[Prognostic Value of Pre-treatment Albumin/Fibrinogen Ratio in Patients with Diffuse Large B-cell Lymphoma].

OBJECTIVE: To investigate the value of pre-treatment albumin/fibrinogen ratio (AFR) on the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of DLBCL patients in the Affiliated Hospital of North Sichuan Medical College from April 2014 to March 2021 were retrieved, and 111 newly diagnosed patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with complete data were included in the study. The clinical, laboratory examination and follow-up data of the patients were collected, and the receiver operating characteristic curve (ROC) was drawn according to patients' AFR before treatment and the survival status at the end of the follow-up, which could be used to preliminarily evaluate the predictive value of AFR for disease progression and patients' survival outcome. Furthermore, the correlation of AFR with the clinical and laboratory characteristics, progression-free survival (PFS) and overall survival (OS) was analyzed, and finally, univariate and multivariate Cox proportional hazard regression models were used to analyze factors affecting PFS and OS of DLBCL patients. RESULTS: The ROC curve indicated that AFR level had a moderate predictive value for PFS and OS in DLBCL patients, with the area under the curve (AUC) of 0.616 (P =0.039) and 0.666 (P =0.004), respectively, and the optimal cut-off values were both 9.06 for PFS and OS. Compared with high-AFR (≥9.06) group, the low-AFR (<9.06) group had a higher proportion of patients with Lugano III-IV stage ( P <0.001), elevated lactate dehydrogenase (P =0.007) and B symptoms (P =0.038). The interim analysis of response showed that the overall response rate (ORR) in the high-AFR group was 89.7%, which was significantly higher than 62.8% in the low-AFR group (P =0.001). With a median follow-up of 18.5 (3-77) months, the median PFS of the high-AFR group was not reached, which was significantly superior to 17 months of the low-AFR group (P =0.009). Similarly, the median OS of high-AFR group was not reached, either, which was significantly superior to 48 months of the low-AFR group (P < 0.001). In multivariate Cox regression analysis, AFR <9.06 was an independent risk factor both for PFS and OS (HR PFS=2.047, P =0.039; HR OS=4.854, P =0.001). CONCLUSION: Pre-treatment AFR has a significant value for the prognosis evaluation in newly diagnosed DLBCL patients.

Microstructural Evolution of SK85 Pearlitic Steel Deformed by Heavy Cold Rolling.

The microstructural evolution of SK85 pearlitic steel cold-rolled up to a 90% rolling reduction was characterized by scanning electron microscopy with electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). SK85 steel exhibits excellent cold rolling performance. The interlamellar spacing of pearlite is refined obviously and a tensile strength of 2318 MPa can be reached for SK85 steel after 90% rolling reduction, an increase of 83% from 1264 MPa before rolling. The EBSD observation indicates that the {001} <110> texture becomes pronounced at a 90% rolling reduction in cold-rolled Sk85 steel. A propagation and multiplication of dislocations occur during rolling as the kernel average misorientation (KAM) angles significantly increase from 0.72° to 2.11°. The XRD analysis reveals that bcc ferrite is transformed into a bct structure at a 90% rolling reduction. The strengthening mechanism was discussed.

[Predictive Value of Pre-treatment Serum Uric Acid Level for Prognosis in Newly Diagnosed Patients with Multiple Myeloma].

