简介：AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

简介：ＴＣＥＬＬＲＥＣＥＰＴＯＲＧＥＮＥＲＥＡＲＲＡＮＧＥＭＥＮＴＡＮＡＬＹＳＩＳＩＮＴＨＥＰＲＩＭＡＲＹＣＵＴＡＮＥＯＵＳＴＣＥＬＬＬＹＭＰＨＯＭＡＱｉｕＢｉｎｇｓｅｎ邱丙森ＷａｎｇＰｉｎｇ１王平ＧａｏＨｏｎｇｙａｎｇ２高红阳ＳｈａｎｇＹｉｆｅｉ２...

简介：AbstractCD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy is effective in refractory/relapsed (R/R) B-cell acute lymphoblastic leukemia (B-ALL). This review focuses on achievements, current obstacles, and future directions in CAR-T research. A high complete remission rate of 68% to 93% could be achieved after anti-CD19 CAR-T treatment for B-ALL. Cytokine release syndrome and CAR-T-related neurotoxicity could be managed. In view of difficulties collecting autologous lymphocytes, universal CAR-T is a direction to explore. Regarding the high relapse rate after anti-CD19 CAR-T therapy, the main solutions have been developing new targets including CD22 CAR-T, or CD19/CD22 dual CAR-T. Additionally, some studies showed that bridging into transplant post-CAR-T could improve leukemia-free survival. Some patients who did not respond to CAR-T therapy were found to have an abnormal conformation of the CD19 exon or trogocytosis. Anti-CD19 CAR-T therapy for R/R B-ALL is effective. From individual to universal CAR-T, from one target to multi-targets, CAR-T-cell has a chance to be off the shelf in the future.

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简介：Objective:Thisstudyaimstoexploretheclinicopathologicfeaturesof112patientswithmantlecelllymphoma(MCL).Methods:Datafrom112MCLcaseswerecollected,andimmunohistochemicalassaywasconducted.Fluorescenceinsituhybridization(FISH)detectedabreakintheCCND1gene.Thet-testwasusedinthestatisticalanalysis.Results:Alltumorcellsinthe112casesexpressedBcell-relatedantigen,including1blastoidsubtypeand1polymorphicsubtype.Amongallcases,106expressedCD5and104expressedcyclinD1.AbreakintheCCND1genewasnotfoundin3caseswithCD5-MCL.IgH/CCND1polyploidwasobservedin2classiccases.Conclusion:MCLisatypeofspecialimmunophenotypicB-celllymphoma.Theprognosesofblastoidandpolymorphicsubtypesarepoor.Specialsubtypesshouldbeclassifiedduringdiagnosis.

简介：AbstractImportance:Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively. Thus far, there are limited data concerning survival and toxicity in Chinese children with Burkitt lymphoma or Burkitt leukemia who have undergone treatment with the non-Hodgkin’s lymphoma Berlin-Frankfurt-Münster-90/95 (NHL-BFM-90/95) protocol.Objective:To analyze outcomes and toxicity in pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia following treatment with the NHL-BFM-90/95 protocol.Methods:Patients aged <18 years with bone marrow involvement/leukemia who were treated with the NHL-BFM-90/95 protocol, with or without rituximab, in Sun Yat-Sen University Cancer Center from April 2004 to December 2018 were included in this retrospective analysis.Results:Twenty-five patients were eligible. Burkitt lymphoma with bone marrow involvement and Burkitt leukemia were present in 10 and 15 patients, respectively. Central nervous system infiltration was not observed in any patients. All patients underwent chemotherapy involving NHL-BFM-90/95 protocol. Six courses of treatment were administered to each patient (v-AA-BB-CC-AA-BB-CC). The BFM-90/95 plus rituximab protocol was administered to 13 patients. The median follow-up interval was 31.9 months (range, 2.5-158 months). Of the 25 patients, four died: three died of tumor progression and one died of therapy abandonment after relief of tumor lysis syndrome. The estimated 5-year event-free survival and overall survival rates were both 85.8% ± 5.0%.Interpretation:Chinese pediatric patients who exhibit Burkitt lymphoma with bone marrow involvement or Burkitt leukemia can achieve optimal treatment outcomes and exhibit good tolerance when using the NHL-BFM-90/95 protocol.

