An international study published in the April 12 issue of the New England Journal of Medicine reports that bone marrow transplants are not the best option for some young patients with acute lymphoblastic leukemia (ALL) who fail to achieve clinical remission following their induction therapy of intense chemotherapy.
The largest study to-date of these pediatric ALL patients revealed that a subset of 72% young children who received additional chemotherapy instead of bone marrow transplantation achieved 10-year survival rates. These patients belong to the group of 85% of children with ALL, whose cancer starts in white blood cells and is destined to become B cells.
Ching-Hon Pui, M.D., chair of the St. Jude Children’s Research Hospital Department of Oncology said:
“Induction failure is a rare event, affecting just 2 to 3 percent of all pediatric ALL patients. But these children are at very high risk for a bad outcome and were always considered candidates for bone marrow transplantation. These results tell us that induction failure should no longer be considered an automatic indication for a transplant.”
Improvements in both chemotherapy and transplantation led the researchers to re-investigate which care is optimal for these patients, however no single institution or nation had sufficient numbers of patients.
First author, Martin Schrappe, M.D., of the University Medical Center Schleswig-Holstein in Kiel, Germany commented:
“This study shows the importance of international collaboration to advance the treatment outcome for these patients.”
Researchers analyzed the outcomes of 44,017 ALL patients, aged 17 years or below, whose cancer was diagnosed during a 15-year period, which ended in December 2000. Each patient was treated on a clinical trial at one of the centers that participated in this international collaborative analysis, which included patients from St. Jude.
The researchers monitored 1,041 patients whose cancer failed to go into remission after a 4 to 6-week induction therapy. The prognosis for patients who fail to respond to induction therapy is usually very bleak.
The findings revealed that whilst the overall long-term survival for childhood ALL patients increased to 80% during the 15-year study period, the survival for those who failed remission after intense induction therapy was just 32%. The researchers point out that the definition of induction failure was slightly different amongst the clinical trials in this analysis.
The findings revealed that some young patients with B-lineage ALL who were treated with additional chemotherapy after their induction therapy failed, had a 72% rate of long-term survival. These patients were aged between 1 to 5 years when their cancer was diagnosed, with many children observed to have over 50 chromosomes in their leukemia cells, instead of the normal 46.
Overall, this applied to 25% of these children whose disease failed to go into remission after induction therapy. None of the children who benefited from additional chemotherapy had any other high-risk markers, such as high white blood cell counts or chromosomal rearrangements involving the MLL gene.
According to the results, for many young ALL patients who fail induction therapy, transplants represent the best hope, including for those whose cancer originated in white blood cells, known as T cells. Although 12 to 15% of childhood ALL consists of T cell ALL, only 38% of patients in the study suffered from T cell ALL. For the transplant, the patient’s own diseased bone marrow is killed before being replaced with blood-producing stem cells from a genetically matched donor.
Transplants expose the patients to various immediate risks and chronic health problems. About 13% of ALL induction failures involved patients who had a genetic alteration known as Philadelphia chromosome. Due to the fact that new drugs achieved a dramatic improvement in patients with this chromosomal rearrangement, these patients were not included in the analysis.
Written By Petra Rattue