Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline-and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n ¼ 17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P ¼ 0.002) at the end of treatment. The mean number of fusion transcript copies/ ABLx10 4 also differed between relapsed and non-relapsed patients: 2385 vs 122 (P ¼ 0.001) after induction, 56 vs 7.6 after intensification (P ¼ 0.0001) and 75 vs 3.3 (P ¼ 0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level 40.1% at the end of treatment than in patients with p0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P ¼ 0.03), respectively. Likewise, using RQ-PCR, a cutoff level of 410 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR 410 compared to 21% for patients with RQ-PCR levels p10 (P ¼ 0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.
We investigated prospectively factors influencing the safety of hematopoietic stem cell (HSC) collection in 453 pediatric donors. The children in the study donated either BM or peripheral blood stem cells (PBSCs) according to center policy. A large variability in approach to donor issues was observed between the participating centers. Significant differences were observed between BM and PBSC donors regarding pain, blood allotransfusion, duration of hospital stay, and iron supplementation; however, differences between the groups undergoing BM vs PBSC donation preclude direct risk comparisons between the 2 procedures. The most common adverse event was pain, reported mainly by older children after BM harvest, but also observed after central venous catheter (CVC) placement for PBSC collection. With regard to severe adverse events, one patient (0.7%) developed a pneumothorax with hydrothorax after CVC placement for PBSC collection.The risk of allotransfusion after BM harvest was associated with a donor age of < 4 years and a BM harvest volume of > 20 mL/kg. Children < 4 years were at higher risk than older children for allotransfusion after BM harvest and there was a higher risk of complications from CVC placement before apheresis. We conclude that PBSC and BM collection are safe procedures in children. (Blood. 2012; 119(12):2935-2942)
This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease.
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