Clinical relevance of serial quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation in children for severe aplastic anemia.
Allogeneic stem cell transplantation (allo-SCT) is a well-established treatment modality for children with severe aplastic anemia (SAA). Treatment failures are rare and mostly caused by graft rejection. Increasing mixed chimerism represents a stage at the very beginning of graft rejection, where immunological intervention might be an effective prophylactic approach. To substantiate this, we: (1) monitored peripheral blood cells from children with SAA after allo-SCT and performed pre-emptive immunotherapy in patients with increasing MC. In all, 23/34 courses of 32 children with SAA after allo-SCT showed a complete chimerism (CC) throughout and 10/34 developed different types of mixed chimerism (MC). Altogether, 4/10 with MC spontaneously developed decreasing MC, 2/10 courses persisted with low proportions of autologous cells below 30% (stable-MC), 4/10 developed increasing MC and one patient showed an autologous recovery. All patients with CC, decreasing MC or stable MC remained in continuous complete remission (CCR). In all, 2/4 patients with increasing MC developed graft rejection. Based on these observations, 2/4 new patients with increasing MC received low-dose DLIs prophylactically, and remained in CCR without any GVHD. These results substantiate that low-dose DLI in children with SAA and increasing MC can prevent graft rejection with a calculable risk to induce severe GVHD.
Hoelle
W
W
Department of Pediatric Hematology and Oncology, University Children's Hospital, Hoppe-Seyler-Strasse 1, D-72070 Tübingen, Germany.
Beck
J F
JF
Dueckers
G
G
Kreyenberg
H
H
Lang
P
P
Gruhn
B
B
Führer
M
M
Niethammer
D
D
Klingebiel
T
T
Bader
P
P
D000293:Adolescent; D000741:Anemia, Aplastic / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D006084:Graft Rejection / Q000188:drug therapy / Q000453:epidemiology / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000453:epidemiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D010641:Phenotype; D012307:Risk Factors; D012720:Severity of Illness Index; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents