Single-dose rituximab plus glucocorticoid versus cyclophosphamide plus glucocorticoid in patients with newly diagnosed acquired hemophilia A: A multicenter, open-label, randomized noninferiority trial.

Acquired hemophilia A (AHA) is a rare but serious bleeding disorder. Randomized controlled trial (RCT) comparing the efficacy of immunosuppression therapy for AHA lacks. We conducted the first multicenter RCT aiming to establish whether the single-dose rituximab combination regimen was noninferior to the cyclophosphamide combination regimen. From 2017 to 2022, 63 patients with newly diagnosed AHA from five centers were randomly assigned 1:1 to receive glucocorticoid (methylprednisolone 0.8 mg/kg per day for the first 3 weeks and then tapered) plus single-dose rituximab (375 mg/m2 ; n = 31) or plus cyclophosphamide (2 mg/kg per day until inhibitor becomes negative, for a maximum of 5 weeks; n = 32). The primary outcome was complete remission (CR, defined as FVIII activity ≥50 IU/dL, FVIII inhibitor undetectable, immunosuppression tapered and no bleeding for 24 h without bypassing agents) rate measured within 8 weeks. The noninferiority margin was an absolute difference of 20%. Twenty-four (77.4%) patients in the rituximab group and 22 (68.8%) patients in the cyclophosphamide group achieved CR, which showed the noninferiority of the single-dose rituximab-based regimen (absolute difference = -8.67%, lower limit of the 95% confidence interval = -13.11%; Pnoninferiority = 0.005). No difference was found in the incidence of treatment-related adverse events. Single-dose rituximab plus glucocorticoid regimen showed similar efficacy and safety, without a reported risk of secondary malignancies or reproductive toxicity seen in cyclophosphamide, it might be recommended as a first-line therapy for AHA, especially in China where there is a young age trend in AHA patients. This trial was registered at ClinicalTrials.gov as #NCT03384277.

Efficacy, safety and bioequivalence of the human-derived B-domain-deleted recombinant factor VIII TQG202 for prophylaxis in severe haemophilia A patients.

INTRODUCTION: Current treatment of severe haemophilia A includes prophylaxis with factor VIII (FVIII) replacement. The supply of plasma-derived FVIII is short in China. PURPOSE: To evaluate the efficacy and safety of a new B-domain deleted (BDD) recombinant FVIII (TQG202) produced by human-derived cells for prophylaxis in severe haemophilia A patients and compare the bioequivalence with Xyntha. METHODS: This multicentre, clinical trial consisted of an open-label, randomized, two-period cross-over trial assessing single-dose pharmacokinetics (PK), and a single-arm clinical trial evaluating the efficacy and safety of 24 weeks of TQG202 prophylaxis, and repeated PK were assessed after prophylaxis phase. The single-dose was 50 IU/kg in PK assessment, and the initial dose was 30 ± 5 IU/kg for prophylaxis. The primary endpoints of prophylaxis were the annualized bleeding rate (ABR) and the incremental recovery rate of the first administration. Adverse events (AEs) were recorded. RESULTS: Twenty-six participants were enrolled in the PK assessment and 81 participants in the prophylaxis phase. Mean age was 25.9 ± 10.8 years and all participants were male. The results of PK assessment showed TQG202 is bioequivalent to Xyntha. The total ABR was 2.0 (95% CI: 1.2-2.9) in prophylaxis phase. The mean incremental recovery rate of the first administration was .027 (95% CI: .026-.028) (IU/ml)/(IU/kg). AEs occurred in 42 participants, with an incidence of 51.9%. One severe AE not related to TQG202 occurred. No participants developed FVIII inhibitors. CONCLUSION: TQG202 shows bioequivalence with Xyntha. The promising efficacy and tolerability in the severe haemophilia A prophylaxis support the use of TQG202in clinical practice.

[Two cases of coagulation factor â ª deficiency caused by compound heterozygous mutations].

