Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia - long-term results of trial ALL-REZ BFM P95/96.
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Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia - long-term results of trial ALL-REZ BFM P95/96. / Eckert, Cornelia; von Stackelberg, Arend; Seeger, Karl; Groeneveld, Tom W L; Peters, Christina; Klingebiel, Thomas; Borkhardt, Arndt; Schrappe, Martin; Escherich, Gabriele; Henze, Günter.
In: EUR J CANCER, Vol. 49, No. 6, 6, 2013, p. 1346-1355.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Minimal residual disease after induction is the strongest predictor of prognosis in intermediate risk relapsed acute lymphoblastic leukaemia - long-term results of trial ALL-REZ BFM P95/96.
AU - Eckert, Cornelia
AU - von Stackelberg, Arend
AU - Seeger, Karl
AU - Groeneveld, Tom W L
AU - Peters, Christina
AU - Klingebiel, Thomas
AU - Borkhardt, Arndt
AU - Schrappe, Martin
AU - Escherich, Gabriele
AU - Henze, Günter
N1 - Copyright © 2012 Elsevier Ltd. All rights reserved.
PY - 2013
Y1 - 2013
N2 - PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT).METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96. We assessed the prognostic value of minimal residual disease (MRD) after induction therapy quantified by PCR using leukaemia clone-specific T-cell receptor/immunoglobulin gene rearrangements.RESULTS: Molecular good responders (MRD < 10(-3), n=46) had a probability of event-free survival (pEFS) at 10 years of 76% standard error (SE) ± 6% and a cumulative incidence of second relapse (CIR) at 10 years of 21% SE ± 6%; pEFS of molecular poor responders (MRD ≥ 10(-3), n=34) at 10 years was 18% SE ± 7% and CIR 61% SE ± 9% (p<0.001). Cox regression analysis revealed MRD after induction to be the strongest independent prognostic parameter with a 6.6-fold increased risk (95% confidence interval 3.3-13.5, p<0.001) for molecular poor responders to suffer a subsequent adverse event compared to good responders.CONCLUSION: In patients with intermediate risk BM relapse of ALL, low MRD after induction is associated with an excellent long-term prognosis with conventional chemo-/radiotherapy whereas patients with insufficient response have an extremely poor prognosis. Therefore, in the subsequent trial ALL-REZ BFM 2002, MRD is used to allocate molecular good responders to conventional post-induction therapy and molecular poor responders to allogeneic HSCT.
AB - PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT).METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96. We assessed the prognostic value of minimal residual disease (MRD) after induction therapy quantified by PCR using leukaemia clone-specific T-cell receptor/immunoglobulin gene rearrangements.RESULTS: Molecular good responders (MRD < 10(-3), n=46) had a probability of event-free survival (pEFS) at 10 years of 76% standard error (SE) ± 6% and a cumulative incidence of second relapse (CIR) at 10 years of 21% SE ± 6%; pEFS of molecular poor responders (MRD ≥ 10(-3), n=34) at 10 years was 18% SE ± 7% and CIR 61% SE ± 9% (p<0.001). Cox regression analysis revealed MRD after induction to be the strongest independent prognostic parameter with a 6.6-fold increased risk (95% confidence interval 3.3-13.5, p<0.001) for molecular poor responders to suffer a subsequent adverse event compared to good responders.CONCLUSION: In patients with intermediate risk BM relapse of ALL, low MRD after induction is associated with an excellent long-term prognosis with conventional chemo-/radiotherapy whereas patients with insufficient response have an extremely poor prognosis. Therefore, in the subsequent trial ALL-REZ BFM 2002, MRD is used to allocate molecular good responders to conventional post-induction therapy and molecular poor responders to allogeneic HSCT.
KW - Humans
KW - Male
KW - Female
KW - Risk Factors
KW - Adolescent
KW - Prospective Studies
KW - Child
KW - Prognosis
KW - Risk Assessment
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Clinical Trials as Topic
KW - Child, Preschool
KW - Recurrence
KW - Hematopoietic Stem Cell Transplantation
KW - Gene Rearrangement
KW - Outcome Assessment (Health Care)/methods/statistics & numerical data
KW - Bone Marrow/pathology
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Immunoglobulins/genetics
KW - Induction Chemotherapy/methods
KW - Neoplasm, Residual/diagnosis
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/surgery
KW - Receptors, Antigen, T-Cell/genetics
KW - Humans
KW - Male
KW - Female
KW - Risk Factors
KW - Adolescent
KW - Prospective Studies
KW - Child
KW - Prognosis
KW - Risk Assessment
KW - Disease-Free Survival
KW - Proportional Hazards Models
KW - Clinical Trials as Topic
KW - Child, Preschool
KW - Recurrence
KW - Hematopoietic Stem Cell Transplantation
KW - Gene Rearrangement
KW - Outcome Assessment (Health Care)/methods/statistics & numerical data
KW - Bone Marrow/pathology
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Immunoglobulins/genetics
KW - Induction Chemotherapy/methods
KW - Neoplasm, Residual/diagnosis
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics/surgery
KW - Receptors, Antigen, T-Cell/genetics
U2 - 10.1016/j.ejca.2012.11.010
DO - 10.1016/j.ejca.2012.11.010
M3 - SCORING: Journal article
C2 - 23265714
VL - 49
SP - 1346
EP - 1355
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
IS - 6
M1 - 6
ER -