BACKGROUND:This study aimed to evaluate glymphatic function using the diffusion tensor imaging along the perivascular spaces (DTI-ALPS) index in patients with acute myeloid leukemia (AML) following chemotherapy and to explore its association with cognitive performance. METHODS:Twenty-one AML patients were assessed 4-8 weeks after their final chemotherapy cycle (PC-AML), along with 20 age- and sex-matched healthy controls (HCs). All participants underwent brain MRI and cognitive assessment. Imaging metrics included cerebrospinal fluid (CSF) volume, basal ganglia perivascular space (BG-PVS) volume fraction, DTI-ALPS index, and blood oxygen level-dependent-CSF coupling. Group comparisons and correlations between glymphatic markers and cognitive scores were analyzed. RESULTS:Post-chemotherapy AML patients exhibited significantly increased CSF volume (PFDR = 0.046) and BG-PVS volume(PFDR = 0.040), alongside a reduced DTI-ALPS index(PFDR = 0.046). Cognitive performance was significantly impaired, with lower Mini-Mental State Examination (MMSE; P < 0.01) and Montreal Cognitive Assessment (MoCA; P < 0.01) scores, and higher Activities of Daily Living (ADL) scores (P < 0.01). BG-PVS volume correlated inversely with MMSE (r = -0.467, P = 0.002) and MoCA (r = -0.396, P = 0.010), while the DTI-ALPS index positively correlated with MoCA (r = 0.417, P = 0.006). CONCLUSION:Post-chemotherapy AML patients exhibit glymphatic system dysfunction and cognitive decline, with a significant association between these alterations. Impairment in glymphatic function, as suggested by these biomarkers, may contribute to cognitive deficits in this context. The DTI-ALPS index and BG-PVS volume represent potential neuroimaging biomarkers, providing new insights into chemotherapy-related cognitive impairment in AML.

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease that accounts for approximately 20% of adult leukemia. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently recognized as one of potentially curative treatments for ALL. Though pretransplant consolidation chemotherapy is generally considered essential, there is limited research on the optimal number of consolidation cycles, which leaves the ideal timing for transplant unclear. In this study, we retrospectively analyzed the clinical outcomes of 40 adult patients diagnosed with Philadelphia chromosome-negative ALL (Ph-negative ALL) who underwent allo-HSCT at our center between January 2014 and May 2025. Among these patients, eighteen received a single cycle of consolidation chemotherapy prior to transplant, while 22 underwent multiple cycles. No statistically significant differences were observed between the single and multiple consolidation groups in terms of overall survival (OS), disease-free survival (DFS), cumulative incidence of relapse (CIR), or non-relapse mortality (NRM). The single consolidation group demonstrated 3-year OS rates of 57%, compared to 56% in the multiple consolidation group (p = 0.83). For DFS, the single consolidation group showed 3-year rates of 51%, versus 52% in the multiple group (p = 0.97). Regarding CIR, the single consolidation group had 3-year rates of 18%, compared to 28% in the multiple group (p = 0.48). In terms of NRM, the single consolidation group exhibited 3-year rates of 25%, versus 20% in the multiple group (p = 0.45). Our real-world findings indicate that a single cycle of pretransplant consolidation chemotherapy yields comparable clinical outcomes compared to multiple cycles. These results provide valuable evidence for potentially shortening the overall treatment duration for adult patients with Ph-negative ALL and may assist clinicians in determining the optimal timing for transplant.

Mutations in Fms-like tyrosine kinase 3 (FLT3) are strongly associated with relapse and resistance in acute myeloid leukemia (AML) patients, and the treatment of relapsed or refractory AML (R/R AML) remains a major clinical challenge. We previously conducted a prospective clinical trial on R/R AML with chemotherapy regimen BHA (bortezomib, homoharringtonine and cytarabine), which demonstrated promising efficacy in patients with FLT3-mutated R/R AML. However, the therapeutic mechanism remains unclear. In this study, we aim to elucidate the therapeutic mechanism of BHA regimen on the basis of its efficacy for FLT3-mutated R/R AML. We retrospectively analyzed twenty-nine patients with R/R AML, after one course of therapy, patients harboring FLT3 mutations had a significantly higher complete remission/complete remission with incomplete hematologic recovery rate than those without FLT3 mutations (46.67

