A new strategy for treating childhood acute myeloid leukemia ( AML ) based on the individual patient's risk of failure, and guided by the results of a highly sensitive technique for identifying leukemic cells, yielded one-year survival rates of almost 90 percent, according to investigators at St. Jude Children's Research Hospital and a national consortium of research Institutes.

The ongoing clinical trial, called AML02, also found that almost 77 percent of survivors were free of leukemia one year from diagnosis. AML02 was the first to use minimal residual disease ( MRD ) measurements in a study of acute myeloid leukemia treatments to make accurate assessments of treatment response for each child, and to adjust treatment accordingly, the researchers reported.

MRD is the tiny but still potentially troublesome population of leukemic cells remaining after the initial phase of chemotherapy ( induction therapy ) is completed.
These cells can replenish the population of leukemic cells and thwart the treatment.
Using flow cytometry, researchers identified abnormal combinations of proteins that appear only on the surface of leukemic cells. This allowed the investigators to quickly and accurately determine the percentage of such cells in bone marrow samples.
Doctors used MRD measurements made after induction to determine if the treatment was eliminating enough leukemic cells to ensure a high probability of success. Based on that information, the doctors modified the intensity of treatment to avoid unnecessary therapy.

Until now, researchers had to rely on the less-accurate technique of microscopic examination to determine which cells in a child's blood sample were leukemic.

A report on these findings was presented at the 47th Annual Conference of the American Society of Hematology in Atlanta, by Jeffrey Rubnitz, of the St. Jude Department of Hematology-Oncology.
AML02 is the first multi-institutional study of a specific St. Jude investigational protocol, according to Rubnitz.

" The future will show if there is a long-term benefit to our being able to identify slow responders and the effect of intensifying therapy for such patients," he said. " But the results of this study are very encouraging because MRD helped us to more accurately assess and re-design therapy for individual children. And the high rate of remission we achieved at one year reflects that achievement."

The multi-center AML02 trial randomly assigns patients to receive either high- or low-dose treatment with Cytarabine ( A ), Daunorubicin ( D ), and Etoposide ( E ) as induction therapy.

After treatment with either high- or low-dose Cytarabine, the researchers measured the drug's level to determine its fate in the body. Such information might help doctors optimize their use of Cytarabine to treat acute myeloid leukemia in the future.

In addition, the researchers identified the patterns of gene activities linked to either success or failure of treatment in each child. This helped them identify children whose leukemic cells carried mutations that put them at high or low risk of failure, or who could be considered at "standard" risk--information that guided the researchers in determining how aggressively to treat each child.

Patients found to have no response to ADE during induction therapy were subsequently treated with low-dose ADE plus Gemtuzumab ozogamicin, while all others received just ADE during the second stage of treatment.
Before receiving the final phase of chemotherapy ( consolidation therapy ) or being given a stem cell transplant, patients were given Gemtuzumab ozogamicin as a single agent if MRD found that 0.1 percent of their bone marrow samples were leukemic.

MRD was able to identify with a significant level of accuracy whether treatment would succeed or fail, allowing the doctors to modify treatment to increase the chance of success.

Among the 112 patients enrolled since October 2002, four died from infections that occurred during or after completion of chemotherapy.

Source: St. Jude Children's Research Hospital, 2005


XagenaMedicine2005