Central nervous system involvement in chronic lymphocytic leukemia: a case report and review of literature.

BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.

Efficacy of chidamide maintenance therapy versus autologous stem cell transplantation versus observation as a post-remission choice in the survival of adult patients with peripheral T-cell lymphoma: Post hoc analysis of a prospective, multicenter, phase 2 study in China.

In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .

Research on Deformation Prediction of VMD-GRU Deep Foundation Pit Based on PSO Optimization Parameters.

As a key guarantee and cornerstone of building quality, the importance of deformation prediction for deep foundation pits cannot be ignored. However, the deformation data of deep foundation pits have the characteristics of nonlinearity and instability, which will increase the difficulty of deformation prediction. In response to this characteristic and the difficulty of traditional deformation prediction methods to excavate the correlation between data of different time spans, the advantages of variational mode decomposition (VMD) in processing non-stationary series and a gated cycle unit (GRU) in processing complex time series data are considered. A predictive model combining particle swarm optimization (PSO), variational mode decomposition, and a gated cyclic unit is proposed. Firstly, the VMD optimized by the PSO algorithm was used to decompose the original data and obtain the Internet Message Format (IMF). Secondly, the GRU model optimized by PSO was used to predict each IMF. Finally, the predicted value of each component was summed with equal weight to obtain the final predicted value. The case study results show that the average absolute errors of the PSO-GRU prediction model on the original sequence, EMD decomposition, and VMD decomposition data are 0.502 mm, 0.462 mm, and 0.127 mm, respectively. Compared with the prediction mean square errors of the LSTM, GRU, and PSO-LSTM prediction models, the PSO-GRU on the PTB0 data of VMD decomposition decreased by 62.76%, 75.99%, and 53.14%, respectively. The PTB04 data decreased by 70%, 85.17%, and 69.36%, respectively. In addition, compared to the PSO-LSTM model, it decreased by 8.57% in terms of the model time. When the prediction step size increased from three stages to five stages, the mean errors of the four prediction models on the original data, EMD decomposed data, and VMD decomposed data increased by 28.17%, 3.44%, and 14.24%, respectively. The data decomposed by VMD are more conducive to model prediction and can effectively improve the accuracy of model prediction. An increase in the prediction step size will reduce the accuracy of the deformation prediction. The PSO-VMD-GRU model constructed has the advantages of reliable accuracy and a wide application range, and can effectively guide the construction of foundation pit engineering.

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis.

Bruton's tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5-63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Efficacy of systematic voice training combined with swallowing function exercises for the prevention of swallowing dysfunction in stroke patients: a retrospective study.

Background: Stroke is a common clinical brain disease, and swallowing dysfunction is one of the most common complications in stroke patients. Despite multiple treatments for swallowing dysfunction, it often leads to a series of complications. Interventions such as systematic voice training and swallowing function exercises have emerged in recent years, but their effectiveness remains unclear. Therefore, this study was conducted to investigate the effect of systematic voice training combined with swallowing function exercise for the prevention of swallowing dysfunction and improving the quality of life of stroke patients. Methods: We retrospectively analyzed 90 stroke patients admitted to Baotou Central Hospital from October 2018 to October 2021 as study subjects, and divided the patients into a combined voice training group (n=45) and a single swallowing exercise group (n=45) according to the interventions. The single swallowing exercise group received routine swallowing function exercise, and the combined voice training group used systematic voice training combined with swallowing function exercise. The incidence of swallowing dysfunction, malnutrition, aspiration pneumonia, and exercise compliance rate were compared between the two groups, and the quality of life of the two groups was evaluated by the Generic Quality of Life Inventory 74 (GQOLI-74) before and after the interventions, respectively. Results: The incidence of swallowing dysfunction, aspiration pneumonia, and malnutrition were lower in the combined voice training group than in the single swallowing exercise group (P<0.05), and there was no statistically significant difference in the exercise compliance rate between the two groups. The combined voice training group had higher psychological dimensions, physical dimensions, social adaptation, and total quality of life scores than the single swallowing exercise group (all P<0.05). Compared with the conventional intervention group, the combined voice training group had higher patient satisfaction (P<0.05). Conclusions: Systematic voice training combined with swallowing function exercise can effectively prevent the occurrence of swallowing dysfunction and improve the quality of life of patients with stroke.

Comprehensive geriatric assessment in newly diagnosed older myeloma patients: a multicentre, prospective, non-interventional study.

