TY - JOUR
T1 - Preemptive alloimmune intervention in high-risk pediatric acute lymphoblastic leukemia patients guided by minimal residual disease level before stem cell transplantation
AU - Lankester, AC
AU - Bierings, MB (Marc)
AU - van Wering, ER
AU - Wijkhuijs, Annemarie
AU - de Weger, RA
AU - Wijnen, JT
AU - Vossen, JM
AU - Versluys, B
AU - Egeler, RM
AU - van Tol, MJD
AU - Putter, H
AU - Revesz, T
AU - Dongen, Jacques
AU - van der Velden, Vincent
AU - Schilham, MW (Marco)
PY - 2010
Y1 - 2010
N2 - Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level >= 1 x 10(-4) were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n = 1-4). The intervention was associated with graft versus host disease >= grade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells. Leukemia (2010) 24, 1462-1469; doi:10.1038/leu.2010.133; published online 10 June 2010
AB - Relapse of pediatric acute lymphoblastic leukemia (ALL) remains the main cause of treatment failure after allogeneic stem cell transplantation (alloSCT). A high level of minimal residual disease (MRD) before alloSCT has been shown to predict these relapses. Patients at risk might benefit from a preemptive alloimmune intervention. In this first prospective, MRD-guided intervention study, 48 patients were stratified according to pre-SCT MRD level. Eighteen children with MRD level >= 1 x 10(-4) were eligible for intervention, consisting of early cyclosporine A tapering followed by consecutive, incremental donor lymphocyte infusions (n = 1-4). The intervention was associated with graft versus host disease >= grade II in only 23% of patients. Event-free survival in the intervention group was 19%. However, in contrast with the usual early recurrence of leukemia, relapses were delayed up to 3 years after SCT. In addition, several relapses presented at unusual extramedullary sites suggesting that the immune intervention may have altered the pattern of leukemia recurrence. In 8 out of 11 evaluable patients, relapse was preceded by MRD recurrence (median 9 weeks, range 0-30). We conclude that in children with high-risk ALL, immunotherapy-based regimens after SCT are feasible and may need to be further intensified to achieve total eradication of residual leukemic cells. Leukemia (2010) 24, 1462-1469; doi:10.1038/leu.2010.133; published online 10 June 2010
U2 - 10.1038/leu.2010.133
DO - 10.1038/leu.2010.133
M3 - Article
C2 - 20535148
SN - 0887-6924
VL - 24
SP - 1462
EP - 1469
JO - Leukemia
JF - Leukemia
IS - 8
ER -