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Acquired aplastic anemia (AA), a heterogeneous bone marrow (BM) failure disease, is mainly mediated by the immune destruction of hematopoietic stem cells (HSCs). Given the predominant role of immunosuppressive therapy (IST) in AA, it is sensible to theorize that variants of cytokine genes might affect the outcome of IST.In this study, we analyzed three single nucleotide polymorphisms (SNPs) of interleukin (IL)-10 gene in promoter region to clarify their relationship with susceptibility, clinical efficacy and prognosis of AA.We observed that CT genotype of IL-10 rs1800896 was associated with a decreased risk of AA (adjusted OR = 0.541 [95% CI 0.295-0.993], p = .047). Besides, the disease severity differed considerably by IL-10 gene promoter genotypes and alleles. Furthermore, IL-10 SNPs influenced efficacy of IST, with unfavorable response exhibited by rs1800871 and rs1800872 in dominant models (GG + AG vs. AA, adjusted OR = 0.409 [95% CI 0.178-0.943, p = .036] for rs1800871 and GG + GT vs. TT, adjusted OR = 0.396 [95% CI 0.173-0.909, p = .028] for rs1800872, respectively).The polymorphisms of IL-10 promoter region were informatively genetic risk factors which might be conducive to the insights into the mechanisms of AA and the design of individual regimens.

Immune-mediated quantitative and qualitative defects of hematopoietic stem/progenitor cells (HSPCs) play a vital role in the pathophysiology of acquired aplastic anemia (AA). Autophagy is closely related to T cell pathophysiology and the destiny of HSPCs, in which autophagy-related gene 5 (ATG5) is indispensably involved. We hypothesized that genetic variants of ATG5 might contribute to AA. We studied six ATG5 polymorphisms in a Chinese cohort of 176 patients with AA to compare with 157 healthy controls. A markedly decreased risk of AA in the recessive models of rs510432 and rs803360 polymorphisms (adjusted odds ratio [OR], 95% confidence interval [CI] = 0.467 [0.236-0.924], P = 0.029 for ATG5 rs510432; adjusted OR [95% CI] = 0.499 [0.255-0.975], P = 0.042 for ATG5 rs803360) was observed. Furthermore, the decreased risk was even more pronounced among nonsevere AA compared with healthy controls under recessive models (adjusted OR [95% CI] = 0.356 [0.141-0.901], P = 0.029 for ATG5 rs510432; adjusted OR [95% CI] = 0.348 [0.138-0.878], P = 0.025 for ATG5 rs803360; adjusted OR [95% CI] = 0.352 [0.139-0.891], P = 0.027 for ATG5 rs473543). Above all, rs573775 can strongly predict the occurrence of newly onset hematological event in patients with AA. Our results indicate that genetic ATG5 variants contributed to AA, which may facilitate further clarifying the underlying mechanisms of AA and making a patient-tailored medical decision.

Liver failure (LF) is a lethal condition characterized by jaundice, coagulation disorders. patients with LF carry a high mortality. Hemophagocytic lymphohistiocytosis (HLH) is established as a rare cause of LF. However, the clinical course of HLH may not be familiar to most hepatologist. We aimed to decipher the characteristics of these patients, to provide experience in the diagnose and management of patients with HLH masquerading as LF. Nine patients initially diagnosed with LF and finally developed HLH between January 2017 and October 2020 were retrospectively included. 78% cases developed LF with no discernable causes. Unexplained cytopenia and recurrent fever with LF may be a red flag for suspicion of HLH. Besides, female maybe predispositional to HLH in the context of LF. Modified DEP regimen was effective to control the fatal inflammatory state, all 9 cases achieved response after only one course. Further, three courses of treatment could substantially make the blood count and liver function return to normalcy, and without recurrence of HLH.

EBV is the most prevalent cause of infection-associated hemophagocytic lymphohistiocytosis (IAHLH), non-EBV IAHLH is observed clinically but less documented. We conducted a retrospective research enrolled 36 cases from 1/1/2015 to 31/12/2019. Intriguingly, 92% cases were immunocompetent individuals prior to the onset of HLH. Clinically, the cardinal features were prolonged high fever, splenomegaly and hemophagocytosis. Bicytopenia occurred in most patients, besides, liver dysfunction was characterized by increased transaminase, bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (γ-GGT) and lactate dehydrogenase (LDH). Immunomodulatory agents should be added to control the overwhelming inflammatory storm without delay. Once a certain pathogen was identified as the causative factor of HLH, cytotoxic agents were withdrawn, specific pathogen-directed treatment was initiated. Further, glucocorticoids were tapered off when a stable state of HLH was achieved. After treatment, about 70% patients were fully recovered without relapse. All in all, non-EBV IAHLH is a special group of HLH with admirable outcome.

