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181 CHAPTER 6 Stem Cell Transplants The first time I met my oncologist, she told me about stem cell trans‑ plants. She didn’t know whether I would be cured with front-line therapy, and she wanted to reassure me that we had backup options. A stem cell transplant is a procedure that uses high doses of antineoplastic drugs, or of radiation, that would ordinarily be toxic to wipe out any cancer cells that have proved resistant to more gentle methods of therapy. There are three basic types of stem cell transplant: autologous transplants, synge‑ neic transplants, and allogeneic transplants. They are distinguished from each other by the source of the stem cells that will repopulate your bone marrow after you receive this treatment. I found the idea of a stem cell transplant frightening, and the prospect of getting one loomed threateningly over me until I had passed the “unlikely to relapse” mark, two years after completing chemo and radiation. However, a stem cell transplant is essentially just an extension of chemotherapy (and sometimes radiation therapy and immunotherapy). While the regimens involved are usually harsher than those involved in standard chemotherapy , making them harder to tolerate, transplant methodologies continue to be improved and extended. As the techniques involved in transplantation technology have been refined, the population eligible for a transplant has increased—so that people who wouldn’t have been eligible for a transplant ten years ago can have them today—and the procedure has become much less difficult to undergo. This isn’t your father’s stem cell transplant. In discussing chemotherapy, I talked about the idea of dose-limiting drug toxicity. The dose-limiting toxicity occurs at drug doses at which the side effects are so severe that you cannot risk taking any more of that drug. If U 182 Treating Lymphoma the dose-limiting toxicity of the drug occurs at a higher concentration than the therapeutic concentration—the dose of drug required to wipe out the cancer—then everything’s fine. The drug gets rid of the cancer; you put up with the side effects, and then move on. Treatment becomes problematic, however, when the dose-limiting toxicity is close to, or below, the therapeutic dose. In this case, you can’t take enough of the drug to wipe out the cancer without incurring the risk of life-threatening complications. Combination chemotherapy takes one approach to this problem. Different antineoplastic drugs with distinct dose-limiting toxicities are given together. The cancer cells are hit simultaneously from several different angles, but no healthy organ or system is excessively stressed. Stem cell transplants take a slightly different approach. In a stem cell transplant, you are given one or more antineoplastic drugs (sometimes combined with total body irradiation, TBI) whose dose-limiting toxicities are due to bone marrow suppression. You take very high doses of these drugs—enough to wipe out the cells in your bone marrow (as well as destroy the cancer). As discussed in more depth in Chapter 10, your lymphocytes, and all the other blood cell types, are derived from hematopoietic—or blood-producing— stem cells found in your bone marrow. These stem cells, which are also found circulating in the blood, essentially function as the “seeds” of the bone marrow , giving rise to all the different types of blood cells. Therefore, eliminating the stem cells in your bone marrow would ordinarily wipe out your immune system, your platelets, and your red blood cells, leaving you subject to the first pathogen that comes along, as well as terribly anemic and vulnerable to massive bleeding in response to the most minor injuries. A truly fragile state of existence! With a stem cell transplant, however, you are saved from this dire fate by an infusion of hematopoietic stem cells, which magically find their way to the proper sites inside your bones to reproduce and reconstitute all your different blood cells. The ability to perform a stem cell transplant—sometimes called a stem cell rescue—allows antineoplastic drugs to be given at much higher doses than normal: up to the point where other dose-limiting toxicities (that don’t show up at normal therapeutic doses) start to emerge. The hope is that such high levels of drugs will eradicate even those populations of cancer cells tough enough to survive normal levels of antineoplastic agents. You’re essentially hitting the cancer with the biggest guns in the therapeutic arsenal, and your stem cells are innocent bystanders shot down in the process...


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