Thrombopoietin receptor agonists regulate myeloid-derived suppressor cell-mediated immunomodulatory effects in ITP.

TPO receptor agonists (TPO-RAs) are a class of clinical second-line regimens for the treatment of primary immune thrombocytopenia (ITP). It can promote megakaryocyte maturation and increase platelet production, but its effect on immunosuppressive cells in patients with ITP has not been explored. Sixty-two ITP patients and 34 healthy controls (HCs) were included in this study. The proportion and functions of myeloid-derived immunosuppressive cells (MDSCs) in ITP patients and HCs were investigated. We found that the proportion and function of MDSCs in ITP patients treated with TPO-RAs were significantly higher than those treated with glucocorticoids (GCs), which was correlated with the clinical efficacy. The proportion and function of cytotoxic Th1 cells and CD8+T cells decreased, while the proportion and immunosuppressive function of Treg cells increased in ITP patients treated with TPO-RAs. We further proved, through MDSC depletion tests, that the inhibitory effect of MDSCs on Th1 cells and the promotion of Treg cells in the original immune micro-environment of GCs-treated ITP patients were impaired; however, these MDSCs' functions were improved in TPO-RAs-treated patients. Finally, we found that the KLF9 gene in MDSCs cells of ITP patients treated with TPO-RAs was down-regulated, which contribute to the higher mRNA expression of GADD34 gene and improved function of MDSCs. These results demonstrate a novel mechanism of TPO-RAs for the treatment of ITP through the assessment of MDSCs and their subsequent impact on T cells, which provides a new basis for TPO-RAs as first-line treatment approach to the treatment of ITP.

Reduced doses of emicizumab achieve good efficacy: Results from a national-wide multicentre real-world study in China.

INTRODUCTION: Reduced doses of emicizumab improve the affordability among patients in developing countries. However, the relationship between variant dose selection and efficacy in the real world of China is still unclear. AIM: This study aimed to investigate the efficacy and safety of emicizumab especially in those on reduced dose regimens in a real-world setting. METHODS: We carried out a multicentre study from 28 hospitals between June 2019 and June 2023 in China and retrospectively analysed the characteristics including demographics, diagnosis, treatment, bleeding episodes, and surgical procedures. RESULTS: In total, 127 patients with haemophilia A, including 42 with inhibitors, were followed for a median duration of 16.0 (IQR: 9.0-30.0) months. Median age at emicizumab initiation was 2.0 (IQR: 1.0-4.0) years. Median (IQR) consumption for loading and maintenance was 12.0 (8.0-12.0) and 4.2 (3.0-6.0) mg/kg/4 weeks, respectively. While on emicizumab, 67 (52.8%) patients had no bleeds, whereas 60 (47.2%) patients had any bleeds, including 26 with treated bleeds. Compared to previous treatments, patients on emicizumab had significantly decreased annualized bleeding rate, annualized joint bleeding rate, target joints and intracerebral haemorrhage. Different dosages had similar efficacy except the proportion of patients with treated spontaneous bleeds and target joints. Adverse events were reported in 12 (9.4%) patients. Postoperative excessive bleeding occurred following two of nine procedures. CONCLUSION: This is the largest study describing patients with HA receiving emicizumab prophylaxis on variant dose regimens in China. We confirmed that nonstandard dose is efficacious and can be considered where full-dose emicizumab is ill affordable.

Venetoclax acts as an immunometabolic modulator to potentiate adoptive NK cell immunotherapy against leukemia.

Natural killer (NK) cell-based immunotherapy holds promise for cancer treatment; however, its efficacy remains limited, necessitating the development of alternative strategies. Here, we report that venetoclax, an FDA-approved BCL-2 inhibitor, directly activates NK cells, enhancing their cytotoxicity against acute myeloid leukemia (AML) both in vitro and in vivo, likely independent of BCL-2 inhibition. Through comprehensive approaches, including bulk and single-cell RNA sequencing, avidity measurement, and functional assays, we demonstrate that venetoclax increases the avidity of NK cells to AML cells and promotes lytic granule polarization during immunological synapse (IS) formation. Notably, we identify a distinct CD161lowCD218b+ NK cell subpopulation that exhibits remarkable sensitivity to venetoclax treatment. Furthermore, venetoclax promotes mitochondrial respiration and ATP synthesis via the NF-κB pathway, thereby facilitating IS formation in NK cells. Collectively, our findings establish venetoclax as a multifaceted immunometabolic modulator of NK cell function and provide a promising strategy for augmenting NK cell-based cancer immunotherapy.

Can COVID-19 Increase Platelet in Adult Immune Thrombocytopenia During the TPO-RA Administration? A Real-World Observational Study.

Introduction: COVID-19 infection has brought new challenges to the treatment of adult patients with immune thrombocytopenia (ITP). In adult ITP patients, there have been no relevant reports exploring the incidence, clinical characteristics, and risk factors of platelet elevation after COVID-19 infection. Materials and Methods: A total of 66 patients with previously diagnosed ITP from December 2022 to February 2023 in a single-center were collected and analyzed for this real-world clinical retrospective observational study. Results: In the platelet count increased group (n = 19), 13 patients (68.4%) were using thrombopoietin receptor agonists (TPO-RA) treatment at the time of COVID-19 infection; the median platelet count was 52 (2-207) ×109/L at the last visit before infection and 108 (19-453) ×109/L at the first visit after infection. In the platelet count stable group (n = 19) and platelet count decreased group (n = 28), 9 (47.4%) and 8 (28.6%) patients were using TPO-RA at the time of infection, respectively. ITP patients treated with TPO-RA had a significantly higher risk of increased platelet count than those not treated with TPO-RA at the time of infection (platelet count increased group vs platelet count decreased group: OR: 5.745, p = 0.009; platelet count increased group vs the non-increased group: OR: 3.616, p = 0.031). In the platelet count increased group, the median platelet count at 6 months post-infection was 67 (14-235) × 109/L, which was significantly higher than the platelet level at the last visit before infection (p = 0.040). Conclusion: This study showed that some adult ITP patients had an increase in platelet count after COVID-19 infection, and this phenomenon was strongly associated with the use of TPO-RA at the time of infection. Although no thrombotic events were observed in this study, it reminds clinicians that they should be alert to the possibility of thrombotic events in the long-term management of adult ITP patients during the COVID-19 pandemic.

Effects of the excitation wavelength and temperature on the zero-phonon emission line of Cr:YAG.

In this work, a detailed study was conducted of the temperature and excitation wavelength-dependent photoluminescence (PL) spectra of the chromium-doped yttrium aluminum garnet (Cr:YAG) transparent ceramic. Focusing on the two sets of zero-phonon lines (ZPLs) of the 2 E→4 A 2 transition in this material, the PL spectra are discovered to evolve significantly with respect to temperature and be highly dependent on the excitation wavelength. Compared to the continuous variation behavior with temperature, an increase in the excitation wavelength leads to a blueshift of the peak position within the regions of 450 nm to 465 nm, 465 nm to 490 nm, and 490 nm to 500 nm, and a sharp change in the PL position at the excitation wavelengths of 465 nm and 490 nm. The electron-phonon coupling (EPC) effect is believed to be more sensitive to the excitation wavelength. Different excitation wavelengths involve different electronic levels participating in the light emission processes, which explains the evolution behavior of the PL peak position with respect to the excitation wavelength. Moreover, the emergence of weak peaks next to the ZPLs at particular temperatures and excitation wavelengths is also observed. This work compares the influence of the temperature and excitation wavelength to the PL properties of the Cr:YAG transparent ceramic, which promotes an advanced understanding of the luminescence behavior of the Cr:YAG transparent ceramics.

Efficacy and safety of QL0911 in adult patients with chronic primary immune thrombocytopenia: A multicenter, randomized, double-blind, placebo-controlled, phase III trial.

