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Background: Extended family donor search other than siblings may yield an HLA matched donor in communities with high rate of consanguinity. The outcome of patients who are transplanted from non‐sibling matched related donors (NS‐MRD) including engraftment and graft versus host disease (GVHD) are scarce in comparison with matched sibling donor (MSD). Methods: We retrospectively reviewed the outcome of all our pediatric hematopoietic stem cell transplantation (HSCT) patients who had non‐sibling matched related donor and controlled them with matched sibling donor HSCT (based on age, indication of HSCT, conditioning regimen, GVHD prophylaxis, serotherapy, stem cell source and cytomegalovirus status). Results: A total of 76 patients were reviewed during study period. Thirty patients (39.5%) in NS‐MRD arm and 46 patients in MSD (60.5%) were identified after matching in age, disease, and conditioning regimens. All patients had similar approach including stem cell source and GVHD prophylaxis (CNI + 2nd agent). Out of the NS‐MRD group, 18 patients (59%) had one of their parents as a donor and the rest as second degree relatives. Both groups were equally distributed and were homogeneous. Both groups had no statistically significant difference in outcome including engraftment, GVHD and Chimerism tests results. GVHD was seen in (13%) NS‐MRD patients compared to (11%) in MSD patients. All patients remain alive with median follow up of 1249 days (431–3525). Conclusions: This study showed no significant difference in allogenic HSCT outcomes between matched sibling donors and non‐sibling matched related donors and support using the same management approach in terms of conditioning therapy, GVHD prophylaxis, and serotherapy only if indicated. [ABSTRACT FROM AUTHOR]

Background: Advances in stem cell transplantation have resulted in improved outcomes. Methods: This is a retrospective study aimed to analyze changes in patient profile, transplantation, graft characteristics, and outcome among 241 pediatric patients who received stem cell transplantation in a single center between 1993 and 2019. Results: In the 2010–2019, compared with the 1993–2009 period, a significantly higher 5‐year overall survival (60% vs. 44%, p =.022) and an event‐free survival (53% vs. 34%, p =.025) were observed. Cumulative incidence of deaths due to relapse or progression between the 1993–2009 and 2010–2019 periods were 33% and 26% respectively (p =.66). Cumulative incidence of non‐relapse mortality was significantly higher during the 1993–2009 period compared with the 2010–2019 period for malignant diseases (57.7% vs. 28.3%, p =.007). The overall survival from acute graft‐versus‐host disease between 1993 and 2009 was 11% versus 46% between 2010 and 2019 (p =.0001). The overall survival from infection in both eras did not show any difference (p =.41). Conclusions: Development in transplantation technology has led to a decrease in non‐relapse mortality and better control of graft‐versus‐host disease. However, relapse and infection remained as major causes of death. Studies evaluating institutional trends in patients undergoing HSCT and analyzing their mortality profile, can improve the management of patients, leading to a reduction in transplant‐related problems. [ABSTRACT FROM AUTHOR]

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: Hematopoietic stem cell transplantation (HSCT) is a common and effective treatment for multiple malignant and non‐malignant pediatric conditions. Graft‐versus‐host disease (GVHD) is a common complication of HSCT that can be prevented with prophylactic use of calcineurin inhibitor (CNI) immunosuppressants. A complication of HSCT and CNI use is pericardial effusion (PEF), which is frequently treated by CNI discontinuation with or without surgical intervention. No studies to date have evaluated the management of PEF without CNI discontinuation as a means of preventing GVHD flares. Methods: In this single‐center retrospective study, we reviewed the management of PEF in pediatric patients post‐HSCT who received conservative or surgical intervention with or without CNI discontinuation between May 2012 and June 2022. Results: Of the patients found to have PEF, all were given tacrolimus for GVHD prophylaxis. Management of PEF included surgical intervention for 83% of patients, and CNI was not discontinued for 83%. None of the patients developed GVHD during the management of PEF. Conclusions: Our results demonstrate that continuation of CNI therapy for GVHD prophylaxis did not negatively impact the disease course of PEF in post‐HSCT patients. [ABSTRACT FROM AUTHOR]

Background: This prospective study aimed to comprehensively understand the changes in intestinal flora at different stages after hematopoietic stem cell transplantation (HSCT) in pediatric patients and to analyze the effect of intestinal flora on acute graft versus host disease (aGVHD), especially on gastrointestinal graft versus host disease (GI GVHD). Methods: A total of 32 children with primary diseases of primary immunodeficiency disease (PID) and thalassemia were included. 16S sequencing was used to characterize the microbiota layout at three time points peri‐transplant including pre‐transplant, Day +3, and Day +30. Results: By comparing the intestinal flora of children with GI GVHD and those without GI GVHD, it suggests that in children with GI GVHD, the distribution of intestinal flora after transplantation was more variable and more chaotic (chao1 index, Friedman test, p =.029). Besides, Veillonella and Ruminococcaceae were more abundant before transplantation, Bifidobacteriaceae and Bacillales were more abundant after transplantation. Comparing children with PID and thalassemia, it was found that the destruction of gut microbiota diversity was more significant in children with thalassemia after transplantation. The comparison of children with 0‐I° aGVHD and II‐III° aGVHD indicates that children with II‐III° aGVHD had more Bilophila before transplantation than children with 0‐I° aGVHD. Additionally, exploratory analyses to evaluate correlations between clinical characteristics (medications, immune cell recovery, etc.) and microbiome features were also performed. Conclusions: This study has synthetically shown the distribution of intestinal flora after allo‐HSCT, and some characteristic bacteria at different stages that may serve as potential biomarkers were screened out additionally, perhaps providing clues for the prevention and treatment of the disease. [ABSTRACT FROM AUTHOR]

