No consensus has been made on the use of PEG-modification recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in patients receiving autologous peripheral blood stem cell transplantation (PBSCT). To evaluate the efficacy and safety of PEG-rhG-CSF in provision of neutrophil support for lymphoma patients receiving autologous PBSCT. This retrospective study included lymphoma patients receiving either PEG-rhG-CSF or rhG-CSF after autologous PBSCT from 2018 to 2021 in two clinics. Hematologic recovery time, incidence of infectious complications and toxicity were compared between these two rhG-CSFs and among different initiation time of PEG-rhG-CSF. Of the 139 subjects included, 93 received PEG-rhG-CSF and 46 received rhG-CSF after transplantation. Compared with rhG-CSF, PEG-rhG-CSF marginally but significantly accelerated the neutrophil engraftment by 1 day (10 vs. 9 days, respectively) with no increasing on the risk of infectious complication and toxicity. In the PEG-rhG-CSF group, 50 patients received the growth factor on day 1, 19 received on day 3 and 24 received on day 5. The neutrophil engraftment was significantly shorter in day 1 and day 3 subgroup (9, 9, and 10 days, respectively), with a lower incidence of febrile neutropenia (82%, 100%, 100%) and documented infections (76%, 100%, 100%) in day 1 subgroup. PEG-rhG-CSF might be an alternative to rhG-CSF for lymphoma patients received autologous PBSCT. Administrating PEG-rhG-CSF on day 1 can achieve both faster hematologic recovery and lower infectious complications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01704-8.
Background: Data on viral kinetics and variants affecting the duration of viral shedding were limited. Our objective was to determine viral shedding in distinct severe acute respiratory syndrome coronavirus 2 variants, including Omicron BA.4/5 and BF.7, and to identify the relevant influencing factors. Methods: We carried out a longitudinal cohort study at Beijing Xiaotangshan Fangcang shelter hospital from May to June 2022 (Omicron BA.4/5) and from November to December 2022 (Omicron BF.7). Nucleocapsid protein (N) and open reading frame (ORF) genes were considered as the target genes of the reverse transcription PCR. The daily results of cycle threshold (CT), including lowest ORF1ab-CT values for days 1-3 post-hospitalisation and lowest N-CT values for days 1-3 post-hospitalisation (CT3minN) and demographic and clinical characteristics were collected. Results: 1433 patients with coronavirus disease 2019 (COVID-19) were recruited from the Fangcang shelter hospital, in which 278 patients were diagnosed with Omicron BA.4/5 and 1155 patients with Omicron BF.7. Patients with BF.7 infection showed a longer duration of viral shedding. The duration of viral shedding was associated with the variants age, alcohol use, the severity of COVID-19 and CT3minN. Moreover, the nomogram had excellent accuracy in predicting viral shedding. Conclusions: Our results indicated that patients with Omicron BF.7 had a longer period of contagiousness than those with BA.4/5. The duration of viral shedding was affected by a variety of factors and the nomogram may become an applicable clinical instrument to predict viral shedding. Furthermore, we developed a new COVID-19 viral shedding predicting model that can accurately predict the duration of viral shedding for COVID-19, and created a user-friendly website to apply this prediction model (https://puh3.shinyapps.io/CVSP_Model/).
Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients.
