Oral arsenic plus imatinib versus imatinib solely for newly diagnosed chronic myeloid leukemia: a randomized phase 3 trial with 5-year outcomes.

PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).

[The Prognostic Value of Prognostic Nutritional Index Combined with D-dimer in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the effects of prognostic nutritional index (PNI) combined with D-dimer on the prognosis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical data of 73 DLBCL patients at initial diagnosis were retrospectively evaluated, and the optimal cut-off point of PNI and D-dimer were determined by ROC curve. The overall survival (OS) rate and progression-free survival (PFS) rate in different subgroups were compared using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis was performed to identify the factors associated with OS. RESULTS: Compared with the low PNI group (PNI<44.775), the high PNI group (PNI≥44.775) had better OS (P =0.022) and PFS (P =0.029), the 2-year OS rates of the two groups were 55.6% and 78.3% respectively (P =0.041). Compared with the high D-dimer group (D-dimer≥0.835), the low D-dimer group (D-dimer<0.835) had better OS (P <0.001) and PFS (P <0.001), the 2-year OS rates of the two groups were 51.4% and 86.8% respectively (P =0.001). Meanwhile, patients in the high PNI+ low D-dimer group had better OS (P =0.003) and PFS (P <0.001) than the other three groups, the 2-year OS rate was statistically different from the other three groups (P <0.05). The multivariate analysis revealed that NCCN-IPI (HR =2.083, 95%CI : 1.034-4.196, P =0.040), PNI (HR =0.267, 95%CI : 0.076-0.940, P =0.040) and PNI+D-dimer (HR =9.082, 95%CI : 1.329-62.079, P =0.024) were the independent risk factors affecting OS in patients with DLBCL. Subgroup analysis showed that PNI, D-dimer, and PNI combined with D-dimer could improve the prognostic stratification in low and low-intermediate risk DLBCL patients. CONCLUSION: High PNI, low D-dimer and combination of high PNI and low D-dimer at initial diagnosis suggest a better prognosis in DLBCL patients.

Frequent Gene Mutations and Their Possible Roles in the Pathogenesis, Treatment and Prognosis of Primary Central Nervous System Lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma with poor prognosis. In recent years, the emergence of genetic subtypes of systematic diffuse large B-cell lymphoma has highlighted the importance of molecular genetics, but large-scale research on the molecular genetics of PCNSL is lacking. Herein, we summarize the frequent gene mutations and discuss the possible pathogenesis of PCNSL. Myeloid differentiation primary response gene 88 (MYD88) and CD79B mutations, which cause abnormal activation of noncanonical nuclear factor-κB, are prominent genetic abnormalities in PCNSL. They are considered to play a major role in the pathogenesis of PCNSL. Other genes, such as caspase recruitment domain family member 11 (CARD11), tumor necrosis factor alpha induced protein 3 (TNFAIP3), transducin (ß)-like 1 X-linked receptor 1, cyclin dependent kinase inhibitor 2A, PR domain zinc finger protein 1, and proviral insertion in murine malignancies 1, are also frequently mutated. Notably, the pathogenesis of immune insufficiency-associated PCNSL is related to Epstein-Barr virus infection, and its progression may be affected by different signaling pathways. The different mutational patterns in different studies highlight the heterogeneity of PCNSL. However, existing research on the molecular genetics of PCNSL is still limited, and further research into PCNSL is required to clarify the genetic characteristics of PCNSL.

[Prognostic Value of A New Risk Stratification Model (R2-ISS) in Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To investigate the significance of a new risk stratification model (R2-ISS) in evaluating the prognosis of newly diagnosed multiple myeloma (MM). METHODS: Clinical data of 116 newly diagnosed MM patients admitted to Lanzhou University Second Hospital from June 2012 to March 2021 were retrospectively analyzed. According to R2-ISS, these patients were divided into four groups: low risk, low-intermediate risk, intermediate-high risk, and high risk. The significance of R2-ISS on prognosis of the patients was analyzed. RESULTS: Survival analysis showed that R2-ISS was associated with progression-free survival (PFS) (P=0.042) and overall survival (OS) (P=0.014). Cox univariate analysis showed that lactate dehydrogenase, serum calcium, serum creatinine, ß2-microglobulin, ISS, R-ISS, R2-ISS, t(4;14), and autologous hematopoietic stem cell transplantation (ASCT) were the influencing factors of OS in newly diagnosed MM patients (all P<0.05). Cox multivariate analysis showed that R-ISS, R2-ISS, and ASCT were independent risk factors affecting OS (all P<0.05). In addition, survival analysis of patients with different R2-ISS showed that ASCT improved PFS and OS. CONCLUSION: R2-ISS has prognostic value for newly diagnosed MM patients, while ASCT can improve the prognosis of patients with different R2-ISS.

