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Mucopolysaccharidosis IVA (MPS IVA; Morquio syndrome) is a lysosomal storage disorder and features systemic skeletal dysplasia that is caused by defective Nacetylgalactosamine-6-sulfate sulfatase (GALNS). Although there are convincing data for hematopoietic stem cell transplantation (HSCT) in certain types of MPS, the studies are limited for MPS IVA and more data is still pending to show the efficacy/safety of HSCT. This study included 3 girls and 7 boys, with a median age of 75,5 months (35-186 months), who underwent allogeneic HSCT for severe MPS IVA between February 12, 2021, and March 10, 2023. Enzyme levels, height growth, the most involved organs (ear, eye, and heart), and the activities of daily living (ADL) scoring system were monitored to assess the benefit of HSCT. In a median follow-up of 20 months (9-34 months), there is no severe transplant-related adverse event was observed. In all cases, normal enzyme levels were reached after HSCT. During the short follow-up period, our cases showed an increase in stature and improvement in daily activity functions. Here we present the data of our HSCT experience in MPS IVA with promising results regarding both safety and efficacy. Although there are signs of amelioration with HSCT, we need more data and long-term follow-up to comment properly on the benefits of HSCT in MPS IVA., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Recent epidemiological studies have increasingly highlighted the antitumor efficacy of IgE owing to the increased malignancy rate in IgE-deficient patients. The purpose of this study, the largest for children, was to determine whether malignant diagnoses in children are associated with IgE deficiency (IgE <2.5 kIU/L). A total of 6821 pediatric patients were reviewed, focusing on patients with IgE below 2.5 kIU/L (n = 599). The causes of IgE testing were evaluated by categorizing them as having cancer, allergies, suspected or diagnosed immunodeficiency, and other conditions. In all but one patient with malignancy, IgE levels were measured after the diagnosis of the disease. Malignancies were observed much more frequently in the low IgE group than in the normal group (10/599, 1.7% and 7/6222, 0.11%; OR = 15.07; 95% CI: 5.72-39.75; p <.0001). According to our analysis, 70% of the patients had leukemia/lymphoma, which is consistent with studies showing that hematologic malignancies are the most frequent cancers linked to IgE deficiency. No increase in the prevalence of cancer was observed in IgE-deficient patients with suspected or diagnosed immunodeficiency. In conclusion, we observed a higher rate of previous malignancy (particularly hematologic cancer) in children with low serum IgE levels. Larger investigations would offer insightful information about the function of low IgE levels in predicting malignancy risk and improving the present diagnostic procedures., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: In this study, we aimed to report long-term follow-up of our pediatric and adult patients with DCLRE1C (DNA cross-link repair 1C) hypomorphic mutation who were diagnosed leaky severe combined immunodeficiency (SCID)., Methods: Eighteen patients (13 children and five adults), aged between 6 and 29 years were included. Clinical and immunological features, including immunoglobulin levels, T and B cells, natural killer cell subsets, regulator T (Treg) cell ratios/markers, and cytokines, were assessed before and after hematopoietic stem cell transplantation (HSCT) and compared with healthy controls., Results: Recurrent infections (78%) and skin manifestations (61%) such as granulomatous skin lesions, warts, and vitiligo were the most common clinical findings. Autoimmune diseases were observed in 33% and malignancy in 17%. Most patients had low serum IgA and B- and T-cell lymphopenia at the first admission. Recent thymic emigrants (RTE), T naive , B naive , CD56 dim CD16 + cell ratios were significantly lower in the patients than in control; however, follicular helper T T FH and Th1 [interferon gamma (IFN-γ)] cell ratios were significantly higher than the control. Although, Treg ratio and its functional receptors tend to be high but not significant. Eleven patients (61.1%) were treated with HSCT. Median follow-up times of transplant patients was 56 (9-67) months., Conclusion: Patients with hypomorphic DCLRE1C mutations may present with variable clinical and laboratory findings at different ages. Our study showed a helper T (Th)1-dominant immune response before and after HSCT. Increased IFN-γ and T FH cells ratio could be a reason of chronic inflammation and autoimmunity developing before and after HSCT. Long-term follow-up of these patients after HSCT will help to better understand the disease and its pathophysiology., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Major histocompatibility complex class II deficiency, a combined immunodeficiency, results from loss of HLA class II expression on antigen-presenting cells. Currently, hematopoietic stem cell transplantation stands as the sole curative approach, although factors influencing patient outcomes remain insufficiently explored., Objectives: To elucidate the clinical, immunologic, and genetic profiles associated with MHC-II deficiency and identify prognostic indicators that affect survival rates., Methods: In this multicenter retrospective analysis, we gathered data from 35 patients with a diagnosis of MHC-II deficiency across 12 centers in Turkey. We recorded infection histories, gene mutations, immune cell subsets, and surface MHC-II expression on blood cells. We conducted survival analyses to evaluate the impact of various factors on patient outcomes., Results: Predominant symptoms observed were pneumonia (n = 29; 82.9%), persistent diarrhea (n = 26; 74.3%), and severe infections (n = 26; 74.3%). The RFXANK gene mutation (n = 9) was the most frequent, followed by mutations in RFX5 (n = 8), CIITA (n = 4), and RFXAP (n = 2) genes. Patients with RFXANK mutations presented with later onset and diagnosis compared with those with RFX5 mutations (P =.0008 and .0006, respectively), alongside a more significant diagnostic delay (P = .020). A notable founder effect was observed in five patients with a specific RFX5 mutation (c.616G>C). The overall survival rate for patients was 28.6% (n = 10), showing a significantly higher proportion in individuals with hematopoietic stem cell transplantation (n = 8; 80%). Early death and higher CD8 + T-cell counts were observed in patients with the RFX5 mutations compared with RFXANK-mutant patients (P = .006 and .009, respectively)., Conclusions: This study delineates the genetic and clinical panorama of MHC-II deficiency, emphasizing the prevalence of specific gene mutations such as RFXANK and RFX5. These insights facilitate early diagnosis and prognosis refinement, significantly contributing to the management of MHC-II deficiency., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited., Objectives: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection., Method: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022., Results: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality., Conclusion: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD., (© 2024 Wiley Periodicals LLC.)

