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Although modern clinical management strategies have improved the outcome of paediatric patients with severe autoimmune and inflammatory diseases over recent decades, a proportion will experience ongoing or recurrent/relapsing disease activity despite multiple therapies often leading to irreversible organ damage, and compromised quality of life, growth/development and long-term survival. Autologous and allogeneic haematopoietic stem cell transplantation (HSCT) have been used successfully to induce disease control and often apparent cure of severe treatment-refractory autoimmune diseases (ADs) in children. However, transplant-related outcomes are disease-dependent and long-term outcome data are limited in respect to efficacy and safety. Moreover, balancing risks of HSCT against AD prognosis with continually evolving non-transplant options is challenging. This review appraises published literature on HSCT strategies and outcomes in individual paediatric ADs. We also provide a summary of the European Society for Blood and Marrow Transplantation (EBMT) Registry, where 343 HSCT procedures (176 autologous and 167 allogeneic) have been reported in 326 children (

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 36461145

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.

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

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 mu g/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 mu g/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 mu g/L), SCA (1655.5 to 1260 mu g/L), and across age groups of 2-6 years (1971.5 to 1499 mu g/L), 7-12 years (1688.5 to 1159.8 mu g/L), and 13-18 years (1496.5 to 1107 mu g/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses >= 30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. Conclusions Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (>= 30 mg/kg/d) may be required to achieve iron balance. C1 [Antmen, Bulent] Acibadem Hosp, Adana, Turkey. [Karakas, Zeynep] Istanbul Univ, Med Fac, Istanbul, Turkey. [Yesilipek, Mehmet Akif; Kupesiz, Osman Alphan] Akdeniz Univ, Med Fac, Antalya, Turkey. [Sasmaz, Ilgen] Cukurova Univ, Med Fac, Adana, Turkey. [Uygun, Vedat; Kurtoglu, Erdal] Antalya Training & Res Hosp, Antalya, Turkey. [Oktay, Gonul] Antakya State Hosp, Antakya, Turkey. [Aydogan, Gonul; Salcioglu, Zafer] Kanuni Sultan Suleyman Training & Res Hosp, Istanbul, Turkey. [Akin, Mehmet] Denizli State Hosp, Denizli, Turkey. [Vergin, Canan] Dr Behcet Uz Child Dis Surg Training & Res Hosp, Izmir, Turkey. [Kazanci, Elif Guler] Dortcelik Child Dis Hosp, Bursa, Turkey. [Unal, Selma] Mersin Univ, Med Fac, Mersin, Turkey. [Caliskan, Umran] Necmettin Erbakan Univ, Meram Med Fac, Konya, Turkey. [Aral, Yusuf Ziya] Adnan Menderes Univ, Med Fac, Aydin, Turkey. [Turkkan, Emine] Okmeydani Training & Res Hosp, Istanbul, Turkey. [Gunes, Adalet Meral] Uludag Univ, Med Fac, Bursa, Turkey. [Tunc, Bahattin] Hematol Oncol Training & Res Hosp, Ankara Child Hlth & Dis, Ankara, Turkey. [Gumruk, Fatma] Hacettepe Univ, Med Fac, Ankara, Turkey. [Ayhan, Aylin Canbolat; Timur, Cetin] Goztepe Training & Res Hosp, Istanbul, Turkey. [Soker, Murat] Dicle Univ, Med Fac, Diyarbakir, Turkey. [Koc, Ahmet; Oymak, Yesim] Harran Univ, Med Fac, Sanliurfa, Turkey. [Ertem, Mehmet] Ankara Univ, Fac Med, Ankara, Turkey. [Yildirmak, Yildiz] Sisli Etfal Training & Res Hosp, Istanbul, Turkey. [Irken, Gulersu] Dokuz Eylul Univ, Med Fac, Izmir, Turkey. [Apak, Hilmi] Istanbul Univ, Cerrahpasa Med Fac, Istanbul, Turkey. [Biner, Betul; Eren, Tugba Gurleyen] Trakya Univ, Med Fac, Edirne, Turkey. [Balci, Yasemin Isik] Pamukkale Univ, Med Fac, Denizli, Turkey. [Kocak, Ulker] Gazi Univ, Med Fac, Ankara, Turkey. [Karasu, Gulsun] Istanbul Zeynep Kamil Women & Childrens Dis Raini, Istanbul, Turkey. [Akkaynak, Diyar] Novartis Saglik Gida & Tarim Urunleri San & Tic A, Istanbul, Turkey. [Patiroglu, Turkan] Erciyes Univ, Med Fac, Kayseri, Turkey.

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

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)

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.

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

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.

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.

The aim of this study was to contribute to clarify the mechanism of cellular immune insufficiency occurring during iron deficiency. We studied the expression of the transferrin receptor (TfR) which is called as CD71, on the surface of T lymphocytes in infants with iron deficiency (with and without anemia). A total of 33 infants, aged between 7 and 26 months were included in this study. These subjects were divided into three groups: (i) latent iron deficiency (LID) (group 1), (ii) iron deficiency anemia (IDA) (group 2), and (iii) healthy infants (group 3). Both CD3 levels and CD71 expression of T lymphocytes were analysed by flow cytometry before and after phytohaemagglutinin (PHA) stimulation. The percentage of CD3(+) lymphocytes in infants with IDA was lower than that in controls after PHA stimulation (mean +/- SD, 48.6 +/-10.5% vs. 70.7 +/-7.8%, P < 0.001). The TfR expression of T lymphocytes (CD3 + CD71%) increased in all three groups after PHA stimulation (P < 0.001). No significant difference was seen among the three groups with respect to CD3 + CD71%. Although there was a reduction in the proliferative capacity of T lymphocytes in infants with IDA, their ability to express transferrin receptor on T-lymphocyte cell surface was normal.