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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), Tnaive, Bnaive, CD56dimCD16+ cell ratios were significantly lower in the patients than in control; however, follicular helper T TFH 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 TFH 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. [ABSTRACT FROM AUTHOR]

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. [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. 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. [ABSTRACT FROM AUTHOR]

Busulfan (BU)-based myeloablative conditioning is a standard conditioning regimen for children with AML; however, it is not clear yet which combination of cyclophosphamide (CY) and fludarabine (FLU) is most effective. We performed a study to compare the results of BUCY120 and BU-FLU in pediatric patients with AML in CR1 undergoing allo-HSCT from matched sibling donors. With the combination of BU, 15 patients were given 120 mg/kg of CY, and 12 patients were given 150 mg/m2 of FLU, respectively, in the condition regimen. Patients treated with BUFLU relapsed less than those treated with BUCY120 (p= 0.03). Moreover, these patients engrafted platelets earlier than the BUCY120 administered patients (p= 0.03). The frequency of complications in both groups was comparable. There was no significant difference in survival analysis between the groups. BUFLU has a low toxicity profile, making it a reasonable choice for children with AML in CR1 with low risk and a lower relapse frequency compared to BUCY120. [ABSTRACT FROM AUTHOR]

Solid organ transplantation from the same donor is an established procedure for end-stage organ failure that developed after a previous hematopoietic stem cell transplantation (HSCT); however, it is rarely done in patients transplanted with unmanipulated haplo-HSCT. There are no pediatric reports regarding the long-term performance of organ transplantation after haplo-HSCT with post-transplant cyclophosphamide (PTCY). A juvenile myelomonocytic leukemia patient, who underwent unmanipulated haplo-HSCT with PTCY from her mother at the age of 3 years, developed chronic liver graft versus host disease (GvHD) which was refractory to specific GvHD treatment. Liver transplantation (LT) from her mother (the donor of her haplo-HSCT) was decided as the next line of treatment. LT was performed on day 540 post-HSCT, and the donor's left lateral segment was appropriately removed and attached to the recipient. The symptoms of GvHD completely regressed in a month. The patient died on day 121 after LT, because of a possible hepato-pulmonary syndrome. Organ failure can develop after allo-HSCT secondary to GvHD and therefore performing HSCT from a haplodonor may be superior to a matched unrelated donor in terms of subsequent organ transplantation for organ failure. [ABSTRACT FROM AUTHOR]

Background: Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency. Methods: We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen. Results: In the conditioning regimen, rituximab was given on Day −11 (375 mg/m2), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days −7 to −4) with 150 mg/m2 of fludarabine (Days −7 to −3). They were transplanted with peripheral blood stem cells, and graft‐versus‐host disease (GVHD) prophylaxis was administered with 10 mg/m2 methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno‐occlusive disease (VOD), high‐grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism. Conclusions: Serine/threonine kinase 4 deficiency is a disease with high mortality post‐HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU‐FLU), GVHD prophylaxis with sirolimus and MMF, and short‐term methotrexate, offers favorable outcomes and is well tolerated in our STK4‐deficient patients. [ABSTRACT FROM AUTHOR]

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 D3 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 D3 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 D3 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. [ABSTRACT FROM AUTHOR]

Aim: In hematopoietic stem cell transplantation (HSCT), the phase of engraftment which can be described as an "immunogenic storm", is also vulnerable to infections and it has been always very hard to discriminate the cause of fever in this special period of HSCT. In this study, we aim to determine if procalcitonin (PCT) could be used to define the cause of fever in the engraftment phase of HSCT. Materials and Methods: This study involves 81 patients who consecutively underwent allogeneic HSCT between October 2017-June 2020 in our pediatric HSCT unit. The patients were divided into two groups due to the origin of the fever during engraftment as infectious fever group (n=42) and the non-infectious fever group (n=39). Results: The median duration of fever for all groups was 4 days (1-11 days) and it was significantly lower in the non-infectious fever group compared to the infectious fever group (3 vs. 4 respectively p=0.001). The median PCT levels was 0.6 ng/mL (0.04-83) for all groups and it was significantly higher in the infectious fever group compared to non-infectious (1.4 vs. 0.3 p<0.001). According to ROC analysis, the cut-off PCT level of 0.515 ng/mL or more had an AUC of 0.817 and may predict the infectious fever with a sensitivity of 81% and a specificity of 76.9%. Conclusion: We observed that PCT may be used to discriminate infectious fever from non-infectious fever at the engraftment phase of HSCT and PCT could be a useful marker for antibiotic treatment strategy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aims were to investigate the incidence of BKV infection and the presence of HC in pediatric patients undergoing HSCT. Twenty‐four children patients (M/F: 17/7) undergoing HSCT in a single center over a period of 1 year were included in the study. The presence of BKV DNA was determined by quantitative real‐time PCR in plasma and urine samples at the following times: before transplantation, twice a week until engraftment time, and weekly for + 100 days. The mean age of the patients was 7.79 ± 5.03 years, the mean follow‐up time was 95.6 ± 25.9 days, and the average number of samples per patient was 15.8 ± 3.2. BKV DNA was detected in at least one urine sample in 91.6% (n: 22) and at least one plasma sample in 75% (n:18) of the patients. The median time to the first BKV DNA positivity in urine and plasma samples was 11 (range: 1‐80) and 32 days (range: 2‐79), respectively. The median value of BKV DNA copies in urine and plasma were 1.7 × 106 (range: 2.8 × 101‐1.2 × 1014) and 1.9 × 103 copies/mL (range: 3‐2.1 × 106), respectively. Thirteen patients (54.2%) had hematuria with BKV viruria; 8 (33.3%) patients had viremia. The median value of the BKV DNA copies in urine and plasma was 4.4 × 107 (range: 65‐1 × 1011) and 2.9 × 103 (range: 7‐7.8 × 104) copies/mL in these patients. Two (15.4%) of the 13 patients with BKV viruria and hematuria were diagnosed with BKV‐related HC. BKV DNA viral load monitoring of urine and plasma in pediatric HSCT patients with a high risk for viral infections is valuable for understanding the development of BKV–related HC. [ABSTRACT FROM AUTHOR]

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 × 104/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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 35.8 kg (range 11–84 kg), 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. [ABSTRACT FROM AUTHOR]

Background: Myasthenia gravis (MG) is a neuromuscular disorder characterized by an autoimmune defect in the neuromuscular junction. In most patients, the autoimmune attack is mediated by antibodies against the acetylcholine receptor (AChR) on the postsynaptic membrane. Deficient immunoregulation, including regulatory T cells, is consistently observed. Extracorporeal photopheresis (ECP) leads to the induction of regulatory T cells that mediate immunologic tolerance in autoimmune diseases; however, the data regarding MG are very limited.Case Report: Here, we report a patient who, during ongoing ECP therapy for his severe, refractory, chronic graft-versus-host disease (cGVHD), developed MG, although he responded very well to ECP, as indicated by the lowering of his chronic cGVHD severity grade to moderate.Results: Despite receiving ECP, our patient developed MG, which was resistant to treatment and required intensive care unit support.Conclusions: Close surveillance is required when ECP is planned as one of the treatment alternatives in myasthenia gravis that develop in cGVHD. [ABSTRACT FROM AUTHOR]