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The role of autologous hematopoietic stem cell transplantation (auto-HSCT) following high-dose chemotherapy has been validated and accepted as a standard treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, its clinical efficacy as frontline therapy remains to be elucidated. This study aimed to examine the feasibility of frontline auto-HSCT for newly diagnosed intermediate/high-risk DLBCL patients. We retrospectively reviewed the data of 223 patients treated with frontline auto-HSCT or chemotherapy alone (year 2008-2014) from four hospitals. The median follow-up time was 29.4 months. Between the two treatment arms among the intermediate/high-risk DLBCL patients, the 3-year overall survival (OS) and progression-free survival (PFS) rates of patients given frontline auto-HSCT were 87.6% and 81.9%, respectively, and the chemotherapy-alone group showed 3-year OS and PFS rates of 64.9% and 59.59%, respectively. Compared with the chemotherapy-alone group, the frontline auto-HSCT could eliminate the adverse impact of non-germinal center B-cell (GCB) type. In addition, in the frontline auto-HSCT group, patients who achieved complete response (CR) at auto-HSCT had a longer survival time than those who did not achieve CR. Our results suggested that frontline auto-HSCT could improve the prognosis of intermediate/high-risk DLBCL patients.

Chemotherapy resistance and the tumor immune microenvironment are dual reasons for the poor therapeutic efficacy of treating acute myeloid leukemia (AML), causing suboptimal clinical outcomes and high relapse rates. Activation of the stimulator of interferon genes (STING) pathway based on innate immunity can effectively improve antitumor immunity. However, traditional STING agonists are limited due to their easy degradation and difficult membrane transport. Here, a bioinspired nanomedicine synergizing chemo- and immunotherapy was developed by activating the STING pathway for targeted and systemic AML cell damage. We show that a leukemia cell membrane (LCM)-camouflaged hollow MnO

Introduction Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin's lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated. Patients and methods Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry. Results We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan-Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time. Discussion These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.

Background The early detection of tumors upon initial diagnosis or during routine surveillance is important for improving survival outcomes. Here, we investigated the feasibility and clinical significance of circulating tumor DNA (ctDNA) detection for Extranodal NK/T-cell lymphoma, nasal type (ENTKL). Methods The plasma ctDNA assessment was based on blood specimens collected from 65 newly diagnosed patients with ENKTL in the hematology medical center of Xinqiao Hospital. Longitudinal samples collected under chemotherapy were also included. The gene mutation spectrum of ENKTL was analyzed via next generation sequencing. Results We found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%) and NOTCH1 (7.7%). The mutation allele frequencies of ATM and JAK3 were significantly correlated with the disease stage, and mutated KMT2D, ASXL3 and JAK3 were positively correlated with the metabolic tumor burden of the patients. Compared with the tumor tissue, ctDNA profiling showed good concordance (93.75%). Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequencies of the genes. Compared with PET/CT, ctDNA has more advantages in tracking residual disease in patients. In addition, patients with mutated KMT2D had higher expression compared with those with wild type, and mutated KMT2D predicted poor prognosis. Conclusion Our results unveil the mutation spectrum of ENKTL patients’ plasma, which can be used to monitor the disease status of the patients exactly, and KMT2D is the most frequently mutated gene with prognosis prediction value. The application of ctDNA sequencing can provide precision treatment strategies for patients. Trial registration This study is registered with chictr.org (ChiCTR1800014813, registered 7 February, 2018-Retrospectively registered).

Y3Al5O12:Ce3+ (YAG:Ce3+) single crystal phosphor (SCP) exhibits high internal quantum efficiency (IQE) and excellent thermal conductivity and stability. Such properties are promising in high-power laser-excited white lighting applications. However, YAG:Ce3+ SCP usually shows low luminous flux and color rendering index (CRI, Ra) when excited by a transmissive laser. In this study, a self-designed three-integrating sphere system was established to characerize the optical performances of YAG:Ce3+ SCP palates under both the reflective and transmissive 455 nm blue laser excitations. Next, its luminous and color rendering properties under transmissive laser excitation were improved by surface roughening treatment and sintering of a CaAlSiN3:Eu2+ (CASN:Eu2+) phosphor-in-borate glass (PiBG) layer. The results revealed that: (1) When the YAG:Ce3+ SCP was excited by blue laser, its forward luminous flux was considerably lower than the backward one; (2) Under transmissive excitation, its luminous flux rolled up with the maximum increase rate of 109.19% when the averaged roughness (Ra) increased from 0.35 to 5.40 μm; (3) After sintering the CASN:Eu2+ PiBG layer on the roughening YAG:Ce3+ SCP, its luminous flux, CRI increased by 31.48% and 117.14%, and its color fidelity index (CFI, Rf) reached up to 82 under the transmissive 3.03 W blue laser excitation.