OBJECTIVE: To evaluate the predictive value of pre-treatment serum uric acid (sUA) level for the prognosis of newly diagnosed multiple myeloma (NDMM) patients. METHODS: The NDMM patients admitted to our center from January 2014 to December 2018 were analyzed retrospectively, and 94 patients among them who were initially treated with bortezomib-based chemotherapy for at least 4 cycles were included in this study. Clinical characteristics, laboratory data and follow-up information were collected, and the predictive value of sUA on the overall survival (OS) of NDMM was evaluated by using receiver operating characteristic (ROC) curve based on the patient's pre-treatment sUA level and the survival status at the end of follow-up, and the correlation of the sUA level with patient's clinical, laboratory characteristics and overall survival (OS) was further analyzed. The univariate and multivariate Cox proportional-hazards model were used to identify the potential factors affecting OS. RESULTS: ROC analysis showed that the area under the curve for predicting OS in NDMM patients with sUA level was 0.702 (P<0.001), and the optimal cut-off value was 455.4 µmol/L. Compared to patients with low sUA (<455.4 µmol/L), patients with higher sUA (≥455.4 µmol/L) were more likely to have international staging system (ISS) stage III disease, beta2-microglobulin (ß2-MG) ≥5.5 mg/L, serum creatinine (sCr) ≥177 µmol/L, serum corrected calcium (cCa) ≥2.75 mmol/L, urea nitrogen (BUN) ≥1×upper limit of normal, and high-risk cytogenetic abnormality (all with P<0.001). At a median follow-up of 22.5 months, the OS of NDMM with lower sUA was significantly better than higher sUA (median OS: not reached vs 32 months, P=0.003). Univariate COX regression analysis identified that age ≥60 years old, ISS stage III, sUA ≥455.4 µmol/L, ß2-MG ≥5.5 mg/L, cCa ≥2.75 mmol/L were risk factors affecting OS. The multivariate COX regression analysis that only age ≥60 years old (HR=2.317, 95%CI: 1.015-5.288, P=0.045) and sUA ≥455.4 µmol/L (HR=2.785, 95%CI: 1.054-7.361, P=0.039) were independent risk factors affecting OS. CONCLUSION: Pre-treatment sUA level is a potential biomarker for the prognosis evaluation in NDMM patients, which deserves a further exploration and verification.

[Short-Term Efficacy and Safety Profile of Generic Bortezomib in the Treatment of Multiple Myeloma].

OBJECTIVE: To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM). METHODS: Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression. RESULTS: Anemia, renal dysfunction, hypoproteinemia and high level of ß 2-microglobulin were all improved rapidly after induction treatment. In 56 patients who had completed at least 4 cycles of chemotherapy, the overall response rate (ORR) was 85.7%, and 64.3% of the patients achieved very good partial response (VGPR) or better, and 28.6% achieved complete remission (CR) or better. In the 19 patients who had already completed all planned induction and consolidation treatment (9 cycles of chemotherapy or 4-6 cycles of chemotherapy plus autologous hematopoietic stem cell transplantation), 84.2% achieved VGPR or better, and 57.9% achieved CR or stringent complete remission (sCR). Median follow-up time was 300 days with data cut-off date of September 20, 2019, and the progression-free survival (PFS) rate and overall survival (OS) rate were 62.1% and 85.3%, respectively. The possible adverse reactions associated with bortezomib were grade 1-2, the most common hematologic adverse reaction was thrombocytopenia (27.4%), and the most common non-hematologic adverse reaction was peripheral neuropathy (43.5%), followed by asthenia (37.1%). CONCLUSION: The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.

[Effect of High Dose Vitamin C on Proliferation and Apoptosis of Acute Myeloid Leukemia Cells].