OBJECTIVE: To investigate the molecular pathogenesis of two coagulation factor Ⅺ (FⅪ) deficiency patients. METHODS: Coagulant assays: activated partial thromboplastin time (APTT), normal pooled-plasma corrected APTT test, PT, PT-INR and one-stage assay of coagulation factors activities were validated to diagnose coagulation factor Ⅺ deficiency. The patients' DNA samples were extracted and all exons and flanking sequences of F11 gene were amplified using PCR. After purified, the products of PCR were sequenced directly, the mutations were detected by comparing with wild sequences and analyzed using some bio-informatics softwares. RESULTS: The two patients were diagnosed with coagulation factor Ⅺ deficiency due to prolonged APTT, corrected APTT and low activities of coagulation factor FⅪ. The results of APTT, FⅪ: C were 88.1s, 1.1% and 107.1s, 3.8%, and the prolonged APTT could be corrected to normal range 32.9 s and 31.5 s, respectively. Through genetic analysis, we discovered compound heterozygous mutations g.1305-1G>A and g.1325delT in patient 1 and the sequencing results of TA plasmid clones showed that the two mutations were located on different strands of chromosomes. Compound heterozygous mutations g.1124A>G and g.1550C>G were detected in patient 2 resulting in Lys357Arg and Cys482Trp. Software analysis indicated the mutations probably brought amino acid sequence changed, protein features affected and splice site changed. CONCLUSION: Compound heterozygous mutations g.1305-1G>A, g.1325delT and g.1124A>G, g.1550C>G had been identified in two coagulation factor Ⅺ deficiency patients which might be responsible for their prolonged APTT and low FⅪ: C. To the best of our knowledge, g.1325delT and g.1550C>G have been reported, while g.1124A>G and g.1305-1G>A are reported for the first time in the literature.

Spectroscopic investigations and density functional theory calculations reveal differences in retention mechanisms of lead and copper on chemically-modified phytolith-rich biochars.

A better understanding of different retention mechanisms of potentially toxic elements (PTEs) by biochars during the remediation of contaminated sites is critically needed. In this study, different spectroscopic techniques including synchrotron-based micro-X-ray fluorescence (µ-XRF), X-ray absorption fine structure (XAFS), and near-edge XAFS spectroscopy (NEXAFS), were used to investigate the spatial distributions and retention mechanisms of lead (Pb) and copper (Cu) on phytolith-rich coconut-fiber biochar (CFB), and ammonia, nitric acid and hydrogen peroxide modified CFB (MCFB) (i.e., ACFB, NCFB and HCFB). The µ-XRF analyses indicated that sorption sites on ACFB and NCFB were more efficient compared to those on CFB and HCFB to bind Pb/Cu. XAFS analyses revealed that the percentage of Pb species as Pb(C2H3O2)2 increased from 22.2% (Pb-loaded CFBs) to 47.4% and 41.9% on Pb-loaded NCFBs and HCFBs, while the percentage of Cu(OH)2 and Cu(C2H3O2)2 increased from 5.8% to 32.8% (Cu-loaded CFBs) to 41.5% and 43.4% (Cu-loaded NCFBs), and 27.1% and 35.1% (Cu-loaded HCFBs), respectively. Due to their similar atomic structures of Pb/Cu, Pb(C2H3O2)2/Pb-loaded montmorillonite and Cu(C2H3O2)2/Cu(OH)2 were identified as the predominant Pb/Cu species observed in Pb- and Cu-loaded MCFBs. The NEXAFS analyses of carbon confirmed that increasing amounts of carboxylic groups were formed on HCFB and NCFB by oxidizing carbon-containing functional groups, which could provide additional active binding sites for Pb/Cu retention. Results from the X-ray photoelectron spectroscopy analyses of nitrogen showed that azido-groups of ACFB played major roles in Pb/Cu retention, while amide-groups and pyridine-groups of NCFB primarily participated in Pb/Cu retention. Overall, density functional theory calculations suggested that silicate and the synergistic effect of hydroxyl and carboxylic-groups on MCFBs were highly efficient in Pb retention, while azido-groups and/or carboxylic-groups played major roles in Cu retention. These results provide novel insights into the PTE retention mechanisms of MCFBs.

Cord-Blood Engraftment Using an Enhanced Dual-Conditioning Regimen for Malignant Hematologic Diseases.

