Phase II study of novel orally PI3Kα/δinhibitor TQ-B3525 in relapsed and/or refractory follicular lymphoma

This registration study assessed clinical outcomes of TQ-B3525,the dual phosphatidylinositol-3-kinase(PI3K)α/δinhibitor,in relapsed and/or refractory follicular lymphoma(R/R FL).This phase II study(ClinicalTrials.gov NCT04324879.Registered March 27,2020)comprised run-in stage and stage 2.R/R FL patients after≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression.Primary endpoint was independent review committee(IRC)-assessed objective response rate(ORR).Based on results(ORR,88.0%;duration of response[DOR],11.8 months;progression-free survival[PFS],12.0 months)in 25 patients at run-in stage,second stage study was initiated and included 82 patients for efficacy/safety analysis.Patients received prior-line(median,3)therapies,with 56.1%refractory to previous last therapies;73.2%experienced POD24 at baseline.At stage 2,ORR was 86.6%(71/82;95%CI,77.3-93.1%),with 28(34.2%)complete responses.Disease control rate was 95.1%due to 7(8.5%)stable diseases.Median time to response was 1.8 months.Among 71 responders,median DOR was not reached;18-month DOR rate was 51.6%.with median follow-up of 13.3 months,median PFS was 18.5(95%CI,10.2-not estimable)months.Median overall survival(OS)was not reached by cutoff date;24-month OS rate was estimated as 86.1%.Response rates and survival data were consistent across all subgroups.Grade 3 or higher treatment-related adverse events were observed in 63(76.8%)cases,with neutropenia(22.0%),hyperglycemia(19.5%),and diarrhea(13.4%)being common.TQ-B3525 showed favorable efficacy and safety for R/R FL patients after≥2 lines prior therapies.

Effect of taurine on immune function in mice with T-cell lymphoma during chemotherapy

Objective: To observe the effect of taurine on immune function in mice with T-cell lymphoma during chemotherapy.Methods: A total of 40 C57 BL/6 mice were selected and randomly divided into 4 groups,namely model group, chemotherapy group, taurine group and chemotherapy + taurine group, each containing 10 mice. Hypodermic injection was adopted to inoculate EL-4 cells in order to establish model of T-cell lymphoma. When the tumor achieved the size of1 cm3, intervention treatments were given to the groups respectively. Mice in model group received 0.2 m L of normal saline which was intraperitoneally injected on Days 1, 8 and 15 with 3 weeks as a cycle; mice in chemotherapy group were administered with 80 mg/kg body weight of gemcitabine which was also intraperitoneally injected on Days 1, 8 and 15 with 3 weeks as a cycle; mice in taurine group were administered with 80 mg/kg body weight of taurine intraperitoneally injected daily for consecutive 8 d; mice in chemotherapy + taurine group were treated in the same manner as the mice in taurine group and chemotherapy group. Five mice were sacrificed at 2 and 3 weeks after intervention respectively, and the tumor tissues were collected and weighted after removal of auxiliary tissue, then the tumor inhibition rate was calculated. The thymus and spleen of mice sacrificed at 3 weeks after intervention were collected and weighted, and thymus and spleen indexes were calculated. Enzyme linked immunosorbent assay was used to detect the serum levels of IL-4, IL-10, IL-12 and IFN-g in mice of each group.Results: The tumor weights in chemotherapy group, taurine group and chemotherapy + taurine group after 2 and 3 weeks of treatment were significantly lower than that in model group(P < 0.05); the tumor weight in chemotherapy + taurine group after 2 and 3 weeks of treatment was significantly lower than that in chemotherapy group(P < 0.05); the tumor inhibition rate in chemotherapy + taurine group was significantly higher than that in chemotherapy group and taurine group(P < 0.05); the thymus and spleen indexes in taurine group and chemotherapy + taurine group were significantly higher than those in chemotherapy group and model group(P < 0.05); the thymus and spleen indexes in chemotherapy group were significantly lower than those in model group(P < 0.05); after 3 weeks of treatment, the serum levels of IL-4, IL-12 and IFN-g in chemotherapy group, taurine group and chemotherapy + taurine group were significantly lower than those in model group(P < 0.05); the IL-4 level in taurine group and chemotherapy + taurine group was significantly lower than that in chemotherapy group(P < 0.05); the serum level of IL-10 in chemotherapy group and chemotherapy + taurine group was significantly higher than that in model group and taurine group(P < 0.05); the serum level of IFN-g in taurine group and chemotherapy + taurine group was significantly lower than that in model group and chemotherapy group(P < 0.05); after treatment of 3 weeks, the serum levels of IL-4 and IL-10 in chemotherapy group, taurine group and chemotherapy + taurine group were significantly lower than those in model group(P < 0.05), and IL-12 level was significantly higher than that in model group(P < 0.05);the level of IFN-g in taurine group and chemotherapy + taurine group was significantly higher than that in model group(P < 0.05), while the level of IFN-g in chemotherapy group was significantly lower than that in the other 3 groups(P < 0.05).Conclusions: Taurine can effectively enhance the immune function of mice with T-cell lymphoma during chemotherapy, reduce the toxicity of chemotherapy.

