[Efficacy and safety of roxadustat in the treatment of refractory non-severe aplastic anemia].

Objective: To evaluate the efficacy and safety of roxadustat in patients with refractory non-severe aplastic anemia (NSAA) . Methods: The clinical data of patients with refractory NSAA who had been treated with roxadustat continuously for at least 3 months and followed up for more than 6 months at Peking Union Medical College Hospital from October 2020 to August 2022 were retrospectively collected. The demographic information, clinical data, treatment efficacy, adverse reactions, and outcomes were evaluated, and the factors influencing efficacy were analyzed. Results: A total of 41 patients were included. The male-to-female ratio was 16∶25, and the median age was 52 (18-84) years. The median duration of roxadustat treatment was 5 (3-20) months, and the median follow-up was 15 (6-26) months. Hematologic improvement-erythroid (HI-E) was 12.2%, 29.3%, 46.3%, 43.9%, and 30.3% at 1, 2, 3, 6, and 12 months, respectively. The rate of transfusion independence was 28.5%, 38.1%, and 33.3% at 3, 6, and 12 months, respectively. Hemoglobin returned to normal in some patients after treatment with roxadustat. The incidence of adverse events was 22%, all of which were grade Ⅰ-Ⅱ and recoverable. No factors that could affect HI-E were identified. By the end of follow-up, 45% of the patients relapsed, with a median time to relapse of 7 (3-12) months. No clonal evolution was observed, and one patient died. Conclusion: Roxadustat effectively improved anemia with good tolerance in patients with refractory NSAA.

Efficacy and safety of immunosuppressive therapy combined with eltrombopag for severe aplastic anemia: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. METHODS: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. RESULTS: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. CONCLUSION: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.

The long-term outcomes and safety of severe aplastic anemia treated with porcine antilymphocyte globulin plus cyclosporine, with or without thrombopoietin receptor agonists: a double-center retrospective study.

BACKGROUND: Porcine antilymphocyte globulin (p-ALG) combined with cyclosporine (CsA) has been commonly used for severe aplastic anemia (SAA) patients, but few studies on the combination of p-ALG and thrombopoietin receptor agonist (TPO-RA). RESEARCH DESIGN AND METHODS: We retrospectively analyzed the data of 85 people with diagnosed SAA who underwent p-ALG plus CsA, with or without TPO-RA from 2014 to 2023. RESULTS: The overall response rates were 55.3% and 65.9% at 3 and 6 months, and the TPO-RA group were 66.7% and 72.3% at 3 and 6 months, without TPO-RA group were 27.8% and 55.6%. In multivariate analysis, baseline platelet count of > 10 × 109/L was a simple predictor of favorable response at 6 months (p = 0.015). The median follow-up time for all patients was 39 months (range 0.4 ~ 104), the 5-year overall survival (OS) rate was 90.6% [95% CI = 82.1-95.2%], and the failure-free survival (FFS) rate was 68.9% [95% CI = 56.6-78.4%]. Having hematologic responses in 6 months was an independent positive predictor for FFS (p = 0.000). Twelve patients (14.1%) suffered from serum sickness, and 9.5% of patients had mild hepatic impairment. CONCLUSIONS: p-ALG along with CsA is an effective choice for patients with SAA. p-ALG combined with TPO-RA may contribute to the early restoration of hematopoiesis.

[Adenocarcinoma with Aplastic Anemia as an Immune-related Adverse Event Caused by Pembrolizumab: Report of a Case].

A 74-year-old man was found a left completely atelectasis on chest X-ray. He had undergone left lower lobe resection because of an adenocarcinoma at the age of 58. Bronchoscopy revealed a tumor near the left upper lobe branch entry that obstructed the lumen, and a biopsy confirmed the diagnosis of adenocarcinoma. A left completion pneumonectomy was performed, but #4L and #10 lymph nodes could not be completely resected. Programmed cell death 1-ligand 1( PD-L1) was positive with tumor proportion score (TPS) 15%, so chemotherapy with pembrolizumab+pemetrexed+carboplatin was started about 1.5 months after surgery. Pancytopenia appeared from the seventh course and did not improve after discontinuation of chemotherapy, so we consulted to the hematologist. He was diagnosed as aplastic anemia by bone marrow biopsy. Aplastic anemia was unresponsive to treatment and chemotherapy could not be resumed. He died of exacerbation of lung cancer.