简介：AbstractBackground:There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China.Methods:From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n = 72) or allo-HSCT (n = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups.Results:Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P= 0.001), chemotherapy-resistant disease (41% vs. 8%, P= 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300).Conclusions:Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

简介：客观：为了改进倔强的脸中部的外部T房间non-Hodgkin鈥檚的功效，有L天门冬氨酰胺酶(LASP)的淋巴瘤(MPTC-NHL)基于抢救化疗。方法：有倔强的MPTC-NHL的21个病人被分析，11patients(LASP组)收到了L天门冬氨酰胺酶基于的抢救化疗由L天门冬氨酰胺酶，长春新碱和dexame-thosone组成。没有L天门冬氨酰胺酶，10个病人(控制组)收到了抢救联合化疗。结果：完全的宽恕率为LASP组是45.6%，0.0%为控制组织(P<0.05)。全面反应率(CR+PR)为LASP组是63.6%，10.0%为控制组织，分别地(P<0.05)。2年的幸存率为LASP组是45.5%，0.0%为控制组织(P<0.05)。LASP的主要不利效果是白细胞减少，浆液bilirubin和多糖症的举起。结论：LASP基于的初步的临床的学习表演抢救化疗可以与倔强的MPTC-NHL改进反应率和病人的2年的幸存率。进一步继续学习是必要的。

简介：AbstractBackground:Conventional treatment has limited efficacy in relapsed/refractory B-cell lymphoma. Since chimeric antigen receptor T-cell (CAR-T) technology has shown high safety and results in high remission rates, we investigated its efficacy and safety in B-cell lymphoma treatment and analyzed potential affecting factors to provide evidence for therapeutic strategies and applications.Methods:We searched databases including PubMed, Embase, and Cochrane up to July 2019. Meta-analysis 1 was conducted to study the efficacy of CAR-T cell for treating B-cell lymphoma, measuring the response rate and complete remission rate as outcomes. Sub-group analysis was performed for age, pathological type, target antigen, co-stimulatory molecule, and conditioning chemotherapy. Meta-analysis 2 was undertaken on the safety of the treatment with the incidence rate of toxicity (cytokine-releasing syndrome [CRS], neurotoxicity) as an outcome.Results:Seventeen studies were included in the systematic review and meta-analysis. It was found that CAR-T cells had good therapeutic effects in the following cases: B-cell lymphoma (patients ≥65 years old); diffuse large B-cell lymphoma pathological type; patients with treatment target antigen other than CD19; patients treated with co-stimulatory molecules other than CD28, including 4-1BB+CD28 or 4-1BB; and patients treated with cyclophosphamide/fludarabine pre-treatment protocol conditioning chemotherapy. Although the CRS and neurotoxicity incidences were high, most were reversible with minimal risk of death.Conclusion:CAR-T cell treatment is safe for clinical application; however, toxicity effects should be monitored.

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简介：披风房间淋巴瘤(MCL)是B房间non-Hodgkin淋巴瘤的好攻击的histotype。疾病不知道了痊愈，它为新奇治疗学的代理人推动迫切需要。(CRM1)Chromosomal区域维护1可以在人的瘤形成起一个作用并且用作癌症治疗的一个新奇目标。这研究总结MCL致病并且在贡献MCL致病的几条重要发信号小径的规定决定CRM1的参与，包括房间周期前进，DNA损坏反应，phosphoinositidekinase-3，原子factor-B激活，和chromosomal稳定性的小径。现出症状之前的潜的研究也被介绍在vitro并且在vivo在MCL在MCL房间线和主要MCL房间把CRM1地位与正常B房间，以及CRM1抑制的治疗学的效率作比较，它使这些代理人成为新奇MCL治疗的潜在的目标。

简介：AbstractIntroduction:There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a low morbidity and a poor prognosis.Case presentation:An 11-year-old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.Conclusion:AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long-term follow-up is still necessary to reduce the risk of morbidity and mortality.