Brucellosis of unknown origin with haemophagocytic syndrome:A case report

BACKGROUND Brucellosis is a contagious bacterial disease caused by Brucella species,which is a leading zoonotic disease worldwide.Most patients with brucellosis have a clear infection source;however,our case had a rare presentation of secondary haemophagocytic lymphohistiocytosis without any epidemiological history.CASE SUMMARY A 50-year-old man was admitted to our hospital with a fever of unknown origin.After laboratory examinations,such as blood culture and bone marrow biopsy,the patient was diagnosed with brucellosis and secondary haemophagocytic lymphohistiocytosis.After antibiotic therapy,the patient was afebrile,and his haemogram recovered to normal,after which he was discharged.CONCLUSION Brucellosis cannot be excluded in patients with clinically unexplained fever,even in those without epidemiologic history.

Refractory case of ulcerative colitis with idiopathic thrombocytopenic purpura successfully treated by Janus kinase inhibitor tofacitinib:A case report

BACKGROUND Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura(ITP) is a rare phenomenon. The management of UC with ITP can be challenging,since a decreased platelet count augments UC.CASE SUMMARY A 24-year-old man with UC and steroid-resistant ITP experienced UC flare.Although continuous infusion of cyclosporine was initiated, UC did not improve.The administration of tofacitinib subsequently led to the induction of remission.The patient has maintained remission of UC and ITP for over one year ontofacitinib treatment. Whole transcriptomic sequencing was performed forinflamed rectal mucosae obtained before and after the initiation of Janus kinase(JAK) inhibitor, suggesting that distinct molecular signatures seemed to beregulated by JAK inhibitors and other conventional therapies including tumornecrosis factor lockers.CONCLUSION Tofacitinib should be considered in refractory cases of UC with ITP.

Progress in oncolytic viruses modified with nanomaterials for intravenous application

In oncolytic virus(OV)therapy,a critical component of tumor immunotherapy,viruses selectively infect,replicate within,and eventually destroy tumor cells.Simultaneously,this therapy activates immune responses and mobilizes immune cells,thereby eliminating residual or distant cancer cells.However,because of OVs’high immunogenicity and immune clearance during circulation,their clinical applications are currently limited to intratumoral injections,and their use is severely restricted.In recent years,numerous studies have used nanomaterials to modify OVs to decrease virulence and increase safety for intravenous injection.The most commonly used nanomaterials for modifying OVs are liposomes,polymers,and albumin,because of their biosafety,practicability,and effectiveness.The aim of this review is to summarize progress in the use of these nanomaterials in preclinical experiments to modify OVs and to discuss the challenges encountered from basic research to clinical application.

Polyarteritis nodosa clinically mimicking nonocclusive mesenteric ischemia

Here, we present the case of a 74-year-old Japanese man with segmental intestinal necrosis, which developed after treatment with pulsed methylprednisolone for mononeuritis multiplex. The patient was weakly positive for myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA). Computed tomography and surgical findings were compatible with nonocclusive mesenteric ischemia (NOMI). He underwent small intestinal resection by emergency surgery and an intestinal fistula was made. Pathologically, necrotizing vasculitis with fibrinoid necrosis was present in medium to small-sized arteries, which was equivalent to Arkin's classification Ⅱ-Ⅳ. Most of the arteries had fibrous intimal thickening, which was considered to obstruct the arteries and thus cause segmental intestinal necrosis. A diagnosis of polyarteritis nodosa (PAN) was made, and intravenous cyclophosphamide pulse therapy was added to the therapeutic regimen. This patient was successfully treated with these multidisciplinary therapies and his stoma was finally closed. This is a very rare and indicative case of PAN weakly positive for MPO-ANCA and clinically mimicking NOMI, which occurred even after treatment with pulsed methylprednisolone.

Cyclophosphamide-associated enteritis presenting with severe protein-losing enteropathy in granulomatosis with polyangiitis:A case report

BACKGROUND Although cyclophosphamide(CPA)is the key drug for the treatment of autoimmune diseases including vasculitides,it has some well-known adverse effects,such as myelosuppression,hemorrhagic cystitis,infertility,and infection.However,CPA-associated severe enteritis is a rare adverse effect,and only one case with a lethal clinical course has been reported.Therefore,the appropriate management of patients with CPA-associated severe enteritis is unclear.CASE SUMMARY We present the case of a 61-year-old woman diagnosed with granulomatosis with polyangiitis based on the presence of symptoms in ear,lung,and,kidney with positive myeloperoxidase-antineutrophil cytoplasmic antibody.She received pulsed methylprednisolone followed by prednisolone 55 mg/d and intravenous CPA at a dose of 500 mg/mo.Ten days after the second course of intravenous CPA,she developed nausea,vomiting,and diarrhea,and was admitted to the hospital.Laboratory testing revealed hypoalbuminemia,suggesting proteinlosing enteropathy.Computed tomography revealed wall thickening of the stomach,small intestine,and colon with contrast enhancement on the lumen side.Antibiotics and immunosuppressive therapy were not effective,and the patient’s enteritis did not improve for>4 mo.Because her condition became seriously exhausted,corticosteroids were tapered and supportive therapies including intravenous hyperalimentation,replenishment of albumin and gamma globulin,plasma exchange,and infection control were continued.These supportive therapies improved her condition,and her enteritis gradually regressed.She was finally discharged 7 mo later.CONCLUSION Immediate discontinuation of CPA and intensive supportive therapy are crucial for the survival of patients with CPA-associated severe enteritis.

