 males and 15 females with an average age of (40.0±16.9) years. Of the 30 patients, 18 (60.0%) were infected with CMV and 6 (20.0%) with EBV. Among them, 17 cases received rabbit anti-human thymocyte immunoglobulin (r-ATG) treatment (r-ATG group), 13 cases received porcine anti-human lymphocyte immunoglobulin (p-ALG) treatment (p-ALG group). The CMV infection rate was significantly higher in the r-ATG group than in the p-ALG group (15/17 vs. 3/13, χ2=13.03, P<0.001); meanwhile, the rate of EBV infection was only slightly higher in the r-ATG group than in the p-ALG group, and the difference did not reach statistical significance (5/17 vs. 1/13, χ2=2.17, P=0.196). In patients infected with CMV, neutrophil, hemoglobin, and platelet counts were significantly decreased during the infection phase, followed by significant increases after CMV clearance ( F=14.48, 11.38, 4.73; all P<0.05). No significant differences in treatment efficacy were found between the r-ATG and p-ALG groups at 3, 6, and 9 months post-IST (all P>0.05). Conclusions:This preliminary study showed that the incidence of CMV and EBV infection in patients with SAA increased after IST, with CMV infections occurring significantly more frequently than EBV infections. The CMV infection rate was significantly higher in patients treated with r-ATG than in those receiving p-ALG. CMV infection was associated with notable alterations in hematological parameters, highlighting the need for close clinical monitoring.
7.Progress of targeted therapy for acute myeloid leukemia
Qiannan YANG ; Xiang ZHANG ; Yi FAN ; Depei WU
Journal of Leukemia & Lymphoma 2025;34(9):565-569
Acute myeloid leukemia (AML) is the most common type of leukemia in adults, which is characterized by a complex genetic background, high heterogeneity, and poor prognosis. With the advance in molecular biology and novel drug development, the pathogenesis of AML has been further elucidated. Some novel therapies for AML have been widely applied, including epigenetic modulators, molecular targeted agents, monoclonal antibodies and antibody-drug conjugates, many of which have been approved and incorporated into treatment guidelines. Targeted monotherapy or combination therapies are precise and show mild adverse effects. Currently, whether targeted therapies can challenge conventional treatment methods for AML patients has become a research focus. This paper reviews the recent progress of targeted therapies for AML (non-acute promyelocytic leukemia).
8.Clinical characteristics and prognostic analysis of newly diagnosed acute myeloid leukemia with critical illness
Peiqi LIANG ; Meng GAO ; Yan XIE ; Bingqing LI ; Qian LI ; Ziyi LIU ; Dong WANG ; Huiying QIU ; Suning CHEN ; Depei WU ; Jianhong FU
Chinese Journal of Hematology 2025;46(1):39-44
Objective:This study retrospectively analyzed the clinical characteristics of patients newly diagnosed with acute myeloid leukemia (AML) who were admitted to the hematology intensive care unit (HCU) with critical illness. It also examined factors associated with critical illness and early mortality in these patients.Methods:Clinical data were collected from 91 newly diagnosed AML patients admitted to the HCU of the Department of Hematology, First Affiliated Hospital of Soochow University, from October 2020 to 2024. Reasons for HCU admission, major therapeutic interventions, and risk factors for critical illness and early mortality were analyzed.Results:The median time from diagnosis to HCU admission was 3 days ( IQR: 3–9 days), and the median HCU stay was 10 days ( IQR: 3–23 days). Of the 91 patients, 71 were admitted to the HCU before induction chemotherapy, while 20 were transferred to the HCU after its initiation. The leading causes of HCU admission were pulmonary infection (78.0% ), respiratory failure (44.0% ), hepatic insufficiency (28.6% ), renal insufficiency (27.5% ), disseminated intravascular coagulation (DIC; 25.3% ), and sepsis (23.1% ). Median Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) and SOFA scores at HCU admission were 14 ( IQR: 11–18) and the median Sepsis Related Organ Failure Assessment (SOFA) score was 7 ( IQR: 4, 10). Major HCU interventions included vasoactive drugs, noninvasive and invasive mechanical ventilation, continuous renal replacement therapy, therapeutic leukocyte clearance, and cardiopulmonary resuscitation. Among patients receiving induction chemotherapy, the composite complete remission rate was 65.4%, and the overall remission rate was 88.5%. Thirty-five (38.5% ) patients died within 28 days of HCU admission. Independent risk factors for 28-day mortality were DIC ( OR=9.350, 95% CI 1.999–43.745, P=0.005), sepsis ( OR=6.817, 95% CI 1.571–29.582, P=0.010), and cardiac insufficiency ( OR=12.281, 95% CI 2.385–63.254, P=0.003) . Conclusion:The main reason for HCU admission in newly diagnosed critically ill AML patients was pulmonary infection. Nearly 40% of patients experisenced early death, and DIC, sepsis, and heart failure were factors influencing early mortatlity.
