Stem Cell Transplant as Cure for Sickle Cell Disease Improves Quality of Life

A recent prospective, mixed-methods cohort study in Amsterdam indicated overall improvement in physical, mental, and social health after non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT) to treat sickle cell disease (SCD).

“The findings of our study are relevant to a large and growing number of SCD patients, as HSCT is increasingly considered in adults with SCD,” wrote Elisabeth Dovern, of the department of hematology at Amsterdam UMC, and colleagues.1 “Psychosocial support throughout the transplant journey is essential for patients to cope with the [post-]transplant challenges and the altered reality and opportunities that follow curative therapy.”

The study examined a total of 17 participants, each ≥ 16 years of age, who were planning to undergo HSCT. Of the participants, 7 were female, 10 were male, 8 had undergone haploidentical donor HSCT, and 9 underwent matched sibling donor HSCT.1

The team collected 9 Patient-Reported Outcomes Measurement Information System (PROMIS®) measures for all 17 participants at baseline, as well as 6, 12, and 18 months post-transplant. These measures were categorized as follows:

• Physical health, including pain interference, physical function, fatigue, and sleep disturbance
• Mental health, including anxiety, anger, and depression
• Social health, including ability to participate in and satisfaction with social roles

Investigators took mean T-scores and compared them against general population values.1

Additionally, they conducted 2 semi-structured interviews with each of the first 10 participants. The first took place before the start of preconditioning, and the second roughly 12-18 months post-transplant. All participants had successfully engrafted and either stopped or were stopping immunosuppressive agents at time of interview.

Initial results indicated worse measurements in all 3 PROMIS® subcategories pre-transplant when compared to population measures. The first round of interviews reflected this, with participants reporting depression, anxiety, and a lack of physical capability. However, investigators noted a substantial improvement was seen across the board after treatment, with several values matching that of the general population. By the 18-month measurement, most participants exhibited T-levels at or above reference values.1

The team noted no significant difference in PROMIS® score improvements between matched sibling donor and haploidentical donor transplant recipients. Investigators suggested that the different conditioning methods do not have a significant impact on quality-of-life improvement. However, they also note that these findings require a larger patient cohort to verify.1

Physical health outcomes exhibited improvement 6 months post-transplant, which investigators believe is due to normalization of hemoglobin values and resolution of SCD-related vaso-occlusive events. At 18 months, pain interference (P <.001) and physical function (P <.001) were above the average population, while sleep disturbance (P = .852) and fatigue (P = .052) were roughly even with average measurements. Likewise, qualitative results indicated a sharp improvement in quality of life; in the second round of interviews, participants reported an increased capacity for physical activity and lower need for sleep.1

Mental health T-values exhibited a more gradual and less pronounced increase post-transplant. After 18 months, anxiety (P = .016), anger (P = .037), and depression (P = .025) were slightly above population measurements. Interviews revealed various mental health challenges during the first year, such as the fear of SCD returning. The team also indicated potential negative side effects to the transplant as a source of anxiety.1

Investigators suggested the “burden of normality”, or the struggle to adjust to a symptomless life after treatment, as another plausible explanation2 Although this has not yet been directly documented for patients with SCD, investigators believe it to be a partial cause for the lower mental health measurements.

Notably, both social health T-values remained relatively low after surgery, rising above the general population only after 18 months (both P <.001). The team believes is a result of lifestyle restrictions due to immunosuppressive therapy. The interviews also revealed some disappointment with social interactions before and during the transplant process.1

Given the significant differences in all PROMIS® categories from pre- to post-operation and the variance in interview responses, Dovern and colleagues point out that the results underscore the importance of providing support for patients entering the curative process.

“The effects of HSCT on mental health are more complex and include many positive effects as well as difficulties with adjustment and processing the psychological aftermath of SCD,” wrote Dovern and colleagues.1 “Incorporation of psychosocial care and patient-reported outcome measures into the treatment plan of SCD patients undergoing HSCT is needed to improve the transplant outcomes and patient experience.”

References

1. Dovern E, Nijland SJ, Braamse AM, et al. Changes in the quality of life of adults with sickle cell disease following allogeneic stem cell transplantation: A mixed‐methods, prospective Cohort Study. HemaSphere. 2025;9(3). doi:10.1002/hem3.70100

2. Baas L, van der Graaf R, van Hoorn ES, Bredenoord AL, Meijer K. The ethics of gene therapy for hemophilia: A narrative review. Journal of Thrombosis and Haemostasis. 2023;21(3):413-420. doi:10.1016/j.jtha.2022.12.027