Peripheral T cell lymphomas (PTCL) is a group of non-Hodgkin lymphomas characterized by substantial molecular heterogeneity, rapid progression, poor therapeutic response, and unfavorable outcomes. In recent clinical studies, antithymocyte globulin (ATG)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the prognosis and survival of patients with PTCL. This study aimed to explore whether ATG has toxic effects on PTCL cells and evaluate whether ATG combined with chemotherapy has a synergistic antitumor effect. Our research revealed that ATG significantly inhibited PTCL cell growth by suppressing cell proliferation and colony formation. Moreover, ATG treatment decreased cell invasion; however, it had no effect on cell cycle arrest in PTCL cells. ATG-induced PTCL cell apoptosis, which was partially reversed by pan-caspase inhibitor and caspase 8 inhibitor. Additionally, ATG was able to induce complement-dependent cytotoxicity in PTCL cells. Of note, the combination of ATG and doxorubicin exhibited an enhanced antitumor effect against PTCL in xenograft mouse models in vivo. The addition of ATG into the chemotherapy regimen may be a beneficial way for treating PTCL.

Post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of hematopoietic stem cell transplantation caused by Epstein–Barr virus (EBV) reactivation due to immunosuppression. Frontline treatment includes the reduction of immunosuppressive therapy and administration of rituximab. However, the incidence of EBV-related PTLD (EBV+ PTLD) continues to increase, and patient prognosis remains poor. In this retrospective study, we designed an exploratory treatment strategy for PTLD using designated reduced-dose donor lymphocyte infusion (DLI) (CD3 + T cells: 5 × 104/kg) for majority patients (11/14). We further analyzed the data of 27 patients with PTLD who underwent transplantation at our institutions. Our therapeutic strategy effectively treated PTLD. In this study, the DLI cohort demonstrated higher overall response and complete remission rates than rituximab monotherapy after two-week intervention. Additionally, the DLI group had a markedly higher 1-year overall survival (OS) than the rituximab group. Similarly, the reduced-dosage DLI group had a significantly higher 1-year OS than the conventional-dosage group. These results indicate that varied treatments (rituximab vs DLI) and DLI dosages (conventional vs reduced) had significant impact on OS. Finally, the reduced-dosage DLI group had a lower risk of non-relapse mortality and acute graft versus host disease than the conventional-dosage group. This study demonstrates that reduced-dosage DLI is a promising treatment for EBV+ PTLD.

Introduction:Despite the increasing use of allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft-versus-host disease (GVHD) remains the main cause of morbidity and mortality, significantly impacting HSCT outcomes. Steroids are the standard first-line treatment for acute GVHD (aGVHD); however, standardized treatment algorithms for patients who do not respond to steroid therapy are lacking. Ruxolitinib is the most promising second-line therapy for steroid-refractory (SR)-GVHD, but data on its first-line use for aGVHD are limited. Methods:In this retrospective study, we analyzed the data of 133 patients with aGVHD who underwent transplantation at our institution. Eighty-three patients received ruxolitinib combined with methylprednisolone, while 50 received methylprednisolone alone as the initial treatment. Results:The ruxolitinib/steroids group had a significantly higher overall response rate (ORR) on day 7 (86%) compared to the steroid-only group (68%; odds ratio [OR]=2.8, 95% confidence interval [CI]: 1.2-6.5, p=0.019). Similarly, ORR on day 14 was higher in the ruxolitinib/steroids group (92% vs. 79%; OR=2.7, 95% CI: 0.9-7.8, p=0.05). Although no statistical differences were observed in overall survival (OS), progression-free survival (PFS), and failure-free survival (FFS) between the two groups, patients who achieved early ORR on days 7 and 14 had better OS, PFS, and FFS. Additionally, in subgroup analysis of patients who underwent peripheral blood stem cell transplantations, the ruxolitinib/steroids cohort had significantly better OS (Hazard Ratio [HR]=0.34, 95% CI: 0.11-1.55, p=0.04), PFS (HR=0.37; 95% CI: 0.12-1.10, p=0.05) and FFS (HR=0.46; 95% CI: 0.19-1.11, p=0.05) compared to the steroid-only cohort. Adverse event (AEs) frequencies were comparable between groups, with the exception of neutropenia (32.5% vs. 12%, p=0.008) and CMV infection (34.9% vs. 18%, p=0.036), which were more frequent in the ruxolitinib/steroid group. Discussion:To the best of our knowledge, this is the first real-world study to demonstrate that adding ruxolitinib to a standard methylprednisolone regimen provides an effective and safe first-line treatment for aGVHD.

