Progress of the pathogenesis in mantle cell lymphoma / 肿瘤研究与临床

Mantle cell lymphoma (MCL) is a rare B cell lymphoma, and its incidence rate is increasing year by year. MCL has the common characteristics of both inert lymphoma and aggressive lymphoma: rapid progress and poor prognosis. The latest research believes that the pathogenesis of MCL is a continuum, and many factors such as cell cycle disorder, SOX11 overexpression, epigenetic aberration play a role in different stages of the disease. This paper mainly reviews the pathogenesis of MCL and new findings of different subtypes from the perspective of molecular genetics,and further analyzes the clinical diversity of MCL. At the same time, the understanding of the pathogenesis of MCL aims to provide potential targets for future treatment of MCL.

A multicenter study of R-ISS staging combined with frailty biomarkers to predict the prognosis and early death in newly diagnosed elderly multiple myeloma patients / 中华老年医学杂志

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone / 中华内科杂志

Objective:To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and dexamethasone (BCD).Methods:A retrospective cohort study. Clinical data were collected in first-relapsed MM patients after BCD treatment from three tertiary hospitals in north China from July 2009 to October 2022. Patients were classified according to the second-line regimen into the immunotherapy group, single novel agent group [either proteasome inhibitor (PI) or immunomodulatory drug (IMiD)], combination treatment group (both PI+IMiD), and traditional treatment group. Responses to second-line regimens and survival data were analyzed. The Kaplan-Meier method was used for survival analysis and the Cox proportional risk model was used for univariate and multivariate analyses.Results:A total of 217 patients were enrolled including 8.8% (19/217) in the immunotherapy group, 48.4% (105/217) in the PI/IMiD group, 29.9% (65/217) in the PI+IMiD group, and 12.9% (28/217) in the traditional treatment group. The median age was 62 years (range 31-83 years) and 56.2% (122/217) were males. The overall response rates (ORRs) in the four groups were 94.7% (18/19) vs. 56.2% (59/105) vs. 73.8% (48/65) vs. 32.1% (9/28) ( χ2=24.55; P<0.001), respectively. The progression-free survival (PFS) of the second-line regimens (2ndPFS) was 17.7 vs. 9.0 vs. 9.2 vs. 4.6 months ( χ2=22.74; P<0.001), respectively, among which patients in the PI/IMiD and PI+IMiD groups had comparable 2ndPFS ( χ2=1.76; P=0.923). Patients with high-risk cytogenetic abnormalities (HRCAs) achieved the longest 2ndPFS of 22.0 months in the immunotherapy group ( χ2=15.03; P=0.002). Multivariate analysis suggested that immunotherapy ( HR=0.11, 95% CI 0.05-0.27), achievement of efficacy of partial response or better ( HR=0.47, 95% CI 0.34-0.66), and non-aggressive relapse ( HR=0.25, 95% CI 0.17-0.37) were independent prognostic factors of 2ndPFS. Conclusion:In this real-world study, immunotherapy was associated with a more favorable efficacy and PFS for first-relapsed MM patients after BCD treatment, with similar outcomes in patients with HRCAs.

Clinical characteristics and survival of newly diagnosed multiple myeloma patients under 40 years old from single center and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and prognosis of very young patients with multiple myeloma (MM).</p><p><b>METHODS</b>We retrospectively analyzed the clinical characteristics and outcome of 35 newly diagnosed MM patients 40 years old or younger during a period of 15 years and compared with published data from western countries.</p><p><b>RESULTS</b>Our study demonstrated that these very young patients were more likely to be in advanced stage of International staging system, IgD isotype, hemoglobin<100 g/L, decreased platelets and deletion of 17p13. With a median follow-up of 17 months (1- 89 months), the median overall survival (OS) of this cohort was 33 months and progression-free survival (PFS) was 13 months, moreover 8 of 17 deaths occurred in the first year after diagnosis. In the univariate analysis, extramedullary infiltration, del (17p13）and renal impairment were associated with reduced PFS (P=0.031, P=0.015, P=000, respectively), while the last two factors also predicted inferior OS (P=0.015, P=0.001), but multivariate analysis showed that only renal impairment independently associated with inferior survival in COX model（PFS: HR=3.953, 95% CI 1.263-12.371, P=0.018; OS: HR=5.769, 95% CI 1.602- 20.771, P=0.007).</p><p><b>CONCLUSION</b>Our research showed for the first time that the clinical characteristics and survival of MM patients ≤ 40 years old in China were different from that in western countries. The special attention should be paid to the patients with their diagnosis and treatment.</p>