Effect of electroacupuncture on cyclic adenosine monophosphate-protein kinase A-vanillic acid receptor subtype 1 of the transient receptor potential/PLK-protein kinase C-vanillic acid receptor subtype 1 of the transient receptor potential pathway based on RNA-seq analysis in prostate tissue in rats with chronic prostatitis/chronic pelvic pain syndrome.

Objective: To investigate the analgesic mechanism of electroacupuncture (EA) in rats with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: Thirty male SD rats were randomly divided into sham group, model group and EA group, with ten rats in each group. The CP/CPPS model was prepared by injecting 50 µL of complete Freund's adjuvant (CFA) into the ventral lobes of the prostate tissue, and the sham group was injected with the same dose of saline. After 14 days of modeling, EA was applied to Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) in the EA group. After four courses, H&E staining was performed to observe the prostate tissue morphology, transcriptome sequencing (RNA-Seq) was performed for each group, and the selected signaling pathways were verified by qRT-PCR. Results: The RNA-Seq analysis results suggested that the analgesic effect of EA on CP/CPPS may be achieved by regulating prostate gene expression, which may be related to multiple biological processes and signaling pathways. qRT-PCR results showed that the vanillic acid receptor subtype 1 of the transient receptor potential (TRPV1), phospholipase C (PLC), protein kinase C (PKC), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were all upregulated in the model group compared to the sham group (p < 0.01). Compared with the model group, TRPV1, PLC, PKC, cAMP, and PKA were all downregulated in the EA group (p < 0.05, p < 0.01). Conclusion: The analgesic mechanism of EA on CP/CPPS may be achieved through modulation of cAMP-PKA-TRPV1/PLC-PKC-TRPV1 signaling pathway.

[A Prognostic Nomogram Based on Response to Bortezomib and BTK Expression for Treatment-Experienced Multiple Myeloma Patients].

OBJECTIVE: To establish a prognostic nomogram based on response to bortezomib and BTK expression for treatment-experienced multiple myeloma patients. METHODS: The Oncomine database was utilized to determine BTK expression, sex, age, albumin, Mayo index, response to bortezomib treatment, follow-up time and survival status in multiple myeloma(MM) patients. Cut-off point for BTK expression was calculated using R software. Univariate and multivariate analyses by Cox proportional hazards regression were then performed. Significant prognostic factors were combined to build a nomogram. The discrimination ability and predictive accuracy of the nomogram were evaluated using the index of concordance (C-index) and calibration curves. RESULTS: Multivariate analysis showed that response to bortezomib, BTK expression and sex were independent risk factors for prognosis. The C-index value of the nomogram made according to the independent risk factors was 0.729 (95%CI, 0.642-0.8164). The calibration curves showed good consistency between predicted and actual survivals for 1-year and 2-year overall survival. CONCLUSION: The proposed nomogram is accurate in predicting the prognosis of patients with MM.

Expression Profiling of L5-S2 Spinal Cord Dorsal Horn in a Rat Model of Chronic Pelvic Pain Syndrome Uncovers Potential Mechanism of Electroacupuncture Mediated Inflammation and Pain Responses.

