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17-04-2012 | General practice | Article

Induction failure occurs in a heterogeneous group of patients with ALL


Free abstract

MedWire News: Children with acute lymphoblastic leukemia (ALL) and remission-induction failure can be subdivided into groups that exhibit varied outcomes and may require tailored treatment strategies, study findings indicate.

Martin Schrappe (St Jude Children's Research Hospital, Memphis, Tennessee, USA) and colleagues explain that failure of remission-induction therapy is a rare, but highly adverse event in children and adolescents with ALL.

In the present study, Schrappe and team examined the outcomes in patients with ALL aged 0 to 18 years who had induction failure, to identify distinct patient subgroups with different outcomes, related to disease characteristics and treatments administered.

Induction failure, defined as the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, occurred in 1041 (2.4%) of 44,017 patients with newly diagnosed ALL who were treated by one of 14 cooperative study groups for Europe, North America, and Asia between 1985 and 2000.

Compared with an unselected pediatric population with ALL, the patients with induction failure had a greater number of unfavorable presenting features, including male gender, age older than 6 years at the time of diagnosis (median, 8.1 years), high leukocyte counts (median, 42×109 per liter), T-cell leukemia, central nervous system involvement, 11q23 chromosomal rearrangement, and the Philadelphia chromosome.

With a median follow-up period of 8.3 years, the 10-year survival rate was estimated at only 32% for patients with induction failure.

Patient subgroups with the worst outcomes included those aged 6 years or older with 25% or more blasts in the bone marrow (M3 marrow) at the end of induction therapy (10-year survival rate, 22%) and patients of any age with T-cell ALL and M3 marrow (10-year survival rate, 19%).

By contrast, 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. Together, these factors accounted for approximately 25% of all patients with induction failure and were associated with a 10-year survival rate above 50%, the researchers note.

A total of 198 patients underwent hematopoietic stem-cell transplantation, whereas 427 received chemotherapy only. The 10-year survival rate was 43% among patients who underwent transplantation, and 41% among patients who did not undergo transplantation.

However, the effect of transplantation on the outcome differed across major prognostic subgroups of patients. Furthermore, patients with T-cell leukemia appeared to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients with precursor B-cell leukemia without other adverse features appeared to have a better outcome with chemotherapy than with transplantation.

"The superiority of chemotherapy to stem-cell transplantation in this group at relatively favorable risk is striking and may substantially affect current practice, since stem-cell transplantation has generally been accepted as the preferred treatment for all cases of induction failure," notes editorialist Karin Rabin (Baylor College of Medicine, Houston, Texas, USA) in The New England Journal of Medicine.

She says that the study contributes "seminal information" about the previously unrecognized heterogeneity within this poor-risk subgroup of ALL.

"From this remarkable collaborative effort we learn that induction failure is not a single entity with a uniform prognosis but rather exhibits biologic and prognostic heterogeneity. It is possible that sophisticated risk stratification and risk-directed treatment may lead to improved outcomes," Rabin concludes.

By Laura Cowen

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