AbstractNewly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; P < 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36–15.75; P < 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31–0.68; P < 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% P = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.

The effects of a second haploidentical bone marrow transplantation with an antithymocyte antibody-containing conditioning regimen after graft failure in patients with severe aplastic anemia remain unclear. Eight severe aplastic anemia patients with graft failure with a median age of 12.5 (range, 3–22) years were retrospectively reviewed. At the second transplantation, they received a median mononuclear cell number of 15.7 (range, 11.2–20.9) × 108/kg or a median CD34+ cell number of 6.2 (range, 2.5–17.5) × 106/kg. They were all successfully engrafted, with a median time of 12.5 (range, 11–16) days for neutrophils and 24 (range, 14–50) days for platelets. Three patients developed skin acute graft-versus-host disease Grades I–II, and another 3 developed limited chronic graft-versus-host disease. All patients successfully recovered after treatment with methylprednisolone (0.5–1 mg/kg/day) and tacrolimus. One patient each died of respiratory failure caused by multidrug-resistant Klebsiella pneumoniae at 8 months and invasive fungal disease at 23 months after transplantation. Six patients survived with a 5-year estimated overall survival of 75% and a median follow-up time of 61 (range, 8–129) months. A second haploidentical bone marrow transplantation with an antithymocyte antibody-containing conditioning regimen was feasible for saving severe aplastic anemia patients with graft failure.

Eltrombopag (EPAG) can improve the efficacy of immunosuppressive therapy (IST) consisting of antithymocyte immunoglobulin (ATG) and cyclosporin in severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous usage of EPAG beyond 6 months. Seventy-four treatment-naive Chinese patients with SAA were administrated with rabbit ATG-based IST plus EPAG for 6 months. Patients not achieving complete remission (CR) at 6 months were treated with EPAG for another 6 months. At 1, 3, 6 and 12 months after IST, the cumulative response rates were 31

Background:Acute myeloid leukemia (AML) is a malignant clonal disease of the myeloid hematopoietic system. Clinically, standard treatment options include conventional chemotherapy as well as hematopoietic stem cell transplantation. Among them, chemotherapy has a remission rate of 60% to 80% and nearly 50% relapse in consolidation therapy. Some patients have a poor prognosis due to the presence of unfavorable factors such as advanced age, hematologic history, poor prognosis karyotype, severe infection, and organ insufficiency, which cannot tolerate or are not suitable for standard chemotherapy regimens, and scholars have tried to find new treatment strategies to improve this situation. In the pathogenesis and treatment of leukemia, epigenetics has received attention from experts and scholars. Objective:To investigate the relationship between OLFML2A overexpression and AML patients. Methods:From The Cancer Genome Atlas, researchers used the data of OLFML2A gene to analyze and study the pan-cancer using R language and then divided the high and low levels of this protein into two groups to study its relationship with the clinical characteristics of the disease. The relationship between the high levels of OLFML2A and various clinical features of the disease was studied with emphasis on the relationship between the high levels of OLFML2A and various clinical features of the disease. A multidimensional Cox regression analysis was also performed to study the factors affecting patient survival. The correlation between OLFML2A expression and immune infiltration through the immune microenvironment was analyzed. The researchers then conducted a series of studies to analyze the data collected in the study. The focus was on the relationship between the high levels of OLFML2A and immune infiltration. Gene ontology analysis was also performed to study the interactions between the different genes associated with this protein. Results:According to the pan-cancer analysis, OLFML2A was differentially expressed in different tumors. More importantly, the analysis of OLFML2A in the TCGA-AML database revealed that OLFML2A was highly expressed in AML. The researchers found that the high levels of OLFML2A were associated with different clinical features of the disease, and that the expression of the protein was different in different groups. Those patients with the high levels of OLFML2A were found to have substantially longer survival times compared to those with low-protein levels. Conclusions:The OLFML2A gene is able to act as a molecular indicator involved in the diagnosis, prognosis, and immune process of AML. It improves the molecular biology prognostic system of AML, provides help for the selection of AML treatment options, and provides new ideas for future biologically targeted therapy of AML.

Eltrombopag (EPAG), a thrombopoietin receptor agonist, was approved for the treatment of severe aplastic anemia (SAA) combined with immunosuppressive therapy (IST). However, the effects of real-life use of low doses of EPAG combined with rabbit antithymocyte globulin (ATG)–based IST in Asian patients with SAA are yet unknown. A total of 121 previously untreated Chinese patients with SAA were enrolled in a multicenter registry of the Chinese Eastern Collaboration Group of Anemia (2014–2020): 67 patients received IST alone and 54 patients received additional EPAG. Patients receiving IST plus EPAG had a higher overall response rate (ORR) at 1 month (P = 0.002), 3 months (P = 0.028), 6 months (P = 0.006), and 12 months (P = 0.031) compared to those receiving IST alone. EPAG was the favorable factor for response efficacy at 6 months. The complete response rate in the EPAG plus IST group was 17% at 3 months, 27% at 6 months, and 32% at 12 months, compared to 7% (P = 0.069), 14% (P = 0.11), and 33% (P = 0.92) for those treated with IST alone. The 2-year overall survival rate in EPAG plus IST and IST alone groups was 98% and 88%, respectively (P = 0.078). The rate of adverse events, including clonal evolution, infection, and transaminitis, was similar in the two cohorts. The addition of EPAG to IST was well-tolerated and associated with high rates of hematologic responses among the previously untreated Chinese patients with SAA.

A retrospective analysis was conducted based on the clinical data from 60 patients older than 16 years from January 2016 to January 2021. All the patients were newly diagnosed with severe aplastic anemia (SAA) with an absolute neutrophil count (ANC) of zero. We compared the hematological response and survival of haploidentical–allogeneic hematopoietic stem cell transplantation (HID-HSCT) (n = 25) and intensive immunosuppressive therapy (IST) (n = 35) treatments. At six months, the overall response rate and complete response were significantly higher in the HID-HSCT group than those in the IST group (84.0

Background Refractory/relapsed acute myeloid leukemia (R/R AML) has unsatisfactory outcomes even after allogeneic hematopoietic stem cell transplantation. Long-term survival is mainly influenced by complete remission (CR) rates after induction therapies. Objectives To investigate CR/CR with incomplete hematologic recovery (CRi) rates and adverse events with a new induction therapy (bortezomib, homoharringtonine, and cytarabine [BHA]) for patients with R/R AML. Methods We enrolled 21 patients with R/R AML (median age, 42 [range, 30–62] years), who received BHA for remission induction (bortezomib, 1.3 mg/m 2 /day on days 1 and 4; homoharringtonine, 4 mg/m 2 /day for 5 days, and cytarabine, 1.5 g/m 2 /day for 5 days). CR and adverse events were assessed. Results After one course of BHA, the CR/CRi and partial remission rates were 38.1% and 14.3%, respectively, with an overall response rate (ORR) of 52.4% in 21 patients. 9 of 21 patients harbored FLT3-ITD or FLT3-TKD mutations, and achieved either CR/CRi or ORR of 66.7% ( P =0.03) by comparison with that in R/R AML without FLT3 mutation. After induction therapy, consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation led to a one-year overall survival of 27.8% in all patients. One-year relapse-free survival was 50% in 8 patients who had achieved CR/CRi after one course of BHA. During induction, non-hematologic adverse events (grade 3/4) commonly were infection (90.5%), hypokalemia (14.4%), hypocalcemia (14.3%), and mucositis (9.5%). In patients achieving CR, the median time to neutrophil count >0.5×10 9 /L and time to platelet count >20×10 9 /L were 15 (13–17) days and 13 (13–18) days, respectively. Conclusion BHA chemotherapy regimen was safe and tolerable to serve as an induction therapy for R/R AML, particularly with FLT3 mutation. The higher CR/CRi rate will give a clue to determine a potentialeffectiveness of BHA for AML patients carrying FLT3 mutation in a further investigation. Clinical trial registration https://www.chictr.org.cn/ , identifier ChiCTR2000029841.