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., (© 2024 Wiley Periodicals LLC.)

Background: Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies., Methods: We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D 3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT., Results: Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D 3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence., Conclusions: Low vitamin D 3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patients., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: In a screening study conducted on adults, the prevalence of sickle cell traits in Antalya was found to be 0.24%. Since no screening studies have been conducted in the neonatal period in our region, the exact incidence has not been determined. In this study, we aim to report our experience of neonatal screening for sickle cell disease in Antalya, Türkiye., Methods: During a 14-month period, 2562 heel prick blood samples, taken on filter paper from Akdeniz University Hospital, Antalya Education and Research Hospital and Antalya Atatürk State Hospital and four other healthcare centers, were studied using the high pressure liquid chromatography method. Blood samples were studied using the `Sickle Cell Short Program` test method on a Bio Rad Variant device., Results: In the study, no patients with sickle cell disease were identified. Four newborns who were sickle cell carriers (0.15%) and two newborns who were Hemoglobin D carriers (0.08 %), were found., Conclusion: Considering the efficiency and cost calculations made as a result of the data obtained from our study, it was concluded that sickle cell screening would not be effective in newborns. It seems more effective and economical to screen the children of parents, who are found to be at risk for Hemoglobin S carriage as a result of premarital tests.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

EBV-associated lymphoproliferative disorders (LPDs) are common in hematopoietic stem cell transplantation (HSCT) with T-cell-depleted grafts, but are extremely rare in HSCT patients with T-cell-replete grafts with post-transplant cyclophosphamide (PTCy). Here we present the cases of two pediatric patients who developed EBV-related LPD after T-cell-replete haplo-HSCT with PTCy. One of these is the first reported case of EBV-positive mucocutaneous ulcer (EBVMCU) developing after PTCy. EBV-related diseases are rare in T-cell-replete haplo-HSCT patients with PTCy. However, in patients with risk factors, it is reasonable to screen for EBV viremia for LPD., (© 2021. Japanese Society of Hematology.)

Background: The use of unmanipulated haploidentical hematopoietic stem cell transplantations (haplo-HSCT) with post-transplant cyclophosphamide (PTCY) in children has emerged as an acceptable alternative to the patients without a matched donor. However, the timing of calcineurin inhibitors (CNIs) used in combination with PTCY is increasingly becoming a topic of controversy., Method: We evaluated 49 children with acute leukemia who underwent unmanipulated haplo-HSCT with PTCY according to the initiation day of CNIs (pre- or post-cyclophosphamide [CY])., Results: There were no significant differences in the overall survival analysis between the 2 groups. The cumulative incidence of relapse at 2 years was 21.2% in the pre-CY group and 38.9% in the post-CY group (p = 0.33). Cytokine release syndrome (CRS) was observed more frequently in the post-CY group (p = 0.04). The overall survival and event-free survival at 2 years in patients with and without CRS in the pre-CY group were 42.9% versus 87.5% (p = 0.04) and 38.1% versus 87.5% (p = 0.04), respectively., Conclusion: Our study shows that the argument for starting CNI administration after CY is tenuous, and the rationale for not starting CNIs before CY needs to be reconsidered., (© 2021 S. Karger AG, Basel.)

