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Haematologica2010; 95(7); 1075-1080; doi: 10.3324/haematol.2009.017889

Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine.

Abstract: Clones of glycosylphosphatidylinositol-anchor protein-deficient cells are characteristic in paroxysmal nocturnal hemoglobinuria and are present in about 40-50% of patients with severe aplastic anemia. Flow cytometry has allowed for sensitive and precise measurement of glycosylphosphatidylinositol-anchor protein-deficient red blood cells and neutrophils in severe aplastic anemia. Methods: We conducted a retrospective analysis of paroxysmal nocturnal hemoglobinuria clones measured by flow cytometry in 207 consecutive severe aplastic anemia patients who received immunosuppressive therapy with a horse anti-thymocyte globulin plus cyclosporine regimen from 2000 to 2008. Results: The presence of a glycosylphosphatidylinositol-anchor protein-deficient clone was detected in 83 (40%) patients pre-treatment, and the median clone size was 9.7% (interquartile range 3.5-29). In patients without a detectable clone pre-treatment, the appearance of a clone after immunosuppressive therapy was infrequent, and in most with a clone pre-treatment, clone size often decreased after immunosuppressive therapy. However, in 30 patients, an increase in clone size was observed after immunosuppressive therapy. The majority of patients with a paroxysmal nocturnal hemoglobinuria clone detected after immunosuppressive therapy did not have an elevated lactate dehydrogenase, nor did they experience hemolysis or thrombosis, and they did not require specific interventions with anticoagulation and/or eculizumab. Of the 7 patients who did require therapy for clinical paroxysmal nocturnal hemoglobinuria symptoms and signs, all had an elevated lactate dehydrogenase and a clone size greater than 50%. In all, 18 (8.6%) patients had a clone greater than 50% at any given time of sampling. Conclusions: The presence of a paroxysmal nocturnal hemoglobinuria clone in severe aplastic anemia is associated with low morbidity and mortality, and specific measures to address clinical paroxysmal nocturnal hemoglobinuria are seldom required.
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Publication Date: 2010-07-03 PubMed ID: 20595102PubMed Central: PMC2895030DOI: 10.3324/haematol.2009.017889Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research examines the presence and potential significance of abnormal cells related to a disease called paroxysmal nocturnal hemoglobinuria (PNH) in patients with a severe condition known as aplastic anemia. Using a specific technique called flow cytometry, the researchers analyzed more than 200 patients to track any changes in the amount and characteristics of these abnormal cells after being treated with a therapy involving anti-thymocyte globulin and cyclosporine.

Research Background

  • The study is based on severe aplastic anemia, a condition where the body stops producing enough new blood cells. Another associated condition is paroxysmal nocturnal hemoglobinuria (PNH), which is characterized by the presence of cells lacking GPI-anchor proteins – a type of deficiency observed in approximately 40-50% of severe aplastic anemia patients.
  • These abnormal cells or “clones” could be observed through a technique called flow cytometry, enabling the precise measurement of GPI-anchor protein-deficient red blood cells.

Research Methodology

  • The researchers conducted a retrospective analysis of PNH clones in 207 consecutive severe aplastic anemia patients who were treated with a regimen of horse anti-thymocyte globulin and cyclosporine between 2000 and 2008. The aim was to track changes in these clones post treatment.

Key Findings

  • Around 40% of the patients had these abnormal cells before the treatment, and the size of these aberrant cell populations often decreased after the immunosuppressive therapy.
  • In a small number of patients (30), an increase in clone size was observed after the treatment. Additionally, very few of these patients had elevated lactate dehydrogenase levels, experienced hemolysis or thrombosis, or required specific interventions.
  • Only 7 patients needed treatment for clinical PNH symptoms, all of whom had elevated lactate dehydrogenase and a clone size greater than 50%.

Conclusions

  • The presence of PNH clones in severe aplastic anemia patients is associated with low morbidity and mortality, suggesting generally positive outcomes. The need for specific treatment addressing clinical PNH symptoms is rare, implying the disease’s manageable nature after the implementation of immunosuppressive therapy.

Cite This Article

APA
Scheinberg P, Marte M, Nunez O, Young NS. (2010). Paroxysmal nocturnal hemoglobinuria clones in severe aplastic anemia patients treated with horse anti-thymocyte globulin plus cyclosporine. Haematologica, 95(7), 1075-1080. https://doi.org/10.3324/haematol.2009.017889

Publication

Haematologica
ISSN: 1592-8721
NlmUniqueID: 0417435
Country: Italy
Language: English
Volume: 95
Issue: 7
Pages: 1075-1080

Researcher Affiliations

Scheinberg, Phillip
  • Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, 20892-1202, USA. scheinbp@mail.nih.gov
Marte, Michael
    Nunez, Olga
      Young, Neal S

        MeSH Terms

        • Adult
        • Anemia, Aplastic / drug therapy
        • Anemia, Aplastic / pathology
        • Animals
        • Antilymphocyte Serum / therapeutic use
        • Clone Cells / pathology
        • Cyclosporine / therapeutic use
        • Drug Therapy, Combination
        • Female
        • Hemoglobinuria, Paroxysmal / drug therapy
        • Hemoglobinuria, Paroxysmal / pathology
        • Horses
        • Humans
        • Immunosuppressive Agents / therapeutic use
        • Male
        • Middle Aged
        • Prognosis
        • Retrospective Studies
        • Young Adult

        Grant Funding

        • Intramural NIH HHS

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