Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial

The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16–60 years of age with newly diagnosed AML other than French–American–British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy

The calamitous perspective of modernity : Sebald's negative ontology

This essay argues that Sebald’s entire work is informed by a negative ontology which has gained particular force and visibility in ‘modernity’, a period beginning, according to Sebald, with Napoleon ‘at the latest’. In a secular echo of the Bible’s teaching that nature is ‘fallen’ Sebald repeatedly hints that Being is misconstructed and that humans, with their apparently limitless capacity to inflict suffering, are subsumed under this verdict too. As possible sources for this view, this essay makes use of Sebald’s papers in the Deutsches Literaturarchiv at Marbach am Neckar (DLA). It then discusses some of the ways in which this negative ontology appears in Sebald’s work and concludes by showing why the author finally considers that the task of art, particularly literature, is to engage in creative activity as a labour of mourning and a demonstration of solidarity with those who suffer