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Outcomes after induction failure in childhood acute lymphoblastic leukemia. N Engl J Med 2012 Apr 12;366(15):1371-81

Date

04/13/2012

Pubmed ID

22494120

Pubmed Central ID

PMC3374496

DOI

10.1056/NEJMoa1110169

Abstract

BACKGROUND: Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL).

METHODS: We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients.

RESULTS: Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only.

CONCLUSIONS: Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche Krebshilfe and others.).

Author List

Schrappe M, Hunger SP, Pui CH, Saha V, Gaynon PS, Baruchel A, Conter V, Otten J, Ohara A, Versluys AB, Escherich G, Heyman M, Silverman LB, Horibe K, Mann G, Camitta BM, Harbott J, Riehm H, Richards S, Devidas M, Zimmermann M

Author

Bruce M. Camitta MD Clinical Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adolescent
Age Factors
Antineoplastic Agents
Child
Child, Preschool
Female
Follow-Up Studies
Fusion Proteins, bcr-abl
Gene Rearrangement
Humans
Infant
Kaplan-Meier Estimate
Leukocyte Count
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Remission Induction
Retrospective Studies
Stem Cell Transplantation
Survival Rate
Treatment Failure
Treatment Outcome
jenkins-FCD Prod-409 d1e206b0be345926047b0d9c353c78a4cce4058b