1. ¹University Children's Hospital, Tübingen, Germany
2. ²University Children's Hospital, Essen, Germany
3. ³University Children's Hospital, Duesseldorf, Germany
4. ⁴Hannover Medical School, Children's Hospital, Hannover, Germany
5. ⁵University Children's Hospital, Freiburg, Germany
6. ⁶University Children's Hospital, Münster, Germany
7. ⁷University Children's Hospital, Jena, Germany
8. ⁸St Jude Children's Research Hospital, Memphis, TN, USA
9. ⁹University Children's Hospital, Frankfurt, Germany
10. ¹⁰University Children's Hospital, Greifswald, Germany

Correspondence: Dr P Bader, Department of Pediatric Hematology and Oncology, University Children's Hospital, Hoppe-Seyler-Strae 1, D-72076 Tübingen, Germany. E-mail: peter.bader@med.uni-tuebingen.de

¹¹Authors contributed equally to this work.

Received 22 August 2003; Accepted 6 November 2003; Published online 1 March 2004.

Abstract

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.