2021 Chinese consensus on the diagnosis and management of primary immune thrombocytopenia in pregnancy

Immune thrombocytopenia(ITP)is an acquired disease characterized by isolated thrombocytopenia,which is one of the most common causes of thrombocytopenia during pregnancy.Women with ITP who have severe thrombocytopenia are at an increased risk for life-threatening obstetric complications.Therefore,we established this consensus statement on the diagnosis and management of ITP during pregnancy(detailed information is available in the Supplementary File,http://links.lww.com7CM9/A978).

Treatment for CD57-negativeγδT-cell large granular lymphocytic leukemia with pure red cell aplasia:A case report

BACKGROUND T-cell large granular lymphocytic leukemia(T-LGLL)is a rare type of aplastic anemia with diverse clinical manifestations.Concomitant diseases are often present at the first manifestation.We describe the treatment of a patient with CD57-negativeγδT-LGLL with pure red cell aplasia(PRCA).CASE SUMMARY A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted.Her condition was diagnosed as CD57-negativeγδT-LGLL with PRCA through bone marrow cytology,bone marrow pathology,bone marrow flow cytometry,bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis,and other tests.Treatment with prednisone,methotrexate,and subcutaneous erythropoietin did not significantly change her hemoglobin level.After treatment with oral cyclophosphamide for 3 mo,her hemoglobin level increased to approximately 100 g/L.After 5 mo of treatment,the patient could perform activities of daily living independently.CONCLUSION The treatment of CD57-negativeγδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.

Etoposide,dexamethasone,and pegaspargase with sandwiched radiotherapy in early-stage natural killer/T-cell lymphoma:A randomized phase III study

Methotrexate,etoposide,dexamethasone,and pegaspargase(MESA)with sandwiched radiotherapy is known to be effective for early-stage extranodal natural killer/T-cell lymphoma,nasal type(NKTCL).We explored the efficacy and safety of reduced-intensity,non-intravenous etoposide,dexamethasone,and pegaspargase(ESA)with sandwiched radiotherapy.This multicenter,randomized,phase III trial enrolled patients aged between 14 and 70 years with newly diagnosed early-stage nasal NKTCL from 27 centers in China.Patients were randomly assigned(1:1)to receive ESA(pegaspargase 2,500 IU/m^(2)intramuscularly on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4)or MESA(methotrexate 1 g/m^(2)intravenously on day 1,etoposide 200 mg orally,and dexamethasone 40 mg orally on days 2–4,and pegaspargase 2,500 IU/m^(2)intramuscularly on day 5)regimen(four cycles),combined with sandwiched radiotherapy.

Shenqi Fuzheng Injection Combined with Chemotherapy for Acute Leukemia:A Meta-Analysis

Objective:To evaluate to the efficacy and safety of Shenqi Fuzheng Injection(SFI)combined with chemotherapy in the treatment of acute leukemia(AL)by meta-analysis.Methods:Pub Med,Cochrane library,Embase,Sino Med,China National Knowledge Infrastructure(CNKI),VIP Journal Integration Platform,Wanfang Database were searched from establishment to November 1,2018.The randomized controlled trials(RCTs)of SFI combined with chemotherapy in the treatment of AL were included.The Cochrane risk assessment form(Rev Man 5.1)was used to evaluate the quality of included studies.Results:A total of 14 RCTs and 1,088 patients was included.The quality evaluation was mostly low risk or unclear.Meta-analysis showed that compared with chemotherapy alone,SFI combined with chemotherapy can improve the total clinical effective rate in patients with AL(RR=1.15,95%CI:1.056–1.177;P=0.0001),and relieve adverse reactions caused by chemotherapy drugs,including infection(RR=0.561,95%CI:0.397–0.792;P=0.001),nausea and vomiting(RR=0.662,95%CI:0.524–0.835;P=0.001),bleeding(RR=0.548,95%CI:0.39–0.768;P=0.0001),cardiotoxicity(RR=0.230,95%CI:0.080–0.660;P=0.006)and hyperhidrosis(RR=0.348,95%CI:0.208–0.581;P=0.0001).The incidence rates of adverse reactions in SFI combined with chemotherapy group were significantly lower than that of the chemotherapy alone group(P<0.01).Conclusions:Shenqi Fuzheng Injection combined with chemotherapy has good efficacy and safety for AL,and it can alleviate the adverse reactions caused by chemotherapy.However,subject to the limitations of the methodological quality of the literature,the conclusions of this study need to be further verified by large-scale and multi-center RCTs.