Outcomes after late bone marrow and very early central nervous system relapse of childhood B-acute lymphoblastic leukemia: a report from the Children's Oncology Group phase III study AALL0433.
Journal
Haematologica
ISSN: 1592-8721
Titre abrégé: Haematologica
Pays: Italy
ID NLM: 0417435
Informations de publication
Date de publication:
01 01 2021
01 01 2021
Historique:
aheadofprint:
30
01
2020
received:
03
09
2019
accepted:
24
01
2020
pubmed:
1
2
2020
medline:
22
5
2021
entrez:
1
2
2020
Statut:
epublish
Résumé
Outcomes after relapse of childhood B-acute lymphoblastic leukemia (B-ALL) are poor, and optimal therapy is unclear. Children's Oncology Group study AALL0433 evaluated a new platform for relapsed ALL. Between March 2007 and October 2013 AALL0433 enrolled 275 participants with late bone marrow or very early isolated central nervous system (iCNS) relapse of childhood B-ALL. Patients were randomized to receive standard versus intensive vincristine dosing; this randomization closed due to excess peripheral neuropathy in 2010. Patients with matched sibling donors received allogeneic hematopoietic cell transplantation (HCT) after the first three blocks of therapy. The prognostic value of minimal residual disease (MRD) was also evaluated in this study. The 3-year event free and overall survival (EFS/OS) for the 271 eligible patients were 63.6% +/- 3.0% and 72.3% +/- 2.8% respectively. MRD at the end of Induction-1 was highly predictive of outcome, with 3-year EFS/OS of 84.9 +/- 4.0% and 93.8 +/- 2.7% for patients with MRD <0.1%, vs. 53.7 +/- 7.8% and 60.6 +/- 7.8% for patients with MRD ≥0.1% (p<0.0001). Patients who received HCT vs. chemotherapy alone had an improved 3-year disease-free survival (77.5 +/- 6.2% vs. 66.9 +/- 4.5%, p=0.03) but not OS (81.5 +/- 5.8% for HCT vs. 85.8 +/- 3.4% for chemotherapy, p=0.46). Patients with early iCNS relapse fared poorly, with a 3-year EFS/OS of 41.4% +/- 9.2% and 51.7% +/- 9.3%, respectively. Infectious toxicities of the chemotherapy platform were significant. The AALL0433 chemotherapy platform is efficacious for late bone marrow relapse of B-ALL, but with significant toxicities. The MRD threshold of 0.1% at the end of Induction-1 was highly predictive of outcome. The optimal role for HCT for this patient population remains uncertain. This trial is registered at clinicaltrials.gov (NCT# 00381680).
Identifiants
pubmed: 32001530
doi: 10.3324/haematol.2019.237230
pmc: PMC7776266
doi:
Banques de données
ClinicalTrials.gov
['NCT00381680']
Types de publication
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
46-55Subventions
Organisme : NCI NIH HHS
ID : U24 CA196173
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA098413
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA098543
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180899
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180886
Pays : United States
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