Multiple myeloma (MM) is a hematological malignancy that poses significant treatment challenges due to its heterogeneity and propensity for relapse and progression. In the last two decades, the therapeutic landscape of MM has changed dramatically, but the disease remains largely incurable, with many patients facing treatment resistance. This review evaluates the current status of MM treatments, emphasizing the limitations of traditional therapies and the emerging role of immunotherapy in improving patient outcomes. It highlights the importance of achieving and maintaining minimal residual disease negativity and a balanced immune response as key treatment goals. Furthermore, it discusses the advancements in immunotherapies that are improving the prospects for patients, particularly those with relapsed or refractory disease. Innovative strategies, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and bispecific T cell engagers, have shown significant promise by targeting the malignant cells and the bone marrow microenvironment, which are essential for disease persistence and resistance to therapy. Future research should focus on refining MM treatment strategies, including the integration of immunotherapy into earlier treatment lines and the development of predictive biomarkers for personalized treatment approaches, ultimately enhancing patient outcomes.

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.

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.

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.

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.

Objective:To investigate the feasibility of the bortezomib, lenalidomide, and dexamethasone (VRD) regimen combined with autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with multiple myeloma (MM) and renal impairment, analyze treatment efficacy and renal responses stratified based on renal dysfunction severity, and explore the prognostic significance of early renal response and its affecting factors.Methods:This retrospective study, conducted at the First Affiliated Hospital of Soochow University, categorized 316 patients with newly diagnosed MM (NDMM) from August 2018 to October 2022 based on renal function for analysis of clinical characteristics, treatment response, and prognosis. Continuous variables were compared using t-tests or Mann-Whitney U tests, categorical variables utilizing Chi-square tests, survival outcomes employing Kaplan-Meier and Log-rank tests, and renal response predictors with logistic regression.Results:Patients were stratified based on baseline estimated glomerular filtration rate (eGFR) : normal [≥90 ml·min -1· (1.73 m 2) -1, n=160], mild [≥60 ml·min -1· (1.73 m 2) -1 to <90 ml·min -1· (1.73 m 2) -1, n=55], moderate [≥30 ml·min -1· (1.73 m 2) -1 to <60 ml·min -1· (1.73 m 2) -1, n=39], and severe impairment [<30 ml·min -1· (1.73 m 2) -1, n=62]. Moderate and severe renal impairment correlated with advanced International Staging System/Revised International Staging System classification, lower hemoglobin levels, frailty, and higher light-chain/IgD subtype prevalence ( P<0.05). Despite younger age ( P=0.001) and higher transplant rates ( P=0.041) in severe cases, overall response rates ( ORR: 93.7% ; ≥VGPR: 82.9% ) were comparable across groups ( P>0.05). Among 24 dialysis-dependent patients at diagnosis, 11 (45.8% ) achieved dialysis independence after induction [median: 3.0 (0.5–4.0) months], including 10 undergoing auto-HSCT. In 89 evaluable patients [baseline eGFR <50 ml·min -1· (1.73 m 2) -1], renal ORR (RORR) was 70.8% [rapid complete response: 31.5% ; rapid partial response: 11.2% ; rapid minimal response (RMR) : 28.1% ]. Renal response predicted better survival (overall survival: HR=0.36, 95% CI: 0.13–0.99, P=0.049). Moderate-to-severe renal impairment was associated with increased transplant-related adverse events and delayed engraftment ( P<0.05) ; however, auto-HSCT significantly improved outcomes after 33.5-month median follow-up (range: 2–65 months). Multivariate analysis identified 1q21+ ( OR=3.58, 95% CI: 1.17–11.02, P=0.026) and light-chain subtype ( OR=2.86, 95% CI: 1.08–7.69, P=0.036) as independent predictors of poor renal response. Conclusion:VRD regimen plus auto-HSCT demonstrates robust efficacy in NDMM, including patients with renal impairment, with a 70.8% RORR and manageable toxicity. Achieving ≥RMR correlates with superior prognosis, whereas 1q21+ and light-chain subtype independently predict inferior renal response.

