Publications by authors named "Kai-Yan Liu"

350 Publications

Educational level and colorectal cancer risk: the mediating roles of lifestyle and dietary factors.

Eur J Cancer Prev 2021 May 7. Epub 2021 May 7.

Department of Epidemiology, School of Public Health, Sun Yat-sen University Department of Colorectal Surgery, Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Objective: The association between the educational level and colorectal cancer risk was controversial in developed countries and evidence was limited in Chinese population. This study aimed to investigate the association between the educational level and colorectal cancer risk in Guangdong Province, China.

Methods: From July 2010 to April 2019, 2502 newly diagnosed colorectal cancer patients and 2538 sex- and age-matched controls were recruited in this case-control study. Multivariable logistic regression models were used to examine the association between the educational level and colorectal cancer risk. Path analysis was used to investigate whether behavioral risk factors potentially mediated the association between the educational level and colorectal cancer risk.

Results: Educational level was inversely associated with the colorectal cancer risk. People who graduated from the college or above had a lower risk of colorectal cancer than those from the primary school or below, with an adjusted odds ratio of 0.42 [95% confidence intervals (CI), 0.34-0.52]. The total, direct and indirect effects of the educational level for the colorectal cancer risk were statistically significant in the path diagram. Path analysis showed that lower red and processed meat intake and higher tea and coffee drinking among high educational participants contributed to the inverse association between the educational level and colorectal cancer risk.

Conclusion: The findings suggested that the educational level was inversely associated with the colorectal cancer risk. The association might be mediated by red and processed meat intake, household and leisure-time activities, and tea and coffee drinking.
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http://dx.doi.org/10.1097/CEJ.0000000000000697DOI Listing
May 2021

Risk factors and outcomes of diffuse alveolar haemorrhage after allogeneic haematopoietic stem cell transplantation.

Bone Marrow Transplant 2021 Apr 12. Epub 2021 Apr 12.

Peking University People's Hospital, Peking University Institute of Haematology, Beijing, China.

Diffuse alveolar haemorrhage (DAH) is a life-threatening pulmonary complication occurring after allogeneic haematopoietic stem cell transplantation (allo-HSCT) without an explicit aetiology or a standard treatment. This study aimed to explore the occurrence and prognosis of DAH after allo-HSCT, in addition to comparing discrepancies in the incidence, clinical characteristics and outcomes of DAH between patients undergoing haploidentical HSCT (HID-HSCT) and matched related donor HSCT (MRD-HSCT). We retrospectively evaluated 92 consecutive patients among 3987 patients with a confirmed diagnosis of DAH following allo-HSCT (HID: 71 patients, MRD: 21 patients). The incidence of DAH after allo-HSCT was 2.3%, 2.4% after HID-HSCT and 2.0% after MRD-HSCT (P = 0.501). The prognosis of patients with DAH after transplantation is extremely poor. The duration of DAH was 7.5 days (range, 1-48 days). The probabilities of overall survival (OS) were significantly different between patients with and without DAH within 2 years after transplantation (P < 0.001). According to the Cox regression analysis, a significant independent risk factor for the occurrence of DAH was delayed platelet engraftment (P < 0.001), and a high D-dimer level (>500 ng/ml) was a significant risk factor for the poor prognosis of DAH. HID-HSCT is similar to MRD-HSCT in terms of the outcomes of DAH.
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http://dx.doi.org/10.1038/s41409-021-01293-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040008PMC
April 2021

Optimal gestational weight gain in Chinese pregnant women by Chinese-specific BMI categories: a multicentre prospective cohort study.

Public Health Nutr 2021 Apr 12:1-11. Epub 2021 Apr 12.

Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou510080, People's Republic of China.

Objective: To establish optimal gestational weight gain (GWG) in Chinese pregnant women by Chinese-specific BMI categories and compare the new recommendations with the Institute of Medicine (IOM) 2009 guidelines.

Design: Multicentre, prospective cohort study. Unconditional logistic regression analysis was used to evaluate the OR, 95 % CI and the predicted probabilities of adverse pregnancy outcomes. The optimal GWG range was defined as the range that did not exceed a 1 % increase from the lowest predicted probability in each pre-pregnancy BMI group.

Setting: From nine cities in mainland China.

Participants: A total of 3731 women with singleton pregnancy were recruited from April 2013 to December 2014.

Results: The optimal GWG (ranges) by Chinese-specific BMI was 15·0 (12·8-17·1), 14·2 (12·1-16·4) and 12·6 (10·4-14·9) kg for underweight, normal weight and overweight pregnant women, respectively. Inappropriate GWG was associated with several adverse pregnancy outcomes. Compared with women gaining weight within our proposed recommendations, women with excessive GWG had higher risk for macrosomia, large for gestational age and caesarean section, whereas those with inadequate GWG had higher risk for low birth weight, small for gestational age and preterm delivery. The comparison between our proposed recommendations and IOM 2009 guidelines showed that our recommendations were comparable with the IOM 2009 guidelines and could well predict the risk of several adverse pregnancy outcomes.

Conclusions: Inappropriate GWG was associated with higher risk of several adverse pregnancy outcomes. Optimal GWG recommendations proposed in the present study could be applied to Chinese pregnant women.
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http://dx.doi.org/10.1017/S1368980021001622DOI Listing
April 2021

Unmanipulated haploidentical hematopoietic stem cell transplantation is an excellent option for children and young adult relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia after CAR-T-cell therapy.

Leukemia 2021 Apr 6. Epub 2021 Apr 6.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking-Tsinghua Center for Life Science, Research Unit of Key Technique for Diagnosis and Treatment of Hematologic Malignancies, Chinese Academic of Medical Sciences, Beijing, China.

