Eltrombopag plus cyclosporine in refractory immune thrombocytopenia: a single-center study.

Background: With the development of thrombopoietin receptor agonists, the prognosis of immune thrombocytopenia (ITP) in patients in whom there was a poor response to first-line treatment has greatly improved. However, there are still some patients who are refractory to eltrombopag. Objectives: To explore the efficacy and safety of eltrombopag combined with low-dose cyclosporine in the management of patients with refractory ITP. Methods: A total of 21 participants with ITP who failed to respond to multiple lines of therapy (including a daily dose of 75 mg of eltrombopag for at least 30 days) treated at The First Affiliated Hospital of Zhejiang Chinese Medical University between January 2018 and August 2022 were included. All enrolled patients subsequently received 50 mg of eltrombopag daily and low-dose cyclosporine (3 mg/kg/d, with an initial target concentration of 75-120 ng/mL). The efficacy and safety of the combined therapies were evaluated. Results: A total of 76.2% (16/21) of the patients responded to the combination of cyclosporine and eltrombopag, with a median time to response of 14.5 (range, 5-37) days. A complete response (platelet count ≥ 100 × 109/L) was observed in 81.3% (13/16) of the patients, among whom 1 patient experienced relapse due to self-reduction in eltrombopag. During a median follow-up of 180 days, there were no relapses, and 70% (7/10) of the patients successfully stopped or decreased concomitant ITP medications. One patient had both a catheter-related deep vein thrombosis and a venous cerebral thrombotic event later; no other severe drug-related adverse events were observed. Conclusion: Combining low-dose cyclosporine with eltrombopag may be an effective alternative for multirefractory ITP that is nonresponsive to eltrombopag alone.

Apolipoprotein-A is a potential prognostic biomarker for severe aplastic anemia patients treated with ATG-based immunosuppressive therapy: a single-center retrospective study.

BACKGROUND: Anti-thymoglobulin (ATG)-based immunosuppressive treatment (IST) is the standard first-line management for patients with severe AA/very severe AA (SAA/VSAA) and is not suitable for allogeneic stem cell transplantation. The response predictor was not fully investigated. OBJECTIVE: The present study attempted to explore other characteristics, such as serum lipid changes, during ATG-based IST and analyzed their significance in predicting IST response and survival. METHODS: A total of 61 newly diagnosed SAA/VSAA patients who received ATG-based IST were enrolled from January 2011 to June 2019. The blood lipid levels, immunoglobulins, and peripheral T lymphocytes were retrospectively collected, and their correlations with IST response, estimated 8.5-year overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: The overall response (OR)/complete remission (CR) at 3, 6, and 9 months was 24.6%/6.6%, 52.5%/14.8%, and 65.6%/23.0%, respectively. Based on the 9-month response effect, patients were divided into IST-response (IST-R) and IST-nonresponse (IST-NR) groups. The subgroup baseline characteristics showed that the disease severity grade, absolute neutrophil granulocyte count (ANC), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein-A (Apo-A) differed between the IST-R and IST-NR groups. Patients with lower Apo-A (< 1.205 g/L) level pretreatment had a better event-free survival (EFS), and a moderate negative correlation was established between the pretreatment Apo-A and 9-month response (P = 0.004). In addition, the T-cell subset and immunoglobulin analyses showed that the responsive patients had a low serum IgA level, which decreased further after therapy. Additionally, a moderate negative correlation was established between the 3-month IgA and 9-month response (P = 0.006). CONCLUSION: Serum Apo-A is a prognostic biomarker for newly diagnosed < 60-year-old SAA/VSAA patients who received ATG-based IST (registered at chictr.org.cn as # ChiCTR2100052979).

Acute rhabdomyolysis in hepatitis-associated aplastic anemia patient undergoing allogeneic hematopoietic stem-cell transplantation: case report and literature review.

BACKGROUND: Hepatitis-associated aplastic anemia (HAAA) is a specific type of aplastic anemia, and hematopoietic stem-cell transplantation (HSCT) is recommended as the first-line. Acute rhabdomyolysis (AR) during hematopoietic stem-cell transplantation (HSCT) is a rare, serious complication, with only 10 cases reported in the world so far. CASE PRESENTATION: Herein, we present a case of AR developing during HLA-haploidentical HSCT in a 55-year-old man who suffered from HAAA. On day 7 after stem cell transfusion, the patient reported a muscle pull in thigh and complained of muscle swelling, pain and change in urine color. Despite the timely diagnosis (based on the levels of myoglobin and creatine kinase, and muscle MRI findings, etc.) and rapid hydration and alkalization, the situation progressed dramatically, and the patient died of multi-organ failure during the preparation for continuous renal replacement therapy (CRRT). Five days after his death, the whole-exome sequencing result confirmed that the patient had a germline missense mutation in SCN4A I 1545 V and ACTN3 R577X. CONCLUSION: AR is a rare but threatening complication during HSCT, especially in cases with kidney dysfunction. The creatine kinase level may not truly and completely reflect the severity and prognosis for cases with localized lesion. We suggest that genetic analysis should be performed for better understanding the pathological changes of AR during HSCT, especially for patients with bone marrow failure.