Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia

Scheinberg, Phillip; Wu, Colin O.; Núñez, Olga; Young, Neal S.

doi:10.1111/j.1365-2141.2008.07450.x

Cited by 187 publications

(175 citation statements)

References 41 publications

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“…These patients (designated subclinical PNH patients) with very small populations of GPI-AP-deficient erythrocytes have no clinical or biochemical evidence of hemolysis and require no specific treatment for PNH. However, finding a population of GPI-AP-deficient erythrocytes in patients with aplastic anemia may be clinically relevant, because some, 19,20 but not all, 21 studies suggest that these patients have a particularly high probability of responding to immunosuppressive therapy with a more rapid rate of onset of response compared with patients with aplastic anemia without a population of GPI-AP-deficient erythrocytes.…”

Section: Subclinical Pnhmentioning

confidence: 99%

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Parker

2011

Hematology

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Despite the availability of safe, effective targeted therapy that controls intravascular hemolysis, the management of paroxysmal nocturnal hemoglobinuria (PNH) remains complicated because of disease heterogeneity and close association with BM failure syndromes. The purpose of this review is to provide a framework for individualizing treatment based on disease classification. According to the recommendations of the International PNH Interest Group, patients can be placed into one of the following 3 categories: (1) classic PNH, (2) PNH in the setting of another BM failure syndrome, or (3) subclinical PNH. The PNH clone in patients with subclinical disease is insufficiently large to produce even biochemical evidence of hemolysis, and consequently, patients who fit into this category require no PNH-specific therapy. Patients with PNH in the setting of another BM failure syndrome (usually aplastic anemia or low-risk myelodysplastic syndrome) have at least biochemical evidence of hemolysis, but typically the PNH clone is small (Ͻ 10%) so that hemolysis does not contribute significantly to the underlying anemia. In these cases, the focus of treatment is on the BM failure component of the disease. Intravascular hemolysis is the dominant feature of classic PNH, and this process is blocked by the complement inhibitor eculizumab. The thrombophilia of PNH also appears to be ameliorated by eculizumab, but the drug has no effect on the BM failure component of the disease. Low-grade extravascular hemolysis due to complement C3 opsonization develops in most patients treated with eculizumab, and in some cases is a cause for suboptimal response to treatment. Allogeneic BM transplantation can cure classic PNH, but treatment-related toxicity suggests caution for this approach to management.

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Section: Subclinical Pnhmentioning

confidence: 99%

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Parker

2011

Hematology

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“…Baseline absolute reticulocyte and lymphocyte counts were defined as simple predictors of response following IST. 42 In children, lower WBC count (o2.0 Â 10 9 /L) was the most significant predictive marker of better response. 43 In patients receiving G-CSF, the lack of a neutrophil response (o0.5 Â 10 9 /L) by day 30 was associated with significantly lower response rate and survival.…”

Section: Future Directions In the Diagnosis Of Acquired Aamentioning

confidence: 99%

Diagnosis of acquired aplastic anemia

Rovó

Thewis

Dufour

2012

Bone Marrow Transplant

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“…For this study, severe AA was defined as a bone marrow cellularity of less than 30% associated with at least two of the following peripheral blood count criteria: (i) absolute neutrophil count (ANC) less than 0.5¥10 /L. 4,19 Baseline laboratory values were defined as the lowest value during the 4 weeks prior to immunosuppressive therapy and were determined prior to transfusions: the prognostic algorithm is, therefore, free of transfusion artifacts.…”

Section: Patientsmentioning

confidence: 99%

“…4,19 Response was evaluated 3, 6 and 12 months after immunosuppressive treatment. We defined relapse as a need for retreatment with ATG following an initial response.…”

Section: Response Criteriamentioning

confidence: 99%

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

Afable¹,

Shaik²,

Sugimoto³

et al. 2011

Haematologica

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BackgroundA combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Design and MethodsTwenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. ResultsResponse rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte globulin or horse anti-thymocyte globulin: 40% versus 55% (P=0.43), 45% versus 58% (P=0.44) and 50% versus 58% (P=0.61), respectively. No differences in early mortality rates or overall survival were observed. We then performed multivariable analyses of response at 6 months and overall survival and identified the presence of a paroxysmal nocturnal hemoglobinuria clone (P=0.01) and a pretreatment absolute reticulocyte count greater than 30¥10 9 /L (P=0.007) as independent predictors of response and younger age (P=0.003), higher pretreatment absolute neutrophil (P=0.02) and absolute lymphocyte counts (P=0.03) as independent predictors of overall survival. None of the immunogenetic polymorphisms studied was predictive of response to immunosupressive therapy. ConclusionsDespite reports suggesting differences in biological activity of different anti-thymocyte globulin preparations, rabbit and horse anti-thymocyte globulin appear to have a similar efficacy for upfront treatment of severe aplastic anemia. (Clinicaltrial.gov: NCT01231841)

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Predicting response to immunosuppressive therapy and survival in severe aplastic anaemia

Cited by 187 publications

References 41 publications

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Management of Paroxysmal Nocturnal Hemoglobinuria in the Era of Complement Inhibitory Therapy

Diagnosis of acquired aplastic anemia

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia

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