DNA Copy Number Variations , Genomics , Mutation , Testicular Neoplasms , Humans , Male , Testicular Neoplasms/genetics , Testicular Neoplasms/pathology , Testicular Neoplasms/classification , Mutation/genetics , DNA Copy Number Variations/genetics , Aged , Middle Aged , Lymphoma/genetics , Lymphoma/pathology , Lymphoma/classification , Exome Sequencing , Aged, 80 and over , Adult , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/classification
The NC10 phylum links anaerobic methane oxidation to nitrite denitrification through a unique O2-producing intra-aerobic methanotrophic pathway. Although numerous amplicon-based studies revealed the distribution of this phylum, comprehensive genomic insights and niche characterization in deep-sea environments were still largely unknown. In this study, we extensively surveyed the NC10 bacteria across diverse deep-sea environments, including waters, sediments, cold seeps, biofilms, rocky substrates, and subseafloor aquifers. We then reconstructed and analysed 38 metagenome-assembled genomes (MAGs), and revealed the extensive distribution of NC10 bacteria and their intense selective pressure in these harsh environments. Isotopic analyses combined with gene expression profiling confirmed that active nitrite-dependent anaerobic methane oxidation (n-DAMO) occurs within deep-sea sediments. In addition, the identification of the Wood-Ljungdahl (WL) and 3-hydroxypropionate/4-hydroxybutyrat (3HB/4HP) pathways in these MAGs suggests their capability for carbon fixation as chemoautotrophs in these deep-sea environments. Indeed, we found that for their survival in the oligotrophic deep-sea biosphere, NC10 bacteria encode two branches of the WL pathway, utilizing acetyl-CoA from the carbonyl branch for citric acid cycle-based energy production and methane from the methyl branch for n-DAMO. The observed low ratios of non-synonymous substitutions to synonymous substitutions (pN/pS) in n-DAMO-related genes across these habitats suggest a pronounced purifying selection that is critical for the survival of NC10 bacteria in oligotrophic deep-sea environments. These findings not only advance our understanding of the evolutionary adaptations of NC10 bacteria but also underscore the intricate coupling between the carbon and nitrogen cycles within deep-sea ecosystems, driven by this bacterial phylum.
In this prospective, multicenter, Phase 2 clinical trial (NCT02987244), patients with peripheral T-cell lymphomas (PTCLs) who had responded to first-line chemotherapy with cyclophosphamide, doxorubicin or epirubicin, vincristine or vindesine, etoposide, and prednisone (Chi-CHOEP) were treated by autologous stem cell transplantation (ASCT) or with chidamide maintenance or observation. A total of 85 patients received one of the following interventions: ASCT (n = 15), chidamide maintenance (n = 44), and observation (n = 26). estimated 3 PFS and OS rates were 85.6%, 80.8%, and 49.4% (P = 0.001). The two-year OS rates were 85.6%, 80.8%, and 69.0% (P = 0.075).The ASCT and chidamide maintenance groups had significantly better progression-free survival (PFS) than the observation group (P = 0.001, and P = 0.01, respectively). The overall survival (OS) differed significantly between the chidamide maintenance group and the observation group ( P = 0.041). The multivariate and propensity score matching analyses for PFS revealed better outcomes in the subjects in the chidamide maintenance than observation groups (P = 0.02). The ASCT and chidamide maintenance groups had significant survival advantages over the observation group. In the post-remission stage of the untreated PTCL patients, single-agent chidamide maintenance demonstrated superior PFS and better OS than observation. Our findings highlight the potential benefit of chidamide in this patient subset, warranting further investigation through larger prospective trials. Clinical trial registration: clinicaltrial.gov, NCT02987244. Registered 8 December 2016, http://www.clinicaltrials.gov/ct2/show/NCT02987244 .
Due to dielectric capacitors' already-obtained fast charge-discharge speed, research has been focused on improving their Wrec. Increasing the polarization and enhancing the voltage endurance are efficient ways to reach higher Wrec, however simultaneous modification still seems a paradox. For example, in the ferroelectric-to-relaxor ferroelectric (FE-to-RFE) phase transition strategy, which has been widely used in the latest decade, electric breakdown strength (Eb) and energy storage efficiency (η) always increase, while at the same time, the maximum polarization (Pmax) inevitably decreases. The solution to this problem can be obtained from another degree of freedom, like defect engineering. By incorporating Bi(Zn2/3Ta1/3)O3 (BZT) into the Ba0.15Ca0.85Zr0.1Ti0.9O3 (BCZT) lattice to form (1 - x)Ba0.15Ca0.85Zr0.1Ti0.9O3-xBi(Zn2/3Ta1/3)O3 (BCZT-xBZT) solid-solution ceramics, in this work, ultrahigh ferroelectric polarization was achieved in BCZT-0.15BZT, which is caused by the polarization double-enhancement, comprising the contribution of interfacial and dipole polarization. In addition, due to the electron compensation, a Schottky contact formed at the interface between the electrode and the ceramic, which in the meantime, enhanced its Eb. A Wrec of 8.03 J cm-3, which is the highest among the BCZT-based ceramics reported so far, with an extremely low energy consumption, was finally achieved. BCZT-0.15BZT also has relatively good polarization fatigue after long-term use, good energy storage frequency stability and thermal stability, as well as excellent discharge properties.
