Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia

Viollier, Romaine; Passweg, Jakob; Gregor, Michael; Favre, Geneviève; Kühne, Thomas; Nissen, C; Gratwohl, Aloïs; Thewis, André

doi:10.1007/s00277-004-0930-3

Cited by 48 publications

(43 citation statements)

References 35 publications

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“…3,4 The molecular target of this T-cell response is still unknown, although in vitro a T-cell-mediated inhibition of aneuploid hematopoietic cells was demonstrated in patients with myelodysplastic syndrome. 5 Immunosuppressive therapy (IST) 6 seems to be the appropriate treatment for an autoimmune disease, but tissue replacement by bone marrow transplantation (BMT) is still the treatment of first choice 7,8 because there have been 20% to 30% IST nonresponders, a significant proportion of patients with subnormal blood counts 9 and a high risk of relapse 10,11 and clonal disease. 12,13 Because of the long latency of response to IST, identification of predictors of response and survival would be helpful to assign patients to the appropriate regimen.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival

Führer¹

2005

Blood

161

126

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IntroductionA more severe form of a given disease negatively affects outcome in almost all human diseases. This seemed likely to apply to severe acquired aplastic anaemia (SAA), the pathophysiology of which is characterized by immune-mediated bone marrow failure. 1 A predominant oligoclonal immune response 2 by autologous T lymphocytes was shown to cause excessive apoptosis in stem and progenitor cells. 3,4 The molecular target of this T-cell response is still unknown, although in vitro a T-cell-mediated inhibition of aneuploid hematopoietic cells was demonstrated in patients with myelodysplastic syndrome. 5 Immunosuppressive therapy (IST) 6 seems to be the appropriate treatment for an autoimmune disease, but tissue replacement by bone marrow transplantation (BMT) is still the treatment of first choice 7,8 because there have been 20% to 30% IST nonresponders, a significant proportion of patients with subnormal blood counts 9 and a high risk of relapse 10,11 and clonal disease. 12,13 Because of the long latency of response to IST, identification of predictors of response and survival would be helpful to assign patients to the appropriate regimen.In children very SAA (vSAA) is predominant (Ͼ 60%). Patients with vSAA are especially prone to develop life-threatening infections. As most of those high-risk patients lack an HLA-identical sibling donor (matched sibling donor; MSD), searching for a matched unrelated donor (MUD) was recommended, despite that BMT from a MUD is still complicated by a high risk of graft rejection and graft-versus-host disease. This recommendation was well founded on the basis of a previous retrospective analysis 14 in which the outcome for children with vSAA was the worst with IST consisting of antithymocyte-globulin (ATG) plus androgens and/or steroids (probability of survival: vSAA, 37%; SAA, 56%).Combined IST with ATG and cyclosporin A (CSA) has been shown to be superior to ATG alone or in combination with androgens in adults, 15,16 and the addition of granulocyte colonystimulating factor (G-CSF) to the treatment regimen was able to improve granulocyte recovery. 17,18 We conducted a prospective multicenter trial comparing combined IST plus G-CSF and BMT 19 to identify prognostic factors for response to therapy and survival. Study designTwo hundred and thirteen patients newly diagnosed with SAA younger than the age of 17 years in 53 centers in Germany and Austria were included in A complete list of the members of the German/Austrian Aplastic Anemia Working Group appears in the "Appendix."Supported by the Friedrich-Baur-Stiftung (43/98), the Wilhelm-Sander-Stiftung (97.080.1), the Dr Sepp und Hanne Sturm Gedä chtnisstiftung, and AMGEN Germany.M.F., U.R., C.N., G.J.-S., W.F., A.B., and C.B.-G. conceived the study, designed the approach, and interpreted the data. M.F. wrote the paper. A.F. performed and interpreted the statistical analysis. I.B. reviewed the bone marrow biopsies to establish the correct diagnosis. 20 Zytogenetics and/or fluorescence in situ hybridization (FISH) analysis for...

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Section: Introductionmentioning

confidence: 99%

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival

Führer¹

2005

Blood

161

126

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“…Transplanted patients spent more time in complete remission without drugs and had longer periods free from symptoms (as well as time with extensive chronic GVHD). 38 …”

Section: Quality-of-life Issues In Aplastic Anemiamentioning

confidence: 99%

Making Therapeutic Decisions in Adults with Aplastic Anemia

Marsh¹

2006

Hematology

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The management of adults presenting with aplastic anemia (AA) requires careful exclusion of other causes of bone marrow failure. Late-onset inherited forms of AA may present in adulthood with subclinical disease. Recent long-term studies of HLA identical sibling donor BMT show excellent survival for patients under the age of 40 years, but chronic graft-versushost disease (GVHD) is still a major problem, impacting on quality of life. Recent improvements in outcome after matched unrelated donor BMT may reflect better donor matching and use of reduced intensity conditioning regimens. For patients treated with immunosuppressive therapy (IST), antithymocyte globulin (ATG) and cyclosporin (CSA) remain the standard regimen with excellent overall survival but less impressive failure-free survival due to nonresponse, relapse and later clonal disorders. The benefit of adding granulocyte colony-stimulating factor (G-CSF) to ATG and CSA is unclear and being assessed in a further prospective European study. Patients who are refractory to conventional IST and currently ineligible for BMT represent difficult management problems. For these patients, new approaches to transplantation are being evaluated, such as fludarabine-based conditioning regimens and the potential use of double umbilical cord blood transplants, but there is a need for new immunosuppressive agents. Improved supportive care is likely to be a major factor in improved outcome of all AA patients whether treated with IST or BMT. Robust predictive factors for response to IST are needed to help in decision making at diagnosis and to help justify exploring novel approaches to therapy.

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“…[3][4][5][6] However, up to 40% of patients eventually relapse, and an additional 10% to 40% develop a secondary clonal disease. 3,4,7,8 Additional immunosuppressive drugs have been added to the ATG/CsA platform with hopes of decreasing relapse and secondary clonal disease, but so far no improvement in outcome has been observed.…”

Section: Introductionmentioning

confidence: 99%

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

Brodsky

Chen

Dorr³

et al. 2010

Blood

105

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Severe aplastic anemia (SAA) is a lifethreatening bone marrow failure disorder that can be treated with bone marrow transplantation, immunosuppressive therapy, and high-dose cyclophosphamide. Here, we report long-term follow-up on 67 SAA patients (44 treatment-naive and 23 refractory) treated with high-dose cyclophosphamide. At 10 years, the overall actuarial survival was 88%, the response rate was 71% with the majority being complete, and the actuarial event-free survival was 58% in 44 treatmentnaive SAA patients. Patients with refractory SAA fared less well after high-dose cyclophosphamide therapy; at 10 years, overall actuarial survival, response, and actuarial event-free survival rates were 62%, 48%, and 27%, respectively. High-dose cyclophosphamide is highly effective therapy for severe aplastic anemia. Large randomized controlled trials will be necessary to establish how results of high-dose cyclophosphamide compare with either bone marrow transplantation or standard immunosuppressive regimens, such as antithymocyte globulin and cyclosporine. (Blood. 2010;

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Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia

Cited by 48 publications

References 35 publications

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival

Making Therapeutic Decisions in Adults with Aplastic Anemia

High-dose cyclophosphamide for severe aplastic anemia: long-term follow-up

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