BACKGROUND:With life expectancies of patients with chronic myeloid leukemia (CML) now approaching those of the general population under tyrosine kinase inhibitor (TKI) therapy, understanding long-term treatment-related toxicities becomes paramount. Although imatinib's nephrotoxic potential is established, the renal safety profiles of second-generation TKIs-dasatinib, nilotinib, and flumatinib-remain incompletely characterized. METHODS:This single-center retrospective study analyzed renal function trajectories in 348 patients with CML receiving first-line imatinib, dasatinib, nilotinib, or flumatinib. Renal function was assessed using serum creatinine and estimated glomerular filtration rate (eGFR). Mixed-effects models incorporating treatment group, time, and their interaction as fixed effects were used to formally compare eGFR trajectories across treatment groups. Chronic renal adverse events and acute kidney injury were also evaluated. RESULTS:Formal comparison of eGFR trajectories across treatment groups revealed a significant time × treatment interaction, indicating differential renal function changes among the 4 TKIs. Significant serum creatinine elevation and eGFR decline were observed in imatinib and flumatinib groups, contrasting with stable creatinine and divergent eGFR patterns in dasatinib (slight increase) and nilotinib (decline) groups. The incidence of chronic renal adverse events varied substantially across cohorts-12.3% (imatinib), 2.6% (nilotinib), 4.3% (dasatinib), and 9.6% (flumatinib). Notably, among 3 documented acute kidney injury cases, all occurred during flumatinib treatment. Furthermore, treatment-free remission achievement did not confer significant renal function recovery, suggesting potential irreversibility of established renal damage. CONCLUSION:TKIs exhibit differential renal safety profiles, underscoring the critical importance of individualized TKI selection based on baseline renal status and implementation of rigorous renal monitoring protocols throughout treatment duration.

Background:T-lineage acute leukemias are aggressive malignancies for which treatment options are limited. Objectives:This study evaluated the efficacy and safety of a non-cytotoxic regimen combining venetoclax, azacitidine, and dexamethasone (VAD) as first-line induction therapy for T-cell acute lymphoblastic leukemia (T-ALL) and T/myeloid mixed-phenotype acute leukemia (T-Myeloid MPAL). Design:We retrospectively analyzed the clinical parameters and survival data of 11 patients with newly-diagnosed T-ALL or T-Myeloid MPAL who received the VAD regimen. Methods:The complete remission (CR) rate and adverse events were assessed. Kaplan-Meier curves were constructed to evaluate survival outcomes. Results:Among 11 patients (7 with early T-cell precursor [ETP] ALL, 2 with T-Myeloid MPAL, and 2 with non-ETP T-ALL), the overall CR rate after one cycle of VAD therapy was 90.9%, with 45.5% achieving measurable residual disease (MRD) negativity by flow cytometry. The historically poor-prognosis ETP-ALL subgroup showed an 85.7% CR rate (6/7), while both T-Myeloid MPAL cases attained MRD negativity. No tumor lysis syndrome or treatment-related mortality occurred. Over a median follow-up of 358 days, all 5 patients who received transplantations remained relapse-free. Conclusion:The VAD regimen demonstrated a high response rate and favorable safety, enabling effective transplantation bridging with avoidance of conventional cytotoxic therapy.

Introduction: NUP98::NSD1, a frequent aberration in acute myeloid leukemia (AML) with NUP98 rearrangements, is characterized by poor remission rates and adverse prognosis. Critically, its co-expression with FLT3-ITD synergistically worsens survival outcomes. Allogeneic stem cell transplantation (allo-HSCT) could overcome this adverse molecular profile. We aimed to refine the transplant timing and strategy to optimize post-HSCT survival. Methods: This retrospective study consecutively enrolled NUP98::NSD1 AML patients co-expressed FLT3-ITD undergoing allo-HSCT at the Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences between 2020 and 2025. Categorical variables were analyzed by Fisher's exact test, and continuous variables by Mann-Whitney U test. Overall survival (OS) and event-free survival (EFS) were calculated according to Kaplan-Meier. Institutional Review Board (IRB) approval was obtained in accordance with the Declaration of Helsinki. Results: A total of 14 AML patients (median age 34, range 15-50) with co-expressed NUP98::NSD1 and FLT3-ITD mutations were consecutively registered and enrolled. Half of the patients (50%) had hyperleukocytosis at diagnosis. Twelve patients (85.7%) obtained additional co-mutations, including WT1 (35.7%), CEBPA (21.4%), CCND3 (14.2%), BCOR (7.1%), NRAS (7.1%), IDH2 (7.1%), and PAX5 (7.1%). Patients demonstrated marked poor responses to chemotherapy. Only 35.7% patients achieved hematologic complete remission (CR) after induction chemotherapy, CR rates 25% (2/8) using standard “7+3” intensive chemotherapy, 75% (3/4) in Venetoclax-involved and 66.7% (2/3) in Gilteritinib-involved regimens, respectively. Almost half (6/14, 42.8%) were defined as refractory/relapse AML. At transplantation, only 7 patients (50%) achieved CR, with 35.7% (5/14) attaining flow cytometry confirmed MRD negativity. Patients were stratified by duration from diagnosis to transplantation into two cohorts: early-HSCT group (≤100d, n=6) and late-HSCT group (>100d, n=8). Baseline disease characteristics were balanced between the two cohorts. Prior to transplantation, early-HSCT group underwent a median of 2 cycles (range: 1-2) of chemotherapy and late-HSCT group underwent a median of 4 cycles (range: 3-6). All patients received myeloablative conditioning (MAC) regimen. Haploidentical transplantation was the predominant type in both cohorts (100% vs 75%). No graft failure was reported. With a median follow-up of 491 days (range: 68-1488), a total of 10 patients survived. In the late-HSCT cohort, two patients relapsed and three died of treatment-related complications in late HSCT cohort, whereas only one GVHD-related death occurred in the early-HSCT group. Notably, early-HSCT demonstrated lower incidences in post-HSCT infectious complications: bacterial/fungal infection (33.3% vs 62.5%), CMV viremia (16.7% vs 37.5%). The difference in rate of grade II-IV aGVHD (50% vs 25%) was not significant. Although with no statistical significance, the early-HSCT cohort showed improved survival in 1-year OS (83.3% vs 62.5%), 1-year EFS (83.3% vs 50%), with lower non-relapsed mortality (NRM) (16.7% vs 25.0%) and a trend toward reduced relapse incidence (0% vs 25.0%).Conclusions: This exploratory study suggests that early allo-HSCT may offer survival advantages in AML patients with co-occurring NUP98::NSD1 and FLT3-ITD mutations, who exhibited poor response to chemotherapy, by avoiding toxicities from multiple cycles of intensive chemotherapy prior to transplantation. Large-scale prospective studies are required to define the optimal transplantation timing.

This study aims to investigate the genetic characteristics of Acute Myeloid Leukemia (AML) patients and identify which patients derive the greatest benefit from a low-intensity regimen of decitabine combined with modified Cytarabine + Aclarubicin + Granulocyte Colony-Stimulating Factor (D-CAG) or intensive chemotherapy (IA regimen). We retrospectively analyzed cytogenetic and molecular data of 331 newly diagnosed AML patients and examined the associations between genetic characteristics, risk status, treatment approaches, and clinical outcomes. The median follow-up duration was 45 months (range: 2-120 months). Patients receiving IA therapy achieved higher complete remission (CR) rates (79.3