9.The combined regimen based on obinutuzumab plus glucocorticoid for 4 cases of relapsed iTTP
Haiju HE ; Yun LI ; Hong TIAN ; Xiaoyan XU ; Jian SU ; Xinxin GE ; Depei WU ; Ziqiang YU ; Jie YIN
Chinese Journal of Hematology 2025;46(1):70-74
Objective:To evaluate the efficacy and safety of obinutuzumab combined with glucocorticoid-based therapy in patients with relapsed immune thrombotic thrombocytopenic purpura (iTTP).Methods:This study analyzed the efficacy and adverse reactions of four patients with relapsed iTTP who were treated with a combination of obinutuzumab and glucocorticoids to assess the effectiveness and safety of the treatment.Results:All four patients had a history of multiple relapses and had previously undergone treatment with rituximab and bortezomib. Three patients exhibited additional autoantibodies. Following the combined therapy, all patients achieved clinical remission, with ADAMTS13 activity returning to normal levels and inhibitors testing negative. During a median follow-up period of 11 months (range: 3–17 months), all patients maintained sustained remission. No severe adverse events were reported during treatment or follow-up.Conclusion:The combination of obinutuzumab and glucocorticoid-based therapy is effective and safe for treating relapsed iTTP.
10.Clinical study on intravenous human immunoglobulin (pH4) for hypogammaglobulinemia and infection risk following CD20 monoclonal antibody therapy in patients with B-cell non-Hodgkin lymphoma
Xuekai LI ; Yifan SHEN ; Depei WU ; Yang XU
Chinese Journal of Hematology 2025;46(5):425-430
Objective:To observe the effect of intravenous human immunoglobulin (pH4) (IVIg) on total immunoglobulin (Ig) levels in patients with B-cell non-Hodgkin lymphoma (NHL) and to evaluate its clinical efficacy in ameliorating hypogammaglobulinemia following CD20 monoclonal antibody therapy.Methods:Clinical data of 98 patients with B-cell NHL who developed hypogammaglobulinemia after CD20 monoclonal antibody therapy and were hospitalized in the Department of Hematology, The First Affiliated Hospital of Soochow University, from January 2018 to June 2022, were retrospectively analyzed. Patients were divided into the IVIg group ( n=70) and the conventional treatment group ( n=28). To exclude the interference of plasma transfusion on total Ig levels, statistical analysis was performed on the IVIg group without plasma transfusion ( n=53) and the conventional treatment group ( n=25). The therapeutic efficacy of IVIg was analyzed by observing its effect on elevating total Ig levels and the duration of this effect. The infection control efficacy of IVIg was assessed by comparing other blood biochemical parameters. The safety of IVIg in clinical application was also evaluated. Results:In the IVIg group, the mean total Ig level within 1-3 days after IVIg treatment was (20.67±4.17) g/L, significantly higher than the pre-treatment level of (17.16±1.76) g/L ( P<0.001). In 22 patients from the IVIg group, total Ig levels at 1-7 days, 8-14 days, and 15-30 days post-treatment were all significantly different compared to pre-treatment levels (all P<0.001). In the conventional treatment group, the mean total Ig level within 1-3 days after hospitalization showed no significant difference compared to the level at admission [ (18.12±1.84) g/L vs (18.43±1.79) g/L, P>0.05]. The proportion of patients in the IVIg group whose total Ig level reached 20 g/L within 1-3 days post-IVIg treatment was significantly higher than that in the conventional treatment group within 1-3 days after admission (57.69% vs 0, P<0.001). In 12 patients from the IVIg group with baseline neutrophil levels below normal, neutrophil levels at 1-3 days, 4-7 days, and 8-14 days post-treatment were significantly increased compared to pre-treatment levels (all P<0.05). The proportion of patients with new-onset infections post-treatment was lower in the IVIg group (22.64%, 12/53) than in the conventional treatment group (36.00%, 9/25), although the difference was not statistically significant ( P>0.05). Among 70 patients in the IVIg group, 8 patients experienced grade 1-2 adverse reactions, including nausea and vomiting in 5 patients, rash in 2 patients, and muscle/joint pain in 1 patient. No grade 3 or higher adverse reactions were observed. Conclusion:IVIg increased Ig and neutrophil levels in patients with B-cell NHL after CD20 monoclonal antibody therapy and may play a role in controlling new-onset infections. IVIg is effective and safe for treating hypogammaglobulinemia secondary to CD20 monoclonal antibody therapy in patients with B-cell NHL.

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