Prokaryotes play a key role in particulate organic matter's decomposition and remineralization processes in the vertical scale of seawater, and prokaryotes contribute to more than 70% of the estimated remineralization. However, little is known about the microbial community and metabolic activity of the vertical distribution in the trenches. The composition and distribution of prokaryotes in the water columns and benthic boundary layers of the Kermadec Trench and the Diamantina Trench were investigated using high-throughput sequencing and quantitative PCR, together with the Biolog EcoplateTM microplates culture to analyze the microbial metabolic activity. Microbial communities in both trenches were dominated by Nitrososphaera and Halobacteria in archaea, and by Alphaproteobacteria and Gammaproteobacteria in bacteria, and the microbial community structure was significantly different between the water column and the benthic boundary layer. At the surface water, amino acids and polymers were used preferentially; at the benthic boundary layers, amino acids and amines were used preferentially. Cooperative relationships among different microbial groups and their carbon utilization capabilities could help to make better use of various carbon sources along the water depths, reflected by the predominantly positive relationships based on the co-occurrence network analysis. In addition, the distinct microbial metabolic activity detected at 800 m, which was the lower boundary of the twilight zone, had the lowest salinity and might have had higher proportions of refractory carbon sources than the shallower water depths and benthic boundary layers. This study reflected the initial preference of the carbon source by the natural microbes in the vertical scale of different trenches and should be complemented with stable isotopic tracing experiments in future studies to enhance the understanding of the complex carbon utilization pathways along the vertical scale by prokaryotes among different trenches.
T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation.
Hematopoietic Stem Cell Transplantation , Humans , Adolescent , Adult , Male , Female , China/epidemiology , Middle Aged , Young Adult , Prognosis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/mortality , Survival Rate , Retrospective Studies , Transplantation, Homologous , Leukemia-Lymphoma, Adult T-Cell/therapy , Leukemia-Lymphoma, Adult T-Cell/mortality , Treatment Outcome , Allografts , Cohort Studies
PURPOSE: The synergistic effects of combining arsenic compounds with imatinib against chronic myeloid leukemia (CML) have been established using in vitro data. We conducted a clinical trial to compare the efficacy of the arsenic realgar-indigo naturalis formula (RIF) plus imatinib with that of imatinib monotherapy in patients with newly diagnosed chronic phase CML (CP-CML). METHODS: In this multicenter, randomized, double-blind, phase 3 trial, 191 outpatients with newly diagnosed CP-CML were randomly assigned to receive oral RIF plus imatinib (n = 96) or placebo plus imatinib (n = 95). The primary end point was the major molecular response (MMR) at 6 months. Secondary end points include molecular response 4 (MR4), molecular response 4.5 (MR4.5), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: The median follow-up duration was 51 months. Due to the COVID-19 pandemic, the recruitment to this study had to be terminated early, on May 28, 2020. The rates of MMR had no significant statistical difference between combination and imatinib arms at 6 months and any other time during the trial. MR4 rates were similar in both arms. However, the 12-month cumulative rates of MR4.5 in the combination and imatinib arms were 20.8% and 10.5%, respectively (p = 0.043). In core treatment since the 2-year analysis, the frequency of MR4.5 was 55.6% in the combination arm and 38.6% in the imatinib arm (p = 0.063). PFS and OS were similar at five years. The safety profiles were similar and serious adverse events were uncommon in both groups. CONCLUSION: The results of imatinib plus RIF as a first-line treatment of CP-CML compared with imatinib might be more effective for achieving a deeper molecular response (Chinadrugtrials number, CTR20170221).
