This article was written in collaboration with Drs. Wendy Bottinor from VCU Health, Richmond, Virginia, and Carrie Lenneman from UAB School of Medicine in Birmingham, Alabama.
Approximately 1 million stem cell or bone marrow transplants are performed worldwide. In the US, 20,000 stem cell transplants (SCT) are performed each year for hematological malignancies such as leukemia or lymphoma. The most common form of transplant is the allogeneic SCT (60% of cases) and involves the transplantation of donor-derived stem cells for the treatment of non-malignant pediatric conditions such as immune deficiencies, hemoglobinopathies, and metabolic diseases. The other form of transplant is the autologous SCT (40%), most common in adults with lymphoma or multiple myeloma and involves using the patient’s own stem cells.
How Does a Stem Cell or Bone Marrow Transplant Work?
A stem cell transplant accomplishes disease eradication through a high dose of chemotherapy and radiation, leading to ablation of the patient’s bone marrow. This phase of treatment is called “conditioning”. This is followed by the transplantation of either the donor-derived stem cells (allogeneic) or the patient-derived stem cells (autologous) which have been harvested prior to conditioning.
What Are the Risks Associated with Stem Cell or Bone Marrow Transplant?
Besides the risk of relapse of cancer, SCT remains associated with significant early and late treatment-related mortality. Infections, direct toxic effects of the chemotherapy, and, in allogeneic SCT only, graft-vs-host disease remains the main cause of death.
Over the last decade, transplant teams across the world have managed to reduce all-cause, early and late, mortality after autologous SCT. In allogeneic SCT, they were successful in reducing graft-vs-host disease and infections early after transplant, but the late mortality remains high. Advanced disease stage at the time of transplant, increasing age of the recipient, and co-morbid medical conditions remain associated with increased morbidity and mortality.
What Are the Late Cardiovascular Effects of Stem Cell or Bone Marrow Transplant?
Cardiovascular disease in pediatric patients is relatively rare. In a study of 661 children undergoing allogeneic SCT and who survived 2 years, stroke occurred in 0.6%, cardiomyopathy in 0.3%, and cardiac mortality in 0.5%. Risk factors included anthracycline treatment, cranial and chest radiation, diabetes mellitus, and hyperlipidemia. Another study of 161 children who survived 5 years after SCT demonstrated the presence of cardiomyopathy in 26%. As in adults, total body irradiation (TBI) and anthracycline were the major risk factors.
Survivors treated with TBI tend to have increased central adiposity (which may not always be correlated with BMI). TBI exposure also has been strongly associated with subsequent dyslipidemia and impaired glucose intolerance with a greater risk of developing diabetes mellitus and metabolic syndrome. Separate from TBI, any abdominal radiation also has been associated with an increased risk of diabetes. The presence of untreated endocrinopathies such as growth hormone deficiency, hypothyroidism, and hypogonadism can further exacerbate these comorbidities.
Compared to non-transplanted childhood survivors, SCT survivors have been shown to have a substantially increased burden of serious chronic conditions and impairments involving virtually every organ system and overall quality of life. This likely reflects the joint contributions of pre-transplant treatment exposures and organ dysfunction, the transplant conditioning regimen, and any post-transplant graft-vs-host disease. In a study of 1244 patients with autologous SCT, the 5-year incidence of heart failure was 5%, rising to 9% at 15 years.
Cardiovascular injury occurs commonly in children treated with SCT, but the true long-term implications are still unknown. As they enter the stages of adolescence and young adulthood, we need to emphasize primary prevention and aggressive risk factor modification and treat hypertension, hyperlipidemia, diabetes mellitus, obesity, and promote a smoke and vape-free environment.
Adult transplant survivors experience mortality rates higher than the general population, and the risk of premature cardiovascular-related death is increased 2- to 3-fold compared with the general population. Again, aggressive risk factor modification and treatment of comorbidities are imperative.
This article was written in collaboration with Drs. Wendy Bottinor from VCU Health, Richmond, Virginia, and Carrie Lenneman from UAB School of Medicine in Birmingham, Alabama.
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