Long-term quality of life after hematopoietic cell transplant for sickle cell disease in childhood: A STELLAR interim analysis.

We prospectively collected PROMIS©25 and PROMIS©29 surveys in the Sickle Cell Transplant Evaluation of Long Term and Late Effects Registry (STELLAR). Mobility and social participation T-scores were decreased; all other domains were within the norm.

Reproductive Health Assessment and Reports of Fertility Counseling in Pediatric and Adolescent Patients with Sickle Cell Disease After Hematopoietic Cell Transplantation.

Conditioning regimens for hematopoietic cell transplant (HCT) in patients with sickle cell disease (SCD) place patients at risk for reproductive health issues. The purpose of this study was to assess reproductive health and reports of fertility counseling in patients with SCD who received a transplant. This was a secondary analysis of gonadal hormone production, future infertility risk assessment, and parent-proxy/patient reports of fertility counseling in SCD transplant recipients who are currently pubertal and were enrolled in the Atlanta sites of the Sickle Cell Transplant Evaluation of Long-term and Late Effects Registry (STELLAR) between May 2017 and October 2023. Clinical information was abstracted from medical records and reproductive health survey data from the STELLAR database. Descriptive statistics were reported as median (interquartile range [IQR]) or percentages. There were 20 females and 12 males in the study population. Females were median (IQR) 19.6 (9.4) years old and males 20.8 (11.4) years old at the time of the study. Transplants most commonly occurred in the decade 2010 to 2019 at 10.7 (4.8) years old for females and 11.1 (4.1) years old for males. Most participants received bone marrow stem cells (95.0% females, 100.0% males) from matched sibling donors (90.0% females, 100.0% males). Participants received one of seven HCT conditioning regimens with cyclophosphamide equivalent doses ranging from 3388 to 9706 mg/m2. The majority of females (90.0%) had diminished ovarian reserve with low anti-Mullerian hormone levels, and 61.1% had premature ovarian insufficiency with two follicle-stimulating hormone levels (FSH) ≥40 mIU/mL post-HCT. All males had normal testosterone levels, but 63.6% had elevated FSH levels suggestive of impaired spermatogenesis post-HCT. Parent proxies (for patients <18 years old) and patients ≥18 years old completed surveys 9.0 years (5.2) and 7.9 years (9.3) since HCT in females and males respectively. Twenty-five percent of parent proxies and 45% of patients reported that they had not been informed by a healthcare provider of the risk of infertility post-transplant. There are high rates of gonadal dysfunction post-HCT, but many parent proxies and patients do not recall being told of the risk for future infertility. More effective methods of education are warranted to ensure SCD patients and their families clearly understand the risk for reproductive health issues post-HCT.

Female Reproductive Health Outcomes after Hematopoietic Cell Transplantation for Sickle Cell Disease: Is Reduced Intensity Better Than Myeloablative Conditioning?

Curative therapy for sickle cell disease (SCD) through hematopoietic cell transplantation (HCT) is associated with a high level of risk for treatment-related gonadal dysfunction and future infertility. Both the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens used for SCD HCT are considered to carry a high risk for ovarian damage. Cyclophosphamide equivalent doses (CEDs) are thought to correlate with the degree of gonadal damage in pediatric oncology patients. We aimed to evaluate ovarian outcomes previously reported from our center, characterize the conditioning regimens as MAC or RIC, and calculate the CED for each regimen. The ovarian outcomes diminished ovarian reserve (DOR), as determined by an anti-Müllerian hormone (AMH) below the normal limits for age and assay or <5%, and premature ovarian insufficiency (POI), defined as a follicle-stimulating hormone (FSH) level >40 mIU/ML, are presented by conditioning regimen from 3 clinical studies from our center (2 published and 1 presented as an abstract in 2022). The studies were not mutually exclusive of patients. CEDs were calculated for each regimen. The CED ranged from 3388 to 9705 mg/m2 for MAC regimens and from 5600 to 18,750 mg/m2 for RIC regimens. DOR was observed in all regimens; however, in one study 2 patients had normal AMH levels after a fludarabine/melphalan regimen, and 1 patient had a normal AMH level after a fludarabine/melphalan/thiotepa regimen. Rates of POI were more variable and ranged from 40% to 100% after MAC regimens and from 0 to 100% after RIC regimens. Female patients with SCD who undergo HCT have very high rates of DOR after both MAC HCT and RIC HCT. Two of the 3 RIC regimens evaluated had higher CEDs than were seen in any of the MAC regimens evaluated. Rates of POI were more variable but may increase with time from transplantation. All SCD patients need to be counseled about the risk of infertility and provided information about fertility preservation.

A Decision Support Tool for Allogeneic Hematopoietic Stem Cell Transplantation for Children With Sickle Cell Disease: Acceptability and Usability Study.

BACKGROUND: Individuals living with sickle cell disease (SCD) may benefit from a variety of disease-modifying therapies, including hydroxyurea, voxelotor, crizanlizumab, L-glutamine, and chronic blood transfusions. However, allogeneic hematopoietic stem cell transplantation (HCT) remains the only nonexperimental treatment with curative intent. As HCT outcomes can be influenced by the complex interaction of several risk factors, HCT can be a difficult decision for health care providers to make for their patients with SCD. OBJECTIVE: The aim of this study is to determine the acceptability and usability of a prototype decision support tool for health care providers in decision-making about HCT for SCD, together with patients and their families. METHODS: On the basis of published transplant registry data, we developed the Sickle Options Decision Support Tool for Children, which provides health care providers with personalized transplant survival and risk estimates for their patients to help them make informed decisions regarding their patients' management of SCD. To evaluate the tool for its acceptability and usability, we conducted beta tests of the tool and surveys with physicians using the Ottawa Decision Support Framework and mobile health app usability questionnaire, respectively. RESULTS: According to the mobile health app usability questionnaire survey findings, the overall usability of the tool was high (mean 6.15, SD 0.79; range 4.2-7). According to the Ottawa Decision Support Framework survey findings, acceptability of the presentation of information on the decision support tool was also high (mean 2.94, SD 0.63; range 2-4), but the acceptability regarding the amount of information was mixed (mean 2.59, SD 0.5; range 2-3). Most participants expressed that they would use the tool in their own patient consults (13/15, 87%) and suggested that the tool would ease the decision-making process regarding HCT (8/9, 89%). The 4 major emergent themes from the qualitative analysis of participant beta tests include user interface, data content, usefulness during a patient consult, and potential for a patient-focused decision aid. Most participants supported the idea of a patient-focused decision aid but recommended that it should include more background on HCT and a simplification of medical terminology. CONCLUSIONS: We report the development, acceptability, and usability of a prototype decision support tool app to provide individualized risk and survival estimates to patients interested in HCT in a patient consultation setting. We propose to finalize the tool by validating predictive analytics using a large data set of patients with SCD who have undergone HCT. Such a tool may be useful in promoting physician-patient collaboration in making shared decisions regarding HCT for SCD. Further incorporation of patient-specific measures, including the HCT comorbidity index and the quality of life after transplant, may improve the applicability of the decision support tool in a health care setting.