Semaphorin 3B membranous nephropathy after hematopoietic stem cell transplantation in a child: a case report and literature review

Early (Day −7) versus Conventional (Day −1) Inception of Cyclosporine-A for Graft-versus-Host Disease Prophylaxis after Unrelated Donor Hematopoietic Stem Cell Transplantation in Children. Long-Term Results of an AIEOP Prospective, Randomized Study

Thyroid dysfunction (hypo- and hyperthyroidism) has been reported as a late effect after hematopoietic stem cell transplantation (HSCT) in children. Short-term effects of HSCT on thyroid function parameters are, however, unclear. We prospectively evaluated thyroid function parameters before and 3 months after HSCT in all children (<21 years) who underwent HSCT during a 2-year period in the Princess Máxima Center, the Netherlands. Among 72 children, none had thyroidal hypothyroidism or hyperthyroidism 3 months after HSCT. Changes in thyroid function parameters (either aberrant thyroid-stimulating hormone [TSH] or free thyroxine [FT4] concentrations) were found in 16% before and in 10% 3 months after HSCT. Reverse triiodothyronine (rT3) was found elevated in 9.3% before and in 37% 3 months after HSCT, which could be related to poor physical condition. An individual decline in FT4 concentration of ≥20% was found in 10.5% (6/57) 3 months after HSCT. In conclusion, thyroidal hypo- and hyperthyroidism are very rare 3 months after HSCT. These results indicate that surveillance for hypo- and hyperthyroidism may start later in time. The changes in thyroid function parameters found 3 months after HSCT might reflect euthyroid sick syndrome.

Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT.

<b>Introduction:</b> Pulmonary complications (PC) are significant causes of morbidity and mortality after hematopoietic stem cell transplantation (HSCT) in children. PC can occur due to infectious and noninfectious causes. In our study we aimed to evaluate pulmonary functions and complications in children after HSCT. <b>Method:</b> 23 children who underwent HSCT at Bahcesehir University, Pediatric Hematology Department between 2011-2014 were enrolled in the study. Demographic characteristics, spirometry tests, lung volumes, CO diffusion capacity, 6-minute walk test results and pulmonary complications were evaluated. <b>Results:</b> 17 patients (74%) were male, mean age was 10.4 ± 4.6 years. Age at HSCT was 8.0 ± 4.7 years, average time after HSCT was 2.4 ± 1.1 years. Indication for HSCT was thalassemia major in 11 patients, acute lymphoblastic leukemia in 5 patients, acute myeloid leukemia in 3 patients, aplastic anemia in 2 patients, severe combined immunodeficiency in one patient and dyskeratosis congenita in one patient. Infectious or noninfectious PC was observed in 12 (52.2%) children (pneumonia: 9 pts, bronchiolitis obliterans: 2 pts, restrictive lung disease: 1 pt). PC developed at mean 6 months (range 1-34 months) after transplantation. No significant diffference was observed in pulmonary function tests and 6-minute walk test results of patients with or without pulmonary complications. <b>Conclusion:</b> Our study showed that pulmonary complications are frequent after HSCT. Failure to demonstrate differences between groups may be due to the low number of cases. Close monitoring and identifying patients at risk is important since early diagnosis and treatment of PC reduces morbidity and mortality.

While acute kidney injury (AKI) has been reported after hematopoietic stem cell transplantation (HCT) in children, the incidence of this condition in the pediatric population has not been fully addressed. To assess the incidence of pediatric AKI after HCT treatment,we conducted a systematic literature review. Databases PubMed, Embase, Cochrane Library, and WOS were searched as of June 2022 to identify studies on the incidence and the risk of death in AKI children undergoing HCT. Random effects and generic inverse variance methods were used, and effect estimates were subsequently derived from individual studies. Twelve cohort studies with 2 159 HCT cases were included in this analysis. The combined estimated incidence of AKI and severe AKI (stage AKI III) was 51% (95% confidence interval (CI) 39-64%) and 12% (95%CI 4-24%), respectively. The estimated incidence of AKI based on RIFLE (pRIFLE), AKIN, and KDIGO criteria was 61% (95%CI 40-82% score I 95.1%), 64% (95%CI 49-79% score I 90.4%), and 51% (95%CI 2-100% score 99.0%), respectively. However, we found no significant correlation between the years of publication of the included studies and the incidence of AKI. Conclusions: AKI affects approximately half of the children after HCT. With the advancements in medical techniques, it is expected that AKI in this population will decrease gradually. What is Known: • Hematopoietic stem cell transplantation is recognized as a treatment for malignant and non-malignant diseases in children. • Hematopoietic stem cell transplantation causes acute kidney injury in children. What is New: • This metanalysis showed that the overall frequency of post-HCT AKI in children is 51%. • The frequency of severe AKI after HCT was found to be 12%.

