Friday 31st March, 2006
Investigators at St. Jude Children's Research Hospital have developed a relatively simple and inexpensive test that identifies children with acute lymphoblastic leukemia (ALL) who have responded well enough to their first round of chemotherapy that they might be successfully treated with a much less aggressive follow-up treatment.
The new test could give hospitals with limited resources an affordable way to improve the outcome of ALL treatment for many children by reducing chemotherapy side effects.
A report on this new technique appears in the March pre-publication online issue of Blood.
The test measures minimal residual disease (MRD)--the small number of leukemic cells that survive after remission induction therapy. This measurement helps clinicians identify patients whose disease is highly responsive to chemotherapy and those who might be cured with milder and less toxic treatment.
The study found that the new test provides results that are acceptably close to those obtained with more complex and expensive MRD tests, which can be performed only at a few cancer centers worldwide. The new assay uses only one test tube with three probes that can distinguish leukemic cells from normal cells in the bone marrow of children with ALL taken after two weeks of chemotherapy, according to the paper's senior author, Dario Campana, M.D., Ph.D., a member of the St. Jude Hematology-Oncology and Pathology Departments.
The high cost and complexity of the more sophisticated MRD tests have impeded their use in countries with limited resources, Campana said. "That limited the number of children who could benefit from MRD assays," he said. "The test we developed will allow clinicians at institutions with limited resources to reliably identify children who could be spared the harsh side effects caused by intense chemotherapy."
The investigators used the new test to examine bone marrow cells collected from 380 children with B-lineage ALL 19 days after the beginning of remission induction therapy. In 211 patients (55.5 percent), the test determined that leukemic cells made up 0.01 percent or more of the cells in the sample. This result closely agreed with the results from the more expensive and complex tests, said Elaine Coustan-Smith, an associate scientist in the same departments and the paper's first author.
The researchers reported that among the patients with 0.01 percent or more of leukemic cells detected by the simplified test on day 19, the incidence of relapse was about 29 percent after 10 years; among patients with levels of leukemic cells lower than 0.01 percent, the incidence of relapse was about 5 percent. The results obtained using the simplified test more accurately predicted whose disease would relapse and whose would respond well to chemotherapy than did standard risk factors, such as age and the presence of certain mutations in the cancer cells.
The St. Jude International Outreach Program (IOP) is now implementing this new test at a partner institution in Brazil, according to the paper's co-author, Raul Ribeiro, M.D., a member of the Department of Hematology-Oncology and IOP director. The pilot project in Recife, Brazil, aims to identify children who have MRD levels lower than 0.01 percent on day 19 so they can be treated with therapy that is less intense than the standard treatment. Previously, 10 percent of the children in Recife receiving standard therapy suffered fatal infections because of immune system suppression caused by the aggressive treatment, Ribeiro noted. Therefore, in addition to improving supportive care for patients, investigators in Recife sought to reduce the intensity of treatment for a select group of patients.
"Clinicians have known since the 1970s that about 40 percent of children with ALL can be cured with less intense therapy," Ribeiro said. "The problem is identifying those children who will be cured with less intense treatment so you can avoid or lessen the complications caused by aggressive therapy. The new MRD test developed at St. Jude can be used to identify patients who might be cured with less intensive treatment approaches. This will decrease the toxicity and the cost of treatment. Hence, we anticipate that the use of our new technique will increase the number of children who can be treated, and reduce the number of children who suffer fatal infections."
The other authors of the paper include Patricia Stow, Yinmei Zhou, Ching-Hon Pui and Gaston Rivera (St. Jude) and Francisco Pedrosa (Instituto Materno-Infantil de Pernambuco, Recife, Brazil).
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