KIM-1, IL-18, and NGAL, in the Machine Learning Prediction of Kidney Injury among Children Undergoing Hematopoietic Stem Cell Transplantation-A Pilot Study.

Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.

Short- and long-term outcome of allogeneic stem cell transplantation in infants: A single-center experience over 20 years.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants. Material and methods: In the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation. Results: The probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III-IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (<3rd percentile) in 37.2% and overt hypothyroidism in 35.4%. In the long-term perspective, 83.3% of survivors were able to attend a regular school. Conclusions: Improvements in unrelated donor availability, and better supportive care resulted in better outcomes. Management of infant allo-HSCT recipients requires the formation of multi-disciplinary specialist teams. In addition, the role of parental empowerment must be acknowledged; for example, in speech therapy and rehabilitation.

Vedolizumab in highly resistant acute gastrointestinal graft-versus-host disease after allogeneic stem cell transplantation: A single-center pediatric series.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a lifesaving procedure in malignant and nonmalignant diseases. However, it is associated with a considerable risk of graft-versus-host disease (GvHD). Steroids are a first-line therapy for acute GvHD (aGvHD), but there is no standard treatment for steroid-resistant (SR) gastrointestinal (GI) aGvHD, which has a poor prognosis. The anti-integrin antibody, vedolizumab, could help in controlling SR GI aGvHD symptoms by blocking lymphocyte extravasation and infiltration of the intestinal wall. OBJECTIVES: To report the outcomes of 3 children with SR GI aGvHD after allo-HSCT, treated with vedolizumab as the last chance drug. MATERIAL AND METHODS: The study included 3 patients aged from 8 to 10 years who underwent HSCT in Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology at Wroclaw Medical University, Poland, and who developed severe SR GI aGvHD. All patients had grade IV SR aGvHD with GI stage 4 manifestation. Vedolizumab was given as salvage therapy after an ineffective treatment with etanercept, basiliximab, ruxolitinib, extracorporeal photopheresis, and mesenchymal stem cell infusions. Vedolizumab was administered intravenously at a dose of 300 mg. RESULTS: Only 1 patient achieved GvHD remission and was alive and well 9 months after the discontinuation of the therapy. One child developed a relapse of malignant disease and eventually died, and the third child died of severe aGvHD. CONCLUSION: Vedolizumab can be safely used in children with SR GI aGvHD, offering an additional chance for heavily pretreated patients. Prospective pediatric studies on both prophylactic and therapeutic use of the drug are warranted, according to the preliminary results.

Successful Salvage Haploidentical Bone Marrow Transplantation in a Child With Hemophagocytic Lymphohistiocytosis, When the Previously Matched Unrelated Donor Tested Positive for SARS-CoV-2 on the Day of Stem Cells Collection.

The coronavirus disease 2019 pandemic has made us adjust our standards and cope with unpredictable circumstances affecting the whole world, including the medical field. A 2-year-old boy diagnosed with X-linked lymphoproliferative disease type 2 with concomitant positive polymerase chain reaction test for Epstein-Barr virus-DNA was admitted to our transplant ward. His treatment scheme had to be modified at the last moment because of a donor disqualification due to a positive polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 just before the apheresis. We decided to perform salvage haploidentical bone marrow transplant from the patient's mother because it was the only possible option. Now, in a 5-month observation period after the hematopoietic stem cell transplantation, our patient is in good general condition. His case convinced us to redirect our approach to transplant procedure preparation. Following the European Group of Blood and Marrow Transplantation recommendations, we use cryopreserved apheresis materials to ensure the availability of stem cell products before the start of a conditioning regimen.

Severe, Reversible Acute Lung Injury During Autologous Hematopoietic Stem Cell Mobilization After Filgrastim in a Child With Neuroblastoma: A Case Report.

Peripheral blood hematopoietic stem cell mobilization is widely performed in a variety of clinical facilities and is believed to be a safe outpatient procedure. In this report, we describe a child with neuroblastoma who developed an extremely severe acute lung injury after granulocyte colony-stimulating factor was used for peripheral hematopoietic stem cell mobilization. A 3-year-old boy with a medical history of patent foramen ovale and secundum atrial septal defect was diagnosed with an MYCN-amplified neuroblastoma and treated with chemotherapy. During stem cell mobilization with filgrastim, the boy was in very good clinical condition, with a peripheral white blood cell (WBC) count of 57.17 K/µL, but he suddenly deteriorated, and nausea, seizures, and nystagmus were observed. The patient developed dyspnea with hemoptysis, and lung computed tomography showed bilateral asymmetrical pulmonary opacification demonstrating an anteroposterior density gradient. Because of rapidly progressing circulatory and respiratory failure, the child was hospitalized in the intensive care unit. Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae. The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.

Factors affecting survival in children requiring intensive care after hematopoietic stem cell transplantation. A retrospective single-center study.

Allo-HSCT is associated with life-threatening complications. Therefore, a considerable number of patients require admission to a PICU. We evaluated the incidence and outcome of PICU admissions after allo-HSCT in children, along with the potential factors influencing PICU survival. A retrospective chart review of 668 children who underwent first allo-HSCT in the Department of Pediatric Hematology/Oncology and BMT in Wroclaw during years 2005-2017, particularly focusing on patients admitted to the PICU within 1-year post-HSCT. Fifty-eight (8.7%) patients required 64 admissions to the PICU. Twenty-four (41.5%) were discharged, and 34 (58.6%) patients died. Among the discharged patients, 6-month survival was 66.7%. Compared with survivors, death cases were more likely to have required MV (31/34; 91.2% vs. 16/24; 66.7% P = .049), received more aggressive cardiac support (17/34; 50% vs. 2/24; 8.3% P = .002), and had a lower ANC on the last day of their PICU stay (P = .004). Five patients were successfully treated with NIV and survived longer than 6 months post-discharge. The intensity of cardiac support and ANC on the last day of PICU treatment was independent factors influencing PICU survival. Children admitted to the PICU after allo-HSCT have a high mortality rate. Mainly those who needed a more aggressive approach and had a lower ANC on the last day of treatment had a greater risk of death. While requiring MV is associated with decreased PICU survival, early implementation of NIV might be considered.