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Taking a Chance on Stem Cell Transplantation

When considering a stem cell transplantation, patients with cancer must be willing to take a chance.

BY JENNIFER KLEM, PHD
PUBLISHED MONDAY, DECEMBER 17, 2012
In February 2006, 33-year-old Mary Krohn of Hartford, Wis., visited her doctor for what she thought was a sinus infection. Despite making a return trip to the clinic and taking two different types of antibiotics, her symptoms worsened over the next four days, prompting her to return for blood work, which revealed she had leukemia.

“I had no clue what leukemia was,” Krohn says. “I think it took a full week for me to realize that it could kill me.”

Within 24 hours of making her diagnosis, Krohn’s doctor had performed a bone marrow biopsy, which confirmed she had acute myeloid leukemia, and in less than five months, she received a hematopoietic stem cell transplantation (HSCT) using donor cells from her sister, who was a good match.

HSCT refers to the process of infusing into a sick person hematopoietic stem cells (HSCs), specialized “mother” cells capable of developing into red and white blood cells, platelets and other bloodforming stem cells, essentially creating new healthy cells to replace abnormal ones.

Although HSCT can be used to treat a variety of non-malignant diseases, it is more frequently used to treat several cancers of the blood and bone marrow, such as acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, non-Hodgkin lymphoma, Hodgkin lymphoma and multiple myeloma.

The origins of HSCT can be traced to the 1950s, when Edward Donnall Thomas, MD, and his colleagues achieved the first successful transplantation in two leukemia patients who received HSCs harvested from their identical twins’ bone marrow. Although their remissions were short-lived (approximately two to three months), the impact of this work was long-lasting and ultimately led to Thomas receiving the Nobel Prize in medicine in 1990. (Known as “the father of bone marrow transplantation,” Thomas died in October at age 92.)

Since then, researchers discovered that small numbers of HSCs travel to the bloodstream and can be drawn from the peripheral (circulating) blood or from blood retrieved from a newborn’s umbilical cord and placenta. This less invasive procedure simplified the collection process and transformed the field, dramatically increasing the number of donors worldwide.

Yet peripheral blood stem cell transplantation still requires stimulation of the donor’s bone marrow with stem cell factors given intravenously, then several days later, a three- to four-hour session where blood is circulated through a pheresis machine that selects stem cells which are then collected and frozen until ready for infusion.

Before HSCT is performed, patients receive high doses of chemotherapy and/or radiation to destroy rapidly dividing cells, which can include both cancerous and healthy bone marrow cells. Once the cells have been destroyed, the patient receives an infusion of previously collected healthy HSCs. These cells travel to the bone marrow, where, within about two to three weeks, they produce healthy, cancer-free blood cells that will ultimately repopulate the blood, helping to re-establish the immune system.

The source of HSCs can be either the patient (called an autologous transplantation) or a donor (called an allogeneic transplantation). Patients who provide their own HSCs have them removed from the bone marrow or the bloodstream prior to chemotherapy or radiation, and the cells are frozen for later use. In other cases, the HSCs come from a donor, which may be an identical twin, another close relative (often a sibling), an unrelated person or even ffrom an unrelated newborn.

The most important factor with donor stem cells is that the group of genes related to the immune system of the donor must match those genes of the immune system of the patient. If they don’t match closely enough, the patient’s immune system could reject the newcomers (the donor cells) or, worse, the donor cells could launch a full-scale attack on the patient’s body.

Identical twins are an exact match, and siblings are more likely to match the patient than the general population, but it is possible that unrelated people are close enough matches as well, which has given rise to bone marrow registries, such as the Be The Match Registry operated by the National Marrow Donor Program, that seek to identify matches for patients from among a large pool of unrelated donors. On the other hand, donor cells can also mount an immune attack on residual malignant cells, a term called “graft versus leukemia effect,” and may result in fewer relapses compared to an autologous transplant.

[Read about the National Marrow Donor Program]

Research published in August in Bone Marrow Transplantation shows that race and ethnicity have a direct impact on the success of transplantation. The registry has achieved a 90 percent rate for some degree of match for Caucasians, 70 percent for Hispanics and Asians, and 60 percent for those of African descent.

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