Background: New‐onset allergic diseases, such as food allergy or atopic dermatitis, can develop after allogeneic transplantation. There are limited reports of new‐onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation in children and adolescents, and its treatment is yet to be established. The pathogenesis may differ from typical atopic dermatitis in terms of alloimmunity including graft‐versus‐host disease. Methods: We present five children and adolescents with new‐onset atopic dermatitis after allogeneic hematopoietic stem cell transplantation. The characteristics and clinical profiles of skin treatment after hematopoietic stem cell transplantation are summarized. Results: Graft‐versus‐host disease prophylaxis included systemic tacrolimus for all patients. After hematopoietic stem cell transplantation, all patients achieved complete donor chimerism of the bone marrow and had acute graft‐versus‐host disease of the skin. After engraftment, all patients had skin lesions that met the international consensus diagnostic criteria for atopic dermatitis. None of the patients met the diagnostic criteria for chronic graft‐versus‐host disease. Topical therapy and skin care based on atopic dermatitis guidelines improved skin condition and atopic dermatitis severity scores in all patients. In addition, type 2 inflammatory markers improved accordingly. Conclusion: Topical therapy and skin care may be effective for transplant‐related atopic dermatitis after hematopoietic stem cell transplantation. When extensive dermatitis is observed after hematopoietic stem cell transplantation, this treatment may avoid excessive immunosuppressive therapy if it meets the diagnostic criteria for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background: There is a well‐documented risk of secondary cutaneous malignancies following allogeneic hematopoietic stem cell transplant (HSCT), but data on risk in pediatric populations are limited. The objective of this study is to perform a systematic review of reported features and outcomes of skin cancers in pediatric allogeneic HSCT recipients. Methods: MEDLINE, EMBASE, CINAHL, Cochrane, and Web of Science were systematically searched (Prospero CRD42022342139). Studies reporting cutaneous cancer outcomes were included if the age at transplant was ≤19 years. Titles, abstracts, and full‐text articles were screened in duplicate. Results: Out of 824 citations that were screened, 12 articles were selected for analysis. The final sample included 67 pediatric HSCT recipients, comprising 65 allogeneic transplant recipients and 2 cases of HSCT with an unknown donor type. The median age at transplant and skin cancer diagnosis were 7.4 and 13 years, respectively. Out of the 67 pediatric HSCT recipients, some patients developed more than one lesion, resulting in 71 lesions. The most common skin cancer type was cutaneous squamous cell carcinoma (32 lesions), followed by basal cell carcinoma (25 lesions). The median latency period between HSCT and skin cancer diagnosis ranged from 0 to 29 years. Identified risk factors for skin cancers included younger age at the time of transplant, exposure to total body irradiation, prolonged post‐transplant immunosuppression, graft versus host disease, and sunburn. Conclusion: Skin cancers are reported in pediatric allogeneic HSCT recipients, and the risk appears to be increased. More data are needed to better characterize this risk. [ABSTRACT FROM AUTHOR]

Background: Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures. Procedures: We performed a retrospective study (2002–2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures. Results: Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow‐up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p =.010), prophylactic or therapeutic mycophenolate use (p =.043 and.046, respectively), steroid use (p =.023), selective CD45RA+ depletion (p =.002), pre‐engraftment syndrome (p =.007), and chronic graft‐versus‐host disease (GVHD) severity (p =.030). Seizures predicted evolution to life‐threatening complications and admission to intensive care (p <.001) and higher mortality (p =.023). A statistically significant association was also found between seizures and sequelae in survivors (p =.029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 [95% CI: 7.45–186.05] and 12.95 [95% CI 2.24–74.80], respectively). Conclusions: Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure. [ABSTRACT FROM AUTHOR]

Background: Operational tolerance after retransplantation of the intestine has never been reported. Purpose: To two recently described intestine transplant recipients with operational tolerance, we now add a third. Methods: Review of case record and immunological testing to confirm donor‐specific hyporesponsiveness in multiple immune cell compartments. Results: Re‐transplanted with a multivisceral liver‐ and kidney‐inclusive intestine allograft at age 12 years, this recipient self‐discontinued immunosuppression 14 years after the retransplant and has been rejection free for 2 years thereafter. As in the two previous reports, immunological testing demonstrated decreased donor‐specific inflammatory response of T‐cytotoxic memory cells and B‐cells, decreased presentation of donor antigen by B‐cells and monocytes, absence of donor‐specific anti‐HLA antibodies, circulating FOXP3 + T‐helper cells, and intact cellular and humoral immunity to cytomegalovirus and Epstein–Barr virus. Additionally, our recipient demonstrated enhanced donor‐activation‐induced apoptosis of alloreactive T‐cytotoxic memory cells. Conclusions: Despite variable paths to tolerance which include graft versus host disease in two previous cases, and rejection‐related loss of the primary isolated intestinal allograft in our recipient, the three cases with operational tolerance are bound by common themes: a relatively large donor antigenic load transmitted during intestine transplantation, and donor‐specific hyporesponsiveness. Cell‐based assays suggest enhanced donor‐induced apoptosis of recipient T‐cells and circulating T‐regulatory cells as mechanistic links between antigenic load and donor‐specific hyporesponsiveness. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of addition of ruxolitinib in Graft‐versus‐Host Disease (GVHD) prophylaxis on pediatric patients with β‐thalassemia major after allogeneic hematopoietic stem cell transplantation(HSCT). Methods: This retrospective study reviewed 49 consecutive β‐thalassemia major pediatric patients who underwent HSCT from unrelated or haploidentical donors from February 2018 to October 2022. All transplantation recipients received cyclosporine A (CsA), mycophenolate mofetil (MMF), and short‐term methotrexate (MTX) as GVHD prophylaxis; while 27 of them in the ruxolitinib group had added ruxolitinib oral to GVHD prophylaxis regimen at 2.5 mg twice daily once successful engraftment after January 2020. Results: The outcome showed that the ruxolitinib group had a lower cumulative incidence than the control group regardless of acute GVHD (22.2% vs.40.9%; p =.153) or chronic GVHD (18.5% vs.40.9%; p =.072); especially, the incidence of grade III‐IV acute GVHD was reported significantly less frequently in ruxolitinib group than that of the control group (0 vs. 27.3%, p =.005). No significant difference was detected between the two groups in EBV (Epstein–Barr virus)/CMV (cytomegalovirus) reactivation and BKV (BK virus) infection (p =.703, 1.000, and.436, respectively). Twenty‐six patients (96.3%) in the ruxolitinib group were alive, while two patients (9.1%) in the control group died of intestinal acute GVHD. The 2‐year overall survival (OS) and thalassemia‐free survival (TFS) were both 96.296% in the ruxolitinib group, while both 90.909% in the control group. Conclusion: This study reveals that ruxolitinib prophylaxis is a promising option to decrease the incidence of grade III‐IV acute GVHD in pediatric patients with β‐thalassemia major. [ABSTRACT FROM AUTHOR]

Background: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non‐invasive biomarkers, such as the beta‐D‐glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta‐D‐glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post‐HCT period. Methods: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post‐HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD. Results: A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%–85.3%), and NPV was over 99% (95% CI: 86.8%–99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%–84.2%) and PPV of 0% (95% CI: 0.0%–6.7%). Conclusions: Fungitell® BDG screening is of limited utility in diagnosing IFD in the post‐HCT period, mainly due to high false‐positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post‐HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low. [ABSTRACT FROM AUTHOR]

Background: Fanconi anemia is a congenital disorder belonging to bone marrow syndromes, with a risk of developing malignancy. Hematopoietic stem cell transplantation is the only curative treatment in these cases. Here, we aimed to report our clinical experience in pediatric patients with Fanconi anemia treated with haploidentical stem cell transplantation and post‐transplant cyclophosphamide, an alternative strategy. Methods: We performed a case report based on clinical records of two patients who signed the informed consent form and were treated at Fundación Valle del Lili. Result: Two pediatric patients, both with reduced‐intensity conditioning, prophylaxis for acute graft‐versus‐host disease with post‐transplant cyclophosphamide. They achieved primary neutrophil/platelets engraftment, and 100% chimerism. Had grade I or II graft‐versus‐host disease resolved? Currently are alive and in complete remission. Conclusions: The use of mismatched related donors for haploidentical stem cell transplantation and post‐transplant cyclophosphamide might be a promising option, and well‐tolerated in pediatric patients. Serial chimerism can be useful during follow‐up. [ABSTRACT FROM AUTHOR]