Objective:To investigate the efficacy of venetoclax combined with hypomethylating agents (Ven-HMA), in patients with core binding factor acute myeloid leukemia (CBF-AML) intolerant to intensive induction therapy.Methods:This study retrospectively analyzed patients newly diagnosed with CBF-AML who were aged <60 years and who received Ven-HMA as induction therapy at the Department of Hematology, the First Affiliated Hospital of Soochow University, between January 2020 and June 2023. Baseline characteristics and treatment responses of the patients were collected.Results:A total of 70 treatment-na?ve patients receiving Ven-HMA induction therapy were enrolled, of which 38 were men and 32 women [median age: 43 (34 - 55) years]. Of the 70 patients, 44 (62.9%) achieved complete remission (CR) /CR with incomplete hematologic recovery (CRi), 16 (22.9%) achieved partial remission, and 10 (14.2%) exhibited no response after one induction cycle. Among the 32 t (8;21) -positive patients with AML, only 8 (25.0%) achieved CR/CRi, of whom 3 (37.5%) remained measurable residual disease (MRD) -positive; among the 38 inv (16) -positive patients, 36 (94.7%) achieved CR/Cri, of whom 12 (33.3%) remained MRD-positive. Patients harboring the CBFβ::MYH11 fusion gene showed significantly higher response rates to Ven-HMA induction than those with the RUNX1:: RUNX1T1 fusion gene ( P<0.01) . Conclusion:Ven-HMA represents a novel therapeutic strategy that exhibits significant efficacy in inv (16) -positive patients; however, it demonstrates relatively lower remission rates in t (8; 21) -positive patients.

This report presents the management of a critically ill 36-year-old woman diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph +ALL) at 28 weeks of gestation. The patient rapidly deteriorated, developing disseminated intravascular coagulation (DIC) , diffuse alveolar hemorrhage (DAH) , septic shock, and multi-organ dysfunction, necessitating admission to the hematological intensive care unit. Given her critical condition and advanced pregnancy, a chemotherapy-free induction regimen comprising imatinib and dexamethasone was initiated, alongside comprehensive supportive measures, including mechanical ventilation, continuous renal replacement therapy (CRRT) , broad-spectrum antibiotics, and high-dose corticosteroids. During treatment, intrauterine fetal demise occurred, and a stillborn was delivered following obstetric intervention. With aggressive treatment, the patient's respiratory failure, DIC, and DAH gradually resolved, and she achieved complete remission. She subsequently received consolidation chemotherapy, CAR-T cell therapy, and allogeneic hematopoietic stem cell transplantation, achieving sustained complete molecular remission on long-term follow-up. This case demonstrates that for critically ill pregnant patients with Ph + ALL, a chemotherapy-free regimen of targeted therapy and corticosteroids, when combined with intensive supportive care, is a safe and effective approach that may offer a therapeutic option for similar cases.

Objective:To evaluate the impact of donor characteristics on the prognosis of myelodysplastic syndrome (MDS) patients undergoing haplo-identical transplantation (HIDT) .Methods:A retrospective analysis of 203 MDS patients who received HIDT was conducted to evaluate how donor factors influenced transplant outcomes.Results:In MDS patients undergoing haploidentical transplantation, donors over 50 years were associated with higher EBV reactivation (2-year cumulative incidence 42.9% vs 22.0% for <50 years old; P=0.010). Female donors were linked to increased severe chronic GVHD compared with male donors (2-year incidence 11.9% vs 4.0% ; P=0.017). Additionally, 2-year overall survival (OS) was slightly lower with female donors than male donors (56.6% vs 69.7% ), but the difference was not statistically significant ( P=0.073). Donor-recipient blood type did not affect post-transplant OS or cumulative relapse rates. Donor-recipient kinship analysis revealed that child donors, compared to haploidentical sibling or parent donors, had lower rates of grade Ⅱ–Ⅳ acute GVHD (27.2% vs 45.7% vs 53.5%, P=0.007) and 2-year EBV reactivation (13.9% vs 29.3% vs 38.9%, P=0.001). For donors under 20 years, donor gender did not significantly affect 2-year OS ( P=0.913), relapse-free survival ( P=0.716), or 100-day incidence of grade Ⅱ–Ⅳ acute GVHD ( P=0.359) . Conclusion:For MDS patients undergoing HIDT, donors over 50 should be avoided. Male and child donors are preferred, while donor gender does not significantly affect outcomes if the donor is under 20 years old.