LATS1 Promotes B-ALL Tumorigenesis by Regulating YAP1 Phosphorylation and Subcellular Localization

Objective YAP1 plays a dual role as an oncogene and tumor suppressor gene in several tumors;differentiating between these roles may depend on the YAP1 phosphorylation pattern.The specific function of YAP1 in B cell acute lymphoblastic leukemia(B-ALL),however,is currently unclear.Thus,in the present study,the role of YAP1 in B-ALL was investigated using relevant cell lines and patient datasets.Methods The effects of shRNA-mediated knockdown on YAP1 and LATS1 levels in the NALM6 and MOLT-4 cell lines were examined using Western blotting,quantitative real-time polymerase chain reaction,flow cytometry,immunostaining,and nude mouse subcutaneous tumorigenesis experiments.Gene expression levels of Hippo pathway-related molecules before and after verteporfin(VP)treatment were compared using RNA-Seq to identify significant Hippo pathway-related genes in NALM6 cells.Results Patients with ALL showing high YAP1 expression and low YAP1-Ser127 phosphorylation levels had worse prognoses than those with low YAP1 protein expression and high YAP1-Ser127 phosphorylation levels.YAP1-Ser127 phosphorylation levels were lower in NALM6 cells than in MOLT-4 and control cells;YAP1 was distributed in the nuclei in NALM6 cells.Knockdown of YAP1 inhibited MOLT-4 and NALM6 cell proliferation and arrested the NALM6 cell cycle in the G0/G1 phase.Before and after VP treatment,the expression of the upstream gene LATS1 was upregulated;its overexpression promoted YAP1-Ser127 phosphorylation.Further,YAP1 was distributed in the plasma.Conclusion LATS1 may downregulate YAP1-Ser127 phosphorylation and maintain B-ALL cell function;thus,VP,which targets this axis,may serve as a new therapeutic method for improving the outcomes for B-ALL patients.

Macrophage regulation of graft-vs-host disease

Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy,but graft-vs-host disease(GVHD)has limited the survival quality and overall survival of hematopoietic stem cell transplantation.Understanding of the immune cells’reaction in pathophysiology of GVHD has improved,but a review on the role of macrophages in GVHD is still absent.Studies have observed that macrophage infiltration is associated with GVHD occurrence and development.In this review,we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD,focusing on the macrophage recruitment and infiltration,macrophage polarization,macrophage secretion,and especially interaction of macrophages with other immune cells.We could conclude that macrophage recruitment and infiltration contribute to both acute and chronic GVHD.Based on distinguishing pathology of acute and chronic GVHD,macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic GVHD.However,the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage polarization.In addition,interaction of macrophages with alloreactive T cells plays an important role in acute GVHD.Meanwhile,the interaction among macrophages,B cells,fibroblasts,and CD4+T cells participates in chronic GVHD development.

Genistein-induced Anticancer Effects on Acute Leukemia Cells Involve the Regulation of Wnt Signaling Pathway Through H4K20mel Rather Than DNA Demethylation

Objective:To investigate the effects and mechanisms of genistein on the gene expression in the Wnt pathway in acute leukemia(AL)cells.Methods:The expression of Wnt pathway genes and cell cycle-related genes were analyzed in two AL cell lines.Pyrophosphate sequencing was performed to determine the methylation degree.Then,the enrichment of H4K20mel and H3K9ac was determined using ChIP-qPCR.Flow cytometry was used to analyze the cell cycle.Results:The IC_(50) of genistein in the two AL cell lines was lower than that for the bone marrow mesenchymal stem cell line.Genistein upregulated H4K20mel,KMT5A and Wnt suppressor genes,including Wnt5a,and downregulated the downstream target genes of Wnt,such as c-myc and β-catenin.The methylation degree and H3K9ac enrichment in the Wnt5a promoter region remained unchanged.However,the enrichment of H4K20mel in the Wnt5a promoter and coding regions increased.In addition,genistein upregulated Phospho-cdc2,Mytl,Cyclin A,Cyclin E2,p21 and Phospho-histone H3,but downregulated Phospho-weel.Cell cycle arrest was induced in the G2/M phase.Conclusion:Genistein inhibits the activation of the Wnt pathway by promoting the expression of Wnt5a through the activation of KMT5A and enrichment of H4K20mel in the Wnt5a gene promoter and coding regions,rather than demethylation.Genistein also blocks the cell cycle in the G2/M phase.Therefore,genistein is a potential anti-leukemia drug.

