National study improves outcome for pediatric AML

December 13, 2005

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 AML 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 on December 12 in Atlanta, Georgia, by Jeffrey Rubnitz, M.D., Ph.D., an associate member 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 AML 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 (GO), 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 GO 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.

"Overall, the MRD and other laboratory studies gave us a extremely helpful insights into how well the course of therapy was helping each individual child," Rubnitz said. "These tools were key to the high overall remission rate and low treatment-related mortality."
-end-
The other researchers involved in this study include Bassem Razzouk, Stanley Pounds, Raul Ribeiro, Ching-Hon Pui, Elaine Coustan-Smith, Dario Campana and Shelly Lensing (St. Jude); Paul Bowman (Cook Children's Medical Center, Forth Worth, TX); Gary Dahl and Norman Lacayo (Stanford University Medical Center, Palo Alto, CA); Jeffrey Taub and Yaddanapudi Ravindranath (Children's Hospital of Michigan-Detroit); Soheil Meshinchi (Children's Hospital, Seattle, WA); and Gladstone Airewele (Texas Children's Cancer Center, Houston, TX).

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fund-raising organization. For more information, please visit www.stjude.org.

St. Jude Children's Research Hospital

Related Leukemic Cells Articles from Brightsurf:

New way to target some rapidly dividing cancer cells, leaving healthy cells unharmed
Scientists at Johns Hopkins Medicine and the University of Oxford say they have found a new way to kill some multiplying human breast cancer cells by selectively attacking the core of their cell division machinery.

Nutrient deficiency in tumor cells attracts cells that suppress the immune system
A study led by IDIBELL researchers and published this week in the American journal PNAS shows that, by depriving tumor cells of glucose, they release a large number of signaling molecules.

Scientists modify CAR-T cells to target multiple sites on leukemia cells
In a preclinical study, scientists engineer new CAR-T cells to attack three sites on leukemia cells, instead of one.

Drug that keeps surface receptors on cancer cells makes them more visible to immune cells
A drug that is already clinically available for the treatment of nausea and psychosis, called prochlorperazine (PCZ), inhibits the internalization of receptors on the surface of tumor cells, thereby increasing the ability of anticancer antibodies to bind to the receptors and mount more effective immune responses.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in M√ľnster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

Closer to identifying leukemic stem cells
Researchers at the Josep Carreras Leukaemia Research Institute have developed innovative diagnostic trials to identify cells resistant to leukemia treatment.

SIRT1 plays key role in chronic myeloid leukemia to aid persistence of leukemic stem cells
Patients with chronic myeloid leukemia are treated with tyrosine kinase inhibitors.

Dead cells disrupt how immune cells respond to wounds and patrol for infection
Immune cells prioritise the clearance of dead cells overriding their normal migration to sites of injury.

Genetically encoded sensor isolates hidden leukemic stem cells
Tel Aviv University researchers have devised a novel biosensor that can isolate and target leukemic stem cells.

Revealed: How the 'Iron Man' of immune cells helps T cells fight infection
The immune system's killer T cells are crucial in fighting viral infections.

Read More: Leukemic Cells News and Leukemic Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.