Due to high heterogeneity, diagnosing MDS can be challenging. Consequently, investigating its pathogenesis and progression mechanisms, and seeking novel targets for diagnosis and treatment, are critical issues that require urgent attention. This study aimed to investigate whether LRRFIP1 might contribute to MDS pathogenesis by modulating the Wnt/β-catenin signaling pathway. In MDS cell lines, mRNA transcriptome sequencing and Dual luciferase reporter gene assays were employed to assess Wnt/β-catenin signaling pathway activity. To explore the biological characteristics of MDS cell lines, CCK8, Annexin-V APC/7-AAD and Annexin V-FITC/PI double staining and fluorescence TUNEL assay, and PI single staining were used. In MDS cell lines, proliferation was notably higher in LRRFIP1-overexpressing cells compared to silenced ones, while cell apoptosis was lower in the former. mRNA transcriptome sequencing revealed LRRFIP1's involvement in modulating the Wnt/β-catenin signaling pathway. LRRFIP1 was found to positively regulate Wnt/β-catenin pathway activity, and synergy between LRRFIP1 and Dvl was observed in enhancing canonical Wnt signaling. LRRFIP1 overexpression significantly upregulated key genes in Wnt signaling pathway (such as β-catenin, Dvl2, Dvl3 and Wnt) at the mRNA level, and notably upregulated non-phosphorylated β-catenin at the protein level. Moreover, BCL-2 and CyclinD1 protein expression was significantly higher in LRRFIP1-overexpressing cells compared to silenced ones, with even greater expression observed in LRRFIP1/Dvl3 co-overexpressing cells. LRRFIP1 can promote the proliferation of MDS cells and inhibit apoptosis, and LRRFIP1 and Dvl can synergistically enhance the activity of the Wnt/β-catenin signaling pathway in MDS, thus providing evidence for LRRFIP1's involvement in the pathogenesis of MDS.

Venetoclax is a first-in-class B-cell lymphoma/lymphoma-2 (BCL-2) inhibitor that induces apoptosis in malignant cells through the inhibition of BCL-2. The clinical response to venetoclax exhibits heterogeneity, and its sensitivity and resistance may be intricately linked to genetic expression. Pharmacokinetic studies following doses of venetoclax (ranging from 100 to 1200mg) revealed a time to maximum observed plasma concentration of 5-8 hours, with a maximum blood concentration of 1.58-3.89 μg/mL, and a 24-hour area under the concentration-time curve of 12.7-62.8 μg·h/mL. Population-based pharmacokinetic investigations highlighted that factors such as low-fat diet, race, and severe hepatic impairment play pivotal roles in influencing venetoclax dose selection. Being a substrate for CYP3A4, P-glycoprotein, and breast cancer resistance protein, venetoclax undergoes primary metabolism and clearance in the liver, displaying low accumulation in the body.The significance of dose modifications (a 50% decrease with moderate and a 75% reduction with strong CYP3A inhibitors) and a cautious two-hour interval when co-administered with P-glycoprotein inhibitors are highlighted by insights from clinical medication interaction studies. Moreover, an exposure-response relationship analysis indicates that venetoclax exposure significantly correlates not only with overall survival and total response rate but also with the occurrence of ≥ 3-grade neutropenia. In real-world studies, common or severe side effects of venetoclax include tumor lysis syndrome, myelosuppression, nausea, diarrhea, constipation, infection, autoimmune hemolytic anemia, and cardiac toxicity, among others. In this review, we summarize the current clinical pharmacology studies and side effects of venetoclax, which showed that the approved dosage of venetoclax is relatively wide, and the dosage for different hematologic populations can be streamlined in the future.

Purpose:This study evaluated the efficacy and safety of a 14-day blinatumomab-venetoclax (BV) regimen as induction therapy for newly diagnosed Ph-negative B-cell acute lymphoblastic leukemia (B-ALL), focusing on rapid remission and tolerability in unfit patients. Patients and Methods:Thirteen patients received venetoclax (100 mg on day 1, 200 mg on day 2, 300 mg on day 3, and 400 mg from days 4 to 14) with blinatumomab (9 to 28 ug/day) for 14 days. Bone marrow assessments were performed at days 14-21. Primary endpoints were complete remission (CR) rate, minimal residual disease (MRD) negativity by flow cytometry, and adverse events. Results:The CR rate after one cycle of BV regimen was 92.3% (12/13), and all patients achieved MRD-negativity; 91.7% (11/12) achieved MRD clearance by day 21. Grade 1-2 cytokine release syndrome occurred in 46.2% (6/13; 1 grade 3). Hematologic toxicity included grade 3-4 neutropenia (92.3%) and thrombocytopenia (46.2%), with only 30.8% febrile neutropenia. All AEs resolved rapidly with supportive care, allowing therapy to continue without interruption. At median follow-up of 283 days, 1-year relapse-free survival rate and overall survival rate were 60.6% and 83.3%. Conclusion:The 14-day BV regimen induced rapid deep remission (91.7% MRD-negative by day 21) with manageable toxicity in Ph-negative B-ALL. Synergistic T-cell activation by venetoclax may explain enhanced efficacy.