Purpose: We aim to explore expression profiles of genes in SCDH of CPPS model rat relevant to pain and inflammation by RNA-Seq and to investigate the mechanism of anti-inflammatory and analgesic of EA. Methods: Thirty-six SD male rats were randomly divided into three groups (n = 12): sham operation, model, and EA. The rat CPPS model was established by injecting CFA into the ventral lobes of the prostate. The rats in EA group were treated at Guanyuan (CV4), Zhongji (CV3), Sanyinjiao (SP6) and Huiyang (BL35) for a total of 20 times, with a frequency of 2/100Hz. Mechanical allodynia, H&E staining and ELISA were used to detect the changes of pain threshold and tissue inflammation; RNA-Seq technique was used for profiling gene changes in SCDH and qRT-PCR was used for further validation. Results: Persistent mechanical allodynia and severe tissue inflammatory reaction both occurred in CPPS rats. After EA therapy, the pain sensitivity and inflammatory response of CPPS rats decreased significantly. RNA-Seq identified that a total of 46 DEGs were significantly up-regulated and 65 DEGs down-regulated after EA. GO enrichment showed that EA was mainly reflected in the regulation of the immune system by participating in the regulation of leukocyte, neutrophil cellular processes and cytokine metabolism. KEGG enrichment demonstrated that signal transduction and immune system were the most significant pathways. We further identified that the expressions of Pik3r2, Akt1, and Casp9 were significantly up-regulated and Jak2 and Stat3 down-regulated in the PI3K-AKT/JAK-STAT signal pathway. Conclusion: Our study revealed that immune and inflammatory responses are the main biological events that induce chronic pelvic pain in rats, and EA can exert anti-inflammatory and analgesic effects by regulating the expression of related genes on PI3K-AKT/JAK-STAT signal pathway in SCDH. This study provided putative novel targets of EA, which may have anti-inflammatory and analgesic effects of CPPS.

Retraction: The lnc-SNHG1 Gene Is Overexpressed and Correlates with Increased White Blood Cell Count, Poor Induction Treatment Response, and Poor Survival Profile in Adult Acute Myeloid Leukemia

Objective: Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) is involved in leukemogenesis via mediating multiple pathways. The current study aimed to further explore its clinical roles in disease risk, clinical features, and prognosis in patients with acute myeloid leukemia (AML). Materials and Methods: A total of 161 adult AML patients, 50 patients as a disease control (DC) group, and 50 healthy individuals as a healthy control (HC) group were enrolled and bone marrow mononuclear cells were collected. Subsequently, reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) was performed to measure lnc-SNHG1 expression. Results: Lnc-SNHG1 expression was higher in AML patients than in the DC and HC groups (both p<0.001), with good value in distinguishing AML patients from DC and HC individuals (area under the curve of 0.726 and 0.884, respectively). Moreover, lnc-SNHG1 expression was positively associated with white blood cell (WBC) count (p=0.008) but was not correlated with other clinical features such as cytogenetics, molecular genetics, and risk stratification (all p>0.05). Lnc-SNHG1 expression was also associated with a lower complete remission (CR) rate (p=0.001). Patients with lnc-SNHG1 expression in the fourth quantile had the worst CR rates compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Furthermore, lnc-SNHG1 expression was correlated with unsatisfactory event-free survival (p<0.001) and overall survival (p=0.002), which were worst in patients with lnc-SNHG1 expression in the fourth quantile compared to patients with lnc-SNHG1 expressions in the first, second, and third quantiles (all p<0.05). Conclusion: Lnc-SNHG1 overexpression is associated with elevated WBC count, poor induction treatment response, and poor survival profile in cases of AML and it may serve as a potential indicator for AML.

Nontargeted and targeted metabolomics approaches reveal the key amino acid alterations involved in multiple myeloma.

