Objective:To identify risk factors for major adverse cardiovascular events (MACE) in patients with multiple myeloma (MM) and to evaluate the performance of an external risk-score-based stratification. Methods:We retrospectively analyzed 162 newly diagnosed MM patients treated at Qingdao University Affiliated Hospital (2017-2023). Baseline demographics, comorbidities, laboratory and echocardiographic indices, and treatment exposures were collected. MACE (heart failure, acute coronary syndrome, malignant arrhythmias, cardiogenic shock, or cardiac sudden death) were adjudicated during therapy. Multivariable logistic regression identified independent risk factors. Progression-free survival (PFS) was compared by Kaplan-Meier analysis. An externally derived 0-4 point cardiovascular risk score was applied and patients were grouped as low (0-1), intermediate (2), or high (3-4) risk. Results:MACE occurred in 31/162 patients (19.14%). Independent risk factors included age at diagnosis (OR = 1.059 per year), cigarette smoking (OR = 3.652), anthracycline exposure (OR = 5.850), and ISS stage III (OR = 2.593; 95% CI: 1.108-6.067; all P < 0.05). Using the external risk score, 79, 54, and 29 patients were classified as low, intermediate, and high risk, respectively, with a stepwise rise in MACE incidence from ≈15% (low) to ≈18% (intermediate) and ≈31% (high). Discrimination of the score for MACE was modest (ROC AUC = 0.594). Patients experiencing MACE had significantly shorter PFS. Conclusion:Age, smoking, anthracycline use, and ISS stage III independently predict MACE in MM. External risk-score stratification demonstrates a clear gradient of risk but only modest discrimination, underscoring the need for prospective validation and optimization (e.g., integrating disease stage and treatment exposures). These findings support proactive cardio-oncology assessment and tailored therapy-particularly in older, smoking, ISS III, and anthracycline-treated patients.

目的 探讨黏膜相关淋巴组织结外边缘区淋巴瘤转化为弥漫大B细胞淋巴瘤病人的临床诊断和治疗.方法 回顾1例原发性淋巴瘤黏膜相关淋巴组织结外边缘区淋巴瘤治疗缓解后出现弥漫大B细胞淋巴瘤转化病人的临床资料,分析其临床表现、治疗经过及预后,并复习相关文献.结果 病人确诊直肠黏膜相关淋巴组织结外边缘区淋巴瘤后,给予R-CHOP方案(利妥昔单抗+环磷酰胺+多柔比星+长春新碱+泼尼松)化疗10疗程后淋巴瘤部分缓解;口服来那度胺维持半年后出现盆腔弥漫大B细胞淋巴瘤转化,考虑淋巴瘤进展,再次给予9疗程R-CHOP方案化疗;后出现中枢神经系统、肾上腺及淋巴结浸润,鞘内注射甲氨蝶呤+阿糖胞苷+地塞米松及大剂量甲氨蝶呤+利妥昔单抗化疗3疗程达部分缓解;后行自体造血干细胞移植治疗后淋巴瘤达完全缓解.口服伊布替尼单药维持治疗至今,现持续缓解3年余.结论 R-CHOP方案化疗基础上的自体造血干细胞移植及伊布替尼单药维持治疗,对发生弥漫大B细胞淋巴瘤组织转化的黏膜相关淋巴组织结外边缘区淋巴瘤病人有良好的治疗效果.

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

目的:探讨真实世界硼替佐米联合来那度胺和地塞米松(VRD)治疗新诊断多发性骨髓瘤(NDMM)的疗效与安全性.方法:回顾性分析2018年1月-2021年4月本中心接受VRD方案治疗的45例NDMM患者的临床资料.结果:所有NDMM患者均予以VRD方案治疗,中位随访时间21个月,完成2个疗程治疗的患者有45例,总有效率为88.9％;完成4个疗程治疗的患者有34例,总有效率为91.2％;完成6个疗程治疗的患者有19例,总有效率为100.0％.1年总生存率为94％,2年总生存率为75％;1年无进展生存率为81％,2年无进展生存率为73％.多因素分析显示,循环浆细胞是影响无进展生存及总生存的独立危险因素.VRD治疗后患者肌酐、肌酐清除率及β2微球蛋白得到明显改善.2个疗程后肾功能逆转率为73.9％(17/23).安全性分析显示,贫血15例(33.3％)、血小板减少13例(28.9％)以及周围神经病变10例(22.2％).5例(11.1％)患者因不能耐受周围神经毒性更换药物治疗,1例(2.2％)患者因不能耐受来那度胺导致的恶心、呕吐更换药物治疗.结论:新药时代NDMM患者应用VRD方案治疗,循环浆细胞是独立危险因素,VRD方案具有良好的疗效及安全性,并且可在一定程度上改善肾功能.

