Chemokine receptor/ligand interactions orchestrate the migration of cells to peripheral tissues such as the skin. We analysed chemokine receptor expression by acute myeloid leukaemic (AML) cells... Show moreChemokine receptor/ligand interactions orchestrate the migration of cells to peripheral tissues such as the skin. We analysed chemokine receptor expression by acute myeloid leukaemic (AML) cells present in peripheral blood (n = 7), bone marrow (n = 6), or skin (n = 11) obtained from 15 paediatric AML patients with skin involvement and in 10 AML patients without skin involvement. High percentages of circulating CCR2(pos) AML cells were only detected in patients with extramedullary disease. Skin-residing AML cells displayed a different set of receptors in situ, namely: CCR5, CXCR4, CXCR7 and CX3CR1. These results suggest the involvement of different chemokine/chemokine receptor interactions in homing and retention of AML blasts in the skin. Pediatr Blood Cancer 2010;55:344-348. (C) 2010 Wiley-Liss, Inc. Show less
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 ... Show moreRelapse 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 Show less
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 ... Show moreRelapse 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 >or=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 >or=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. Show less
Lankester, A.C.; Bierings, M.; Wering, E. van; Wijkhuis, A.; Weger, R. de; Wijnen, J.; ... ; Schilham, M. 2010