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Total body irradiation (TBI) is the cornerstone of conditioning regimens in pediatric hematopoietic stem cell transplantation for acute lymphoblastic leukemia. As the late effects and survival comparison between TBI and chemotherapy were well analyzed before, in this study, we aim to focus on the first 100 days and early complications of transplantation., Methods: This retrospective study involves 72 pediatric patients (0 to 18 y) underwent first hematopoietic stem cell transplantation for acute lymphoblastic leukemia between October 2015 and May 2019. Patients are divided into 2 groups regarding conditioning regimens. Conditionings includes either TBI 1200 cGy/6 fractions/3 days and etoposide phosphate or busulfan, fludarabine, and thiotepa. Busulfan was administered IV and according to body weight., Results: The incidences of acute graft versus host disease grade 2 to 4, veno-occlusive disease, capillary leakage syndrome, thrombotic microangiopathy, blood stream infection, hemorrhagic cystitis and posterior reversible encephalopathy syndrome before day 100 were similar for both conditioning regimens; however, patients received TBI-based conditioning had significantly longer neutrophil engraftment time (17.5 vs. 13 d, P=0.001) and tended to have more engraftment syndrome (ES) (45.5% for TBI vs. 24.0% for chemotherapy, P=0.069). Multivariate analysis showed that TBI-based conditioning was associated with a longer neutrophil engraftment time (hazard ratio [HR]=1.20, P=0.006), more cytomegalovirus (CMV) reactivation (HR=3.65, P=0.038) and more ES (HR=3.18, P=0.078)., Conclusions: Our findings support chemotherapy-based regimens with early neutrophil engraftment, less ES and CMV reactivation compared with TBI. Although there is no impact on survival rates, increased incidence of ES and CMV reactivation should be considered in TBI-based regimens., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Post-transplant relapse has a dismal prognosis in children with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Data on risk factors, treatment options, and outcomes are limited., Procedure: In this retrospective multicenter study in which a questionnaire was sent to all pediatric transplant centers reporting relapse after allo-HSCT for a cohort of 938 children with acute leukemia, we analyzed 255 children with relapse of acute leukemia after their first allo-HSCT., Results: The median interval from transplantation to relapse was 180 days, and the median follow-up from relapse to the last follow-up was 1844 days. The 3-year overall survival (OS) rate was 12.0%. The main cause of death was disease progression or subsequent relapse (82.6%). The majority of children received salvage treatment with curative intent without a second HSCT (67.8%), 22.0% of children underwent a second allo-HSCT, and 10.2% received palliative therapy. Isolated extramedullary relapse (hazard ratio (HR): 0.607, P = .011) and relapse earlier than 365 days post-transplantation (HR: 2.101, P < .001 for 0-180 days; HR: 1.522, P = .041 for 181-365 days) were found in multivariate analysis to be significant prognostic factors for outcome. The type of salvage therapy in chemosensitive relapse was identified as a significant prognostic factor for OS., Conclusion: A salvage approach with curative intent may be considered for patients with post-transplant relapse, even if they relapse in the first year post-transplantation. For sustainable remission, a second allo-HSCT may be recommended for patients who achieve complete remission after reinduction treatment., (© 2020 Wiley Periodicals LLC.)

Objective: The selection of graft-vs. -host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA-associated adverse events in the first 100 days of pediatric HSCT., Materials and Methods: This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus-based immunosuppression within 100 days of transplant., Results: The reasons for conversion to tacrolimus were low level of CSA (n = 70), aGvHD (n = 63), CSA-associated neurotoxicity (n = 15), CSA-associated nephrotoxicity (n = 10), hypertension (n = 10), allergic reactions (n = 9), ES (n = 7), CSA-associated hepatotoxicity (n = 5), and vomiting (n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0-100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty-nine patients (15%) experienced tacrolimus-associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients)., Conclusion: Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: ALD is a rare X-linked peroxisomal metabolic disorder with many distinct phenotypes of disease that emerge on a wide scale from adrenal insufficiency to fatal cALD which progresses to a vegetative state within a few years. Currently, HSCT is the only treatment method known to stabilize disease progression in patients with cALD. In this study, we aim to report our HSCT experience in patients with cALD and the factors that determine the success of HSCT, as a single-center experience., Methods: The study cohort involves 23 boys with cALD and three patients with ALD trait and new-onset abnormal behavior who underwent allogeneic HSCT between January 2012 and September 2019 in our transplantation center. Loes scoring, NFS, scale and MFD were performed for evaluating the severity of the cerebral disease. The study cohort was divided into two groups according to baseline NFS and Loes score: early-stage (NFS ≤ 1 and Loes score <9) and advanced stage (NFS > 1 or Loes score ≥9)., Results: The pretransplant stage of disease impacted both OS and MFD-free survival. The estimated OS and MFD-free survival at 3 years in patients with advanced disease were 46.1% (95% CI 19.0-73.2) and 23.1% (95% CI 0.2-46.0), respectively, and all patients with the early disease were alive (p: .004) and MFD-free (p < .001) at 3 years., Conclusion: This study demonstrated that early HSCT is vital in patients with cALD. The early-stage disease had a significant survival advantage and free from disease progression after HSCT., (© 2021 Wiley Periodicals LLC.)

The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty-four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real-time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow-up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1-80) and 32 days (range: 2-79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 10 6 (range: 2.8 × 10 1 -1.2 × 10 14 ) and 1.9 × 10 3 copies/mL (range: 3-2.1 × 10 6 ), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 10 7 (range: 65-1 × 10 11 ) and 2.9 × 10 3 (range: 7-7.8 × 10 4 ) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV-related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV-related HC., (© 2020 Wiley Periodicals LLC.)

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy., (© 2020 John Wiley & Sons Ltd.)

Although advancements have been made in monitoring and preventing viral infections in HSCT patients, CMV reactivation still remains a critical post-transplant complication. Adoptive cell therapy is an alternative to pharmacotherapy of CMV infection in refractory patients. We retrospectively reviewed CMV infection cases after allogeneic HSCT who received U-DLI as treatment. In total, five pediatric patients between the ages of 0.5-16 years that received U-DLI for a post-HSCT CMV infection were evaluated. The dose of CD3+ lymphocytes administered in DLI was 5 × 10 4 /kg, except in one patient transplanted from his sibling. One patient, who was transplanted from an unrelated donor, received U-DLI from his haploidentical mother. CMV titers dramatically reduced after U-DLI. If the availability of CMV-specific CTL is an issue, we propose that one should consider using the U-DLI therapy with low cell dose from a seropositive donor. In case the stem cell donor is seronegative and a seropositive donor is unavailable, using the U-DLI therapy from seropositive, haploidentical donors is a promising way of treatment. More studies need to be conducted to further confirm the safety and efficacy of this treatment procedure., (© 2020 Wiley Periodicals LLC.)

Deficiency of the CD40L, expressed on the surface of T lymphocytes, is caused by mutations in the glycoprotein CD40L (CD154) gene. Resulting defective humoral and cellular responses cause a clinical presentation that includes recurrent sinopulmonary bacterial infections, opportunistic infections, sclerosing cholangitis, neutropenia, and autoimmune manifestations. HSCT represents the only curative treatment modality. However, the therapeutic decision to use HSCT proves challenging in many cases, mainly due to the lack of a phenotype-genotype correlation. We retrospectively reviewed patients with CD40L deficiency who were transplanted in Antalya and Göztepe MedicalPark Pediatric HSCT units from 2014 to 2019 and followed by Akdeniz University School of Medicine Department of Pediatric Immunology. The records of eight male cases, including one set of twins, were evaluated retrospectively. As two transplants each were performed on the twins, a total of ten transplants were evaluated. Conditioning regimens were predominantly based on myeloablative protocols, except for the twins, who received a non-myeloablative regimen for their first transplantation. Median neutrophil and platelet engraftment days were 13 (range 10-19) and 14 (range 10-42) days, respectively. In seven of ten transplants, a CMV reactivation was developed without morbidity. None of the patients developed GVHD, except for one mild case of acute GVHD. All patients survived, and the median follow-up was 852 days. Our data show that HSCT for patients with CD40 ligand deficiency is a potentially effective treatment for long-term disease control., (© 2020 Wiley Periodicals LLC.)

Currently, there is no guideline for the treatment of patients with congenital dyserythropoietic anemia (CDA) type II. One approach is to follow-up patients with transfusions, on the basis of individually determined target hemoglobin levels, and iron chelation according to the thalassemia guidelines. In some transfusion-dependent CDA II patients, splenectomy reduces the number of transfusions; however, the only known curative option for CDA II patients is hematopoietic stem cell transplantation (HSCT). Only a few published case reports of allogeneic HSCT in CDA II patients are available. Here, we review the literature and add our data of a CDA II patient who developed transfusion dependence and was cured with HSCT.

