Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific single-chain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-ζ signaling domain. We further investigate the function of CLL-1 CAR-T cells. The CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML.

Background: Interleukin-6 (IL-6) was proposed to be associated with the severity of coronavirus disease 2019 (COVID-19). The present study aimed to explore the kinetics of IL-6 levels, validate this association in COVID-19 patients, and report preliminary data on the efficacy of IL-6 receptor blockade. Methods: We conducted a retrospective single-institutional study of 901 consecutive confirmed cases. Serum IL-6 concentrations were tested on admission and/or during hospital stay. Tocilizumab was given to 16 patients with elevated IL-6 concentration. Results: 366 patients were defined as common cases, 411 patients as severe, and 124 patients as critical according to the Chinese guideline on diagnosis and treatment of COVID-19. The median concentration of IL-6 was < 1.5 pg/ml (IQR < 1.50–2.15), 1.85 pg/ml (IQR < 1.50–5.21), and 21.55 pg/ml (IQR 6.47–94.66) for the common, severe, and critical groups respectively (P < 0.001). The follow-up kinetics revealed serum IL-6 remained high in critical patients even when cured. An IL-6 concentration higher than 37.65 pg/ml was predictive of in-hospital death (AUC 0.97 [95% CI 0.95–0.99], P < 0.001) with a sensitivity of 91.7% and a specificity of 95.7%. In the 16 patients who received tocilizumab, IL-6 concentrations were significantly increased after administration, and survival outcome was not significantly different from that of propensity-score matched counterparts (n = 53, P = 0.12). Conclusion: Serum IL-6 should be included in diagnostic work-up to stratify disease severity, but the benefit of tocilizumab needs further confirmation. Trial registration retrospectively registered.

Thalidomide induces γ-globin expression in erythroid progenitor cells, but its efficacy on patients with transfusion-dependent β-thalassemia (TDT) remains unclear. In this phase 2, multi-center, randomized, double-blind clinical trial, we aimed to determine the safety and efficacy of thalidomide in TDT patients. A hundred patients of 14 years or older were randomly assigned to receive placebo or thalidomide for 12 weeks, followed by an extension phase of at least 36 weeks. The primary endpoint was the change of hemoglobin (Hb) level in the patients. The secondary endpoints included the red blood cell (RBC) units transfused and adverse effects. In the placebo-controlled period, Hb concentrations in patients treated with thalidomide achieved a median elevation of 14.0 (range, 2.5 to 37.5) g/L, whereas Hb in patients treated with placebo did not significantly change. Within the 12 weeks, the mean RBC transfusion volume for patients treated with thalidomide and placebo was 5.4 ± 5.0 U and 10.3 ± 6.4 U, respectively (P < 0.001). Adverse events of drowsiness, dizziness, fatigue, pyrexia, sore throat, and rash were more common with thalidomide than placebo. In the extension phase, treatment with thalidomide for 24 weeks resulted in a sustainable increase in Hb concentrations which reached 104.9 ± 19.0 g/L, without blood transfusion. Significant increase in Hb concentration and reduction in RBC transfusions were associated with non β0/β0 and HBS1L-MYB (rs9399137 C/T, C/C; rs4895441 A/G, G/G) genotypes. These results demonstrated that thalidomide is effective in patients with TDT.

Objective: Fear of cancer recurrence (FCR) is a common psychosocial sequela among cancer survivors, but data on patients with multiple myeloma are scarce. This study calculated the prevalence of FCR and identified family and social factors that predict FCR in the study population.Methods: We recruited 127 myeloma patients and their partners to participate in a cross‐sectional survey from a regional tertiary cancer centre in China. The questionnaires included items on demographic characteristics and from the fear of disease progression simplified scale, family hardiness index and Social Support Scale. Univariate and multivariate regression was used to identify predictors of FCR.Results: Of the participants, 56.4% patients reported high‐level FCR, which was similar to the partner‐reported proportion. The partners' FCR was positively associated with the patients' FCR, while family hardiness and social support were statistically significant, negative predictors.Conclusions: Interventions to mitigate partners' FCR and improve family hardiness and social support may help with the psychological adjustment and well‐being of myeloma patients.

Causes of death in persons with haematological cancers include the index cancer, a new cancer or a seemingly unrelated cause such as cardio-vascular disease. These causes are complex and sometimes confounded. We analyzed trends in cause of death in 683,333 persons with an index haematological cancer diagnosed in 1975–2016 reported in the Surveillance, Epidemiology and End Results dataset. Non-cancer deaths were described using standardized mortality ratios. The index cancer was the predominant cause of death amongst persons with plasma cell myeloma, acute lymphoblastic leukaemia and acute myeloid leukaemia. Non-cancer death was the major cause of death in persons with chronic lymphocytic leukaemia, Hodgkin lymphoma and chronic myeloid leukaemia, mostly from cardio-vascular diseases. The greatest relative decrease in index-cancer deaths was amongst persons with Hodgkin lymphoma, chronic myeloid leukaemia and chronic lymphocytic leukaemia, where the proportion of non-cancer deaths increased substantially. Changing distribution of causes of death across haematological cancers reflects substantial progress in some cancers and suggests strategies to improve the survival of persons with haematological cancers in the future.