PURPOSE: Multiple myeloma (MM), a kind of malignant neoplasm of clonal plasma cells in the bone marrow, is a refractory disease. Understanding the metabolism disorders and identification of metabolomics pathways as well as key metabolites will provide new insights for exploring diagnosis and therapeutic targets of MM. METHODS: We conducted nontargeted metabolomics analysis of MM patients and normal controls (NC) using ultra-high-performance liquid chromatography (UHPLC) combined with quadrupole time-of-flight mass spectrometry (Q-TOF-MS) in 40 cases of cohort 1 subjects. The targeted metabolomics analysis of amino acids using multiple reaction monitoring-mass spectrometry (MRM-MS) was also performed in 30 cases of cohort 1 and 30 cases of cohort 2 participants, to comprehensively investigate the metabolomics disorders of MM. RESULTS: The nontargeted metabolomics analysis in cohort 1 indicated that there was a significant metabolic signature change between MM patients and NC. The differential metabolites were mainly enriched in metabolic pathways related to amino acid metabolism, such as protein digestion and absorption, and biosynthesis of amino acids. Further, the targeted metabolomics analysis of amino acids in both cohort 1 and cohort 2 revealed differential metabolic profiling between MM patients and NC. We identified 12 and 14 amino acid metabolites with altered abundance in MM patients compared to NC subjects, in cohort 1 and cohort 2, respectively. Besides, key differential amino acid metabolites, such as choline, creatinine, leucine, tryptophan, and valine, may discriminate MM patients from NC. Moreover, the differential amino acid metabolites were associated with clinical indicators of MM patients. CONCLUSIONS: Our findings indicate that amino acid metabolism disorders are involved in MM. The differential profiles reveal the potential utility of key amino acid metabolites as diagnostic biomarkers of MM. The alterations in metabolome, especially the amino acid metabolome, may provide more evidences for elucidating the pathogenesis and development of MM.

[Clinical Significance of sFLC/MP Level and Light Chain Escape in Patients with Multiple Myeloma Relapse].

OBJECTIVE: To explore the effects of serum free light chain (sFLC) and monoclonal protein (MP) on the efficacy and prognosis of patients with multiple myeloma relapse, and investigate the clinical value of light chain escape (LCE). METHODS: The relationship between sFLC/MP levels and clinical features and outcomes in 71 patients with multiple myeloma after relapse were retrospective analyzed. The patients were divided into MO group, MLC group and LCE group according to different levels of sFLC/MP after relapse. Then the clinical indicators, efficacy, survival after relapse (SAR) and overall survival (OS) of the patients in each group were compared. Meanwhile a paired sample t test was used to analyze the relevant indicators of the patients before and after relapse in LCE group. RESULTS: There were significant differences in ISS stage, the levels of Hb, PLT, ALB, SFLC/MP and the proportion of myeloplasma cells afte relapse (P<0.05). The initial treatment effect of the patients in MO group was better than those in the other groups, and the LCE group was the worst (P<0.05). Comparison of relevant indicators between the patients before and after relapse in LCE group showed that the levels of MP, Hb and PLT decreased significantly, while sFLC, LDH and Cr increased significantly (P<0.05). Multivariate analysis showed that MO was the independent risk factor affecting SAR, while MO and LCE were the independent risk factors affecting OS (P<0.05) of the patients.The average SAR of the patients in MO, MLC and LCE group was 41, 28.6 and 23.5 months (P=0.002), and the average OS was 79.6, 57.9 and 41 months (P<0.001), respectively. The patients in MO group showed longer SAR and OS, while the LCE group was the shortest. CONCLUSION: After relapse, patients only with elevated MP levels have a better curative effect and prognosis, while only with elevated sFLC levels have poor curative effects and prognosis, which suggesting that sFLC/MP levels can be used as a good indicator for predicting the prognosis of multiple myeloma patients.The appearance of LCE indicates disease progression, poor prognosis and early relapse.

Efficacy and safety of daratumumab in the treatment of multiple myeloma: a systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of combination regimens containing daratumumab in patients with multiple myeloma (MM). METHODS: A systematic search of publications listed on electronic databases (PubMed®, The Cochrane Library, Science Direct and Web of Science) between inception and 13 November 2020 was conducted to find randomized controlled trials (RCTs) that included patients with MM that were treated with combination regimens containing daratumumab. RESULTS: A total of seven RCTs were included (n = 4268 patients). Meta-analysis showed that compared with the control group, the group containing daratumumab showed a significantly better overall response rate and a complete response or better. Daratumumab improved efficacy in both standard-risk and cytogenetically high-risk patients with MM. The prevalence of neutropenia (≥grade 3) and pneumonia was significantly higher in the daratumumab group compared with the control group. CONCLUSION: The available evidence demonstrated that the clinical application of combination regimens containing daratumumab improved the efficacy in patients with MM and had acceptable safety.

