Improving Long-term Outlook for Children with Acute Lymphoblastic Leukemia
For children battling Acute Lymphoblastic Leukemia, post-treatment testing that measures the amount of leftover disease cells in the bloodstream or bone marrow can provide critical clues to their long-term prognosis. Now a new test calle Flow Cytometry can better detect residual disease after treatment to better anticipate relapses.
Plainview, NY (PRWEB) September 27, 2006
For children battling Acute Lymphoblastic Leukemia, post-treatment testing that measures the amount of leftover disease cells in the bloodstream or bone marrow can provide critical clues to their long-term prognosis. That’s because numerous medical studies have confirmed that the greater the amount of residual leukemic cells in blood and bone marrow, the more likely is the risk of leukemia to relapse after remission. Fortunately, a laboratory technique called Flow Cytometry is able to detect minimal residual disease (MRD) more accurately than previous tests, giving doctors and patients the information they need to predict and manage their future health care needs.
“Acute Lymphoblastic Leukemia is the most commonly diagnosed childhood malignancy, accounting for nearly a quarter of all childhood malignancies diagnosed each year in the U. S.,” notes Dr. Kambiz Merati M. D., a NY-area hematopathologist with Acupath Laboratories. “While the ‘cure rate’ [percentage of patients who remain disease-free for five years after treatment] has risen dramatically over the past two decades, Acute Lymphoblastic Leukemia also has a fairly high recurrence rate of about 20 percent,” Dr. Merati adds. “For these children, it is imperative that we find better ways to anticipate relapses, so they are more likely to be re-diagnosed early and treated successfully.”
For years the standard test used to detect minimal residual disease after patients have completed treatment has been the polymerase chain reaction, or PCR, test. It identifies residual leukemia cells by searching for rearranged genes in the blood, which could develop into full-fledged leukemia again. Although its detection sensitivity is very high, PCR cannot detect a certain proportion of recurrent ALLs.
“Most cases of Acute Lymphoblastic Leukemia are comprised of very immature B - or T-cells. Since these leukemic cells are in a very primitive state, the gene rearrangements that are subject to detection by PCR might not have happened in them yet. Therefore, they might not be detectable by this technique” Dr. Merati explains. “Flow Cytometry, on the other hand, successfully identified MRD in almost all cases in a recent study,” he adds. According to this and similar studies, PCR fails to work in about 10% of cases with minimal residual disease, while the Failure rate of the Flow Cytometry is only 3%.1 “Interestingly,” Dr. Merati comments, “this makes Flow Cytometry particularly valuable for infants with ALL, where up to 40% of cases do not show the gene rearrangement detectable by PCR.”
Flow Cytometry identifies and sorts atypical cells using antibodies tied with fluorescent dyes, a technique that is simple, time-efficient and often more accurate than PCR. “Flow Cytometry testing is far less laborious and time-consuming than PCR, and so the results are often available to the physician within 24 hours,” Dr. Merati notes. “This technique also tends to be more informative than PCR in terms of subtypes of cells studied, as well as outcome prediction” he adds. In fact, according to a study in the March 2005 issue of the British Journal of Haematology, Flow Cytometry was more sensitive than gene rearrangement studies in detecting minimal residual disease, identifying it in 91% of all cases compared to 84% with PCR.
An accurate MRD assessment is a crucial component of every ALL patient’s long-term health care management plan, because the risk of recurrence is so high, and because it is so closely linked to MRD levels. In addition, studies have shown that the sooner patients relapse after their first treatment, the more difficult it is to eradicate the disease the second time around. Early detection of recurrence can enable physicians to customize treatment plans to fit the individual patient’s needs, from salvage chemotherapy to stem-cell transplant, with the goal of achieving long-term, disease-free survival.
“Childhood cancer can be a devastating diagnosis for families,” Dr. Merati says. “Fortunately, over the past several decades the pediatric oncology and pathology research communities have committed massive resources to the search for treatments and techniques that will improve and extend the lives of children with cancer and their families,” he concludes.
1. Four-color flow cytometry bypasses limitations of IG/TCR polymerase chain reaction for minimal residual disease detection in certain subsets of children with acute lymphoblastic leukemia. Robillard N, Cave H, Mechinaud F, Guidal C, Garnache-Ottou F, Rohrlich PS, Avet-Loiseau H, Garand R. Haematologica. 2005 Nov;90(11):1516-23
About Dr. Kambiz Merati
Dr. Kambiz Merati, M. D. is specialist in the field of Hematopathology. Dr. Merati received his medical training at Tehran University of Medical Sciences and is board certified in the American Board of Pathology in Anatomic and Clinical Pathology. Dr. Merati is currently with Acupath Laboratories in Plainview, NY www. acupath. com.
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