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AML SCT-BFM 2007 was the first hematopoietic stem cell transplantation (HCT) trial in Germany to comply with the European Clinical Trials Directive, and aimed to standardize pediatric HCT for acute myeloid leukemia (AML) across centers in Germany, Austria, and the Czech Republic. Children with high-risk features and a good early response achieving a complete first remission (CR-1) and those in CR-2 after a first relapse were stratified to receive HCT from a matched donor after myeloablative conditioning consisting of busulfan, cyclophosphamide, and melphalan. Four-year EFS and OS were 61 and 70%. Cumulative incidence of relapse (CIR) was 22%. TRM was 15% and correlated with age reaching 9% (SE 3%) in children younger than 12 years and 31% (SE 9%) in older children and adolescents. Children with poorly responding primary disease or relapse were allocated to receive early HCT after a cytoreductive regimen with fludarabine, amsacrine, and cytarabine, followed by reduced intensity conditioning and prophylactic donor lymphocyte infusions. Four-year EFS and OS were 49 and 53%. CIR was 38% and TRM 11%. For patients with primary poor response disease, early use of RIC HCT followed by prophylactic DLI can induce long-term remissions in more than 50% (EFS 46% (SE 9%)).

Juvenile myelomonocytic leukemia (JMML) is a clonal myeloproliferative disorder of early childhood. In all, 21 patients with JMML who received donor leukocyte infusion (DLI) after allogeneic hematopoietic stem cell transplantation (HSCT) for either mixed chimerism (MC, n = 7) or relapse (n = 14) were studied. Six patients had been transplanted from an HLA-matched sibling and 15 from other donors. Six of the 21 patients (MC: 3/7 patients; relapse: 3/14 patients) responded to DLI. Response rate was significantly higher in patients receiving a higher total T-cell dose (>= 1 x 10(7)/kg) and in patients with an abnormal karyotype. None of the six patients receiving DLI from a matched sibling responded. Response was observed in five of six patients who did and in one of 15 children who did not develop acute graft-versus-host disease following DLI (P = 0.01). The overall outcome was poor even for the responders. Only one of the responders is alive in remission, two relapsed, and three died of complications. In conclusion, this study shows that some cases of JMML may be sensitive to DLI, this providing evidence for a graft-versus-leukemia effect in JMML. Infusion of a high number of T cells, strategies to reduce toxicity, and cytoreduction prior to DLI may improve the results.

Immunoglobulin and T-cell receptor gene rearrangements as PCR-based targets are stable markers for monitoring minimal residual disease in acute lymphoblastic leukemia after stem cell transplantation