Correlation analysis of long non-coding RNA TUG1 with disease risk, clinical characteristics, treatment response, and survival profiles of adult Ph- Acute lymphoblastic leukemia.

BACKGROUND: Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) is reported to be involved in the progression and development of several malignancies; however, its role in Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) is unknown. The present study aimed to explore the correlation of lncRNA TUG1 with disease risk, disease condition, and prognosis of adult Ph- ALL. METHODS: Total 101 adult Ph- ALL patients and 40 bone marrow (BM) donors were included, followed by detection of BM monocyte cell lncRNA TUG1 expression by reverse transcription-quantitative polymerase chain reaction. According to the quantiles of lncRNA TUG1 expression in Ph- ALL patients, these patients were divided into four tiers: tier 1 (ranked in 0%~25%), tier 2 (ranked in 25%~50%), tier 3 (ranked in 50%~75%), and tier 4 (ranked in 75%~100%). RESULTS: LncRNA TUG1 was upregulated in Ph- ALL patients compared with healthy donors. Further analysis indicated that in Ph- ALL patients, higher lncRNA TUG1 tier was correlated with the presence of central nervous system leukemia, increased white blood cell level, and bone marrow blasts. Furthermore, higher lncRNA TUG1 tier was negatively associated with complete remission (CR) within 4 weeks, total CR, and allogeneic hematopoietic stem cell transplant achievement. In addition, higher lncRNA TUG1 tier was associated with decreased disease-free survival and overall survival, which was further verified to be an independent factor by Cox's regression analysis. CONCLUSION: lncRNA TUG1 presents potential to be a novel biomarker for disease risk assessment and survival surveillance in Ph- ALL management.

[The Influence of CONUT Score on the Prognosis of Patients with Multiple Myeloma].

OBJECTIVE: To explore the influence of controlling nutritional status (CONUT) score on the prognosis of newly diagnosed patients with multiple myeloma (MM). METHODS: The clinical data 119 patients with MM who were diagnosed according to the international myeloma diagnostic criteria in Lanzhou University Second Hospital from April 2010 to October 2018 were collected and retrospectively analyzed. The relationship between clinical indexes, including age, sex, MM type, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), absolute monocyte count (AMC), hemoglobin (Hb), platelet (PLT), ß2-microglobulin (ß2-MG), lactate dehydrogenase (LDH), albumin (ALB), globulin (GLO), cholesterol (CHO), serum creatinine (Scr), etc, and CONUT score was discussed to explore the prognostic value of these indicators. SPSS 25.0 software was used for statistical analysis. Progression-free survival(PFS) and overall survival (OS) between different subgroups were calculated by Kaplan-Meier curves and difference between survival curves was detected by Log-rank tests. Receiver operating characteristic (ROC) curve was used to estimate the most discriminative cutoff value of CONUT score for predicting OS. Mann-Whitney U test was used for non-parametric samples, and chi-square test for categorical variables. Univariate and multivariate analysis were performed by using COX proportional hazards model to identify factors associated with OS. RESULTS: Compared with high-scoring group, low-scoring group had a better OS ï¼»median OS was 43.3 months and 127.67 months, respectively, 95% confidence interval (CI): 57.065-78.345, P=0.038ï¼½. At the same time, the low-scoring group also had higher level of ALC, ANC, AMC, Hb, PLT, ALB, and CHO but lower of GLO. Multivariate survival analysis showed that age (HR=1.027, 95%CI: 1.000-1.054, P=0.048), AMC (HR=11.284, 95%CI: 22.968-42.897, P<0.001), CONUT score (HR=1.198, 95%CI: 1.036-1.385, P=0.015), M protein (non-IgG/IgG type) type (HR=0.503, 95%CI: 0.259-0.977, P=0.043) were independent factors affecting the prognosis of MM patients. CONCLUSION: The CONUT score as an immune-nutrition score is a convenient and easy-to-obtain index to effectively predict the prognosis of MM patients.

