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Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.

Terapia profiláctica antibiótica; Niños; Vacunación Teràpia profilàctica antibiòtica; Nens; Vacunació Antibiotic prophylactic therapy; Children; Vaccination Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.

Hemoglobinopathies are the most common single-gene diseases and are estimated to affect millions of people worldwide. Thalassemia and sickle cell disease are the most prevalent diseases of this group. Today, despite the decreasing number of newborns diagnosed with a hemoglobinopathy, it remains an important health problem for many countries. Although regular red blood cell (RBC) transfusions, advanced iron chelation, and supportive therapy alternatives have improved life expectancy, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with hemoglobinopathies to prevent irreversible organ damage. Modern transplantation approaches and careful posttransplantation follow-up of patients have improved survival outcomes, and HSCT has now been performed in several patients with hemoglobinopathies worldwide. Considering current experiences, hematopoietic stem cell transplantation is recommended in cases of β-thalassemia (β-thal) in the presence of a matched family or unrelated donor, without secondary organ damage due to transfusion. In patients with sickle cell anemia, transplantation indications include transfusion dependence and cases of secondary organ damage. Recently, gene therapy as a possible treatment option has yielded promising results, though it is not in routine clinical use at its current stage.

BACKGROUND Hematopoietic stem cell transplantation (HSCT) is a curative therapy option for hematologic malignancies. Iron overload is common in this patient group and can impact short-term and long-term nonrelapse mortality. STUDY DESIGN Retrospective observational cohort study. AIMS To evaluate the effect of iron load on early and late HSCT outcomes in patients with acute leukemia and myelodysplasia to assess the necessity of reducing iron load. PATIENTS AND METHODS Sixty patients who underwent HSCT in pediatric stem cell transplantation unit between 2000 and 2012 were evaluated retrospectively. The patients were divided into those with pretransplantation serum ferritin levels above and below the median value of 1299 ng/mL. RESULTS Forty-two (70%) of the patients were male, mean ages of the low and high ferritin groups were 85.43±9.42 and 118.56±10.04 months, respectively. Acute graft-versus-host disease (GVHD) within the first 100 days and acute liver GVHD were significantly more common in the high ferritin group (P

Background Genetic deficiencies of immune system, referred to as inborn errors of immunity (IEI), serve as a valuable model to study human immune responses. In a multicenter prospective cohort, we evaluated the outcome of SARS‐CoV‐2 infection among IEI subjects and analyzed genetic and immune characteristics that determine adverse COVID‐19 outcomes. Methods We studied 34 IEI patients (19M/15F, 12 [min: 0.6‐max: 43] years) from six centers. We diagnosed COVID‐19 infection by finding a positive SARS‐CoV‐2 PCR test (n = 25) and/or a lung tomography scoring (CORADS) ≥4 (n = 9). We recorded clinical and laboratory findings prospectively, fitted survival curves, and calculated fatality rates for the entire group and each IEI subclass. Results Nineteen patients had combined immune deficiency (CID), six with predominantly antibody deficiency (PAD), six immune dysregulation (ID), two innate immune defects, and one in the autoinflammatory class. Overall, 23.5% of cases died, with disproportionate fatality rates among different IEI categories. PAD group had a relatively favorable outcome at any age, but CIDs and IDs were particularly vulnerable. At admission, presence of dyspnea was an independent risk for COVID‐related death (OR: 2.630, 95% CI; 1.198–5.776, p, 34 IEI patients aged between 0.6 and 43 years, eight patients (23.5%) succumbed to COVID‐19, indicating a highly vulnerable condition to COVID‐19. Laboratory markers associated with mortality included elevated acute phase reactants, ferritin, troponin T, TLS, and reduced ALC levels, albumin, and baseline IgG. Coughing, dyspnea, CORADS category 4–6, and negative SARS‐CoV‐2 PCR at admission were among the predictors of lethal outcome.

Up to 40% of donor-recipient pairs in SCT have some degree of ABO incompatibility, which may cause severe complications. The aim of this study was to describe available options and survey current practices by means of a questionnaire circulated within the EBMT Pediatric Diseases Working Party investigators. Major ABO incompatibility (donor's RBCs have antigens missing on the recipient's cell surface, towards which the recipient has circulating isohemagglutinins) requires most frequently an intervention in case of bone marrow grafts, as immediate or delayed hemolysis, delayed erythropoiesis and pure red cell aplasia may occur. RBC depletion from the graft (82%), recipient plasma-exchange (14%) were the most common practices, according to the survey. Graft manipulation is rarely needed in mobilized peripheral blood grafts. In case of minor incompatible grafts (donor has isohemagglutinins directed against recipient RBC antigens), isohemagglutinin depletion from the graft by plasma reduction/centrifugation may be considered, but acute tolerability of minor incompatible grafts is rarely an issue. According to the survey, minor ABO incompatibility was either managed by means of plasma removal from the graft, especially when isohemagglutinin titer was above a certain threshold, or led to no intervention at all (41%). Advantages and disadvantages of each method are discussed.

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2–18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective “real-world-practice” study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

Sickle cell disease is one of the most common, life-threatening, non-communicable diseases in the world and a major public health problem. Following the implementation of simple preventive and therapeutic modalities, infant mortality has almost been abolished in high-income countries, but only a small amount of progress has been made in improving survival in adulthood. Progressive end-organ damage, partly related to a systemic vasculopathy, is increasingly recognised. With the availability of a variety of novel disease-modifying drugs, gene addition and gene editing strategies, matched sibling donor haematopoietic stem cell transplantation (HSCT) in children (offering an overall survival rate of 95% and an event-free survival rate of 92%), and encouraging outcomes after alternative donor HSCT, the new challenge is to risk stratify patients, revise transplantation indications, and define the best therapeutic approach for each patient. The ultimate challenge will be to enable these advances in low-income and middle-income countries, where disease prevalence is highest and where innovative strategies are most needed.

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.

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 Goztepe 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.

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 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

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

El síndrome de Pearson (SP) comparte varias características con la anemia de Diamond-Blackfan (ADB), incluida la anemia grave de inicio temprano, por lo que es importante hacer un diagnóstico diferencial. El diagnóstico diferencial de la ADB y el SP es fundamental, ya que los pacientes con ADB podrían responder al tratamiento con corticoesteroides, presentar remisión o beneficiarse del trasplante de células madre hematopoyéticas(TCMH). Sin embargo, los pacientes con SP tienen un pronóstico diferente, con un riesgo muy elevado de acidosis, problemas metabólicos y disfunción pancreática, y una expectativa de vida menor en comparación con aquellos con ADB. En este artículo, presentamos el caso de un paciente sometido a TCMH para la ADB, pero que luego fue diagnosticado con SP tras desarrollar algunas complicaciones. 2-s2.0-85117616680 34569763

HLA-haploidentical transplantation (haplo-HCT) using post-transplantation-cyclophosphamide (PT-Cy) is a feasible procedure in children with malignancies. However, large studies on Haplo-HCT with PT-Cy for childhood acute lymphoblastic leukemia (ALL) are lacking. We analyzed haplo-HCT outcomes in 180 children with ALL. Median age was 9 years, and median follow-up was 2.7 years. Disease status was CR1 for 24%, CR2 for 45%, CR+3 for 12%, and active disease for 19%. All patients received PT-Cy day +3 and +4. Bone marrow (BM) was the stem cell source in 115 patients (64%). Cumulative incidence of 42-day engraftment was 88.9%. Cumulative incidence of day-100 acute graft-versus-host disease (GVHD) grade II-IV was 28%, and 2-year chronic GVHD was 21.9%. At 2 years, cumulative incidence of nonrelapse mortality (NRM) was 19.6%. Cumulative incidence was 41.9% for relapse and 25% for patients in CR1. Estimated 2-year leukemia free survival was 65%, 44%, and 18.8% for patients transplanted in CR1, CR2, CR3+ and 3% at 1 year for active disease. In multivariable analysis for patients in CR1 and CR2, disease status (CR2 [hazard ratio {HR} = 2.19; P = .04]), age at HCT older than 13 (HR = 2.07; P = .03) and use of peripheral blood stem cell (PBSC) (HR = 1.98; P = .04) were independent factors associated with decreased overall survival. Use of PBSC was also associated with higher NRM (HR = 3.13; P = .04). Haplo-HCT with PT-Cy is an option for children with ALL, namely those transplanted in CR1 and CR2. Age and disease status remain the most important factors for outcomes. BM cells as a graft source is associated with improved survival.

Eligibility criteria for hematopoietic stem cell transplantation (HSCT) in acute lymphoblastic leukemia (ALL) vary according to disease characteristics, response to treatment, and type of available donor. As the risk profile of the patient worsens, a wider degree of HLA mismatching is considered acceptable. A total of 138 children and adolescents who underwent HSCT from HLA-identical sibling donors (MSDs) and 210 who underwent HSCT from matched donors (MDs) (median age, 9 years; 68% male) in 10 countries were enrolled in the International-BFM ALL SCT 2007 prospective study to assess the impact of donor type in HSCT for pediatric ALLThe 4-year event-free survival (65 +/- 5% vs 61 +/- 4%; P = .287), overall survival (72 +/- 4% versus 68 +/- 4%; P=.235), cumulative incidence of relapse (24 +/- 4% versus 25 +/- 3%; P=.658) and nonrelapse mortality (10 +/- 3% versus 14 +/- 3%; P =.212) were not significantly different between MSD and MD graft recipients. The risk of extensive chronic (cGVHD) was lower in MD graft recipients than in MSD graft recipients (hazard ratio [HR], .38; P=.002), and the risks of severe acute GVHD (aGVHD) and cGVHD were higher in peripheral blood stem cell graft recipients than in bone marrow graft recipients (HR, 2.06; P=.026). Compared with the absence of aGVHD, grade I-Il aGVHD was associated with a lower risk of graft failure (HR,.63; P =.042) and grade III-IV aGVHD was associated with a higher risk of graft failure (HR, 1.85; P=.020) and nonleukemic death (HR, 8.76; P

