What Are The Long-Term Side Effects of Autologous Stem Cell Transplant?
by Dr. C.D. Buckner M.D. updated 4/2020
Survivors of Stem Cell Transplant Report Health Problems
According to a recent article published in the *Journal of Clinical Oncology,*long-term survivors of stem cell transplants have greater medical needs than the general public. However, overall rates of subsequent disease and hospitalization were not increased in these survivors when compared to their counterparts.
Stem cell transplantation (SCT) is a common therapeutic approach in the treatment of various cancers. SCT utilizes above-normal doses of chemotherapy and/or radiation therapy, followed by the infusion of a patient’s or donor’s hematopoietic stem cells (immature blood cells). Long-term follow-up of patients who are considered cured following SCT is necessary to determine if any long-term health effects are related to treatment. If so, patients may be adequately monitored for specific health-related issues.
Researchers from the Fred Hutchinson Cancer Center and the University of Washington recently conducted a study to determine if any health-related issues were strongly associated with patients who underwent SCT for the treatment of their cancer. The study included 137 patients who had survived 10 years following a SCT. Patients reported details of their health status according to standardized questionnaires. Researchers also evaluated medical records. The results were compared to the general public according to corresponding age, sex, and race.
Overall, survivors of SCT and the general population had similar incidences of most diseases and hospitalization. However, survivors had increased musculoskeletal stiffness, cramps, weakness, joint swelling, cataract surgery, hepatitis C, sexual problems, memory and attention difficulties, urinary frequency or leaking, use of psychotropic medication, restrictions in social function, and denial of life and health insurance. But, despite these complications, survivors reported similar rates of employment, marital satisfaction, divorce, and psychological health as their counterparts.
The researchers concluded that long-term survivors of SCT had greater medical needs than the general population; however, overall disease and hospitalization rates were similar between the two groups. The authors state that issues such as stiffness, pain, or weakness should be evaluated in this group of patients to understand possible biological causes. (1)
There are several long-term or late side effects that result from the chemotherapy and radiation therapy used in autologous stem cell transplant. The frequency and severity of these problems depends on the radiation or chemotherapy used to treat the patient. It is important to have the doctors providing your care explain the specific long-term side effects that can occur with the actual proposed treatment. Some examples of complications you should be aware of include the following:
Cataracts occur in the overwhelming majority of patients who receive total body irradiation in their treatment regimen. In patients who receive chemotherapy without total body irradiation, cataracts are much less frequent. The onset of cataracts begins at 18 to 24 months following treatment. Patients who have received large doses of steroids will have an increased frequency and earlier onset of cataracts. Patients are advised to have slit lamp eye evaluations annually with early correction with artificial lenses.
A common concern for cancer patients receiving therapy, particularly high doses of therapy, is that treatment will harm their ability to conceive and bear children. Research suggests that infertility is more common with radiation than chemotherapy and women who do conceive are as likely as non-transplant patients to have normal delivery.
The overwhelming majority of women who receive total body irradiation will be sterile. However, some prepubertal and adolescent females do recover ovulation and menstruation. In patients who receive chemotherapy-only preparative regimens, the incidence of sterility is more variable and more age related (i.e., the older the woman is at the time of treatment, the more likely chemotherapy will produce anovulation). These are important considerations because of the need for hormone replacement. All females should have frequent gynecologic follow-up examinations.
The overwhelming majority of men who receive total body irradiation will become sterile. Sterility is much more variable after chemotherapy-only regimens. Men should have sperm counts performed to determine whether or not sperm are present and should be examined over time, as recovery can occur.
Although long-term survivors of stem cell transplants are less likely to conceive, outcomes of pregnancies appear to be similar to that of the general population. To address this issue in survivors of stem cell transplants, researchers from several medical institutions in the U.S. conducted a study to investigate the possible differences in reproductive function in long-term survivors of stem cell transplantation.
A questionnaire was completed by 241 patients who were treated with an autologous stem cell transplant and 378 who were treated with an allogeneic stem cell transplant. Questions addressed pregnancies and births among women who had undergone stem cell transplant or were partners of men who underwent stem cell transplant. The patients were between the ages of 21 and 45 years. The median age at the time of the stem cell transplant was 33 years, and the median time since the transplant was nearly 8 years. Results from patients were compared to results from their siblings who had not been diagnosed with cancer.
- The rate of conception was lower among survivors of stem cell transplantation compared to siblings who did not have cancer.
- Factors associated with no reports of conception were older patient age at the time of transplantation (30 years or older), female sex, and the use of total body irradiation during treatment.
- Once pregnancy occurred, rates of miscarriage or stillbirth were similar between survivors of transplantation compared to siblings who had not been diagnosed with cancer.