简介：AbstractBackground:The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with high-risk (HR) T-cell acute lymphoblastic leukemia (T-ALL) in first complete remission (CR1) is still under evaluation. Moreover, relapse is the main factor affecting survival. This study aimed to explore the effect of allo-HSCT (especially haploidentical HSCT [haplo-HSCT]) on improving survival and reducing relapse for HR childhood T-ALL in CR1 and the prognostic factors of childhood T-ALL in order to identify who could benefit from HSCT.Methods:A total of 74 newly diagnosed pediatric T-ALL patients between January 1, 2012 and June 30, 2018 were enrolled in this retrospective study. Patients were stratified into the low-risk chemotherapy cohort (n = 16), HR chemotherapy cohort (n = 31), and HR transplant cohort (n = 27). Characteristics, survival outcomes, and prognostic factors of all patients were then analyzed.Results:Patient prognosis in the HR chemotherapy cohort was significantly worse than that in the low-risk chemotherapy cohort (5-year overall survival [OS]: 58.5% vs. 100%, P = 0.003; 5-year event-free survival [EFS]: 54.1% vs. 83.4%, P = 0.010; 5-year cumulative incidence of relapse [CIR]: 45.2% vs. 6.3%, P = 0.011). In HR patients, allo-HSCT improved the 5-year EFS and CIR compared to that of chemotherapy (5-year EFS: 80.1% vs. 54.1%, P = 0.041; 5-year CIR: 11.6% vs. 45.2%, P = 0.006). The 5-year OS was higher in the HR transplant cohort than that in the HR chemotherapy cohort (81.0% vs. 58.5%, P = 0.084). Minimal residual disease re-emergence was an independent risk factor for 5-year OS, EFS, and CIR; age ≥10 years was an independent risk factor for OS and EFS; and high white blood cell count was an independent risk factor for EFS and CIR.Conclusion:Allo-HSCT, especially haplo-HSCT, could effectively reduce relapse of children with HR T-ALL in CR1.

简介：Aim:Toisolateandtransplantgermcellsfromadultmousetestesfortransplantation.Methods:Inordertodistinguishtransplantedcellsfromendogenouscellsofrecipients,donortransgenicmiceexpressinggreenfluorescentprotein(GFP)wereused.Germcellswerecollectedfromthedonorsat10-12weeksofageandspermatogoniawereconcentratedbypercollfractionationandtransplantedintorecipientseminiferoustubulesthathadbeenpreviouslytreatedwithbusulfanat5weeksofagetoremovetheendogenousspermatogeniccells.Results:Twentyweeksafterthetransplantation,awidespreadGFPsignalwasobservedintherecipientseminiferoustubules.Thepresenceofspermatogenesisandspermatozoawasconfirmedinsectionsof12outof14testestransplanted(86%).However,whengermcellsweretransplantedwithoutconcentrationthesuccessratewaszero(0/9).Conclusion:Germcellsfromadultmousetestescanbesuccessfullytransplantedintorecipientseminiferoustubulesifthecellpopulationisrichinspermatogoniaandthepercollfractionationisusefulinobtainingsuchacellpopulation.

简介：TcellhomeostasiscommonlyreferstothemaintenanceofrelativelystableTcellnumbersintheperipherallymphoidorgans.AmongthelargenumbersofTcellsintheperiphery,Tcellsexhibitstructuraldiversity,I.e.,theexpressionofadiverserepertoireofTcellreceptors(TCRs),andfunctionaldiversity,I.e.,thepresenceofTcellsatna(I)ve,effector,andmemorydevelopmentalstages.AlthoughthehomeostasisofTcellnumbershasbeenextensivelystudied,investigationofthemechanismsunderlyingthemaintenanceofstructuralandfunctionaldiversityofTcellsisstillatanearlystage.ThefundamentalfeaturethroughoutTcelldevelopmentistheinteractionbetweentheTCRandeitherselforforeignpeptidesinassociationwithMHCmolecules.Inthisreview,wepresentevidenceshowingthathomeostasisofTcellnumberanddiversityismediatedthroughcompetitionforlimitingresources.ThenumberofTcellsismaintainedthroughcompetitionforlimitingcytokines,whereasthediversityofTcellsismaintainedbycompetitionforself-peptide-MHCcomplexes.Inotherwords,diversityoftheself-peptiderepertoirelimitsthestructural(TCR)diversityofaTcellpopulation.Wespeculatethatcognatelowaffinityself-peptides,actingasweakagonistsandantagonists,regulatethehomeostasisofTcelldiversitywhereasnon-cognateornullpeptideswhichareextremelyabundantforanygivenTCR,maycontributetothehomeostasisofTcellnumberbyprovidingsurvivalsignals.Moreover,self-peptidesandcytokinesmayformspecializednichesfortheregulationofTcellhomeostasis.