Although chimeric antigen receptor T-cell (CAR-T) therapy produces a high complete remission rate among patients with relapsed/refractory B-cell acute lymphoblastic leukemia, relapse remains an urgent issue. It is uncertain whether consolidative haploidentical-allogeneic hematopoietic stem cell transplantation (haplo-HSCT) is suitable for achieving sustainable remission. Therefore, we aimed to assess the efficacy and safety of bridging CAR-T therapy to haplo-HSCT. Fifty-two patients with relapsed/refractory Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia who underwent haplo-HSCT after CAR-T therapy were analyzed. The median time from CAR-T therapy to haplo-HSCT was 61 days. After a median follow-up of 24.6 months, the 1-year probabilities of event-free survival, overall survival, and cumulative incidence of relapse were 80.1% (95% confidence interval (CI), 69.0-90.9), 92.3% (95% CI, 85.0-99.5), and 14.1% (95% CI, 10.7-17.4), respectively, while the corresponding 2-year probabilities were 76.0% (95% CI, 64.2-87.7), 84.3% (95% CI, 74.3-94.3), and 19.7% (95% CI, 15.3-24.0), respectively. No increased risk of 2-year cumulative incidence of graft-versus-host disease, treatment-related mortality, or infection was observed. A pre-HSCT measurable residual disease-positive status was an independent factor associated with poor overall survival (hazard radio: 4.201, 95% CI: 1.034-17.063; P = 0.045). Haplo-HSCT may be a safe and effective treatment strategy to improve event-free survival and overall survival after CAR-T therapy.
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http://dx.doi.org/10.1038/s41375-021-01236-yDOI Listing
April 2021

The Prognostic Significance of Fusions in Adult Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: A Comprehensive Cohort Study From a Single Chinese Center.

Front Oncol 2021 17;11:632532. Epub 2021 Mar 17.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, National Clinical Research Center for Hematologic Disease, Beijing, China.

Novel recurrent fusion gene types such as zinc finger protein 384 () fusions have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with the application of next-generation sequencing technologies. However, the comprehensive large-scale clinical cohort study for clarifying their prognostic significance remains scarce to date. A total of 242 consecutive adult Ph-negative BCP-ALL patients treated in our institute were retrospectively screened fusions at diagnosis by multiplex real time quantitative PCR. fusions were identified in 47 patients (19.4%) and all belonged to B-other ALL (having no high hyperdiploid karyotype, -, -, -, or rearrangement). In the whole cohort, patients with fusions had significantly higher 3-year relapse-free-survival (RFS) and tended to have a higher 3-year overall survival (OS) than those with no fusions (80.1% 52.5%, = 0.013; 67.6% 54.0%, = 0.10). For patients receiving chemotherapy alone and received allogeneic-hematologic stem cell transplantation (allo-HSCT) were censored at the time of transplantation, patients with fusions had both similar RFS and similar OS to B-other ALL patients with no fusions (RFS: P =0.94 and 0.30; OS: P =0.94 and 0.51). For patients receiving transplantation, those with fusions had significantly higher 3-year RFS than B-other ALL patients with no fusions and their OS were similar (P = 0.022 and 0.24). Only two of 31 patients with fusions and receiving allo-HSCT relapsed, individually occurred 66.8 and 69.8 months after transplantation. Therefore, fusion is common in adult BCP-ALL, which may define a new group from BCP-ALL containing no classical fusion transcript with better prognosis through receiving allo-HSCT.
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http://dx.doi.org/10.3389/fonc.2021.632532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010301PMC
March 2021

[Comparison of Plasma Components between Frozen Plasma and Fresh Frozen Plasma].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Apr;29(2):615-619

Peking University People's Hospital,Peking University Institute of Hematology, Beijing 100044,

Objective: To compare the plasma components of frozen plasma (FP) and fresh frozen plasma (FFP).

Methods: Twenty samples of FP and 20 samples of FFP from Beijing Red Cross Blood Center were randomly selected. Immediately after plasma melting, 12 plasma components including coagulation factor, fibrinolytic system and anticoagulation protein were detected, including activated partial thromboplastin time (APTT), prothrombin time (PT), coagulation factor Ⅷ (FⅧ) activity, coagulation factor Ⅴ (FⅤ) activity, fibrinogen(FIB) level, ADAMTS-13 activity, von Willebrand factor(vWF) activity, D-dimer (D-dimer, DD), fibrin degradation products (FDP), antithrombin (AT), protein C (PC), and protein S (PS). All these coagulation components between the two types of plasma were compared and analyzed.

Results: Compared with FFP, APTT in FP was significantly prolonged(t=3.428, P<0.01), and PT was also significantly prolonged(z=-2.140, P<0.05), and FⅧ activity was decreased (t=-3.372, P<0.01), but all in the reference range, and PS activity was decreased(t=-2.458,P<0.05), there was no statistical difference in the other part between two types of plasma(P>0.05).

Conclusion: FP can substitute FFP in the treatment of some diseases, although it is lack of some coagulation factors and anticoagulation protein.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.02.049DOI Listing
April 2021

The impact of the combination of KIT mutation and minimal residual disease on outcome in t(8;21) acute myeloid leukemia.

Blood Cancer J 2021 Apr 1;11(4):67. Epub 2021 Apr 1.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

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http://dx.doi.org/10.1038/s41408-021-00461-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016839PMC
April 2021

Acute Cholecystitis Following Allogeneic Hematopoietic Stem Cell Transplantation: Clinical Features, Outcomes, Risk Factors, and Prediction Model.

Transplant Cell Ther 2021 Mar 24;27(3):253.e1-253.e9. Epub 2020 Dec 24.