CHARACTERIZING FLUORESCENCE LIFETIME OF NAD(P)H IN HUMAN LEUKEMIC MYELOID CELLS AND MONONUCLEAR CELLS

The aim of this er vito study was to explore the potential of using the fluorescence lifetime of intraellular reduced nicotinamide adenine dinucleotide(phosphate)(NAD(P)H)as a label-free indicator to characterize the di ferencs between human leukemic myeloid cells and normal mononuclear cells(MNC).The steady-state and time-resolved autofuorescence of two human leukemic myeloid cell lines(K562,HL60)and MNC were measured by a spectrofuorimeter.According to excitation-enmission matrix(EEM)analysis,the optimal emission of NAD(P)H in these cells suspensions occurred at 445 nm.Furthermore,the fuorescence lifetimes of NAD(P)H in leukemic myeloid cells and MNC were determined by fitting the time-resolved autofuorescence data.The mean fuorescence lifetimes of NAD(P)H in K562,HL60,and MNC cells were 557±1.19,4.45±0.71,and 7.31±0.60 ns,respectively.There was a significant diference in the mean lifetime of NAD(P)H between leukemic myeloid cells and MNC(p<0.05).The difference was essentally caused by the change in relative concentration of free and protein-bound NAD(P)H.This study suggests that the mean fuorescence lifetime of NAD(P)H might be a potential label-free indicator for differentiating leukemic myeloid cells from MNC.

Age-related modifications of macrophages influenced by “inflammageing”in graft vs. host disease

Most studies focus on the adaptive immune cells in the GVHD pathogenesis,while little is known about innate immune cells in GVHD occurrence and development,especially macrophages.Meanwhile,a higher incidence of graft versus host disease(GVHD)is also found in the elderly patients.Though advances have been made in the modification of macrophages influenced by the inflamm-ageing,there is still no review on the role of macrophages in GVHD and the association between GVHD and the altered macrophages by inflamm-ageing.In this review,we focus on the potential age-related modifications of macrophage in GVHD,which contributes to the change of morbidity and mortality of GVHD.Via literature review,we found that the infiltration of macrophages is associated with GVHD and macrophages are modified in inflamm-ageing state,including the proliferation,migration,phagocytosis,antigen presentation,interaction with other immune cells,and pro-fibrosis.We suppose that altered macrophage functions in inflamm-ageing state contribute to GVHD in elderly patients.

Genetics analysis of haptoglobin gene in Fujian Han nationality

To study the genetic features(characteristics)of haptoglobin gene,four different age groups of Fujian Han people were investigated.The phenotypes of the hap-toglobin of four different groups were analyzed by using polyacrylamide gel electrophoresis.The frequency of Hp^(1) in the population of Fujian Han nationality accounted for 0.340,among which children,youths,middle aged and elder groups were 0.307,0.338,0.363 and 0.383,respect-ively.The Hp^(0-0)phenotype frequency was 0.026 in which the four age groups accounted for 0.032,0.046,0.014 and 0.014,respectively.The frequency of Hp^(1)gene is rising with increasing age.The frequency of Hp^(0-0)phenotype is highest in the middle aged group and then tends to drop with increasing age.

Efficacy and safety of tandem autologous stem cell transplantation in multiple myeloma:a retrospective single-center analysis

To the Editor:Upfront autologous stem cell transplantation(ASCT)has been an integral part of the management of young and eligible older patients with newly diagnosed multiple myeloma(NDMM)for over three decades.Tandem stem cell transplantation was defined as two planned sequential ASCTs within 3 to 6 months.More than two decades after its introduction,trials exploring the utility of tandem transplants have yielded mixed results.The role of tandem ASCT in multiple myeloma(MM)remains unclear and controversial.In the EMN02/HOVON95 study.

Exosome miRNAs profiling in serum and prognostic evaluation in patients with multiple myeloma

MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China

Background: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.

