Page 26 Complete Your CE Test Online - Click Here that lowers CYP 2D6 production do not get the same benefit from tamoxifen as women who metabolize the drug normally. There are other antiestrogens for women who are not expected to respond to tamoxifen; specifically, the aromatase inhibitors – such as anastrozole, letrozole, and exemestane – can be used for ER-positive breast cancers. However, there is currently no requirement or recommendation from U.S. experts that women be tested to find out if their CYP 2D6 levels are adequate before starting tamoxifen. Women who have higher CYP 2D6 levels because of a different genetic mutation may get higher levels of active drug and may be more prone to side effects and toxicities. Unfortunately, there are other germline mutations that can cause problems in cancer treatment. People who have a dihydropyrimidine dehydrogenase (DYPD) mutation can have much higher toxicity and even fatalities with the commonly used cancer drug, 5-fluorouracil. Thiopurine methyltransferase (TPMT) mutations, which affect about 1 in 300 people, can result in unexpected toxicity with mercaptopurines. People with UDP-glycosyl-transferase 1A1 mutations can have increased toxicity from irinotecan, with dose-limiting diarrhea and leukopenia. Those with methylenetetrahydrofolate reductase mutations (MTHFR) can have much worse toxicity to methotrexate. Again, most of these problems are discovered after chemotherapy begins, if they are discovered at all. Many cancer treatment centers do not test for these genetic mutations even if they have to stop therapy. This is another reason it is so crucial to assess and document responses to cancer treatment. If treatment with the problem drug is allowed to progress in the face of these mutations, it can result in death (see “Resources for Nurses”). Hematopoietic stem cell transplants Hematopoietic stem cell transplants (HSCT) provide healthy blood- forming stem cells to replace cells that were destroyed by treatment (and sometimes by disease). The blood-forming stem cells that are used in transplants can come from bone marrow, the bloodstream, or umbilical cords. Transplants can be one of the following: ● ● Autologous: The stem cells come from the patient and are eventually infused into the same patient. ● ● Allogeneic The stem cells come from someone else. The donor may be a blood relative but can also be an unrelated match, including banked cord blood from newborns. ● ● Syngeneic: The stem cells come from a patient’s identical twin. To reduce possible side effects and improve the chances that an allogeneic transplant will work, the donor’s blood-forming stem cells must match. This matching involves human leukocyte antigens (HLA) that determine a person’s tissue type. A match works better when all six of the major HLA antigens match. Sometimes a donor with one mismatched antigen (e.g., a five out of six match) is used. When a transplant uses cord blood from newborns, perfect HLA matching is not as important for success. In unrelated adult donors, sometimes professional will try to match even more than the six major antigens, which requires a deeper look at HLA typing than has been done routinely. Research continues in this area because it can be very difficult to find high level HLA matches for HSCTs. In most cases, stem cell transplants do not work directly against the cancer. Instead, they allow the patient to recover after treatment with very high doses of radiation therapy, chemotherapy, or both. However, in multiple myeloma and some types of leukemia, the stem cell transplant may work against cancer directly through an effect called graft-versus-tumor that can occur after allogeneic transplants. Graft- versus-tumor occurs when white blood cells from the donor attack cancer cells that remain in the body after high-dose cancer treatment treatments. This effect improves the success of the treatments. High doses of chemo and radiation work better at killing cancer cells than standard doses do, but they also cause the bone marrow to completely stop working. The HSCT rescues the patient from this lethal situation by providing new stem cells to replace the ones killed by the treatment. Most patients stay in the specialized transplant center hospital during at least part of the transplant process, which can take a few months to complete. The process begins with treatment of high doses of chemotherapy, radiation therapy (usually total body irradiation, or TBI), or a combination of the two. This goes on for a week or two. After a few days of rest, the patient gets an IV infusion of the blood-forming stem cells. After receiving the stem cells, there is the wait for engraftment, when the new stem cells start making new blood cells. Rarely, a graft will not take; the donor cells can be destroyed. During this procedure, when the patient has little to no immune function (either because the graft has not started working or because of immunosuppressant drugs), latent infections the recipient had can recrudesce and cause complications, some severe. After blood counts return to normal, it takes much longer for the immune system to fully recover: several months for autologous transplants and one to two years for allogeneic or syngeneic transplants. Who receives stem cell transplants? Stem cell transplants are most often used to help people with leukemia, neuroblastoma, multiple myeloma, and some lymphomas. Stem cell transplants for other types of cancer are being studied in clinical trials. Side effects of stem cell transplants The high doses of cytotoxic chemotherapy for conditioning before stem cell transplant can cause severe pancytopenia with anemia and high risk of bleeding and infection. The progress of the transplant is monitored by frequent blood counts. As the newly transplanted stem cells produce blood cells, blood counts go up. Many of the side effects are similar to those seen with chemotherapy and high-dose radiation, although there is one side effect that is specific to the allogeneic transplant process, graft- versus-host disease (GVHD). Allogeneic transplant recipients often develop graft-versus-host disease, in which white blood cells from the donor (the graft) recognize cells in the recipient’s body (the host) as foreign and attack them. This problem can damage skin, liver, gut, and many other organs. It can occur early or later and may be short-term or become chronic. Graft-versus-host disease can be treated with steroids or other drugs that suppress the recipient’s immune system. The closer the match between the donor and recipient, the less likely graft-versus-host disease is to occur. GVHD is related to the graft-versus-cancer effect, but the graft-versus-cancer can occur even in well-matched donor-recipient pairs. Special diet needs, GI disturbances, and chemoradiation side effects The conditioning regimen given before a stem cell transplant can cause side effects that make it hard to eat, such as mouth sores and nausea. People who are having trouble eating might find it helpful to speak with a dietitian (see “Diarrhea” and other problems listed in the “Symptom Management” section). The toxicities of chemotherapy are typically magnified because of the extreme doses used in HSCT. Treatment assessments and interventions At each visit with the outpatient, the nurse should assess adherence to appointment, laboratory monitoring, at-home medications, symptom control, and other parts of the treatment plan. The nurse should also inquire about side effects and new problems and concerns; reassess previously identified problems; and assess for any unmet physical or psychosocial needs, educational and informational needs, and any referral needs. The patient and family may need additional information on drug-food interactions, what to do when doses of medication are missed, oral chemotherapy drugs, and more. Inpatients are easier to observe, but big-picture assessment may be lost in all of the treatment and side effects that are likely to be going on. If the patient has a family caregiver visiting, that is usually a good time to go over the concerns the patient and family have about the treatment effects and coping at home. Involving home caregivers In assessing symptoms during treatment, it is often helpful to talk with family members or others who are caring for the patient at home. An open-ended question about how the patient seems to be functioning at home is a good way to start. Family members who help care for the