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Aplastic anemia: immunosuppressive therapy in 2010.

ABSTRACT: Acquired aplastic anemia (AA) is the typical bone marrow failure syndrome characterized by an empty bone marrow; an immune-mediated pathophysiology has been demonstrated by experimental works as well as by clinical observations. Immunusuppressive therapy (IST) is a key treatment strategy for aplastic anemia; since 20 years the standard IST for AA patients has been anti-thymocyte globuline (ATG) plus cyclosporine A (CyA), which results in response rates ranging between 50% and 70%, and even higher overall survival. However, primary and secondary failures after IST remain frequent, and to date all attempts aiming to overcome this problem have been unfruitful. Here we review the state of the art of IST for AA in 2010, focusing on possible strategies to improve current treatments. We also discuss very recent data which question the equality of different ATG preparations, leading to a possible reconsideration of the current standards of care for AA patients.

SUBMITTER: Risitano AM

PROVIDER: S-EPMC3206528 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Aplastic anemia: immunosuppressive therapy in 2010.

Risitano Antonio M AM Perna Fabiana F

Pediatric reports 20110601

Acquired aplastic anemia (AA) is the typical bone marrow failure syndrome characterized by an empty bone marrow; an immune-mediated pathophysiology has been demonstrated by experimental works as well as by clinical observations. Immunusuppressive therapy (IST) is a key treatment strategy for aplastic anemia; since 20 years the standard IST for AA patients has been anti-thymocyte globuline (ATG) plus cyclosporine A (CyA), which results in response rates ranging between 50% and 70%, and even highe ...[more]

PMID: 22053283

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Immunosuppressive therapy for pediatric aplastic anemia: a North American Pediatric Aplastic Anemia Consortium study.

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| S-EPMC6886407 | biostudies-literature

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| S-EPMC4430492 | biostudies-literature

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| S-EPMC6800043 | biostudies-literature

Allo-HSCT compared with immunosuppressive therapy for acquired aplastic anemia: a system review and meta-analysis.

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Project description: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.

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Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia.

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| S-EPMC5990670 | biostudies-literature

Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naive Patients with Aplastic Anemia in Japan.

Project description:Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naïve and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.

| S-EPMC8112980 | biostudies-literature

Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia.

Project description:Horse anti-thymocyte globulin (h-ATG) and ciclosporin are the initial therapy for most patients with severe aplastic anaemia (SAA), but there is no practical and reliable method to predict response to this treatment. To determine whether pretreatment blood counts discriminate patients with SAA who have a higher likelihood of haematological response at 6 months to immunosuppressive therapy (IST), we conducted a single institution retrospective analysis on 316 SAA patients treated with h-ATG-based IST from 1989 to 2005. In multivariate analysis, younger age, higher baseline absolute reticulocyte count (ARC), and absolute lymphocyte count (ALC) were highly predictive of response at 6 months. Patients with baseline ARC > or = 25 x 10(9)/l and ALC > or = 1 x 10(9)/l had a much greater probability of response at 6 months following IST compared to those with lower ARC and ALC (83% vs. 41%, respectively; P < 0.001). This higher likelihood of response translated to greater rate of 5-year survival in patients in the high ARC/ALC group (92%) compared to those with a low ARC/ALC (53%). In the era of IST, the baseline ARC and ALC together serve as a simple predictor of response following IST, which should guide in risk stratification among patients with SAA.

| S-EPMC4149225 | biostudies-literature

A multicenter phase II study on the efficacy and safety of hetrombopag in patients with severe aplastic anemia refractory to immunosuppressive therapy.

Project description:BackgroundIn this single-arm phase II study (NCT03557099), we evaluated the efficacy and safety of hetrombopag, a small molecule thrombopoietin (TPO) receptor agonist, in patients with severe aplastic anemia (SAA) who were refractory to standard first-line immunosuppressive therapy (IST).MethodsSAA patients who were refractory to standard first-line IST were given hetrombopag orally at an initial dose of 7.5 mg once daily to a maximum of 15 mg once daily, for a total of 52 weeks. The primary endpoint was proportion of patients achieving hematologic responses in ⩾1 lineage at week 18.ResultsA total of 55 eligible patients were enrolled and received hetrombopag treatment. This study met its primary endpoint, with 23 [41.8%, 95% confidence interval (CI) = 28.7-55.9] patients achieving hematologic response in ⩾1 lineage at week 18 after initiation of hetrombopag treatment. Twenty-four (43.6%, 95% CI = 30.3-57.7) and 27 (49.1%, 95% CI = 35.4-62.9) of the 55 patients responded in ⩾1 lineage at weeks 24 and 52, respectively. Median time to initial hematologic response was 7.9 weeks (range = 2.0-32.1). The responses were durable, with a 12-month relapse-free survival rate of 82.2% (95% CI = 62.2-92.2). Adverse events occurred in 54 (98.2%) patients, and 28 (50.9%) patients had treatment-related adverse events. Seventeen (30.9%) patients had adverse events of grade ⩾3. Serious adverse events occurred in 15 (27.3%) patients and three deaths (5.5%) were reported.ConclusionHetrombopag showed encouraging efficacy with durable hematologic responses in patients with SAA who were refractory to IST. Hetrombopag was well tolerant and safe for long-term use.Clinicaltrialsgov identifierNCT03557099.

| S-EPMC8972928 | biostudies-literature

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