We examined outcomes of 51 pediatric patients with relapsed acute leukemia (AL) who underwent a second allogeneic hematopoietic stem cell transplantation (alloHSCT). After a median follow-up of 941 days (range, 69-2842 days), leukemia-free survival (LFS) and overall survival (OS) at 3 years were 26.6% and 25.6%, respectively. The nonrelapse mortality rate (NMR) and cumulative incidence of relapse (CIR) were 36.4% and 42.4%, respectively. The Cox regression analysis demonstrated that the risk factors at second transplantation for predicting limited LFS were active disease (hazard ratio (HR) = 5.1), reduced intensity conditioning (RIC) (HR = 5.0), matched unrelated donor (MUD) (HR = 3.4) and performance score <80 (HR = 3.2). Pediatric patients with AL who relapsed after their first alloHSCT may survive with a second alloHSCT. Disease status, conditioning intensity, donor type, and performance score at the second transplantation are the relevant risk factors. A score based on these factors may predict the results of the second transplantation.

Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant., Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant., Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices., Results: Of 76 patients with LRBA deficiency from 29 centers (median follow-up, 10 years; range, 1-52), 24 underwent HSCT from 2005 to 2019. The overall survival rate after HSCT (median follow-up, 20 months) was 70.8% (17 of 24 patients); all deaths were due to nonspecific, early, transplant-related mortality. Currently, 82.7% of patients who did not receive a transplant (43 of 52; age range, 3-69 years) are alive. Of 17 HSCT survivors, 7 are in complete remission and 5 are in good partial remission without treatment (together, 12 of 17 [70.6%]). In contrast, only 5 of 43 patients who did not receive a transplant (11.6%) are without immunosuppression. Immune deficiency and dysregulation activity scores were significantly lower in patients who survived HSCT than in those receiving conventional treatment (P = .005) or in patients who received abatacept or sirolimus as compared with other therapies, and in patients with residual LRBA expression. Higher disease burden, longer duration before HSCT, and lung involvement were associated with poor outcome., Conclusion: The lifelong disease activity, implying a need for immunosuppression and risk of malignancy, must be weighed against the risks of HSCT., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dedicator of cytokinesis 8 (DOCK8) deficiency is the main cause of the autosomal recessive hyper-IgE syndrome (HIES). We previously reported the selective loss of group 3 innate lymphoid cell (ILC) number and function in a Dock8-deficient mouse model. In this study, we sought to test whether DOCK8 is required for the function and maintenance of ILC subsets in humans., Methods: Peripheral blood ILC1-3 subsets of 16 DOCK8-deficient patients recruited at the pretransplant stage, and seven patients with autosomal dominant (AD) HIES due to STAT3 mutations, were compared with those of healthy controls or post-transplant DOCK8-deficient patients (n = 12) by flow cytometry and real-time qPCR. Sorted total ILCs from DOCK8- or STAT3-mutant patients and healthy controls were assayed for survival, apoptosis, proliferation, and activation by IL-7, IL-23, and IL-12 by cell culture, flow cytometry, and phospho-flow assays., Results: DOCK8-deficient but not STAT3-mutant patients exhibited a profound depletion of ILC3s, and to a lesser extent ILC2s, in their peripheral blood. DOCK8-deficient ILC1-3 subsets had defective proliferation, expressed lower levels of IL-7R, responded less to IL-7, IL-12, or IL-23 cytokines, and were more prone to apoptosis compared with those of healthy controls., Conclusion: DOCK8 regulates human ILC3 expansion and survival, and more globally ILC cytokine signaling and proliferation. DOCK8 deficiency leads to loss of ILC3 from peripheral blood. ILC3 deficiency may contribute to the susceptibility of DOCK8-deficient patients to infections., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Despite the increasing performance of allogeneic hematopoietic cell transplantation over the last decades, graft-versus-host disease (GVHD) remains the main cause of morbidity and mortality. The efficacy of ruxolitinib against GVHD has been demonstrated in adult studies; however, very few studies have been conducted in children., Procedure: This study aimed to evaluate the efficacy of ruxolitinib in 29 children with steroid-refractory acute or chronic GVHD. Twenty-five (87%) patients received at least three different immune modulator agents, including methylprednisolone, before initiating ruxolitinib., Results: All grade 2 acute GVHD patients completely responded to ruxolitinib treatment; 82% of high-grade (3-4) acute GVHD patients and 80% of chronic GVHD (moderate-severe) patients had at least a partial response. Of seven patients with bronchiolitis obliterans, five had a partial response after ruxolitinib. Of 29 patients, 22 were administered steroids at any time in the first month of acute GVHD or the first three months of chronic GVHD during ruxolitinib usage, which was significantly tapered by the end of the observation period., Conclusion: Steroid-refractory acute and chronic pediatric GVHD patients treated with ruxolitinib had a high overall response rate, with the additional benefit of steroid sparing., (© 2020 Wiley Periodicals, Inc.)

