Despite improved prognosis in acute myelogenous leukaemia (AML) children with Down syndrome (DS), therapy-related toxicity remained a problem. We compared 67 DS patients from study AML-BFM 98 with 51 DS patients of the previous study AML-BFM 93, and the non-DS groups of both studies. Compared to non-DS patients, DS patients were treated with reduced anthracycline doses, without high-dose cytarabine/ mitoxantrone and without cranial irradiation. AML-DS patients were in median 1.8 years old, and 102/118 (86%) showed the typical morphology of acute megakaryoblastic leukaemia. In study 93, seven DS patients did not receive AML-specific chemotherapy, and treatment modifications were more common. Results improved significantly for patients treated in study 98 with a 3-year survival of 9174 vs 7077% in study 93 (P ¼ 0.001). There were no differences in outcome concerning the age groups 0-p2 and 2-p4 years (event-free survival for treated patients 0-p2 years 8374%, 2-p4 years 8177%). The cumulative incidence of relapses was significantly lower in DS (773%) than in non-DS patients (2877%). Therapy-related toxicity was generally lower in DS patients treated according to study 98. We conclude that a standardised and dose-reduced treatment schedule including the main components of AML treatment is advisable for AML children with DS.

In spite of a highly intensive and effective treatment, the frequency of anthracycline-associated cardiomyopathy was low in the AML-BFM studies.

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Background: Gemtuzumab ozogamicin (GO) is an immunoconjugate consisting of the CD33 antibody and calicheamicin, a potent cytotoxic agent. Developed for targeted treatment of CD33-positive AML, studies in adults showed its efficacy in relapsed and refractory AML. Patients and Method: We report 12 children with multiple relapsed or refractory AML receiving GO as compassionate use. 11 children had initially been treated according to the AML-BFM 93 or 98 protocol, 1 girl received relapse treatment (liposomal daunorubicin/FLAG) due to secondary AML. After relapse, 10 children received an intensive relapse therapy (AML-BFM 97 or international AML-Relapse Study 2001/01). 2 of them had been transplanted in first or second CR before GO therapy. Results: 5 of 12 children responded to treatment with blast reduction to below 5%, but no child achieved CR after GO. Time until reoccurrence of blasts in almost all children with GO response was 3–8 months. In 5 children stem cell transplantation (SCT) was performed after GO therapy. 4 of them suffered from further progression of AML, 1 boy is in second remission with a follow-up of 8 months. 2 children had severe side effects. An anaphylactic reaction with severe hypotension was managed by catecholamine support and intensive care. In 1 girl, who relapsed after SCT in first remission, a veno-occlusive disease of the liver occurred, but could be treated successfully with defibrotide. Conclusion: GO therapy can induce blast reduction in children who have no further conventional treatment options. Frequency and severity of adverse events are limited, and therapy seems to be feasible for children with a sufficient general condition. Controlled studies are necessary to learn more about efficacy and side effects, especially implications for further therapy.