Allogeneic Stem Cell Transplants Effective for CML

Allogeneic Stem Cell Transplants Effective for CML that Doesn’t Respond to Gleevec®.

According to an article recently published in the journal Blood, an allogeneic stem cell transplant is an effective treatment approach among patients with CML or ALL that does not respond to Gleevec® (imatinib).

Chronic myeloid leukemia (CML), also called chronic granulocytic leukemia, is a cancer that originates in the immune cells. It affects approximately 4,600 people annually in the U.S. In CML large numbers of young immune cells 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 properly, leaving patients susceptible to infection.

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

The majority of cases of CML are Philadelphia chromosome-positive (Ph-positive). In such cases a genetic abnormality, referred to as the Philadelphia chromosome, results in the constantly activated growth of cancer cells. Roughly 30% of adult patients with ALL also have this genetic abnormality.

Historically, the only curative option for patients with CML was an allogeneic stem cell transplant. An allogeneic stem cell transplant 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.

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.

One treatment option for CML is Gleevec, a biological agent that binds to and slows or stops the uncontrolled growth of cancer cells with the Philadelphia chromosome genetic mutation. Unfortunately, a small number of patients who are treated with Gleevec do not achieve anticancer responses; researchers are evaluating optimal treatment approaches for these patients.

One approach being evaluated is the use of lower doses of therapy prior to the infusion of a donor’s stem cells, referred to as a reduced-intensity, non-myeloablative, or mini-allogeneic stem cell transplant. A mini allogeneic transplant relies heavily on the donor’s stem cells attacking the patient’s cancer cells.

Researchers from M.D. Anderson Cancer Center recently conducted a clinical trial to evaluate the effectiveness of an allogeneic stem cell transplant among patients with CML or Ph-positive ALL who did not have an anticancer response to Gleevec. This small trial included nine patients with CML and one patient with ALL.

  • A complete disappearance of cancer cells (as detected through molecular laboratory methods) was achieved in seven of the ten patients.
  • Of these seven patients, six remain with no evidence of cancer cells.
  • Two of the three patients treated with a mini allogeneic transplant are still alive.
  • There were no deaths related to treatment.

The researchers concluded that an allogeneic stem cell transplant appears to be an effective treatment choice for patients with CML or PH-positive ALL whose cancer does not respond to Gleevec. Patients with this disease may wish to speak with their physician regarding their individual risks and benefits of an allogeneic stem cell transplant.

Reference: Jabbour E, Cortes Kantarjian HM, et al. Allogeneic stem cell transplantation for patients with chronic myeloid leukemia dn acute lymphocytic leukemia after Ccr-Abl kinase mutation-related failure. Blood. 2006;108:1421-1423.

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