Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) continues to be a cornerstone in the treatment of severe aplastic anemia (SAA). The advancement of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) has broadened therapeutic possibilities, particularly for patients lacking fully HLA-matched donors. However, it still remains unclear which type of graft source is better for SAA patients underwent haplo-HSCT.

This study aimed to assess the clinical outcomes of haplo-HSCT using granulocyte colony-stimulating factor (G-CSF)-primed peripheral blood (G-PB) as the graft source, comparing them to a control group receiving G-CSF-primed bone marrow (BM) plus G-PB (BM + PB).

This was a single-center, retrospective, case-pair cohort study. Between January 2020 and December 2023, a total of 278 consecutive SAA patients received haplo-HSCT in Peking University People's hospital. In total, 22 patients receiving haplo-HSCT using PB were included in this study. To minimize the impact of potential confounders in this study, we used the propensity score matching (PSM) method to match patients who underwent haplo-HSCT with G-PB plus G-BM in the same time with a 3:1 ratio using nearest neighbor matching. In the end, 88 patients were included in this study. 22 patients received PB stem cells as graft, while 66 patients received G-CSF-primed BM plus PB as graft.

The PB group demonstrated greater neutrophil (100% vs. 93.9%, p=0.04) and platelet engraftment (95.5% vs. 89.0%, p=0.03) incidence compared to the BM + PB group. There were no significant differences in the cumulative incidences of grade II-IV (13.6% vs. 25.8%, p = 0.28) or grade III-IV acute graft-versus-host disease (aGVHD) (4.5% vs. 4.6%, p = 0.99) between the PB group and BM+PB group. The PB group (36.7%) exhibited a trend toward a higher incidence of chronic GVHD compared to BM+PB group (24.1%); however, the difference between the two groups was not statistically significant. Moreover, the immune reconstitution of CD3+T cells, CD4+T cells, CD8+T cells and CD19+B cells were also comparable between two groups. At three years post haplo-HSCT, the probabilities of overall survival (OS), failure-free survival (FFS) and GVHD-free/failure-free survival (GFFS) were 86.1% versus 87.9% (p = 0.90), 86.1% versus 83.3% (p = 0.73) and 76.5% versus 75.2% (p = 0.70) for PB and BM + PB group, respectively. In univariate analysis, graft source did not influence the clinical outcomes after HSCT.

This study illustrated the safety and efficacy of haplo-HSCT with PB as single graft source as the treatment for SAA, providing a basis for further potential optimization of the current protocol. In the future, this conclusion should be further tested by prospective randomized trails.

The aim of this work was to investigate the therapeutic effect of modified Shisiwei Jianzhong Decoction (SJD) on aplastic anemia (AA) and its potential pharmacological mechanism from the perspective of mitophagy. A comprehensive approach combining network pharmacology, mendelian randomization, molecular docking and animal experiments was applied to evaluate the properties of SJD against AA. By integrating multiple databases, it was determined that SJD exerted its therapeutic effect on AA by targeting three key targets [mammalian target of rapamycin (MTOR), poly(ADP-ribose) polymerase 1 (PARP1) and Sirtuin 1 (SIRT1)] through four core compounds (quercetin, resveratrol, genistein and curcumin). Mendelian randomization analysis identified MTOR as a risk factor for AA occurrence while PARP1 was a protective factor. Results of animal experiments showed that SJD improved peripheral blood counts and promoted the proliferation of hematopoietic stem cells. Mechanistically, SJD, especially at high dose, played a therapeutic role in AA by activating mitophagy-related proteins PTEN induced kinase 1 (PINK1)/Parkin and inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/MTOR pathway. This study revealed for the first time the core chemical composition of SJD and its pharmacological effects against AA, which can restore hematopoietic function by activating mitophagy. The results provide inspiration for the clinical application of traditional Chinese medicine in AA treatment.

Periodontitis is a common oral condition that can have a significant impact on the overall health of the body. In recent years, attention has been paid to potential relationships between periodontitis and various hematological disorders. This publication aims to present information available in the literature on this relationship, focusing on examples of red blood cell disorders (such as aplastic anemia and sickle cell anemia) and white blood cell disorders (such as cyclic neutropenia, maladaptive trained immunity, clonal hematopoiesis, leukemia, and multiple myeloma). Understanding these associations can help physicians and dentists better diagnose, monitor, and treat patients associated with both groups of conditions, highlighting the need for interdisciplinary care for patients with oral disorders and hematologic diseases.

