Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long‐term observation follow‐up

Saracco, Paola; Quarello, Paola; Iori, Anna Paola; Zecca, Marco; Longoni, Daniela; Svahn, Johanna; Varotto, Stefania; Vecchio, Giovanni Carlo Del; Dufour, Carlo; Ramenghi, Ugo; Bacigalupo, Andrea; Locasciulli, Anna

doi:10.1111/j.1365-2141.2007.06903.x

Cited by 93 publications

(89 citation statements)

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“…A recent Italian study of childhood AA showed a 16% cumulative incidence of relapse, which is comparable with that found in our study. 10 Multivariate analysis of the data from this retrospective multicenter study shows that the use of danazol was the most statistically significant risk factor for relapse. From 1992 to 2007, 441 children with newly diagnosed AA were treated with immunosuppressive therapy consisting of antithymocyte globulin and cyclosporine with (the AA-92 study) or without danazol (the AA-97 study).…”

Section: Discussionmentioning

confidence: 99%

“…9 A report from the Italian Association of Pediatric Hematology and Oncology focused mainly on the response to cyclosporine and dependence after immunosuppressive therapy. 10 A single-center retrospective analysis from the National Institutes of Health showed excellent long-term survival with a 33% cumulative incidence of relapse at 10 years in children with severe AA who responded to the standard immunosuppressive therapy; however, a detailed analysis of relapse that included risk factors was not provided. 11 We previously conducted two prospective multicenter studies: the AA-92 and AA-97, which began in November 1992 and October 1997, respectively.…”

Section: Introductionmentioning

confidence: 99%

“…To select the optimal therapy for such patients, a detailed analysis concerning relapse after response to immunosuppressive therapy is very important; however, analyses of relapse of AA in children after the standard combined immunosuppressive regimen are very limited. [9][10][11] Although the European Group for Blood and Marrow Transplantation (EMBT) reported an analysis of relapse of AA after immunosuppressive therapy in a large number of patients, the study populations were primarily adults treated in the 1970s and 1980s with antithymocyte globulin monotherapy. 9 A report from the Italian Association of Pediatric Hematology and Oncology focused mainly on the response to cyclosporine and dependence after immunosuppressive therapy.…”

Section: Introductionmentioning

confidence: 99%

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Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

et al. 2011

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BackgroundAlthough the therapeutic outcome of acquired aplastic anemia has improved markedly with the introduction of immunosuppressive therapy using antithymocyte globulin and cyclosporine, a significant proportion of patients subsequently relapse and require second-line therapy. However, detailed analyses of relapses in aplastic anemia children are limited. Design and MethodsWe previously conducted two prospective multicenter trials of immunosuppressive therapy for children with aplastic anemia: AA-92 and AA-97, which began in 1992 and 1997, respectively. In this study, we assessed the relapse rate, risk factors for relapse, and the response to secondline treatment in children with aplastic anemia treated with antithymocyte globulin and cyclosporine. ResultsFrom 1992 to 2007, we treated 441 children with aplastic anemia with standard immunosuppressive therapy. Among the 264 patients who responded to immunosuppressive therapy, 42 (15.9%) relapsed. The cumulative incidence of relapse was 11.9% at 10 years. Multivariate analysis revealed that relapse risk was significantly associated with an immunosuppressive therapy regimen using danazol (relative risk, 3.15; P=0.001) and non-severe aplastic anemia (relative risk, 2.51; P=0.02). Seventeen relapsed patients received additional immunosuppressive therapy with antithymocyte globulin and cyclosporine. Eight patients responded within 6 months. Seven of nine non-responders to second immunosuppressive therapy received hematopoietic stem cell transplantation and five are alive. Eleven patients underwent hematopoietic stem cell transplantation directly and seven are alive. ConclusionsIn the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia. Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

et al. 2011

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“…[8][9][10][11][12] While ATG is administered as an intravenous infusion over 5 days in hospitalized patients, patients receive CSA orally for 6 months or more. There is controversy about the adequate duration of treatment, as differing recommendations are being made 13 based on little knowledge from clinical trials.…”

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confidence: 99%

“…A recently published paper by the Italian pediatric group came to the conclusion that CSA tapering was best done over many years to decrease relapse risks. 13 Continuing the study might have been worthwhile if only to shed more light on the important question of the impact of early versus late withdrawal of immunosuppressants. This study again confirms that short-term survival is excellent in these patients (>90%), and this includes obviously some of the patients who do not respond and patients who relapse, as well as the option of rescue bone marrow transplantation in patients in whom a donor can be found.…”

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confidence: 99%

Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?

Passweg¹,

Thewis²

2009

Haematologica

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A plastic anemia is a heterogeneous disease, a form of marrow failure that presents with pancytopenia of abrupt or insidious onset and an empty marrow. There are marrow and peripheral blood criteria (bone marrow cellularity <30%; reticulocytes <20×10 9 /L, platelets <20×10 9 /L, and neutrophils <0.5×10 9 /L) to define the severity of the condition. 1 The disease is termed severe when two out of three peripheral blood criteria are met, moderate if less than two are met, and very severe if the neutrophil count is below 0.2×10 9 /L. Severity has long been established as a prognostic criterion as it has been difficult to keep patients with severe neutropenia alive. The reticulocyte criterion will have to be re-evaluated as results of modern automated reticulocyte counters overestimate reticulocyte counts at low levels and do not, therefore, correlate well with manual counting results obtained by brilliant cresyl blue staining. Obviously, the diagnostic criteria established by Bruce Camitta were defined at a time when automated counters were not available. In a study published in this issue of the journal the reticulocyte criterion was set at 60×10 9 /L using an automated counting method. The diagnostic work-up includes testing for paroxysmal nocturnal hemoglobinuria by flow cytometry and cytogenetics and exclusion of hereditary marrow failure syndromes. This work-up is becoming increasingly complex as new hereditary forms are being identified and because the search for a hereditary form should no longer be limited to the pediatric age group. 2 The interpretation of clonal cytogenetic anomalies such as trisomy 8 and monosomy 7 is equally difficult as patients with a classical presentation of severe aplastic anemia and clonal hematopoietic anomalies should not be diagnosed as having a myelodysplastic syndrome based on the cytogenetic anomaly alone. Aplastic anemia is rare. The incidence is 1-2 new cases per million per year. It occurs in all age groups but is found more commonly among the young. The incidence is higher in south-east Asia and in poor countries; this may be due to viral infections and exposure to toxins.A series of studies in the past established that the combination of anti-thymocyte globulin (ATG) of horse origin, obtained by sensitizing horses with human lymphocytes or thymocytes, and cyclosporine A (CSA) is the standard treatment for aplastic anemia in patients not eligible for marrow transplantation.3 Results of transplantation and immunosuppression are roughly equivalent with graft-versus-host disease and graft failure being problems associated with transplantation and treatment failure, relapse and secondary clonal disorders such as myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria and leukemia being associated with immunosuppressive treatment. [4][5][6] Immunosuppression to treat severe aplastic anemia was initially pioneered by Georges Mathé and Bruno Speck among others. It is of interest that the first patients so treated received haploidentical marrow along with ATG and it took a...

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Acquired Aplastic Anaemia

Marsh

Young

2010

Postgraduate Haematology

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Cyclosporin A response and dependence in children with acquired aplastic anaemia: a multicentre retrospective study with long‐term observation follow‐up

Cited by 93 publications

References 29 publications

Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group

Immunosuppressive treatment for aplastic anemia: are we hitting the ceiling?

Acquired Aplastic Anaemia

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