The researchers concluded that survivors of stem cell transplantation who were older at the time of the procedure, female gender, and who received total body irradiation were more likely to experience a lower rate of conception. However, once pregnancy occurred among these survivors, outcomes, including miscarriage or stillbirth, were similar to those of their siblings who had not undergone a transplant. Patients diagnosed with cancer who are to undergo stem cell transplantation should speak with their physician regarding their individual issues surrounding reproductive health.
Treatment with chemotherapy and radiation therapy is known to increase the risk of developing a new cancer. These are called “secondary cancers” and may occur as a late complication of high-dose chemotherapy. For patients with breast cancer treated with high-dose chemotherapy, the risk of developing a secondary cancer has been reported to be less than 2 percent. Patients with lymphoma treated with high-dose chemotherapy and autologous stem cell transplant appear to have about an 8 to 10 percent chance of developing a secondary cancer if treated with total body irradiation and 2 to 4 percent if treated with high-dose chemotherapy and no radiation. Patients with lymphoma treated with conventional chemotherapy have also been reported to have a 4 to 8 percent risk of developing a secondary cancer. How much additional risk occurs from high-dose chemotherapy is unclear; however, high-dose radiation clearly increases the risk of developing a secondary cancer.
High-dose chemotherapy and autologous stem cell transplant is increasingly used to treat certain cancers because it improves cure rates. Patients should be aware of the risk of secondary cancer following high-dose chemotherapy treatment and discuss the benefits and risks of high-dose chemotherapy with their primary cancer physician.
Risk of Solid Cancers Increased for Some Patients Undergoing Allogeneic Stem Cell Transplants
According to an early online publication in the journal Cancer, some patients who have undergone an allogeneic stem cell transplant are at a higher risk of developing solid cancers (cancers that do not originate in the blood or lymph), particularly if their donor was a female.
Allogeneic stem cell transplants are a common treatment for some types of cancers, particularly leukemias or lymphomas. The process of an allogeneic stem cell transplant typically includes the use of high-dose chemotherapy or total body irradiation. These treatment approaches tend to kill more cancer cells than conventional doses; however, they are also associated with more severe side effects.
Researchers from British Columbia, Canada, recently conducted a clinical study to review the incidence of second solid cancers that developed among patients who underwent an allogeneic stem cell transplant. This study included 926 patients who underwent an allogeneic stem cell transplant; the majority of these participants had been initially diagnosed with leukemia.
- The occurrence of a second solid cancer at ten years was 3.1% for these patients-nearly twice that of the general population.
- Patients who received stem cells from a female donor had a 3.8-fold greater risk of developing a second solid cancer than patients who received stem cells from a male.
- The greatest risk of developing a second solid cancer was among male patients who had received stem cells from a female donor, and the least risk of developing a second solid cancer was among female patients who had received stem cells from a male donor.
- Patients who were older at the time of the transplant had an increased risk of developing a second solid cancer.
The researchers concluded that patients who undergo an allogeneic stem cell transplant are at an increased risk of developing a subsequent solid cancer, particularly patients who receive stem cells from a female donor and those who are older when they undergo a transplant.
The data regarding women donors has not been published prior to this study, and the authors recommend further evaluation of this issue.
Patients who are to undergo an allogeneic stem cell transplant may wish to speak with their physician regarding their individual risks for developing subsequent cancers as well as appropriate screening measures for these cancers.
Salivary Gland Dysfunction
Salivary gland dysfunction is a common complication of stem cell transplant. Salivary secretion rates can be substantially reduced during the conditioning regimen phase and are more common with total body irradiation (TBI) than chemotherapy. Salivary gland function can also be negatively impacted by medications used during transplant and as a complication of graft verses host disease in allogeneic stem cell transplant. Learn about the treatment of Xerostomia here.
- Syrjala K, Langer S, Abrams J, Storer B, Martin P, et al. Late Effects of Hematopoietic Cell Transplantation Among 10-Year Adult Survivors Compared With Case-Matched Controls. Journal of Clinical Oncology. 2005; 23:6596-6606.
- Gallagher G, Forrest D. Second Solid Cancers After Allogeneic Hematopoietic Stem Cell Transplantation. Cancer [early on-line publication]. 2006. November 27, 2006. DOI: 10.1002/cncr.22375 .
- Carter A, Robison L, Francisco L, et al. Prevalence of Conception and Pregnancy Outcomes after Hematopoietic Cell Transplantation: Report from the Bone Marrow Transplant Survivor Study. Bone Marrow Transplantation. Advanced online publication. April 10, 2006. doi: 10.1038/sj.bmt.1705364.
- Major salivary gland damage in allogeneic hematopoietic progenitor cell transplantation assessed by scintigraphic methods