Subacute sclerosing panencephalitis (SSPE) is a progressive and fatal disease caused by reactivation of a mutated measles virus in brain tissue. The process of reactivation is yet to be elucidated. In this study, the possible roles of the Th1 (interleukin [IL]-12, interferon [IFN]-γ) and the Th17 axis (IL-23, IL-17, IL-22), particularly of IL-17, in the pathogenesis of SSPE were investigated. Briefly, mononuclear cells from SSPE patients were stimulated using measles virus peptide, and the release of IL-12, IL-23, IL-22, IFN-γ, and IL-17 cytokines was measured using enzyme-linked immunosorbent assay and/or enzyme-linked immunosorbent spot assay (ELISpot). We found that in comparison to the mononuclear cells obtained from healthy donors, cells from SSPE patients exhibited increased levels of IL-12, IL-23, IL-17, IL-22, and IFN-γ cytokines in response to measles virus stimulation. However, the same result was not obtained with cytomegalovirus and phytohemagglutinin. Using flow cytometry, mononuclear cells obtained from SSPE patients and healthy controls were also analyzed for the presence of intracellular IL-17 in response to measles virus stimulation. On stimulation, the number of IL-17-positive cells were found to be higher among mononuclear cells obtained from the patients. In addition, the numbers of IL-17- and IFN-γ-positive cells were significantly increased in SSPE patients. In conclusion, this study demonstrates that both the IL-12/IFN-γ and the IL-23/IL-17/IL-22 pathways are functionally abnormal in SSPE pathogenesis. Targeting these pathways and their specific pro-inflammatory mediator production may provide a new strategy to suppress SSPE development.

Background: Post-Cy administration for GVHD prophylaxis in unmanipulated haploidentical HSCT has resulted in improved outcomes in recent years. Studies in children are lacking and accordingly we present the outcomes of 62 haploidentical transplantation for high-risk children., Procedure: We retrospectively assessed 62 transplants in 60 patients who underwent haploidentical-related HSCT with unmanipulated stem cells and for whom Post-Cy was used for GVHD prophylaxis., Results: Myeloid reconstitution was achieved on day + 30 for 57 of the 62 patients. The median follow-up of the surviving 39 patients (63%) was 26 months, with a range of 6-57 months. The OS and EFS at 2 years were 64.6% (52.0%-77.2%, 95% CI) and 58.9% (46.1%-71.7%, 95% CI), respectively. The only factor in our multivariate analysis that contributed to an inferior EFS was a poor remission status prior to HSCT (HR, 8.30; 1.08-63.56; P = 0.041, 95% CI)., Conclusion: The results of T-cell replete haploidentical transplantation with Post-Cy GVHD prophylaxis in high-risk pediatric patients are promising. However, further research is needed to determine the factors that have affect HLA compatibility for predicting the success of haploidentical transplantations., (© 2019 Wiley Periodicals, Inc.)

Background: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent., Method: Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered., Results: The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow-up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene., Conclusion: In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen., (© 2019 Wiley Periodicals, Inc.)

Here we describe a 10-year-old girl with combined immunodeficiency presenting as recurring chest infections, lung disease and herpetic skin infections. The patient experienced two hematopoietic stem cell transplantations and despite full chimerism, she developed bone marrow aplasia due to adenovirus infection and died at post-transplant day 86. Immunologic investigation revealed low numbers of TRECs/KRECs, a severe reduction of memory B cells, absence of isohemagglutinins, and low IgG levels. Whole exome sequencing (WES) identified a novel heterozygous mutation in RAC2(c.275A > C, p.N92 T). Flow cytometric investigation of neutrophil migration demonstrated an absence of chemotaxis to fMLP. Cell lines transfected with RAC2 [N92 T] displayed characteristics of active GTP-bound RAC2 including enhanced NADPH oxidase-derived superoxide production both at rest and in response to PMA. Our findings broaden the clinical picture of RAC2 dysfunction, showing that some individuals can present with a combined immunodeficiency later in childhood rather than a congenital neutrophil disease., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Severe combined immunodeficiency (SCID) is the most serious PID, characterized by T cell lymphopenia and lack of antigen-specific T cell and B cell immune responses, inevitably leading to death within the first year of life if hematopoietic stem cell transplantation (HSCT) is not performed., Purpose and Methods: Since SCID is a common type of PID with an estimated incidence of 1/10.000 in Turkey, a retrospective analysis of HSCT characteristics, survival, immune recovery, and the major clinical features of SCID prior to HSCT is the aim of this multi-transplant center-based analysis., Results: A total of 234 SCID patients transplanted between the years 1994 and 2014 were included in the study. Median age at diagnosis was 5 months, at transplantation, 7 months, B- phenotype and RAGs were the most common defects among others. Immune phenotype did not seem to have an effect on survival rate (p > 0.05), Immunoglobulin (Ig) requirement following HSCT did not differ between B+ and B- phenotypes (p > 0.05). Overall survival rate was 65.7% over a period of 20 years. It increased from 54% (1994-2004) to 69% (p = 0.052) during the last 10 years (2005-2014). Ten-year survival after HSCT has improved over time although the difference was not significant. Infection at the time of transplantation (p = 0.006), mismatched related donor (MMRD) (haploidentical parents), and matched unrelated donor (MUD) donor transplants p < 0.001 were the most important factors, significantly affecting the outcome., Conclusions: This is the first multicenter study with the largest data obtained from transplanted SCID patients in Turkey. Early diagnosis with newborn screening (NBS) together with emerging referrals, treatment by transplantation centers, and specialized teams are mandatory in countries with high parental consanguinity such as Turkey.

