Background Relapsed and refractory multiple myeloma (RRMM) is generally associated with a poor prognosis. Objectives This real-world study aims to evaluate the efficacy and safety of the carfilzomib–pomalidomide–dexamethasone (KPd) regimen in patients with RRMM. Design A multicenter, retrospective study was conducted in four centers in China. Methods RRMM patients who received at least 1 cycle of KPd across four centers were retrospectively included and stratified by prior lines of treatment, survival outcomes and safety profile were analyzed. Results A total of 82 patients were enrolled. Based on the lines of treatment (LOT) at KPd initiation, patients were stratified into second-line (2L, n=39), third-line (3L, n=26), and fourth-line or beyond (4L+, n=17) groups. Among 72 response-evaluable patients, the overall response rate (ORR) was 69.4%, with ORRs of 79.4%, 73.9%, and 40.0% in the 2L, 3L, and 4L+ groups, respectively. After a median follow-up of 10.8 months, the median progression-free survival (mPFS) for the entire cohort was 22.5 months, while the median overall survival (mOS) was not reached (NR). The mPFS was NR, 22.5, and 10.1 months (P=0.178), and the mOS was NR, NR, and 11.6 months (P=0.019) for patients receiving KPd in the 2L, 3L, and 4L+ settings, respectively. Multivariable analysis identified elevated lactate dehydrogenase (LDH) level (HR=3.489, 95% CI: 1.557–7.823) and LOT ≥4 (HR=2.791, 95% CI: 1.086–7.177) as independent predictors of inferior PFS (P<0.05), while LOT ≥4 (HR=3.917, 95% CI: 1.258–12.200) was also associated with worse OS (P=0.019). Grade ≥3 adverse events (AEs) occurred in 12.8%, 50.0%, and 47.1% of patients in the 2L, 3L, and 4L+ groups, respectively. Conclusion The KPd regimen demonstrated favorable clinical efficacy and manageable toxicity in RRMM, particularly in those with early-line relapse.

PurposeThe standard first-line R-CHOP regimen achieves cure in only approximately 50% of patients. Polatuzumab vedotin (Pola) is a novel antibody-drug conjugate targeting the B-cell receptor component CD79b; however, evidence regarding its real-world efficacy remains relatively limited. This retrospective study aims to evaluate the clinical efficacy of Pola in combination therapy.MethodsA retrospective analysis was conducted on 140 patients with complete clinical records treated at the Affiliated Hospital of Qingdao University between September 2022 and September 2025. Among them, 114 patients received combination regimens containing Pola, while 26 patients received regimens without Pola. Given the limited follow-up duration, this study primarily assessed interim efficacy, with preliminary survival data also reported.ResultsAmong the 140 eligible patients, 4 deaths and 20 disease progressions occurred. The age range was 23–91, with a median age of 67; 45.0% were female. An ECOG performance status ≥2 was observed in 16.4% of patients, and 20.7% presented with B symptoms. Elevated LDH levels were found in 57.9% of patients. Ann Arbor stage III or IV disease was present in 65.0% of patients, and an IPI score >2 was recorded in 50.7%. Double-expressor lymphoma was diagnosed in 40.0% of cases. Bone marrow involvement was detected in 20.0% of patients, while 83.6% had lymph node extracapsular extension. Immunohistochemistry staining showed 36 patients (25.7%) with GCB subtype and 99 patients (70.7%) with non-GCB subtype. Median follow-up was 11 months (95% CI: 10.85–13.15). The objective response rate (ORR) was 94.4% in the Pola group and 70.0% in the non-Pola group (OR = 7.1, 95% CI: 2.0–27.2, P<0.001). Complete remission (CR) rates were 53.7% and 20.0%, respectively (OR = 4.6, 95% CI: 1.7–14.9, P = 0.002). The Pola group showed a statistically significant advantage in progression-free survival (PFS). Six-month PFS rates were 90.4% (95% CI: 84.8%–96.3%) for the Pola group and 76.9% (95% CI: 62.3%–94.9%) for the non-Pola group, while 12-month PFS rates were 87.2% (95% CI: 80.5%–94.6%) and 67.9% (95% CI: 51.7%–89.2%), respectively.ConclusionCombination regimens containing Polatuzumab vedotin demonstrated a marked interim efficacy advantage, which may translate into potential long-term survival benefits.

Acute graft-versus-host disease (aGVHD) remains a life-threatening complication that limits the efficacy and application of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early identification and diagnosis of aGVHD is significant for improving the outcomes of allo-HSCT. We retrospectively analyzed the dendritic cell (DC) subsets in peripheral blood (PB) of patients who received allo-HSCT before transplantation and at engraftment to evaluate the correlation between DC subsets and the occurrence of aGVHD. The results showed that the proportion and count of myeloid dendritic cells (mDCs) before transplantation were positively correlated with the occurrence and severity of aGVHD, while the proportion and count of mDCs at engraftment were negatively correlated with those. In addition, patients with higher proportion and count of mDCs before transplantation developed aGVHD earlier, whereas those without aGVHD had the lowest proportion and count of mDCs before transplantation. The proportions and counts of DC subsets at engraftment were not significantly correlated with the onset time of aGVHD. Receiver operating characteristic (ROC) curve analysis demonstrated that the count of mDCs in PB before transplantation had greater sensitivity and specificity in predicting aGVHD (AUC = 0.8002, P < 0.0001) compared to plasmacytoid DCs (pDCs) and total DCs. Multivariate logistic regression analysis confirmed that the count of mDCs in PB before transplantation and at engraftment were independent factors in predicting the occurrence of aGVHD (OR = 9.907, P = 0.018, 95

Objective Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to evaluate the effect of recombinant human thrombopoietin (rhTPO) on aGVHD using retrospective clinical data and a xenogeneic GVHD mouse model. Methods We retrospectively analyzed 162 patients who underwent allo-HSCT between 2016 and 2018, comparing outcomes between those treated with rhTPO and those who were not. Additionally, a murine GVHD model was established using irradiated Balb/c mice that received allogeneic PBMCs. Mice were treated with different doses of rhTPO to assess organ pathology, immune cell subsets, and cytokine expression. PBMCs from humans were also treated with rhTPO to assess proliferation and differentiation in vitro. Results were presented as odds ratios (OR) with 95 % confidence intervals (CI), and statistical significance was set at P < 0.05. P > 0.05 was considered statistically significant. All experiments were repeated for 3 times. Results Clinical analysis showed that rhTPO use and older patient age were independently associated with a lower incidence of aGVHD (P = 0.007 and P = 0.014, respectively). In the xenogeneic mouse model, rhTPO mitigated tissue pathology and modulated immune cell subsets. In vitro, rhTPO regulated PBMC proliferation and enhanced lymphocyte differentiation. Conclusions rhTPO may reduce the risk of aGVHD by modulating immune responses and protecting tissues, supporting its potential role as an adjunct therapy in allo-HSCT.

BackgroundHematopoietic stem cell transplantation (HSCT) offers a potentially curative option for severe aplastic anemia (SAA). However, graft failure (GF) remains a life-threatening complication following HSCT. Haploidentical HSCT may serve as an effective salvage therapy for the treatment of GF.Case presentationThis report describes a 3-year-old girl with acquired SAA who experienced GF twice following matched unrelated donor (MUD) transplantations. Successful engraftment was ultimately achieved through a third haploidentical donor HSCT. This work was conducted in accordance with the Declaration of Helsinki and the Declaration of Istanbul.ConclusionsBased on our experience with this case, we conclude that a third HSCT with a haploidentical donor represents a viable approach to extending survival.

