[Relapse of childhood ALL, AML and MDS after allogeneic stem cell transplantation can be prevented by donor lymphocyte infusion in a critical stage of increasing mixed chimerism].
BACKGROUND
Mortality in children with acute leukemias or MDS after allogeneic stem cell transplantation (allo-SCT) is mostly determined by relapses. It was recently shown by us that patients who develop increasing quantities of autologous hematopoietic cells in peripheral blood (increasing mixed chimerism, in-MC) after allo-SCT do significantly more often relapse (P < 0.0001) than patients with a complete chimerism (CC). In a small series of patients with in-MC, the relapse rate could be significantly reduced by administration of donor lymphocytes (DLI).


METHODS
A prospective multicenter study was initiated under the question whether number of relapses can be significantly reduced either by withdrawal of post-transplant immunosuppression and/or by DLI in the critical stage of in-MC.


RESULTS
Highly repetitive determination of the genetic status of 114 children with acute leukemias or MDS (ALL: n = 41, AML: n = 39, MDS: n = 34) revealed 55 cases with CC and 43 with in-MC. Relapses occurred significantly (P < 0.0001) more often in patients with in-MC (25/43) than in patients with CC (12/55). In-MC-patients showed a significantly (P < 0.01) enhanced event free survival rate (11/24) when DLI was given and/or post-transplant immunosuppression was stopped compared to patients which did not receive such an interventional regimen (1/19). Two in-MC-patients developed fatal GVHD after immunological intervention.


CONCLUSIONS
These data substantiate that prophylactic immunotherapy on the basis of in-MC is a powerful treatment approach to suppress relapses of acute leukemias and MDS after allo-SCT.
Beck
J F
JF
Abteilung für Pädiatrische Hämatologie und Onkologie, Universitäts-Kinderklinik Greifswald, Germany. beck@uni-greifswald.de
Klingebiel
T
T
Kreyenberg
H
H
Schaudt
A
A
Wölle
W
W
Niethammer
D
D
Bader
P
P
D002423:Cause of Death; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000401:mortality / Q000517:prevention & control; D006801:Humans; D007116:Immunization, Passive; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D008297:Male; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013601:T-Lymphocytes / Q000637:transplantation; D018183:Transplantation Chimera
D007166:Immunosuppressive Agents