Peking University Institute of Hematology, Peking University People's Hospital, Beijing, China; Collaborative Innovation Center of Hematology, Peking University, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; National Clinical Research Center for Hematologic Disease, Beijing, China. Electronic address:

Acute cholecystitis (AC) is a potentially fatal complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, only limited information is available on its clinical features, outcomes, and risk management strategies. This retrospective, nested, case-control study included 6701 patients undergoing allo-HSCT at our center from January 2004 to June 2019. In total, 72 patients (1.1%) were diagnosed with AC; among these, acute acalculous cholecystitis had a slightly higher prevalence (42 patients, 58.3%). Patients with moderate and severe AC exhibited remarkably worse overall survival (P = .001) and non-relapse mortality (P = .011) than others. Survival of haploidentical HSCT recipients with AC was comparable to that for patients with human leukocyte antigen (HLA)-identical donors. Age ≥ 18 years, antecedent stage II to IV acute graft-versus-host disease, and total parenteral nutrition were identified as potential risk factors for AC following allo-HSCT, while haploidentical transplantations were not more susceptible to AC than HLA-identical HSCT. Based on these criteria, a risk score model was developed and validated to estimate the probability of AC following allo-HSCT. The model separates all patients into low-, intermediate-, and high-risk groups and thereby provides a basis for early detection of this complication in the management of allo-HSCT.
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http://dx.doi.org/10.1016/j.jtct.2020.12.016DOI Listing
March 2021

Wilms' tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.

BMC Cancer 2021 Mar 19;21(1):292. Epub 2021 Mar 19.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Chinese Academy of Medical Sciences, 2019RU029, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

Background: Sequential monitoring of Wilms' tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children.

Methods: Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan-Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM.

Results: Of the 151 consecutive patients included, the median age was 10 years (range, 1-17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/10 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25-6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies.

Conclusions: Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.
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http://dx.doi.org/10.1186/s12885-021-08022-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980537PMC
March 2021

A risk score system for stratifying the risk of relapse in B cell acute lymphocytic leukemia patients after allogenic stem cell transplantation.

Chin Med J (Engl) 2021 03 12;134(10):1199-1208. Epub 2021 Mar 12.

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing 100044, China.

Background: For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT.

Methods: A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables.

Results: All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P  < 0.001, P = 0.004, and P  < 0.001, respectively) and worse LFS (P  < 0.001, P = 0.017, and P  < 0.001, respectively), and OS (P  < 0.001, P = 0.009, and P  < 0.001, respectively) than patients without MRD after transplantation, transplanted in CR1, and with cGVHD. A risk score for predicting relapse was formulated with the three above variables. The 5-year relapse rates were 6.3%, 16.6%, 55.9%, and 81.8% for patients with scores of 0, 1, 2, and 3 (P  < 0.001), respectively, while the 5-year LFS and OS values decreased with increasing risk score.

Conclusion: This new risk score system might stratify patients with different risks of relapse, which could guide treatment.
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http://dx.doi.org/10.1097/CM9.0000000000001402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143760PMC
March 2021

Haploidentical Stem Cell Transplantation With a Novel Conditioning Regimen in Older Patients: A Prospective Single-Arm Phase 2 Study.

Front Oncol 2021 26;11:639502. Epub 2021 Feb 26.

National Clinical Research Center for Treatment of Hematological Disease, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.

Haploidentical stem cell transplantation (haplo-SCT) has demonstrated encouraging results in younger patients. There is also an increasing need for haplo-SCT in older patients. However, the high risk of treatment-related mortality (TRM) in older patients is still a major concern. We aimed to investigate a novel conditioning regimen (Bu/Flu/Cy/ATG) followed by haplo-SCT in older patients. This prospective, single-arm clinical trial was performed at Peking University Institute of Hematology, China. Patients were enrolled if they were (1) diagnosed with acute leukemia or MDS; (2) without MSD and MUD, and with HID available; and (3) age ≥55 years. The Bu/Flu/Cy/ATG regimen consisted of the following agents: Ara-C (2 g/m/day, injected i.v.) on days-10 and-9; BU (9.6 mg/kg, injected i.v. in 12 doses) on days-8,-7, and-6; Flu (30 mg/m/day, injected i.v.) from day-6 to day-2; Cy (1 g/m/day, injected i.v.) on days-5 and-4; semustine (250 mg/m, orally) on day-3 and antithymocyte globulin (ATG) [2.5 mg/kg/day, rabbit, SangStat (Lyon, France)] on days-5,-4,-3, and-2. The primary endpoint was 1-year TRM. From April 1, 2018 to April 10, 2020, a total of 50 patients were enrolled. All patients achieved neutrophil engraftment with complete donor chimerism. The cumulative incidence of grade 2-4 aGVHD at day-100 was 22.0%. The cumulative incidences of CMV viremia and EBV viremia on day 100 were 68.0 and 20.0%, respectively. The cumulative incidence of TRM at 1-year was 23.3%. and the cumulative incidence of relapse (CIR) at 1 year after transplantation was 16.5%. The overall survival (OS) and leukemia-free survival (LFS) at 1 year were 63.5 and 60.2%, respectively. The outcomes were also comparable with patients who received Bu/Cy/ATG regimen using a propensity score matching method. In conclusion, this study suggested that a novel conditioning regimen followed by haploidentical HSCT might be a promising option for older patients. The study was registered as a clinical trial. www.ClinicalTrials.gov, identifier: NCT03412409.
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http://dx.doi.org/10.3389/fonc.2021.639502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952870PMC
February 2021

Minimal residual disease monitoring and preemptive immunotherapies for frequent 11q23 rearranged acute leukemia after allogeneic hematopoietic stem cell transplantation.

Ann Hematol 2021 May 13;100(5):1267-1281. Epub 2021 Mar 13.

National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.