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-pomalidomide-dexamethasone (KPd) in patients with relapsed and refractory multiple myeloma (RRMM). Methods: We performed a retrospective multicenter analysis to evaluate the efficacy and safety of KPd regimen in 81 patients with RRMM registered in the Eastern Shandong Myeloma Collaborative Group. All patients received at least 1cycle of KPd. KPd was performed in RRMM patients as follows: intravenous carfilzomib at a dose of 20mg/m2 on days 1 and 2, and then 27mg/m2 on days 8, 9, 15, and 16 of the first cycle and days 1, 2, 8, 9, 15, and 16 of subsequent cycles, dexamethasone 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23, and pomalidomide 4 mg orally on days 1-21 of each 28-day cycle. Results: The median age at the start of KPd regimen was 63 years old (range, 38-74),39 were male and 42 were female. Among 81 patients included, 22.2% of them have received upfront autologous hematopoietic stem cell transplantation. Before patients received KPd regimen, there were 39 (48.2%),25 (30.9%) and 17 (20.9%) patients have already received prior 1-line, 2-line, and ≥ 3-line treatment, respectively. 91.4% of patients previously exposed to bortezomib (45.7% refractory), 63.0% exposed to lenalidomide (35.8% refractory), and 32.1% exposed to anti-CD38 monoclonal antibody (16.1% refractory). 63.0% of patients exposed to both bortezomib and lenalidomide (25.9% double refractory), and 24.7% exposed to bortezomib, lenalidomide and CD38 antibody (3.7% triple refractory). There were 36(44.4%) and 31(38.3%) patients with ISS stage III and extramedullary disease, respectively. 30.9% of patients had prior history of high blood pressure and 21.0% of patients had a history of cardiovascular disease (coronary disease, heart failure, arrhythmia, etc.). The median duration of treatment was 3 months. Among 69 patients available for response assessment, the objective response rate (ORR) (≥partial response) was 66.5%(n=46) with 42.0% achieving ≥very good partial response and 31.9% achieving≥complete response. After a median follow-up of 6 months, he median progression-free survival (PFS) and overall survival (OS) were 12.7 months (95%CI: 6.83, Not estimable) and not reached (95% CI: 11.17, Not estimable), respectively. A total of 79 adverse events were observed in 33(40.7%) KPd cases and Grade I, Grade II and Grade III events were accounted for 36.7%(n=29),40.5% (n=32) and 22.8%(n=18), respectively. Grade III events were only observed in 12 patients and no higher events were observed. Infections(n=5), cardiovascular(n=5) and cytopenia(n=3) events were most frequent reported Grade III events, no patients died due to KPd related adverse events. Conclusion: KPd regimen showed considerable clinical benefits among RRMM in a real-world setting, and the adverse effects after KPd are controllable.

BACKGROUND Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an important treatment for severe aplastic anemia (SAA). It is known that SAA can evolve into malignant clonal diseases, such as acute myeloblastic leukemia (AML) or myelodysplastic syndrome. However, the transformation of SAA into AML after allo-HSCT is a rare phenomenon. Here, we report a case of SAA transformed into AML after patient received human leucocyte antigen (HLA)-matched sibling peripheral blood stem cell transplantation. CASE REPORT A 51-year-old female patient presented with petechiae and fatigue and received a diagnosis of idiopathic SAA. The immunosuppressive therapy combined with umbilical cord blood transplantation failed for this patient. Then, she received HLA-matched sibling allogeneic peripheral blood stem cell transplantation (allo-PBSCT). However, 445 days after allo-PBSCT, the patient had a diagnosis of AML by bone marrow puncture. Donor-recipient chimerism monitoring and cytogenetic analysis confirmed that the leukemia was donor cell origin. Notably, a new HOXA11 mutation was detected in the peripheral blood of the patient after transplantation by whole-exome sequencing, which was the same gene mutation detected in the donor. The patient received 1 cycle of induction chemotherapy with azacytidine and achieved complete remission. However, the leukemia relapsed after 2 cycles of consolidation chemotherapy. Unfortunately, the patient died of leukemia progression 575 days after allo-HSCT. CONCLUSIONS The mechanism of how normal donor hematopoietic cells transform to leukemia in the host remains unclear. Donor cell leukemia provides a unique opportunity to examine genetic variations in donors and hosts with regards to the progression to malignancy.