Addition of eltrombopag (E-PAG) to intensive immunosuppressive therapy (IST) contributes to restoring hematopoiesis in patients with severe aplastic anemia (SAA). Used at relatively low doses in the East Asian population, the efficacies of E-PAG and the predictors for efficacy are not clear. We conducted a retrospective, multicenter study to analyze the efficacy and the possible predicting factors at 6 months in 58 adult SAA patients with rabbit ATG-based IST and E-PAG. The response rate and complete response rate at 6 months were 76% and 21%, respectively. The baseline reticulocyte percentage [area under a curve (AUC)=0.798, 95% confidence interval (CI) 0.640-0.956, P=0.006], absolute reticulocyte count (ARC) (AUC =0.808, 95%CI 0.647-0.970, P=0.004), red cell distribution width – coefficient of variation (RDW-CV) (AUC=0.722, 95%CI 0.494-0.950, P=0.040), and absolute lymphocyte count (ALC) (AUC=0.706, 95%CI 0.522-0.890, P=0.057) were highly predictive of response at 6 months. The tipping values of reticulocyte percentage, ARC, RDW-CV, and ALC were 0.45%, 7.36×109/L, 11.75%, and 1.06×109/L, respectively. The sensitivity and specificity of reticulocyte percentages were 81.6% and 66.7%; ARC were 86.8% and 66.7%, RDW-CV were 94.7% and 55.6%; ALC were 55.3% and 88.9%. At a median follow-up of 15.5 months, the 2-year cumulative overall survival was 92%. The baseline reticulocyte percentage, ARC, RDW-CV, and ALC were potential factors in predicting a favorable effect of rabbit-ATG based IST plus E-PAG in SAA patients of East Asia (ChiCTR2100045895).Clinical Trial Registrationhttp://www.chictr.org.cn/edit.aspx?pid=125480&htm=4, identifier ChiCTR2100045895.

Background Eltrombopag (EPAG) could improve the efficacy of immunosuppressive therapy (IST) consisted by antithymocyte immunoglobulin (ATG) and cyclosporin (CsA) in untreated severe aplastic anemia (SAA) patients. This study explored whether patients with SAA could benefit from continuous use of EPAG beyond 6 months. Methods From February 2018 to October 2021, 92 Chinese patients who were 2 years of age or older with a new diagnosis of acquired SAA and were not eligible for front-line hematopoietic stem-cell transplantation were collected in the China Eastern Cooperation Group for Anemia (CECGA). Patients were treated with rabbit ATG (r-ATG) based IST consisting of CsA. Patients over 12 years old and aging 6-11 years old took EPAG orally at dose of 75mg and 37.5mg once daily, respectively; EPAG was administered with 1.25 mg per kilogram per day for patients with age distribution between 2 and 5 years. Generally, all patients were treated with EPAG at least 6 months. The lack of response at 6 months, relapse, HSCT, development of a clonal hematologic disease including myelodysplastic syndrome, and acute myelogenous leukemia, or disease- or treatment-related death are regarded as events in event free survival (EFS). Results The median age was 38 (2-78) years, with 18 patients (20%) under 18 years old and 21 patients (43%) over 60 years old. In the whole cohort, 61 patients (66%) were diagnosed as SAA and 31 patients (34%) with very severe aplastic anemia (vSAA). At 3, 6 and 12 months, the actuarial overall response rates (ORR) were 55% (51 of 92), 73% (67 of 92) and 81% (60 of 74) and complete response (CR) rates were 11% (10 of 92), 20% (18 of 92) and 34% (25 of 74), respectively. 18 patients (20%) who achieved CR within 6 months were under steady state. In 49 patients with PR at 6 months, 14 (35%) of 40 patients who were continuously exposed to EPAG improved to CR within 6.5 (3 ~ 10) months of median time after 6 months. Among 25 patients who failed at 6 months, 11 patients continued to use EPAG, and 5 patients (45%) improved responses with extended median time of 3 (1 ~ 6) months after 6 months (Figure 1). The cumulative effect curve showed that 93% and 58% of all 12 months remission and CR occurred within 6 months. In patients with PR and NR at 6 months, the better 2-year event free survival (EFS) was found in whom continued to use EPAG (75% vs. 26%, P=0.001) (Figure 2). Discussion EPAG plus IST were used to treat previously untreated SAA patients in prospective studies. The ORR and CR rate at 6 months were 68% ~ 94% and 26% ~ 58%, respectively [1, 2]. We found that 93% of all 12 months remission occurred within 6 months for patients treated with IST and EPAG. It is suggested that EPAG should be used in sufficient dosage at least 6 months. It has been reported that patients with CR and PR were present with better OS of 100% and 92%, while OS of non-responders was 47% (P=0.0016), effect was demonstrated as a predictor for 4-year OS [3]. For patients with PR and NR at 6 months in our study, it was found that not only the response rates, but also the 2-year EFS were improved by continuous usage of EPAG, compared to them discontinued EPAG. In conclusion, additional EPAG to IST mainly take effect within 6 months. Continuous administration of EPAG could improve the hematologic response and EFS in patients without achieving CR at 6 months. REFERENCE [1]. Townsley DM, Scheinberg P, Winkler T, et al., Eltrombopag Added to Standard Immunosuppression for Aplastic Anemia. N Engl J Med, 2017. 376(16): p. 1540-1550. [2]. Peffault de Latour R, Kulasekararaj A, Iacobelli S, et al., Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia. N Engl J Med, 2022. 386(1):11-23. [3]. Assi R, Garcia-Manero G, Ravandi F, et al., Addition of Eltrombopag to Immunosuppressive Therapy in Patients with Newly Diagnosed Aplastic Anemia. Cancer, 2018. 124(21):4192-4201. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disease. Allogeneic hematopoietic stem cell transplantation from a matched sibling donor (MSD-HSCT) and intensive immunosuppressive therapy (IST) are 2 major comparable treatments for SAA. As the addition of eltrombopag (EPAG) to standard IST therapy has greatly improved the survival prognosis of SAA, whether MSD-HSCT or IST/EPAG is the better choice has become a matter of debate. A study was performed involving 99 patients with newly diagnosed acquired SAA from 5 medical centers, including 48 MSD-HSCT cases and 51 IST/EPAG cases, which consisted of rabbit antithymocyte globulin or porcine-antilymphocyte globulin, cyclosporine plus eltrombopag. The results suggested that patients treated with MSD-HSCT or IST/EPAG had similar overall survival (OS) rates exceeding 95% (P = .97). However, the event-free survival rate (EFS) of IST/EPAG (71.0%) was significantly lower than that of MSD-HSCT (89.6%), P = .04. Subgroup analysis indicated that the OS of the MSD-HSCT group was superior to that of the IST/EPAG group (100% versus 85.7%, P = .04) among those with very severe aplastic anemia (VSAA). Both the complete response rate (CR) and overall response rate (OR) with MSD-HSCT were significantly higher than those with IST/EPAG (CR: 79.2% versus 15.7%, P < .001; OR: 97.9% versus 72.6%, P = .001). In conclusion, IST/EPAG or MSD-HSCT treatment achieves an equally high OS in SAA, but MSD-HSCT leads to a better OS in patients with VSAA and shows advantages in improving EFS and accelerating hematopoietic reconstruction in patients with SAA.