Flumatinib is a novel second-generation tyrosine kinase inhibitor (2G-TKI), which was approved in November 2019 in China. A previous phase III study evaluated the efficacy and safety of flumatinib as a first-line therapy for patients with chronic phase chronic myeloid leukemia (CML-CP). However, randomized trials comparing flumatinib with other 2G-TKIs remain lacking. To assess the efficacy and safety of flumatinib versus nilotinib as a first-line treatment for CML-CP. A multicenter retrospective study. We retrospectively analyzed 101 and 64 patients treated with flumatinib and nilotinib during the same period, respectively. Patients in the flumatinib group were significantly older than patients in the nilotinib group (median age, 44 vs 37 years; p = 0.004). The optimal response and treatment failure rates at 24 months were comparable between the two groups. At 12 months, 85.1% and 88.2% of patients in the flumatinib and nilotinib groups, respectively, achieved a major molecular response (MMR; p = 0.648). By 24 months, 9.9% and 12.5% of patients suffered treatment failure in the flumatinib and nilotinib groups, respectively (p = 0.602). At 9, 12, and 24 months, the rate of MR4 (a BCR::ABL1 transcript level ⩽0.01%) achievement was significantly higher in patients treated with nilotinib than in those treated with flumatinib (26.0% vs 53.7%, p = 0.007; 40.4% vs 60.8%, p = 0.044; and 41.7% vs 80.8%, p = 0.042, respectively). In addition, elevated alanine aminotransferase or aspartate aminotransferase (ALT/AST), glucose, and serum lipid; hyperbilirubinemia; rash; and alopecia were more frequent among patients receiving nilotinib, whereas diarrhea was more frequent in those receiving flumatinib. Flumatinib is a suitable alternative as a first-line treatment for patients with CML-CP to achieve a fast MMR with better tolerability.

OBJECTIVE:To explore the genetic background for a patient with refractory myelodysplastic/myeloproliferative neoplasm (MDS/MPN) with co-morbid neutrophilia patient. METHODS:A MDS/MPN patient who was admitted to the First Affiliated Hospital of Nanjing Medical University in May 2021 was selected as the study subject. RNA sequencing was carried out to identify fusion genes in his peripheral blood mononuclear cells. Fusion gene sequence was searched through transcriptome-wide analysis with a STAR-fusion procedure. The novel fusion genes were verified by quantitative real-time PCR and Sanger sequencing. RESULTS:The patient, a 67-year-old male, had progressive thrombocytopenia. Based on the morphological and molecular examinations, he was diagnosed as MDS/MPN with co-morbid neutropenia, and was treated with demethylating agents and Bcl-2 inhibitors. Seventeen months after the diagnosis, he had progressed to AML. A novel fusion gene NCOR1::GLYR1 was identified by RNA-sequencing in his peripheral blood sample, which was verified by quantitative real-time PCR and Sanger sequencing. The patient had attained morphological remission after a DCAG regimen (a combinatory chemotherapy of decitabine, cytarabine, aclarubicin and granulocyte colony-stimulating factors) plus Chidamide treatment. A significant decrease in the NCOR1::GLYR1 expression was revealed by quantitative real-time PCR at post-chemotherapy evaluation. CONCLUSION:NCOR1::GLYR1 gene is considered as the pathogenic factor for the MDS/MPN patient with neutropenia.

Glioma is a refractory malignant tumor with a powerful capacity for invasiveness and a poor prognosis. This study aims to investigate the role and mechanism of tubulin beta class IVA (TUBB4A) in glioma progression. The differential expression of TUBB4A in humans was obtained from databases and analyzed. Glioma cells U251-MG and U87-MG were intervened by pcDNA3.1(+) and TUBB4A overexpression plasmid. MTT, CCK8, LDH, wound healing, transwell, and western blotting were used to explore whether TUBB4A participates in the development of glioma. Reactive oxygen species (ROS) were detected by the DCFH-DA probe. Mitochondrial membrane potential (MMP) was examined by JC-1. It was found that TUBB4A expression level correlated with tumor grade, IDH1 status, 1p/19q status, and poor survival in glioma patients. In addition, TUBB4A overexpression inhibited the proliferation, migration, and invasion of U251-MG and U87-MG, while increasing the degree of apoptosis. Notably, TUBB4A overexpression promotes ROS generation and MMP depolarization, and induces mitophagy through the PINK1/Parkin pathway. Interestingly, mitochondria-targeted ROS scavenger reversed the effect of TUBB4A overexpression on PINK1/Parkin expression and mitophagy, whereas mitophagy inhibitor did not affect ROS production. And the effect of TUBB4A overexpression on mitophagy and glioma progression was consistent with that of PINK1/Parkin agonist. In conclusion, TUBB4A is a molecular marker for predicting the prognosis of glioma patients and an effective target for inhibiting glioma progression by regulating ROS-PINK1/Parkin-mitophagy pathway.

