Reproductive health issues common in SCD after stem cell transplant
Young patients often not informed about future infertility risks, per study
Reproductive health issues were found to be common after a stem cell transplant among young people with sickle cell disease (SCD), most of whom underwent the procedure at approximately 11 years of age, according to a recent analysis of STELLAR data.
The observed reproductive health issues, which included abnormalities in the production of sex hormones, occurred in both female and male SCD patients. Also, many patients — now with median ages of 19 for women and 20 for men — and parents reported that they were not informed about future infertility risks associated with the procedure.
Given these findings, the researchers noted that “more effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues [after a stem cell transplant].”
Further, “this study also supports the need for improved access to fertility counseling and fertility preservation resources for this unique patient population,” the researchers wrote.
The study, “Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation,” was published in the journal Transplantation and Cellular Therapy.
SCD patients underwent stem cell transplant at about age 11
People with SCD produce a faulty version of hemoglobin — the protein that carries oxygen in red blood cells — which causes red blood cells to take on a sickle-like shape. These cells tend to die prematurely and are prone to getting trapped inside blood vessels, blocking blood flow. This in turn can cause patients to develop anemia, along with other SCD symptoms and complications.
When successful, a stem cell transplant can cure SCD. The procedure usually entails replacing hematopoietic stem cells, which are capable of giving rise to all blood cells, with those obtained from a healthy donor. Its ultimate goal is to enable SCD patients to produce healthy red blood cells.
However, chemotherapy agents often are part of the conditioning regimens that are required before patients can receive the transplant. These agents may damage the gonads — ovaries and testes — which are the reproductive organs that produce reproductive cells (eggs and sperm) and sex hormones. This may lead to a decrease in sex hormones and compromise patients’ fertility.
According to researchers, “there are limited data on gonadal dysfunction and reproductive late effects post-transplant for SCD,” with “a dearth of studies that capture patient-reported fertility [counseling] and reproductive outcomes” following the procedure.
To assess reproductive health and fertility issues in people with SCD, a team led by researchers at Children’s Healthcare of Atlanta analyzed data from the STELLAR study, which evaluated the long-term health outcomes of SCD patients who had received a stem cell transplant at least one year before.
Clinical information was obtained from patient medical records and a reproductive health survey. A total of 20 female patients, with a median age of 19.6 at the time of the survey, and 12 males, with a median of 20.8, were included in the analysis.
These individuals underwent a stem cell transplant at a median of 10.7 years for female patients, and 11.1 years for male patients. Most received bone marrow stem cells that were harvested from matched sibling donors.
Reproductive issues post-transplant include ovarian insufficiency
Before the transplant, a large proportion of patients were treated with the oral medication hydroxyurea (47.4 % females and 45.5% males). This was followed by treatment with both hydroxyurea and blood transfusions (21.1% females and 18.2% males).
Also, most participants had documentation regarding fertility counseling in their medical records, usually only after the transplant; one female patient underwent fertility preservation.
After the transplant, most female patients (90%) had a reduction of ovarian reserve — the total number of egg cells remaining in the ovaries — as evidenced by low or undetectable levels of anti-Mullerian hormone.
Moreover, among the 18 female individuals in whom follicle-stimulating hormone (FSH) levels were measured after the transplant, 11 (61.1%) had FSH levels of 40 milli-international units per milliliter or higher. FSH is a hormone that normally stimulates gonad function. These levels were consistent with ovarian insufficiency, which happens when the ovaries stop working properly before the age of 40.
All males had normal levels of testosterone — the primary male sex hormone. However, most males with available data had high levels of FSH (63.6%), suggesting impaired sperm cell production after the transplant.
Preliminary data from STELLAR suggests that gonadal dysfunction post-transplant is common in patients with SCD and highlights the need for more effective patient education tools.
Survey data was gathered after the transplant from parents, if the patients were younger than 18, and from patients themselves if they were 18 and older.
That data indicated that 25% of the parents and 45% of the patients reported not being told by their healthcare providers about infertility risks following the transplant.
“In conclusion, preliminary data from STELLAR suggests that gonadal dysfunction post-transplant is common in patients with SCD and highlights the need for more effective patient education tools,” the researchers wrote.
“We anticipate that long term data from this cohort will generate more robust findings that will contribute to the development of late effects guidelines and care plans that are specific to the gonadal health of the SCD population post-transplant,” they wrote.
About the Author