Superiority of allogeneic hematopoietic stem cell transplantation to nilotinib and dasatinib for adult patients with chronic myelogenous leukemia in the accelerated phase

In the tyrosine kinase inhibitor （TKI） era, imatinib is the first-line therapy for patients with chronic myeloid leukemia （CML） in chronic or accelerated phase. Although second-generation TKIs （TKI2）, including dasatinib and nilotinib, are appropriate treatment regimens for patients with disease that progressed to accelerated phase following imatinib therapy, allogeneic hematopoietic stem cell transplantation （allo-HSCT） is the only curative therapy. This study retrospectively analyzed the efficacy of TKI2 and HSCT for treatment of CML in accelerated phase. Ninety-three patients with CML registered in the Chinese CML alliance database from February 2001 to February 2014 were enrolled and divided into the TKI2 （n = 33） and allo-HSCT （n = 60） groups. In the TKI2 group, 26 and 7 patients received nilotinib and dasatinib, respectively, as initial TKI2 and 11 patients transferred to the alternative TKI2 after failure to one TKI2. In the allo-HSCT group, 22 （36.7%）, 35 （58.3%）, and 3 （10%） patients underwent aHo-HSCT from an HLA-matched sibling donor, HLA mismatched/haploidentical donor, and unrelated donor, respectively. All patients in the HSCT group were engrafted. Overall, 69.7%, 48.5%, and 45.5% of patients presented hematological, cytogenetic, and major molecular responses, respectively, to at least one of TKI2. All 60 patients （100%） achieved CHR and cytogenetic response in the HSCT group. Patients in the TKI2 group exhibited lower 5-year overall survival rate （42.9% vs. 86.4%, P = 0.002）, 5-year event-free survival rate （14.3% vs. 76.1%, P 〈 0.001）, and 5-year progression-free survival （28.6% vs. 78.1%, P 〈 0.001） than those in the alIo-HSCT group. Multivariate analysis showed that male sex and TKI2 therapy were predictors of poor overall survival, whereas hemoglobin 〈 100 g/L and TKI2 therapy were predictors of poor event-free survival and progression-free survival. These results indicated that allo-HSCT may be superior to nilotinib and dasatinib for adult patients with CML in accelerated phase.

Long-term outcome of tyrosine kinase inhibitor treatment in children and adolescents with newly diagnosed chronic myeloid leukemia in chronic phase

Chronic myeloid leukemia(CML)is relatively rare in children,with an average annual incidence of 0.6 to 1.0 case per million in children<15 years and 2.2 cases per million in adolescents aged 15 to 19 years,accounting for 2%to 3%and 9%of all newly diagnosed leukemia cases in these two age groups,respectively.[1]Imatinib mesylate(IM)was approved by the US Food and Drug Administration(FDA)in 2003 and has gradually replaced hematopoietic stem cell transplantation(HSCT)as the first-line treatment for pediatric patients with chronic-phase CML(CML-CP).[2]However,IM treatment is discontinued in 25%to 29%of pediatric patients with CML-CP because of drug resistance or intolerance.[3]For such patients,second-generation tyrosine kinase inhibitors(2G-TKIs),including dasatinib and nilotinib,were approved by the FDA as first-and second-line therapies in 2017 and 2018,respectively.[2]However,given the rarity of this neoplasm and the lack of clinical trial data,treatments for pediatric CML follow the recommended adult regimen,and little is known about the long-term efficacy and safety of these treatments in children and adolescents.[2]Furthermore,there are few reports detailing the sequential use of IM as first-line treatment followed by 2G-TKIs as second-line therapy in Chinese pediatric patients with CML.Therefore,there is a strong need to investigate the long-term effects of IM treatment in a large cohort of Chinese pediatric patients.In this report,we retrospectively analyzed the long-term follow-up results of 58 pediatric patients with CML-CP treated with IM as first-line therapy and 2G-TKIs as second-line therapy in a single South China center.

TCP1 regulates Wnt7b/β-catenin pathway through P53 to influence the proliferation and migration of hepatocellular carcinoma cells

Dear Editor,Molecular chaperones are critical mediators of oncogenesis and necessary for cell survival.1 The cytoplasmic chaperone TRiC(Tcomplex protein-1 ring complex,also known as CCT)comprises two back-to-back stacked rings,with each ring containing eight subunits(CCT1–CCT8).2 And the effects of CCT subunits on tumors may be different.However,the roles of the CCT1 subunit(also known as TCP1)in hepatocellular carcinoma(HCC)and its molecular mechanism have not been investigated thoroughly.Understanding these details can provide new ideas and strategies for treating HCC.