Objective: To evaluate the efficacy and safety of sequential prophylaxis with letermovir injection and tablets for Cytomegalovirus(CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: The study included 18 patients who completed allo-HSCT at the Blood Disease Hospital, Chinese Academy of Medical Sciences from December 2023 to March 2024. Letermovir injection was initiated on day 0 post-transplant, followed by a switch to letermovir tablets for sequential prophylaxis up to day 90. The primary outcome was the CMV breakthrough rate at 90 days post-transplant, and the second outcomes were the incidence of viral infections such as EBV and the status of hematopoietic reconstitution. Results: At 90 days post-transplant, among the 18 allo-HSCT patients who received sequential prophylaxis with letermovir injection and tablets, no CMV infection was observed in all patients, resulting in a CMV infection breakthrough rate of 0%. Four patients had EB virus (EBV) viremia (22.22%), of which one patient developed PTLD (5.6%). The median time for neutrophil engraftment was 15 (11-18) days; no related liver and kidney function damage was observed during the medication process. Conclusion: Preliminary research results indicate that sequential prophylaxis with letermovir injection and tablets is safe and effective for post-allo-HSCT CMV infection.

BACKGROUND:Peripheral T cell lymphomas (PTCLs) are prototypical epigenetic malignancies with invariably poor prognoses. Novel and effective therapeutic strategies are needed to improve clinical outcomes, particularly in relapsed/refractory patients. METHODS:We conducted a multicenter phase 2 study to evaluate the therapeutic efficacy of azacitidine and chidamide, alone or in combination with gemcitabine and oxaliplatin (GemOx), in patients with relapsed/refractory PTCLs (registration number: ChiCTR2000037232). The primary endpoint was the best overall response rate. FINDINGS:As of May 1st, 2024, thirty patients were evaluable for efficacy and toxicity. The best overall response rate was 53.3%, meeting its primary endpoint. Among the patients with angioimmunoblastic T cell lymphoma (AITL; N = 19), a numerically higher response rate was observed, regardless of whether chemotherapy was combined, compared to patients with non-AITL. After a median follow-up of 36.6 months, median progression-free survival and overall survival were 7.1 and 8.7 months, respectively. Patients with AITL who received combination chemotherapy (N = 12) achieved the most promising response rates (overall response rate, 91.7%; complete remission rate, 66.7%) and survival outcomes (median progression-free survival, 17.2 months; median overall survival, 38.8 months). The most common grade 3-4 toxicities were neutropenia (40.0%) and thrombocytopenia (30.0%). CONCLUSIONS:The combination of epigenetic therapy with GemOx was well tolerated and highly effective in patients with relapsed/refractory PTCLs. Patients with AITL, in particular, may benefit more from this combination treatment and should be the focus of future studies. FUNDING:This work was funded by the Natural Science Foundation of Jiangsu Province (BK20232039).

Background: As the overall survival (OS) of patients with multiple myeloma (MM) improves, the incidence of second primary malignancy (SPM) in long-term complications increases. However, there are limited data regarding MM as a SPM. Therefore, this study aimed to determine the time trends in the incidence of MM, as well as the incidence and survival of patients with MM as the SPM. Methods: Kaplan-Meier survival analysis was performed to determine the survival curve, while a log-rank test was used to determine OS. Results: A total of 794 patients were diagnosed with MM among 7,921 patients with hematologic malignancy between 2009 and 2017. The incidence of MM showed an annual upward trend, increasing from 9.3% [2009-2011] to 10.8% [2015-2017]. Of the 794 patients with MM, 16 were diagnosed as the SPM commonly secondary to cancers of the lung (n=4), colon (n=3), breast (n=3), and other (n=6). The median survival of patients with MM as the SPM was 24.5 months (range, 1-95 months). The patients with MM without multiple malignancies had significantly longer survival (median, 46.5 months; range, 17-132 months; Conclusions: This retrospective study suggests that the incidence of MM may be increasing annually and that the survival of patients with MM as the second primary malignant was significantly shorter than that of those without multiple malignancies.