To explore a more effective conditioning regimen for umbilical cord blood transplantation (UCBT) to treat hematologic malignancies, we conducted a cohort study of a fludarabine/busulfan/cytarabine plus cyclophosphamide 200 mg/kg regimen. Forty-two consecutive patients with leukemia, myelodysplastic syndrome, or lymphoma received the regimen. The median number of infused total nucleated cells per kilogram was 5.5 × 107 (1.81-20.6), the median number of infused CD34+ cells per kilogram was 1.58 × 105 (0.58-6.6), and the median follow-up for surviving patients was 37 months (4.0-79.5 months). The cumulative incidence of neutrophil engraftment at 31 days was 100% [95% confidence interval (CI): 0.9159-1.0], and the median time to neutrophil engraftment was 19 days. The cumulative incidence of nonrelapse mortality was 12.76% (95% CI: 0.0455-0.2356) at 180 days and 3 years. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.6% and 59.6%, respectively. Especially in patients who received transplants in the early and intermediate stages, the 3-year OS and DFS rates were 90.3% (95% CI: 0.805-1.0) and 76.2% (95% CI: 0.608-0.956), respectively. The regimen significantly improved engraftment and survival, indicating that the high graft failure of UCBT was caused by rejection.

Defect-related luminescence behavior of a Mn4+ non-equivalently doped fluoroantimonate red phosphor.

Non-equivalent or non-octahedral substitution is a crucial strategy to gain Mn4+-doped fluoride red phosphors with a short fluorescence lifetime, whereas the impact of their structural defects on the photoluminescence (PL) properties remains unrevealed. Here, a non-equivalently doped RbSbF6:Mn4+ (RSFM) with a high quantum efficiency of 88% and a thermal stability of 121% at 425 K is newly reported to probe the defect-related PL behavior. Formation energy calculations imply that an interstitial defect was formed to balance the charge and stabilize the crystal structure. Concentration-dependent decay studies reveal that Mn4+ emission is quenched mainly by energy transfer to a neighboring defect . The large ionic radius of Sb5+ and defect leading to a premature optimal doping (0.11 mol%) is demonstrated by the refined contrast of the crystal structure and substitution mode among various Mn4+-doped prototypes. A couple of medium 4T2 state energies and the energy difference between the Mn4+ level with the valence band maximum enable its superior thermal stability. A higher defect concentration slightly aggravates this thermal quenching. Using the RSFM red phosphor in a white light-emitting diode offers a wide-color-gamut of 121% NTSC for backlight displays. This work would provide a new perspective to understand the defect effect on the PL behavior of special Mn4+ asymmetrically doped fluorides.

Disorder-Induced Broadband Near-Infrared Persistent and Photostimulated Luminescence in Mg2SnO4:Cr3.

Materials with near-infrared (NIR) persistent luminescence (PersL) and NIR-to-NIR photostimulated luminescence (PSL) properties are attractive platforms for photonic energy harvesting and release. In this work, we develop Mg2SnO4:Cr as a broadband NIR PersL and NIR-to-NIR PSL material (luminescence maxima at ∼800 nm) and reveal the origin of the PersL and PSL properties. The material has an inverse spinel structure with the Mg2+ and Sn4+ disorder at the Wyckoff 16d site based on the Rietveld refinement. Cr K-edge X-ray absorption near-edge structure (XANES) spectra uncover that the doped Cr ions have a +3 valence state and occupy the disordered (Mg,Sn) site with octahedral coordination. The disorder results in multiple Cr3+ centers, and the broadband luminescence originates from the 4T2(4F) → 4A2 transition of Cr3+ at sites with intermediate crystal field strength. The distribution of trap depths is continuous according to the analysis of thermoluminescence (TL) spectra using the initial rising method, which relates to the random distribution of Mg2+ and Sn4+ at the second coordination sphere of the Cr3+ centers rather than the oxygen-related defects. Stimulating the material with a NIR laser, the NIR PersL gets significantly enhanced due to a PSL process. The broadband PersL and PSL are detectable beyond 100 h and have good tissue penetrability and therefore the developed Mg2SnO4:Cr3+ has potential in applications of optical information storage/reading and autofluorescence-free bioimaging. Finally, three crystal and electronic structure factors are proposed for screening new Cr3+-activated PersL and PSL materials.

Site Occupancies, VUV-UV-vis Photoluminescence, and X-ray Radioluminescence of Eu2+-Doped RbBaPO4.

