According to a recent article published in The Lancet, allogeneic stem cell transplantation improves survival over intensive chemotherapy in children diagnosed with very high-risk acute lymphocytic leukemia (ALL).

ALL, also called acute lymphoblastic leukemia, is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells called stem cells. These 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 develop 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. Some patients are considered at higher risk than others for the recurrence of their disease, which almost invariably leads to death. Variables that place patients at a higher risk are specific genetic abnormalities, high levels of cancerous cells detected in the blood or bone marrow, and resistance to treatment. Patients at a higher risk appear to benefit from more aggressive therapies, such as a stem cell transplant.

The procedure of an allogeneic stem cell transplant includes the use of high doses of therapy in an attempt to kill more cancer cells than conventional doses of therapy. However, these high doses also tend to kill more blood cells, leaving patients susceptible to life-threatening infection, anemia, and bleeding. Therefore, hematopoietic stem cells, or immature blood cells, are collected either from the patient (autologous) or from a donor (allogeneic) prior to therapy and infused into the patient following high-dose therapy. The stem cells mature into blood cells once infused to provide normal levels of blood cells and reduce risks associated with low levels of blood cells. Prior to the high doses, however, many patients receive initial therapy referred to as induction therapy. Most patients achieve a disappearance of detectable cancer cells following induction therapy, a state referred to as induction remission or first complete remission. Even though mortality rates associated with an allogeneic stem cell transplant remain high, research continues to confirm that the rate of cure outweighs the risk of mortality from the treatment procedure in ALL.

A recent study was directly compared an allogeneic stem cell transplant to intensified chemotherapy in pediatric patients with ALL. This study included 357 patients who were treated in medical institutions in seven countries. Patients were considered to be at “very-high-risk”, had completed induction therapy and were in first complete remission. They were either treated with an allogeneic stem cell transplant with stem cells were donated from a relative, or intensified chemotherapy. At 5 years, cancer-free survival was higher in patients treated with an allogeneic stem cell transplant: approximately 57% compared with nearly 41% in patients treated with intensified chemotherapy. Overall survival at 5 years was also improved for those treated with a transplant: 56% compared with 50% for those treated with intensified chemotherapy. Patients with the poorest prognosis derived the greatest benefit from transplantation.

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The researchers concluded that an allogeneic stem cell transplant provides superior cancer-free and overall survival compared with intensified chemotherapy in high-risk pediatric patients with ALL. Longer follow-up may reveal even greater survival differences between the two groups of patients. Parents of children with ALL may wish to speak with their physician regarding their child’s individual risks and benefits of undergoing an allogeneic stem cell transplant.

Reference: Balduzzi A, Valsecchi M, Uderzo C, et al. Chemotherapy versus allogeneic transplantation for very-high-risk childhood acute lymphoblastic leukaemia in first complete remission: comparison by genetic randomisation in an international prospective study. The Lancet. 2005; 366:635-642.

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