Objectives: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey., Methods: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 μg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice., Results: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 μg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 μg/L), SCA (1655.5 to 1260 μg/L), and across age groups of 2-6 years (1971.5 to 1499 μg/L), 7-12 years (1688.5 to 1159.8 μg/L), and 13-18 years (1496.5 to 1107 μg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range., Conclusions: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.

Immune reconstitution inflammatory syndrome (IRIS) is a clinical condition emerging after immune recovery of an immunocompromised status, mostly in human immunodeficiency virus infected patients but also in several other settings, such as the recovery from the severe combined immunodeficiency status after hematopoietic stem cell transplantation. Herein, we report a patient transplanted for severe combined immunodeficiency who developed IRIS for 2 times, namely shortly after transplantation and after donor lymphocyte infusion. Pediatric transplant teams need to be aware of the previous IRIS phenomenon of BCG-adenitis while making the decision of donor lymphocyte infusions.

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to <18 years with β-thalassemia major (TM) who underwent hematopoietic stem cell transplantation (HSCT) and had evidence of iron overload (serum ferritin >1000 µg/L; cardiac MRI T2* <20 ms, or liver iron concentration [LIC; by MRI R2]  ≥5 mg/g). Patients received deferasirox at an initial dose of 10 mg/kg/day, with up-titration to a maximum of 20 mg/kg/day. The study continued for 52 weeks and included a total of 27 patients (mean age, 9.1 ± 3.8 years; 70.4% male). One patient (3.7%) was lost to follow-up. The majority of patients (n = 20; 74.1%) were able to achieve the intended dose of 20 mg/kg/day. No deaths occurred. A total of 134 adverse events (AEs) were reported in 25 patients (92.6%) during the study. The majority of patients had grade 1 or 2 AEs, with only 8 patients (29.6%) experiencing grade 3 AEs. Only 10 AEs occurring in 4 patients (14.8%) were suspected to be related to deferasirox (ALT/AST increase, n = 4; urinary tract infection, n = 1). The deferasirox dose had to be adjusted or interrupted for 6 AEs occurring in 4 patients (14.8%). A total of 6 serious AEs occurred in 3 patients (11.1%), none of which were suspected to be related to deferasirox. From baseline to week 52, there were decreases in median concentrations of alanine aminotransferase (ALT), from 30.0 to 17.0 IU/L, and aspartate aminotransferase (AST), from 35.5 to 26.0 IU/L. Median serum creatinine and cystatin C concentrations were similar at baseline and week 52. There was a continuous and significant decrease in median serum ferritin level from 1718.0 µg/L at baseline to 845.3 µg/L following 52 weeks of therapy (P < .001); 9 patients (33.3%) achieved a level of <500 µg/L. There was also a significant decrease in median LIC (from 8.6 to 4.1 mg/g; P < .001) and an increase in median cardiac T2* (from 26.0 to 28.0 ms; P = .520) from baseline to week 52. Our findings indicate that deferasirox treatment at doses up to 20 mg/kg/day reduces the iron burden in children with TM post-HSCT, with a manageable safety profile., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies., Materials and Methods: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey., Results: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time., Conclusion: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

We examined outcomes of 62 pediatric patients with relapsed or refractory non-Hodgkin lymphoma (rr-NHL) who underwent hematopoietic stem cell transplantation (HSCT). The overall survival (OS) and event-free survival (EFS) rates were 65% and 48%, respectively. Survival rates for patients with chemosensitive disease at the time of HSCT were significantly higher than those of patients with chemoresistant disease (69% vs. 37%, p = .019 for OS; 54% vs. 12%, p < .001 for EFS; respectively). A chemoresistant disease at transplantation was the only factor that predicted a limited OS (hazard ratio = 10.00) and EFS (hazard ratio = 16.39) rates. Intensive chemotherapy followed by HSCT could be an effective strategy for treating children with rr-NHL and may offer improved survival for a significant group of pediatric patients, particularly those with chemosensitive disease at transplantation.