Antineoplastic Agents , Arsenic , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Imatinib Mesylate/adverse effects , Arsenic/therapeutic use , Pandemics , Treatment Outcome , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Antineoplastic Agents/adverse effects
Background: Lianhuaqingwen (LHQW), a traditional Chinese medicine comprised of 13 herbal extracts renowned for their robust heat-clearing and detoxifying properties, has gained widespread utilization in China but has yet to garner similar recognition abroad. It is believed to exhibit efficacy in ameliorating symptoms in individuals afflicted with coronavirus disease 2019 (COVID-19). However, the precise impact of LHQW on viral shedding (VS), particularly in the context of mild or asymptomatic infections caused by the Omicron BF.4/5 or BF.7 variants of COVID-19, remained inadequately elucidated. Consequently, a real-world study was conducted, involving patients diagnosed with COVID-19, with the primary objective of ascertaining the effectiveness of LHQW in this specific clinical context. Methods: We conducted an investigation on Omicron-infected patients through a single-center, propensity score-matched real-world study conducted at Xiaotangshan Fangcang Hospital from May to November 2022. A total of 3,368 COVID-19 patients were enrolled in the study, all of whom presented mild or asymptomatic infections caused by either BF.4/5 or BF.7 strains of the virus. Demographic and clinical data were systematically collected from medical records. Patients were allocated to receive treatment with LHQW (designated as the treatment group) or received no LHQW treatment (designated as the not-treated/no-treatment group). Viral load was quantified utilizing quantitative real-time PCR (qPCR), and the duration of VS was defined as the time interval between the initial negative test result and the date of COVID-19 diagnosis or symptom onset. Results: The study encompassed a cohort of 3,368 patients, and following propensity score matching, a subset of 296 patients was meticulously chosen for subsequent analysis. Notably, baseline characteristics exhibited disparities between the treatment and not-treated/no-treatment groups. However, post-matching, these characteristics achieved a commendable level of comparability. Our findings unequivocally demonstrated that there existed no statistically significant disparity in VS. This holds true when comparing patients subjected to LHQW treatment against those not administered LHQW, as well as when contrasting individuals presenting asymptomatic and mild COVID-19 manifestations. Conclusion: No statistically significant difference in VS was observed between patients who underwent LHQW treatment and those who did not. Additional investigations are imperative to provide a comprehensive assessment of LHQW's efficacy, particularly in patients afflicted with severe COVID-19 or those infected with viral strains distinct from BF.4/5 or BF.7.
OBJECTIVE: To summarize the clinical characteristics, therapeutic effect and prognostic factors of patients with Hodgkin's lymphoma (HL). METHODS: A total of 129 patients with HL diagnosed in Peking University Third Hospital from January 2010 to March 2021 who were given at least one efficacy assessment after treatment were enrolled, and their clinical data, including sex, age, pathological type, Ann Arbor stage, ECOG score, blood test, ß2-microglobulin, lactate dehydrogenase level, albumin level were collected. The clinical characteristics, therapeutic effect and long-term prognosis of the patients were summarized and analyzed. RESULTS: In classical HL, nodular sclerosis HL accounted for the highest proportion of 51.6%, followed by mixed cellularity HL (36.5%), lymphocyte-rich classical HL (3.2%), and lymphocyte depletion HL (0.7%), while nodular lymphocyte predominant HL accounted for 4.8%. The 3-year overall survival (OS) rate of HL patients was 89.8%, and 5-year OS was 85.0%. The 3-year progression-free survival (PFS) rate was 73.4%, and 5-year PFS was 63.1%. Multivariate regression analysis indicated that IPI score was an independent negative factor, while hemoglobin (Hb) level was an independent positive factor for OS in HL patients. When the mediastinal mass size was 9.2 cm, it was most significant to judge the survival status of HL patients. 5-year OS and 5-year PFS were 97.4% and 76.0% in early-stage HL patients without large mass, respectively, while in patients with advanced-stage HL was 83.4% and 55.9% (both P < 0.05). After 2-4 courses of treatment, the overall response rate (ORR) of patients who received chemotherapy combined with radiotherapy was 95.0%, while that was 89.6% in those with chemotherapy alone. CONCLUSIONS: The overall prognosis of patients with HL is satisfactory, especially those in early-stage without large mass. IPI score and Hb level are independent risk factors for the prognosis of HL patients. A 9.2 cm mediastinal mass can be used as the cut-off value for the prognosis of Chinese HL patients.
