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According to an article recently published in the journal Blood, patients with AML who are at a high risk of cancer progression following standard therapy may benefit from an unrelated allogeneic stem cell transplant.

Acute myeloid leukemia (AML) is a cancer of the bone marrow and blood characterized by the rapid, uncontrolled growth of immature white blood cells known as myelocytes. The disease is more common in adults than in children; average age at diagnosis is more than 65 years.

Treatment of AML often begins with induction therapy (initial treatment) that includes chemotherapy to produce a complete remission (defined as the disappearance of leukemia cells in the bone marrow and normalization of the white blood cell, red blood cell, and platelet levels). After induction therapy, patients generally receive additional treatment (consolidation therapy) to reduce the likelihood of leukemia recurrence. Depending upon prognosis, age of the patient, and/or other existing medical conditions, consolidation therapy can range from extremely aggressive to less aggressive.

An allogeneic stem cell transplant, considered an extremely aggressive treatment option, involves the use of high doses of therapy, which kill a greater amount of cancer cells than standard doses. Unfortunately, the high doses of therapy also cause a significant reduction in blood cells, resulting in a patient's susceptibility to infection, bleeding, and the need for blood transfusions. Often, the infections caused by these high doses of therapy are life-threatening.

To restore levels of blood cells
stem cells, which are immature blood cells, are collected from a donor and infused into the patient following high-dose therapy. These donor stem cells can also mount an attack against the patient's cancer cells. Unfortunately, these donor cells can also attack a patient’s healthy cells, causing a potentially life-threatening condition called graft-versus-host disease (GVHD). Stem cells donated by a relative (related donor) tend to carry a lower risk of GVHD than those from an unrelated donor.

A drawback of an allogeneic stem cell transplant is that treatment-related mortality and side effects can be substantial; researchers have thus focused on curative options that are more easily tolerated. However, for patients with very aggressive AML and those who are younger, an allogeneic stem cell transplant still appears to provide optimal outcomes.

Researchers affiliated with the International Blood and Marrow Transplant Registry recently conducted a clinical study evaluating the use of allogeneic stem cell transplants with unrelated donors for patients with AML. This trial included 261 patients with AML in first remission (when disease is undetectable for the first time following treatment) or second remission (the second time following two different treatment courses that disease is undetectable) who were 60 years of age or younger. Patients in this trial were divided into three groups: those who had a high, intermediate, or low risk of developing a cancer recurrence following standard therapies.

The following results include patients in first remission:

• At five years overall survival was between 29–30% for all groups of patients.
• At five years mortality related to treatment was 47% for patients at a high risk of developing a recurrence, 53% for patients at an intermediate risk of developing a recurrence, and 63% for patients at a low risk of developing a recurrence.
• Cancer recurrence rates were 8%, 17%, and 26%, respectively for patients with low, intermediate, and high risks of developing a cancer recurrence.

The following results include patients in second remission:

• At five years overall survival was 45%, 37%, and 36%, respectively, among patients with a low, intermediate, and high risk of developing a cancer recurrence.
• At five years mortality related to treatment was 46%, 46%, and 30%, respectively among patients with a low, intermediate, and high risk of developing a cancer recurrence.
• Cancer recurrence rates were 12%, 18%, and 32%, respectively, among patients with a low, intermediate, and high risk of developing a cancer recurrence.

The researchers concluded that an unrelated allogeneic stem cell transplant can provide AML patients 60 years of age or younger who are in first remission and have a high risk of a cancer recurrence overall survival rates at five years that are comparable to those among patients with a lower risk of a recurrence. However, this trend did not seem to hold true for patients in second remission. Furthermore, mortality related to treatment was high.

Patients with AML who are at a high risk of developing a cancer recurrence and do not have a related donor for an allogeneic stem cell transplant may wish to speak with their physician regarding their individual risks and benefits of an unrelated stem cell transplant.

Reference: Tallman MS, Dewald GW, Sandham S, et al. Impact of cytogenetics on outcome of matched unrelated donor hematopoietic stem cell transplantation for acute myeloid leukemia in first or second complete remission. Blood. 2007; 110:409-417.

1 التعليقات:

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June 5, 2009 at 1:47 PM  

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