Dataset Information

Sickle Cell Transplantation Evaluation of Long-term and Late Effects Registry (STELLAR) to Compare Long-term Outcomes After Hematopoietic Cell Transplantation to Those in Siblings Without Sickle Cell Disease and in Nontransplanted Individuals With Sickle Cell Disease: Design and Feasibility Study.

ABSTRACT:

Background

There are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD).

Objective

This study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States.

Methods

The Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study (BMTSS) surveys, health-related quality of life (HRQOL) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25 or Pediatric Profile-29 survey, chronic graft-versus-host disease (cGVHD) using the symptom scale survey, daily pain using an electronic pain diary, the economic impact of HCT using the financial hardship survey, sexual function using the PROMIS Sexual Function SexFSv2.0 survey, and economic productivity using the American Time Use Survey (ATUS). We also piloted retrieval of clinical data previously submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR); recorded demographics, height, weight, blood pressure, waist and hip circumferences, timed up and go (TUG) test, and handgrip test; and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA.

Results

Of 100 eligible post-HCT patients, we enrolled 72 (72%) participants aged 9-38 (median 17) years. We also enrolled 19 siblings aged 5-32 (median 10) years and 28 nontransplanted controls with SCD aged 4-46 (median 22) years. Of the total 119 participants, 73 (61%) completed 85 sets of surveys and 41 (35%) contributed samples to the biorepository. We completed ATUS interviews of 28 (24%) participants. We successfully piloted retrieval of data submitted to the CIBMTR and expanded recruitment to multiple sites in the United States, Canada, the United Kingdom, and Nigeria.

Conclusions

It is feasible to recruit subjects and conduct study procedures for STELLAR in order to determine the long-term and late effects of HCT for SCD.

International registered report identifier (irrid)

DERR1-10.2196/36780.

SUBMITTER: Krishnamurti L

PROVIDER: S-EPMC9301564 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Sickle cell disease (SCD) is a severe autosomal recessively inherited disorder of the red blood cell characterized by erythrocyte deformation caused by the polymerization of the abnormal hemoglobin, which leads to erythrocyte deformation and triggers downstream pathological changes. These include abnormal rheology, vaso-occlusion, ischemic tissue damage, and hemolysis-associated endothelial dysfunction. These acute and chronic physiologic disturbances contribute to morbidity, organ dysfunction, and diminished survival. Hematopoietic cell transplantation (HCT) from HLA-matched or unrelated donors or haploidentical related donors or genetically modified autologous hematopoietic progenitor cells is performed with the intent of cure or long-term amelioration of disease manifestations. Excellent outcomes have been observed following HLA-identical matched related donor HCT. The majority of SCD patients do not have an available HLA-identical sibling donor. Increasingly, however, they have the option of undergoing HCT from unrelated HLA matched or related haploidentical donors. The preliminary results of transplantation of autologous hematopoietic progenitor cells genetically modified by adding a non-sickling gene or by genomic editing to increase expression of fetal hemoglobin are encouraging. These approaches are being evaluated in early-phase clinical trials. In performing HCT in patients with SCD, careful consideration must be given to patient and donor selection, conditioning and graft-vs.-host disease regimen, and pre-HCT evaluation and management during and after HCT. Sociodemographic factors may also impact awareness of and access to HCT. Further, there is a substantial decisional dilemma in HCT with complex tradeoffs between the possibility of amelioration of disease manifestations and early or late complications of HCT. The performance of HCT for SCD requires careful multidisciplinary collaboration and shared decision making between the physician and informed patients and caregivers.

Project description:ImportanceIndividuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD.ObjectiveTo estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD.Design, setting, and participantsCohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018.Main outcomes and measuresLife expectancy, quality-adjusted life expectancy, and projected lifetime income.ResultsThe estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates.Conclusions and relevanceIn this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.

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