Hodgkin Disease , Humans , Hodgkin Disease/therapy , Adult , Male , Prognosis , Female , Survival Rate , Young Adult
Background: Frail elderly patients with newly diagnosed multiple myeloma (NDMM) have inferior survival and less benefit from high-dose therapies. This prospective study aimed to investigate the efficacy, safety, and quality of life (QoL) of induction treatment of ixazomib/lenalidomide/dexamethasone (IRd) and ixazomib/pegylated liposomal doxorubicin/dexamethasone (IDd) followed by ixazomib/dexamethasone (Id) maintenance therapy in frail, elderly patients with NDMM. Methods: From July 2019 to December 2021, this non-randomized concurrent controlled clinical study enrolled 120 NDMM patients aged ≥65 years with frailty defined by the International Myeloma Working Group (IMWG) frailty score or Mayo geriatric scoring system. The enrolled patients received 6-8 cycles of IRd or IDd followed by Id maintenance therapy for a minimum of 2 years at the discretion of physicians based on patient's clinical characteristics (chiCTR1900024917). Findings: The median age was 71 years and 55% of the patients were males. The overall response rate (ORR) was 82% and 77%, complete response (CR) rate was 25% and 12% for IRd and IDd groups, respectively. The difference in ORR of the Idd group minus the IRd group was -5.36% (95% CI: -18.9% to 8.19%), indicating that the ORR of the IDd group was neither inferior nor non-inferior to the IRd group. After a median follow-up of 34.3 months, the median progression-free survival (PFS) was 21.6 and 13.9 months, OS was not reached and 29.2 months in IRd and IDd groups, respectively. 28 and 33 patients discontinued induction therapy, 20 and 19 discontinued maintenance therapy in IRd and IDd groups, respectively. Cumulative Grade 3 or higher hematological adverse events (AEs) occurred in 10 of the 60 patients (17%) and non-hematological AEs occurred in 15 of the 60 patients (25%) in the IRd group, while 13 of the 60 patients (22%) and 21 of the 60 patients (35%) in the IDd group. Patients were observed with clinically significant improvement in QoL when compared with that at baseline in both IRd and IDd groups by evaluation per cycle (P < 0.0001). Interpretation: The results demonstrated that compared with IRd regimen, IDd regimen showed no significant advantage, but the survival of the IDd group was shorter than that of the IRd group, indicating an all-oral outpatient triplet regimen with IRd, which has low toxicity and has improved QoL, could be the viable first-line treatment option for frail NDMM patients. Funding: The Young Elite Scientist sponsorship program by bast of Beijing Association for Science and Technology (No. BYESS2023116) and Beijing Medical Award Foundation (No. YXJL-2018-0539-0073).
OBJECTIVE: To analyze the clinical characteristics, treatment, and prognosis of adult patients with early T-cell precursor acute lymphoblastic leukemia/lymphoma (ETP-ALL/LBL). METHODS: Clinical data of 113 T lymphoblastic leukemia/lymphoma (T-ALL/LBL) patients from January 2006 to January 2019 were collected from three hematology research centers, including Peking University Third Hospital, the First Medical Center of Chinese PLA General Hospital and Institute of Hematology and Blood Diseases Hospital, Chinese Medical University. The clinical characteristics and prognosis of ETP-ALL/LBL patients were analyzed compared with non-ETP-ALL/LBL patients. RESULTS: In 113 T-ALL/LBL patients, 13 cases (11.5%) were diagnosed as ETP-ALL/LBL, including 11 males, with a median age of 28(18-53) years. Compared with non-ETP-ALL/LBL patients, there were no significant differences in age, sex, incidence of large mediastinal mass, clinical stage, international prognostic index (IPI) score, white blood cell (WBC) count and lactate dehydrogenase (LDH) level among ETP-ALL/LBL patients. Among 13 ETP-ALL/LBL patients, 9 cases (69.2%) achieved complete remission (CR), and there was no statistically significant difference in response rate induced by chemotherapy between ETP-ALL/LBL patients and non-ETP-ALL/LBL patients. Among patients who received chemotherapy without allogeneic hematopoietic stem cell transplantation (allo-HSCT), ETP-ALL/LBL group had a worse 5-year overall survival (OS) rate compared with non-ETP-ALL/LBL group (0 vs 7.1%, P =0.008), while in patients with allo-HSCT, there was no significant difference for 5-year OS rate between the two group (37.5% vs 40.2%, P >0.05). Multivariate Cox regression analysis showed that CR after induction therapy, allo-HSCT, and LDH level were independent prognostic factors affecting T-ALL/LBL patients. CONCLUSION: No significant difference in response rate induced by chemotherapy is observed between ETP-ALL/LBL and non-ETP-ALL/LBL patients. Allo-HSCT consolidation after induction of remission therapy may have significant favorable influence on OS for patients with ETP-ALL/LBL.