Background: Non‐severe aplastic anemia is more likely to develop into severe aplastic anemia, and there is no widely accepted treatment plan at present. Hematopoietic stem cell transplantation might be a new therapeutic strategy. Methods: Retrospectively analyzed 32 patients with non‐severe aplastic anemia who underwent hematopoietic stem cell transplantation from September 2007 to September 2020, and the 5‐year estimated overall survival rate and the incidence of graft‐versus‐host disease were analyzed to evaluate the efficacy and safety of hematopoietic stem cell transplantation in the treatment of pediatric non‐severe aplastic anemia. Results: Thirty‐two patients who underwent transplantation, 29 patients (90.6%) survived, 3 patients (9.4%) died. The incidence of acute graft‐versus‐host disease was 51.6% (16/31), including 15 cases (48.4%) of grade I‐II and 1 case (3.2%) of grade III–IV. The incidence of chronic graft‐versus‐host disease was 38.7% (12/31). The 5‐year overall survival rate was 91.8%. Conclusions: Hematopoietic stem cell transplantation is a practicable, safe, and effective treatment option for non‐severe aplastic anemia pediatric patients who are suitable for transplant. [ABSTRACT FROM AUTHOR]

Background: Infants are subjected to hematopoietic stem cell transplantation (HSCT) due to malignant and non‐malignant diseases. However, specific data concerning the outcome and transplantation‐related complications in infants, as a separate age group, are limited. Our aim was to evaluate the impact of infancy on the outcome, toxicity, and complications after HSCT. Methods: We retrospectively analyzed data of 55 infants that underwent HSCT in our unit from May 1997 until February 2020, emphasizing on the probability of overall survival (OS) and the cumulative incidence (CI) of transplantation‐related mortality (TRM) and complications. Results: We report a probability of OS of 61%, a CI of TRM at day 100 and 365 post transplantation of 22% and 30%, respectively, and additionally a CI of graft failure, acute graft‐versus‐host disease (GvHD), and infectious complications, 18%, 44%, and 39%, respectively. No statistically significant association was detected between the above mentioned parameters and diagnosis, the use of myeloablative or non‐myeloablative/reduced toxicity conditioning regimens or the type of donor. Conclusions: We conclude that HSCT in infancy is associated with significant mortality and morbidity. This is possibly attributed to endogenous, age‐related factors. More specifically, infants may be at a higher risk of toxicities due to the immaturity of developing vital organs and the deficiency of the newly adopted immune system that predisposes them to infectious complications. The development of GvHD further augments the danger of infections, in a potential vice‐versa relationship. Moreover, there are few data on pharmacokinetics of chemotherapy agents, making safe and efficacious drug administration hard. [ABSTRACT FROM AUTHOR]

Background: Graft‐versus‐host disease (GVHD) is a rare but serious complication after pediatric liver transplantation (LTx). Early diagnosis is difficult due to nonspecific presenting symptoms and non‐pathognomonic skin histopathological features. The aim of this article was to describe a case of pediatric GVHD after LTx and to review available data on pediatric GVHD highlighting the diagnostic difficulty. We also propose a diagnostic algorithm to improve the diagnostic capability and increase clinical awareness about this potentially fatal condition. Methods: We did a comprehensive literatures review on studies on GvHD following pediatric LTx between 1990 and February 2021, chimerism study by short tandem repeat (STR), HLA typing by sequence‐specific oligonucleotide (SSO) method, and flowcytometry crossmatch. Results: Our search yielded 23 case reports. The most common clinical manifestations were fever and rash (91%) followed by diarrhea. Mortality rate was 36.8% mainly due to sepsis and organ failure. Diagnosis was challenging and chimerism study to confirm donor engraftment was performed on only half of the cases. Prevalence of "donor dominant HLA one‐way matching" typically occurs in homozygous parents‐to‐child transplantation was 75% in cases with HLA testing. Conclusion: So far, there are no available standard diagnostic criteria for GVHD following pediatric LTx. Recognition of multiple risk factors through proper laboratory assessment can predict the occurrence, and early chimerism study can confirm suggestive clinical manifestation. The strong likelihood of developing GVHD in "donor one‐way HLA match" and the severe problems imposed by this complication may justify avoidance of HLA homozygous parent's donation. [ABSTRACT FROM AUTHOR]

Background: Anti‐human T‐lymphocyte immunoglobulin is commonly used as prophylaxis for graft‐versus‐host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. Patients and Methods: Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. Results: The incidences of acute and chronic GVHD were statistically not different between three groups (p =.20 and p =.13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p =.007) and severe acute GVHD (p =.001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p =.04 and p =.037) with no difference between 20 and 30 mg/kg. Conclusion: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population. [ABSTRACT FROM AUTHOR]

Background: Myb‐like, SWIRM, and MPN domains 1 (MYSM1) is a histone H2A deubiquitinase, has been discovered as one of the transcriptional regulators, and regulates the expression of specific transcription factors, which are essential for immunohematology development. Mutation in MYSM1 in humans leads to a rare autosomal recessive disease that has recently been known as inherited bone marrow failure syndrome 4 (BMFS4) associated with congenital bone marrow failure, immunodeficiency, and developmental aberrations. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for immunohematology defects. Methods: In this paper, we report a pediatric patient with BMFS4 who suffered from pancytopenia and immunodeficiency affecting B cells and was successfully treated with HSCT from an HLA‐identical father at 6 years old of age. Fludarabine‐based reduced intensity conditioning was used and resulted in full donor chimerism. Results: Acute graft versus host disease (GVHD) grade II involving skin and gastrointestinal tract was observed, which was controlled with prednisolone. Conclusion: She achieved B‐cell recovery, and no blood or platelet transfusion was reported 1 year after HSCT. [ABSTRACT FROM AUTHOR]

Background: Pneumatosis cystoides intestinalis (PCI) is a disorder in which widespread air sacs are present in mucosa, submucosa, subserosa, and intraabdominal area of the intestinal wall. It has a heterogeneous clinical presentation as a rare complication of intestinal graft‐versus‐host disease (GVHD). Computed tomography is the preferred imaging method for the diagnosis. Since the air sacs could be ruptured spontaneously, the presence of free air in the peritoneal cavity does not confirm intestinal perforation. The conservative treatment approach is sufficient in cases that do not require urgent surgical intervention, such as perforation or obstruction. Case: Here, we present a 2.5‐year‐old patient diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH), who underwent allogeneic hematopoietic stem cell transplantation from a matched unrelated donor (MUD) and developed PCI secondary to intestinal GVHD 14th months after HSCT. Conclusions: Pneumatosis cystoides intestinalis, which is a rare complication, should be kept in mind, especially in patients with intestinal GVHD and receiving intensive immunosuppressive, octreotide, and steroid treatment after HSCT. [ABSTRACT FROM AUTHOR]

