Early Allo-SCT May Not be Optimal for Certain Patients with Low-Risk CML

According to results recently presented at the 43rd annual meeting of the American Society of Hematology, evidence suggests that early an allogeneic stem cell transplant may not be the best approach for some patients with low-risk chronic myeloid leukemia.

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer of the white blood cells. The bone marrow contains early blood-forming cells called stem cells, which grow and mature into 3 blood cell types: red blood cells, which provide oxygen to tissues; platelets, which aid in blood clotting; and white blood cells, which fight infection. In the case of CML, large numbers of young granulocytes (a type of white blood cell) do not mature, resulting in an excess accumulation of these cells. These leukemia cells then crowd the bone marrow and blood, suppressing formation and function of other blood cells normally present in these areas. In addition, the leukemia cells cannot perform their function in the body properly, leaving patients susceptible to infection.

CML begins with a chronic phase, during which few clinical problems, if any, present themselves. However, if left untreated, the chronic phase progresses into acute phases characterized by fast-growing and aggressive cancer. These phases are called the accelerated and blastic phases. Patients reaching these have a poor prognosis for long-term survival.

High-dose therapy and allogeneic stem cell transplantation is the only curative treatment option for patients with CML. High-dose chemotherapy and/or radiation therapy tend to be more effective at killing cancer cells than lower doses of therapy. However, the high doses also kill blood-forming cells (stem cells) that are produced in the bone marrow, leaving patients susceptible to infection, anemia and uncontrolled bleeding. In order to rescue low levels of blood cells caused by high-dose therapy, stem cells are collected from either blood or bone marrow, stored and then infused into the patient following the high-dose therapy. In an allogeneic transplant, stem cells are collected from a related or unrelated donor.

Although an allogeneic SCT is the only curative treatment option for CML, many variables influence the outcome for an individual patient. Advanced age, disease status at the time of transplant, the donor source and donor match are all factors that affect a patient’s prognosis.

Researchers from the German CML Study Group recently conducted a clinical trial directly comparing initial treatment with IFN therapy to an allogeneic SCT for patients with CML. Interferon (IFN) is a biologic therapy used to stimulate the body’s own immune system to fight cancer which is often used in the treatment of CML. There were 195 patients without a related stem cell donor who received IFN therapy. Patients who did not respond to IFN underwent additional intensive chemotherapy. One-hundred-three patients received a related allogeneic SCT. Four years following treatment, the survival rates for patients treated with IFN were 91% for low-risk patients and 81% overall. For patients undergoing an allogeneic stem cell transplant, survival rates four years following therapy were 66% for low-risk patients and 61% overall. Furthermore, 29% of patients died from complications directly attributable to undergoing an allogeneic SCT.

These authors concluded that patients with low-risk chronic phase CML may benefit more from IFN therapy than allogeneic SCT. Future trials may determine patient characteristics that help define appropriate individual treatment options. Patients should discuss the risks and benefits of SCT with their treating physician. Specifically, patients should inquire about the results of SCT at specific institutions as cure rates may range from 50% to 95% depending on the institution. Clinical trials evaluating Gleevec® and other promising therapies are also being performed. Two sources of ongoing information regarding clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (www.cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Proceedings from the 43rd annual meeting of the American Society of Hematology, abstract #3036, Orlando, Florida, December 2001)

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