Persons with acute lymphocytic leukemia often undergo a treatment regimen, consisting of an intensive initial course, intensive second course, and a long-term maintenance course of chemotherapy. This aggressive treatment approach is used to help prevent recurrences, or relapses, of the cancer. However, if doctors were able to determine more precisely the likelihood of a recurrence, then the more intensive treatments could be administered to persons at high risk, while others could be spared unnecessary treatments. Recently, Italian researchers reported that a sensitive test, called the polymerase chain reaction, may provide the ability to make this distinction.
Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a cancer characterized by the presence of too many white blood cells, called lymphocytes, in the blood and bone marrow. ALL is associated with a genetic cell abnormality in approximately 50% of cases. One of the most common of these abnormalities is a switching, or translocation, of 2 chromosomes: chromosome 4 and chromosome 11. This abnormality, referred to as t(4:11), is most common in infants with ALL who are younger than 1 year (70%), but also occurs in children and adults with ALL (5-10%). Persons with this form of ALL often have a very high white blood cell count, enlargement of the spleen and liver, and sometimes involvement of the brain and spinal column. Therapy for t(4:11)-associated ALL commonly includes chemotherapy that is more intensive than that used to treat other forms of ALL. In addition, improved outcomes have been reported using high-dose cytarabine (a chemotherapy), supported by an allogeneic stem cell transplantation, a procedure performed to help restore the young blood-producing cells in the bone marrow.
Even after therapy, small amounts of cancer cells may be left in the bone marrow, and may grow and cause a recurrence (return) of the cancer at some point. In the past, researchers have not been able to test for the presence of these remaining cancer cells and so could not precisely predict who was likely to have a recurrence and who was not. Now, emerging evidence suggests that a test called the polymerase chain reaction (PCR) is able to detect a small number of remaining leukemia cells—1 among a million normal bone marrow cells—in persons with t(4:11)-associated ALL. The PCR works by tracking the genetic cell abnormality associated with the cancer cells.
Researchers in Italy monitored 3 infants and 22 adults who were in remission after receiving treatment for t(4:11)-associated ALL. All patients had a PCR positive for leukemia cells before treatment; 44% had a PCR negative for these cells after treatment. Thirteen of the 14 patients who still had a positive PCR after treatment suffered a recurrence an average of 4 months later. Of the 11 patients who had a negative PCR after treatment, 5 developed a positive PCR and suffered a recurrence. All remaining patients who had a negative PCR after therapy are still in remission, up to 96 months later.
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These findings are important because they show that the PCR clearly identifies persons with t(4:11)-associated ALL who are currently in remission but are likely to have a recurrence later. For this reason, there is potential for using PCR results to determine which of these patients needs further treatment, perhaps with more intensive therapy and a stem cell transplant. Finally, this test may offer the same promise for persons with ALL with other types of genetic cell abnormalities. Individuals who have this type of disease may wish to talk with their doctor about the risks and benefits of the PCR test and of participating in a clinical trial in which promising new treatment approaches are being studied. Two sources of information on ongoing clinical trials include clinical trials listing services provided by the National Cancer Institute (cancer.gov) and eCancerTrials.com. eCancerTrials.com also performs personalized clinical trial searches on behalf of patients. (Blood, Vol 95, No 1, pp 96-101, 2000)
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