RbBaPO4:Eu2+ phosphors have been prepared by a high-temperature solid-state reaction method, and the structure was determined by Rietveld refinement based on powder X-ray diffraction (P-XRD) data. Their VUV-UV-vis photoluminescence properties are systematically investigated with three objectives: (1) based on low-temperature spectra, we clarify the site occupancies of Eu2+, and demonstrate that the doublet emission bands at ∼406 and ∼431 nm originate from Eu2+ in Ba2+ [Eu2+(I)] and Rb+ [Eu2+(II)] sites, respectively; (2) an electron-vibrational interaction (EVI) analysis is conducted to estimate the Huang-Rhys factors, the zero-phonon lines (ZPLs) and the Stokes shifts of Eu2+ in Rb+ and Ba2+ sites; (3) the studies on luminescence decay of Eu2+(I) reveal that dipole-dipole interaction is mainly responsible for the energy transfer from Eu2+(I) to Eu2+(II), and the energy migration between Eu2+(I) is weak. Finally, the X-ray excited luminescence (XEL) spectrum indicates that the light yield of the sample RbBa0.995Eu0.005PO4 is ∼17 700 ph/MeV, showing its potential application in X-ray detecting.

Comparison of Antifungal Prophylaxis Drugs in Patients With Hematological Disease or Undergoing Hematopoietic Stem Cell Transplantation: A Systematic Review and Network Meta-analysis.

Importance: Several antifungal drugs are available for antifungal prophylaxis in patients with hematological disease or who are undergoing hematopoietic stem cell transplantation (HSCT). Objective: To summarize the evidence on the efficacy and adverse effects of antifungal agents using an integrated comparison. Data Sources: Medline, EMBASE, and the Cochrane Central Register of Controlled Clinical Trials were searched to collect all relevant evidence published in randomized clinical trials that assessed antifungal prophylaxis in patients with hematological disease. Sources were search from inception up to October 2019. Study Selection: Studies that compared any antifungal agent with a placebo, no antifungal agent, or another antifungal agent among patients with hematological disease or undergoing HSCT were included. Of 39 709 studies identified, 69 met the criteria for inclusion. Data Extraction and Synthesis: The outcome from each study was estimated using the relative risk (RR) with 95% CIs. The Mantel-Haenszel random-effects model was used. The reliability and validity of the networks were estimated by addressing inconsistencies in the evidence from comparative studies of different treatments. Data were analyzed from December 2019 to February 2020. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses for Network Meta-analysis (PRISMA-NMA) guideline. Main Outcomes and Measures: The primary outcomes were invasive fungal infections (IFIs) and mortality. The secondary outcomes were fungal infections, proven IFIs, invasive candidiasis, invasive aspergillosis, fungi-related death, and withdrawal owing to adverse effects of the drug. Results: We identified 69 randomized clinical trials that reported comparisons of 12 treatments with at total of 14 789 patients. Posaconazole was the treatment associated with the best probability of success against IFIs (surface under the cumulative ranking curve, 86.7%; mean rank, 2.5). Posaconazole treatment was associated with a significant reduction in IFIs (RR, 0.57; 95% CI, 0.42-0.79) and invasive aspergillosis (RR, 0.36; 95% CI, 0.15-0.85) compared with placebo. Voriconazole was associated with a significant reduction in invasive candidiasis (RR, 0.15; 95% CI, 0.09-0.26) compared with placebo. However, posaconazole was associated with a higher incidence of withdrawal because of the adverse effects of the drug (surface under the cumulative ranking curve, 17.5%; mean rank, 9.2). In subgroup analyses considering efficacy and tolerance, voriconazole might be the best choice for patients undergoing HSCT, especially allogenic HSCT; however, posaconazole was ranked as the best choice for patients with acute myeloid leukemia or myelodysplastic syndrome. Conclusions and Relevance: These findings suggest that voriconazole may be the best prophylaxis option for patients undergoing HSCT, and posaconazole may be the best prophylaxis option for patients with acute myeloid leukemia or myelodysplastic syndrome.

Host Differential Sensitization toward Color/Lifetime-Tuned Lanthanide Coordination Polymers for Optical Multiplexing.

