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Objectives: Graft‐versus‐host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. Materials and Methods: This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. Results: Despite the GvHD prophylaxis, grade II–IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI‐related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p =.013). There was no significant difference between the groups in terms of engraftment syndrome, veno‐occlusive disease, CMV reactivation, PRES, or graft rejection. Conclusion: Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI. [ABSTRACT FROM AUTHOR]

Background: Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency. Methods: We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen. Results: In the conditioning regimen, rituximab was given on Day −11 (375 mg/m2), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days −7 to −4) with 150 mg/m2 of fludarabine (Days −7 to −3). They were transplanted with peripheral blood stem cells, and graft‐versus‐host disease (GVHD) prophylaxis was administered with 10 mg/m2 methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno‐occlusive disease (VOD), high‐grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism. Conclusions: Serine/threonine kinase 4 deficiency is a disease with high mortality post‐HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU‐FLU), GVHD prophylaxis with sirolimus and MMF, and short‐term methotrexate, offers favorable outcomes and is well tolerated in our STK4‐deficient patients. [ABSTRACT FROM AUTHOR]

Background: Post‐transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Data on risk factors, treatment options, and outcomes are limited. Procedure: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo‐HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo‐HSCT. Results: The median interval from transplantation to relapse was 180 days, and the median follow‐up from relapse to the last follow‐up was 1844 days. The 3‐year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo‐HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P =.011) and relapse earlier than 365 days post‐transplantation (HR: 2.101, P <.001 for 0‐180 days; HR: 1.522, P =.041 for 181‐365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS. Conclusion: A salvage approach with curative intent may be considered for patients with post‐transplant relapse, even if they relapse in the first year post‐transplantation. For sustainable remission, a second allo‐HSCT may be recommended for patients who achieve complete remission after reinduction treatment. [ABSTRACT FROM AUTHOR]

The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty‐four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real‐time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow‐up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1‐80) and 32 days (range: 2‐79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101‐1.2 × 1014) and 1.9 × 103 copies/mL (range: 3‐2.1 × 106), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65‐1 × 1011) and 2.9 × 103 (range: 7‐7.8 × 104) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV‐related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV–related HC. [ABSTRACT FROM AUTHOR]