OBJECTIVE:To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients.METHODS:The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively.RESULTS:A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival.CONCLUSION:In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

The present study proposes metronomic chemotherapy (CPT), including prednisolone, cyclophosphamide, and thalidomide, as a treatment for patients with severe symptomatic indolent T‐cell lymphoproliferative disorder of the gastrointestinal tract. The encouraging efficacy and excellent safety profile of CPT suggest the clinical potential of this combination.

Although classic Hodgkin lymphoma (cHL) is highly curable with current treatment paradigms, therapy fails in 10-25% of patients. This prospective multicenter phase II study attempted to investigate the efficacy and safety of the combination of tislelizumab with gemcitabine and oxaliplatin (T-GemOx) in relapsed or refractory cHL. Participants received six to eight courses of gemcitabine (1 g/m2 on day 1) and oxaliplatin (100 mg/m2 on day 1) combined with tislelizumab (200 mg on day 2) at 21-day intervals, followed by tislelizumab maintenance (every 2 months for 2 years). The main outcome measure was the best complete remission rate. As of August 2022, a total of 30 patients had been consecutively enrolled and given induction therapy. The best overall response rate and complete remission rate were 100% (95% confidence interval [CI]: 88.4-100%) and 96.7% (95% CI: 82.8-99.9%), respectively. The median duration of follow-up after initiation of T-GemOx was 15.8 months. The 12-month progression-free survival rate without autologous stem cell transplant was 96% (95% CI: 74.8-99.4%). There were 122 adverse events recorded, of which 93.4% were grade 1 or 2. Thrombocytopenia (10%) and anemia (6.7%) were the most common grade 3 or 4 adverse events. Overall, T-GemOx demonstrated promising antitumor activity with manageable toxicities as a salvage treatment for relapsed or refractory cHL. A longer follow-up duration is required to determine whether maintenance therapy with tislelizumab rather than transplantation can be curative following such a highly active regimen. This trial was registered with the Chinese Clinical Trials Registry (http://www.chictr.org.cn) on June 1, 2020, identifier ChiCTR2000033441.

Background:In the era of immunotherapy, autologous stem cell transplantation (ASCT) in first-line therapy in patients with mantle cell lymphoma (MCL) has been a controversial topic. This report aimed to explore the association between ASCT and MCL survival through a systematic review with meta-analysis.Methods:We performed a systematic search of original articles published from inception to September 2021 using PubMed, MEDLINE, Embase, and Cochrane Library databases.Results:We included studies that compared ASCT with non-ASCT consolidation in newly diagnosed transplant-eligible MCL. The endpoints were progression-free survival (PFS) and overall survival (OS). There were seven eligible studies (one randomized clinical trial, one prospective cohort study, and five observational studies) published between 2012 and 2021, in which the total number of participants was 3,271. In the non-intensive induction subgroup, patients with ASCT experienced a significant PFS but no OS benefit compared with those without ASCT. In the intensive induction subgroup, the PFS benefit from ASCT still existed but largely attenuated; no OS benefit was observed though only one study was suitable for evaluation. When compared to the rituximab maintenance arm, ASCT had a worse PFS and OS.Conclusions:In the rituximab plus HiDAC era, the benefit of ASCT as a component of first-line treatment has been weakened. First-line maintenance strategy instead of ASCT seems worth exploring .