Optical multiplexing based on luminescent materials with tunable color/lifetime has potential applications in information storage and security. However, the available tunable luminescent materials reported so far still suffer from several drawbacks of low efficiency or poor stability, thus restraining their further applications. Herein, we demonstrate a strategy to develop efficient and stable lanthanide coordination polymers (LCPs) with tunable luminescence as a new option for optical multiplexing. Their multicolor emission from green to red and naked-eye-sensitive green emission with tunable lifetime (from ca. 300 to ca. 600 µs) can be controlled by host differential sensitization and energy transfer between lanthanide ions. The quantum efficiencies of developed samples range from around 20 % to 46 % and the luminescence intensity/lifetime appear quite stable in polar solvents up to ten weeks. Furthermore, with the aid of inkjet printing and concepts of luminescence lifetime imaging and time-gated imaging, we illustrate their promising applications of information storage and security in spatial and temporal domains.

The stability of coordination polyhedrons and distribution of europium ions in Ca6BaP4O17.

In this work, the coordination polyhedron stabilities and distributions of europium ions in Ca6BaP4O17 (CBPO) luminescent materials are investigated. The density functional theory (DFT)-based first principles calculation results show that the PO4 tetrahedrons can tilt in the structure, which leads to the atomic distortion of O13 and O12 in CBPO and the Eu2+/Eu3+-doped systems. The energy scale of about ∼0.1 eV suggests that stabilities of coordination polyhedrons are easily influenced by dynamic factors. The atomic distortion and vacancy of work as charge compensations in CBPO:Eu3+, and three lattice sites of europium are extracted and summarized. The X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) confirm that Eu3+ can occupy the Ca1, Ca2 and Ba sites of CBPO. The combination of first principles calculation and X-ray absorption fine structure (XAFS) provides more information about microstructures of luminescent materials.

Nomogram for Predicting the Overall Survival of Adult Patients With Primary Gastrointestinal Diffuse Large B Cell Lymphoma: A SEER- Based Study.

Background: The aim of this study was to establish a precise prognostic model, based on significant clinical parameters, for predicting the overall survival (OS) of adult patients with primary gastrointestinal diffuse large B cell lymphoma (GI DLBCL). Materials and Methods: The data of 7,121 GI DLBCL patients, diagnosed between 1997 and 2015, were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. These patients were randomly divided into two sequential cohorts: training (n = 5,697) set and validation (n = 1,424) set. ROC methodology and calibration curves were explicitly used to evaluate the predictive performance of nomogram. Results: The median OS in the training cohort was 76 months (1-239 months), and 3, 5, and 10-year OS rates were 60.3, 53.9, and 39.5%, respectively. Age at diagnosis, Ann Arbor stage, and marital status were important clinical predictors of OS. These characteristics were used to build a nomogram. The AUC of the nomogram for predicting 3, 5, and 10-year OS were 0.669, 0.692, and 0.740, respectively. All RUC and calibration curves revealed good accuracy in predicting prognosis of GI DLBCL. Conclusion: In summary, the established nomogram was validated to predict OS for adult patients with GI DLBCL. This predictive model could help clinicians identify high-risk patients to improve their prognosis.

Higher Level of Peripheral Blood CD34 Positive Cells Presented with Unfavorable Prognosis in Intermediate-Low Risk Acute Promyelocytic Leukemia.

Our previous work has demonstrated that some acute promyelocytic leukemia (APL) patients had significantly elevated circulating CD34+ cell count (≥ 10 × 106/L), and these patients with higher CD34+ cell level usually presented with high-risk disease (WBC > 10,000/µL). The aim of this study was to investigate whether circulating CD34+ cell count is a prognostic marker in intermediate-low risk APL patients. In this study, 76 intermediate-low risk APL patients and 56 age-adjusted healthy volunteers were evaluated. Enumeration of CD34+ cells was investigated before the treatment. A cut-off value of 10 × 106/L CD34+ cells could just distinguish APL patients with adverse prognostic factors from others and may have the power to predict shorter progression-free survival (PFS) and poor prognosis. Higher count of CD34+ cells was usually associated with nonclassical chromosomal translocation, PML/RARα gene complex fusion, APL history, chemotherapy-related APL, disease progression, second tumor, extramedullary infiltration, FLT3-ITD positive mutation, atypical morphology, BM promyelocyte CD56/CD34 positive expression, myelofibrosis, PCR-positive PML/RARa gene fusion but FISH-negative, marrow necrosis and shorter PFS. Our results suggest that the level of CD34+ cells can be further the stratification of disease risk, a higher CD34+ cell count may be indicative of inferior survival and serve as an adverse biomarker for intermediate-low risk APL.