Effect of arsenic trioxide on proliferation and apoptosis of U266 cells and its relationship with the expression variation of VEGF

The aim of this article is to explore the effect of arsenic trioxide(As2O3)on the proliferation and apopto-sis of myeloma cell line U266 and its relationship with the expression variation of vascular endothelial growth factor(VEGF).The viability and apoptosis of U266 cells were observed by methylthiazolyl-tetrazolium(MTT)assay and terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL).The effect of As2O3 on the VEGF expression of U266 cells were tested by enzyme linked immunosorbent assay(ELISA)and reverse transcrip-tion-polymerase chain reaction(RT-PCR)analysis.We found that As2O3 could significantly inhibit the growth of U266 cells,and the concentration for 50%growth inhibition(IC50)was 2 mmol/L.After treatment with 2,5,10 mmol/L As2O3 for 36 hours,dose-dependent apop-tosis of U266 cells was observed.After treatment with 2,5,10 mmol/L As2O3 for 72 hours,a dose-dependent reduc-tion of VEGF in the supernatant of U266 cells culture was found.As far as single cells are concerned,nevertheless,the expression of VEGF mRNA did not vary.So we draw the conclusion that As2O3 could induce the apoptosis of U266 cells and inhibit their proliferation,decrease the tumor load,and lead to the reduction of VEGF in the culture supernatant,but not change the expression of VEGF in single U266 cells.

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).

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.

基于个体化机器学习的原发性免疫性血小板减少症危重出血预测模型:一项全国前瞻性队列研究

原发性免疫性血小板减少症(ITP)中少见但至关重要的危重出血事件,给患者的预后、生活质量和治疗决策带来严重影响。尽管有一些研究探讨了ITP中与危重出血相关的风险因素,但目前尚缺乏大样本数据、大规模多中心研究结果以及针对ITP患者致命出血事件的预测模型。本研究首次采用国际血栓与止血学会新提出的ITP致命出血标准,利用大样本数据开发了首个基于机器学习的在线应用,用于预测ITP患者的致命出血.研究中,我们使用中国各地大型多中心数据进行开发,并对全国39家医疗中心进行为期一年的外部测试,得到了较好的训练、验证和测试数据集预测能力该基于新算法的便捷网络工具能够快速识别ITP患者的出血风险,辅助临床决策,有望未来降低不良事件的发生。

单倍型造血干细胞移植中抗胸腺细胞球蛋白的最适剂量:一项多中心、随机对照研究的长期随访

探索抗胸腺细胞球蛋白(ATG)最佳剂量是优化"北京方案"单倍型造血干细胞移植(haplo-HCT)疗效的重要步骤.本研究弥补了探索ATG剂量的前瞻性、多中心、随机对照试验尤其是长期随访资料的匮乏.纳入408例白血病患者,年龄为14~65岁,采用"北京方案"行haplo-HCT,依据所用ATG剂量被1:1随机分为7.5 mg/kg(n=203,ATG-7.5)组和10mg/kg(n=205,ATG-10.0)组.中位随访时间为1968(1300~2710)天.两组的5年中重度慢性GVHD发生率、非复发死亡率、复发率、无病生存率、无GVHD/无复发生存率均无显著差异.5年晚发合并症两组间无显著差异.但ATG-10.0组的CMV/EBV相关死亡率显著高于ATG-7.5组(9.8%vs.1.5%;P=0.003).由此可见,相对于10 mg/kg ATG,行haplo-HCT的患者更能获益于7.5mg/kgATG带来的GVHD和感染之间的平衡.因此,本研究不仅有助于优化"北京方案"中ATG的使用,更有意义的是秉持持续探索的科学态度提高临床研究的意识、水平,为通过系列临床研究回答亟需解决的临床问题提供了示范.