BackgroundLong-term outcomes of hematopoietic stem cell transplantation (HSCT) in children with juvenile metachromatic leukodystrophy (MLD) have been investigated systematically, while short-term effects of HSCT on the course of the disease remain to be elucidated.ResultsIn this study, the clinical course was evaluated over the first 24 months following HSCT, conducted at our center in 12 children with juvenile MLD (mean follow-up 6.75 years, range 3–13.5) and compared with 35 non-transplanted children with juvenile MLD. Motor function (GMFM-88 and GMFC-MLD), cognitive function (FSIQ), peripheral neuropathy (tibial nerve conduction velocity), and cerebral changes (MLD-MR severity score) were tested prospectively.Seven children remained neurologically stable over a long period, five exhibited rapid disease progression over the first 12 to 18 months after transplantation. In the latter, time from first gross motor symptoms to loss of independent walking was significantly shorter compared with non-transplanted patients at the same stage of disease (p < 0.02). Positive prognostic factors were good motor function (GMFM = 100%, GMFC-MLD = 0) and a low MR severity score (≤ 17) at the time of HSCT.ConclusionsOur results show that if disease progression occurs, this happens early on after HSCT and proceeds faster than in non-transplanted children with juvenile MLD, indicating that HSCT may trigger disease progression.

The paediatric population of 19 eastern European countries amounts to approximately 80 million children. Between 1985 and 2004, the number of centres performing haematopoietic stem cell transplantation (HSCT) in children increased from 1 in 1985 to 24 in 2004 and the yearly number of paediatric HSCTs rose from 1 in 1985 to 291 in 2004. Altogether, 2342 transplants were reported to the EBMT Registry during this time (Poland 953, Czech Republic 501, Hungary 269, Russia 217, Croatia 129, Slovakia 71, Bulgaria 45, Serbia and Montenegro 36, Slovenia 35, Belarus 33, Estonia 26, Lithuania 19 and Romania 8). Out of the 2342 transplants, 1487 (63.5%) transplants were performed in paediatric centres, 453 (19.3%) in centres for adults and 402 (17.2%) in combined centres. The number of children who underwent autologous HSCT (auto-HSCT) was 1053 (45%), whereas 1289 (55%) underwent allogeneic HSCT (allo-HSCT). Peripheral blood (PB) was the source of HSC in 751 (71.3%) out of 1053 auto-transplants, BM in 246 (23.4%) and PB+BM in 52 (4.9%) (missing data in 4, that is, 0.4%). Among the 1289 allo-transplants, BM was the source of HSC in 827 (64.3%), PB in 416 (32.3%), CB in 23 (1.8%) and BM+PB in 14 (1.1%) (missing data in 9, that is, 0.7%). Among them, 728 (57.4%) obtained HSC from MSD, 322 (25.4%) from UD, 195 (15.4%) from MMFD, 14 (1.1%) from CB family donor and 9 (0.7%) from CB unrelated donor (missing data in 21, that is, 1.6%). The number of children who underwent allo-HSCT for malignant diseases was 945 (73.4%), including ALL 376 (29.2%), AML 234 (18.2%), CML 177 (13.8%), MDS 97 (7.5%), NHL 35 (2.7%) and other malignancy 31 (2.4%), while 339 (26.9%) for non-malignant disorders, including SAA 202 (15.7%), immunodeficiencies 61 (4.7%), inborn errors of metabolism 40 (3.1%), Fanconi anaemia 19 (1.5%) and others 17 (1.3%). Out of 1053 recipients of auto-HSCT, 168 (16%) were transplanted for neuroblastoma, 129 (12.2%) for NHL, 124 (11.7%) for AML, 114 (10.8%) for ALL, 109 (10.4%) for Hodgkin's disease, 62 (5.9%) for Ewing's sarcoma, 16 (1.5%) for CNS tumour, 15 (1.4%) for Wilms tumour and 316 (30%) for other tumours. In 2001, the EBMT in collaboration with the European School of Haematology (ESH) developed the Outreach Programme, that is a programme supporting emerging HSCT projects and transplant centres in countries with limited resources and/or experience.