A poorer prognosis is thought to be associated with “double expressor lymphomas,” which are a subtype of diffuse large B cell lymphomas (DLBCL) that co-express MYC and BCL2. While the role of ubiquitin-specific peptidase 37 (USP37) in lung cancer, where it mediates the deubiquitination and stabilization of c-myc, has been well-documented, its involvement in DLBCL remains unexplored. The use of RT-PCR, immunohistochemistry, or WB test allowed for the detection of elevated USP37 in DLBCL tissues and cells. In order to understand the function of USP37 in DLBCL, keloid DLBCL cells were transfected with si-USP37 using Lipofectamine 3000. When tested on DLBCL cells, USP37 increased cell proliferation and inhibited cell cycle progression. USP37 controls the process of deubiquitination to stabilise c-myc proteins. The overexpression of c-Myc facilitated cell proliferation and prevented the cell cycle of DLBCL cells stimulated by si-USP37, which should be taken into consideration. Furthermore, USP37 depletion consistently hinders the development of tumour xenografts in mouse models. Overexpressing c-myc, however, may partially counteract this impact. The data show that USP37 may be a potential therapeutic target for DLBCL, and that it may enhance the course of the disease by deubiquitinating c-myc via direct interactions with c-myc.

BACKGROUND:This study investigates the role of CXXC5 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) within the bone marrow microenvironment, utilizing advanced methodologies such as single-cell RNA sequencing (scRNA-seq), CRISPR-Cas9, and proteomic analysis. METHODS:We employed flow cytometry to isolate HSCs from bone marrow samples, followed by scRNA-seq analysis using the 10x Genomics platform to examine cell clustering and CXXC5 expression patterns. CRISPR-Cas9 and lentiviral vectors facilitated the knockout and overexpression of CXXC5 in HSCs. The impact on HSCs was assessed through qRT-PCR, Western blot, CCK-8, CFU, and LTC-IC assays, alongside flow cytometry to measure apoptosis and cell proportions. A mouse model was also used to evaluate the effects of CXXC5 manipulation on HSC engraftment and survival rates. RESULTS:Our findings highlight the diversity of cell clustering and the significant role of CXXC5 in HSC regulation. Knockout experiments showed reduced proliferation and accelerated differentiation, whereas overexpression led to enhanced proliferation and delayed differentiation. Proteomic analysis identified key biological processes influenced by CXXC5, including cell proliferation, differentiation, and apoptosis. In vivo results demonstrated that CXXC5 silencing impaired HSC engraftment in a bone marrow transplantation model. CONCLUSION:CXXC5 is crucial for the regulation of HSC self-renewal and differentiation in the bone marrow microenvironment. Its manipulation presents a novel approach for enhancing HSC function and provides a potential therapeutic target for hematological diseases.

肥大细胞白血病（mast cell leukemia，MCL）是系统性肥大细胞增生症（systemic mastocytosis，SM）中罕见的一种类型。2016年的WHO造血与淋巴组织肿瘤分类将SM分为五种亚型 [1]：惰性SM（indolent SM，ISM）、冒烟型SM（smoldering SM，SSM）、SM伴血液系统肿瘤（SM with associated hematologic neoplasm，SM-AHN）、侵袭性SM（aggressive SM，ASM）和MCL。MCL病情进展快，诊断困难，而合并嗜酸性粒细胞增多又增加了MCL诊断和治疗的难度。现报告我院新近诊断的一例MCL合并嗜酸性粒细胞增多患者并对相关文献进行复习，以提高对此罕见疾病诊疗的认识。

Background: Fusarium is a conditional pathogen that can cause invasive infection in patients with hematological diseases under immune function. Methods: A case of recurrent and refractory Philadelphia chromosome-positive acute lymphoblastic leukemia was treated with allogeneic hematopoietic stem cell transplantation after chimeric antigen receptor-modified T cells treatment. Results: During transplantation, disseminated Fusarium infection occurred, involving the skin, liver, spleen and central nervous system, and the patient eventually died. Conclusions: Early identification of Fusarium infection based on the characteristic rash and timely antifungal treatment can improve the cure rate.