To explore the clinical characteristics, diagnosis, and treatment of chronic lymphocytic leukemia with secondary pancytopenia. Here, a case of pancytopenia secondary to chronic lymphocytic leukemia is reported. Additionally, a review of relevant chronic lymphocytic leukemia literature was conducted to summarize its diagnosis, clinical characteristics, treatment history, and experience. After treatment with cyclosporine A, the patient's chronic lymphocytic leukemia continued to resolve, and hematopoiesis returned to normal. Cyclosporine A therapy resulted in improved patient outcomes. However, the mechanism by which cyclosporine A rebuilds the immune microenvironment and its antileukemia effect in the body remains to be studied.

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (−), and lysozyme (Lys) (−). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.

目的:探讨不同分型多发性骨髓瘤(MM)患者血清唾液酸水平及其临床意义.方法:回顾性分析2013年1月1日-2019年10月31日青岛大学附属医院的175例MM患者,对其临床特点、实验室检查结果及预后进行统计学分析.结果:IgA型患者、轻链型患者唾液酸水平明显高于健康者(P＜0.05),而IgG型患者唾液酸水平与健康者比较差异无统计学意义(P＞0.05),同时IgA型患者唾液酸水平明显高于轻链型患者(P＜0.05).IgA型患者的唾液酸水平与球蛋白、尿酸、血沉、血钙、单克隆免疫球蛋白、受累轻链与未受累轻链比值、骨髓涂片浆细胞数呈正相关(P＜0.05),与血红蛋白、白蛋白、乳酸脱氢酶呈负相关(P＜0.05);轻链型患者的唾液酸水平与球蛋白、肌酐、血沉、受累轻链与未受累轻链比值呈正相关(P＜0.05),与血红蛋白呈负相关(P＜0.05).在IgA型及轻链型患者中唾液酸水平随疾病的不同阶段动态变化,当疾病缓解时唾液酸水平降低,疾病进展时唾液酸水平升高.多因素分析表明,唾液酸是轻链型MM的预后独立危险因素.轻链型患者中高唾液酸组与低唾液酸组的Kaplan-Meier生存分析显示,高唾液酸组有更短的无进展生存期(16.96个月,95％ CI 10.03～23.87 vs34.07个月,95％CI 27.00～41.14,P=0.003).结论:血清唾液酸可作为反映IgA型及轻链型MM患者肿瘤负荷的良好指标,且初诊时高唾液酸往往提示预后不良.

Background: Advanced lung cancer inflammation index (ALI) is known to predict the overall survival of patients having some solid tumors or B-cell lymphoma. The study investigates the predictive value of ALI in multiple myeloma (MM) patients and the correlation between ALI and prognosis. Methods: A database of 269 MM consecutive patients who underwent chemotherapy between December 2011 and June 2019 in the Affiliated Hospital of Qingdao University was reviewed. ALI cut-off value calculated before the initial chemotherapy and post 4 courses treatment were identified according to the receiver operating characteristic (ROC) curve, and its association with clinical characteristics, treatment response, overall survival (OS), and progression-free survival (PFS) were assessed. Results: Patients in the low ALI group (n=147) had higher risk of β2 microglobulin elevation, more advanced ISS (International Classification System stage), and TP53 gene mutation, with significantly lower median overall survival (OS; 36.29 vs. 57.92 months, P = 0.010) and progression-free survival (PFS; 30.94 vs. 35.67 months, P = 0.013). Independent risk factors influencing the OS of MM patients were ALI (P = 0.007), extramedullary infiltration (P = 0.001), TP53 (P = 0.020), Plt (P = 0.005), and bone destruction (P = 0.024). ALI (P = 0.005), extramedullary infiltration (P = 0.004), TP53 (P = <0.001), Plt (P = 0.017), and complex chromosome karyotype (P = 0.010) were independent risk factors influencing the PFS of MM patients. Conclusions: ALI is a potential independent risk factor predicting the prognosis of newly diagnosed MM patients.

