Study Compares HSCT Outcomes Among Conditioning Approaches in Patients with SCD

A study presented at the 65th ASH Annual Meeting & Exposition compared hematopoietic stem cell transplantation (HSCT)-related outcomes between patients with sickle cell disease (SCD) who received different serotherapies (anti-thymocyte globulin or alemtuzumab) in matched related donor (MRD) HSCT.

Time-to-event analyses were conducted up to three years and were calculated using the Kaplan–Meier method. Outcomes included overall survival (OS); rejection-free survival (RFS), where death and rejection were considered events; and severe graft-versus-host disease (GVHD)-free RFS (GRFS), with death, RFS, and severe GVHD as events. Lastly, GVHD was estimated using Fine-Gray competing risk analyses, factoring in death as a competing event and censoring for rejection.

Conditioning regimens included myeloablative with alemtuzumab (n=66; 32%), non-myeloablative with alemtuzumab (n=49; 23%), myeloablative with horse anti-thymocyte globulin (n=71; 34%), and myeloablative with rabbit anti-thymocyte globulin (n=23; 11%). The median recipient and donor ages at HSCT were 8.4 and 9.3 years, respectively, with similar distribution across cohorts.

The myeloablative with alemtuzumab group exhibited a less severe clinical phenotype, while the non-myeloablative with alemtuzumab group showed decreased pulmonary function. The non-myeloablative with alemtuzumab exhibited the earliest time to neutrophil engraftment, required fewer platelet infusions, and had a shorter hospital stay at a median of 13 days, eight infusions, and 21 days, respectively. Readmissions were highest for myeloablative with alemtuzumab at 77% (compared with 64% overall). Graft rejection occurred only in non-myeloablative with alemtuzumab (n=4; 8.2%) and myeloablative with rabbit anti-thymocyte globulin (n=2; 8.7%).

The three-year cumulative incidence of grade 3/4 acute GVHD was highest in non-myeloablative with alemtuzumab at 12% compared with 0% to 7% overall (P=.130). For any chronic GVHD, non-myeloablative with alemtuzumab had a significantly higher cumulative incidence at 33% (95% CI, 0.19-0.46) compared with 9% to 19% overall (P=.001).

The three-year RFS was slightly lower, though not significantly, in non-myeloablative with alemtuzumab at 87% (95% CI, 0.78-0.97) compared with 91% to 97% in other cohorts (P=.260). The three-year GRFS was significantly lower in non-myeloablative with alemtuzumab at 69% (95% CI, 0.57-0.83) compared with 83% to 94% overall (P=.001). When controlling for age, GRFS in non-myeloablative with alemtuzumab for those aged ≥13 years was significantly lower at 59% (95% CI, 0.40-0.88) compared with 74% to 100% in other cohorts (P=.007).

The investigators concluded, “the potential benefit of non-myeloablative must be balanced against risk of rejection and GVHD, thus providers should carefully consider such when selecting conditioning.”

Reference

John T, Chellapandian D, Shah R, et al. Regimen intensity and age affect transplant-related outcomes after matched related donor hematopoietic cell transplantation for sickle cell disease: a STAR registry study. Abstract #4909. Presented at the 65th American Society of Hematology Annual Meeting; December 9-12, 2023; San Diego, California.