WOS: 000426572200002, PubMed ID: 28404539, Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. Materials and Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with beta-thalassemia major (n = 1658, 83.4%) and intermedia (n = 215, 10.8%). Results: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all beta-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged, Ege Children's Foundation; Novartis Pharmaceuticals CorporationNovartis, The authors thank Caglar Serdar, Aylin Gokduman, and Tolga Turgay of Plexus Information Technologies for their website support. The current study and the work presented here are from an Investigator Initiated Trial, which was sponsored by the Ege Children's Foundation and funded by Novartis Pharmaceuticals Corporation.

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.

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 × 106/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 × 106/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 × 106 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.

Background Immunodysregulation polyendocrinopathy enteropathy x-linked(IPEX) syndromeis a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined. Objective This analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors. Methods Clinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed. Results We confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS. Conclusions Patients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen., GRAPHICAL ABSTRACT

Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.

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.

KILIC, SUAR CAKI/0000-0001-7489-2054; Hazar, Volkan/0000-0002-1407-2334 Uygun, Vedat ; Karasu, Gulsun Tezcan (isu author) 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. WOS:000509125100001 31981413 Q1

PubMedID: 30300449 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

WOS: 000478208700001, PubMed ID: 31321910, 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., Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Turkish Pediatric Hematology Association, This study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) and the Turkish Pediatric Hematology Association.

Although the calculated carrier frequency for point mutations of the β-globin gene is around 10% for Antalya Province, nothing is known about the profile of large deletional mutations involving the β-globin gene. In this study, we aimed to screen common deletional mutations in the β-globin gene cluster in patients for whom direct DNA sequencing was not able to demonstrate the mutation(s) responsible for the disease phenotype.Thirty-one index cases selected with a series of selection events among 60 cases without detected β-globin gene mutation from 580 thalassemia-related cases tested by direct sequencing over the last 4 years in our diagnostic center were screened for the most common 8 different large deletional mutations of the β-globin gene cluster by gap-PCR.We detected 1 homozygous and 9 heterozygous novel unrelated cases for the Turkish inversion/deletion (δβ)0 mutation in our series of 31 cases. Our study showed that the Turkish inversion/deletion (δβ)0 mutation per se accounts for 16.6% of the unidentified causative alleles and also accounts for 1.5% of all detected mutations over the last 4 years in our laboratory.Since molecular diagnosis of deletional mutations in the β-globin gene cluster warrants different approaches, it deserves special attention in order to provide prenatal diagnosis and prevention opportunities to the families involved. We conclude that the Turkish inversion/deletion (δβ)0, as the most prevalent deletional mutation detected so far, has to be routinely tested for in Antalya, and the gap-PCR approach has valuable diagnostic potential in the patients at risk.Amaç: Beta-globin genindeki nokta mutasyonlarının sıklığı Antalya bölgesi için yaklaşık %10 olarak belirlenmiş olmasına rağmen, beta-globin genini içine alan büyük delesyonel tip mutasyonların profili hakkında hiçbir şey bilinmemektedir. Bu çalışmada, DNA dizi analizi yöntemiyle beta-globin geninde hastalığın oluşmasından sorumlu mutasyon(lar) tespit edilememiş talasemili olgularda beta-globin gen kümesinde yaygın görülen büyük delesyonel mutasyonları taramayı amaçladık. Gereç ve Yöntemler: Son dört yıl boyunca tanı merkezimizde DNA dizi analizi yöntemiyle test edilmiş, talasemiyle ilişkilendirilen 580 olgu arasından öncelikle beta-globin geni mutasyonu belirlenememiş 60 olgu seçildi. Bu 60 olgu arasından bir seri seleksiyon işlemi uygulanarak nihai olarak belirlenmiş 31 hasta, beta-globin gen kümesinde en yaygın görülen sekiz farklı büyük delesyonel tip mutasyon için gap-PCR yöntemiyle tarandı. Bulgular: Otuz bir olgudan oluşan serimiz içerisinde, Türk tipi inversiyon/delesyon (δβ)0 mutasyonu açısından heterozigot olan dokuz yeni olgu ve homozigot olan bir yeni olgu belirlendi. Çalışmamız Türk tipi inversiyon/delesyon (δβ)0 mutasyonunun, laboratuvarımızda son dört yıl boyunca tespit edilmiş tüm mutasyonların %1,5’ini ve DNA dizi analizi yöntemiyle mutasyon tespit edilemeyen alellerin ise %16,6’sını oluşturduğunu gösterdi. Sonuç: Beta-globin gen kümesinde delesyonel tip mutasyonlar farklı moleküler yöntemlerle tespit edilebilir. Bu durum prenatal teşhis ve hastalığı önleme fırsatı sağlayabildiği için özel bir ilgi gerektirmektedir. Sonuç olarak, toplumumuzda şu ana kadar belirlenmiş en sık görülen delesyonel tip mutasyon olan Türk tipi inversiyon/delesyon (δβ)0 mutasyonu Antalya’da rutin olarak test edilmelidir ve gap-PCR yöntemi risk altındaki hastalar için önemli bir tanı potansiyeline sahiptir.

