Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes.

Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various genetic causes, and if it remains untreated, patients succumb to infections during the first 2 years of life. PURPOSE AND METHODS: This study reported retrospective data from 72 infants diagnosed with SCID including their major clinical features, HSCT characteristics, and outcomes over a 20-year period (1997-2017). RESULTS: Sixty-one of 72 SCID patients in the study underwent HSCT from 1997 to 2017. Median ages at the time of diagnosis and transplantation were 3.5 months and 5 months, respectively. Consanguinity was present in 68% of the patients, and T - B - NK + phenotype was predominantly identified. The overall survival was 80.3% over a 20-year period. However, the patients transplanted during an active infection had a lower survival rate of 73.9% compared to 100% for patients transplanted infection-free or with a previous infection that had resolved. The survival rate was significantly higher among recipients of HLA-identical transplants (92.9%), compared to recipients of mismatched related transplants (70%). The overall survival increased from 50 (1997-2006) to 85% (2007-2017) during the last 10 years. CONCLUSIONS: This is one of the largest single-center studies in Turkey with extensive experience about SCID patients. Early diagnosis of SCID patients before the onset of an infection and early transplantation are shown to be extremely important factors affecting the outcome and increasing the survival regardless of the donor type based on the results of this study.

ST2 and Reg3α: Can they predict aGvHD, steroid refractoriness and transplant-related mortality in pediatric patients after HSCT?

BACKGROUND/AIM: There are several complications of hematopoietic stem cell transplantation. Without any doubt, most important of these is aGvHD that increases transplant-related mortality. The aim of this study is to investigate whether ST-2 and Reg3α levels measured at an early stage in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation can be individual biomarkers identifying future GvHD and predicting treatment response. MATERIALS AND METHODS: From January 2019 to January 2021, 27 patients undergoing hematopoietic stem cell transplantation for primary immunodeficiency or hematopoietic diseases formed the study group. During their follow-up, the patients were classified into two groups as those developing and those not developing aGvHD. Nineteen healthy volunteers from a similar age group who needed their blood samples drawn for other reasons and who did not have any history of chronic disease, infection or medication use formed the control group. Blood samples of patients scheduled to have allogeneic HSCT were obtained before the administration of the preparative regimen, on Day +7 post-transplant and on the day of diagnosis if they developed aGvHD. Serum samples were stored at -20ºC until the day of processing. ST2 and Reg3α levels were measured using the ELISA method. RESULTS: For patients who developed aGvHD (n = 13), ST2 levels obtained before the transplantation, on Day +7 post-transplant and on the day of aGvHD diagnosis (in patients developing GvHD) were significantly higher compared to the healthy Control Group (p-value <0.05). As regards to the samples obtained on the same days, ST2 levels did not differ significantly among patients who developed and those who did not develop GvHD (n = 14; p-value >0.05). ST2 levels of samples obtained on the days that acute skin and gastrointestinal tract GvHD developed did not differ significantly between these two groups (p-value >0.05). Reg3α levels of the pre-transplant samples, on Day +7 after the transplantation and on the day of aGvHD diagnosis did not show any difference between any of the groups (p-value >0.05). As only two patients died after transplantation, thus correlation of ST2 and Reg3α levels with transplant-related mortality could not be proven. CONCLUSION: The results of this study suggest that ST2 and Reg3α levels are neither diagnostic nor prognostic or predictive biomarkers of aGvHD, steroid resistance or transplant-related mortality in pediatric patients. This study can be regarded as a pilot study because of the small patient population; more research involving a larger patient population is required.

Evaluation of thymopoiesis in healthy Turkish children aged 0-6 years.

BACKGROUND: Early diagnosis and effective treatment serve as life-saving procedures for primary immunodeficiencies (PIDs) which are very common and a major public health problem in Turkey. Severe combined immunodeficiency (SCID) is constitutively a T-cell defect in which naïve T-cell development is defective due to the mutations in genes responsible for the T cell differentiation and insufficient thymopoiesis. So, assessment of thymopoiesis is very important in the diagnosis of SCID and several combined immune deficiencies (CIDs). METHODS: The purpose of this study is to examine thymopoiesis in healthy children via measurement of recent thymic emigrants (RTE); T lymphocytes that express CD4, CD45RA and CD31 to establish the RTE reference values in Turkish children. RTE were measured in the peripheral blood (PB) of 120 healthy infants and children between 0-6 years including cord blood samples, by flow cytometry. RESULTS: The absolute count of RTE cells and their relative ratios were found to be higher during the first year of life, being highest at the 6th month and tending to decrease significantly by age following birth (p=0.001). In the cord blood group, both values were lower than those in the 6-month-old group. The absolute lymphocyte count (ALC) varying by age, was found to reduce to 1850/mm³ in 4-years and after. CONCLUSIONS: Here we evaluated normal thymopoiesis and established the normal reference levels of RTE cells in the peripheral blood of healthy children aged between 0-6 years. We believe that the collected data will contribute to early diagnosis and monitoring of immune reconstitution; serving as an additional fast and reliable marker for many PID patients especially for SCID including many other CIDs, especially in nations where newborn screening (NBS) via T cell receptor excision circles (TREC) has not yet become available.