The appropriateness of allogeneic hematopoietic stem cell transplantation (HSCT) in children and adolescents with leukemia in whom complete remission is not possible remains unclear. This retrospective analysis aimed to investigate the outcomes associated with HSCT, and the risks of HSCT in children and adolescents with nonremission acute lymphoblastic leukemia (ALL). Data from the Japan Society for Hematopoietic Cell Transplantation registry on 325 patients with nonremission ALL (aged <21years, with blasts in the peripheral blood and/or bone marrow) who had undergone HSCT between January 2001 and December 2015 were evaluated. To assess survival, we developed a scoring system using significant adverse pre-HSCT variables. Overall, 247 patients died. The median length of follow up among survivors was 1145days, and the 3-year overall survival was 22% (95% confidence interval [CI]: 18-27%). A low performance score, presence of >25% bone marrow blasts, T-cell phenotype, poor-risk or normal cytogenetics, and history of HSCT were predictors of a poor outcome. Patients scoring 0-1 (n=109), 2 (n=91), and 3-7 (n=125) had a 3-year overall survival of 41% (95% CI: 31-51%), 21% (95% CI: 13-31%), and 7% (95% CI: 3-12%), respectively. These results support HSCT in certain nonremission patients. Even in patients without complete remission, outcomes differed according to pre-HSCT factors. A scoring system could help determine the appropriateness of HSCT in children and adolescents with nonremission ALL.

Background Treatment improvement in hematopoietic stem cell transplantation (HSCT) in children has lowered HSCT-associated mortality rate, with increased long-term survivors’ complications. The metabolic syndrome (MetS), as well as growth failure observed among HSCT survivors, can be related to the patient’s primary illness or a complication of the HSCT. Aim To assess the frequency and possible risks of MetS and growth failure among HSCT survivors treated at our center. Patients and methods This study included 22 patients who underwent HSCT between 2011 and 2020 at the Pediatric Blood and Marrow Transplant Unit, Ain Shams University Hospital and survived for more than 1 year after HSCT with a mean age of 12.95 years, and a mean duration posttransplant of 5.95 years. Three patients were transplanted for malignant diseases, and all patients received chemotherapy only in a conditioning regimen. Detailed medical history, physical examination, and laboratory assessment, including complete blood count, fasting plasma glucose, fasting insulin, homeostatic model assessment of insulin resistance, glycated hemoglobin, fasting lipid profile, thyroid function and growth hormone stimulation tests for patients with height less than −3 SD were done. Results The frequency of MetS in our study was 4.5%, with 40.9% showing two components of MetS and 18.1% having one component of MetS. Dyslipidemia was detected in 68.2% with 50% developed hypertriglyceridemia, 45.4% had low high-density lipoprotein-cholesterol. 36.4% showed insulin resistance, 4.5% had impaired fasting glucose, yet none was diabetic. 9.1% had elevated blood pressure, and 4.5% had abdominal obesity. Multivariate analysis confirmed a significant positive association (P=0.019) between acute graft-versus-host disease and insulin resistance and a significantly elevated free T3 among patients with insulin resistance (P=0.011). Conclusion The current study proved a high prevalence of MetS components, specifically dyslipidemia (68.2%) and insulin resistance (36.4%) among HSCT survivors, mandating regular screening of MetS components in the long-term follow-up of those survivors.

Hematopoietic stem cells can be found in the bloodstream and have the ability to grow into any type of blood cell. These stem cells can be removed from the blood stream and then given to a patient to treat different types of cancerous and noncancerous diseases. You can learn more about stem cells and hematopoietic stem cell transplantation on the next page. ### Hematopoietic Stem Cell Transplantation Hematopoietic stem cell transplantation is the main treatment for a number of inherited and acquired diseases. In this issue of Neurology , Faraci et al. (Faraci M, Lanino E, Dini G, et al. Severe neurologic complications after hematopoietic stem cell transplantation in children. Neurology 2002;59:1895–1904.) describe severe neurologic complications in 272 children who underwent hematopoietic stem cell transplantation. Nervous system complications are a common cause of side effects of stem cell transplantation, and little has been written about them in children. ### How the Study Was Performed The authors studied the medical records of children who had hematopoietic stem cell transplantation to see what kinds of serious nervous system complications occurred. They also collected other information to see if any of the following factors were linked to serious nervous system complications: ### How Common Were Serious Nervous System Complications? Serious nervous system complications were seen in 14% of the children in this study and a cause of death in 8.5%. These complications commonly occurred in the first year after the transplantation was performed. The main risk factors for serious nervous system complications can be found …

To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.