艾沙康唑(isavuconazole)是一种新型二代三唑类抗真菌药物,于2015年在美国获批上市用于治疗侵袭性曲霉病(invasive aspergillosis, IA)和毛霉病 (invasive mucormycosis, IM)[1].艾沙康唑有口服和静脉注射两种剂型,具有生物利用度高、体内半衰期长、抗菌谱广、安全性好等优势.研究表明,艾沙康唑口服制剂作为预防用药,可替代泊沙康唑用于高危血液病患者或异基因造血干细胞移植(allogeneic hematopoietic stem cell transplantation, allo-HSCT)患者侵袭性真菌病(invasive fungal disease, IFD)的预防 [2].

目的:分析浆母细胞淋巴瘤(PBL)患者的临床和病理特征、鉴别诊断、治疗及预后.方法:回顾性分析青岛大学附属医院2013年9月至2020年4月确诊并治疗的7例PBL患者的临床资料,并进行文献复习.结果:7例PBL患者均为HIV阴性,其中男3例,女4例,中位年龄63(51～75)岁.1例为腹股沟淋巴结起病,其余6例为结外器官受累起病,初诊Ann Arbor分期Ⅳ期5例,3例存在B症状.所有患者瘤细胞弥漫表达CD38,其次为CD138和MUM-1,B细胞标志物CD20少见,EBER阳性1例.3例患者接受原发病灶切除术,5例患者以CHOP样方案作为一线化疗方案,其中1例完全缓解并接受自体造血干细胞移植,6例死亡.7例患者中位生存时间7.2(0.8～46.7)个月.结论:PBL侵袭性强,易累及结外组织,多数患者确诊时处于晚期;尚无统一治疗方案,对化疗反应差,死亡率高;有研究报道硼替佐米的应用和自体造血干细胞移植在一定程度上有助于延长患者生存.

嗜血细胞综合征(hemophagocytic syndrome,HPS)又称嗜血细胞性淋巴组织细胞增生症(he-mophagocytic lyphohistiocytosis,HLH),是以淋巴细胞及巨噬细胞增生伴嗜血细胞增多引起全血细胞减少及多脏器浸润为特征的一组疾病[1].发热、肝脾肿大、全血细胞减少、肝功能异常等是其主要临床表现[2,3].霍奇金淋巴瘤合并HLH患者的预后极差[4].现报告青岛大学附属医院收治的1例霍奇金淋巴瘤(hodgkin lymphomoa,HL)合并HLH的病例诊治经过并复习相关文献,报道如下.

目的 探讨慢性淋巴细胞白血病并发隐球菌性脑膜炎的临床特点、诊治方法和经验.方法 报告1例慢性淋巴细胞白血病并发隐球菌性脑膜炎病人,并复习相关文献,总结其病因、临床特点、诊治经过及治疗经验.结果 病人经两性霉素B规范治疗后脑脊液中未再检测到隐球菌,效果显著.结论 慢性淋巴细胞白血病并发隐球菌性脑膜炎较为少见,容易漏诊,病死率极高,早期诊断和积极治疗可获得较好的预后.

