Pediatric Sickle Cell Disease Patients on Hydroxyurea Have Higher Rates of Surgical Splenectomy.

INTRODUCTION: We sought to investigate whether hydroxyurea therapy is associated with the need for surgical splenectomy among patients with sickle cell disease (SCD). We hypothesized that as hydroxyurea gained widespread use, surgical splenectomy among pediatric patients with SCD occurred at a higher rate and older age among those taking hydroxyurea. METHODS: In this retrospective cross-sectional study, the Pediatric Health Information System was queried for all SCD International Classification of Diseases 9/10 diagnosis codes and splenectomy procedure codes from January 1, 2005, to December 31, 2020. Hydroxyurea use was defined as at least one hospital admission with hydroxyurea listed as a medication. The rates of surgical splenectomy, age at splenectomy, hospital length of stay, and incidence of blood transfusion during the splenectomy admission were compared among patients receiving hydroxyurea versus those not receiving hydroxyurea. Additional subanalysis was performed in the Hemoglobin-SS, Hemoglobin-SC, and Other cohorts separately. RESULTS: During the study period, 28,520 patients were identified. All patients with SCD receiving hydroxyurea had a significantly higher rate of surgical splenectomy compared with the nontreatment group (7.2% versus 3.2%, P = 0.01). The age at surgical splenectomy was significantly younger among Hemoglobin-SS patients receiving hydroxyurea (5.7 [5.1, 6.4] y versus 6.6 [5.8, 7.4] y; P < 0.01). There were no significant differences in length of stay or incidence of blood transfusion during the surgical splenectomy admission between treatment groups. CONCLUSIONS: Hydroxyurea use in children is associated with higher rates of surgical splenectomy and occurs at a younger age in the Hemoglobin-SS population. Although these findings warrant further investigation for causality, it provides useful information to clinicians and patients alike, allowing for more informed decision-making.

Successful Liver Transplantation for Adolescent Patient With Pyruvate Kinase Deficiency-induced Cirrhosis.

We present the case of a successful liver transplant in a young adult patient with cholestasis and cirrhosis secondary to severe pyruvate kinase (PK) deficiency. Liver transplant resulted in resolution of liver dysfunction, decreased need for blood transfusions and eligibility for bone marrow transplantation. This case represents the third reported patient in the literature with severe PK deficiency who successfully underwent liver transplant as a result of profound cholestasis and liver failure. Explant pathology demonstrated a lack of significant iron deposition indicating that PK deficiency predisposes the liver to injury independent of transfusion-related iron overload.

Real-Time PCR: an Effective Tool for Measuring Transduction Efficiency in Human Hematopoietic Progenitor Cells.

Accurate measurement of gene transfer into hematopoietic progenitor cells is an essential prerequisite for assessing the utility of gene therapy approaches designed to correct hematologic defects. We developed a reliable method to measure transduction efficiency at the level of the progenitor cell with real-time polymerase chain reaction (PCR) analysis of individual progenitor-derived colonies. We hypothesized that this method would demonstrate better sensitivity and specificity than are currently achievable with conventional PCR. An oncoretroviral vector containing the enhanced green fluorescent protein was used to transduce human CD34+ cells derived from bone marrow or granulocyte-colony-stimulating factor-mobilized peripheral blood. Progenitor assays were set up and colonies plucked after visualization by fluorescence microscopy. By analyzing microscopically identified fluorescent samples and nontransduced samples, we calculated an overall sensitivity and specificity of 90.2 and 95.0%, respectively. Real-time PCR had higher specificity and sensitivity than conventional PCR as analyzed by generalized linear models (P = 0.002 and P = 0.019, respectively). In conclusion, we found real-time PCR to have superior sensitivity and specificity compared to conventional PCR in determining transduction efficiency of hematopoietic progenitor cells.