Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group

TY - JOUR

T1 - Use of allogeneic hematopoietic stem-cell transplantation based on minimal residual disease response improves outcomes for children with relapsed acute lymphoblastic leukemia in the intermediate-risk group

AU - Eckert, Cornelia

AU - Henze, Günter

AU - Seeger, Karlheinz

AU - Hagedorn, Nikola

AU - Mann, Georg

AU - Panzer-Grümayer, Renate

AU - Peters, Christina

AU - Klingebiel, Thomas

AU - Borkhardt, Arndt

AU - Schrappe, Martin

AU - Schrauder, André

AU - Escherich, Gabriele

AU - Sramkova, Lucie

AU - Niggli, Felix

AU - Hitzler, Johann

AU - von Stackelberg, Arend

PY - 2013/7/20

Y1 - 2013/7/20

N2 - PURPOSE: In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).PATIENTS AND METHODS: In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.RESULTS: The probability of event-free survival for patients with MRD ≥ 10(-3) was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10(-3) could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) -ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).CONCLUSION: Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.

AB - PURPOSE: In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).PATIENTS AND METHODS: In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.RESULTS: The probability of event-free survival for patients with MRD ≥ 10(-3) was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10(-3) could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) -ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).CONCLUSION: Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Child

KW - Child, Preschool

KW - Combined Modality Therapy

KW - Disease-Free Survival

KW - Female

KW - Hematopoietic Stem Cell Transplantation

KW - Humans

KW - Induction Chemotherapy

KW - Male

KW - Neoplasm, Residual

KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma

KW - Recurrence

KW - Risk Factors

KW - Transplantation, Homologous

KW - Treatment Outcome

U2 - 10.1200/JCO.2012.48.5680

DO - 10.1200/JCO.2012.48.5680

M3 - SCORING: Journal article

C2 - 23775972

VL - 31

SP - 2736

EP - 2742

JO - J CLIN ONCOL

JF - J CLIN ONCOL

SN - 0732-183X

IS - 21

ER -