[Single non-blood-related umbilical cord blood transplantation using a reduced-intensity conditioning regimen for the treatment of severe aplastic anemia].

Objective: To evaluated the clinical efficacy of a reduced-intensity preconditioning regimen for single non-blood-related umbilical cord blood transplantation (sUCBT) in the treatment of severe aplastic anemia (SAA) . Methods: The clinical data of 63 patients with SAA who underwent sUCBT from January 2021 to July 2023 at the Department of Hematology of the First Affiliated Hospital of USTC were retrospectively analyzed. Fifty-two patients received total body irradiation/total bone marrow irradiation (TMI) combined with fludarabine or a cyclophosphamide- conditioning regimen (non-rATG group) , while 11 patients received rabbit anti-human thymocyte immunoglobulin (rATG) combined with TMI, fludarabine, or the cyclophosphamide-conditioning regimen (rATG group) . All patients received cyclosporine A and mycophenolate mofetil for graft-versus-host disease (GVHD) prophylaxis. Complications post-transplantation and long-term survival were compared between the two groups. Results: The baseline parameters were balanced between the two groups (P>0.05) . In the rATG group, all patients achieved stem cell engraftment, and in the non-rATG group, five patients had primary graft failure. There was no significant difference in the cumulative incidence of neutrophil engraftment at 42 days after transplantation or platelet engraftment at 60 days between the two groups. The incidence of grade Ⅱ-Ⅳ acute GVHD in the rATG group was significantly lower than in the non-rATG group (10.0% vs. 46.2% , P=0.032) , and the differences in the cumulative incidences of grade Ⅲ/Ⅳ acute GVHD and 1-year chronic GVHD were not statistically significant (P=0.367 and P=0.053, respectively) . There were no significant differences in the incidences of pre-engraftment syndrome, bacterial bloodstream infections, cytomegalovirus viremia, or hemorrhagic cystitis between the two groups (P>0.05 for all) . The median follow-up time for surviving patients was 536 (61-993) days, and the 1-year transplantation related mortality (TRM) of all patients after transplantation was 13.0% (95% CI 6.7% -24.3% ) . Among the patients in the non-rATG and rATG groups, 15.5% (95% CI 8.1% -28.6% ) and 0% (P=0.189) , respectively, had mutations. The 1-year overall survival (OS) rate of all patients after transplantation was 87.0% (95% CI 75.7% -93.3% ) . The 1-year OS rates in the rATG group and non-rATG group after transplantation were 100% and 84.5% , respectively (95% CI 71.4% -91.9% ) (P=0.198) . Conclusion: The preliminary results of sUCBT with a low-dose irradiation-based reduced-intensity conditioning regimen with fludarabine/cyclophosphamide for the treatment of patients with SAA showed good efficacy. Early application of low-dose rATG can reduce the incidence of acute GVHD after transplantation without increasing the risk of implantation failure or infection.

Aplastic anaemia following antibiotic use for urinary tract infection.

Aplastic anaemia is often associated with recent viral illnesses to include EBV and parvovirus along with certain medications such as anticonvulsants and sulfa containing antibiotics. We describe a case report of a female patient in her 70s who presented with pancytopenia after being treated with nitrofurantoin and ciprofloxacin for suspected urinary tract infection. She underwent an extensive workup to rule out alternative aetiologies of her pancytopenia to include a broad viral, autoimmune and malignancy evaluation which were unrevealing. Given her recent exposure to ciprofloxacin and nitrofurantoin and marrow recovery following removal of these agents, it was presumed that antibiotic exposure was the underlying cause of her aplastic anaemia.

Activity and safety of eltrombopag in combination with cyclosporin A as first­line treatment of adults with severe aplastic anaemia (SOAR): a phase 2, single-arm study.

BACKGROUND: Antithymocyte globulin (ATG)-based immunosuppression is standard in front-line treatment for people with severe aplastic anaemia without a histocompatible donor or who are 40 years or older. However, ATG requires in-hospital administration, is associated with infusion-related toxicities and has limited availability worldwide. In this study, we investigated the activity and safety of an ATG-free regimen of eltrombopag with cyclosporin A as a potential treatment for patients with severe aplastic anaemia who might not have access to or cannot tolerate horse-ATG. METHODS: SOAR was a multicentre, single-arm phase 2 trial investigating eltrombopag and cyclosporin in adult (≥18 years) patients with severe aplastic anaemia who were treatment-naive and had an Eastern Cooperative Oncology Group performance status of less than 2. Participants were recruited from 20 hospitals in ten countries. Eltrombopag was initiated at 150 mg (100 mg in patients of Asian ethnicity) and cyclosporin at 10 mg/kg per day (adjusted to a trough of 200-400 µg/L) orally from day 1 to 6 months. The primary outcome was an overall haematological response rate by 6 months in the intention-to-treat population. This is the final report of the primary analysis period. The trial was registered with ClinicalTrials.gov, NCT02998645, and has been completed. FINDINGS: 54 patients were enrolled between May 11, 2017, and March 23, 2020. 34 (63%) patients were male and 20 (37%) were female. 22 (41%) were Asian, 22 (41%) were White, one (2%) was Native American or Alaska Native, one (2%) was Black or African American, and eight (15%) were other race or ethnicity. 35 patients (65%) completed 6 months of treatment with eltrombopag and cyclosporin and six (11%) completed the cyclosporin tapering period up to month 24. Overall haematological response rate by month 6 of treatment was 46% (25 of 54; 95% CI 33-60). The most reported adverse events were increased serum bilirubin (in 22 patients [41%]), nausea (16 [30%]), increased alanine aminotransferase concentration (12 [22%]), and diarrhoea (12 [22%]). Eight patients died on-treatment, but no deaths were considered related to the treatment. INTERPRETATION: Eltrombopag and cyclosporin was active as front-line treatment of severe aplastic anaemia, with no unexpected safety concerns. This approach might be beneficial where horse-ATG is not available or not tolerated. FUNDING: Novartis Pharmaceuticals.

Progress in medical therapy in aplastic anemia: why it took so long?

The treatment of aplastic anemia (AA) has significantly advanced in the last 50 years, evolving from a fatal condition to one where survival rates now exceed 80-85%. Hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have become the primary treatments, with the latter widely adopted due to factors like the scarcity of compatible donors, patient age, comorbidities, and limited HSCT access. A therapy breakthrough was the introduction of antithymocyte globulin (ATG), with its effectiveness further boosted by cyclosporine. However, it took years to achieve another major milestone in management. Initially, treatments aimed to intensify immunosuppression following the success of the ATG-cyclosporine combination, but these methods fell short of expectations. A major turning point was combining immunosuppression with stem cell stimulation, surpassing the efficacy of IST alone. Earlier, growth factors had shown limited success in AA treatment, but thrombopoietin receptor agonists represented a significant advancement. Initially applied alone as salvage, these were later combined with IST, forming the most effective current regimen for medically managing SAA. Horse ATG is the preferred formulation combined with cyclosporine and eltrombopag. This progress in AA treatment offers improved outcomes for patients afflicted with this once-lethal disease.

[How to think about the clinical classifications of acquired aplastic anemia].

Paying attention to the diagnosis and classification of acquired aplastic anemia (AA) is the basis for improving the efficacy and the guarantee for the correct exploration of the pathological mechanism, which is of great clinical and academic significance. At present, AA classification is still based on clinical characteristics, which is a historical product of academic development.It is beneficial to guide symptomatic treatment and for the onset of curative treatment. However, the clinical classification of AA cannot replace the pathological mechanism classification to guide the treatment of the root cause. The classification of the pathological mechanism of AA determines the choice of treatment strategy, and can provide a basis for the study of etiology and prevention, and is also the future research direction. Paying attention to the classification of the pathological mechanism of AA is the basis for improving the efficacy and the guarantee for the correct exploration of the pathological mechanism. Modern medicine has entered the era of "molecular targets" and "precision", and how to treat clinical classification based on clinical characteristics is an important issue faced by clinicians. When many different mechanisms of bone marrow failure isolated from AA patients can be accurately identified, that is, when the clinically diagnosed AA has been truly purified into a disease with a clear pathological mechanism, the clinical classification of AA can help to choose the root cause strategy. This article mainly focuses on how to view the clinical classification of AA for the reference of colleagues.

Clinical impact and characteristics of erythroid dysplasia in adult aplastic anaemia: Results from a multicentre registry.

Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini-D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non-severe AA patients, a response to anti-thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini-D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia-free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis.

Efficacy and safety of avatrombopag in combination with immunosuppressive therapy in treatment-naïve and relapsed/refractory severe aplastic anaemia: protocol for the DIAAMOND-Ava-FIRST and DIAAMOND-Ava-NEXT Bayesian Optimal Phase II trials.

INTRODUCTION: Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and ciclosporin is standard of care for patients with severe aplastic anaemia (sAA) not eligible or suitable for allogeneic stem cell transplant. While patients respond to IST, few achieve complete responses and a significant proportion are refractory or relapse. The addition of eltrombopag, a thrombopoietin-receptor agonist (TPO-A), to IST has been shown to improve haematological responses in sAA. Avatrombopag is a second-generation TPO-A with potential advantages over eltrombopag. However, to date avatrombopag has not been studied in sAA. METHODS AND ANALYSIS: Investigator-initiated, single-arm registry-based Bayesian Optimal Phase II trial of avatrombopag conducted in two cohorts, patients with untreated sAA (FIRST cohort) and in patients with sAA that has relapsed or is refractory to IST (NEXT cohort). In the FIRST cohort, participants receive IST (equine ATG and ciclosporin) plus avatrombopag from day 1 until day 180 at 60 mg oral daily, with dose adjusted according to platelet count. Participants in the NEXT cohort receive avatrombopag at 60 mg oral daily from day 1 until day 180, with or without additional IST at the discretion of the treating clinician.For each cohort, two primary endpoints (haematological response and acquired clonal evolution) are jointly monitored and the trial reviewed at each interim analysis where a 'go/no-go' decision is made by evaluating the posterior probability of the events of interests. ETHICS AND DISSEMINATION: The trial has received ethics approval (Monash Health RES-18-0000707A). The trial conduct will comply with ICH-GCP and all applicable regulatory requirements. The results of the trial will be submitted to a peer-review journal for publication. TRIAL REGISTRATION NUMBER: ACTRN12619001042134, ACTRN12619001043123.

A multicentre ambispective observational study into the incidence and clinical management of aplastic anaemia in Spain (IMAS study).

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

Plain language summary of RACE study results: addition of eltrombopag to standard treatment of severe aplastic anemia.

WHAT IS THIS SUMMARY ABOUT?: Severe aplastic anemia (SAA) and very severe aplastic anemia (vSAA) are blood diseases of the bone marrow. If a suitable donor for bone marrow transplant as initial treatment is unavailable, standard immunosuppression is used. Standard immunosuppression treatment includes horse antithymocyte globulin (hATG) and cyclosporin A (CsA). This summary investigated the results of standard immunosuppression treatment (Group A) versus standard immunosuppression treatment with a medication called eltrombopag (Group B) in participants with SAA and vSAA. Eltrombopag is a medicine that improves the blood platelet level and is taken by mouth (orally). WHAT WERE THE RESULTS OF THE STUDY?: Compared to Group A, more participants in Group B showed increased blood cell level to a normal range without SAA or vSAA and faster treatment response. Side effects were similar in both groups even with the addition of eltrombopag for Group B. Participants in both groups reported feeling well after 6, 12 and 24 months. Differences in the participant-reported scores (overall health, physical, emotional, and social) between Group A and Group B were minimal. WHAT DO THE RESULTS OF THE STUDY MEAN?: Immunosuppression treatment (hATG plus CsA) with eltrombopag benefited participants with SAA and vSAA and could be the new standard for SAA in persons who cannot undergo bone marrow transplant. At this time, eltrombopag is only approved in specific countries to treat the condition under study that is discussed in this summary. Clinical Trial Registration: NCT02099747 (RACE study).

Emodin suppresses adipogenesis of bone marrow derived mesenchymal stem cells from aplastic anemia via increasing TRIB3 expression.

BACKGROUND: Increasing evidence indicate that enhanced adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) could contribute to the adiposity alteration in marrow microenvironment of aplastic anemia (AA). Identifying small molecule drugs with role in inhibiting adipogenesis of BM-MSCs may represent a novel direction in AA therapy by improving BM-MSCs mediated marrow microenvironment. METHODS: For the purpose, we isolated AA BM-MSCs through whole bone marrow cell culture, evaluated a series of small molecule drugs using the in vitro adipogenic differentiation model of BM-MSCs, and finally focused on emodin, a natural anthraquinone derivative. Subsequently, we systematically investigated the molecular mechanism of emodin in attenuating adipogenic process by means of microarray profiling, bioinformatics analysis and lentivirus-mediated functional studies and rescue assay. RESULTS: We found that emodin presented significantly suppressive effect on the in vitro adipogenic differentiation of AA BM-MSCs. Further mechanistic investigation revealed that emodin could increase the expression of Tribbles homolog 3 (TRIB3) which exhibited remarkably decreased expression in AA BM-MSCs compared with the normal counterparts and was subsequently demonstrated as a negative regulator in adipogenesis of AA BM-MSCs. Besides, TRIB3 depletion alleviated the suppressive effect of emodin on the adipogenic differentiation of AA BM-MSCs. CONCLUSION: Our findings propose that emodin mediated TRIB3 up-regulation alleviates the adipogenic capacity of AA BM-MSCs, and emodin could serve as a potential therapeutic regimen for AA therapy.

Clinical characteristics of hepatitis-associated aplastic anemia in children.

To understand the current situation of hepatitis-related aplastic anemia (HAAA) in children, we analyzed the patients with HAAA admitted to our hospital in the past 5 years to understand the disease characteristics and prognosis. The clinical data of patients with HAAA admitted to our hospital from February 2017 to May 2022 were retrospectively analyzed. A total of 81 patients with HAAA, 56 males and 25 females. The median onset age was 5.9 years. The median time from hepatitis to occurrence of hemocytopenia was 30 days, and the median follow-up time was 2.77 years. There were 23 cases (28.5%) of severe aplastic anemia (SAA), 50 cases of very severe aplastic anemia (VSAA), and 8 cases of non-severe aplastic anemia (NSAA). At the beginning of the disease, cytotoxic T lymphocyte (CTL) was higher than normal in 60% of patients, and the median CD4/CD8 ratio was 0.2. As of follow-up, 72 children survived, 4 were lost, and 5 died. Thirty-four cases were treated with immunosuppressive therapy (IST), with a median follow-up time of 0.97 years. The total reaction rate was 73.5% (25/34), the complete reaction rate was 67.6% (23/34), and the nonreaction rate was 26.5% (9/34). Multivariate analysis suggested that co-infection was an independent risk factor affecting the efficacy of IST at 6 months, with an OR value of 16.76, 95% CI (1.23, 227.95), P=0.034. No independent influencing factors were found at the end of follow-up. The proportion of CTL cells in peripheral blood of children with HAAA is relatively increased, and IST is effective in 73.5% of children. Co-infection may prolongs the time to response to IST.