Introduction: The only curative treatment for severe aplastic anemia in children is an allogeneic stem cell transplant; however, few patients have a matched related or unrelated donor. Haploidentical stem cell transplantation (haplo‐SCT) using bone marrow (BM) and peripheral blood stem cells (PBSC) has been recently described as effective and safe. In this study, we retrospectively report the outcome of twelve pediatric patients who underwent haplo‐SCT using only PBSC. Methods: The conditioning regimen consisted on rabbit anti‐thymocyte globulin (r‐ATG) 2.5 mg/kg/d on days −7, −6,‐5, and −4, and cyclophosphamide (Cy) 50 mg/kg/d on days −3 and −2. We used Cy 50 mg/kg/d on days +3 and +4, tacrolimus and mycophenolic acid as graft versus host disease (GVHD) prophylaxis. Results: The median follow‐up was 1,099 days (45–1258 days). The overall survival rate up‐to‐date is 83.3%. In 10 of the 12 patients, a sustained graft was achieved. None of the patients had acute or chronic GVHD. Conclusions: Haplo‐SCT could be established as a first‐line treatment when there is no matched related or unrelated donor. According to this short sample and previous reports, PBSC are a feasible option effectively used as the sole source of stem cells. Additionally, post‐transplant cyclophosphamide remains a good strategy for GVHD prevention. [ABSTRACT FROM AUTHOR]

Background: Endoscopically obtained mucosal biopsies are the gold standard for diagnosing acute graft‐versus‐host disease of the gastrointestinal tract (GI‐GVHD). There is no consensus on the ideal endoscopic approach in children. We aimed to ascertain which gastrointestinal sites and endoscopic approaches were most helpful for diagnosing acute GVHD and whether clinical symptoms can guide the endoscopic approach. Method: A single‐center retrospective review of all pediatric stem cell transplants (SCT) between January 1, 2007, and December 31, 2018. Of those with histologically diagnosed GI‐GVHD, sensitivities of individual GI sites for making the diagnosis were calculated. Clinical symptoms were compared with GI site yielding diagnosis. Results: 216 allogeneic SCTs were performed in 199 patients. 37 of 52 suspected GI‐GHVD cases underwent endoscopy. There was marked variability in the endoscopic approaches chosen. 82% of these cases had lower gastrointestinal symptoms. 21 cases had histologically proven GI‐GVHD. 19 (90%) of these had GVHD of non‐gastrointestinal sites; 10 (48%) had concurrent infections. The most‐sensitive GI sites were the rectosigmoid and duodenum (86% and 76%, respectively). Overall sensitivity of upper GI endoscopy (UGIE) and lower GI endoscopy (LGIE) was 86% and 90%, respectively. There was no statistically significant association between clinical symptoms and site at which histological diagnosis was obtained. Conclusion: We observed variability in the endoscopic approach used by clinicians. UGIE and sigmoidoscopy had high sensitivities for diagnosing GVHD, regardless of symptoms. LGIE had minimal additional diagnostic value. This would support a standardized approach with UGIE and sigmoidoscopy for all children with suspected GI‐GVHD. [ABSTRACT FROM AUTHOR]

Background: While operational tolerance has been previously described in isolated intestinal transplant, reports of this phenomenon in combined liver‐intestine transplant are lacking. Case Description: We detail a unique case of a patient who received a composite allograft including liver, pancreas, and small bowel due to short gut syndrome secondary to gastroschisis complicated by volvulus. The indication for transplantation was permanent dependence on total parenteral nutrition, end‐stage liver disease, recurrent sepsis, and persistent stomal variceal hemorrhage. The patient developed severe graft‐versus‐host disease with grade 3 skin involvement, ophthalmic, and pulmonary involvement with 53% donor T‐cell chimerism. She required aggressive therapy including high‐dose methylprednisolone, rituximab, cyclophosphamide, and alemtuzumab. Due to infection concerns following depletion of her lymphocytes, immunosuppression was discontinued with close surveillance of her allograft. Nearly 10 years later, the patient has continued off all immunosuppression without evidence of rejection or graft dysfunction and demonstrates immunocompetence with normal functional immune assays and development of appropriate live vaccination titers. Conclusion: This report of operational tolerance following pediatric composite liver‐pancreas‐intestine transplantation provides evidence that the complex immunologic balance in intestinal transplantation may on rare occasions favor immunosuppression reduction or even discontinuation. Future trials of immunosuppression minimization in this population may be warranted. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive prophylaxis is usually given to decrease the development of acute graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Belatacept is a Cytotoxic T‐lymphocyte‐associated protein 4, blocking agent, an immunosuppressive agent used for organ rejection prevention in adult renal transplant recipients. Methods: We describe two children in whom belatacept was successfully used for GvHD prophylaxis. Case 1 was noncompliant with prior immunosuppressive therapy for aplastic anemia, and Case 2 developed severe thrombotic microangiopathy (TMA) precluding the use of calcineurin inhibitors (CNI) or mTOR inhibitors. Results and Conclusion: Belatacept was found to be a safe alternative in preventing GvHD in 2 patients in whom traditional prophylactic therapies were not possible to use. [ABSTRACT FROM AUTHOR]

Background: Membranous nephropathy (MN) is the most common cause of glomerulopathy after hematopoietic cell transplantation (HCT), most often occurring in the setting of graft versus host disease (GVHD). Twenty percent of patients will fail to respond to standard therapy and may progress to end stage renal disease. Here we present the case of a pediatric patient who developed chronic oral GVHD more than one‐year post‐HCT, who subsequently developed nephrotic syndrome (anasarca, nephrotic range proteinuria, hypoalbuminemia) and had a renal biopsy consistent with MN. Treated with ibrutinib for her GVHD, and steroids, tacrolimus, and rituximab for her MN, she failed to achieve even partial remission of her kidney disease after 8 months. Due to steroid toxicity and 0% CD19 cells on lymphocyte subpopulation flow cytometry, the decision was made to trial plasma cell depletion therapy with daratumumab. Method: She received three doses of daratumumab at weeks 1, 4, and 17. Results: Her nephrotic syndrome resolved and her serum albumin was greater than 3.0 gm/dl by week 10. She was weaned off of both steroids and tacrolimus by week 16, at which time she had near‐complete remission of her renal disease. Conclusion: Daratumumab may be an important, novel therapeutic option for post‐HCT MN patients who are not responsive to standard therapies. [ABSTRACT FROM AUTHOR]

Acute graft‐versus‐host disease (GvHD) has been a clinical problem in solid organ transplant that includes intestine due to the donor lymphoid tissue mass which accompanies the intestinal component of the graft. We report a case that demonstrated the efficacy and feasibility of ruxolitinib a JAK 1/2 inhibitor in the treatment of chronic steroid‐refractory GVHD (SR‐GVHD). The child developed SR‐GVHD following a composite intestine transplant (small bowel, colon, liver, and pancreas). And after receiving ruxolitinib 1.25 mg (0.15 mg/kg/dose) per gastric tube (G‐tube) daily, the child appeared to have improved skin rash and sigmoidoscopy was negative. Nonetheless, we encourage close monitoring of hematologic and infectious adverse effect during dose escalation, and individualizing patient maximum effective dose with the least adverse effect possible. We stress the importance of early diagnosis and hyper‐alertness of GVHD in intestinal transplant patients. [ABSTRACT FROM AUTHOR]

Background: No previous paediatric study has evaluated the frequency of diagnostic disagreement between clinical standard histopathological assessment (CSHA) and retrospective, independent, histopathological assessment (RIHA) of gastrointestinal Graft‐Versus‐Host Disease (GI‐GVHD) Methods: In a retrospective cohort study, based on gastrointestinal biopsies collected from allogeneic HSCT‐treated children (<18 years) with symptom‐based GI‐GVHD, we evaluated; disagreement of histopathology‐based GI‐GVHD diagnosis in CSHA vs RIHA, and potential clinical consequences of differences between the assessments. The CSHA‐based diagnoses were retrieved from histopathology reports. The RIHA was performed by one pathologist, blinded to the CSHA outcomes and based on the minimal criteria for histopathology‐based GI‐GVHD diagnosis by the NIH 2014. Results: Seventy children with 92 endoscopic occasions (including 22 re‐endoscopies) were enrolled. GI‐GVHD was observed in 73% (67/92) of the endoscopies in the RIHA and in 54% (50/92) in the CSHA (P =.014). The RIHA confirmed 94% (47/50) with GI‐GVHD and 52% (22/42) with non‐GI‐GVHD diagnoses, established in the CSHA. Disagreement, that is endoscopic occasions with GI‐GVHD solely detected in RIHA or detection of GI‐GVHD in CSHA but not in RIHA, was observed in 20/42 (48%) and 3/50 (6%), respectively (McNemar's test, P =.0008). The risk of a subsequent re‐endoscopy was higher in endoscopic occasions with GI‐GVHD detected in RIHA but not in CSHA vs if non‐GI‐GVHD were detected in both readings (P =.005). Conclusion: Our results suggest that in children with symptom‐based GI‐GVHD without histopathological confirmation in CSHA, a second, NIH 2014 based histopathological assessment should be considered before performing a re‐endoscopy. [ABSTRACT FROM AUTHOR]

aGvHD remains a major obstacle to successful HSCT. We report our experience on steroid-refractory aGvHD III and IV from 1989 to 2017. Ninety patients with aGvHD III or IV were stratified according to the HSCT year: 1989-1998, 1999-2007, and 2008-2017 and to aGvHD extension (GvHD III vs IV) and finally the probability of OS, RI, and TRM was calculated accordingly. aGvHD III patients had a substantial improvement over time: day 100 OS raised from 64% (95% CI 39-89) in the first cohort to 100% in the latest (P = .022), and it was mainly due to a reduction of TRM (it was 28% [95% CI 12-65] in the first cohort to 0% in the latest (P = .01). The aGvHD IV patients did not present a significant improvement. Day 100 OS was 42% (95% CI 16-68) in the first group and 54% (95% CI 25-83) in the year 2008-2017 (P = NS), and the day-100 TRM was very similar (it was 57% [95% CI 36-90] in the first cohort and 45% [95% CI 23-89] in the latest (P = NS). We report significant improvements in OS and TRM in patients diagnosed with grade III aGvHD. Patients with the most severe aGvHD appear to have no or fewer benefits on long-term outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Myeloablative conditioning before allogeneic HSCT during childhood exposes to serious long‐term complications, especially gonadal dysfunction. Pubertal issues are less described than other post‐HSCT sequelae in childhood. Methods: Pubertal development and biological gonadal parameters were assessed in a retrospective monocentric cohort of prepubertal patients who underwent HSCT after myeloablative conditioning with TBI or busulfan between 1981 and 2017. Results: Seventy‐four patients (28 girls and 46 boys) were included. No spontaneous pubertal development was found in 50% of girls and 10% of boys (P <.001), and delayed puberty or no spontaneous pubertal development was found in 57% of girls and 24% of boys (P =.009). HRT was used in 82% of girls and 24% of boys (P <.001). In univariate analysis, TBI conditioning (P =.05), female sex (P <.001), acute GVHD (P =.05), extensive chronic GVHD (P =.021), steroid treatment >6 months (P =.016), and malignant diseases (P =.016) were associated with no spontaneous pubertal development, whereas TBI conditioning (P =.003) and extensive chronic GVHD (P =.005) were associated with delayed puberty. In multivariate analysis, factors independently associated with no spontaneous puberty onset were female sex (P =.001) and age >10 years (P =.033). Factors independently associated with delayed puberty were extensive chronic GVHD (P =.041) and age >10 years (P =.031). Conclusion: This study highlighted the toxicity of MAC in prepubescent children: TBI did worse, but this was especially true for the most susceptible patients (girls, leukemic patients, and patients older than 10 years). It suggests a possible role of GVHD in delayed puberty. [ABSTRACT FROM AUTHOR]

Antithymocyte globulin is a major drug in transplantation. rATG has been successfully used to prevent graft‐versus‐host disease in allogeneic HSCT. However, its first infusion is associated with reactions ranging from simple fevers to distributive shocks and may interfere with the transplant conditioning. To evaluate the impact of rATG infusion rate on clinical tolerability, we conducted a retrospective study of all pediatric allogeneic HSCT patients who received rATG (Thymoglobulin®) as part of their conditioning at Lille University Hospital from 2003 to 2018. Until 2012, patients received rATG with a theoretical infusion time of 12 hours (12H group, n = 33). From 2012, they had a theoretical infusion time of 4 hours (4H group, n = 43). Patients from the 12H arm presented more ≥ grade 3 infusion‐related reactions at first dose (70% versus 44%, P =.027), had significantly higher fever (median of 39.6°C versus 39.2°C, P =.002), and needed a greater use of symptomatic treatments. However, they received a slightly higher first dose of rATG (median of 2.7 versus 2.3 mg/kg, P =.042). In view of these results, a rATG infusion time of 4 hours can be a relevant option for pediatric transplant centers to avoid interference with the conditioning regimen and facilitate medical surveillance. [ABSTRACT FROM AUTHOR]

PAP is a rare disease characterized by the accumulation of surfactant materials in the alveolar spaces due to the imbalance of surfactant homeostasis (production and clearance). We herein report a case of an 8‐year‐old girl who developed PAP after BMT from her mother for the treatment of DBA. The anemia was improved by BMT; however, respiratory dysfunction due to graft‐versus‐host disease gradually progressed. She eventually underwent right single LDLLT from her mother when she was 14 years old. A pathological examination of the excised lung confirmed the finding of diffuse bronchiolitis obliterans and unexpectedly revealed widespread alveolar proteinosis. Interestingly, the GGO of her native left lung on chest X‐ray was improved after LDLLT. We present the very unique clinical course of this patient and discuss the mechanisms underlying the development of PAP after BMT and its improvement after LDLLT from the same donor. [ABSTRACT FROM AUTHOR]

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood–derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus–associated late‐onset hemorrhagic cystitis (BKV‐HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV‐HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106/kg once a week until the symptoms improved. The median follow‐up time was 1432 (89‐2080) days. The median frequency of MSC infusion was 2 (1‐3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36‐56.9) ×108/mL before MSC infusion and 2.67 (0‐56.3) ×108/mL after MSC infusion; the difference was not significant (P =.219). There were no significant differences in the overall survival, disease‐free survival, and the incidence of relapse and acute and chronic graft‐versus‐host disease between the MSC infusion group and non‐MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein‐Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood–derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV‐HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long‐term infection, or survival of patients with leukemia. [ABSTRACT FROM AUTHOR]

CHARGE syndrome is a rare congenital malformation syndrome which may share symptoms with DiGeorge syndrome. Complete DiGeorge syndrome (cDGS) is a severe form of DiGeorge syndrome, characterized by a CD3+ T‐cell count of <50/mm3 due to athymia, and is fatal without immunologic intervention. We performed peripheral blood lymphocyte transfusion (PBLT) from an HLA‐identical sibling without pretransplant conditioning in a CHARGE/cDGS patient with a novel CHD7 splice site mutation. Cyclosporine and short‐term methotrexate were used for graft versus host disease (GVHD) prophylaxis, and neither acute nor chronic GVHD was observed. After PBLT, T‐cell proliferative response to phytohemagglutinin and concanavalin A recovered, and intractable diarrhea improved. EBV infection, evidenced by a gradual increase in the viral genome copy number to a maximum of 2861 copies/μgDNA on day 42 after PBLT, resolved spontaneously. HLA A2402 restricted, EBV‐specific CTLs were detected from peripheral blood on day 148, and EBV seroconversion was observed on day 181. Thus, EBV‐specific immunity was successfully established by PBLT. Our results indicate that PBLT is a simple and effective therapy to reconstitute immune systems in CHARGE/DiGeorge syndrome. [ABSTRACT FROM AUTHOR]

Abstract: GI perforation after stem cell transplantation is extremely rare and is associated with poor prognosis. In addition, the clinical limitations of MMF are associated with GI intolerance and hematologic suppression. However, the exact mechanism whereby MMF induces changes in GI mucosa is unknown. Currently, there is no definite method to distinguish between GI toxicity associated with MMF and GVHD. It is important to recognize association between MMF and the histologic changes mimicking GVHD, given that GVHD is a significant differential diagnosis in stem cell transplant patients. MMF‐induced colitis and GI perforation are extremely rare but should be considered in patients presenting with diarrhea and abdominal pain. Histology and clinical features are helpful to distinguish this condition from ischemic colitis. Early recognition of GI perforation is necessary for proper diagnosis and subsequent intervention. Emergency medical treatment and laparotomy have been shown to reduce the risk of fatal complications in patients presenting with GI symptoms suspected of GI perforation. [ABSTRACT FROM AUTHOR]

Abstract: Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with β‐thalassemia major. A matched sibling or a related donor is usually found in only 25%‐30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT‐based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow‐up of 25 (1‐92) months and 22.5 (1‐50) months, respectively (P=.757). The thalassemia‐free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow‐up of 24 (1‐92) and 16.5 (1‐50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft‐versus‐host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non‐infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan‐based regimen using PBSC grafts. [ABSTRACT FROM AUTHOR]

HLH occurring after HSCT is a relatively rare disease. Many conditions may mimic or trigger HLH in post-HSCT period (eg, cytokine release syndrome, engraftment syndrome, graft rejection/failure, acute graft- vs- host disease, infections systemic inflammatory response syndrome/sepsis, and thrombotic microangiopathy). Moreover, this period is usually marked by febrile illness, cytopenia, and a "cytokine storm" leading to elevation of inflammatory biomarkers like ferritin and sCD25. These parameters overlap with the diagnostic criteria for HLH. Such confounding factors make the management of post-HSCT HLH quite challenging. We illustrate this critical issue with case report of a patient who was diagnosed with HLH after allogeneic HSCT for tAML. He received MP and CsA for HLH but VP-16 was not administered due to fear of severe myelosuppression. Fortunately, he responded well to treatment and remains in remission to date. We recommend caution while using HLH-94/HLH-2004 guidelines for the diagnosis and management of post-HSCT HLH. In this article, we pinpoint these issues with a brief review of all the pediatric cases and clinical studies of post-HSCT HLH along with a critical evaluation of its various diagnostic criteria. Finally, based on the limitations of current diagnostic criteria, we suggest a need for formulating disease-specific diagnostic criteria for post-HSCT HLH. [ABSTRACT FROM AUTHOR]

Abstract: BOS is the pulmonary manifestation of cGvHD post‐allogeneic HSCT. Survival and treatment of this often fatal complication have not improved over the last 20 years and there is no clear standard of care. For the past 10 years, BOS was treated in our center with monthly cycles of HDPS. We reviewed the outcomes of patients with post‐HSCT BOS who met the diagnostic criteria for BOS as per the NIH consensus and were treated with at least one cycle of methylprednisolone at a dose of 10‐30 mg/kg/d×3 d. We collected demographic and clinical data, responses to treatment and results of pulmonary function tests at several time points. Between January 2007 and January 2014, 12 patients were treated with HDPS for post‐HSCT BOS. Five patients (42%) had a good response to treatment; four patients (33%) stabilized with moderate lung disease; and three patients (25%) progressed to end‐stage disease. No significant acute side effects attributable to the HDPS treatment were identified. HDPS may be an effective treatment option for all but the most severely ill patients with post‐HSCT BOS. [ABSTRACT FROM AUTHOR]

Abstract: Alemtuzumab is a humanized mAb targeted to CD52. Alemtuzumab is highly immunosuppressive with the ability to deplete T and B cells (in addition to other immune cell lines). A growing understanding of the PKs, dosing, and timing of administration of alemtuzumab has allowed for the study of its use as a conditioning agent for allogeneic HCT. The highly immunosuppressive properties of the drug are particularly appealing in the setting of non‐malignant HCT, where GVHD provides no clinical benefit and relapse of malignancy is not applicable. In addition, the degree of immune suppression achieved with alemtuzumab has allowed for a reduction in the intensity of myeloablative cytotoxic agents included in some HCT conditioning regimens, allowing for fewer acute and late toxicities. This review paper will provide a comprehensive summary of the mechanism of action, PKs, dosing, and timing of alemtuzumab, a brief description of its use in various allogeneic HCT protocols for non‐malignant conditions and a summary of the data regarding its use for GVHD therapy. The goal of this review was to provide an understanding as to how alemtuzumab might be safely incorporated into HCT conditioning regimens for children with non‐malignant disease, allowing for expanded access to curative HCT therapy. [ABSTRACT FROM AUTHOR]

Abstract: This study's purposes were to diagnose intractable hemolytic anemia and to provide guiding treatment for the affected family members. We performed NGS in a panel of 600 genes for blood diseases on a patient with obscure hemolytic anemia and her parents. We confirmed the diagnosis of pyruvate kinase deficiency, identified a novel homozygous mutation of the PKLR gene ( NM_000298: exon 6: c.T941C: p.I314T), and ruled out other blood diseases in the Chinese family. Furthermore, amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of PKLR gene mutation. The proband received cord blood and bone marrow from the second child of the mother for hematopoietic stem cell transplantation and achieved normal hematopoiesis. The genetic characterization analysis and genotype‐phenotype correlation study of PKLR gene suggested that NGS was an effective method to confirm the molecular diagnosis of intractable hemolytic anemia. The identification of the mutation aided in prenatal diagnosis in the second pregnancy and the effective clinical management of the affected family. [ABSTRACT FROM AUTHOR]

Abstract: Viral infections remain one of the most important complications following allogeneic HSCT. Few reports compare virus infection between different donor types in pediatric patients. We retrospectively analyzed viral infections and the outcome of one hundred and seventy‐one pediatric patients (median 7.38 years) who underwent allogeneic HSCT from matched related donor (MRD, n = 71), 10 of 10 HLA allele‐matched unrelated donors (MUD1; n = 29), 9 of 10 HLA allele‐matched unrelated donors (MUD2; n = 40), and haploidentical donors (n = 31). PCR screening for BK virus, adenovirus, Epstein‐Barr virus, parvovirus B19, human herpesvirus 6, and CMV were performed routinely weekly. Infections between 0‐30, 31‐100, and 101 days‐2 years were identified separately. BK virus and CMV reactivations were significantly low in MRD transplant patients (P = .046 and P < .0001, respectively), but incidences of all virus infections between MUD1, MUD2, and haplo‐HSCT were found statistically not different. The OS was found to be affected by having one or multiple virus infection (P = .04 and P = .0008). Despite antiviral prophylaxis and treatments, post‐transplant viral infections are associated with reduced overall survival. Haplo‐HSCT is comparable with MUD transplantation in the setting of viral infections. A larger study group and prospective studies are needed to confirm this observation. [ABSTRACT FROM AUTHOR]

Abstract: In SCT, death from transplant‐related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non‐malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000‐2004), B (2005‐2008), and C (2009‐2013), and an improvement in 5‐year OS and a decrease in 5‐year TRM were observed over these time periods; that is, OS was 61.5%, 60.3%, and 79.5% (P = .062), and TRM was 19.9%, 7.9%, and 0.0% (P < .001) in periods A, B, and C, respectively. On multivariate analysis, the prognostic factor for TRM for all patients was administration of danaparoid (HR = 0.109, 95% CI = 0.033‐0.363, P < .001), and for patients with hematological malignancies in allogeneic SCT, the prognostic factors were danaparoid (HR = 0.046, 95% CI = 0.006‐0.326, P = .002) and advanced disease at SCT (HR = 4.802, 95% CI = 1.734‐13.30, P = .003). A reduction in TRM after SCT was observed over the time periods, and supportive care with danaparoid was found to be significantly effective in reducing TRM in SCT for children. [ABSTRACT FROM AUTHOR]

HPC infusions have been associated with a variety of adverse events related to either patient or HPC product-related factors. Studies documenting infusion-related AEs in children are limited. We reviewed HPC infusion records in 354 children. Infusion-related adverse events were classified as follows: grade 0-absent, grade I-mild, grade II-moderate, grade III-severe, grade IV-life-threatening, and grade V-death. The percentage of patients with grade 0, I, and II- IV AEs was as follows: 0 = 67%, I = 23.4%, and II-V = 9.6% (one patient had fatal anaphylactic reaction to dimethyl sulfoxide). The incidence of grade II- IV hypertension was 7.1%. There was a higher incidence of AEs with infusion of allogeneic bone marrow versus allogeneic PBSCs (47.4% vs 25.3%, P = .001). Cryopreserved products had a lower incidence of infusion-associated AEs compared with fresh HPC products (24% vs 39.4%, P = .003). Allogeneic HPC infusion volume (>100 mL) was a significant risk factor for infusion-associated AEs ( P < .001). Patients >10 years who received autologous HPC infusions had higher risk of AEs when compared to patients <10 years ( P = .01). Our study demonstrated that despite a high incidence of infusion-associated hypertension, HPC infusion is relatively safe in children. Investigating strategies to optimize management of hypertension in the setting of HPC infusion is warranted. [ABSTRACT FROM AUTHOR]

GF is one of the fatal complications of allogeneic HSCT. To rescue patients with primary GF, a second HSCT should be conducted as soon as possible, but the optimal donor source and technique have yet to be established. In this study, we retrospectively analyzed six children with hematologic malignancies who received TCR-haploidentical second HSCT for primary GF. The median interval between the prior HSCT and the second HSCT was 37.5 days. All patients received fludarabine and ATG containing reduced-intensity re-conditioning before the second HSCT. All patients, except one who died early, achieved both neutrophil and Plt engraftment at a median time of 15 and 33 days, respectively. Chimerism analysis showed that all engrafted patients achieved complete donor chimerism within 3 weeks. Four patients developed acute GVHD, and three patients developed chronic GVHD. TRM occurred in two patients. Median follow-up of the four survivors was 6.8 years, and all remained in sustained remission until the last follow-up. These results suggested that a TCR-haploidentical second HSCT for pediatric patients is feasible, and this approach may provide a potent option for children with primary GF. [ABSTRACT FROM AUTHOR]

Severe aGv HD is a life-threatening complication after allogeneic HSCT. The GI tract is considered to play a key role in aGvHD, where the disease process can start and is one of the major target organs. Here, we present a case of a one-year-old child with a life-threatening GI- aGvHD stage IV, post- HSCT, resistant to steroids and MMF for 4 weeks. He was successfully treated with placenta-derived DSC. [ABSTRACT FROM AUTHOR]

We conducted a retrospective analysis of outcomes for children and young adults with sAML/ sMDS who underwent HSCT at our institution. Thirty-two patients (median age 20 years) with sAML (n=24) and sMDS (n=8) received HSCT between 1990 and 2013. The median time from sAML/ sMDS diagnosis to HSCT was 4.1 months (range: 1.2-27.2 months). The transplant regimens were primarily busulfan based (n=19). BM was the primary donor source (n=15). Eleven recipients were transplanted with residual disease. At a median follow-up of 62.3 months (range: 0.4-250.9 months), 14 patients had disease recurrence. Acute GVHD, grade III/ IV, occurred in three patients. Causes of death were as follows: disease relapse (n=12), infection (n=2), pneumonia (n=1), pulmonary hemorrhage (n=1), acute GVHD (n=1), and graft failure (n=1). A PS of ≥90% at the time of HSCT had a significant impact on PFS ( P=.02). Patients achieving pretransplant primary CR (n=8) and those with sMDS and RA (n=6) had prolonged PFS ( P=.04). On multivariate analysis, shorter time to transplantation (≤6 months from diagnosis of sAML/ sMDS) was associated with superior OS ( P=.0018) and PFS ( P=.0005). [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G- CSF for stem cell mobilization (G- CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106/L (0.02-0.21) in SS- BM donors and 0.18×106/L (0.09-0.67) in GP- BM donors ( P=.03). Median of CD34+ cell count given to recipients was 2.6×106/recipient body weight (1.3-19.3) in SS- BM yields and 3.8×106/recipient body weight (1.1-10.2) in GP- BM yields, respectively. Multiple regression analysis showed that donor height and pre-G- CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors. [ABSTRACT FROM AUTHOR]

Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched ( MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute Gv HD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality ( HR = 0.57; p = 0.005), reduced TRM ( HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic Gv HD ( HR = 0.49; p = 0.01), and more acute Gv HD ( HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT. [ABSTRACT FROM AUTHOR]

Gv HD is a rare and serious complication of organ transplantation. The literature is sparse following solid organ transplantation. The aim of this report was to review the literature of GvHD in paediatric solid organ transplantation. We searched PubMed for English-language full-text manuscripts between 1990 and 2015 for eligible studies. A total of 28 publications were found pertaining to paediatric Gv HD following solid organ transplantation. Gv HD had a mean incidence of 11% (range 8.3-13.4%) following SBTx and 1.5% following liver transplantation. Where described, the most common sites for presentation of Gv HD were the skin (87%), the native GI tract (43%), the lungs (7%), the eyes (4%), HA (4%), and the kidneys (1%). Diagnosis was confirmed with biopsy (93%) and/or chimerism (41%). Treatments used include steroids (80%), of which 75% showed partial or complete resolution. Mortality was 33.3% (range 0-100%). Novel therapies include ECP and MSC therapy. Gv HD is a rare but serious disease with high mortality. Novel therapies may offer hope in the future, but currently there is limited evidence for their efficacy in the context of intestinal or liver transplantation. [ABSTRACT FROM AUTHOR]

There are few reports on the clinical significance of MRD before HSCT in pediatric ALL. We retrospectively analyzed the clinical significance of FCM-based detection of MRD ( FCM- MRD) before allogeneic HSCT in pediatric ALL. Of 38 pediatric patients who underwent allogeneic HSCT for the first time between 1998 and 2014, 33 patients were in CR and five patients were in non- CR. The CR group was further divided into two groups based on the pretransplant FCM- MRD level: the MRDneg (<0.01%; 30 patients) group and the MRDpos (≥0.01%; three patients) group. There were significant differences in the three-yr event-free survival rates between the CR and non- CR group, and between the MRDneg and MRDpos group. The three-yr cumulative RI in the MRDneg group were 27.3% ± 8.8%, whereas two of the three patients in the MRDpos group relapsed within one yr after HSCT. The clinical outcome of the MRDpos group was as poor as that of the non- CR group in pediatric ALL. Therefore, an improvement in pretransplant treatment that aims to achieve a more profound remission would contribute to reducing the risk of relapse. [ABSTRACT FROM AUTHOR]

Timely and reliable detection of viruses is of key importance in early diagnosis of infection(s) following allogeneic HSCT. Among the immunocompetent, infections with BKPy V and JCPyV are mostly subclinical, while post- HSCT, the former may cause HC and the latter PML. The epidemiology and clinical impact of the newly identified KIPyV, WUPyV, MCPyV, and TSPyV in this context remain to be defined. To assess the incidence and clinical impact of BKPyV, JCPyV, KIPyV, WUPyV, MCPyV, and TSPyV infections, we performed longitudinal molecular surveillance for DNAemias of these HPyVs among 53 pediatric HSCT recipients. Surveillance pre- HSCT and for three months post- HSCT revealed BKPyV DNAemia in 20 (38%) patients. Our data demonstrate frequent BKPyV DNAemia among pediatric patients with HSCT and the confinement of clinical symptoms to high copy numbers alone. MCPyV and JCPyV viremias occurred at low and TSPyV viremia at very low prevalences. KIPyV or WUPyV viremias were not demonstrable in this group of immunocompromised patients. [ABSTRACT FROM AUTHOR]

A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.2%) or UBMT (73.9%) in 2000-2010. However, EFS rates in RBMT (73.2%) and UBMT (62.2%) were better than that in UCBT (49.5%), and the difference between RBMT and UCBT was significant (p = 0.01). The EFS rate of patients conditioned by RIC (74.6%) was comparable or slightly better than in those who underwent MAC with irradiation (57.9%) or without irradiation (54.2%) in 2000-2010. A more pronounced trend was observed toward differential EFS for UCBT in 2000-2010: RIC (62.9%), MAC with irradiation (20.0%), and MAC without irradiation (42.1%). The difference between RIC and MAC with irradiation was significant (p < 0.03). In summary, we report a Japanese registry analysis of HSCT for IEM with improving survival in UCBT. The introduction of RIC after 2000 was considered to contribute to this improvement. UCBT could be recommended for those who lack an HLA-identical sibling donor. [ABSTRACT FROM AUTHOR]

GVHD and graft failure are serious problems in CBT. PES after CBT also occurs frequently and is associated with transplantation-related complications such as acute GVHD. We reviewed medical records for 70 consecutive child CBT recipients between December 1997 and April 2015. Forty-nine patients received prophylaxis against GVHD with CsA or Tac in combination with mPSL from day +7 ( mPSL group), and 21 patients received CsA or Tac with MTX on day +1 and day +3 ( MTX group). Neutrophil engraftment was detected in 59 patients (84.3%). Neutrophil engraftment rate in the MTX group was significantly higher than that in the mPSL group (21/21 (100%) and 38/49 (77.6%), respectively, p = 0.027). PES developed in 35 patients, and the incidence of PES in the mPSL group was significantly higher than that in the MTX group (p = 0.036). The incidence of severe acute GVHD (grade III or IV) in the MTX group was significantly lower than that in the mPSL group (p = 0.049). Although this study was a small-scale study, the results showed that increase in the rate of engraftment and decrease in the incidence of early immune reactions such as PES and severe acute GVHD could be achieved by early commencement of immunosuppression using MTX. [ABSTRACT FROM AUTHOR]