简介：AbstractBackground:Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms.Methods:Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student’s t test or analysis of variance.Results:BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 μg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB).Conclusions:BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.

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简介：Objective:Correctnutritionalassessmentisessentialforleukemiapatientsafterhematopoieticstemcelltransplantation(HSCT).ThisstudyaimedtoinvestigatethebestnutritionalassessmentmethodforleukemiapatientsafterHSCT,andfindthepossiblenutritionalriskofthepatientsduringthetransplantationprocessinordertointerveneinthepatientswithnutritionalrisksandundernourishedpatientstimely,sothattheentiretransplantationprocesscouldbesuccessfullycompleted.Methods:Aprospectivestudywasperformedin108leukemiapatientsafterHSCT,anddifferentnutritionalassessmentmethods,includingnutritionalriskscreening2002(NRS2002),mininutritionalassessment(MNA),subjectiveglobeassessment(SGA)andmalnutritionaluniversalscreeningtools(MUST),wereused.Theassociationsbetweennutritionalstatusofthesepatientsandnutritionalassessmentmethodswereanalyzed.Results:Atotalof108patientscompletedSGA,and99patientscompletedNRS2002,MNAandMUST.Duringthetreatmentprocess,85.2%ofthepatientslostweight,wherein,50%lostweightgreaterthan5%,and42.6%hadsignificantlyreducedfoodintake.Fornutritionalriskassessment,thepositiveratesofNRS2002,MNAandMUSTwere100%,74.7%and63.6%,respectively.Therewasasignificantdifference(P<0.05)amongthepositiveratesofNRS2002,MNAandMUST.Inundernutritionassessment,thepositiverateofSGA(83.3%)wassignificantlyhigherthanthatofMNA(17.2%)(P<0.05),andtheincidencerateofnutritionalriskamongleukemiapatients≤30yearsoldwasgreaterthanthatofpatients>30yearsold(P<0.05).Conclusions:PatientswithleukemiawereinpoornutritionalstatusduringandafterHSCT.Theleukemiapatients≤30yearsoldhadagreaterincidencerateofnutritionalrisk.Asnutritionalriskscreeningtool,thespecificityofNRS2002isnothigh,butitcanbeusedforevaluatingnutritionaldeficiencies.MNAisagoodnutritionalriskscreeningtool,butnotanadequatetoolfornutritionalassessment.Ifassessmentofundernutritionisneces

简介：T房间受体(TCR)的结扎独自是不够的导致T淋巴细胞的完整的激活。介绍房间(APC)和T房间的抗原上的另外的ligand受体相互作用(costimulation)被要求。T房间costimulation被显示了为得到有效T房间回答必要，包含在T房间开发期间的所有阶段。然而，costimulation由影响T房间的功能的机制仍然需要被阐明。在最近的年里，在癌症，传染疾病以及自体免疫的疾病作为潜在的治疗在costimulation的研究被献殷勤。在这评论，我们讨论了调整T房间增长，房间周期前进，cytokine生产，幸存，和存储器开发的细胞内部的costimulation信号。一般来说，phosphoinositide-3kinase(PI3K)的小径/proteinkinaseB(PKB，也作为Akt知道)/nuclear因素B(NF-B)可能对许多costimulatory效果中央。通过这些小径，costimulation由survivin和曙光B表示的维护控制T房间扩大和增长，并且由调整bcl-2家庭成员的表达式支撑长期的T房间幸存和存储器开发。