Acquired aplastic anemia (AA) is a recognized immune-mediated disorder and abnormally activated T lymphocyte-mediated bone marrow destruction is considered to be its main pathogenesis. Whether abnormal activation of T lymphocytes would also damage bone marrow-derived MSCs remains to be further studied. The aim of this study was to analyze the extent of T lymphocyte activation and the levels of Th1/Th2 cytokines of AA patients, and to explore the immunomodulatory effects of BM-MSCs on IL-2-stimulated T lymphocyte activation and cytokine production in vitro by means of transwell co-culture assay and flow cytometry measurement. The intermediate (CD25+) activated T cells were dominant in peripheral blood, while the early (CD69+) and late (HLA-DR+) activated T cells were predominant in bone marrow. Severe AA patients have an obviously higher proportion of CD3+CD8+CD69+ T cells than NSAA cases. The levels of IL-2 and IL-6 in AA patients were slightly elevated and INF-γ was mildly decreased in comparison with normal individuals. BM-MSCs derived from AA could not effectively inhibit the IL-2-induced activation of T cells with higher proportions of CD25+CD3+CD4+, CD69+CD3+CD4+ and CD25+CD3+CD8+ T cells after co-culture, and they showed a decreased ability to balance the Th1/Th2 cytokine production. Moreover, they had less robust osteogenic differentiation and more prone to adipogenic differentiation. We concluded that abnormally excessive T cell activation accompanied by abnormal cytokine secretion may impair the function of BM-MSCs in children with aplastic anemia.

Aplastic anemia (AA) is a bone marrow failure disease caused by T cell hyperfunction. Although the overall response rate has been improved by immunosuppressive therapy (IST) plus Eltrombopag, 30% of patients have either no response or relapse. We therefore attempted to find other ways to improve the outcomes of AA patients. Traditional Chinese medicine has the advantages of low cost, reasonable effects, and few side effects. More and more clinical studies have confirmed that traditional Chinese medicine has a beneficial role in treating AA patients. This article reviews the potential mechanism of traditional Chinese medicine or its active ingredients in the treatment of AA. These include improving the bone marrow microenvironment, regulating immunity, and affecting the fate of hematopoietic stem cells. This provides useful information for further treatment of AA with integration of traditional Chinese and Western medicine and the development of new treatment strategies.

The pathophysiology of acquired aplastic anemia (aAA) is most associated with T cell mediated immune dysfunction, but the role of CD4- CD8- double negative T cells (DNTs) in pediatric patients with aAA is unclear. In this study, we aimed to investigate the proportion of TCR-αβ+ DNTs in pediatric patients with aAA and correlation with the response to immunosuppressive therapy (IST).

Assessment of DNTs from peripheral blood was done by sensitive multi-color flow cytometry. The potential clinical value of TCR-αβ+ DNTs was then assessed by the receiver operating characteristic (ROC) curves.

The retrospective study evaluated 164 pediatric patients with aAA and 105 healthy donors (HD). Our data showed higher proportion of TCR-αβ+ DNTs in total lymphocytes [1.04% (0.79%-1.40%) vs 0.69% (0.47%-0.87%), p < 0.001] and CD3+ T cells [1.52% (1.10%-1.96%) vs 1.10% (0.70%-1.40%), p < 0.001] in aAA compared to HD. Patients with SAA/VSAA achieving complete response (CR) after IST had a higher proportion of TCR-αβ+ DNTs at initial diagnosis, than those not achieving CR for total (1.21%±0.39 vs 0.78%±0.38, p < 0.05) and CD3+ T cells (1.74%±0.53 vs 1.15%±0.59, p < 0.05). The ROC analysis showed areas under the curves (AUCs) for TCR-αβ+ DNT proportion in lymphocytes and CD3+ T cells were 0.756 (cutoff value 1.33, p < 0.05) and 0.758 (cutoff value 1.38, p < 0.05), respectively. And the complete response rate was higher in TCR-αβ+ DNT proportion high group than in TCR-αβ+ DNT proportion low group at baseline (p < 0.001).

Our observations suggest that elevated TCR-αβ+ DNTs seems to play a role in the pathogenesis of aAA, and it was involve in immune response to IST.