目的:提高对慢性淋巴细胞白血病（CLL）合并第二肿瘤的认识。方法:报道青岛大学附属医院2例给予伊布替尼治疗的CLL患者，分别合并腹腔消化道来源腺癌和鳞状细胞癌，并复习相关文献。结果:2例CLL患者在确诊后，在给予伊布替尼过程中合并第二肿瘤。结论:应积极评估CLL病情，严格遵守CLL治疗指征标准，早期发现治疗第二肿瘤。

OBJECTIVE:To study the high risk factors for the transformation into acute myeloid leukemia(AML) in patients with intermediate and high risk myelodysplastic syndrome(MDS) treated by decitabine-based regimen. METHODS:The clinical characterstics of 60 intermediate and high risk MDS patients and the factors of its transformed into AML were retrospectively analyzed. RESULTS:The overall response rate(ORR) of the patients suffered from intermediate and high risk MDS treated by decitabine-based regimen was 65.0％(39/60), among the 60 cases 17 achieved complete remission(CR), 5 achieved morrow complete remission(mCR), 4 achieved partial remission(PR) and 13 achieved hematologic improvement(HI). Twenty-one cases(35.0%) were transformed into AML among 60 cases of intermediate and high risk MDS treated by decitabine-based regimen. The median time of transformation from intermediate and high risk MDS into AML was 10.0 months(1.6-32.0). χ2 or Fisher's exact test showed that 2016 WHO MDS diagnostic subgrouping, myeloid hyperplasia markedly active, delayed interval of decitabine-based treatment associated with the transformation from intermediate to high risk MDS into AML (χ2=9.878，P=0.031；χ2=4.319，P=0.038；χ2=6406，P=0.011); Univariate analysis of Kaplan-Meier test showed that 2016 WHO MDS diagnostic subgroups, bone marrow blast cell ratio, bone marrow dysplasia coefficients, prolonged interval of decitabine-based treatment associated with the transformation from intermediate and high risk MDS into AML (P=0.015，P=0.008，P=0.012，P=0.032); multivariate analysis showed the bone marrow blast cell ratio and the bone marrow dysplasia coefficients were independent risk factors for the transformation from intermediate to high risk MDS into AML (P=0.022，P=0.018). CONCLUSION:The bone marrow blast cell ratio and the bone marrow dysplasia coefficients are independent risk factors of transformation into AML in the patients with intermediate and high risk MDS treated by decitabine-based regimen. The regular interval of dicitabine treatment is beneficial to maintain the stability of patients conditions.

The correlations and prognostic value of neutrophil to lymphocyte ratio, immunophenotype and cytogenetic abnormalities in patients with newly diagnosed multiple myeloma Hu Juanjuan, Nie Shumin, Gao Yan, Yan Xueshen, Huang Junxia, Li Tianlan, Liu Shanshan, Mao Chunxia, Zhou Jingjing, Xu Yujie, Wang Wei, Meng Fanjun, Feng Xianqi Department of Hematology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China; Department of Neurology, the Affiliated Hospital of Qingdao University, Qindao 266000, China Corresponding author: Feng Xianqi, Email:qdfxq2005@163.com

多发性骨髓瘤(multiple myeloma,MM)是好发于中老年人的一种恶性克隆性浆细胞病,发病率占所有人类肿瘤的1％,占血液系统恶性肿瘤的13％,在过去的20年其中位生存期已从3年增长至6年[1].

OBJECTIVE:Decitabine is reported to be valuable in treating multiple malignant blood diseases. However, the application of decitabine in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML) has not been fully examined. Thus, our study aimed to investigate the clinical efficacy and safety of decitabine in treating such patients.MATERIALS AND METHODS:Clinical data of MDS or AML patients treated with decitabine were retrospectively analyzed. All the patients were regularly followed up, and the risk factors affecting clinical efficacy were also detected.RESULTS:A total of 36 patients (MDS, n = 27; AML, n = 9) were included in the study. The response rate of MDS patients was 55%, and there were three cases (15%) of complete remission (CR), three cases (15%) of marrow CR, and five cases (15%) of hematologic improvement. It was about three cycles to achieve the best efficiencies. Gender, age, percentage of blasts in bone marrow, International Prognostic Scoring System risk group, and cytogenetic factors were not associated with response rate. The median overall survival of MDS patients was 8 (1-44) months. Agranulocytosis (P = 0.037) and severe anemia (P = 0.044) were the independent factors for prognosis. The complete response rate of AML was 33.3%. From the investigation, infection was the most common complication in our cohort, especially lung infection with the incidence of 27.8%.CONCLUSIONS:Our data demonstrated that decitabine was effective and relatively safe in treating MDS and AML. Patients with agranulocytosis and severe anemia were prone to have poor survival, which should be monitored in clinical practice.

目的:研究胎盘生长因子(PLGF)及骨髓微血管密度(MVD)在多发性骨髓瘤(MM)骨髓活检组织中的表达情况及临床意义.方法:应用免疫组织化学染色方法检测40例MM患者及10例正常者骨髓活检组织PLGF及MVD的表达情况,电脑采集图像并使用Image Pro Plus6.0软件分析结果.结果:与正常者骨髓活检组织比较,MM患者骨髓活检组织的PLGF及MVD表达显著升高(均P＜0.05);在MM患者中低血红蛋白者的MVD表达较高血红蛋白者显著升高(P＜0.05),但在MM分期、分型、溶骨性损害、年龄之间均差异无统计学意义.结论:PLGF及MVD在骨髓瘤较正常骨髓组织表达明显增多,骨髓血管增多在MM的发病中起到重要作用.