BACKGROUND: Multiple myeloma is a disease of the older people, whose prognoses are highly heterogeneous. The International Myeloma Working Group (IMWG) proposed a geriatric assessment (GA) based on age, functional status and comorbidities to discriminate between fit and frail patients. Given the multidimensional nature of frailty and the relatively recent exploration of frailty in the field of MM, reaching a consensus on the measurement of frailty in MM patients remains challenging. OBJECTIVE: We sought to assess the feasibility of performing a comprehensive GA (CGA) in older MM patients in a real-world and multicentre setting and to evaluate their baseline CGA profiles. RESULTS: We studied 349 older patients with newly diagnosed MM (age range, 65-86 years). Our results showed that a CGA is feasible for older MM patients. Using the IMWG-GA criteria, we identified significantly more frail patients in our cohort comparing to in the IMWG cohort (43% vs 30%, P = 0.002). In the IMWG-GA 'fit' group, risk of malnutrition, depression and cognitive impairment remains. The median follow-up time was 26 months (range 1-38). The median overall survival (OS) was 34.7 months, and the estimated 3-year OS rate was 50%. A high MNA-SF score (MNA-SF ≥ 12), low GDS score (GDS ≤ 5) and high CCI score (CCI ≥ 2) can be used to predict the OS of older patients with newly diagnosed MM. This study is registered at www.clinicaltrials.gov (NCT03122327). CONCLUSIONS: Our study justifies the need for a CGA in older patients with newly diagnosed MM.

Identification of miRNA-34a and miRNA-155 as prognostic markers for mantle cell lymphoma.

OBJECTIVE: MicroRNAs (miRNAs) with functional relevance have not been previously identified in mantle cell lymphoma (MCL). Here, we aimed to evaluate the relationships between miR-34a and miR-155-5p and MCL clinicopathology and prognosis. METHODS: Seventy-five paraffin-embedded tissue samples from patients with MCL who completed at least four cycles of chemotherapy from January 2006 to October 2016, and 27 samples from control patients with reactive lymphoid hyperplasia (RLH), were collected. MiRNA expression levels were measured by qRT-PCR. RESULTS: The miR-155-5p levels were significantly higher in patients with MCL than in the controls. The Eastern Cooperative Oncology Group (ECOG) ≥ 2 and Sex-Determining Region Y-Box transcription factor 11 (SOX11) < median value (M) groups presented lower miR-34a expression than the ECOG < 2 and SOX11 ≥ M groups, respectively. MiR-155-5p expression differed between low, intermediate, and high MCL International Prognostic Index risk groups. The AUCs of miR-34a and miR-155-5p were 0.5819 and 0.7784, respectively. The median survival times of the miR-34a ≤ 0.2150 and miR-155-5p > 2.11 groups were shorter than those of the miR-34a > 0.2150 and miR-155-5p ≤ 2.11 groups, respectively. CONCLUSIONS: Low miR-34a and elevated miR-155-5p levels may be correlated with poor prognosis in MCL.

The combination of chidamide with the CHOEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study.

OBJECTIVE: To assess the efficacy and safety of the novel histone deacetylase inhibitor, chidamide, in combination with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (Chi-CHOEP) for untreated peripheral T-cell lymphoma (PTCL). METHODS: A prospective, multicenter, single arm, phase 1b/2 study was conducted. A total of 128 patients with untreated PTCL (18-70 years of age) were enrolled between March 2016 and November 2019, and treated with up to 6 cycles with the Chi-CHOEP regimen. In the phase 1b study, 3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximum-tolerated dose and recommended phase 2 dose (RP2D). The primary endpoint of the phase 2 study was 2-year progression-free survival (PFS). RESULTS: Fifteen patients were enrolled in the phase 1b study and the RP2D for chidamide was determined to be 20 mg, twice a week. A total of 113 patients were treated at the RP2D in the phase 2 study, and the overall response rate was 60.2%, with a complete response rate of 40.7%. At a median follow-up of 36 months, the median PFS was 10.7 months, with 1-, 2-, and 3-year PFS rates of 49.9%, 38.0%, and 32.8%, respectively. The Chi-CHOEP regimen was well-tolerated, with grade 3/4 neutropenia occurring in approximately two-thirds of the patients. No unexpected adverse events (AEs) were reported and the observed AEs were manageable. CONCLUSIONS: This large cohort phase 1b/2 study showed that Chi-CHOEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

Effects of Twist1 on drug resistance of chronic myeloid leukemia cells through the PI3K/AKT signaling pathway.

This study aimed to investigate the effects of Twist1 on the drug resistance of chronic myeloid leukemia (CML) cells through the PI3K/AKT signaling pathway. K562 and KCL-22 cells were modeled for imatinib resistance, so as to analyze the effects of inhibiting Twist1 and the pathway on the therapeutic effect of imatinib on imatinib-resistant CML cells, and to find the mechanism of action of Twist1 on affecting the resistance. After the CML cells were successfully resistant to imatinib, Twist1 expression increased again in the cells and the PI3K/AKT signaling pathway was further activated. After the silence of the Twist1 expression, the imatinib-resistant CML cells were more sensitive to imatinib, and the PI3K/AKT signaling pathway was inhibited, and the expression level of p-AKT protein significantly reduced. According to further experiments, imatinib enhanced its inhibitory effect on the growth of the imatinib-resistant CML cells after the activation of the pathway was inhibited by an LY3023414 inhibitor. In conclusion, Twist1 and the PI3K/AKT signaling pathway are over-activated during the formation of the CML cells resistant to imatinib. The silence of Twist1 can reverse the resistance through the pathway.

Elevated SOX11 mRNA level correlates with favorable prognosis in mantle cell lymphoma.

