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, A.C.
AU - Bierings, M.B.
AU - van Wering, E.R.
AU - Wijkhuis, A.J.
AU - de Weger, R.A.
AU - Wijnen, J.T.
AU - Vossen, J.M.
AU - Versluijs, A.B.
AU - Egeler, R.M.
AU - Tol, M.J.
AU - Putter, H.
AU - Révész, T.
AU - van Dongen, J.J.M.
AU - Velden van der, V.H.J.
AU - Schilham, M.W.
PY - 2010/8
Y1 - 2010/8
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
KW - pediatric
KW - acute lymphoblastic leukemia
KW - minimal residual disease
KW - allogeneic stem cell transplantation
KW - donor lymphocyte infusion
KW - BONE-MARROW-TRANSPLANTATION
KW - TIME QUANTITATIVE PCR
KW - VERSUS-HOST-DISEASE
KW - DONOR LEUKOCYTE INFUSIONS
KW - GENE REARRANGEMENTS
KW - T-CELLS
KW - EXTRAMEDULLARY RELAPSE
KW - LYMPHOCYTE INFUSION
KW - CHILDREN
KW - GRAFT
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 -