Age-related severity and distribution of haemophilic arthropathy of the knee, ankle and elbow among Chinese patients with haemophilia.

INTRODUCTION AND AIMS: Age-related severity and distribution of haemophilic arthropathy (HA) among Chinese patients with haemophilia using the Haemophilia Early Detection with Ultrasound (HEAD-US) system have not been extensively studied. METHODS: In our study, 89 patients with moderate and severe haemophilia were recruited. A total of 534 joints (knees, ankles and elbows on both sides included) were evaluated using musculoskeletal ultrasound (MSKUS) and scored using the HEAD-US system. RESULTS: Prevalence and average number of HA were 39.1% and 0.7, 90.6% and 3.2, 94.1% and 4.5, and 100% and 4.3 for ages ≤10, 11-20, 21-30 and 31-40 years, respectively. Prevalence and mean number of knee, ankle and elbow arthropathies also increased with age, although joint damages progressed in unparallel patterns. A significant difference in synovium subscores was observed between patients aged <10 and >10 years. An increasing tendency was observed in cartilage and subchondral bone subscores along with age before 30 years. No significant difference in mean joint scores was found between patients receiving on-demand therapy and those receiving on-demand to low-dose prophylactic therapy. CONCLUSIONS: Haemophilic arthropathy developed in early childhood and progressed mainly before 30 years of age among Chinese patients with haemophilia, although in different ways among the knee, ankle and elbow.

Hepatitis B virus infection and 1q21 amplification in multiple myeloma.

Hepatitis B virus (HBV) is a hepatotropic and a lymphotropic virus. An association between HBV and hematologic malignancies has been determined previously; however, the association between HBV infection and multiple myeloma (MM) remains controversial. The present study aimed to assess the prevalence of HBV infection in patients with MM, and investigate their characteristics and prognostic significance. The clinical data of 165 patients with MM who had received at least four cycles of chemotherapy between April 2008 and February 2017 at Nanjing Drum Tower Hospital (Nanjing, China) were collected. HBV markers were determined using ELISA. The rates of acute or chronic HBV infection and resolved HBV infection in patients with MM were 12.12 and 26.06%, respectively. The gain of 1q21 was significantly more prevalent in the patients who were classified as HBV-positive compared with the patients who were classified as HBV-negative (54 vs. 38.2%; P=0.048), and the level of alanine transaminase in patients who were classified as HBV-positive was significantly increased compared with the non-infected group (63.29 vs. 24.66 U/l; P=0.043). Lactate dehydrogenase, serum creatinine and serum calcium levels were additionally determined to be significant risk factors of overall survival. The progression-free survival (PFS) of patients who were classified as HBV-positive was decreased compared with patients who were classified as HBV-negative (18.97 vs. 29.67 months; P=0.006), and being HBV-positive was determined to be an independent prognostic factor of PFS. HBV infection may contribute to MM progression through 1q21 amplification, and improved monitoring of HBV markers in patients with MM may be required.

Vincristine-loaded platelets coated with anti-CD41 mAbs: a new macrophage targeting proposal for the treatment of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder in which platelet-reactive autoantibodies accelerate the destruction of platelets. Macrophages play an important role in ITP through Fc receptor (FcR)-mediated antigen presenting and platelet clearance. In this study, a novel drug delivery system of vincristine-loaded platelets coated with anti-CD41 mAbs (CD41-VCR-PLT, CD41-VLP) was successfully established. The therapeutic effects and safety of CD41-VLP in vitro and in vivo were evaluated, and the possible mechanism was also explored. The results showed that PLT-CD41 could load VCR with high drug loading (DL) and encapsulation efficiency (EE), which were up to 41.16 ± 1.92% and 60.73 ± 2.79%, respectively, where platelets had no obvious morphological or functional changes. CD41-VLP could facilitate vincristine accumulation in macrophages, where the intracellular VCR concentration was 30.72 ± 3.11% at 72 h, which was significantly increased compared with the other groups (P < 0.01), thus inhibiting macrophage cell viability and inducing apoptosis. The cell viability inhibition rate and total apoptosis rate were 73.06 ± 5.26% and 69.70 ± 4.26%, respectively, both much higher than those of the other groups (P < 0.05). In the ITP mouse model, CD41-VLP increased the platelet count in peripheral blood, which was 720 ± 197.98 × 109 L-1, and significantly improved the platelet count compared with that in the VCR group (P < 0.05); moreover, it reduced the systemic toxicity and peripheral neurotoxicity of vincristine. The possible mechanism was that CD41-VLP could precisely target M1 macrophages in spleen and liver tissues through FcγR, thus reducing the platelet destruction caused by M1 macrophages. Therefore, CD41-VLP provides a new targeted therapy for ITP treatment.