The prognosis of 11q23/KMT2A-rearranged (KMT2A-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important prognostic factor for relapse. Thus, we aimed to identify the evolution of KMT2A before and after allo-HSCT and the efficacy of preemptive immunotherapies for KMT2A-r AL patients receiving allo-HSCT. KMT2A expression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutive KMT2A-r AL patients. Pre-HSCT KMT2A positivity was correlated with post-HSCT KMT2A positivity (correlation coefficient=0.371, P<0.001). The rates of achieving KMT2A negativity after allo-HSCT were 96.6%, 92.9%, and 68.8% in the pre-HSCT low-level group (>0, <0.1%), intermediate-level group (≥ 0.1%, <1%), and high-level group (≥1%), respectively. The rates of regaining KMT2A positivity after allo-HSCT were 7.7%, 35.7%, 38.5%, and 45.5% for the pre-HSCT KMT2A-negative, low-level, intermediate-level, and high-level groups, respectively (P<0.001). The 4-year cumulative incidence of relapse after allo-HSCT was as high as 53.7% in the pre-HSCT KMT2A expression ≥ 0.1% group, which was compared to the KMT2A-negative group (15.1%) and KMT2A <0.1% group (31.2%). The clinical outcomes of patients with post-HSCT KMT2A positivity were poorer than those of patients with persistent KMT2A negativity. Although post-HSCT preemptive immunotherapies might help to achieve KMT2A negativity, the long-term efficacy was unsatisfactory. Thus, pre-HSCT KMT2A positivity was significantly associated with post-HSCT KMT2A positivity. The clinical outcomes of patients with post-HSCT KMT2A positivity were poor, which might not be overcome by commonly used immunotherapies.
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http://dx.doi.org/10.1007/s00277-021-04488-xDOI Listing
May 2021

Co-Reactivation of Cytomegalovirus and Epstein-Barr Virus Was Associated With Poor Prognosis After Allogeneic Stem Cell Transplantation.

Front Immunol 2020 16;11:620891. Epub 2021 Feb 16.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Treatment of Hematological Disease, Beijing, China.

Reactivation of cytomegalovirus (CMV) or Epstein-Barr virus (EBV) is common after hematopoietic stem cell transplantation (HSCT). Previous researches have demonstrated that either CMV or EBV reactivation is associated with poor outcomes of HSCT. However, few studies investigate the impact of CMV and EBV co-reactivation after HSCT. In this study, we described the clinical characteristics of HSCT recipients with CMV and EBV co-reactivation (defined as CMV and EBV viremia occur at the same period of time). We conducted a longitudinal study of 247 patients who underwent HSCT in our center. A total of 24 (9.7%) patients had CMV and EBV co-reactivation. These patients showed higher incidence of viral pneumonitis (P=0.005). Patients with CMV and EBV co-reactivation had significant lower 1-year overall survival (OS) (P=0.004) and lower 1-year leukemia free survival (LFS) (P=0.016). Our further analysis suggested that duration of CMV (P=0.014), EBV (P<0.001), and CD4+CD25+ T cell counts at day 30 post-transplantation (P=0.05) are independent risk factors of virus co-reactivation. In conclusion, patients who developed co-reactivation of CMV and EBV had poor prognosis in terms of lower 1-year OS and LFS, and the CMV and EBV co-reactivation was associated with prolonged CMV or EBV duration and poor CD4+CD25+ T cell reconstitution at day 30 post-transplantation.
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http://dx.doi.org/10.3389/fimmu.2020.620891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921792PMC
February 2021

Iron intake with the risk of breast cancer among Chinese women: a case-control study.

Public Health Nutr 2021 Feb 23:1-13. Epub 2021 Feb 23.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou510080, People's Republic of China.

Objective: The current study evaluated the associations between different forms and sources of Fe and breast cancer risk in Southern Chinese women.

Design: Case-control study. We collected data on the consumption of Fe from different forms and food sources by using a validated FFQ. Multivariable logistic regression and restricted cubic spline (RCS) analysis was used to reveal potential associations between Fe intake and breast cancer risk.

Setting: A case-control study of women at three major hospitals in Guangzhou, China.

Participants: From June 2007 to March 2019, 1591 breast cancer cases and 1622 age-matched controls were recruited.

Results: In quartile analyses, Fe from plants and Fe from white meat intake were inversely associated with breast cancer risk, with OR of 0·65 (95 % CI 0·47, 0·89, Ptrend = 0·006) and 0·76 (95 % CI 0·61, 0·96, Ptrend = 0·014), respectively, comparing the highest with the lowest quartile. No associations were observed between total dietary Fe, heme or non-heme Fe, Fe from meat or red meat and breast cancer risk. RCS analysis demonstrated J-shaped associations between total dietary Fe, non-heme Fe and breast cancer, and reverse L-shaped associations between heme Fe, Fe from meat and Fe from red meat and breast cancer.

Conclusion: Fe from plants and white meat were inversely associated with breast cancer risk. Significant non-linear J-shaped associations were found between total dietary Fe, non-heme Fe and breast cancer risk, and reverse L-shaped associations were found between heme Fe, Fe from meat or red meat and breast cancer risk.
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http://dx.doi.org/10.1017/S1368980021000471DOI Listing
February 2021

Interferon-α may help prevent molecular relapse of chronic myeloid leukemia after the discontinuation of tyrosine kinase inhibitors.

Ther Adv Hematol 2021 22;12:2040620720986643. Epub 2021 Jan 22.

Peking University People's Hospital, Institute of Hematology, National Clinical Research Center for Hematologic Disease, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People's Republic of China.

Background: Currently, the goal of chronic myeloid leukemia (CML) treatment is normal survival and good quality of life without life-long treatment, namely, "treatment-free remission" (TFR). At present, approximately only 50% of patients with CML with a deep molecular response are able to discontinue tyrosine kinase inhibitor (TKI) without experiencing molecular relapse [MR; loss of major molecular response (MMR)]. In addition, prior interferon (IFN) treatment is associated with a higher rate of TFR.

Methods: We aimed to evaluate the feasibility of TKI discontinuation in Chinese patients with CML and determine whether IFN could prevent MR when used after TKI discontinuation in patients with 0.0032% < ⩽0.1%. Therefore, we retrospectively analyzed the data of patients with CML who discontinued TKI treatment at our center.

