Outcomes after induction failure in childhood acute lymphoblastic leukemia.

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.).

• Authors: Martin Schrappe, Stephen P Hunger, Ching-Hon Pui, Vaskar Saha, Paul S Gaynon, André Baruchel, Valentino Conter, Jacques Otten, Akira Ohara, Anne Birgitta Versluys, Gabriele Escherich, Mats Heyman, Lewis B Silverman, Keizo Horibe, Georg Mann, Bruce M Camitta, Jochen Harbott, Hansjörg Riehm, Sue Richards, Meenakshi Devidas, Martin Zimmermann
• Journal: The New England journal of medicine (N Engl J Med) Vol. 366 Issue 15 Pg. 1371-81 (Apr 12 2012) ISSN: 1533-4406 [Electronic] United States
• PMID: 22494120 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Fusion Proteins, bcr-abl

Topics

• Adolescent
• Age Factors
• Antineoplastic Agents (therapeutic use)
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Fusion Proteins, bcr-abl (genetics)
• Gene Rearrangement
• Humans
• Infant
• Kaplan-Meier Estimate
• Leukocyte Count
• Male
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, genetics, mortality, therapy)
• Prognosis
• Remission Induction
• Retrospective Studies
• Stem Cell Transplantation
• Survival Rate
• Treatment Failure
• Treatment Outcome