PURPOSE: To explore the prognostic value of SOX11 in patients with mantle cell lymphoma (MCL). METHODS: The clinical data and paraffin-embedded tissue of 75 primary MCL in Shanxi Tumor Hospital were collected, and the MCL international prognostic index (MIPI) was rechecked in all cases according to simplified (sMIPI) formula. The expression of SOX11 mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and the relationship of survival with SOX11 mRNA and MIPI in MCL patients was evaluated. RESULTS: Median survival was 44 months in cases with low-risk, 31 months in cases with intermediate-risk and 30 months in cases with high-risk. There was statistically significant difference between low-risk and high-risk group (p=0.0033), while there was no statistical difference between low-risk group and intermediate-risk group (p=0.1067) and the intermediate-risk group and high-risk group (p=0.6149). Furthermore, cases were divided into group SOX11mRNA

Autologous peripheral blood stem cell transplantation in children and adolescents with non-Hodgkin lymphoma.

The aim of this study was to evaluate the effect and safety of autologous peripheral blood stem cell transplantation (APBSCT) in children and adolescents with non-Hodgkin lymphoma (NHL). Ten patients with NHL were analyzed retrospectively. In all the patients, lymph node enlargement was most frequently detected. Patients with a mediastinal mass presented with a cough, palpitation and shortness of breath. Extranodal patients presented with abdominal pain, inability to walk and vaginal bleeding. All patients underwent APBSCT with conditioning regimens BEAM or BuCy. Among them, four patients with B-cell NHL received rituximab in addition to the conditioning regimen. Hematopoietic reconstitution was observed in all patients. Severe toxicity and transplant-related mortality were not observed. Prior to APBSCT, nine patients with a status of complete response (CR) and CR unconfirmed achieved continuing complete remission. Only one patient with partial response succumbed to progressive disease. APBSCT in children and adolescents with NHL is a safe, convenient and efficient treatment. The BEAM conditioning regimen was shown to be effective and tolerable for children and adolescents with NHL. Rituximab is a safe agent in the transplantation. The CR status at the time of transplantation demonstrated a higher survival rate.

Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

[Significance of myc gene rearrangement and its correlation with prognosis in diffuse large B cell lymphoma].

OBJECTIVE: To study the relationship between myc gene rearrangement and myc protein expression in diffuse large B cell lymphoma (DLBCL), and their correlation with prognosis. METHODS: One hundred and six cases of DLBCLs with follow-up data were analyzed using interphase fluorescence in situ hybridization (FISH) technique. Immunophenotyping analysis for CD20, CD3, myc, Mum-1, CD10, bcl-6 was also performed using EnVision immunohistochemistry. RESULTS: The percentages of tumor cells expressing myc, Mum-1, CD10 and bcl-6 were 70.8%, 56.6%, 21.7% and 26.4%, respectively. Twenty six cases (24.5%) were of GCB type and the rest (75.5%) were of non-GCB (non germinal center) type. The myc rearrangement was identified in 13 (12.3%) of 106 cases. 13 cases showed to be of non-GCB type. There was no correlation between myc rearrangement and myc protein expression. DLBCLs (n = 13) with myc rearrangement showed significantly poorer overall survival (OS) and progression free survival (PFS), with a median OS and PFS time of 4.7 and 3.2 months, respectively (for OS and PFS, P < 0.001). Multivariate analysis using Cox proportional hazard model confirmed that myc rearrangement, ECOG performance status of 2-4, immunophenotyping subgroup and myc protein were independent factors affecting the prognosis and significantly associated with the survival. However, myc rearrangement was the strongest prognostic factor. CONCLUSIONS: DLBCL with myc gene rearrangement is a subgroup of non-GCB DLBCL with poor outcome. It is an independent and useful factor for prognosis in DLBCL. Expression of myc is influenced by many factors and myc rearrangement may be one of these factors.

The clinical study of extranodal natural killer cell lymphoma, nasal type.

To analyze the clinical characteristics, treatment of extranodal NK/T-cell lymphoma, nasal type, the term "nasal type" describes in the nasal cavity and also in the extranasal sites. There were 82 patients with nasal NK/T lymphoma (group 1) and 11 patients with extranasal NK/T lymphoma (group 2). In group 1, 4 patients gave up treatment. Five patients received radiotherapy (RT) alone. Fifty-seven patients were treated with combination of chemotherapy and RT. Sixteen patients received chemotherapy alone. Most patients (82.9%) had stage I/II disease and a high frequency (about one-third) of B symptoms. The CR rate was 53.8%. The OS rate was 62.8% (49/78 cases). Three patients died in relation to L-asparaginase. Three patients with late relapses occurred at 10 and 17 years from CR, respectively. In group 2, except that one patient received chemoradiotherapy, 10 patients received chemotherapy. Seven patients died. The OS rate was 36.4%. Our study suggested that nasal and extranasal variants of extranodal NK/T lymphoma, nasal type represented different clinical behavior and prognosis. For comparison, extranasal NK/T lymphoma is more aggressive and higher mortality than nasal NK/T lymphoma.