Objective: QL0911, a recombinant human thrombopoietin mimetic peptide-Fc fusion protein, is a romiplostim (Nplate®) biosimilar used to treat primary immune thrombocytopenia (ITP). This phase III study aimed to assess the efficacy and safety of QL0911 in adult patients with chronic primary ITP over a 24-week treatment period. Methods: We conducted a double-blind, placebo-controlled, phase III study in patients diagnosed with primary ITP for at least 12 months who had received at least one first-line ITP treatment with no response or recurrence after treatment, or who relapsed after splenectomy at 44 sites in China. Patients were randomly allocated (2:1 ratio) to QL0911 or placebo injection subcutaneously once weekly at an initial dose of 1 µg/kg for 24 weeks. The doses were adjusted to maintain the target platelet counts from 50 × 109/L to 200 × 109/L. Patients and investigators were blinded to the assignment. The primary endpoints were the proportion of patients who achieved a durable platelet response at week 24 (platelet count, ≥ 50 × 109/L during 6 of the last 8 weeks of treatment) and safety. The study was registered at ClinicalTrials.gov (NCT05621330). Results: Between October 2019 and December 2021, 216 patients were randomly assigned (QL0911,144; placebo,72). A durable platelet response was achieved by significantly more patients in the QL0911 group (61.8%, 95% CI: 53.3-69.8; P < 0.0001) than in the placebo group (0%). The mean duration of platelet responses was 15.9 (SE: 0.43) weeks with QL0911, and 1.9 (SE:0.26) week with placebo. Consistent results were achieved in subgroup analyses categorized by baseline splenectomy status (yes/no), concomitant ITP treatment (yes/no), and baseline platelet count (≤ 10 × 109/L, > 10 × 109/L, ≤ 20 × 109/L, > 20 × 109/L, and < 30 × 109/L). The incidence of TEAEs was comparable between the QL0911 and the placebo groups (91.7% and 88.9%, respectively). The most common adverse events overall were ecchymosis (28.5% for QL0911 vs. 37.5% for placebo), upper respiratory tract infections respiratory tract infections (31.9% for QL0911 vs. 27.8% for placebo), and gingival bleeding (17.4% for QL0911 vs. 26.4% for placebo). Conclusion: QL0911 was well-tolerated and increased and maintained platelet counts in adults with ITP. QL0911, a biosimilar to romiplostim (Nplate®), may be a novel treatment option for patients with ITP who have failed or relapsed from first-line treatment in China. Ongoing studies will provide further data on long-term efficacy and safety in such patient populations.

Selinexor Synergistically Promotes the Antileukemia Activity of Venetoclax in Acute Myeloid Leukemia by Inhibiting Glycolytic Function and Downregulating the Expression of DNA Replication Genes.

Introduction: The BCL-2 inhibitor venetoclax has been widely used in the treatment of acute myeloid leukemia (AML); however, AML patients treated with venetoclax gradually develop resistance. The exportin-1 (XPO1) inhibitor selinexor can synergistically promote the antileukemia activity of venetoclax, but the mechanism remains unclear. Methods and Results: Annexin V/7-aminoactinomycin D assays were used to examine the effects of a combination of venetoclax and selinexor (VEN+SEL) on AML cell lines and primary AML cells. RNA sequencing and oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) determinations by a Seahorse XF analyzer were employed to investigate the molecular mechanism of the toxicity of the VEN+SEL combination to AML cells. The cytotoxicity of NK cell combined with VEN+SEL combination was assessed in vitro using flow cytometry. VEN+SEL enhanced the apoptosis of AML cells (KG-1A and THP-1) and primary AML samples in vitro. The ECAR and OCR results demonstrated that the VEN+SEL combination significantly inhibited glycolytic function. RNA sequencing of THP-1 cells demonstrated that DNA replication-related genes were downregulated after treatment with the VEN+SEL combination. Conclusion: This study indicated that selinexor can synergistically enhance the antileukemia activity of venetoclax in AML cells in vitro by inhibiting glycolytic function and downregulating DNA replication-related genes. Based on our experimental data, combining selinexor with venetoclax is an appropriate advanced treatment option for AML patients.

