A serious complication of aplastic anemia (AA) is an evolution to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). In a previous nationwide retrospective study, development of MDS/AML with monosomy 7 was observed in a significant proportion (22%) of AA children who were treated with cyclosporine and G-CSF. In an examination of the risk factors for such malignant transformation, our previous prospective study suggested a close relationship between use of G-CSF and secondary MDS/AML in nonresponders to immunosuppressive therapy (IST). However, a recent nationwide survey showed a prominent decreased in incidence of secondly MDS/AML. Here, we attempt to address the question as to why the incidence of malignant transformation-monosomy 7 has recently decreased in Japan. Between 1988 and 2003, 60 patients (30 male, 30 female; median age, 9 years; range, 0–17 years) at two hospitals received IST consisting of antithymocyte globulin (ATG) and cyclosporine with or without G-CSF and survived more than 1 year after diagnosis of AA. Because 13 IST nonresponders received alternative donor BMT as salvage therapy, we evaluated the incidence of malignant transformation in the 47 patients who did not received BMT. Because all patients were enrolled in the prospective multicenter study since 1993, which was the year that the Japan Marrow Donor Program was established, we compared the incidence of MDS/AML among children who were diagnosed between 1988 and 1992 (group A: n=27, with all but one receiving G-CSF), and those who were diagnosed between 1993 and 2003 (group B: n=20, with 12 receiving G-CSF). MDS with monosomy 7 was observed in 7 of the 27 patients (26%) in group A, and all of these received G-CSF, with the evolution occurring between 17 and 102 months after diagnosis, while no of the 20 patients in group B developed MDS/AML during the follow up of 1 to 11 years (median of 6 years; p=0.014). The response rate to IST did not differ significantly between group A and group B (50% vs 60%, p=). Three of 14 (21%) IST nonresponderss in group A and 10 of 12 (83%) non responders in group B received BMT from an alternative donor (p<0.01). The duration of G-CSF therapy was significantly longer in group A than in group B (186 days vs 56 days, p<0.01).

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