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Measuring Minimal Residual Disease Levels Proves to Be a Powerful Tool for Guiding Leukemia Treatment

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Key Points

  • A total of 93.5% of patients who participated in the minimal residual disease–directed therapy trial were alive 5 years after their cancer was diagnosed.
  • Overall long-term survival was 97.9% or better for 244 patients in this study classified as “low risk.”
  • Regardless of other risk factors, patients with a minimal residual disease level of 1% or more on day 19 of therapy were far less likely to be alive and cancer-free 10 years later, compared with patients with lower minimal residual disease levels.

According to a prospective study led by researchers at St. Jude Children's Research Hospital, measuring the concentration of leukemia cells in patient bone marrow during the first 46 days of chemotherapy may help boost survival of young leukemia patients by better matching patients with the right intensity of chemotherapy. The findings, reported by Pui et al in The Lancet Oncology, stem from a study of 498 children and adolescents with acute lymphoblastic leukemia (ALL) enrolled in a St. Jude–led protocol between 2000 and 2007. The clinical trial was reported to be the first to use measurement of residual leukemia cells—or minimal residual disease—in bone marrow to help guide therapy.

Study Details

“This analysis shows that minimal residual disease–directed therapy clearly contributed to the unprecedented high rates of long-term survival that patients in this study achieved,” said Ching-Hon Pui, MD, Chair of the St. Jude Department of Oncology. Overall, 93.5% of patients were alive 5 years after their cancer was diagnosed. “Minimal residual disease proved to be a powerful way to identify high-risk patients who needed more intensive therapy and helped us avoid overtreatment of low-risk patients by reducing their exposure to chemotherapy,” said Dr. Pui.

Researchers hope the findings will expand the use of minimal residual disease measurements to guide leukemia treatment in children and adults.

The technique might also help identify patients who could be cured with less intensive chemotherapy, Dr. Pui said. Overall long-term survival was 97.9% or better for 244 patients in this study classified as “low risk” based on a variety of factors, including age at diagnosis and minimal residual disease of less than 1% on day 19 of treatment. “Given the excellent outcome, it will be important to determine if treatment can be further reduced in this subgroup of patients,” Dr. Pui said.

A Better Alternative

In countries with limited resources, Dr. Pui said the findings suggest that results of minimal residual disease on day 19 can be used to reduce treatment-related deaths by identifying patients who will likely be cured with low-intensity chemotherapy. “This study demonstrates these patients have an extremely low risk of relapse,” he said.

The study showed that measuring minimal residual disease just twice during remission induction therapy, at day 19 and day 46, rather than multiple times during the more than 2 years of treatment, was sufficient to guide treatment of most pediatric ALL patients. A change in protocol will help save money and protect patients from the discomfort and risks associated with bone marrow aspiration for minimal residual disease testing. Minimal residual disease measurements should continue, however, to guide treatment of patients with detectable minimal residual disease on day 46 of treatment. That is a level of 0.01% or more, which translates into one leukemia cell in 10,000 normal cells.

Minimal residual disease was not a perfect predictor of relapse risk. Cancer returned in 26 of the 430 patients with undetectable minimal residual disease when treatment ended after 120 weeks. Researchers are working to develop even more sensitive methods for tracking treatment response to identify those at risk for having their cancer return.

Overall, researchers showed that regardless of other risk factors, including age at diagnosis or the initial white blood cell count, patients with a minimal residual disease level of 1% or more on day 19 of therapy were far less likely than other young leukemia patients to be alive and cancer-free 10 years later. Having detectable leukemia cells on day 46 of treatment was also associated with lower survival.

Minimal residual disease levels on days 19 and 46 led to the reclassification of 50 patients from low risk to a higher risk leukemia that warranted more intensive therapy. Researchers credited the change with boosting survival.

Dr. Pui is the corresponding author of The Lancet Oncology article.

The research was supported by the National Institutes of Health and ALSAC. For full disclosures of the study authors, visit www.thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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