Treatment of immune thrombocytopenia with hetrombopag olamine tablets in a Kabuki syndrome patient with new KMT2D mutations.

Kabuki syndrome (KS) is a rare multisystem-affecting genetic disorder, and usually accompanied with autoimmune disorders such as immune thrombocytopenic purpura (ITP). Here, we report a 16-year-old patient with Kabuki syndrome with ITP and observe the therapeutic effect of TPO agonist hetrombopag olamine tablets. The duration of maintenance therapy and follow up were both 17 months. Whole exon sequencing (WES) of the patient's peripheral blood showed c.5775_5778del (p. Leu1926LysfsTer120) heterozygous mutation in the KMT2D gene, which was not reported before.

Manipulation of Temperature-Dependent Luminescence Behaviors of Mn4+-Activated Fluoride Phosphors.

In this paper, the giant tunability of thermal behaviors, i.e., from thermal deterioration to substantial growth, is firmly demonstrated for the vibronic luminescence of Mn4+ ions in fluoride phosphors. Such peculiar behavior is uncovered to be associated with the thermal excitation of a low-frequency phonon bath, and a theoretical model involving the excitation-wavelength-dependent populations of vibronic levels and the temperature-dependent nonradiative recombination processes is successfully constructed. Two main governing parameters, namely, the thermal activation energy Ea and the involved average phonon energy ΔE, are thus determined for the distinct thermal behaviors of Mn4+-ion luminescence. This demonstration may pave the way for manipulating the thermal behaviors of vibronic luminescence in solids to some extent.

Strain evolution and confinement effect in InAs/AlAs short-period superlattices studied by Raman spectroscopy.

Raman spectra of two series of InAs/AlAs short-period superlattices were measured at room temperature to investigate the impact of strain on the phonon modes taking into consideration the confinement effect and interface mode. The evolution of strain in the InAs layer and the AlAs layer was studied in (InAs)2/(AlAs)2 superlattices grown at various temperatures (400-550 °C). While the strain existed in the AlAs layer remained almost constant, the strain in the InAs layer varied significantly as the growth temperature increased from 500 to 550 °C. The confinement effect on the optical phonons was analyzed based on results from (InAs)n/(AlAs)n grown at 450 °C (n = 2, 3, 4, and 5). Additionally, the confinement effect was found to be stronger in shorter periods with higher interface quality. The interface phonon modes were resolved between the longitudinal optical and transverse optical phonon modes, which assist in the rough estimation of the thickness of the layers. The disorder-activated acoustic phonon modes at the low-frequency side were also addressed.

The Addition of Hypomethylating Agents to Low-Intensity Induction Chemotherapy Does Not Improve Outcomes in Elderly Acute Myeloid Leukemia Patients: A Single-Center Retrospective Study.

Background and Objectives: This study aimed to evaluate whether the addition of hypomethylating agents (HMA) to low-intensity chemotherapy can enhance the clinical efficacy of induction treatment for elderly acute myeloid leukemia (AML) patients who are unsuitable for standard induction therapy. Materials and Methods: This study retrospectively analyzed 117 patients over 60 years old who were initially diagnosed with AML and received low-intensity induction treatment in the Department of Hematology in Anhui provincial hospital from January 2015 to December 2020. Twenty-three patients were excluded, and the remaining 94 patients were divided into two groups according to the selection of induction regimens. Results: Forty-four patients received HMA combined with low-intensity chemotherapy, and the other 50 patients received only low-intensity induction chemotherapy. Forty-three patients (45.7%) obtained complete remission (CR) after the initial induction treatment. The CR rate in the HMA plus low-intensity chemotherapy group was 34.1% (15/44), and in the single low-intensity chemotherapy group was 56.0% (28/50) (p = 0.04). The 30 days cumulative early death rates were 9.1% (95% CI: 3.5-22.4%) in the HMA plus low-intensity chemotherapy group and 6.0% (95% CI: 2.0-17.5%) in the single low-intensity chemotherapy group, respectively (p = 0.59), and the one-year cumulative relapse rates were 21.1% (95% Cl: 9.8-41.9%) and 33.3% (95% Cl: 20.3-51.5%), respectively (p = 0.80). The one-year overall survival (OS) rates for patients in the HMA plus low-intensity chemotherapy group and the single low-intensity chemotherapy group were 37.3% (95% Cl: 23.1-51.5%) and 55.4% (95% Cl: 40.5-67.9%), respectively (p = 0.098), and the one-year event-free survival (EFS) rates were 8.5% (95% Cl: 2.2-20.6%) and 20.6% (95% Cl: 9.1-35.3%), respectively (p = 0.058). Conclusions: This study showed that the addition of HMA to low-intensity induction chemotherapy does not improve prognosis in elderly AML patients who are unsuitable for standard induction chemotherapy.

