Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Clinical features and treatment outcomes of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: a single center retrospective analysis of 64 patients in China.

AIM: To investigate the clinical features, treatment and prognosis of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). METHODS: A retrospective analysis was performed on 64 patients with POAML who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2006 to December 2018. RESULTS: With a median follow-up of 61mo (range, 2-156mo), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10y reached 94.5% and 61.5%, respectively. Median OS time and PFS time were not reached. During this period, only 3 patients died, but none of them died directly due to disease progression. One patient (1.6%) developed transformation to diffuse large B-cell lymphoma (DLBCL). Of the 56 patients achieved complete remission after first-line treatment, 5 (8.9%) developed local and/or systemic relapse eventually. Patients ≥60y had significantly shorter PFS than younger patients (P=0.01). For patients with early stages (Ann Arbor stage I and stage II), univariate analysis confirmed that radiotherapy dose lower than 32 Gy were independently associated with shorter PFS (P=0.04). Other factors including gender, bone marrow involvement, the initial location of the disease, and the laterality were not associated with PFS. CONCLUSION: The data from our center indicate that POAML has a slow clinical progression and has an excellent clinical outcome. Patients with POAML harbor a continual risk of relaps and transformation to aggressive subtype of lymphoma.

Activated hippo signal pathway inhibits cell proliferation and promotes apoptosis in NK/T cell lymphoma cells.

BACKGROUND: Natural Killer T-Cell Lymphoma (NKTCL) is a subtype of Non-Hodgkin's Lymphoma, and its morbidity is ranked the first of T-Cell Lymphoma. Hippo signaling pathway is involved in the pathogenesis of tumors. However, the role of Hippo signaling pathway in the oncogenesis of NKTCL still remains unclear. METHODS: The expressions of mammalian sterile 20-like kinase 1 (MST1) and Yes-associated protein (YAP) were investigated by RT-PCR and Western blotting. Cell viability was detected by MTT assays. Cell cycle and cell apoptosis were determined by flow cytometry. Cell proliferative capacity was detected by colony formation assay. Nude mice xenograft models were established and the tumor sections were analyzed by immunohistochemistry (IHC) staining. RESULTS: The expression of MST1 was significantly down-regulated in NKTCL tissues (n = 30) and cell lines, while the expression of YAP was significantly up-regulated, and the phosphorylation of YAP was inhibited. Overexpression of MST1, knockdown of YAP, or verteporfin (VP) treatment could inhibit cell proliferation, and promote cell cycle arrest and apoptosis in NKTCL cells, while knockdown of MST1 and overexpression of YAP promoted cell proliferation. Additionally, Bcl-2/Bax ratio and downstream effectors of Hippo signaling pathway (c-myc, survivin, cyclinD1, CTGF, and TEAD) were significantly decreased when MST1 was overexpressed and YAP was knocked down or after VP treatment. Furthermore, our mice model demonstrated that activation of Hippo signal pathway suppressed the tumorigenesis of NKTCL. CONCLUSION: The activation of Hippo signal pathway via overexpressing MST1 or down-regulating YAP can inhibit the tumorigenesis of NKTCL.

Drug-induced skin toxicity and clinical nursing of VitK cream on colorectal cancer patients.

To discuss the impact of 0.1% vitamin K1 (VitK1) cream on cetuximab-induced skin toxicity for colorectal cancer patients. 60 colorectal cancer patients with cetuximab therapy after hospitalization, were divided into experimental group (Ward A) and control group (Ward B) according to personnel sequential number, with 30 cases in each group. Routine nursing was implemented on control group. For experimental group, on the routine nursing basis, 0.1% VitK1 cream was smeared on face, neck, chest, back and nail (toenail) edge with three times one day at the application of cetuximab day. After cetuximab applied in 8 weeks, both skin itch and dry skin for patients in experimental group were significantly improved compared those in control group, showing statistically significant difference (W=708.000, P=0.001: W=662. 500, P=0.000). 0.1% VitK1 cream was conducive to improve both skin itch and dry skin symptoms in the cetuximab-induced skin toxicity for colorectal cancer patients.

Fotemustine, teniposide and dexamethasone in treating patients with CNS lymphoma.

PURPOSE: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. PATIENTS AND METHODS: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. RESULTS: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR:38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. CONCLUSION: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

[Experimental study of extract from Prunella vulgaris inducing B, T lymphoma cell apoptosis].

