Erfan Nur

Sickle cell disease (SCD)‐related organ complications are a major cause of morbidity and mortality in patients with SCD. We sought to assess whether hematopoietic stem cell transplantation (HSCT) stabilizes, attenuates, or exacerbates organ decline. We performed a systematic review and meta‐analysis of trials investigating organ function before and after HSCT in patients with SCD. We searched MEDLINE/PubMed and EMBASE up to September 21, 2023. Continuous data were expressed as standardized mean difference (SMD) and pooled in a weighted inverse‐variance random‐effects model; binomial data were expressed as risk ratio (RR) using the Mantel–Haenszel random‐effects meta‐analyses. Of 823 screened studies, 34 were included in this review. Of these, 17 (774 patients, 23.6% adults, 86.3% HLA‐identical sibling donor, 56.7% myeloablative conditioning regimen) were included in the meta‐analyses. Pulmonary function remained stable. Mean tricuspid regurgitant jet velocity decreased but did not reach statistical significance. In children, estimated glomerular filtration rate decreased (SMD −0.80, p = .01), and the presence of proteinuria increased (RR 2.00, p = <.01), while splenic uptake and phagocytic function improved (RR 0.31, p = <.01; RR 0.23, p = <.01). Cerebral blood flow improved (SMD −1.39, p = <.01), and a low incidence of stroke after transplantation in high‐risk patients was found. Retinopathy and avascular osteonecrosis were investigated in only one study, showing no significant changes. While HSCT can improve some SCD‐related organ dysfunctions, transplantation‐related toxicity may have an adverse effect on others. Future research should focus on identifying individuals with SCD who might benefit most from HSCT and which forms of organ damage are more likely to exacerbate post‐transplantation.

Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side‐effects, high costs, and the lack of availability in many countries with a high prevalence of hereditary anemias. In this phase III randomized placebo‐controlled trial, we assigned adults with non‐transfusion‐dependent hereditary anemias with mild‐to‐moderate iron overload to receive esomeprazole (at a dose of 40 mg twice daily) or placebo for 12 months in a cross‐over design. The primary end point was change of liver iron content measured by MRI. A total of 30 participants were enrolled in the trial. Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55 mg Fe/g dw larger than after treatment with placebo (95%CI [0.05 to 1.06]; p = 0.03). Median baseline liver iron content at the start of esomeprazole was 4.99 versus 4.49 mg Fe/g dw at start of placebo. Mean delta liver iron content after esomeprazole treatment was −0.57 (SD 1.20) versus −0.11 mg Fe/g dw (SD 0.75) after placebo treatment. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. In summary, esomeprazole resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non‐transfusion‐dependent hereditary anemias. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators.