Improved Splenic Function after Stem Cell Transplant for Sickle Cell Disease

Introduction: Splenic dysfunction is a critical complication of SCD that begins in early childhood and can cause fatal sepsis. Hematopoietic stem cell transplant (HSCT) is a proven cure for SCD, however, its long-term effect on the spleen in patients who had SCD is not well characterized. This information could be helpful to further inform medical professionals and families considering HSCT for SCD. Better understanding of the splenic function of patients after transplant for SCD could also provide important information regarding these patients' future risk of infection and other possible problems related to asplenia.

Methods: We conducted a retrospective cohort study of pediatric patients who had HSCT for SCD at two transplant centers. Patients were excluded for analysis if they had pre-HSCT splenectomy, died less than one year post-transplant, failed to engraft, or had no post-HSCT spleen function testing. Tc⁹⁹m liver-spleen (LS) scans and red blood cell (RBC) pit counts, validated tests to evaluate the spleen in SCD, were used to assess splenic function. Splenic uptake on scans was classified as either present or absent. RBC pit count was classified as either normal or abnormal. If a patient had multiple LS scans or RBC pit counts post-HSCT, then the most recent test was used for this analysis.

Results: Fifty-five evaluable patients were identified (53 patients with a post-HSCT LS scan, 29 patients with a post-HSCT RBC pit count, and 27 patients with both tests). Almost all (52/55, 95%) patients had hemoglobin SS or Sβ⁰ disease. Median age at transplant was 8.8 years (range 1.8-22.0 years). Conditioning regimen and stem cell source varied, however, 48/55 (87%) received myeloablative conditioning and an HLA-identical sibling donor HSCT. At a median 2.0 years post-HSCT (range 0.9-8.9 years), 48/53 (91%) had spleen uptake present on LS scan. At a median 3.2 years post-HSCT (range 1.0-11.4 years), 24/29 (83%) had a normal RBC pit count. Analysis of patients who had both pre- and post-HSCT tests showed that patients had significantly improved outcomes post-HSCT:

All patients (17/17, 100%) with LS scan spleen uptake pre-HSCT had uptake present post-HSCT compared to 15/19 (79%) patients with absent spleen uptake pre-HSCT had uptake present post-HSCT (p=0.11). Four patients had absent spleen uptake at 1 year post-HSCT but had uptake present at 2 years post-HSCT.

Conclusion: Our study represents the largest comprehensive evaluation of long-term splenic function in patients after HSCT for SCD. Our results suggest that successful HSCT mitigates damage to the spleen induced by SCD. In patients with splenic function pre-transplant, HSCT appears to preserve this function. In patients lacking splenic function, HSCT appears to engender the return of function in most, but not all patients.