Severe Thrombocytopenia Due to Bone Marrow Failure in Children With Dyskeratosis Congenita Does Not Respond to Eltrombopag Treatment: Case Series.

Dyskeratosis congenita is a rare inherited disease with classic cutaneous symptoms, sometimes accompanied with more severe extracutaneous manifestations such as bone marrow failure, which can be lethal. Eltrombopag is an orally available thrombopoietin receptor agonist in clinical use for increasing platelet levels in patients with immune thrombocytopenia and aplastic anemia. Here, 3 pediatric patients with dyskeratosis congenita are presented with varying disease severity, in which off-label eltrombopag treatment had no clinical effect on bone marrow failure. This, in addition to the negative results in a previous case report, supports the preclusion of eltrombopag use in dyskeratosis congenita.

Real-world outcomes with immunosuppressive therapy for aplastic anemia in patients treated at the University of Michigan.

Aplastic anemia (AA) is a rare bone marrow failure disorder that is treated with either allogeneic stem cell transplant or immunosuppressive therapy (IST) consisting of antithymocyte globulin (ATG), cyclosporine (CSA), and eltrombopag. While outcomes are favorable in younger patients, older patients (>60) have significantly worse long-term survival. The dose of ATG is often reduced in older patients and those with multiple comorbidities given concerns for tolerability. The efficacy and safety of dose-attenuated IST in this population is largely undescribed. We performed a retrospective review of patients with AA treated with IST. Our analysis was confounded by changes in practice patterns and the introduction of eltrombopag. We identified 53 patients >60 years old, of which, 20 received dose-attenuated IST, with no statistically significant difference in overall survival between full and attenuated dose cohorts. Overall response rates in both cohorts were similar at 6 months at 71% and 68%. There were more documented infectious complications in the full dose cohort (13 vs. 3). This supports the consideration of dose-attenuated IST in older patients with concerns about tolerance of IST. Lastly, our data confirmed favorable outcomes of younger patients receiving IST, especially in combination with eltrombopag.

High- vs regular-dose recombinant human thrombopoietin plus cyclosporine A in patients with newly diagnosed non-severe aplastic anemia: a retrospective cohort study.

BACKGROUND: Cyclosporine A (CsA) and regular doses of recombinant human thrombopoietin (rhTPO) can accelerate platelet recovery in patients with non-severe aplastic anemia (NSAA). However, it is unclear whether CsA plus rhTPO at a higher dose can further increase the efficacy. METHODS: Data from patients with newly diagnosed NSAA, who had been treated with CsA in combination with different doses of rhTPO between February 2021 and August 2021 at Peking Union Medical College Hospital, were reviewed. All the enrolled patients had been treated with CsA at 3-5 mg/(kg/d), and patients were further classified into high-dose (with rhTPO 30000U qd × 14 days for 2 months) group or regular-dose (with rhTPO 15000U qd × 7days for 3 months) group. The treatment response and therapy-related adverse events were compared. RESULTS: 36 patients including 16 (44.4%) in the high-dose and 20 (55.6%) in the regular-dose group were enrolled. The baseline characteristics were compatible between the two groups. The platelet counts were significantly higher at 1/3/6 months in the high-dose group (p = 0.028, 0.0063 and p = 0.040, respectively). The high-dose group had a significantly shorter time to platelet transfusion independence ([1 (0.5-6) months vs 2.5 (1-12) months, p = 0.040]). There was no significant difference in overall response and complete response rate between the two groups at 1/3/6/12 months (p > 0.05). Treatment-related morbidities were similar between the two groups (p > 0.05). CONCLUSIONS: Adding a higher dose of rhTPO can further accelerate platelet recovery and platelet transfusion independence in patients with newly diagnosed NSAA.