ObjectiveWe aimed to evaluate the efficacy and toxicity of decitabine in patients with myelodysplastic syndrome (MDS), as well as the influencing factors related to efficacy.MethodsThe clinical data of 27 patients with MDS treated with decitabine retrospectively were analyzed to evaluate the best efficiencies and the effects of the factors such as age, gender, agranulemia (granulocyte<0.5×109/L)、severe anemia (Hb<60 g/L), thrombocytopenia (platelet <30×109/L), cell line deficiency (≥two cell lines) on the best efficiencies. We analyzed the overall survival (OS) by Log-rank test and explored the factors that could affect the prognosis by multivariable COX regression analysis.ResultsThe overall response rate of the 27 MDS patients under decitabine treatments was 55%. It was about 3 cycles which could achieve the best efficiencies. The factors such as age, gender, karyotype, severe anemia, agranulemia (granulocyte< 0.5×109/L), thrombocytopenia (platelet<30×109/L), multilineage cytopenia (≥2 lineage) had&nbsp;no relationship with the efficacy. The overall survival (OS) of all the 27 patients with MDS was 8 (1-44) months. The statistical difference of the OS was significant in the group of sex and agranulocytosis (respectively,P=0.017 andP=0.026). The results showed that the agranulocytosis and severe anemia could affect the prognosis, respectively,P=0.037 Exp (B) 0.219 andP=0.044 Exp (B) 18.308, by multivariable COX regression analysis. Myelosuppression and lung infection (33.3%) was the most common adverse reactions of decitabine in patients with MDS.ConclusionsThere was a higher overall response rate in patients with MDS treated with decitabine. We also found that the difference of the OS was significant in the group of gender and agranulocytosis. The agranulocytosis and severe anemia were the factors which could affect the OS. There are still many questions in regard to alternative decitabine treatment regimens such as improving remission rate and response, which need to be answered.

目的 了解正常核型急性髓系白血病(AML)病人核仁磷酸蛋白1(NPM1)、FMS样酪氨酸激酶3(FLT3)基因突变的发生频率,并探讨基因突变伴随的临床特征及对近期预后的影响.方法 收集94例初治的正常核型AML病人(M3除外),行NPM1、FLT3基因突变检测.结果 94例正常核型AML病人,NPM1基因突变阳性率为40.43％;FLT3内部串联重复突变(FLT3-ITD)阳性率为28.72％;NPM1并FLT3-ITD基因突变阳性率为14.89％;FLT3点突变(FLT3-TKD)阳性率为7.45％.与无突变组相比,NPM1+/FLT3组发病年龄、外周血白细胞和血小板计数、骨髓原始细胞比例均较高,差异有显著性(t=2.048～2.072,P＜0.05).NPM1 /FLT3-ITD+组外周血白细胞计数和骨髓原始细胞比例均较无突变组高(t=2.549、2.784,P＜0.05).NPM1 +/FLT3组1疗程化疗诱导完全缓解率为87.50％,高于无突变组的63.89％(x2 =4.205,P＜0.05);NPM1 /FLT3-ITD+组完全缓解率为53.85％,与无突变组比较差异无统计学意义(P＞0.05).结论 NPM1、FLT3基因突变是正常核型AML病人中常见的分子学异常,此两种基因突变检测对AML病人的个体化治疗及预后评估有重要意义.

Objective To investigate the expression and significance of breast cancer suscepterbility gene 1 (BRCA1) in leukemia.Methods Fluorescent quantitative reverse transcription-polymerase PCR was used to investigate the expression of BRCA1 in 18 patients with ALL-L2 (13 denovo ALL patients,5 relapsed ALL patients),20 patients with CML-CP and 15 normal controls.Results The mRNA expression of BRCA1 in denovo patients with ALL was lower than that in normal control,with statistical significance (P ＜ 0.05).The mRNA level of BRCA1 in ALL patients in CR was higher compared with before to cure, with statistical significance (P ＜ 0.05),but lower than that in normal control,without statistical significance(P ＞ 0.05).The mRNA expression of BRCA1 in patients with relapsed ALL was lower than that in normal control with statistical significance (P ＜ 0.05), and lower than that in denovo patients with ALL, without statistical significance (P ＞ 0.05).The mRNA level of BRCA1 showed no difference in CML-CP patients compared with normal control (P ＞ 0.05). Conclusion The different expression of BRCA1 in leukemia indicates that he has closely relationship with the prognosis of leukemia and guides the clinical diagnosis and treatment.