OBJECTIVE: To investigate the effects of extract from Prunella vulgaris on proliferation of human B lymphoma cell line Raji cells anf T lymphoma cell line Jurkat cells and discuss the mechanism. METHODS: Used different concentrations of extract from Prunella vulgaris to treat Raji and Jurkat cells and collected cells after 48 h respectively, the proliferation inhibition rate, the DNA Ladder and the apoptosis rate of Raji and Jurkat cells were examined by MTT assay, agarose gel electrophoresis and flow cytometry respectively; Western blot was used to detect the change of BCL-2, BAX protein. RESULTS: Different concentrations of the extract from Prunella vulgaris could inhibit the proliferation of both Raji and Jurkat cells remarkably (P < 0.01), the IC50 of Raji cells, 18.01 +/- 0.92 microg/mL, was lower than that of Jurkat, the difference was significant statistically (P < 0.05); Apoptosis related DNA Ladder appeared after treated Raji and Jurkat cells with the extract from Prunella vulgaris; Compared with the control group, with the increase of the concentration of the extract from Prunella vulgaris, the early cell apoptosis rate of Raji and Jurkat were all increased,the early cell apoptosis rate of the extract from Prunella vulgaris of 15, 20 and 25 microg/mL treated Raji and Jurkat cells were (9.46 +/- 0.25)%, (21.68 +/- 0.46)%, (35.03 +/- 0.35)% and (4.06 +/- 0.14)%, (13.59 +/- 0.23)%, (22.92 +/- 0.20)% respectively. With the same concentration, the early apoptosis rate of Raji cells was higher than that of Jurkat cells significantly (P < 0.01); Compared with the control group, with the in- crease of the concentration of the extract from Prunella vulgaris, the expression of BCL-2 protein was down-regulated and BAX up-regulated, With the same concentration, the decline degree of BCL-2 protein expression and the increase degree of BAX protein expression in Raji cells was more remarkable than that in Jurkat cells, the difference was significant (P < 0.05). CONCLUSION: The extract from Prunella vulgaris can inhibit the proliferation of lymphoma cells and the inhibition is realized by inducing apoptosis, the mechanism of inducing cell apoptosis with extract from Prunella vulgaris is probably related with the BAX and BCL-2 protein expression, the inhibition effect on Raji cells is greater than that of Jurkat cells.

[Study on proteomics of Jurkat cells treated with the extracts from Prunella vulgaris].

OBJECTIVE: To analyse the differential proteins of Jurkat cells after treated with the extracts from Prunella vulgaris using two-dimensional electrophoresis and mass spectrum. METHODS: Jurkat cell growth inhibitive effect of the extracts from Prunella vulgaris was analyzed by MTT assay. The total proteins of the cells were extracted after treated with the extracts in a dose of 20 microg/mL. Then 2D and MALDI-TOF-MS were used to assess the differential proteins. RESULTS: The extracts from Prunella vulgaris could depress the proliferation of Jurkat cells in a dose-dependent manner. After 2-DE and MALDI-TOF-MS,11 proteins were identified successfully, including glyceraldehyde-3-phosphate dehydrogenase, coagulation factor VII, Heterogeneous nuclear ribonucleoprotein L, heat shock 70 kDa protein 8 isoform 2, immunoglobulin heavy chain variable region, heterogeneous nuclear ribonucleoprotein A2/B1, zinc finger protein 43, chaperonin containing TCP1, subunit 6A (zeta 1), isoform CRA_b, etc. CONCLUSION: The extracts from Prunella vulgaris could inhibit the growth of Jurkat cells significantly, and lead the proteomics change of Jurkat cells, which may be related to the anti-tumor effect of the extracts from Prunella vulgaris.

Analysis of serum proteome profiles of non-Hodgkin lymphoma for biomarker identification.

Serum samples from non-Hodgkin lymphoma (NHL) patients who had not undergone chemotherapy, lymphnoditis patients, and healthy adults were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) to detect the differentially expressed serum proteins. Models were developed to distinguish between the healthy adult group and the NHL group, with a sensitivity of 69% and specificity of 90%, and between the lymphnoditis group and the NHL group with a sensitivity of 74% and specificity of 84%. A protein with the m/z of M10 197.91 u was expressed at a significantly higher level in the NHL group, compared to the other groups. Furthermore, differences were also significant among different stages of NHL and among samples with different International Prognosis Index (IPI) scores or lactase dehydrogenase (LDH) levels. The three identified proteins may offer a new serological approach for early diagnosis, differential diagnosis, and pathogenic investigation of NHL. And the protein with the m/z of M10 197.91 u may be a new serological biomarker for monitoring treatment response and evaluating the prognosis of patients with NHL.