Cytomegalovirus-Specific T Cells from Third-Party Donors Successfully Treated Refractory Cytomegalovirus Retinitis after Unrelated Umbilical Cord Blood Transplantation.

Umbilical cord blood (UCB) transplants (UCBTs) are becoming increasingly common in the treatment of a variety of hematologic and nonhematologic conditions. The T cells from UCB are naïve T cells, which have not yet been exposed to antigens and therefore do not contain T cells with specific immune functions against viruses. Cytomegalovirus (CMV) infections occur in more than 80% of patients after UCBT compared to other types of transplantation. Anti-CMV medications are currently restricted, with ganciclovir, foscarnet, and valganciclovir being the most common in China; however, with limited efficacy and considerable side effects, all these drugs are susceptible to viral resistance. In recent years, cytomegalovirus-specific T cells (CMVST) have advanced the treatment of viral infections in immunodeficient patients. CMVST usually uses the same donor as hematopoietic stem cell transplantation. CMVST should be administered to UCBT patients because of the absence of donors after UCBT. In China, there is no report on the use of CMVST to treat CMV infection after UCBT, and foreign reports are also limited. This paper reported a 20-year-old male patient with acute myeloid leukemia who developed cytomegalovirus retinitis (CMVR) after umbilical cord blood transplantation. After ineffective viral treatment, he was treated with a third-party donor CMVST and was successfully transformed into CMV nucleic acid negative.

Standard-Intensity Induction and Intermediate/High-Dose Cytarabine Consolidation Can Improve Survival for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Cohort Study.

BACKGROUND: There is great uncertainty in the treatment of elderly patients with acute myeloid leukemia (AML), which leads to great challenges in treatment decision. The aim of this study is to find more suitable induction therapy and consolidation therapy for elderly AML patients. METHODS: A total of 149 consecutive newly diagnosed elderly AML patients (aged ≥60 years) who received induction chemotherapy in our medical center from January 2015 to December 2019 were retrospectively analyzed. RESULTS: After the first induction treatment, the complete remission/or complete remission with incomplete hematologic recovery (CR/CRi) rates in the standard-intensity chemotherapy group was significantly higher than that in the low-intensity chemotherapy group (58.2% vs 32.9%, p = 0.003). Compared with the low-intensity chemotherapy, the incidence of severe infection in the standard-intensity chemotherapy was significantly increased (p < 0.001), but the early mortality was comparable. One hundred and seven patients received minimal residual disease (MRD) examination after the first induction treatment; and MRD was negative accounting for 51.9% in the standard-intensity chemotherapy group, while only 32.7% in the low-intensity group (p = 0.05). The 2-year-overall survival (OS) of patients in standard-intensity induction chemotherapy group (37.2%) was slightly higher than that in low-intensity induction chemotherapy group (23.4%) (p = 0.075). Eighty-one CR/CRi patients received intermediate or high dose cytarabine (n = 35) or sequential chemotherapy regimens (n = 46) as consolidation treatment. The 2-year OS and event-free survival (EFS) of patients in the intermediate or high-dose cytarabine group were significantly higher than those in the sequential chemotherapy regimens group (73.0% vs 38.5%, p = 0.002; 54.8% vs 35.0%, p = 0.035). CONCLUSION: Our results showed that standard-intensity induction chemotherapy can significantly improve the CR rate for elderly AML patients, and does not increase the early mortality; consolidation therapy with intermediate or high-dose cytarabine can significantly improve EFS and OS for elderly AML patients achieved CR.

Dose tapering to withdrawal stage and long-term efficacy and safety of hetrombopag for the treatment of immune thrombocytopenia: Results from an open-label extension study.

BACKGROUND: The efficacy of hetrombopag in Chinese patients with immune thrombocytopenia (ITP) has been demonstrated in a randomized, double-blind, placebo-controlled, multicenter, phase III trial (NCT03222843). OBJECTIVE: This study aimed to report comprehensive data on a ≤6-week dose tapering to withdrawal (Stage 3) and an additional 24-week long-term extension period (Stage 4) in this phase III trial. PATIENTS/METHODS: Patients who fulfilled the screening criteria were eligible to enter Stage 3 or 4. During Stage 3, hetrombopag was gradually tapered to withdrawal. During Stage 4, hetrombopag treatment was initiated at 2.5, 3.75, 5, or 7.5 mg once daily. The efficacy endpoints during Stage 3 or 4 and the safety profile during the entire treatment period were reported. RESULTS: Among 194 patients who entered Stage 3, 171 (88.1%) relapsed. The median time to the first relapse since the start of Stage 3 was 15.0 days (95% CI, 14.0-16.0). In Stage 4, 144 (42.5%) patients responded at ≥75% of their assessments and 254 (74.9%) patients achieved platelet count ≥30 × 109 /L at least once, which was at least twice their baseline platelet count in the hetrombopag group (n = 339). The most common adverse events were upper respiratory tract infection (53.1%), thrombocytopenia (27.1%), and urinary tract infection (21.2%) in the hetrombopag group. CONCLUSION: The majority of patients who experienced dose tapering to withdrawal experienced a relapse. Long-term treatment with hetrombopag was effective in increasing and maintaining platelet count within the desired range in Chinese adults with ITP. Hetrombopag was well tolerated.

High-dose cytarabine monotherapy is superior to standard-dose cytarabine- based multiagent sequential treatment cycle for consolidation treatment in adult (14-59 years) AML patients according to European Leukemia Net 2022 risk stratification.

Introduction: We firstly investigate based on 2022 European Leukemia Net (ELN) risk stratification, whether standard-dose cytarabine based multiagent sequential chemotherapy (SDMSC) is more beneficial than high-dose cytarabine (HDAC) monotherapy in consolidation for the survival of adult acute myeloid leukemia (AML) patients. Methods: One hundred and eighty-three AML patients with complete remission (CR) were evaluated. Results and discussion: The 3-year relapse rate was 33.4% in the HDAC group and 50.5% in the SDMSC group (p=0.066). The 3-year overall survival (OS) and event-free survival (EFS) rates in the HDAC group (69.2%, 60.7%) were significantly higher than that in the SDMSC group (50.8%, 42.1%) (p=0.025, 0.019). For patients in the intermediate risk group, the 3-year OS and EFS rates in the HDAC group (72.5%, 56.7%) were higher than that in the SDMSC group (49.1%, 38.0%) (p=0.028, 0.093). This study indicates that for young adult AML patients, HDAC consolidation achieves a higher long-term survival than SDMSC, especially for patients in the intermediate-risk group according to the 2022 ELN risk stratification.

Luminescence performance and vibronic behavior of Mn4+-activated Ca14-xKxAl10Zn6O35 deep-red phosphor.