Hematopoietic Stem Cell Transplantation , Leukemia-Lymphoma, Adult T-Cell , Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, T-Lymphoid , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Adult , Humans , Male , Middle Aged , Pathologic Complete Response , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Prognosis , Retrospective Studies , Female , Adolescent , Young Adult
Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.
Sovleplenib (HMPL-523) is a selective spleen tyrosine kinase (Syk) inhibitor with antitumor activity in preclinical models of B-cell malignancy. We conducted a dose-escalation and dose-expansion phase I study of sovleplenib in patients with relapsed/refractory mature Bcell tumors. Dose escalation followed a 3+3 design; patients received oral sovleplenib (200-800 mg once daily [q.d.] or 200 mg twice daily [b.i.d.], 28-day cycles). During dose expansion, patients were enrolled into four cohorts per lymphoma classification and treated at the recommended phase 2 dose (RP2D). Overall, 134 Chinese patients were enrolled (dose escalation, n=27; dose expansion, n=107). Five patients experienced dose-limiting toxicities: one each of amylase increased (200 mg q.d.), febrile neutropenia (800 mg q.d), renal failure (800 mg q.d.), hyperuricemia and blood creatine phosphokinase increased (200 mg b.i.d.) and blood bilirubin increased and pneumonia (200 mg b.i.d.). RP2D was determined as 600 mg (>65 kg) or 400 mg (≤65 kg) q.d. The primary efficacy end point of independent review committee-assessed objective response rate in indolent B-cell lymphoma was 50.8% (95% CI, 37.5-64.1) in 59 evaluable patients at RP2D (follicular lymphoma: 60.5%, marginal zone lymphoma: 28.6%, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, 0%). The most common (≥10% patients) grade ≥3 treatment-related adverse events in the doseexpansion phase were decreased neutrophil count (29.9%), pneumonia (12.1%) and decreased white blood cell count (11.2%). Pharmacokinetic exposures increased doseproportionally with ascending dose levels from 200-800 mg, without observed saturation. Sovleplenib showed antitumor activity in relapsed/refractory B-cell lymphoma with acceptable safety. Further studies are warranted.
1q21+ is a common cytogenetic abnormality in multiple myeloma (MM) and is considered an independent predictor of poor prognosis; however, its impact on extramedullary disease (EMD) remains unknown. Our study reviewed the clinical relevance and prognostic value of 1q21+ status in 92 patients with NDMM and EMD. 1q21+ was detected in 23.9% (22/92) of patients. Patients with 1q21+ presented with advanced International Staging System stages (P = 0.006), lower level of hemoglobin (P = 0.004), higher percentage of plasma cells in the bone marrow (P < 0.001), higher level of serum ß2-microglobulin (7.24 g/L vs. 3.85 g/L, P = 0.003), and higher levels of lactic dehydrogenase (LDH) (206.5 U/L vs. 177 U/L, P = 0.019). The prevalence of soft tissue-related EMD (EMD-S) (54.5% vs. 18.6%, P < 0.001), renal dysfunction (50.5% vs. 17.7%, P = 0.002), and hypercalcemia (27.3% vs. 7.1%, P = 0.011) was also higher. 1q21+ was strongly associated with other high-risk cytogenetic abnormalities, including IgH/FGFR3 (22.7% vs. 4.3%, P = 0.007) and IgH/MAF translocations (22.7% vs. 1.4%, P < 0.001). 1q21+ patients had significantly shorter overall survival (OS) and progression-free survival (PFS) (OS: 24 months vs. 47 months, P = 0.002; PFS: 14 months vs. 38 months, P < 0.001); the poor survival outcomes could not be reversed by autologous hematopoietic stem cell transplantation. Multivariate analysis suggested that 1q21+ , EMD-S, elevated lactate dehydrogenase (LDH) levels, and P53 deletion were independent risk factors for poor prognosis in patients with EMD. In patients with 1q21+ EMD, hypercalcemia, elevated LDH levels, and P53 deletion were independent adverse risk prognostic factors.
Chromosomes, Human, Pair 1 , Multiple Myeloma , Humans , Multiple Myeloma/mortality , Multiple Myeloma/diagnosis , Multiple Myeloma/blood , Male , Female , Middle Aged , Retrospective Studies , Aged , Chromosomes, Human, Pair 1/genetics , Adult , Prognosis , Chromosome Aberrations , Aged, 80 and over , Survival Rate
