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).

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

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.

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.