Treatment of Aplastic Anemia with Antilymphocyte Globulin and Methylprednisolone with or without Cyclosporine

Frickhofen, Norbert; Kaltwasser, J. P.; Schrezenmeier, Hubert; Raghavachar, Aruna; Vogt, H.; Herrmann, F; Freund, Mathias; Meusers, P.; Salama, A; Heimpel, Hermann

doi:10.1056/nejm199105093241901

Cited by 394 publications

(246 citation statements)

References 34 publications

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“…28,29 Complication of clinically relevant PNH has been described in 15% to 25% of the patients with AA treated by IST. [30][31][32][33][34][35] Moreover, regardless of typical manifestations of PNH, GPI anchor-deficient, "PNH-type" cells are detectable at even higher frequencies (up to 67%) when assessed by sensitive flow cytometry using antibodies to CD55 or CD59 and/or fluorescent aerolysin (FLAER). 36,37 Another major category of late clonal diseases includes MDS and AML.…”

Section: Late Clonal Diseases In Aamentioning

confidence: 99%

Clonal hematopoiesis in acquired aplastic anemia

Ogawa

2016

Blood

154

130

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Clonal hematopoiesis (CH) in aplastic anemia (AA) has been closely linked to the evolution of late clonal disorders, including paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), which are common complications after successful immunosuppressive therapy (IST). With the advent of high-throughput sequencing of recent years, the molecular aspect of CH in AA has been clarified by comprehensive detection of somatic mutations that drive clonal evolution. Genetic abnormalities are found in ∼50% of patients with AA and, except for PIGA mutations and copy-neutral loss-of-heterozygosity, or uniparental disomy (UPD) in 6p (6pUPD), are most frequently represented by mutations involving genes commonly mutated in myeloid malignancies, including DNMT3A, ASXL1, and BCOR/BCORL1. Mutations exhibit distinct chronological profiles and clinical impacts. BCOR/BCORL1 and PIGA mutations tend to disappear or show stable clone size and predict a better response to IST and a significantly better clinical outcome compared with mutations in DNMT3A, ASXL1, and other genes, which are likely to increase their clone size, are associated with a faster progression to MDS/AML, and predict an unfavorable survival. High frequency of 6pUPD and overrepresentation of PIGA and BCOR/BCORL1 mutations are unique to AA, suggesting the role of autoimmunity in clonal selection. By contrast, DNMT3A and ASXL1 mutations, also commonly seen in CH in the general population, indicate a close link to CH in the aged bone marrow, in terms of the mechanism for selection. Detection and close monitoring of somatic mutations/evolution may help with prediction and diagnosis of clonal evolution of MDS/AML and better management of patients with AA.

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Section: Late Clonal Diseases In Aamentioning

confidence: 99%

Clonal hematopoiesis in acquired aplastic anemia

Ogawa

2016

Blood

154

130

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“…1 It has been also demonstrated that the combination of ATG and CyA is superior to ATG or CyA alone in terms of hematologic response. 2,3 Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor that mainly stimulates the proliferation and differentiation of granulocyte precursors; however, a stimulatory effect of G-CSF on multipotential hematopoietic stem cells has also been demonstrated. 4 Clinically, G-CSF can induce a short-term increase in the neutrophil count in most patients with AA.…”

Section: Introductionmentioning

confidence: 99%

Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

Teramura

Kimura

Iwase

et al. 2007

Blood

103

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We report the results of a randomized study to elucidate whether addition of granulocyte colony-stimulating factor (G-CSF) to immunosuppressive therapy is valuable for the treatment of severe aplastic anemia (SAA) in adults. A total of 101 previously untreated patients (median age, 54 years; range, 19 to 75 years) were randomized to receive antithymocyte globulin (ATG) and cyclosporin A (CyA) (G-CSF؊ group) or ATG, CyA, and G-CSF (G-CSF؉ group). In the G-CSF؉ group, the hematologic response rate at 6 months was higher (77% vs 57%; P ‫؍‬ .03) than in the G-CSF؊ group. No differences were observed between the groups in terms of the incidence of infections and febrile episodes. There were no differences between the G-CSF؊ group and the G-CSF؉ group in terms of survival (88% vs 94% at 4 years), and the development of myelodysplastic syndrome (MDS)/acute leukemia (AL) (1 patient vs 2 patients). However, the relapse rate was lower in the G-CSF؉ group compared with the G-CSF؊ group (42% vs 15% at 4 years; P ‫؍‬ .01). Further follow-up is required to elucidate the role of G-CSF in immunosuppressive therapy for adult SAA. (Blood.

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“…ATG has become the golden standard in immunosuppressive treatment of aplastic anemia (AA). Remission rates to combined immunosuppression with ATG, cyclosporin A, and corticosteroids reach up to 60-80% in aplastic anemia [4,5]. However, the mechanism of action responsible for induction of remissions in AA is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia

2009

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Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are currently used successfully for immunosuppressive treatment of aplastic anemia. In this study we have investigated whether commercial ATG/ALG preparations contain antibodies against glycosylphosphatidyl-inositol anchored proteins (GPI-AP), which could be responsible for emergence of GPI-deficient populations in aplastic anemia after ATG/ALG therapy. We analyzed four commercial ATG/

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Treatment of Aplastic Anemia with Antilymphocyte Globulin and Methylprednisolone with or without Cyclosporine

Cited by 394 publications

References 34 publications

Clonal hematopoiesis in acquired aplastic anemia

Clonal hematopoiesis in acquired aplastic anemia

Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia

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