目的 探讨骨髓纤维化(MF)与非霍奇金淋巴瘤(N H L)病人的骨髓病理特征及其对预后影响.方法 对215例NHL病人(其中96例合并MF)的临床资料回顾分析,观察病人骨髓病理学特点,比较合并与未合并MF病人治疗6个周期缓解率、总生存率(OS)及无疾病进展生存率(PFS)的差异.结果 Ⅲ期和Ⅳ期NHL病人较Ⅰ期和Ⅱ期更易合并MF(Z=-2.548,P<0.05).合并MF的NHL病人脾大例数较未合并MF的NHL病人多,两组比较差异有显著性(χ2=13.019,P<0.05).合并MF病人化疗后3～4度骨髓抑制发生率较未合并MF者高(Z=-3.413,P<0.05).合并和未合并MF的NHL病人治疗6周期完全缓解率差异无显著性(χ2=0.261,P>0.05).寿命表分析显示,合并MF的NHL病人1、2、3年PFS及OS分别为83％、68％、55％和86％、85％、60％,未合并MF的NHL病人的1、2、3年PFS及OS分别为94％、81％、81％和96％、95％、95％,两组OS及PFS比较差异有显著性(χ2=6.077、5.443,P<0.05).COX回归生存分析显示,合并MF是影响淋巴瘤病人OS(RR=0.357,95％CI=0.136～0.933,P<0.05)和PFS(RR=0.459,95％CI=0.239～0.884,P<0.05)的独立不良预后因素.结论 MF是NHL病人预后的危险因素,合并MF可降低NHL病人的PFS及OS,可能与化疗后严重骨髓抑制引起早期死亡有关.

Three dimensional (3D) culture has gradually become a research hotspot in the field of drug screening, stem cell research, and tissue engineering due to its more physiological-like morphology and function. In this study, we compared the differences of cell proliferation, population, protein expression and chemoresistance profiles between two dimensional (2D) and 3D culture of acute lymphoblastic leukemia (ALL) Jurkat cell line. Polycaprolactone (PCL) is used for 3D culture owing to its biochemical properties and compatibility. Culturing of ALL Jurkat cell line in collagen type I coated polycaprolactone scaffold for 168 h increased cell proliferation, attachment, as well as the drug resistance to cytarabine (Ara-C) and daunorubicin (DNR) without changing the original CD2+CD3+CD4+dimCD8-CD34-CD45+dim phenotype, compared to uncoated PCL scaffold and tissue culture plate systems. Molecularly, increased chemoresistance is associated with the upregulation of discoidin domain receptor 1 (DDR1) and transcription factor STAT3. Inhibition of DDR1 activity by DDR1-specific inhibitor DDR-IN-1 accelerated cell death in the presence of Ara-C, DNR or their combination. These results demonstrated that 3D culture enhances chemoresistance of ALL Jurkat cell line by increasing DDR1 expression. Importantly, the cell adhesion-mediated drug resistance induced by DDR1 in the scaffold was similar to the clinical situation, indicating the 3D culture of cancer cells recapitulate the in vivo tumor environment and this platform can be used as a promising pre-clinic drug-screen system.

目的 评估骨髓纤维化、骨髓增生异常综合征相关预后系统对我国急性髓系白血病(AML)、骨髓增生异常综合征(MDS)伴骨髓纤维化的预后效力,探讨AML/MDS伴骨髓纤维化预后因素.方法 回顾性分析134例AML及MDS伴骨髓纤维化患者病例资料,采用PMF-IPSS、DIPSS、IPSS-Chinese、DIPSS-Chinese、MYSEC-PM、MDS-IPSS、IPSS-R、WPSS对其进行预后分组及评估,并分析预后因素.结果 PMF-IPSS、DIPSS、IPSS-Chinese、DIPSS-Chinese、MYSEC-PM、MDS-IPSS、IPSS-R、WPSS均不能对AML/MDS伴骨髓纤维化患者进行准确预后,在MDS-IPSS、WPSS基础上增加骨髓纤维化分级可改善其预后效力.有脾肿大(P=0.015)、有输血依赖(P=0.008)、纤维化分级≥2级(P<0.001)、CRP>5.0 mg/L(P=0.032)是AML/MDS伴骨髓纤维化的不良预后因素.结论 目前缺乏AML/MDS伴骨髓纤维化的预后系统,脾肿大、输血依赖、纤维化分级及CRP与其预后相关,或许可为预后评估及治疗提供新的选择.