We conducted a prospective, phase II, multicenter, single-arm study to evaluate the efficacy and safety of deferasirox in patients age >2 to 1000 mu g/L; cardiac MRI T2* = 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 mu g/L at baseline to 845.3 mu g/L following 52 weeks of therapy (P

Extracorporeal photopheresis (ECP) is a difficult procedure to perform in the pediatric population. This is a retrospective review of 12 pediatric patients who underwent photopheresis with the Therakos Cellex system for graft-versus-host disease (GVHD). Acute GVHD (aGVHD) occurred in 6 patients, and overlap syndrome and chronic GVHD (cGVHD) occurred in 4 and 2 patients, respectively. The ECP regimen was the same for all aGVHD and cGVHD patients: initially, every week (2 sessions/wk) for 2 months; next, every 2 weeks for 2 months; and finally, every month for at least 1 year. Improvement was observed in 7 of 10 aGVHD patients (70%) and in 4 of 6 cGVHD patients (66%). Eleven patients had skin involvement before ECP; 9 of them responded to treatment (81%). Gastrointestinal involvement occurred in 8 patients; 5 of them experienced improvement during ECP treatment (62%). All 4 patients with liver involvement failed to respond. No serious adverse reactions occurred. In conclusion, our study demonstrates that ECP with the Therakos Cellex system is a safe treatment option for GVHD in children, allowing the tapering of immunosuppressants by at least half.

The congenital amegakaryocytic thrombocytopenia (CAMT) is a syndrome characterized by preservation of granulocytic and erythroid cells during genesis, with a gradual or progressive decrease in the number of megakaryocytic series of cells in the bone marrow. At later times, most patients develop aplastic anemia. It is important to rule out specific causes of thrombocytopenia that develop in the early stages of CAMT. Typically, there are no specific somatic abnormalities that accompany this deadly disease. Here we present three CAMT cases that presented with different clinical diagnoses, with various physical anomalies in two of those cases. The first patient was examined because of a cytomegalovirus infection. The second patient had been referred with a suspected neonatal alloimmune thrombocytopenia, whereas the third patient presented with chronic immune thrombocytopenic purpura. Subsequently, all three patients were diagnosed with CAMT. Two of the patients had physical anomalies. In particular, the first patient had a duplex urinary system. To our knowledge, this is the first patient with CAMT to have a duplicated collecting sysem. The second patient had a secundum atrial septal defect, an atypical facial appearance, and growth retardation. Since CAMT could also be observed outside the neonatal period, the differential diagnosis for thrombocytopenia should be considered for all age groups. Moreover, it should be considered that CAMT may also be accompanied with somatic abnormalities.

WOS: 000350548500005, PubMed ID: 25546368, BackgroundBAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance. ObjectivesTo demonstrate superiority of prophylaxis vs. on-demand therapy with BAY 81-8973 in patients with severe hemophilia A. Patients/MethodsIn this multinational, randomized, open-label crossover study (LEOPOLD II; ClinicalTrials.gov identifier: NCT01233258), males aged 12-65years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30IUkg(-1)), 3-times-weekly prophylaxis (30-40IUkg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs) andimmunogenicity were also assessed. ResultsEighty patients (on demand, n=21; twice-weekly prophylaxis, n=28; 3-times-weekly prophylaxis, n=31) were treated and analyzed. MeanSD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 +/- 7.2; 3-times-weekly, 4.3 +/- 6.5; combined, 4.9 +/- 6.8) vs. on-demand treatment (57.7 +/- 24.6; P, Bayer HealthCare AG, Leverkusen, GermanyBayer AGBayer Healthcare Pharmaceuticals; Bayer HealthCare PharmaceuticalsBayer AGBayer Healthcare Pharmaceuticals, This study was funded by Bayer HealthCare AG, Leverkusen, Germany. Medical writing assistance was provided by Erin P. Scott for Complete Healthcare Communications, Inc. (Chadds Ford, PA) and was fully funded by Bayer HealthCare Pharmaceuticals.

