Monocytopenia and mycobacterial infection (MonoMAC) syndrome is a rare disease. Herein, we reported a 65-year-old Asian woman, previously diagnosed with myelodysplastic syndrome (MDS), suffering from recurrent pneumonia, intermittent fever, fatigue, and chest tightness lasting for five months. She was ultimately diagnosed with MonoMAC syndrome with Mycobacterium kansasii ( M. kansasii ) infection and GATA2 mutation through metagenomic generation sequencing (mNGS) of peripheral blood specimen, for which she was given anti-NTM therapy. Her situation significantly improved within 2 weeks of therapy. We discussed the clinical features, genetic characteristic, and prognosis of this disorder, aiming to further elucidate this rare syndrome. For MDS/AML patient with recurrent mixed infection and pancytopenia (especially with monocyte absence), MonoMAC syndrome should be highly suspected, and germline mutation and pathogen sequencing should be performed.

Bushen Jianpi Quyu Formula (BSJPQYF), an experienced formula, has been used to treat aplastic anemia (AA) more than three decades. To determinate the effect of BSJPQYF on AA, we constructed an immune-mediated AA mouse model. All mice were divided into four groups: control, model, low dose (0.85 g/mL), and high dose (1.7 g/mL BSJPQYF) group. They were administered with different concentrations of BSJPQYF or normal saline for 14 days. Besides, components of BSJPQYF were analyzed by electrospray ionization and mass spectrometry (ESI-MS). Subsequently, mouse peripheral blood and femurs were collected, and bone marrow mesenchymal stem cells (BMSCs) were isolated by fluorescence-activated cell sorting (FACS). Among them, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ) were measured by ELISA assay, PI3K, AKT, p-AKT, NF-κB, p-NF-κB, TNF-α, and cleaved caspase-3 proteins were detected by western blot. Compared with standard compounds, we identified three compounds of BSJPQYF, namely, icariin, kaempferol and tanshinone iia, as potentially effective compounds for the treatment of AA. Through an in vivo study, we found the administration of BSJPQYF in high dose for 14 days could significantly increase peripheral blood count and bone marrow (BM) cells, meanwhile decrease TNF-α, TGF-β, and IFN-γ levels. Besides, it could suppress the protein expression of PI3K and the phosphorylation of AKT and NF-κB to restrict the protein expression of TNF-α, eventually reduce the protein expression of cleaved caspase-3. This study demonstrated the therapeutic effects of BSJPQYF in AA, which could alleviate myelosuppression through inhibiting the expression of the PI3K/AKT/NF-κB signaling pathway.

Myelodysplastic syndrome (MDS) is a group of disorders involving hematopoietic dysfunction, with a leukemic transformation characteristic. The risk based therapeutic strategy was well applied in clinical. And for patients with IPSS low or intermediate risk-1, NCCN guideline recommended hematopoietic stimulation therapy, immune suppression therapy (IST), as well as demethylation therapy, along with best supportive care. Eltrombopag (EPAG) was firstly approved as the second line option for immune thrombocytopenia (ITP), and recently it was also investigated for treatment of aplastic anemia and MDS. In MDS, based on available reports, the EPAG was mostly used along with hypomethylating-agent, or as salvage treatment after treatment failure. However, there was study showed that the combination of EPAG to azacitidine (AZA) may worsen platelet recovery, with lower response rate and increased trend of leukemic transformation. The successful EPAG monotherapy for MDS case was report, with complete hematologic remission and blasts elimination. To date, limited study was focus on investigating the benefit of EPAG as initial monotherapy for transfusion dependent (TD) patients with low to intermediate risk-1 MDS, as well as its safety. Herein, we reviewed cases of elderly TD-MDS patients who received EPAG as front-line single treatment in our center, and 7 patients was enrolled from July, 2019 to September, 2020. Patients received EPAG 25mg to a maximum 75mg. The side effects, numbers of transfusion, improvement of peripheral blood and bone-marrow blast were recorded. The 12weeks overall response rate was 85.7%, with 2 robust response (RR), and 4 hematologic response. In patients got response, 66.7% (4/6) became platelet transfusion independent, with an answering period from 19 days to 55 days. No drug adverse events were observed within 12 week-treatment, and no obvious increased blasts as well as myelofibrosis were observed. 2 patients repeated the next-generation sequencing, and no new mutations were found. After the 12-week treatment, the 2 RR patients were still taking EPAG and got continued complete remission with a median follow up of two years. Two patient (No.3 and No.4) relapsed after EPAG withdrawn and became transfusion depend again. Patient No.1 and No.6 died of infection and cerebral hemorrhage during the follow up. In summary, EPAG may improve the hematopoiesis of TD-patient with low to intermediate risk-1 MDS, and was well tolerant with a dose of 25mg to 75mg for Asian population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Acquired aplastic anemia (AA) is a bone marrow failure disorder characterized by pancytopenia, and immunosuppressive therapy (IST) is the optional first-line management. Several studies identified the influencing factors on IST response; however, there are still a considerable number of patients suffering from poor prognoses. In this study, we enrolled 61 AA patients aged ≤ 40 years old, and whole-exome sequencing (WES) found unexpected high FANC heterozygous germline mutations (28/61, 45.9%). Patients with FANC mutations have a significantly lower absolute reticulocyte count and CD34+ % in the bone marrow and also lower 3-, 6-, and 9-month IST response than that without mutation, which were 0% vs. 25% (P = 0.017), 26.3% vs. 42.1% (P = 0.495), and 29.4% vs. 72.2% (P = 0.011), especially in anti-thymocyte globulin combined with the cyclosporin A (ATG + CsA) group, which were 0% vs.33.4% (P = 0.143), 25% vs.83.3% (P = 0.103), and 25% vs. 100% (P = 0.003), respectively. The event-free survival in the FANCwt group was also better than that in the FANCmut group (P = 0.016) and also showed in patients who received ATG + CsA treatment (P = 0.045). In addition, all the adverse effects of FANC germline mutation were not significant in stem cell–transplanted group. Our result indicated that the WES-based detection of FANC heterozygous germline mutations may have a great meaning in predicting IST response of acquired AA. This study was registered at chictr.org.cn (# ChiCTR2100054992).

B. A rare case of long-term complications of squamous cell carcinoma in haemophilia B after arthrocentesis, and review of the literature.