Results: Forty-nine patients who discontinued TKI therapy after achieving MR 4.5 were included in this study, and the median follow-up time from TKI discontinuation was 27 (7, 75) months. Nineteen patients eventually lost MMR, and the TFR rate of the 49 patients was 67% (95% confidence interval 53.6%, 80.3%) at 12 months. The duration of MR 4.5 ⩾54 months and duration of imatinib ⩾85 months were significantly associated with a higher TFR rate. Of the 22 patients with 0.0032% < ⩽0.1%, 12 received IFN-α treatment. The median IFN-α therapy duration was nine (2, 18) months, and three patients eventually lost MMR. Three patients discontinued IFN-α after 2, 2.5, and 10 months, and maintained MMR for 9, 8, and 11 months after IFN discontinuation, respectively. Of the 10 patients not receiving IFN-α treatment, eight eventually lost MMR. The MR-free survival rate was significantly different between the patients treated with and those treated without IFN-α over 24 months (70.7% 15.0%, = 0.002).

Conclusion: These results indicate that after TKI discontinuation, IFN-α can be administered to patients with 0.0032% < ⩽0.1%, which may help prevent MR.
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http://dx.doi.org/10.1177/2040620720986643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841675PMC
January 2021

HCMV modulates c-Mpl/IEX-1 pathway-mediated megakaryo/thrombopoiesis via PDGFRα and αvβ3 receptors after allo-HSCT.

J Cell Physiol 2021 Feb 21. Epub 2021 Feb 21.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.

Thrombocytopenia is a common complication of human cytomegalovirus (HCMV) infection in immunocompromised hosts, which contributes to poor prognosis even in patients receiving antiviral treatment. Here, we investigated the megakaryo/thrombopoiesis process, including the involvement of the c-Mpl/IEX-1 pathway, after HCMV infection, identified receptors mediating the interaction between megakaryocytes (MKs) and HCMV, and explored novel therapeutic targets. Our data shows that HCMV directly infects megakaryocytes in patients with HCMV DNAemia and influences megakaryopoiesis via the c-Mpl/IEX-1 pathway throughout megakaryocyte maturation, apoptosis, and platelet generation in vivo and in vitro. After treatment with inhibitors of PDGFRα and αvβ3, the HCMV infection rate in MKs was significantly reduced, suggesting that IMC-3G3 and anti-αvβ3 are potential therapeutic alternatives for viral infection. In summary, our study proposes a possible mechanism and potential treatments for thrombocytopenia caused by HCMV infection and other viral diseases associated with abnormal hemostasis.
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http://dx.doi.org/10.1002/jcp.30335DOI Listing
February 2021

Pre-transplantation cytoreduction does not benefit advanced myelodysplastic syndrome patients after myeloablative transplantation with grafts from family donors.

Cancer Commun (Lond) 2021 Apr 10;41(4):333-344. Epub 2021 Feb 10.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, P. R. China.

Background: The role of pre-hematopoietic stem cell transplantation (HSCT) cytoreduction with either induction chemotherapy (IC) or hypomethylating agents (HMAs) in treating advanced myelodysplastic syndrome (MDS) remains debatable. We aimed to evaluate pre-HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre-HSCT cytoreduction and those with best supportive care.

Methods: We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor (HID, n = 162) or matched related donor (MSD, n = 66) with uniform myeloablative conditioning regimens between January 2015 and December 2018. Of these 228 patients, 131 (57.5%) were treated exclusively with pre-HSCT best supportive care (BSC), 49 (22.5%) were given HMA, and 48 (21.1%) received both IC and HMA. Propensity score-matching analysis, multivariate analyses, and subgroup analyses were performed to elucidate the impact of pre-HSCT strategies on transplant outcomes.

Results: The 3-year relapse-free survival (RFS) rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts (P = 0.189) and were 78.2%, 66.7%, and 73.2% for the BSC, HMA, and HMA+IC groups, respectively (P = 0.269). A propensity score-matching analysis confirmed that the 3-year RFS rates were 81.9%, 87.5%, and 66.9% for BSC, cytoreduction complete remission (CR), and cytoreduction non-CR groups, respectively (P = 0.051). Multivariate analyses demonstrated that pre-HSCT cytoreduction, older patient age, monosomal karyotype, and interval between diagnosis and HSCT were poor prognostic factors for RFS. In the subgroup analyses, BSC was associated with longer RFS compared to cytoreduction among the younger patients, those with international prognostic scoring system intermediate-2/high risk at diagnosis, and those with intermediate/poor cytogenetics.

Conclusions: Different pre-HSCT therapies did not yield discrepant post-HSCT outcomes. No benefit in terms of post-HSCT outcomes were correlated with pre-HSCT cytoreduction in advanced MDS even for cytoreduction CR patients. Early referral to HSCT is essential for advanced MDS patients.
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http://dx.doi.org/10.1002/cac2.12140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045915PMC
April 2021

[The Predict Significance of ALDH Activity to the Relapse of t(8;21) Acute Myeloid Leukemia Patients at Complete Remission].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2021 Feb;29(1):43-48

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing 100044, China,E-mail:

Objective: To investigate the predict significance of the high aldehyde dehydrogenase activity (ALDH) propitiation to the relapse of t(8;21) acute myeloid leukemia(AML) patients before and after treatment.

Methods: Bone marrow samples of 23 t(8;21) AML patients diagnosis and achieved complete remission in our hospital from April 2015 to June 2016 were collected, then flow cytometry method was used to detect the activity of ALDH, relationship between it and relapse was analyzed.