WOS: 000400127500011, PubMed ID: 28192253, Preimplantation genetic diagnosis involves the diagnosis of a genetic disorder in embryos obtained through in vitro fertilization, selection of healthy embryos, and transfer of the embryos to the mother's uterus. Preimplantation genetic diagnosis has been used not only to avoid the risk of having an affected child, but it also offers, using HLA matching, preselection of potential HLA-genoidentical healthy donor progeny for an affected sibling who requires bone marrow transplantation. Here, we share the hematopoietic stem cell transplantation results of 52 patients with different benign and malign hematological or metabolic diseases or immunodeficiencies whose donors were siblings born with this technique in Turkey since 2008. The median age of the patients' at the time of the transplantation was 8 years (range, 3 to 16 years) and the median age of the donors was 2 years (range,.5 to 6 years). The most common indication for HSCT was thalassemia major (42 of all patients, 80%). The stem cell source in all of the transplantations was bone marrow. In 37 of the transplantations, umbiliCal cord blood of the same donor was also used. In 50 of the 52 patients, full engraftment was achieved with a mean of 4.6 x 10(6) CD 34(+) cells per kg of recipient weight. Ninety-six percent of the patients have been cured through hematopoietic stem cell transplantation without any complication. Primary engraftment failure was seen in only 2 patients with thalassemia major. All of the donors and the patients are alive with good health status. Preimplantation genetic diagnosis with HLA matching offers a life-saving chance for patients who need transplantation but lack an HLA genoidentical donor. (C) 2017 American Society for Blood and Marrow Transplantation.

PubMedID: 25345697 Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* * with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ? 10 ms) or liver (LIC

Bone marrow transplantation is called hematopoetic stem cell transplantation (HSCT), since peripheral blood and umbilical cord blood can also be used as sources of stem cell currently. In children, bone marrow transplantation is used as a definite treatment method in many diseases including hemoglobinopaties, immune deficiencies, bone marrow failure and congenital metabolic diseases in addition to hematological malignancies. In addition to the underlying disease, the most important factors which have an impact on prognosis include infections which develop during the process of transplantation and graft-versus-host disease. In this article, it was aimed to give brief information on stem cell sources, preparation therapies, HSCT indications and post-transplantation complications in children.

Background A risk associated with the iron chelator deferiprone is the development of neutropenia or agranulocytosis. Accordingly, the product label recommends weekly blood monitoring and immediate interruption of treatment upon detection of an absolute neutrophil count (ANC)

SummaryUmbilical cord blood (UCB) from an human leucocyte antigen (HLA)-identical sibling can be used for transplantation of patients with malignantand non-malignant diseases. However, the low cellular content of mostUCB units represents a limitation to this approach. An option to increasecell dose is to harvest bone marrow (BM) cells from the same donor andinfuse them along with the UCB. We studied 156 children who receivedsuch a combined graft between 1992 and 2011. Median age was 7 yearsand 78% of patients (n = 122) were transplanted for non-malignant dis-eases, mainly haemoglobinopathies. Acute leukaemia (n = 26) was the mostfrequent malignant diagnosis. Most patients (91%) received myeloablativeconditioning. Median donor age was 1 7 years, median infused nucleatedcell dose was 24 4 9 10 7 /kg and median follow-up was 41 months. Sixty-days neutrophil recovery occurred in 96% of patients at a median of 17 d.The probabilities of grade-II-IV acute and chronic graft-versus-host disease(GVHD) were 19% and 10%, respectively. Four-year overall survival was90% (68% malignant; 97% non-malignant diseases) with 3% probability ofdeath. In conclusion, combined UCB and BM transplantation from anHLA-identical sibling donor is an effective treatment for children withmalignant and non-malignant disorders with high overall survival and lowincidence of GVHD.Keywords: haematopoietic stem cell transplantation, cord blood, bonemarrow.