Introduction Increasing evidence has demonstrated that plasmacytoid dendritic cells (PDCs) in the tumor microenvironment (TME) play an important role in tumorigenesis and progression. PDC infiltration has been found in certain malignancies such as classic Hodgkin’s lymphoma and chronic myelomonocytic leukemia. Our previous work reported that PDC infiltration could occur in acute myeloid leukemia (AML), but the clinical significance of PDC in AML has not been thoroughly investigated. Patients and Methods Here, we evaluated the clinical significance of PDC to AML transition in a leukemia microenvironment. The frequency of PDCs in 80 acute myelomonocytic leukemia (AML-M4) and 83 acute monocytic leukemia (AML-M5) patients was determined by flow cytometry. Results We found 62 cases with PDC infiltration. These patients showed higher numbers of bone marrow blasts, higher mean Hb concentration, and required more cycles of chemotherapy before achieving complete remission (CR), but had lower white blood cell and platelet counts compared to patients without PDC infiltration. Drug sensitivity analysis showed that patients with PDC infiltration had lower sensitivity to standard chemotherapy regimens. Kaplan–Meier survival curves demonstrated that patients with PDC infiltration had a shorter overall survival (OS) time and progression-free survival time. Discussion These results suggested that PDC infiltration can be used for risk stratification of AML-M4/M5, and PDCs may transdifferentiate into leukemia in an AML microenvironment.

Additional file 3: Table S3. Correlation between ATM mutation status and clinicopathological features of ENKTL.

Additional file 2: Table S2. Correlation between KMT2D mutation status and clinicopathological features of ENKTL.

BackgroundExtranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis. Early detection of tumors at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising noninvasive tool for monitoring disease status. Here, we investigated the feasible of ctDNA detection in ENTKL.MethodsPlasma ctDNA was assessment were based on blood specimens that were collected from 65 patients recently diagnosed with ENKTL at the hematology medical center of Xinqiao Hospital, longitudinal samples collected under chemotherapy also included. Gene mutation spectrum of ENKTL was analyzed via cancer personalized profiling sequencing (CAPP-Seq). This study is registered with ClinicalTrials.gov (ChiCTR1800014813)ResultsFrom February 2017 to September 2019, 65 patients were enrolled, we found that the most frequently mutated genes were KMT2D (23.1%), APC (12.3%), ATM (10.8%), ASXL3 (9.2%), JAK3 (9.2%), SETD2 (9.2%), TP53 (9.2%), NOTCH1 (7.7%). The mutation frequencies of KMT2D was significantly higher in stage III-IV, and mutations in KMT2D, ASXL3 and JAK3 were significantly correlated with the metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed good concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes. Compared with PET/CT, ctDNA has more advantages for tracking residual disease in patients. In addition, we also found that mutated KMT2D predicted poor prognosis in patients.ConclusionCollectively, our results provide evidence that ctDNA may serve as a novel precision medicine biomarker in ENKTL.

With the advent of tyrosine kinase inhibitors (TKIs), the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) has entered a new era. The efficacy of TKIs compared with other ALL treatment options is emphasized by a rapid increase in the number of TKI clinical trials. Subsequently, the use of traditional approaches, such as combined chemotherapy and even allogeneic hematopoietic stem cell transplantation (allo-HSCT), for the treatment of ALL is being challenged in the clinic. In light of the increased use of TKIs in the clinic, several questions have been raised. First, is it necessary to use intensive chemotherapy during the induction course of therapy to achieve a minimal residual disease (MRD)-negative status? Must a patient reach a complete molecular response/major molecular response before receiving allo-HSCT? Does MRD status affect long-term survival after allo-HSCT? Is auto-HSCT an appropriate alternative for allo-HSCT in those Ph+ ALL patients who lack suitable donors? Here, we review the recent literature in an attempt to summarize the current status of TKI usage in the clinic, including several new therapeutic approaches, provide answers for the above questions, and speculate on the future direction of TKI utilization for the treatment of Ph+ ALL patients.

Extranodal NK/T-cell lymphoma, nasal type (ENTKL), is an aggressive hematological malignancy with poor prognosis, early detection of tumor at initial diagnosis or during routine surveillance is important for improving survival outcomes. Molecular profiling of circulating tumor DNA (ctDNA) is a promising non-invasive tool for monitoring disease status. Here, we assessed the gene mutation spectrum of plasma ctDNA in ENKTL by CAPP-Seq, we found that the mostly frequently mutated genes were MGA (33.3%), TP53 (30%), ASXL3 (28.3%), DDX3X (25%), BCORL1 (25%), TRAF3 (21.7%), NOTCH3 (21.7%), STAT5B (21.7%), EP300 (21.7%), APC (20%), ATM (18.3%), TNFRSF14 (16.7%), KMT2D (16.7%), EZH2 (16.7%) and SETD2 (16.7%), mutation frequency of MGA and TP53 were significantly higher in stage III-IV, and mutation of MGA, TP53, NOTCH3, et al were significantly correlated with metabolic tumor burden of the patients. Compared with tumor tissue DNA, ctDNA profiling showed well concordance. Serial ctDNA analysis showed that treatment with chemotherapy could decrease the number and mutation allele frequency of genes, compared with PET/CT, ctDNA has more advantage for track residual disease of the patients, in addition, we also found that patients with mutated MGA, TP53, SETD2, APC predicted poor prognosis. Collectively, our results provide evidence the proof of concept that ctDNA may serve as novel precision medicine biomarker in ENKTL. Trial Registration: ClinicalTrials identifier: ChiCTR1800014813. Funding Statement: This project was supported by grants from the National Natural Science Fund for Youth (No. 81600166), and the technique innovation and applied program of Chongqing (cstc2018jscx-msybX0052). Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: All participants provided informed written consent before undergoing any study-related procedures in accordance with the Declaration of Helsinki. This study was approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20180005).