Results: All the patients were followed up for a median of 32 (2-52) months. The median percentage of CD34CD38 and CD34CD38ALDH cells among nucleated cells were 2.7 (0.36-35.7)% and 0.017 (0.0013-0.62)% at diagnosis, respectively. Among the bone marrow samples in patients achieved CR, the median percentage of CD34CD38 cells was 0.035 (0.0064-0.66)%, and it was significantly decreased as compared with the percentage at diagnosis (P<0.001); The median percentage of CD34CD38ALDH cells was 0.014 (0.0019-0.24)%, and it showed no different as compared with the percentage at diagnosis (P=0.45). Survival analysis showed that patients with higher percentage of CD34CD38 and CD34CD38ALDH cells at diagnosis tended to the lower 3-year relapse-free survival (RFS) (P=0.27 and 0.21). Furthermore, patients with higher percentage of CD34CD38 and CD34CD38ALDH cells when achieved CR had a significant lower 3-year RFS rates (P=0.010 and 0.0044) as compared with those with lower percentage of CD34CD38 and CD34CD38ALDH cells. Multivariate analysis showed that higher percentage of CD34CD38ALDH cells when achieved CR was an independent factor affecting RFS of the patients.

Conclusion: The percentage of CD34CD38ALDH cells at CR in t(8;21) AML patients could predicts relapse, and had more profound predictive significance for relapse than the percentage of CD34CD38 cells.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2021.01.007DOI Listing
February 2021

Haploidentical hematopoietic stem cell transplantation for patients with myeloid sarcoma: a single center retrospective study.

Ann Hematol 2021 Mar 8;100(3):799-808. Epub 2021 Jan 8.

Peking University People's Hospital, Peking University Institute of Hematolo, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantationgy, National Clinical Research Center for Hematologic Disease, No.11, Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential strategy for myeloid sarcoma (MS). The previous reports focused mainly on matched sibling donor (MSD) or matched unrelated donor (MUD) transplantation. There are no reports on haploidentical HSCT (haplo-HSCT) in MS. We retrospectively reviewed 14 MS patients who underwent haplo-HSCT. All patients achieved complete donor engraftment. The median time for neutrophil engraftment and platelet engraftment were 10 (12-21) days and 18 (8-31) days. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) and 3-year cumulative incidence of chronic GVHD were 37.7% (95%CI, 23.2-52.1%) and 35.7% (95%CI, 22.2-49.2%). Cytomegalovirus (CMV) reactivation was documented in 86% patients, and only one patient developed CMV pneumonia. Treatment-related mortality occurred in one (7%) patient. The 1- and 3-year cumulative incidence of relapse was 21.4% (95%CI, 11.8-31.1%) and 35.7% (95%CI, 22.4-49.0%). The probability of overall survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 64.3% (95%CI, 43.5-95.0%), respectively. The probability of disease-free survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 57.1% (95%CI, 36.3-89.9%), respectively. In conclusion, haplo-HSCT is a feasible method for patients with MS who have no MSD or MUD.
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http://dx.doi.org/10.1007/s00277-020-04383-xDOI Listing
March 2021

Allogeneic hematopoietic stem cell transplantation for intermediate-risk acute myeloid leukemia in the first remission: outcomes using haploidentical donors are similar to those using matched siblings.

Ann Hematol 2021 Feb 7;100(2):555-562. Epub 2021 Jan 7.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Research Unit of Key Technique for Diagnosis and Treatments of Hematologic Malignancies, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, No 11 Xizhimen South Street, Beijing, 100044, China.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group: 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.
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http://dx.doi.org/10.1007/s00277-020-04359-xDOI Listing
February 2021

Dynamic immune profiling identifies the stronger graft-versus-leukemia (GVL) effects with haploidentical allografts compared to HLA-matched stem cell transplantation.

Cell Mol Immunol 2021 May 6;18(5):1172-1185. Epub 2021 Jan 6.

Peking University People's Hospital & Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, No. 11 South Street of Xizhimen, Xicheng District, 100044, Beijing, China.

Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.
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http://dx.doi.org/10.1038/s41423-020-00597-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093297PMC
May 2021

Human herpesvirus 6 reactivation in unmanipulated haploidentical hematopoietic stem cell transplantation predicts the occurrence of grade II to IV acute graft-versus-host disease.

Transpl Infect Dis 2020 Dec 16:e13544. Epub 2020 Dec 16.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.

Background: Human herpesvirus 6 (HHV-6) reactivation is relatively common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the incidence of HHV-6 reactivation and the clinical outcomes following unmanipulated haploidentical HSCT (haplo-HSCT) remain unknown.

Method: We prospectively monitored blood HHV-6 DNA using real-time quantitative polymerase chain reaction weekly until day 100 post unmanipulated haplo-HSCT in patients with hematological malignancies.

Results: From November 2016 to March 2017, 102 patients (58 male and 44 female, median age 25(2-58) years old) were enrolled. Within 100 days post-transplantation, 27 patients (27/136, 19.9%) developed HHV-6 viremia with a median onset time of 14 (7-98) days. The cumulative incidence of HHV-6 reactivation on day 100 post-HSCT was 25.5 ± 4.3% in haplo-HSCT. The median HHV-6 copy number was 1.45 × 10 (5.48 × 10 -2.00 × 10 ) copies/ml. The HHV-6 viremia duration time was 7 days in 23 patients, 14 days in one patient and 21 days in one patient. In multivariate analysis, prior HHV-6 reactivation was an independent risk factor for grade 2-4 graft-versus-host disease (GVHD). But it did not influence the overall survival (OS)(HR 1.624, 95%CI 0.768-3.432, P = .204), disease-free survival (DFS) (HR 1.640, 95%CI 0.799-3.367, P = .177) and non-relapse mortality (NRM) (HR 1.644, 95%CI 0.670-4.038, P = .278).

Conclusion: The reactivation of HHV-6 after unmanipulated haploidentical transplantation predicts the occurrence of grade 2-4 a-GVHD, but it may not influence the overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM).
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http://dx.doi.org/10.1111/tid.13544DOI Listing
December 2020

Dietary Polyamines Intake and Risk of Colorectal Cancer: A Case-Control Study.

Nutrients 2020 Nov 22;12(11). Epub 2020 Nov 22.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

Polyamines (including putrescine, spermidine, and spermine) are small, cationic molecules that are necessary for cell proliferation and differentiation. Few studies have examined the association of dietary polyamines intake with colorectal cancer risk. The aim of this study was to evaluate total polyamines, putrescine, spermidine, and spermine intake in relation to colorectal cancer risk in China. In total, 2502 colorectal cancer cases and 2538 age-(5-year interval) and sex-matched controls were recruited from July 2010 to April 2019. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated by multivariable unconditional logistic regression after adjustment for various potential confounding factors. Higher intake of total polyamine, putrescine and spermidine was significantly associated with reduced risk of colorectal cancer. The adjusted ORs for the highest compared with the lowest quartile of intake were 0.60 (95% CI 0.50, 0.72; < 0.001) for total polyamines, 0.35 (95% CI 0.29, 0.43; < 0.001) for putrescine and 0.79 (95% CI 0.66, 0.95; = 0.001) for spermidine, respectively. However, higher intake of spermine was associated with increased risk of colorectal cancer, with an adjusted OR of 1.58 (95% CI 1.29, 1.93; < 0.001). This data indicate that higher intake of total polyamines, putrescine and spermidine, as well as lower intake of spermine, is associated with a decreased risk of colorectal cancer.
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http://dx.doi.org/10.3390/nu12113575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700244PMC
November 2020

The incidence, clinical outcome, and protective factors of mixed chimerism following hematopoietic stem cell transplantation for severe aplastic anemia.

Clin Transplant 2021 Feb 20;35(2):e14160. Epub 2021 Jan 20.

Peking University People's Hospital, Peking University Institute of Hematology, Peking, China.

Objectives: The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation.

Methods: A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained.

Results: Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort.

Conclusions: Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.
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http://dx.doi.org/10.1111/ctr.14160DOI Listing
February 2021

Ruxolitinib is an effective salvage treatment for multidrug-resistant graft-versus-host disease after haploidentical allogeneic hematopoietic stem cell transplantation without posttransplant cyclophosphamide.

Ann Hematol 2021 Jan 7;100(1):169-180. Epub 2020 Nov 7.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China.

The purpose of our study is to identify the efficacy of ruxolitinib in human leukocyte antigen (HLA) haploidentical hematopoietic stem cell transplantation (haplo-HSCT) recipients with multidrug-resistant (MDR)-graft-versus-host disease (GVHD, n = 34). MDR-GVHD was defined as GVHD showing no improvement after at least 3 types of treatments. The median number of previous GVHD-therapies was 4 for both MDR-acute GVHD (aGVHD) and MDR-chronic GVHD (cGVHD). For MDR-aGVHD (n = 15), the median time to response was 10 days (range 2 to 65), and the overall response rate (ORR) was 60.0% (9/15), including 40.0% (6/15) complete response (CR) and 20.0% (3/15) partial response (PR). The 1-year probability of overall survival after ruxolitinib was 66.7%. The rates of hematologic and infectious toxicities were 73.3% and 46.7% after ruxolitinib treatment. For MDR-cGVHD (n = 19), the median time to response was 29 days (range 6 to 175), and the ORR was 89.5% (17/19), including 26.3% (5/19) CR and 63.2% (12/19) PR. All patients remained alive until our last follow-up. The rates of hematologic and infectious toxicities were 36.8% and 47.4% after ruxolitinib treatment. Ruxolitinib is an effective salvage treatment for MDR-GVHD in haplo-HSCT recipients.
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http://dx.doi.org/10.1007/s00277-020-04273-2DOI Listing
January 2021

Long-term follow-up of CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation.

Cytotherapy 2020 12 26;22(12):755-761. Epub 2020 Aug 26.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China. Electronic address:

Background Aims: The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive.

Methods: The authors focused on the survival of 35 patients with B-cell acute lymphoblastic leukemia who relapsed after allo-HSCT and received CAR T cells.

Results: Of the 34 eligible patients, 30 achieved minimal residual disease-negative complete remission (CR), with a total CR rate of 85.7% (79.8-91.6%). There were 14 patients who received various forms of additional therapy after achieving CR. After a median follow-up of 20.7 months, it was noted that 17 patients had relapsed at a median of 4.5 months (2-34 months). The cumulative recurrence rate (RR) at 18 months was 68.3% (57.6-79.0%). Additional treatment did not reduce the RR but seemed to delay the time to relapse (mean: 5.9 months vs 13.1 months; P = 0.046). Patients with a lower tumor burden (≤10%) had a lower RR (25.0% vs 78.6% at 12 months; P = 0.006). The overall survival (OS) rate for the CR patients was 30.0% (20.3-29.7%) at 18 months, with a median OS of 12.7 months.

Conclusions: The authors' study indicated that for patients who relapsed after HSCT, although a high CR rate was achieved after CAR T therapy, the long-term efficacy was unsatisfactory. It is necessary to optimize additional treatment, including a second HSCT, to further improve long-term efficacy after CAR T infusion.
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http://dx.doi.org/10.1016/j.jcyt.2020.08.002DOI Listing
December 2020

Both Methylation and Copy Number Variation Participated in the Varied Expression of PRAME in Multiple Myeloma.

Onco Targets Ther 2020 31;13:7545-7553. Epub 2020 Jul 31.

Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, People's Republic of China.

Purpose: The cancer-testis antigen, which is a preferentially expressed antigen of melanoma (PRAME), is an ideal target for immunotherapy and cancer vaccines. Since the expression of this antigen is relevant to therapy responses, the heterogeneity in its expression and the underlying mechanism need to be investigated.