Outcomes in refractory diffuse large B-cell lymphoma:results fromamulticenter real-world study in China

Background:Diffuse large B-cell lymphoma(DLBCL)patients refractory to rituximab-based immunochemotherapy have a dismal prognosis.However,the definition of refractory DLBCL remains inconsistent and no large cohort study data is available from Asian countries.To validate the definition and outcomes of refractory DLBCL in China,we conducted a multicenter,retrospective cohort study.Methods:The REtrospective AnaLysis of Treatment REspoNse of refractory DLBCL(REAL-TREND)study was performed using real-world data from 8 centers in China.DLBCL patients with curative intent were included in the REAL-TREND dataset.Overall survival(OS)was estimated using the Kaplan-Meier method and compared by the log-rank test.Due to heterogeneity in response rates among different centers,the response rates of refractory patients were pooled using random-effect models.Multivariate survival analysis was performed using the Cox regression model.Results:A total of 2778 DLBCL patients diagnosed between January,2010 and December,2015 were enrolled to this study.After validating previous definitions,the SCHOLAR-1 study was most suitable to define refractory DLBCL.The estimated 5-year cumulative incidence of refractory patients was 20%(95% confidence Interval[CI]=18%-22%).After the determination of refractory disease,overall response rate and complete remission rate were 30%(95%CI=22%-38%)and 9%(95%CI=4%-15%),respectively.Patients with either no response to immunochemotherapy or relapse within 12 months after stem-cell transplantation had inferior survival with a median OS of 5.9 months(95%CI=5.5-7.1 months)and 2-year OS rate of 16%(95%CI=12%-20%).International prognostic index score 4-5(hazard ratio[HR]=2.22;95%CI=1.47-3.35),central nervous systemrelapse(HR=1.43;95%CI=1.04-1.97),and best response status(HR=2.68;95%CI=1.42-5.03 for partial remission.HR=5.97,95%CI=3.21-11.11 for stable disease/progressive disease)were independent unfavorable prognostic factors.Conclusions:This is the first large-scale Asian cohort study focusing on outcomes of refractory DLBCL.The definition of the SCHOLAR-1 study identifies patients with homogenously inferior survival,thus is appropriate to select refractory DLBCL.Due to poor clinical outcomes in the rituximab era,patients with refractory DLBCL may be potential candidates for novel treatment modalities.

Haploidentical transplantation has a superior graft-versus-leukemia effect than HLA-matched sibling transplantation for Ph- high-risk B-cell acute lymphoblastic leukemia

Background: Compared with human leukocyte antigen (HLA)-matched sibling donor (MSD) transplantation, it remains unclear whether haploidentical donor (HID) transplantation has a superior graft-versus-leukemia (GVL) effect for Philadelphia-negative (Ph-) high-risk B-cell acute lymphoblastic leukemia (B-ALL). This study aimed to compare the GVL effect between HID and MSD transplantation for Ph- high-risk B-ALL.Methods: This study population came from two prospective multicenter trials (NCT01883180, NCT02673008). Immunosuppressant withdrawal and prophylactic or pre-emptive donor lymphocyte infusion (DLI) were administered in patients without active graft-versus-host disease (GVHD) to prevent relapse. All patients with measurable residual disease (MRD) positivity posttransplantation (post-MRD+) or non-remission (NR) pre-transplantation received prophylactic/pre-emptive interventions. The primary endpoint was the incidence of post-MRD+.Results: A total of 335 patients with Ph- high-risk B-ALL were enrolled, including 145 and 190, respectively, in the HID and MSD groups. The 3-year cumulative incidence of post-MRD+ was 27.2% (95% confidence interval [CI]: 20.2%-34.7%) and 42.6% (35.5%-49.6%) in the HID and MSD groups(P = 0.003), respectively. A total of 156 patients received DLI, including 60 (41.4%) and 96 (50.5%), respectively, in the HID and MSD groups (P= 0.096). The 3-year cumulative incidence of relapse was 18.6% (95% CI: 12.7%-25.4%) and 25.9% (19.9%-32.3%;P = 0.116) in the two groups, respectively. The 3-year overall survival (OS) was 67.4% (95% CI: 59.1%-74.4%) and 61.6% (54.2%-68.1%;P = 0.382), leukemia-free survival (LFS) was 63.4% (95% CI: 55.0%-70.7%) and 58.2% (50.8%-64.9%;P= 0.429), and GVHD-free/relapse-free survival (GRFS) was 51.7% (95% CI: 43.3%-59.5%) and 37.8% (30.9%-44.6%;P= 0.041), respectively, in the HID and MSD groups.Conclusion: HID transplantation has a lower incidence of post-MRD+ than MSD transplantation, suggesting that HID transplantation might have a superior GVL effect than MSD transplantation for Ph- high-risk B-ALL patients.Trial registration: ClinicalTrials.gov: NCT01883180, NCT02673008.