Detection of serum DKK1 in multiple myeloma and myeloma bone disease / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the association between the level of serum DKK1 and disease course of multiple myeloma（MM）as well as myeloma bone disease.</p><p><b>METHODS</b>This study enrolled 145 cases of MM（including 79 newly diagnosed MM, 19 responded MM, 47 relapsed or progressive MM） whose lytic bone disease were evaluated by conventional radiography, ELISA was used to detect the concentration of serum DKK1.</p><p><b>RESULTS</b>Serum DKK-1 elevated in newly diagnosed MM compared with normal donors［2 155（646-35 251）vs 1 487（646-2 577） ng/L, P=0.000］, those responded［1 136（431- 3 582） ng/L, P=0.001］and relapsed/progressive MM［1 695（431-3 582） ng/L, P=0.037］, and the level of relapsed/progressive MM was marginally higher than the responded ones. Moreover, MM patients without lytic lesions in conventional radiography had significantly lower DKK- 1 levels than those with lytic bone disease［1 910（660-26 925）vs 2 519（646-35 251） ng/L, P=0.005］. Notably serum DKK-1 correlated with the number of bone lesions［0 vs 1-3 vs >3 lesions: 1 910（660-26 925）vs 2 155（1 369-5 974）vs 2 547（646-35 251）ng/L, P=0.018].</p><p><b>CONCLUSION</b>DKK-1 serum concentration correlated with disease course of MM and myeloma bone disease, indicating that DKK-1 was an important factor for the extent of bone disease, which supporting the hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.</p>

The impact of renal function on prognostic value of β₂-microglobulin of ISS stage system in multiple myeloma patients--Clinical data analysis of 666 patients in a single center / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the influence of renal function on the level of β₂-microglobulin (β₂-MG) as prognostic factor in newly diagnosed multiple myeloma (MM) patients, and to analyze the overall survival (OS) in different level of β₂-MG with relatively normal or abnormal renal function in MM patients.</p><p><b>METHODS</b>According to the level of β₂-MG, 666 newly diagnosed MM patients were divided into three groups as β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L. According to the level of serum creatinine, these patients were divided into two groups:serum creatinine <177 μmol/L as relatively normal group, serum creatinine ≥177 μmol/L as abnormal group.</p><p><b>RESULTS</b>Among 666 patients, there were 416 male and 250 female, the median age was 58 (25-86) years old. Comparison of OS among β₂-MG<3.5, 3.5-<5.5, ≥5.5 mg/L groups indicated that the median OS of the three groups were 85.75 (95% CI 70.99-100.50), 47.25 (95% CI 40.98-53.53) and 35.05 (95% CI 30.75-39.35) months, respectively (P<0.01). Comparison of OS between serum creatinine <177 and ≥177 mmol/L groups, the median OS of the two groups were 64.67 (95% CI 56.57-72.77) and 32.74 (95% CI 27.74-37.73) months, respectively (P<0.01). In β₂-MG≥5.5 mg/L, the median OS of relatively normal and abnormal groups were 37.25 (95% CI 31.45-43.06) and 32.55 (95% CI 26.26-38.83) months, respectively (P=0.142).</p><p><b>CONCLUSION</b>High level of β₂-MG and renal function correlated with shorter survival of MM patients. Higher level of β₂-MG with abnormal renal function can't change the prognostic value of β₂-microglobulin on MM.</p>

Curve of labor duration in 2 140 nulliparous women / 中华围产医学杂志

Objective To analyze labor duration in nulliparous women and discuss the change about curve of labor duration. Methods Two thousand, one hundred and forty nulliparous, full-term pregnant, singleton, cephalic presentation and vaginal delivery women who delivered at Peking University First Hospital were included. There were 1 300 cases between January 1, and December 31, 2009, while 840 cases between January 1, and May 31, 2013. A retrospective study was conducted. Data on maternal age, gestational age at delivery, body mass index at delivery, newborn weight, time of labor initiation, cervical dilatation and the amount of bleeding within the first 24 h after delivery were recorded. Data were compared by t test and χ2 test. The median time span corresponding to one-centimeter-increase in cervical dilatation was calculated. Results (1)Compared with data from 2009, the maternal age [(29.0±3.0) vs (29.6±2.8) years, t=4.77], incidence of postpartum hemorrhage [1.8%(24/1 300) vs 4.3%(36/840),χ2=11.17], proportion of induced labor [37.3%(485/1 300) vs 64.0%(538/840),χ2=146.23] and proportion of analgesia during labor [54.2%(705/1 300) vs 61.5% (517/840), χ2=11.15] were all higher in 2013 (all P<0.01). (2)The median (minimum–maximum) time span corresponding to a one-centimeter-increase in cervical dilatation was 3-4 cm which corresponded to 2.2 h(0.8-4.3 h), 4-5 cm which corresponded to 1.9 h(0.6-4.0 h), 5-6 cm which corresponded to 1.8 h(0.5-4.0 h), 6-7 cm which corresponded to 1.6 h(0.5-2.0 h), 7-8 cm which corresponded to 1.8 h(0.8-2.0 h), 8-9 cm which corresponded to 1.3 h(0.2-2.5 h), and 9-10 cm which corresponded to 0.6 h(0.1-2.5 h). The curve of labor duration showed a slow uptrend with time on the horizontal axis and cervical dilatation on the vertical axis. Conclusions The curve of labor duration exhibits a slow uptrend with neither an acceleration phase nor a deceleration phase. It is important to redefine the time span of labor duration in China for appropriate clinical treatment.