Objectives: To clear the obscure conclusion on the prediction value of paroxysmal nocturnal haemoglobinuria (PNH) clones in severe aplastic anaemia (SAA) patients treated with immunosuppressive therapy (IST). Methods: We retrospectively analyzed 219 consecutive SAA patients treated with IST from October 2008 to October 2015 and evaluated the haematological responses to IST. Results: The presence of a PNH clone was detected in 55 (25.1%) patients prior to IST [37/88 by flow cytometry (FCM) and 18/131 by fluorescent aerolysin (FLAER)] and 27 disappeared after IST (23/37 in initial FCM group, 4/18 in initial FLAER group, p = 0.005). In patients without an initial clone, 12 (30.0%) cases in FCM and 17 (19.5%) in FLAER groups presented a PNH clone at least once after IST (p < 0.001). In patients with a pre-treatment PNH clone detected by FCM, the 3-, 6- and 12-month response rates were higher than patients without (p = 0.006; 0.002 and 0.002, respectively). And in FLAER group, the 3-month response rate was significantly higher in those with a prior clone (p = 0.017), however, the 6- and 12-month response rates showed no differences (p = 0.105, p = 0.144, respectively). By multivariate analysis, a shorter interval between diagnosis and treatment is associated with a better response and survival. Conclusions: A more reliable FLAER method allows us to draw a conclusion that PNH clone predicts a faster response but not a higher response rate to IST. Once a diagnosis is confirmed, the IST should be initiated as soon as possible.

Rationale: Systemic forms of chronic active Epstein-Barr virus infection (CAEBV) can predispose a patient to a protracted course of fulminant hemophagocytic lymphohistiocytosis, which has a poor prognosis. Epstein-Barr virus (EBV) infection may persist even after theoretically curative hematopoietic stem cell transplantation. Patient concerns: A female patient with CAEBV underwent chemotherapy followed by allogeneic hematopoietic stem cell transplantation from her human leukocyte antigen-matched sister. Neutrophil and platelet engraftment was observed on day +12 and +10. Full donor chimerism (DC) was achieved on Day +21. Diagnoses: From day +38, EBV-DNA in the blood was persistently positive, and DC declined. We attempted empirical interventions such as withdrawal of immune suppression, multiple donor lymphocyte infusion, stem cell boost, and interferon-α treatment. However, EBV-DNA copies continued to increase aggressively, whereas DC decreased rapidly and then reached a nadir of 63.27%. Interventions: Salvage programmed death 1 (PD-1) antibody treatment was administered as salvage therapy at +69 and +84. Outcomes: EBV-DNA was negative on day +97 and was ultimately undetectable. Equivalently, a full and stable DC was obtained at +97. Lessons: We summarize a case of PD-1 antibody used as salvage treatment in a post-transplant patient with CAEBV, which was eradicated and full DC was obtained. This case suggests that the PD-1 antibody appears to be a promising option for fighting EBV and mixed DCs.

Acquired bone marrow failure syndromes (aBMFS) encompass a wide range of diseases. A study to investigate WT1 expression in BM was conducted in 387 patients with aBMFS in China. The WT1 level in patients with aplastic anemia (AA) was significantly lower than that in patients with paroxysmal nocturnal hemoglobinuria (PNH, p = .023) and myelodysplastic syndrome (MDS, p

Hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) have been widely accepted as the standard first-line treatments for severe aplastic anemia (SAA). However, most of the patients with SAA had a slim chance to access these strategies in developing countries. Here, we reported 10-year results in a cohort of 232 patients with SAA who received a novel IST of CsA, levamisole, and danazol (CsA&LMS-based regimen). The cumulative incidence of response was 52.1% at 6 months, 66.4% at 12 months, and 77.1% at 24 months. The 10-year overall survival (OS) and failure-free survival was 60.2% and 48.3%, respectively. Positive predictors of OS in multivariate analysis were higher pretreatment ANC, younger age, higher pretreatment absolute reticulocyte count (ARC), and response within 6 months. The probability of CsA&LMS discontinuation was 50.2% at 10 years. With a slow CsA&LMS taper, the actuarial risk for relapse was only 9.5%. The cumulative incidence of MDS/AML was 8.2% at 10 years. The long-term follow-up information demonstrated that the CsA&LMS regimen could be a promising strategy for patients with SAA in developing countries.