OBJECTIVE: To investigate the effects of high dose vitamin C on proliferation and apoptosis of acute myeloid leukemia (AML) cell lines including HL-60, U937 and primary CD34+ leukemia cells in AML. METHODS: CD34+ cells were sorted by using immunomagnetic cell sorting system, then the primary CD34+ leukemia cells, including HL-60 and U937 cell lines were cultured in vitro. Cells in each group were treated with different concentrations of vitamin C, the survival rate of cells was determined by MTT assay, the apoptosis rate of cells was evaluated by Annexin V/PI double staining, the expression of apoptotic proteins-including cleaved caspase 3, cleaved caspase-9 and cleaved PARP were detected by Western blot. RESULTS: The proliferation of HL-60 and U937 cells could be inhibited by high dose vitamin C, which showed a concentration-dependent manner (r=-0.9664; r=-0.9796). HL-60 and U937 cells were treated with different concentrations of vitamin C (8 and 20 mmol/L) for 24 hours, respectively, it was found that with the increasing of vitamin C concentration, cell apoptosis rate was significantly increased (r=0.9905; r=0.9971), and the expression of apoptosis related proteins including cleaved caspase 3, cleaved caspase-9 and cleaved PARP was aslo significantly increased with the increasing of concentration. In addition, it was found that with or without the mutation of TET2, high dose vitamin C could inhibit the proliferation (r=-0.9719; r=-0.9699) and promote the apoptosis (r=0.9998; r=0.9901) of primary CD34+ leukemia cells in AML, which showed a dose-dependent manner, but it showed no effect on the proliferation (r=-0.2032) and apoptosis (r=0.1912) of normal CD34+ cells. CONCLUSION: High dose vitamin C can inhibit the proliferation and promote the apoptosis of acute myeloid leukemia cells, and selectively kill primary CD34+ leukemia cells in AML.

Baseline Red Blood Cell Distribution Width Correlates with Disease Activity and Therapeutic Outcomes in Patients with Systemic Lupus Erythematosus, Irrespective of Anemia Status.

BACKGROUND: Red blood cell distribution width (RDW) has been recently found to reflect systemic inflammation in addition to anisocytosis, and its value for assessing disease activity of systemic lupus erythematosus (SLE) has been addressed in two studies, but its correlation with therapeutic outcomes and disease flare has not been evaluated. METHODS: One hundred and ninety-six newly diagnosed patients with SLE (all-SLE), including 105 non-anemic patients (na-SLE) and 91 patients with anemia (a-SLE) were prospectively studied. Baseline RDW of SLE patients was compared with that of control subjects. Correlations between RDW and disease activity, traditional laboratory parameters, clinical features, therapeutic outcomes, and disease flare were examined. RESULTS: RDW was exclusively higher in all-SLE, na-SLE, a-SLE than in controls (p < 0.001), but no significant difference of RDW was found between na-SLE and a-SLE (p = 0.27). More active disease scored with SLE Disease Activity Index 2000 (SLEDAI-2K) was present in patients with elevated RDW (> 15%) than normal RDW (= 11 - 15%) irrespective of anemia status (p < 0.001), and positive correlation between RDW with SLEDAI-2K was also disclosed independent of anemia status (r = 0.576, 0.614, 0.542, respectively for all-, na- and a-SLE, all with p < 0.001). Additionally, RDW positively correlated with high-sensitivity C-reactive protein (hsCRP) in all-SLE (r = 0.352, p < 0.001), na-SLE (r = 0.430, p < 0.001), and a-SLE (r = 0.315, p = 0.002). Among all clinical features, only the incidence of pulmonary arterial hypertension (PAH) was likely to be higher in elevated-RDW SLE than in normal-RDW SLE (χ2 = 4.135, p < 0.05). Patients received stratified therapy of remission induction based on their disease activity. A significantly higher rate of response (complete and partial response) was observed in normal-RDW than in elevated-RDW patients (all-SLE: 92.2% vs. 74.1%, p = 0.001; na-SLE: 92.3% vs. 77.5%, p = 0.04; a-SLE: 92% vs. 70.7%, p = 0.012). During a 12-month follow-up of the 166 responders, significantly greater flare-free survival was observed in normal-RDW than in elevated-RDW patients (68.8% vs. 29.8%, p = 0.002; 53.6% vs. 28.1%, p = 0.027; 55.9% vs. 31.4%, p = 0.032, respectively, for all-, na- and a-SLE). CONCLUSIONS: Our findings suggest that baseline RDW is an easily available parameter not only capable of reflecting SLE overall activity, but also predicting therapeutic outcomes and the risk of disease flare irrespective of anemia status.

[FLT3 mutation in acute promyelocytic leukemia patients with extramedullary relapse].