Acquired aplastic anemia (AA) is recognized as an immune-mediated disorder resulting from active destruction of hematopoietic cells in bone marrow (BM) by effector T lymphocytes. Bulk genomic landscape analysis and transcriptomic profiling have contributed to a better understanding of the recurrent cytogenetic abnormalities and immunologic cues associated with the onset of hematopoietic destruction. However, the functional mechanistic determinants underlying the complexity of heterogeneous T lymphocyte populations as well as their correlation with clinical outcomes remain to be elucidated. To uncover dysfunctional mechanisms acting within the heterogeneous marrow-infiltrating immune environment and examine their pathogenic interplay with the hematopoietic stem/progenitor pool, we exploited single-cell mass cytometry for BM mononuclear cells of severe AA (SAA) patients pre- and post-immunosuppressive therapy, in contrast to those of healthy donors. Alignment of BM cellular composition with hematopoietic developmental trajectories revealed potential functional roles for non-canonically activated CD4⁺ naïve T cells in newly-diagnosed pediatric cases of SAA. Furthermore, single-cell transcriptomic profiling highlighted a population of Th17-polarized CD4⁺CAMK4⁺ naïve T cells showing activation of the IL-6/JAK3/STAT3 pathway, while gene signature dissection indicated a predisposition to proinflammatory pathogenesis. Retrospective validation from our SAA cohort of 231 patients revealed high plasma levels of IL-6 as an independent risk factor of delayed hematopoietic response to antithymocyte globulin-based immunosuppressive therapy. Thus, IL-6 warrants further investigation as a putative therapeutic target in SAA.

Aplastic anemia (AA) is an auto-activated T cell-mediated bone marrow failure. Cyclosporine is often used to treat non-severe AA, which demonstrates a more heterogeneous condition than severe AA. The response rate to cyclosporine is only around 50% in non-severe AA. To better predict response to cyclosporine and pinpoint who is the appropriate candidate for cyclosporine, we performed phenotypic and functional T cell immune signature at single cell level by mass cytometry from 30 patients with non-severe AA. Unexpectedly, non-significant differences of T cell subsets were observed between AA and healthy control or cyclosporine-responder and non-responders. Interestingly, when screening the expression of co-inhibitory molecules, T cell trafficking mediators, and cytokines, we found an increase of cytotoxic T lymphocyte antigen 4 (CTLA-4) on T cells in response to cyclosporine and a lower level of CTLA-4 on CD8⁺ T cells was correlated to hematologic response. Moreover, a decreased expression of sphingosine-1-phosphate receptor 1 (S1P₁) on naive T cells and a lower level of interleukin-9 (IL-9) on T helpers also predicted a better response to cyclosporine, respectively. Therefore, the T cell immune signature, especially in CTAL-4, S1P₁, and IL-9, has a predictive value for response to cyclosporine. Collectively, our study implies that immune signature analysis of T cell by mass cytometry is a useful tool to make a strategic decision on cyclosporine treatment of AA.

Idiopathic aplastic anaemia (IAA) is a heterogeneous autoimmune disease characterised by pancytopenia and bone marrow failure. The objective of the study was to investigate the clusters of lymphocyte subset in newly diagnosed IAA patients and explore their correlation with clinical characteristics.

A total of 124 newly diagnosed IAA patients were enrolled. Lymphocyte subset was detected by flow cytometry. Cluster analysis was conducted to identify subgroups of patients based on lymphocyte subset.

Cluster analysis classified patients into four distinctive subgroups: Cluster 1 (CD4⁺ T cells dominant), Cluster 2 (CD8⁺ T cells dominant), Cluster 3 (NK cells dominant) and Cluster 4 (B cells dominant). Patients in Clusters 1 and 4 suffered more severe disease status than ones in Clusters 2 and 3 (p = .013). And with it, patients in Cluster 2 had the highest white blood cell count, haemoglobin level, reticulocyte count and reticulocyte percentage, while patients in Cluster 3 had the lowest lymphocyte percentage and the highest neutrophil count (all p < .05). Unexpectedly, patients in Cluster 3 tended to have superior curative effect than ones in other clusters, an ordinal logistic regression analysis further confirmed the independent correlation between Cluster 3 and good response to treatment. Lymphocyte subset clustering may serve as a biomarker for assessing disease severity and treatment efficacy in newly diagnosed IAA patients.Key MessagesNewly diagnosed IAA patients could be classified into 4 distinctive subgroups with similar immune patterns by using cluster analysis of lymphocyte subset.Clusters of lymphocyte subset were closely correlated with disease severity and treatment response of IAA.Lymphocyte subset clustering may serve as a promising tool for assessing disease severity and treatment efficacy in newly diagnosed IAA patients.