ABSTRACTObjectivesThe clinical characteristics, risk factors and survival prognosis of pericardial effusion (PE) after haematopoietic stem cell transplantation (HSCT) in children were investigated.MethodsClinical data of children who underwent HSCT at the Children's Hospital Affiliated with Chongqing Medical University from January 2016 to December 2022 were analysed retrospectively. Cox proportional hazards regression and the Kaplan-Meier method were used to analyse the risk factors for post-HSCT PE and its impact on outcomes, respectively.ResultsWe enrolled 452 patients with HSCT: 307 males and 145 females, with a median age of 3.4 (1.8 to 6.5) years at transplantation. Forty-five patients (10%) had PE within a median time of 25 (10.5 to 44) days, 42 (93%) within 100 days. Three patients with large PE were treated with pericardiocentesis and drainage, while the others were treated conservatively. Of the 45 patients with PE, 24 survived, and their PE disappeared after treatment. Graft-versus-host disease (GVHD) grade, abnormal pre-HSCT electrocardiogram, hepatic veno-occlusive disease (HVOD), pulmonary infection and Epstein–Barr virus (EBV) infection were risk factors for PE. The overall survival (OS) rates at 1, 3, and 5 years were 86.0%, 84.2%, and 82.3%, respectively. PE had a significant negative effect on OS after HSCT (P < 0.0001). Particularly, one patient with large PE died of pericardial tamponade.ConclusionsPost-HSCT PE usually occurred within 100 days. GVHD grade, abnormal pre-HSCT electrocardiogram, HVOD, pulmonary infection and EBV infection were closely related to PE. PE had a significant negative effect on OS rate.

The origins of hematopoietic stem cell transplantation (HSCT) in children and adolescents with cancer can be traced back over 50 years ago to the original reports of Thomas et al. [1, 2]. Thomas et al. initially reported the results of syngeneic transplants in twins with leukemia who had been conditioned with superlethal doses of total body radiation (TBI) [1, 2]. Since that groundbreaking observation over 50 years ago, additional sources of stem cells have been investigated in children and adolescents with a variety of malignant conditions including human leukocyte antigen (HLA)matched sibling or related allogeneic donors, matched unrelated adult donors, sibling and unrelated cord blood donors, haploidentical donors, and autologous bone marrow or peripheral blood. Currently, there are a variety of malignant conditions that occur in children and adolescents that may benefit from HSCT during different stages of their treatment and can be subdivided into hematopoietic neoplasms and solid tumors (Table 19.1). We have summarized the state of the science of HSCT in children with cancer in the remainder of this chapter.

Hematopoietic stem cell transplantation (HSCT) in children is a high-tech field of medicine that combines the latest achievements of pediatric hematology, oncology, immunology, transfusiology, molecular biology and cell therapy. The success of HSCT is largely owing to the unique experience of international and national cooperation between transplant centers. A regular joint analysis of transplantation activity, focused on identifying trends and problems that require theoretical and practical solutions, is one of the most important components of such cooperation. The present work summarizes the experience of HSCT in all major pediatric centers in Russia for the period 2015–2018.

The aim of this study is to determine the ultrasound criteria in the diagnosis of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after hematopoietic stem cell transplantation (HSCT) in children. A total of 158 pediatric patients underwent HSCT between January 2016 and January 2018. In all, 71 patients with clinically suspicious hepatic VOD/SOS have been followed with serial ultrasound examinations. Hepatomegaly, gallbladder wall thickening, ascites, pleural effusion, reverse flow in the portal vein, and diameter and peak systolic velocity of the hepatic artery were evaluated. Patients were divided into 2 groups retrospectively: VOD/SOS and non-VOD/SOS. The predictive value of all findings was determined, respectively. Gallbladder wall thickening, increase of diameter and peak systolic velocity of the hepatic artery, and the presence of ascites are highly predictive for VOD/SOS (P=0.001 and < 0.05). The reversed portal venous flow was developed in 3 patients in the VOD/SOS group, no significant difference was found between the 2 groups (P>0.05). Hepatomegaly was recorded in 29 (70.7%) patients in the VOD/SOS group, 13 of them was presented related to a primary disease. Pleural effusion is not associated with the diagnosis of VOD/SOS (P>0.05). Gallbladder wall edema, an increase of peak systolic velocity of the hepatic artery, and the presence of ascites are highly related to the diagnosis of VOD/SOS in children after HSCT. Ultrasound findings must be correlated with clinical criteria.