Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group.
OBJECTIVE
Minimal residual disease (MRD) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia (ALL) in retrospective analysis. To verify this, the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group conducted a prospective trial.


METHODS
Between March 1999 and July 2005, 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocols and receiving stem-cell transplantation in >or= second remission were enrolled. MRD quantification was performed by real-time polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements.


RESULTS
Probability of event-free survival (pEFS) and cumulative incidence of relapse (CIR) in 45 patients with MRD >or= 10(-4) leukemic cells was 0.27 and 0.57 compared with 0.60 and 0.13 in 46 patients with MRD less than 10(-4) leukemic cells (EFS, P = .004; CIR, P < .001). Intermediate-risk patients (strategic group S1) with MRD >or= 10(-4) leukemic cells (n = 14) had a pEFS of 0.20 and CIR of 0.73, whereas patients with MRD less than 10(-4) leukemic cells (n = 21) had a pEFS of 0.68 and CIR of 0.09 (EFS, P = .020; CIR, P < .001). High-risk patients (S3/4, third complete remission) who received transplantation with an MRD load of less than 10(-4) leukemic cells (n = 25) showed a pEFS and CRI of 0.53 and 0.18, respectively. In contrast, pEFS and CRI were 0.30 and 0.50 in patients who received transplantation with an MRD load of >or= 10(-4) leukemic cells. Multivariate Cox regression analysis revealed MRD as the only independent parameter predictive for EFS (P = .006).


CONCLUSIONS
MRD is an important predictor for post-transplantation outcome. As a result, new strategies with modified stem-cell transplantation procedures will be evaluated in ALL-BFM trials.
Bader
Peter
P
Children's Hospital of the JW Goethe University, Frankfurt, Main, Germany. peter.bader@kgu.de
Kreyenberg
Hermann
H
Henze
Günter H R
GH
Eckert
Cornelia
C
Reising
Miriam
M
Willasch
Andre
A
Barth
Andrea
A
Borkhardt
Arndt
A
Peters
Christina
C
Handgretinger
Rupert
R
Sykora
Karl-Walter
KW
Holter
Wolfgang
W
Kabisch
Hartmut
H
Klingebiel
Thomas
T
von Stackelberg
Arend
A
D000293:Adolescent; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D018365:Neoplasm, Residual / Q000401:mortality*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D012008:Recurrence; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous