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Abstract Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as a complex cytokine storm. This hyperactive immune response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements in its treatment. The cytokine storm plays a crucial role in the treatment of HLH. Investigating the detailed mechanisms behind cytokine storms offers insights into targeted therapeutic approaches, potentially aiding in early intervention and improving the clinical outcome of HLH patients. To date, there is only one targeted therapy, emapalumab targeting interferon-γ, that has gained approval for primary HLH. This review aims to summarize the current treatment advances, emerging targeted therapeutics and underlying mechanisms of HLH, highlighting its newly discovered targets potentially involved in cytokine storms, which are expected to drive the development of novel treatments and offer fresh perspectives for future studies. Besides, multi-targeted combination therapy may be essential for disease control, but further trials are required to determine the optimal treatment mode for HLH.

Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APL). However, the management of high-risk APL has not been conclusively established. The optimal dosage of anthracycline in the induction has long been debated when ATO is added. Objectives: To explore the management of high-risk APL regarding the optimal dosage of anthracycline in the induction and the predicators of prognosis. Design: This was a retrospective study in the real-world setting. Methods: High-risk APL patients defined as white blood cell (WBC) greater than 10 × 10 9 /L who received ATO-based induction regimens were included. Data on clinical characteristics, treatment regimens, and prognosis including early death (ED) and overall survival (OS) were collected from medical records. Risk factors of ED and OS were analyzed. Results: This research included a total of 130 participants. Fifty (38.5%) patients received ATO+ATRA dual induction plus standard-dose anthracycline (ATO + ATRA + stDNR). Fifty-nine (45.4%) patients received ATO + ATRA with consecutive low-dose anthracycline (ATO + ATRA + ldDNR). Twenty-one (16.2%) patients were treated with ATO and various chemotherapies (ATO + others). Compared with the other two groups, the ATO + ATRA + stDNR group had the lowest ED rate of 4.0% (10.2% and 52.4%, respectively; p

Abstract The outbreak of coronavirus disease 2019 (COVID-19) posed an unprecedented challenge on public health systems. Despite the measures put in place to contain it, COVID-19 is likely to continue experiencing sporadic outbreaks for some time, and individuals will remain susceptible to recurrent infections. Chimeric antigen receptor (CAR)-T recipients are characterized by durable B-cell aplasia, hypogammaglobulinemia and loss of T-cell diversity, which lead to an increased proportion of severe/critical cases and a high mortality rate after COVID-19 infection. Thus, treatment decisions have become much more complex and require greater caution when considering CAR T-cell immunotherapy. Hence, we reviewed the current understanding of COVID-19 and reported clinical experience in the management of COVID-19 and CAR-T therapy. After a panel discussion, we proposed a rational procedure pertaining to CAR-T recipients with the aim of maximizing the benefit of CAR-T therapy in the post COVID-19 pandemic era.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296–7.979, P =.012), a platelet count ≤ 15,000/μL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044–2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088–3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360–5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717–15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532–12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Abstract Background Hetrombopag, a novel thrombopoietin receptor agonist, has been found in phase I studies to increase platelet counts and reduce bleeding risks in adults with immune thrombocytopenia (ITP). This phase III study aimed to evaluate the efficacy and safety of hetrombopag in ITP patients. Methods Patients who had not responded to or had relapsed after previous treatment were treated with an initial dosage of once-daily 2.5 or 5 mg hetrombopag (defined as the HETROM-2.5 or HETROM-5 group) or with matching placebo in a randomized, double-blind, 10-week treatment period. Patients who received placebo and completed 10 weeks of treatment switched to receive eltrombopag, and patients treated with hetrombopag in the double-blind period continued hetrombopag during the following open-label 14-week treatment. The primary endpoint was the proportion of responders (defined as those achieving a platelet count of ≥ 50 × 109/L) after 8 weeks of treatment. Results The primary endpoint was achieved by significantly more patients in the HETROM-2.5 (58.9%; odds ratio [OR] 25.97, 95% confidence interval [CI] 9.83–68.63; p

Abstract Despite considerable progress has been achieved in the treatment of acute myeloid leukemia over the past decades, relapse remains a major problem. Novel therapeutic options aimed at attaining minimal residual disease-negative complete remission are expected to reduce the incidence of relapse and prolong survival. Natural killer cell-based immunotherapy is put forward as an option to tackle the unmet clinical needs. There have been an increasing number of therapeutic dimensions ranging from adoptive NK cell transfer, chimeric antigen receptor-modified NK cells, antibodies, cytokines to immunomodulatory drugs. In this review, we will summarize different forms of NK cell-based immunotherapy for AML based on preclinical investigations and clinical trials.

The original article [1] contains several errors.

Abstract Background Previous research suggested that single gene expression might be correlated with acute myeloid leukemia (AML) survival. Therefore, we conducted a systematical analysis for AML prognostic gene expressions. Methods We performed a microarray-based analysis for correlations between gene expression and adult AML overall survival (OS) using datasets GSE12417 and GSE8970. Positive findings were validated in an independent cohort of 50 newly diagnosed, non-acute promyelocytic leukemia (APL) AML patients by quantitative RT-PCR and survival analysis. Results Microarray-based analysis suggested that expression of eight genes was each associated with 1-year and 3-year AML OS in both GSE12417 and GSE8970 datasets (p