Clinical features, epidemiology, and treatment of Shwachman-Diamond syndrome: a systematic review.

BACKGROUND: Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS. METHODS: We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included. RESULTS: The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years. CONCLUSIONS: Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.

Population Pharmacokinetics of Cyclosporine in Chinese Pediatric Patients With Acquired Aplastic Anemia.

Cyclosporine (CsA) is a component of the first-line treatment for acquired aplastic anemia (acquired AA) in pediatric patients. This study aimed to develop a population pharmacokinetic (PK) model of CsA in Chinese pediatric patients with acquired AA to inform individual dosage regimens. A total of 681 CsA whole blood concentrations and laboratory data of 157 pediatric patients with acquired AA were retrospectively collected from two hospitals in Shanghai. A nonlinear mixed-effect model approach was used to build the population PK model. Potential covariate effects of age, body weight, and biochemical measurements (renal and liver functions) on CsA PK disposition were evaluated. Model fit was assessed using the basic goodness of fit and a visual predictive check. The CsA concentration data were accurately described using a two-compartment disposition model with first-order absorption and elimination. Body weight value was implemented as a fixed allometric function on all clearance and volume of distribution parameters. Total bilirubin level was identified as a significant covariate on apparent clearance (CL/F), with a 1.07% reduction per 1 nmol/L rise in total bilirubin level. The final estimates for CL/F and central volume (Vc/F) were 29.1 L/h and 325 L, respectively, for a typical 28 kg child. Other covariates (e.g., gender, age, albumin, hemoglobin, hematocrit, serum creatinine, and concomitant medication) did not significantly affect the PK properties of CsA. This population PK model, along with a maximum a posteriori Bayesian approach, could estimate individual PK parameters in pediatric patients with acquired AA to conduct individual CsA therapy.

Evaluating the Efficacy and Anti-infective Effect of High-dose Intravenous Immunoglobulin Adjuvant Therapy for Acquired Aplastic Anemia Children.

BACKGROUND: The efficacy and anti-infective effect of high-dose intravenous immunoglobulin (HDIVIG) in severe or very severe aplastic anemia children were evaluated. PATIENTS AND METHODS: In total, 61 patients who underwent immunosuppressive therapy were retrospectively reviewed. The non-IVIG group (30 cases) received rabbit-antithymocyte protein (R-ATG, 3 to 5 mg/kg/d, for 5 consecutive days)+cyclosporin A (CSA), and the HDIVIG group (31 cases) underwent R-ATG+CSA+immunoglobulin (1 g/kg/d, for 2 consecutive days, once a month, 6 times). RESULTS: The early effective rate was higher in the HDIVIG group (P=0.020). However, the long-term effective rate and the 5-year overall survival rates difference were not statistically significant (P=0.717, 0.419). The infection rate and severe infection rate in the HDIVIG group were lower (P=0.003, 0.008). The infection-related mortality differences were not statistically significant after ATG application (P>0.05). In the HDIVIG group, 9 patients were nonresponders. Among the nonresponders, 8 patients' first-dose IVIG was given within 7 days before ATG. CONCLUSIONS: HDIVIG may increase the early effective rate and reduce early infection and serious infection for aplastic anemia children, but failed to reduce the infection-related mortality.