Hemoglobin beta (HBB): c.*+96TC substitution is very rare among β-globin gene mutations and its clinical significance remains to be clarified. The present study aimed to investigate the role of HBB: c.*+96TC in the β-thalassemia intermedia phenotype in a Turkish family. The proband and parents were screened for β-globin gene mutations via direct sequencing. Hematological and physical examination results were recorded, and correlated according to genotype. The proband was compound heterozygous for Cod 8 (-AA) and HBB: c.*+96TC, whereas his mother and father were heterozygous for Cod 8 (-AA) and HBB: c.*+96TC, respectively. The father had almost normal hematological findings, whereas the mother had the typical β-thalassemia trait phenotype. The proband was diagnosed as mild β-thalassemia intermedia based on hepatosplenomegaly and hematological findings. To the best of our knowledge this is the first report of HBB: c.*+96TC mutation in a Turkish family. HBB: c.* 96TC substitution is a very rare, but clinically relevant β-globin gene mutation. Additionally, we think that if 1 spouse is a carrier for β-globin gene mutation the other should be screened for silent mutations, such as HBB: c.*+96TC mutation of the β-globin gene, even if she/he does not have any clinical or hematological signs of the β-thalassemia trait phenotype.Hemoglobin beta (HBB): c.*+96TC, β-globin geninde çok nadir görülen ve klinik önemi henüz tam olarak aydınlatılamamış bir değişimdir. Bu çalışmada; bir Türk ailede HBB: c.*+96TC değişiminin beta-talasemi intermedia fenotipi üzerine etkisini araştırmayı amaçladık. Beta-talasemi intermedia ön tanılı çocuk ile anne ve babasının β-globin gen mutasyonları DNA dizi analizi yöntemiyle tarandı. Aile bireylerinin hematolojik ve klinik bulguları elde edilerek, genotipleri ile birlikte değerlendirildi. Direkt DNA dizi analizi yöntemiyle mutasyon taranması sonucunda, olgunun Cod 8 (-AA) ve HBB: c.*+96TC mutasyonları açısından birleşik heterozigot olduğu belirlendi. Annenin Cod 8 (-AA) mutasyonu, babanın ise HBB: c.*+96TC mutasyonu yönünden taşıyıcı oldukları görüldü. Anne klasik beta-talasemi taşıyıcı bulgularına sahip iken, babanın klinik ve hematolojik açıdan normale yakın olduğu belirlendi. Diğer yandan olgu, hematoloji bulgularına ek olarak, hepato-splenomegalinin varlığı ile ılımlı tip beta-talasemi intermedia tanısı aldı. Bu çalışmada, HBB: c.*+96TC değişimi ilk kez bir Türk ailesinde bildirilmektedir. Cod 8 (-AA) ve HBB: c.*+96TC değişimleri açısından birlikte heterozigot olan olguda, sadece Cod 8 (-AA) mutasyonu ile açıklanamayacak klinik bulguların gözlenmesi nedeniyle, HBB: c.*+96TC’ nın taşıyıcılarda sessiz, ancak başka bir mutasyonla birlikte olduğunda hastalık şiddetini artıran, klinik açıdan önemli bir β-globin geni mutasyonu olduğu sonucuna varıldı. Ayrıca, çiftlerden birinin taşıyıcılığının genetik testlerle kesinleştiği durumlarda, diğerinin klinik ve hematolojik olarak taşıyıcı bulgularına sahip olmasa bile, HBB: c.*+96TC gibi hematolojik açıdan sessiz mutasyonlar için taranması gerektiğini önermekteyiz.

Hematopoietic cell transplantation is an established treatment option with curative potential for a variety of clinical conditions. The last decade especially witnessed a remarkable increase in HCT activity in Turkey. In 2014, 696 pediatric and 2631 adult (total 3327) HCT were performed in Turkey. Corresponding transplant rates per 10 million inhabitants for autologous-HCT and allogeneic-HCT were 226 and 202, respectively. Total HCT procedures in Turkey increased 177% in the last 5 years and 791% in the last 14 years. This report focuses mainly on HCT activity of Turkey in 2014 based on the national HCT registry and presents a general picture of national HCT activity. (c) 2016 Elsevier Ltd. All rights reserved.

Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients

Alpha-mannosidosis is a rare lysosomal storage disorder with an autosomal recessive inheritance. Deficient alpha-mannosidase activity leads to lysosomal accumulation of mannose-rich oligosaccharides. The disease characterized by mental retardation, skeletal changes, hearing impairment, and recurrent infections. Stem cell transplantation has been shown to be an effective treatment. It works by providing increased levels of α-mannosidase in the localized extracellular milieu to provide improvements in skeletal malformations, neurocognitive, and sensorineural function. In this case report, we describe a pair of siblings with α-mannosidosis who successfully underwent HSCT from matched unrelated donors. In both siblings, enzyme levels reached to normal limits and improvements in clinical symptoms were recognized early after HSCT. We conclude that HSCT should be considered as a therapeutic approach in patients with alpha-mannosidosis before disease-related complications have developed.

Objective: The aim of this study was to document hematopoietic stem cell transplantation (HSCT) activity and trends at our treatment center. Material and Methods: Data collected over a 10-year period were retrospectively analyzed, concentrating primarily on types of HSCT, transplant-related mortality (TRM), stem cell sources, indications for HSCT, and causes of death following HSCT. Results: In total, 222 allogeneic (allo)-HSCT (87.4%) and 32 autologous (auto)-HSCT (12.6%) procedures were performed between 1998 and 2008. Stem cells obtained from unrelated donors were used in 22.6% (50/222) of the allo- HSCTs. Cord blood was the source of hematopoietic stem cells (HSC) in 12.2% of all transplants. The most common indication for allo-HSCT was hemoglobinopathy (43.2%), versus neuroblastoma (53.1%) for auto-HSCT. The TRM rate 1 year post transplantation was 18.3% ± 2.5% for all transplants, but differed according to transplantation type (23.5% ± 7.9% for auto-HSCT and 17.5% ± 2.6% for allo-HSCT). The most common cause of death 1 year post HSCT was infection (35.9%). Conclusion: The TRM rate in the patients that underwent allo-HSCT was similar to that which has been previously reported; however, the TRM rate in the patients that underwent auto-HSCT was higher than previously reported in developed countries. The selection of these patients to be transplanted must be made attentively.

