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Paediatric Leukemia

Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective

Summary:

Children with leukemias and increasing mixed chimerism (increasing MC) after allogeneic stem cell transplantation have the highest risk to relapse. Early immunological intervention was found to be effective in these cases. To substantiate this on a defined group of pediatric acute myelogenous leukemia (AML) patients, we performed serial analysis of post transplant chimerism and pre-emptive immunotherapy in patients with increasing MC. In total, 81 children were monitored, 62 patients revealed complete chimerism (CC), low-level MC or decreasing MC. Increasing MC was detected in 19 cases. Despite early immunological intervention relapse was still significantly more frequent in patients with increasing MC (9/19) than in patients with CC, low-level or decreasing MC (8/62, P<0.005). The probability of 3-year event-free survival (EFS) was 52% for all patients (n=81), 59% for patients with CC, low-level MC, 60% for patients with decreasing MC (n=62), and 28% for patients with increasing MC (n=19, P<0.005). Patients with increasing MC who received early immunological intervention showed a significantly enhanced probability for event-free survival (pEFS 36%, n=15) compared to patients with increasing MC without intervention (pEFS 0%, n=4, P<0.05). These results prove that pediatric AML patients with increasing MC are at highest risk for relapse and that early immunological intervention can prevent relapse in these patients.

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Acknowledgements

We thank all participating centers and all colleagues who included less than four patients in the study: Prof Dr W Holter, University Children's Hospital Erlangen; Prof Dr S Müller-Weihrich, University Children's Hospital München-Schwabing; Dr I Schmidt, München v Haunersches Kinderspital; Prof Dr C Bender-Götze, München-Poliklinik. This work was supported by the ‘Deutsche Krebshilfe’ (70-2178-Kl I)’, Bonn, Germany, the ‘Fortüne-Programm’ of the University of Tuebingen (925-0-0) and by the ‘Förderverein für Krebskranke Kinder Tübingen e.V.’, Tübingen, Germany. We are indebted to Nicole Ata for the critical reading of the manuscript and helpful suggestions.

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Bader, P., Kreyenberg, H., Hoelle, W. et al. Increasing mixed chimerism defines a high-risk group of childhood acute myelogenous leukemia patients after allogeneic stem cell transplantation where pre-emptive immunotherapy may be effective. Bone Marrow Transplant 33, 815–821 (2004). https://doi.org/10.1038/sj.bmt.1704444

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