Peripheral Blood Monitoring Instead of Bone Marrow Effective in Children

Peripheral Blood Monitoring Instead of Bone Marrow Effective in Children Treated with Acute Lymphoblastic Leukemia

According to a recent article published in the journal Blood, peripheral (circulating) blood appears to be at least as effective as bone marrow samples for the detection of minimal residual disease in children treated for T-cell acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to tissue; and platelets, which help blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells, such as red blood cells, platelets and other white blood cells. ALL is an aggressive cancer that must be treated aggressively for optimal chances of a cure.

Overall cure rates for children with ALL are approximately 70% to 80%. Treatment of ALL may include chemotherapy, radiation, biological therapies and/or stem cell transplantation. The initial treatment regimen is referred to as remission induction or induction therapy. Following induction therapy, more treatment, called consolidation therapy, is given in an attempt to eliminate all remaining cancer. Maintenance therapy is then given for approximately 2 to 3 years. Although most patients achieve a complete remission (complete disappearance of detectable cancer) following induction or consolidation therapy, some patients may have some cancer cells remaining, which are responsible for cancer relapses. Minimal residual disease (MRD) refers to cancer cells that are detectable at a molecular level and produce no symptoms. Patients with MRD often suffer from a cancer relapse, with a cure rate of only approximately 30%. Therefore, researchers aim to eliminate even MRD in order to obtain optimal chances of a cure. Monitoring MRD allows physicians to track a patient's remission more closely and therefore define future optimal treatment options.

The usual method for monitoring MRD in patients with leukemia is to perform sophisticated laboratory tests on bone marrow samples. A bone marrow test involves the placement of a hollow needle into the bone marrow (spongy material inside bones). It is often performed on the hip bone and can be quite traumatic for children who have to undergo frequent monitoring, sometimes requiring heavy sedation or anesthesia. Recently, researchers from St. Jude Children's Research Hospital compared the results of peripheral blood, which is a simple procedure during which a sample of blood can be obtained from a vein in the arm to bone marrow samples in children with ALL.

The researchers used a laboratory method called flow cytometry which is able to detect one leukemic cell among 10,000 cells. In this study, both blood and bone marrow samples were obtained from 226 children with either T-cell or B-cell ALL. Results from both blood and bone marrow tests were directly compared. Samples from both blood and bone marrow were identical in patients with T-cell ALL. However, only 37 blood samples of 104 bone marrow samples of B-cell detected MRD. Surprisingly, the relapse rate for children with B-cell ALL who had MRD detected on peripheral blood samples was 80%, compared to only 13% in patients with MRD only detected in the bone marrow.

These researchers concluded that peripheral blood testing was just as effective as bone marrow samples in determining MRD in T-cell ALL. Conversely, peripheral blood was not reliable in detecting MRD in patients with B-cell ALL. However, it appeared that patients with B-cell ALL who had MRD detectable in peripheral blood had a higher risk of relapse than those with MRD detected only in bone marrow. These patients may wish to consider aggressive therapy in order to reduce their risk of a relapse. Parents with children who have ALL may wish to speak with their physician about the results of this clinical trial and risks of relapse according to MRD testing.

Reference: Coustan-Smith E, Sancho J, Hancock ML, et al. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia.

Blood. 2002;100:2399-2402.

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