Objective:This study aims to explore the clinical characteristics of T-cell large granular lymphocyte leukemia (T-LGLL) patients with STAT3 mutation status and provide a reference for clinical management of such patients.Methods:The clinical data of T-LGLL patients between 2009 and 2019 in Jiangsu Province Hospital were retrospectively analyzed. Differences in baseline clinical data, treatment responses, and survival outcomes in patients with STAT3 mutations or with no mutations were compared.Results:A total of 80 patients were included, including 66 patients without STAT3 mutation and 14 patients (17.5%) with STAT3 mutation. The frequency of Y640F mutation was the highest (42.9%) . Compared with non STAT3 mutation group, STAT3 mutation group had lower HGB (67.5 g/L vs 82.5 g/L, P=0.018) , lower neutrophil count (0.665×10 9/L vs 1.465×10 9/L, P<0.001) , higher LDH (229 U/L vs 198 U/L, P=0.041) , higher ferritin (402.5 g/L vs 236.0 g/L, P=0.029) , higher expression rate of TCR Vβ subfamily (89.2% vs 65.4%, P=0.014) and higher proportion of patients with treatment indications (100% vs 74%, P=0.033) . The complete remission rates of STAT3 mutation group and non mutation group were 38.5% and 32.7%, respectively, with no significant difference ( P=0.748) . The overall response rate of first-line immunosuppressive therapy in STAT3 mutation group and non mutation group were 69.2% and 69.4%, respectively, with no significant difference ( P=1.000) . The median follow-up time was 63 (2-121) months. There was no significant difference in the overall survival time between the two groups ( P=0.170) . Conclusions:T-LGLL patients with STAT3 mutations seems to be correlated with an increased tumor burden and high treatment demand, and had a good response to first-line immunotherapies. The prognostic significance of STAT3 mutation in T-LGLL patients requires further validation.

目的:探讨芦可替尼治疗SF3B1基因突变的骨髓增生异常综合征（MDS）/骨髓增殖性肿瘤（MPN）伴环状铁粒幼细胞增多和血小板增多（RS-T）、骨髓纤维化（MF）的难治性贫血效果。方法:回顾性分析南通大学附属建湖医院收治的1例SF3B1基因突变MPN/MDS-RS-T伴MF难治性贫血患者的临床资料，并进行文献复习。结果:该患者2016年9月开始先后予以沙利度胺联合糖皮质激素、地西他滨、来那度胺联合糖皮质激素治疗，均无效，严重依赖红细胞输注。2019年10月给予芦可替尼15 mg，2次/d，治疗2周后患者血红蛋白上升，随访3个月后血红蛋白依然稳定，脱离红细胞输注。结论:芦可替尼对SF3B1基因突变的MPN/MDS-RS-T伴MF难治性贫血患者可能有效，值得进一步积累病例进行探索。

Introduction Primary breast marginal zone lymphoma (PBMZL) is a rare occurrence and less is known about its characteristics, treatments, and outcomes. Methods We retrospectively reviewed 370 cases of early-stage PBMZL from the Surveillance, Epidemiology, and End Results database. Statistical analyses were performed to describe clinical features, determine prognostic factors, and compare different therapeutic strategies. Results At a median follow-up of 68.5 months, the 5-year overall survival (OS) and disease-specific survival (DSS) rate were 81.2 and 95.4%, respectively. We divided the cohort into four treatment groups and compared their characteristics and survival: radiotherapy (RT) ± surgery (Sx) (n = 142, 38.4%), Sx alone (n = 71, 19.2%), any chemotherapy (CT) (n = 63, 17.0%), and none of the above (n = 94, 25.4%). Age of onset and laterality of lesions tended to relate to the choice of different treatments. Multivariate Cox analysis showed that advanced age (>60 years), concomitant tumor, and any CT ( vs RT ± Sx) predicted poorer OS, while for DSS, there was no meaningful indicator (P > 0.05). Patients aged >60 years or treated with any CT seemed to have shorter DSS, but the difference only approached statistical significance. Then we applied a propensity score-matched analysis to demonstrate that neither RT- nor Sx-containing therapy could bring a better OS or DSS. The competing risk model suggested that CT was the only contributor to higher PBMZL-specific mortality. Conclusion Our results show an indolent behavior of early-stage PBMZL with long-term survival. Conventional oncological treatments fail to bring survival benefits; especially CT is detrimental to survival, suggesting that observation may be advisable in the management of early-stage PBMZL, and further research on novel targeted agents is warranted for patients in need.