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Friday 31st March, 2006
A new test could give hospitals with limited resources an
affordable way to improve the outcome of ALL treatment.
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
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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).