Ask the doctor…

Stem Cells for Transplant: How Much is Enough?

“My doctor has tried to collect stem cells for my autologous transplant, but so far he has not collected enough CD34+ cells. What are CD34+ cells? How much is enough?”

Philip McCarthy MD, Roswell Park Cancer Institute, New York responds:

CD34+ cells are a type of white blood cell that has a particular marker on its cell surface. CD34+ cells contain the stem cells of the blood cell system. These stem cells can produce exact copies of themselves to maintain a constant supply in the bone marrow. They also produce other cells, which eventually evolve into white blood cells, red blood cells and platelets.

If the number of CD34+ cells infused into a patient following high-dose chemotherapy or radiotherapy is too small, the patient may not be able to produce a sufficient number of blood cells after transplant. The number of stem cells required for transplant differs depending on the stem cell source (blood versus bone marrow versus cord blood).

When harvesting stem cells for an autologous blood stem cell transplant, usually a minimum of two million CD34+ cells per kilogram of patient body weight are required. There is some data suggesting that a patient engrafts better with more CD34+ cells, but this is not uniformly accepted by all BMT centers. Twice that amount may be collected, particularly if the patient is considering more than one transplant.

Before stem cells can be collected from the bloodstream, they must first be “mobilized” or moved there from the bone marrow.  A cell growth factor called Neupogen® (filgrastim, G-CSF), given by injection to patients several days before the stem cell collection, usually moves enough stem cells from the bone marrow to the bloodstream. Unfortunately, in some patients, particularly those who have had a lot of prior chemotherapy, Neupogen® alone does not work. When this occurs, Neupogen® or another cell growth factor called Leukine® (sargramostim, GM-CSF), plus chemotherapy may be used to mobilize enough stem cells for collection. Another option is to supplement the cells collected from the bloodstream with a bone marrow harvest.

Patients with multiple myeloma are usually able to produce sufficient stem cells for collection with Neupogen® alone. Patients with Hodgkin’s disease or non-Hodgkin’s lymphoma can have more difficulty.  Approximately 25-30% don’t mobilize properly with Neupogen® alone.

A new drug called plerixafor (Mozobil™), when used with Neupogen®, appears to increase the number of stem cells that can be moved into the bloodstream for collection. This drug has not yet been approved by the FDA. In two Phase III clinical trials involving 600 patients with multiple myeloma or non-Hodgkin’s lymphoma, those who received a combination of Mozobil™ and Neupogen® were able to collect the targeted number of cells for transplant faster than those who received Neupogen® alone. In the trial involving patients with multiple myeloma, 72% of those who received the combination of Mozobil™ and Neupogen® produced the target number of stem cells within two days or less. In contrast, only 34% of those who received Neupogen® alone reached the target after two days of stem cell collection. In the trial involving patients with non-Hodgkin’s lymphoma, 59% of those who received Mozobil™ and Neupogen® achieved the target number of stem cells in four days or less. Only 20% of patients who received Neupogen alone reached the target in four days.

For related and unrelated donor blood stem cell transplants, most people will mobilize well with Neupogen® alone. However, 3-5 percent of normal donors don’t mobilize. When this occurs, the stem cells collected from the bloodstream is supplemented by a bone marrow harvest, rather than by the addition of chemotherapy.

Although it is possible to transplant a patient with less than the optimal amount of CD34+ stem cells, it is dicey. It will take longer for the patient to begin producing sufficient blood cells, during which time he or she will be at risk for infection and bleeding. Some patients could have long-term issues with poor count recovery, such as prolonged red cell and platelet transfusion requirements or chronic Neupogen® or Leukine® usage. Sometimes the low red counts do not respond to red cell stimulation with erythropoietin, forcing the need for prolonged red cell transfusions that could lead to iron overload. If the patient ever needs any type of chemotherapy or radiation following transplant, poor marrow function might make this therapy impossible.

There is a cooperative group study examining the long-term use of lenalidomide or placebo after transplant to prevent recurrence following autotransplant for myeloma. Lenalidomide can suppress the white blood cell and platelet counts. Poor marrow function could prevent this drug from being used for maintenance therapy. A high CD34+ count does not guarantee fast count recovery but it helps ensure a better outcome.           

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