OBJECTIVE: To evaluate the role of FLT3 gene mutation in acute promyelocytic leukemia (APL) patients with extramedullary relapse. METHODS: The blood and bone marrow samples were collected from 2 APL patients with extramedullary relapse and FLT3 gene mutation was detected with these samples. The correlation between FLT3 gene mutation and extramedullary relapse was analyzed. RESULTS: A rare point mutation Asn841Gly (A841G) of FLT3-TKD and a novel mutation (c. 1209_1210insT/p. K404X) of WT1 were detected in a APL patient who suffered CNS relapse, while a rare point mutation Asp839Gly (D839G) of FLT3-TKD and a novel mutation Arg458Pro (c. 1373G>C) of WT1 were found in another APL patient who suffered testicular relapse. CONCLUSION: The rare point mutation of FLT3 as well as the novel mutation of WT1 were found in APL with extramedullary relapse.

Acute promyelocytic leukemia with Flt3-TKD and WT1 mutations relapsing in a testicle and followed by systemic relapse.

Extramedullary relapse is a rare phenomenon in patients with acute promyelocytic leukemia (APL), especially that derived from urogenital systems like the testicles. In this report, we describe an APL patient who had received standard induction/maintenance therapy resulting in durable remission for 4.5 years, when he presented with a unilateral testicular mass confirmed as myeloid sarcoma; this was followed by systemic relapse of APL. Retrospective analysis of the involved blood and bone marrow samples at the time of the initial diagnosis revealed a rare point mutation of FLT3-TKD and a novel mutation of WT1. These mutations were detected recurrently throughout the course of the disease. After reinduction therapy with arsenic trioxide and all-trans retinoic acid combined with daunorubicin, complete hematological remission was achieved for the ensuing salvage allogeneic hematopoietic stem cell transplant.

[Expression of tumor suppressor gene pten in patients with myelodysplastic syndrome and acute myeloid leukemia].

To study the expression and significance of pten gene in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), RT-PCR and Western blot were respectively applied to detect pten mRNA and PTEN protein in Jurkat cells (as negative control), in bone marrow nucleated cells of 35 patients with MDS, 45 patients with AML and 20 normal control. The results showed that pten mRNA expression could not be detected in Jurkat cells, and the positive rate in MDS patients (77.1%) was significantly lower than that in normal control group (90.0%) (p > 0.05), while significant difference was found between AML patients and normal control (60.0% vs 90.0%, p < 0.05); the positive rate in MDS-RAEB patients (70.0%) was lower than that in MDS-RCMD (86.7%); positive rate in de novo and relapsed AML patients (53.3%) was lower than that in AML patients in CR (73.3%), but statistics tests did not show significant difference (p > 0.05). The results of relative expression level of pten mRNA in all groups indicated that both relative expression levels in MDS patients and AML patients were definitely lower than that in normal control group (p < 0.005); the relative expression level in MDS-RAEB patients was lower than that in MDS-RCMD patients (p < 0.05); and in de novo and relapsed AML patients was obviously lower than that in AML patients in CR (p < 0.001). However, there was no significant difference between MDS and AML patients (p > 0.05). The positive rate of PTEN protein expression in both MDS (65.7%) and AML (54.8%) patients were lower than that in normal control (90.0%) (p < 0.05), and there was no significant difference when comparing MDS-RCMD patients (80.0%) with MDS-RAEB patients (55.0%) (p > 0.05), but positive rate of PTEN protein expression in de novo and relapsed AML patients (44.4%) was significantly lower than that in AML patients in CR (73.3%) (p < 0.05). It is concluded that the complete loss of pten mRNA in MDS and AML is uncommon, but the relative expression level in both diseases is significantly lower than that in normal people. The positive rates of PTEN protein expression in both MDS and AML patients are lower, compared with normal people, but are not in accordance with the expression of pten mRNA. The abnormalities of pten gene expression may be involved in the pathogenesis of MDS and AML.