Chidamide induces long-term remission in rare subcutaneous panniculitis-like T-cell lymphoma: An unusual case report and literature review.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare primary cutaneous lymphoma composed of CD8+ cytotoxic T-cell that is primarily localized in the subcutaneous tissue. No standard treatments are currently available for SPTCL due to its rarity. Chemotherapy, radiotherapy, immunosuppressive agents, and hematopoietic stem cell transplantation (HSCT) have been used frequently, however, the effects of these treatment approaches remain controversial. In this report, we present an unusual case of SPTCL in a 47-year-old woman whose initial symptoms were atypical. The patient was started on etoposide, vincristine, cyclophosphamide, doxorubicin, and prednisone (EPOCH) chemotherapy once diagnosed. After two cycles of chemotherapy, her clinical symptoms were not significantly improved. Subsequently, histone deacetylase (HDAC) inhibitor chidamide was added to the chemotherapy from the third cycle. She recovered gradually and achieved complete remission (CR) after four cycles of chemotherapy combined with chidamide, followed by chidamide monotherapy for maintenance. More than 1 year after the therapy, she remained in CR. Our case illustrates, for the first time, chidamide can be an effective agent to induce long-term remission for rare SPTCL.

YF-H-2015005, a CXCR4 Antagonist, for the Mobilization of Hematopoietic Stem Cells in Non-Hodgkin Lymphoma Patients: A Randomized, Controlled, Phase 3 Clinical Trial.

Background: YF-H-2015005, a novel CXCR4 antagonist, has been proven to increase the quantities of circulating hematopoietic stem cells (HSCs), which results in an adequate collection of HSCs in non-Hodgkin lymphoma (NHL) patients. Methods: This was a multicenter, double-blind, randomized (1:1), placebo-controlled phase III clinical trial. All patients received granulocyte colony-stimulating factor (G-CSF) for up to 8 consecutive days. YF-H-2015005 or placebo was administrated on the evening of day 4 and continued daily for up to 4 days. Apheresis was conducted 9-10 h after each dose of YF-H-2015005 or placebo. The primary endpoint was the proportion of NHL patients procuring ≥5 × 106/kg CD34+ HSCs within ≤4 apheresis sessions. Results: In total, 101 patients with NHL were enrolled. The proportions of patients achieving primary endpoint were 57 and 12% in YF-H-2015005 and placebo groups, respectively (P < 0.001). Moreover, a higher proportion of YF-H-2015005-treated patients reached a minimum target collection of ≥2 × 106/kg CD34+ HSCs in ≤4 apheresis days compared to placebo-treated patients (86 vs. 38%, P < 0.001). Furthermore, the median time to collect ≥2 or 5 × 106/kg CD34+ HSCs were 1 and 3 days in YF-H-2015005-treated patients, but 4 days and not reached in placebo-treated patients, respectively. No severe treatment emergent adverse events were observed in both YF-H-2015005 treatment and placebo groups. Conclusions: YF-H-2015005 plus G-CSF regimen was a tolerable combination with high efficacy, which might be used to rapidly mobilize and collect HSCs in NHL patients.

Chemokine receptor CXCR4: An important player affecting the molecular-targeted drugs commonly used in hematological malignancies.

INTRODUCTION: A variety of molecular-targeted drugs have been widely used in hematological malignancies and have shown great advances. Nevertheless, as the use of drugs in clinical practice increases, the problem of relapse or of the disease being refractory to treatment is becoming apparent. This problem is closely related to the C-X-C chemokine receptor 4 (CXCR4). AREAS COVERED: This review focuses mainly on the effect of CXCR4 on molecular-targeted drug resistance in hematological malignancies as well as the clinical efficacy of CXCR4 antagonists combined with molecular-targeted drugs. Relevant literatures published between 2006 and 2020 were searched using PubMed/Medline for this review. EXPERT OPINION: Monoclonal antibodies and non-antibody molecular-targeted drugs provide new therapeutic approaches for B-lineage malignancies and leukemia, but the clinical activity of these drugs is affected by CXCR4. In general, high CXCR4 expression or mutation inhibits the effects of molecular-targeted drugs, but there are exceptions, and in studies of proteasome inhibitors bortezomib (Bz) in multiple myeloma (MM), low CXCR4 expression or loss of CXCR4 was associated with Bz resistance (BzR) and poor treatment outcomes. Given that CXCR4 is a critical mediator of molecular-targeted drug resistance, numerous studies have combined molecular-targeted drugs with CXCR4 antagonists, which synergistically enhance the anti-proliferative/pro-apoptotic effect of molecular-targeted drugs.

[IL-1ß and TNF-α up-regulate the expression of glial cell line-derived neurotrophic factor (GDNF) and down-regulate its receptors in rat intestinal smooth muscle cells].

Objective To observe the effects of interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α) on glial cell line-derived neurotrophic factor (GDNF) and its receptors in rat intestinal smooth muscle cells (ISMCs). Methods ISMCs were isolated by modified enzyme digestion in SD rats, and the positive rates of smooth muscle α-actin (α-SMA) and desmin were observed by immunocytochemical staining. ISMCs were treated with IL-1ß and TNF-α for 48 hours alone or in combination. The relative mRNA expression of GDNF, receptor tyrosine kinase (Ret) and GDNF family receptor alpha-1 (GFRα1) were measured by real-time quantitative PCR. Results High-purity ISMCs were obtained by modified enzyme digestion, and over 95% of the cells expressed α-SMA and desmin. Compared with the control group, TNF-α could promote the expression of GDNF and inhibit GFRα1, but had no effects on Ret. In contrast, IL-1ß could inhibit Ret but had no effects on GDNF and GFRα1. Notably, when IL-1ß and TNF-α were combined, the expression of GDNF was up-regulated, while RET and GFRα1 were down-regulated. Conclusion IL-1ß and TNF-α can up-regulate the expression of GDNF and down-regulate its receptors in rat ISMCs.

Clonal evolution of AML1-ETO coexisting with BCR-ABL and additional chromosome abnormalities in a blastic transformation of chronic myeloid leukemia.

Blast crisis develops in a minority of patients with chronic myeloid leukemia even in the era of tyrosine kinase inhibitor (TKI) therapy. Reports suggest that we know little about the mechanism of BCR-ABL and AML1-ETO co-expression in blast crisis of chronic myeloid leukemia, and that other chromosomal abnormalities also coexist. Here, we document an unusual and interesting case of a 51-year-old female diagnosed in the chronic phase of chronic myeloid leukemia. After undergoing TKI treatment for 3 months, her bone marrow aspirates in the chronic phase had transformed to blast crisis. Molecular genetic testing indicated she was positive for p210 form of BCR-ABL (copy number decreased from 108.91% to 56.96%) and AML1-ETO fusion (copy number, 5.65%) genes and had additional chromosomal abnormalities of t(8; 21)(q22; q22)/t(9; 22)(q34; q11), t(2; 5)(p24; q13) and an additional +8 chromosome.

[Value of Red Blood Cell Distribution Width and Fibrinogen Level for Evaluation of the Therapeutic Efficacy and Prognosis in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the value of red blood cell distribution width (RDW) and fibrinogen (Fib) level for the evaluation of therapeutic efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The relationship between RDW/Fib at initial diagnosis and efficacy and the clinical outcome was retro-spectively analyzed based on the study of 105 patients with DLBCL. The patients were divided into two groups: low RDW group (≤15%) and high RDW group (>15%), low Fib group (Fib≤4 g/L) and high Fib group (Fib>4 g/L) according to the normal values of RDW and Fib. Therapeutic efficacy, overall survival (OS) time and progression free survival (PFS) time were compared between two groups. The correlation between each factors and efficacy, prognosis was analyzed by univariate and multivariate regression. RESULTS: The therapeutic efficacy (P<0.001), OS time(P=0.004), and PFS time(P=0.007) were poorer in the high RDW group as compared with the low RDW group. The efficacy (P=0.015) and PFS time(P=0.04) were poorer in the high Fib group as compared with the low Fib group. Multivariate analysis showed that high RDW was the independent risk factor for efficacy of DLBCL patients (OR=3.394, 95% CI 1.093-10.539, P=0.035). CONCLUSION: High RDW and high Fib associate with poor efficacy in DLBCL patients.