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Risk factors associated with poor response to immunosuppressive therapy in acquired aplastic anemia: A meta-analysis of retrospective studies.

ABSTRACT: Acquired aplastic anemia (AA) is a rare hematological disease characterized by bone marrow hypocellularity and varying degrees of pancytopenia. Immunosuppressive therapy (IST) is currently one of the first-line treatments for AA; however, unresponsiveness remains a major concern. Although previous studies have suggested several common risk factors for unresponsiveness, there are currently no widely accepted predictors. Therefore, a meta-analysis of clinical trials including information on factors associated with unresponsiveness of AA to IST was performed in the present study. The PubMed, Embase and Cochrane Library databases were searched for clinical studies on AA evaluating the association between risk factors and unresponsiveness to IST. After the factors were defined from the selected studies, the association between these factors and unresponsiveness to IST was analyzed using Review Manager software. A total of 10 studies comprising 1,820 cases were included in the present meta-analysis. The following factors were identified as predictors of unresponsiveness: Age (?60 years), sex, absolute neutrophil count, severity of the disease, paroxysmal nocturnal hemoglobinuria clone, human leukocyte antigen (HLA)-DR2 and cytogenetic abnormalities (CAs). Among these factors, only age (?60 years) [odds ratio (OR)=1.65], HLA-DR2 negativity (OR=2.72) and CAs (OR=1.93) exhibited a statistically significant association with unresponsiveness to IST (P=0.006, P=0.04 and P=0.01, respectively). In conclusion, the present meta-analysis revealed that age ?60 years, HLA-DR2 negativity and CAs are risk factors for unresponsiveness to IST. This result may enable clinicians to select an effective therapeutic scheme for patients with AA and even provide novel clues to the pathogenesis of AA.

SUBMITTER: Wang J

PROVIDER: S-EPMC7086236 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Risk factors associated with poor response to immunosuppressive therapy in acquired aplastic anemia: A meta-analysis of retrospective studies.

Wang Jia J Shen Ping P Wu Xiangru X Jin Wenjie W

Experimental and therapeutic medicine 20200219 4

Acquired aplastic anemia (AA) is a rare hematological disease characterized by bone marrow hypocellularity and varying degrees of pancytopenia. Immunosuppressive therapy (IST) is currently one of the first-line treatments for AA; however, unresponsiveness remains a major concern. Although previous studies have suggested several common risk factors for unresponsiveness, there are currently no widely accepted predictors. Therefore, a meta-analysis of clinical trials including information on factor ...[more]

PMID: 32256799

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Project description:Background and objectiveImmunosuppressive 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.MethodsWe 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.ResultsA 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.ConclusionEPAG 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.

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Risk factors associated with poor response to immunosuppressive therapy in acquired aplastic anemia: A meta-analysis of retrospective studies.

Publications

Risk factors associated with poor response to immunosuppressive therapy in acquired aplastic anemia: A meta-analysis of retrospective studies.

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