TY - JOUR
T1 - Efficacy and toxicity of high-risk therapy of the Dutch Childhood Oncology Group in childhood acute lymphoblastic leukemia
AU - van Binsbergen, Annelien L.
AU - de Haas, Valérie
AU - van der Velden, Vincent H.J.
AU - de Groot-Kruseman, Hester A.
AU - Fiocco, Marta F.
AU - Pieters, Rob
N1 - Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2022/2
Y1 - 2022/2
N2 - Background: Children with acute lymphoblastic leukemia (ALL) and high-risk (HR) features have a poor outcome and are treated with HR blocks, often followed by allogenic stem cell transplantation (SCT). Procedure: This article analyses the outcomes of children treated with HR blocks between 2004 and 2017 according to DCOG ALL10/11 protocols. 1297 patients with newly diagnosed ALL were consecutively enrolled, of which 107 met the HR criteria (no complete remission; minimal residual disease (MRD) > 10–3 after consolidation; “MLL-AF4” translocation and in ALL-10 also poor prednisone response). Patients were treated with one induction and consolidation course followed by three HR chemotherapy blocks, after which they received either SCT or further chemotherapy. MRD levels were measured at end of induction, consolidation, and after each HR block. Results: At five years, the event-free survival was 72.8% (95% CI, 64.6-82.0), and the cumulative incidence of relapse was 13.0% (95% CI, 6.3-19.8). Patients with only negative or low-positive MRD levels during HR blocks had a significantly lower five-year cumulative incidence of relapse (CIR) of 2.2% (95% CI, 0-6.6) compared with patients with one or more high-positive MRD levels (CIR 15.4%; 95% CI, 3.9-26.9). During the entire treatment protocol, 11.2% of patients died due to toxicity. Conclusions: The high survival with HR blocks seems favorable compared with other studies. However, the limit of treatment intensification might have been reached as the number of patients dying from leukemia relapse is about equal as the number of patients dying from toxicity. Patients with negative or low MRD levels during HR blocks have lower relapse rates.
AB - Background: Children with acute lymphoblastic leukemia (ALL) and high-risk (HR) features have a poor outcome and are treated with HR blocks, often followed by allogenic stem cell transplantation (SCT). Procedure: This article analyses the outcomes of children treated with HR blocks between 2004 and 2017 according to DCOG ALL10/11 protocols. 1297 patients with newly diagnosed ALL were consecutively enrolled, of which 107 met the HR criteria (no complete remission; minimal residual disease (MRD) > 10–3 after consolidation; “MLL-AF4” translocation and in ALL-10 also poor prednisone response). Patients were treated with one induction and consolidation course followed by three HR chemotherapy blocks, after which they received either SCT or further chemotherapy. MRD levels were measured at end of induction, consolidation, and after each HR block. Results: At five years, the event-free survival was 72.8% (95% CI, 64.6-82.0), and the cumulative incidence of relapse was 13.0% (95% CI, 6.3-19.8). Patients with only negative or low-positive MRD levels during HR blocks had a significantly lower five-year cumulative incidence of relapse (CIR) of 2.2% (95% CI, 0-6.6) compared with patients with one or more high-positive MRD levels (CIR 15.4%; 95% CI, 3.9-26.9). During the entire treatment protocol, 11.2% of patients died due to toxicity. Conclusions: The high survival with HR blocks seems favorable compared with other studies. However, the limit of treatment intensification might have been reached as the number of patients dying from leukemia relapse is about equal as the number of patients dying from toxicity. Patients with negative or low MRD levels during HR blocks have lower relapse rates.
KW - Child
KW - Disease-Free Survival
KW - Hematopoietic Stem Cell Transplantation
KW - Humans
KW - Neoplasm, Residual/diagnosis
KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis
KW - Prognosis
KW - Recurrence
KW - Remission Induction
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85117123974&partnerID=8YFLogxK
U2 - 10.1002/pbc.29387
DO - 10.1002/pbc.29387
M3 - Article
C2 - 34648216
AN - SCOPUS:85117123974
SN - 1545-5009
VL - 69
SP - e29387
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 2
M1 - e29387
ER -