Background and Objectives: Although several studies have reported on the use of children as donors for peripheral blood stem cells (PBSC), data on the predictive factors of CD34+ stem cell yield in healthy pediatric donors are very limited., Design and Method: We retrospectively analyzed factors predicting the yield for a target CD34 cell dose of >3×10 6 /kg recipient body weight in 140 apheresis in 100 healthy pediatric donors. The donors were evaluated in four groups assigned according to their ages of being 0-4 years, 5-9 years, 10-14 years and 15-18 years. 38 donors underwent second apheresis, two of which required third apheresis., Results: Median age and body weight were 9.8 years (range: 2-18 years) and 35.8kg (range 11-84kg), respectively. The median number of CD34+ cells in first apheresis was 3.9×10 6 /kg of recipient body weight (RBW) (range: 0.03-33×106/kg RBW). Sixty-two out of 100 donors (62%) needed only one apheresis. The CD34+ cell count in stem cell product and the amount of CD34+ cell yield considering donors' body weight obtained from the first apheresis was not statistically different among defined age groups. On multivariate analysis, variables that had a significant impact on CD34+ cell collection being more than 3×10 6 kg RBW were donor to recipient weight ratio and periperal CD34+ cell count., Conclusion: Our data suggest that CD34+ stem cell yield can be predicted from circulating CD34+ cell concentration on apheresis day and donor to recipient weight ratio in healthy pediatric donors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

DIDS is a unique form of combined immune deficiency characterized by an unusual susceptibility to cutaneous viral infections, severe allergies with eosinophilia and elevated immunoglobulin E titers, autoimmunity, and cancer. HSCT is considered the standard of care for this deadly disease. We have retrospectively analyzed the outcome of allogeneic HSCT from unrelated donors in patients with DIDS. Data from four patients, with five transplants, are presented. All patients received transplants from unrelated donors' BM, except for one patient who received a cord blood transplant. The conditioning regimens were based on myeloablative protocols for BM derived transplants; a NM regimen was pursued for the patient who received a cord blood transplant, which resulted in graft rejection. Although recurrent pneumonia and skin infections resolved immediately after transplantation, all patients subsequently developed human herpesvirus infection, including cutaneous herpetic lesions, cytomegalovirus reactivation, and zona zoster, which could be attributed to the use of ATG. Despite the presence of serious morbidities prior to transplantation, all patients recovered successfully. DIDS can be successfully treated with allogeneic HSCT from unrelated donors following a myeloablative conditioning regimen, with a reasonable safety profile., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We explored the clinical course of acute high-grade gastrointestinal graft-versus-host disease in children in a single center. This was a retrospective analysis of 28 pediatric patients who presented with a clinical diagnosis of stage III and IV acute graft-versus-host disease (aGVHD) of the gastrointestinal system (GIS). Generally, skin involvement was the initial manifestation of aGVHD that began in the first 3 weeks of hematopoietic stem cell transplantation (HSCT); on the other hand, GIS involvement predominated after the second week of HSCT. Reported adult data show a survival rate of only 25%; however, our study showed more favorable outcomes in children with a survival rate of 55%. We monitored levels of albumin and immunoglobulin G and observed low levels overall during treatment of unresponsive patients, although only albumin levels were shown to be significantly different. We observed a significant increase in mortality with the use of antithymocyte globulin in GIS aGVHD, although antithymocyte globulin used for graft-versus-host disease prophylaxis had no demonstrable effect on GIS aGVHD mortality. Whether the significantly lower GIS aGVHD mortality among the children recruited in our study than among their historical adult counterparts is a primary result of the specific attributes of the pediatric GIS, or whether it originated from HSCT kinetics remains to be determined by future studies.

Recently, haploidentical transplantations have been performed with unmanipulated BM or PBSC. This approach is becoming more widely adopted with the use of PTCY. However, there is limited evidence about this approach in children. We present 15 children who received 16 haploidentical HSCT with unmanipulated BM or PBSC using PTCY for GVHD prophylaxis. Post-transplant CY(50 mg/kg IV) was given on the third and fifth day, and CsA or tacrolimus with MMF or MP was also used for GVHD prophylaxis. All patients engrafted at a median of 16 and 18 days for neutrophil and thrombocyte recovery, respectively. Grades II-III acute GVHD developed in seven patients, and mild chronic GVHD was found in two patients. Two patients died within the first 100 days due to sepsis (TRM 12.5%). Eleven patients are currently alive, with a median follow-up of 12 months (range 6-22 months). The 12-month OS and DFS were 75 ± 10.8% and 68.8 ± 11.6%, respectively. Our results with these high-risk patients are encouraging for haploidentical HSCT in pediatric patients. Future studies should continue to assess haploidentical HSCT, including comparison of other modalities, in a primary pediatric population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)