Molecular cytogenetic pathogenesis of multiple myeloma: reports in the 55th ASH annual meeting / 白血病·淋巴瘤

The effect of molecular cytogenetics in pathogenesis of multiple myeloma (MM) is fundamental.The risk stratification system that based on molecular cytogenetics of MM is widely applicable in the prognosis of MM.The aberration of molecular cytogenetics is the most important marker of MM.At the same time,high-risk MM is associated with intra-clonal tumor heterogeneity and clonal evolution.The research of intra-clonal tumor heterogeneity and clonal evolution which based on the aberration of molecular cytogenetics will provide some additional information of the biology of MM and contribute to the optimum treatment for MM patients.

The relationship between C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma / 中华内科杂志

Objective To explore the association of C20orf54 gene rs3746804 position single nucleotide polymorphism and susceptibility to esophageal squamous cell carcinoma (ESCC).Methods Purification of genomic DNA from whole blood was used the Maxwell(R) 16 System.rs3746804 in C20ort54 was detected by direct sequencing in 434 ESCC patients from Changzhi (Shanxi province) and Linzhou (Henan province) and 554 healthy controls from Changzhi,Linzhou and including immigrators from Linzhou to Changzhi.Results For rs3746804,the genotypic frequencies of CT(37.5％ vs 51.0％,37.5％ vs 52.0％),CC (44.2％ vs 34.8％,44.2％ vs 33.0％) in Changzhi ESCC patients showed significant differences with healthy Changzhi controls and the healthy immigrator controls (all P ＜ 0.05),and the frequencies of TT(18.3％ vs 4.1％) and CC (44.2％ vs 54.6％) in Changzhi ESCC patients showed significant differences with Linzhou ESCC patients (all P ＜0.05).The genotypic frequencies of TT (4.1％ vs 15.0％),CT (41.2％ vs 52.0％) and CC(54.6％ vs 33.0％) showed significant differences between Linzhou ESCC patients and the healthy immigrator controls (all P ＜ 0.05),and the frequencies of TT (4.1％ vs 14.1％) and CC (54.6％ vs 34.8％) showed significant differences between Linzhou ESCC patients and Changzhi healthy controls (all P ＜ 0.01).Meanwhile,there were significant differences between ESCC patients (including Changzhi and Linzhou ESCC patients) and healthy controls (including the healthy Changzhi,Linzhou and immigrator controls) in genotypic frequencies of CT(39.2％ vs 48.7％) and CC (48.8％ vs 38.2％) (all P ＜ 0.01).CT and CT + TT genotype could decrease the risk of ESCC compared with the CC genotype (OR =0.630,95％ CI0.481-0.826 ; OR =0.654,95％ CI 0.507-0.844).Conclusion There is a closed relationship between SNP rs3746804 in C20orf54 and susceptibility to ESCC.

A comparison and significance of plasma riboflavin levels in patients with esophageal squamous cell carcinoma versus Linzhou healthy migrants in Changzhi of Shanxi / 中华内科杂志

ObjectiveTo study the relationship between plasma riboflavin levels and esophageal squamous cell carcinoma.Methods We detected and compared plasma concentrations of riboflavin in patients with esophageal squamous cell carcinoma (ESCC) and immigrants of Linzhou living in Changzhi.Plasma riboflavin levels were quantified in 445 ESCC patients,689 healthy control subjects and 347 immigrants of Linzhou living in Changzhi by using enzyme-linked immunosorbent assay.ResultsThe plasma riboflavin levels in patients with ESCC were significantly lower than those in the healthy controls and immigrants of Linzhou living in Changzhi [ (731.69 ± 330.67 ) μg/L vs ( 1090.43 ± 445.08 ) μg/L,(731.69 ± 330.67) μg/L vs ( 897.58 ± 177.78) μg/L,respectively,all P ＜ 0.05 ],and the plasma riboflavin levels of the healthy controls were higher than those in the immigrants of Linzhou living in Changzhi (P ＜ 0.05).ConclusionPatients with ESCC have decreased plasma riboflavin levels as compared with the healthy controls and immigrants of Linzhou living in Changzhi,there exists a lack of riboflavin in ESCC patients,but the specific mechanism needs further study.