In this study, a significant improvement of deep-red luminescence was successfully achieved via the substitution approach in the Mn4+-activated Ca14-xKxAl10Zn6O35 phosphor. The optimal Mn4+ doping level x was determined by studying luminescence concentration quenching behavior. The measured photoluminescence (PL) spectrum showed five distinct vibronic structures with the main peak centered at 712 nm. A theoretical simulation work was conducted for comparison, and the predominant phonon mode involving in the vibronic transition process was revealed. From the temperature-dependent PL spectra, an abnormal luminescence enhancement was observed at the temperature rising from T=100 to 340 K, and the underlying phonon-assisted luminescence mechanism was theoretically disclosed. Finally, we studied the temperature-dependent luminescence lifetime, and the primary phonon energy in the vibronic behavior was identified from the fitting work.

Efficacy of Venetoclax Combined with Decitabine-Based Treatment for Heavily Pre-Treated Relapsed or Refractory AML Patients in a Real-World Setting.

PURPOSE: We report the efficacy and safety of venetoclax plus decitabine-based treatment in heavily pre-treated relapsed or refractory acute myeloid leukaemia (RR-AML) in a real-world setting. PATIENTS AND METHODS: There were 22 patients in this study and the median age was 47.5 (12-84) years old, including 11 males and 11 females. Among them, 8 patients were relapsed AML including 2 patients relapsed after HSCT and 14 patients with primary refractory AML including 4 secondary AML. The median number of cycles of previous chemotherapy was 4 (range, 2-10). RESULTS: After a course of venetoclax plus decitabine-based treatment, 9 patients achieved complete remission (CR) and 1 patient achieved complete remission with incomplete haematological recovery (CRi). The overall response rate (ORR) was 45.5% and the CR rate was 40.9%, and the median time to reach CR/CRi was 21 (13-46) days. Four of the 10 CR/CRi patients relapsed again, and the median time of relapse was 5 (1.0-24) months. The one-year overall survival rate was 31.8%, and the median survival time was 6 months (95% CI, 1-9 months). The one-year overall survival rate of 10 CR/CRi patients was 59.1%, and the 12 NR patients was 10.4% (p=0.001). Nausea and vomiting occurred in 11 patients (50.0%). All patients had grade IV neutropenia and IV thrombocytopenia (100%). Pneumonia occurred in 14 patients (63.6%) and septicaemia occurred in 2 patients (9.0%). The cause of death in all patients was primary disease progression, and no patients died due to the side effects. CONCLUSION: The efficacy of venetoclax plus decitabine-based treatment in the real-world treatment of heavily pre-treated RR-AML is similar to that in clinical trials, and the side effects are controllable.

Pharmacokinetic, efficacy and safety evaluation of B-domain-deleted recombinant FVIII (SCT800) for prophylactic treatment in adolescent and adult patients with severe haemophilia A.

INTRODUCTION: SCT800 is a recombinant human B-domain-deleted coagulation factor VIII (BDDrFVIII) developed in China. AIM: To evaluate the repeat pharmacokinetics (PKs), efficacy, and safety of SCT800 in previously treated Chinese adolescent and adult patients with severe haemophilia A. METHODS: A phase III, multicentre, prospective, open-label, single-arm trial was conducted at 12 medical centres. Subjects received treatment for 24 weeks. PKs were assessed at the initial and repeated dosing 24 weeks later. The primary endpoint was annualized bleeding rate (ABR). Breakthrough bleeding episodes and inhibitor development were assessed. RESULTS: A total of 71 of 73 patients completed the study, and 18 were enrolled for the repeat PK investigation. Total exposure was 5643 exposure days. Overall, SCT800 showed comparable repeat PK profiles. The total ABR was 2.82 (95% confidence interval 2.01-3.96). During prophylaxis, 43.8% of patients had no bleeding episodes. The majority (89.4%) of bleeding episodes were controlled with 1-2 injections of SCT800, the success rate (defined as 'excellent' or 'good' haemostatic response) for the treatment of bleeding episodes was 92.6%. The incidence of treatment-related adverse events was 53.4%. Drug-related AE incidence was 4.1%. The observed AEs were similar to those of other coagulation factor VIII, but lower in frequency. No subject developed an inhibitor, and no other safety concerns were identified. CONCLUSIONS: SCT800 has robust PK characteristics, and is safe and efficacious for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with severe haemophilia A.