Prognostic Value of 1q21 Gain in Multiple Myeloma.

BACKGROUND: Multiple myeloma (MM) is a heterogeneous disease characterized by chromosomal translocation, deletion, and amplification in plasma cells, resulting in a huge heterogeneity in its outcomes. In the era of novel agents such as bortezomib, thalidomide, and the cycles of treatment, risk stratification by chromosomal aberrations may enable a more rational risk-stratification selection of therapeutic approaches in patients with MM. PATIENTS AND METHODS: We performed a retrospective study in 63 patients with MM; 29 (46.03%) with 1q21 gain and 34 (53.97%) without gain. RESULT: In all patients, we did not find that the patients with 1q21 gain had significantly better survival compared with patients without 1q21 gain (overall survival, P = .6916; progression-free survival, P = .8740). However, in 1q21 gain patients, we found that the bortezomib group had significantly better survival compared with the non-bortezomib group in terms of both the 3-year estimated overall survival (82.3% vs. 18.8%; P = .0154) and progression-free survival (62.8% vs. 8.75%; P = .0385). CONCLUSION: 1q21 gain detected by fluorescence in situ hybridization is not as high risk for poor prognosis with regard to time for overall survival. And the clinical outcome of patients with 1q21 gain can be improved in those who received no less than 4 cycles of bortezomib-based therapy (bortezomib, thalidomide, and dexamethasone).

Higher single dose of bortezomib plus thalidomide and dexamethasone is a promising therapy for newly diagnosed multiple myeloma.

BACKGROUND: Bortezomib in combination with thalidomide and dexamethasone (VTD) has been widely used for newly diagnosed multiple myeloma (MM). The aim of this study was to evaluate the efficacy and safety of a new high-dose bortezomib plus thalidomide and dexamethasone as an induction and consolidation therapy regimen for MM. METHODS: A total of 93 patients with previously untreated symptomatic MM were enrolled in this single-center study. In group-1, 40 patients received bortezomib 1.6 mg/m2 and dexamethasone 40 mg on days 1, 6 and 11, plus thalidomide 100 mg on days 1-21 (VTD-1). In group-2, 53 patients received bortezomib 1.3 mg/m2 and dexamethasone 40 mg on days 1, 4, 8 and 11 in combination with thalidomide 100 mg on days 1-21 (VTD-2). RESULTS: The odds ratio rates after 2 cycles of VTD and the best response during this study were 95% vs. 81.1% (P=0.044), and 95% vs. 90.6% (P=0.349) in group-1 and group-2, respectively. The best CR rate in group-1 was higher than that in group-2 [52.5% vs. 45.3% (P=0.316)]. In group-1, only 2 of 21 patients who achieved CR relapsed from the disease, as did 9 of 24 patients in group-2 (P=0.031). The median PFS in group-1 and group-2 were 34 and 28.8 months (P=0.969), and the median OS in group-1 and group-2 were 33.5 and 46.4 months (P=0.987). In group-1 and group-2, the median CD34+ cells of stem cell collection were 3.68×106 vs. 5.84×106 cells/kg (P=0.179). Patients in group-1 had a lower incidence of peripheral neuropathy than group-2 [32.5% vs. 41.5% (P=0.371)]. CONCLUSIONS: High-dose bortezomib at a dose of 1.6 mg/m2 in combination with thalidomide and dexamethasone was well tolerated and highly efficient as an induction and consolidation therapy for MM.