目的 总结输血依赖型非重型再生障碍性贫血(TD-NSAA)患者的临床特点及转归.方法 收集2013年12月至2017年1月就诊于中国贫血东部协作组各医院的124例TD-NSAA患者临床资料,分析临床表现、输血频率、实验室检查结果、并发症、转归及相关因素.结果 共纳入124例TD-NSAA,中位病程38(3～363)个月,中位年龄32(3～80)岁.常见并发症有肝肾功能损害(42例,33.9.％)、糖尿病或糖耐量异常(24例,19.3％)、严重感染(29例,23.4％)、铁超负荷(53/101,52.5％).环孢菌素(CsA)治疗119例,23例有效(19.3％);抗人胸腺细胞免疫球蛋白(ATG)联合CsA治疗30例,17例有效(56.7％)(P＜0.001).57例进展为SAA(46.0％),中位进展时间24(3～216)个月.中性粒细胞绝对值＜0.5x109/L、严重感染和铁超负荷是SAA进展的危险因素(P=0.022,P=0.025,P=0.001).转变为阵发性睡眠性血红蛋白尿症11例、骨髓增生异常综合征2例、急性髓系白血病1例,10例死亡(8.1％).结论 TD-NSAA患者病程迁延,易并发重要脏器功能损伤和疾病进展;CsA治疗效果欠佳,ATG联合CsA强化免疫抑制治疗可能改善预后,值得探索.

In sight of different pharmacokinetics between races, the recommended dose is 75mg/d for Asian using eltrombopag [1]. However, the efficacy and safety of antithymocyte immunoglobulin (ATG) and cyclosporin A (CsA) with eltrombopag are still largely unknown for adult Asian patients with severe aplastic anemia (SAA).

Prospective trials showed the clinical efficacy of eltrombopag in refractory/relapsed aplastic anemia (AA), with up to 40% hematologic improvement [1]. Moreover, eltrombopag was combined with frontline immunosupressive therapy (IST) consisited of antithymocyte immunoglobulin (ATG) and cyclosporin (CsA), with an overall response rate exceeding 80% [2]. The metabolism of eltrodopag is different in disparate population. Currently, the recommended dose is 75 mg/d for East Asian populations [2], Pretreatment clinical and laboratory characteristics predicting eltrombopag response are still unclear in severe AA (SAA) patients of real-world in East Asian.