Clinical efficacy of high-dose dexamethasone with sequential prednisone maintenance therapy for newly diagnosed adult immune thrombocytopenia in a real-world setting.

OBJECTIVE: As first-line treatments for newly diagnosed adult immune thrombocytopenia (ITP), high-dose dexamethasone (HD-DXM) and conventional-dose prednisone achieve good initial responses, but their long-term efficacy is poor. To improve the long-term outcome of newly diagnosed ITP, we explored the efficacy and safety of HD-DXM with sequential prednisone maintenance therapy. METHODS: This retrospective study in a real-world setting assessed 72 consecutive newly diagnosed ITP patients administered first-line HD-DXM with sequential prednisone maintenance therapy from 1 June 2016 to 31 December 2019. RESULTS: Seventy patients obtained response (97.2%), and 55 achieved sustained response (SR) (76.4%). Fifty-three obtained complete remission (CR) (73.6%), and 39 achieved continuous CR at 6 months (54.2%). Among 36 anti-nuclear antibody-positive patients, 100% achieved response, and 28 achieved CR (77.8%). Among 24 antithyroid antibody-positive patients, 23 (95.8%) achieved response, and 20 achieved CR (83.3%). For patients with initial response, the 12-month probability of SR was 78.6%. For patients with initial CR, the 12-month probability of continuous CR was 64.2%. At 12 months, 21.4% of patients with initial response and 11.3% of patients with initial CR showed loss of treatment response. CONCLUSIONS: HD-DXM with sequential prednisone as the first-line treatment for newly diagnosed ITP patients may achieve good clinical efficacy.

Outcomes of Adolescents and Young Adults Compared with Children with Acute Leukemia after Single-Unit Unrelated Cord Blood Transplantation Using Myeloablative Conditioning without Antithymocyte Globulin.

BACKGROUND: Although the use of cord blood transplantation (CBT) is becoming more frequent in acute leukemia, considering the relationship between the low stem cell dose and graft failure, whether use of CBT for adolescents and young adults (AYAs) is appropriate remains uncertain. METHODS: A retrospective registry-based analysis of clinical outcomes and immune reconstitution was conducted for 105 AYAs and 187 children with acute leukemia who underwent single-unit CBT using myeloablative conditioning (MAC) without antithymocyte globulin (ATG). RESULTS: Outcomes were similar between AYAs and children, except for nonrelapse mortality (NRM) and recovery rates of neutrophils and platelets. The 30-day cumulative incidence of neutrophil engraftment was similar between AYAs and children, but children had faster rates of neutrophil and platelet recovery than AYAs. The median time to neutrophil engraftment was earlier in children than in AYAs (AYAs, 19 days, 95% confidence interval [CI] 17.3-21.7; children, 16 days, 95% CI 13.1-19.5, p = 0.00003). The incidence of platelet recovery on day 120 was higher in children than in AYAs (AYAs, 80%, 95% CI 71-81%; children, 88%, 95% CI 82-92%, p = 0.037). CD34+ cell dose was the only independent factor influencing both neutrophil and platelet recovery. The cumulative incidence of NRM at 2 years was higher among AYAs than among children (AYAs, 27.5%, 95% CI 20-37%; children, 15%, 95% CI 10-21%, p = 0.008). Conditioning regimen was an independent factor influencing NRM. With respect to immune reconstitution, natural killer cell counts quickly recovered to normal levels 1-month post-CBT in both children and AYAs. CD8+ T-cell counts were higher in children than in AYAs at 1 and 3 months post-CBT. CD4+ T-cell counts were similar in both children and AYAs after CBT. CONCLUSION: AYAs with acute leukemia have outcomes of single-unit CBT using MAC without ATG that are as good as those of children. Thus, single-unit CBT using modified MAC without ATG is an acceptable choice for both AYAs and children who do not have a suitable donor.