Introduction: Hematopoietic stem cell transplantation (HSCT) using a human leukocyte antigen (HLA)-identical sibling donor is a proven cure for Sickle Cell disease (SCD). Allogeneic non myeloablative HSCT from HLA-matched related donors results in event-free survival rates (EFS) of 87% to 92%, overall survival (OS) rates of 97% to 100%, and 0% acute or chronic graft-versus host disease (GVHD) in SCD adults. However, a significant obstacle is the availability of suitable HLA-matched related donors. According to literature, there is an unmet need for alternative donors, as less than 20% of SCD patients present a matched sibling donor (MSD) in the United States of America, with a mean number of siblings per patient <1 (0.73) when half-siblings and siblings who had sickle cell anemia were excluded. Alternative donor stem cell sources include autologous stem cell or haploidentical familial donor stem cell. Other important barriers exist, as evidenced by the fact that some patients have healthy siblings, but never underwent HLA typing. In this context, we sought to characterize our cohort of eligible SCD adult patients for HSCT, to assess donor availability in a French Referral Center.

Method: We carried out a descriptive analysis of adult SCD patients who were candidates for HSCT in our institution, according to their HLA status. HLA typing was performed between 2020 and 2024 in this cohort who have never undergone HLA typing before, and concerns only fully healthy siblings (half-siblings and siblings who had sickle cell anemia were not included).

Results: 124 patients (45% female) were included in the analyses: 118 patients (95%) were homozygous SS genotype, four (3,2%) were S-beta° and two (<2%) were SO Arab. Median age was 35 years-old [20-58]; mean number at HLA typing of healthy siblings per patient was 1,92 (1-6); median number was 2 [1-3]. Patients were treated with Hydroxycarbamide (HU) (93%), chronic transfusion therapy (27%), L Glutamine (12%) -combined therapy with HU in 80%- or Voxelotor (5%). Vaso occlusive (VOC) profile was the mean reason (93%) for HSCT discussion, followed by neurologic involvement (intra-cranial cerebral vasculopathy) (10%) and Delayed Hemolysis Transfusion Reaction (DHTR) (13%). Concerning HLA typing, sixty-two patients (50%) had at least one MSD with a mean number of healthy siblings per patient at HLA typing of 2 (1-5); median was 2 [1-3]; five patients had >1 MSD and one patient had three MSD. Sixty-two patients (50%) had a not-MSD (haplo-identical familial donor or different HLA) with mean number of siblings per patient at HLA typing of 1.8 (1-6); median was 2 [1-3]. For patients with a MSD, treatment with HU was noted for 87% of them, chronic transfusion therapy for 22%, L Glutamine for 11% -combined therapy with HU in 57%- and Voxelotor for 6% of them. VOC profile was the mean reason for HSCT discussion (89%) in MSD group followed by neurologic involvement (13%). DHTR was noted in 21%; kidney transplant prior to HSCT discussion was noted in 2 patients.

Twenty patients from this cohort underwent an allogenic HSCT in our center between 2020-2024 with 19 allogenic non-myeloablative HSCT in MSD group (31%) showing EFS and OS rates of 100%, with a median follow-up of 9 months [1-54]. One HSCT was noted in non-MSD group with a haploidentical familial donor performed on June 2024. Three patients (2.4%) died before HSCT was performed with a MSD for two patients and a haploidentical familial donor for one.

Conclusion: In our referral center at Henri Mondor hospital, we show a higher rate (50%) of MSD after HLA typing of adult candidates for HSCT, compared to literature (18%). Our results could be related to family configurations with a higher number of siblings per patient (1,92). The ethnic origin of our SCD cohort (40% from West Africa, 29% from Central Africa and 26% from West Indies) has probably an impact on the number of potential healthy siblings. Increasing the number who can undergo an HSCT will require increasing the size of the donor pool, so systematic HLA typing should be encouraged at an early stage in the course of the disease, especially in adult patients who have never undergone the test, before the presence of definitive organ damage. To ensure that patients and families are informed about HSCT, HLA typing of full siblings of patients with SCD should be a clinical priority

Disclosures

De Luna:Vertex: Consultancy; Pfizer: Other: Sponsor HEMOPROVE trial NCT05199766. Bartolucci:Novartis: Consultancy, Other: member advisory board and member steering commitee; Bluebird: Consultancy; Roche: Consultancy; JazzPharma: Consultancy; Emmaus: Consultancy; Innovhem: Other: Founder; Addmedica: Consultancy, Other: member advisory board; Pfizer: Consultancy.

This content is only available as a PDF.
2024
Sign in via your Institution