Patients And Methods: Plasma cell sorting was performed in 48 newly diagnosed multiple myeloma (MM) patients. Real-time quantitative PCR was performed to examine the PRAME transcript levels and gene copy numbers. Bisulfate clone sequencing of the PRAME promoter and exon 1b regions was performed in 4 patients. Quantitative methylation-specific PCR of the +287 CpG site was performed for all patients. The human MM cell lines RPMI8226, LP-1 and MOLP-2 were treated with 5-azacytidine.

Results: The median PRAME transcript level was 3.1% (range: 0-298.3%) in the plasma cells sorted from the 48 MM patients. Eleven (22.9%) and 37 (77.1%) patients were individually categorized into the PRAME low- and high-expression groups according to the cut-off value of 0.05%. The methylation ratios of the promoter and the 3' region of exon 1b region were both negatively related to the transcript levels. The degrees of methylation at the +287 CpG site were significantly negatively related to the transcript levels in all 48 patients (r=-0.44, P=0.0018), and those in the high-expression group (r=-0.69, P<0.0001) but not those in the low-expression group (r=-0.27, P=0.43). All 5 patients with homozygous deletions were categorized into the low-expression group. There were no significant differences in the PRAME transcript levels between the hemizygous deletion (n=8) and no deletion (n=35) groups (P=0.40). Furthermore, the PRAME transcript levels significantly increased in the MM cell lines after treatment with 5-azacytidine.

Conclusion: Both methylation and copy number variation may participate in the regulation of PRAME expression in MM; in patients with no homozygous deletion, PRAME expression is mainly controlled by methylation, and a proportion of fairly low expression is caused by homozygous deletion.
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http://dx.doi.org/10.2147/OTT.S240979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402861PMC
July 2020

Outcomes of symptomatic venous thromboembolism after haploidentical donor hematopoietic stem cell transplantation and comparison with human leukocyte antigen-identical sibling transplantation.

Thromb Res 2020 10 24;194:168-175. Epub 2020 Jun 24.

Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China; Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China; Collaborative Innovation Centre of Hematology, Peking University, Beijing, China; National Clinical Research Center for Hematologic Disease, China. Electronic address:

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is regarded as a curative therapy for majority of hematologic malignancies and some non-malignant hematologic diseases. Venous thromboembolism (VTE) has become increasingly recognized as a severe complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Objectives: To show the characteristics of VTE after haploidentical donor hematopoietic stem cell transplantation (HID-HSCT) and make comparisons with matched related donor HSCT (MRD-HSCT).

Patients/methods: A retrospective nested case-control study design was used, cases with VTE and matched controls were selected, with 3534 patients underwent HID-HSCT and 1289 underwent MRD-HSCT.

Results: During follow-up, 114 patients with VTE were identified. The incidence of VTE in HID-HSCT group was similar to that of MRD-HSCT group (2.4% versus 2.3%, P = 0.92). In HID-HSCT group, VTE occurred at a median time of 92.5 days, which was earlier than MRD-HSCT group (243.5 days). For HID-HSCT, advanced disease status, cardiovascular risk factors, acute graft-versus-host disease (aGVHD), and relapse were the independent risk factors for VTE. For MRD-HSCT, cardiovascular risk factors, aGVHD, and relapse were associated with VTE. Overall survival (OS) of patients following HID-HSCT and MRD-HSCT were similar, but the OS in patients with VTE was significantly lower than patients without VTE.

Conclusions: There was no statistical difference in the incidence of VTE after HID-HSCT compared with MRD-HSCT. The development of VTE adversely impacted the OS after allo-HSCT.
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http://dx.doi.org/10.1016/j.thromres.2020.06.036DOI Listing
October 2020

Comparison of different cytomegalovirus diseases following haploidentical hematopoietic stem cell transplantation.

Ann Hematol 2020 Nov 30;99(11):2659-2670. Epub 2020 Jul 30.

Peking University Institute of Hematology, Peking University People's Hospital, Xicheng District Xizhimen South Street No. 11, Beijing, 100044, China.

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.
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http://dx.doi.org/10.1007/s00277-020-04201-4DOI Listing
November 2020

Associations between serum concentration of flavonoids and breast cancer risk among Chinese women.

Eur J Nutr 2021 Apr 18;60(3):1347-1362. Epub 2020 Jul 18.

Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.

Purpose: In vitro and in vivo studies suggested that flavonols, flavones, flavanones and flavan-3-ols have preventive effects on breast carcinogenesis. Epidemiological evidence about the associations between these flavonoid biomarkers and breast cancer risk is limited. This study aimed to investigate the association between serum concentration of these flavonoids and breast cancer risk among Chinese women.

Methods: This hospital-based case-control study recruited 792 breast cancer cases and 813 age frequency-matched (5-year interval) controls who provided eligible blood samples in Guangdong Province, China. Ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure flavonoids. Unconditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence internal (CI).

Results: Higher concentrations of serum flavonols, isorhamnetin, kaempferol, flavanones and naringenin were significantly associated with lower breast cancer risk, with adjusted ORs (95% CIs) for the highest versus the lowest group of 0.66 (0.49-0.89) for flavonols, 0.52 (0.38-0.70) for isorhamnetin, 0.60 (0.45-0.80) for kaempferol, 0.65 (0.49-0.87) for flavanones and 0.45 (0.34-0.60) for naringenin, respectively. Significant positive associations were observed between serum flavan-3-ols, epigallocatechin, epigallocatechin-3-gallate and breast cancer risk. No significant associations were observed for serum quercetin, flavones, apigenin, luteolin, hesperetin, catechin, epicatechin and epicatechin-3-gallate with overall breast cancer risk.

Conclusions: This study suggested that serum flavonols and flavanones were inversely associated with breast cancer risk and serum flavan-3-ols were positively associated with breast cancer risk. Serum flavones were not associated with overall breast cancer risk. These findings warrant further confirmation in prospective studies.
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http://dx.doi.org/10.1007/s00394-020-02331-zDOI Listing
April 2021