Objectives: An observational study was conducted to explore postmarketing safety and efficacy of Deferasirox (DFX) in comparison with conventional Desferrioxamine (DFO) in chelation-naive children with transfusional iron overload. Methods: Transfusion-dependent children (aged ≤5 yr) who had serum ferritin above 1000 μg/L and had been prescribed either first-line DFX or DFO for at least 12 months to maintain serum ferritin between 500 and 1000 μg/L were included. Initial DFX dose was 20 mg/kg/d for 7 d a week, and DFO dose was 25–35 mg/kg/d subcutaneously, given for 5 d a week. Dose adjustments were based on serum ferritin changes and safety markers. The primary efficacy endpoint was change in serum ferritin from baseline. The effect of transfusional iron loading rate (ILR) and different doses of chelators on serum ferritin was also assessed. Results: A total of 111 patients were observed for a median of 2.29 yr on DFX (n = 71) and 2.75 yr on DFO (n = 40). Absolute change in serum ferritin from baseline to the last available observation was not significant with DFX (91 μg/L, P = 0.5) but significantly higher with DFO (385 μg/L, P

Background: Children with β-thalassemia major (β-TM) have multiple risk factors for developing cognitive impairment. The aim of the present study was to evaluate cognitive function in patients with β-TM. Methods: Twenty children with β-TM were enrolled into the study and were compared with a control group consisting of 21 healthy children. All participants were evaluated with neuropsychological tests and event-related potentials (ERP). Results: All of the participants had normal IQ scores, but the patient group had significantly lower full-scale, performance, and verbal IQs compared with the control group (P

There is limited data about the long-term treatment outcome and prognosis of childhood acute lymphoblastic leukemia (ALL) in developing countries. Our study was designed to assess survival data and identify risk factors. Data of 142 children with ALL who were treated with a modified BFM 95 protocol between 1997 and 2007 were evaluated. The median age was 4.3 years. Complete remission (CR) rate after induction phase was 93.5%; with 2.1% induction-related mortality and 0.7% having resistance disease. Of complete responders, 67.1% are in continuous CR with a median follow-up of 63 months (range: 24 to 153 mo). Treatment-related mortality was 17.7% and the total rate of treatment abandonment was 3.5%. The probability of event-free survival was 67.3% (95% confidence interval 59.3-75.3) at 4 years and 63.2% (95% confidence interval 54.4-72.0) at 8 years. This report examines children with ALL treated with a modified ALL-BFM 95 protocol in a tertiary care center in Turkey with adequate follow up and demonstrates the need for improvements especially for patients with unfavorable risk group and strategies to reduce deaths from infection in CR to keep pace with cure rates in developed countries.

OBJECTIVE It was assessed whether cystatin C (cysC) could be used as a marker of glomerular filtration rate (GFR) by considering the technetium-99m diethylenetriamine penta-acetate (Tc-99m DTPA)-two blood sample method (GFRTc-99m DTPA) as the reference in pediatric patients under chemotherapeutic treatment. METHODS The chemotherapy group (CG) consisted of 31 patients (21 females, 10 males median age: 8.2 years; range: 2-16 years) who had been planned to receive allogenic hematopoietic stem cell transplantation. All patients in the CG received conditioning regimen (includes chemotherapy protocol) before hematopoietic stem cell transplantation. In addition, 21 patients (14 females, seven males median age: 9.5 years; range: 4-16 years) without any chemotherapy (nonchemotherapy group: nCG) were also prospectively investigated. Serum cysC, serum creatinine, GFRTc-99m DTPA, and GFR with a cysC-based formula (GFRcysC) were analyzed. Tubular function was also assessed. RESULTS Although we found good correlation between GFRTc-99m DTPA and cysC (r = -0.78), GFRTc-99m DTPA and GFRcysC (r = 0.91), cysC and creatinine (r = 0.91) in nCG, the same correlations were poor in CG (r = -0.42, r = 0.43, r = 0.46, respectively). Tubular function was impaired after chemotherapy. Bias+/-1.96 SD values were -6+/-15.7 and -3+/-54.8 ml/min/1.73 m in nCG and CG, respectively. Precision was also better in nCG (10 ml/min/1.73 m) than in CG (27.6 ml/min/1.73 m). CONCLUSION Serum cysC and GFRcysC cannot reflect GFR accurately in pediatric patients under chemotherapeutic treatment. Tubular cell damage induced by chemotherapeutics could be a responsible factor through the impairment of tubular absorption and metabolism of cysC.

SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 x 10(7)/kg and CD34(+) cell number was 3, 74 x 10(5)/kg in Case 1. Those cell numbers were 8, 8 x 10(7)/kg and 5, 34 x 10(5)/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.

Several investigators have been looking for less toxic conditioning regimen for stem cell transplantation in Fanconi anemia (FA) patients because of sensitivity to DNA cross-linking agents and tendency to malignancy. We report 16 multitransfused FA patients who underwent peripheral stem cell transplantation from 13 related and 3 unrelated donors. Although the first 6 patients received thoraco-abdominal irradiation + cyclophosphamide + antithymocyte globulin (regimen A) for conditioning, fludarabine (FLU) + cyclophosphamide + antithymocyte globulin (regimen B) were used in the last 10 patients in which 3 of them received unrelated graft. Cyclosporin A was given alone for the related allografts but also included mycophenolate mofetil for the unrelated allograft as graft versus host disease prophylaxis. We observed a lower risk of peritransplant morbidity and mortality with fewer and milder graft versus host disease in FLU based group. We lost 3 patients in regimen A group and 1 of them from secondary acute myeloid leukemia. Three patients are alive with transfusion independent. In regimen B group, 9 of 10 patients are alive with normal hematologic parameters and full donor chimerism. The longest follow-up durations are 90 and 60 months in regimen A and B, respectively. In conclusion, FLU based conditioning is more effective and successful with lower toxicity in multitransfused FA patients. However, it needs more experience and longer follow up duration.

Objectives This is a prospective, randomized, and open-label clinical trial that examines the efficiency and safety of PIP/TAZO monotherapy in comparison to cefepime (CEF), for the empirical treatment of pediatric cancer patients with neutropenia and fever. Methods One hundred thirty-one consecutive febrile episodes in 70 neutropenic pediatric cancer patients received randomized treatment either with piperacillin/tazobactam (PIP/TAZO) 80 mg/kg piperacillin/10 mg/kg tazobactam every 6 hr or CEF 50 mg/kg every 8 hr. Clinical response was determined at completion of therapy. Duration of fever, neutropenia, hospitalization, the need for modification of the therapy, and mortality rates were compared between the two groups. Results One hundred twenty-seven episodes in 69 patients (35 females, 34 males) with a median age of 4.2 years were assessed for efficiency (65 PIP/TAZO, 62 CEF). The frequency of success without modification of treatment was nearly identical for both PIP/TAZO (60.0%) and CEF (61.3%) (P > 0.05). The overall response rate, with or without modification of assigned treatment, was 96.9% for PIP/TAZO and 98.4% for CEP (P > 0.05). Infection-related mortality at the end of the febrile episode was 2.4%. Duration of fever and hospitalization were not different between the treatment groups. No major side effects were observed in neither of the groups. Conclusions PIP/TAZO treatment was as effective and safe as CEF monotherapy as an initial empirical regimen in pediatric cancer patients with fever and neutropenia. Pediatr Blood Cancer 2009;53:610–614. © 2009 Wiley-Liss, Inc.

Objectives The aim of this study was to assess glomerular and tubular renal function after HSCT in children in a prospective trial. Methods Renal function was assessed prospectively before HSCT (on day −10), on days +30, +100, and at least 6 months after transplantation in 34 patients (21 females/13 males) with a mean age of 8.2 years. The following parameters were investigated: glomerular filtration rate (GFR) by creatinine clearance (CrCl), cystatin C (CysC)-based formula and plasma clearance of radiolabeled diethylenetriaminepentaacetic acid (99mTc-DTPA), urinary excretion of β2-microglobulin (β2M), β-N-acetylglucosaminidase (β-NAG), fractional excretion of sodium (FENa) and fractional tubular phosphate reabsorption (TP/CrCl). Results Nine patients (26.4%) suffered from acute renal insufficiency within the first 100 days after transplantation. All patients who developed acute renal insufficiency were treated successfully without renal replacement therapy. Age, sex, primary diagnosis, sepsis, veno-occlusive disease, acute graft versus host disease, and use of vancomycin were not significant risk factors for the development of acute renal insufficiency. The medians 99mTc-DTPA-based GFR of patients after HSCT showed a statistically significant decrease when compared with pre-transplant values. β-NAG excretion was significantly elevated in the first 30 days after HSCT. Conclusion Acute and chronic renal impairment can be developed in patients who undergo HSCT even though the pre-transplant renal function is in normal limits and the conditioning regimen does not include TBI. Both glomerular and tubular renal function evaluation should be part of a long-term follow-up in children following HSCT. Pediatr Blood Cancer 2009;53:197–202. © 2009 Wiley-Liss, Inc.

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.