We explored the clinical course of acute high-grade gastrointestinal graft-versus-host disease in children in a single center. This was a retrospective analysis of 28 pediatric patients who presented ...with a clinical diagnosis of stage III and IV acute graft-versus-host disease (aGVHD) of the gastrointestinal system (GIS). Generally, skin involvement was the initial manifestation of aGVHD that began in the first 3 weeks of hematopoietic stem cell transplantation (HSCT); on the other hand, GIS involvement predominated after the second week of HSCT. Reported adult data show a survival rate of only 25%; however, our study showed more favorable outcomes in children with a survival rate of 55%. We monitored levels of albumin and immunoglobulin G and observed low levels overall during treatment of unresponsive patients, although only albumin levels were shown to be significantly different. We observed a significant increase in mortality with the use of antithymocyte globulin in GIS aGVHD, although antithymocyte globulin used for graft-versus-host disease prophylaxis had no demonstrable effect on GIS aGVHD mortality. Whether the significantly lower GIS aGVHD mortality among the children recruited in our study than among their historical adult counterparts is a primary result of the specific attributes of the pediatric GIS, or whether it originated from HSCT kinetics remains to be determined by future studies.
Background
ALD is a rare X‐linked peroxisomal metabolic disorder with many distinct phenotypes of disease that emerge on a wide scale from adrenal insufficiency to fatal cALD which progresses to a ...vegetative state within a few years. Currently, HSCT is the only treatment method known to stabilize disease progression in patients with cALD. In this study, we aim to report our HSCT experience in patients with cALD and the factors that determine the success of HSCT, as a single‐center experience.
Methods
The study cohort involves 23 boys with cALD and three patients with ALD trait and new‐onset abnormal behavior who underwent allogeneic HSCT between January 2012 and September 2019 in our transplantation center. Loes scoring, NFS, scale and MFD were performed for evaluating the severity of the cerebral disease. The study cohort was divided into two groups according to baseline NFS and Loes score: early‐stage (NFS ≤ 1 and Loes score <9) and advanced stage (NFS > 1 or Loes score ≥9).
Results
The pretransplant stage of disease impacted both OS and MFD‐free survival. The estimated OS and MFD‐free survival at 3 years in patients with advanced disease were 46.1% (95% CI 19.0–73.2) and 23.1% (95% CI 0.2–46.0), respectively, and all patients with the early disease were alive (p: .004) and MFD‐free (p < .001) at 3 years.
Conclusion
This study demonstrated that early HSCT is vital in patients with cALD. The early‐stage disease had a significant survival advantage and free from disease progression after HSCT.
Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The ...advent of next‐generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon‐based targeted NGS panel, which contained 18 most common SCID‐related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease‐causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom‐made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK− SCID). Incidence of autosomal‐recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom‐made sequencing panel was able to identify and confirm the previously known and novel disease‐causing variants with high accuracy.
We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell ...Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.
Background
Post‐Cy administration for GVHD prophylaxis in unmanipulated haploidentical HSCT has resulted in improved outcomes in recent years. Studies in children are lacking and accordingly we ...present the outcomes of 62 haploidentical transplantation for high‐risk children.
Procedure
We retrospectively assessed 62 transplants in 60 patients who underwent haploidentical‐related HSCT with unmanipulated stem cells and for whom Post‐Cy was used for GVHD prophylaxis.
Results
Myeloid reconstitution was achieved on day + 30 for 57 of the 62 patients. The median follow‐up of the surviving 39 patients (63%) was 26 months, with a range of 6‐57 months. The OS and EFS at 2 years were 64.6% (52.0%‐77.2%, 95% CI) and 58.9% (46.1%‐71.7%, 95% CI), respectively. The only factor in our multivariate analysis that contributed to an inferior EFS was a poor remission status prior to HSCT (HR, 8.30; 1.08‐63.56; P = 0.041, 95% CI).
Conclusion
The results of T‐cell replete haploidentical transplantation with Post‐Cy GVHD prophylaxis in high‐risk pediatric patients are promising. However, further research is needed to determine the factors that have affect HLA compatibility for predicting the success of haploidentical transplantations.
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.
Extracorporeal photopheresis (ECP) is a difficult procedure to perform in the pediatric population. This is a retrospective review of 12 pediatric patients who underwent photopheresis with the ...Therakos Cellex system for graft-versus-host disease (GVHD). Acute GVHD (aGVHD) occurred in 6 patients, and overlap syndrome and chronic GVHD (cGVHD) occurred in 4 and 2 patients, respectively. The ECP regimen was the same for all aGVHD and cGVHD patients: initially, every week (2 sessions/wk) for 2 months; next, every 2 weeks for 2 months; and finally, every month for at least 1 year. Improvement was observed in 7 of 10 aGVHD patients (70%) and in 4 of 6 cGVHD patients (66%). Eleven patients had skin involvement before ECP; 9 of them responded to treatment (81%). Gastrointestinal involvement occurred in 8 patients; 5 of them experienced improvement during ECP treatment (62%). All 4 patients with liver involvement failed to respond. No serious adverse reactions occurred. In conclusion, our study demonstrates that ECP with the Therakos Cellex system is a safe treatment option for GVHD in children, allowing the tapering of immunosuppressants by at least half.
Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, ...and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.
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