Hematopoietic stem cell transplantation in patients with severe combined immunodeficiency: A single-center experience

Objective: The aim of this study was to determine the factors affecting outcomes in patients who underwent hematopoietic stem cell transplantation (HSCT) with the diagnosis of severe combined immunodeficiency (SCID). Furthermore, our aim is to share our singlecenter experience of HSCT among SCID patients. Materials and Methods: The data of patients who underwent HSCT with the diagnosis of SCID between January 2014 and January 2021 in the pediatric bone marrow transplant unit of Istanbul Medipol University were retrospectively analyzed. Demographic and clinical data, treatment regimens, donor source, type of transplantation, pre- and post-transplantation infections, and complications were evaluated. Results: Among fifteen patients who underwent HSCT, 5 (33%) were female. The mean age at diagnosis was 3 months (1-6 months), and at transplantation 6 months (3-10 months). The mean time from diagnosis to transplantation was 3 months (2-9 months). There was a history of consanguineous marriage in thirteen (87%) and sibling death in eight (53%) cases. As donors, six (40%) were siblings and five (33%) were unrelated, while four (27%) patients underwent haploid transplantation. Four (27%) patients died during the first 100 days of transplantation. The median follow-up period was 23 months (9-61 months). Overall survival probability was calculated as 73%. Conclusion: SCID should be considered as an emergency in pediatrics. Devastating complications, including severe organ damage, lifethreatening infections, and even death, could appear in case of diagnostic delay. HSCT is a currently available curative treatment option. Subjects with a confirmed diagnosis should be referred to the appropriate bone marrow transplant center and treated as soon as possible

Clinical, genetic, and outcome characteristics of pediatric patients with primary hemophagocytic lymphohistiocytosis

Objectİive: In this study, we sought to describe the clinical, laboratory, and genetic characteristics of patients diagnosed with primary hemophagocytic lymphohistiocytosis. Thus, we aimed to evaluate the early diagnosis and appropriate treatment options for pediatric hemophagocytic lymphohistiocytosis patients. Materials and Methods: Medical records of 9 patients diagnosed with primary hemophagocytic lymphohistiocytosis between November 2013 and December 2019 were analyzed retrospectively. Clinical, genetic, and laboratory characteristics, family histories, initial complaints, physical examination findings, age at diagnosis, treatment choices, and clinical follow-up of all patients were investigated. Results: The mean age at diagnosis was 11 months (range: 1.5 months to 17 years). Genetic analysis was performed in all patients, and a disease-related mutation was detected in 8 (89%) of them. Among clinical features, 6 (66%) patients had fever, 5 (56%) had splenomegaly, 4 (44%) had lymphadenopathy, 4 (44%) had skin rash, and 4 (44%) had neurological findings. Hemophagocytosis was observed in the bone marrow samples of 6 (66%) patients. Disease remission was achieved in 7 (78%) patients. Hematopoietic stem cell transplantation was performed in 7 (78%) patients. Conclusion: Hemophagocytic lymphohistiocytosis may present with different clinical symptoms that can cause a significant diagnostic delay. The only curative treatment option in primary hemophagocytic lymphohistiocytosis patients is hematopoietic stem cell transplantation. The chemotherapy should be started as early as possible, in order to achieve a disease remission. Patients should be referred to the appropriate bone marrow transplant center for hematopoietic stem cell transplantation as soon as they reach the disease remission

Hematopoietic stem cell transplantation and high dose chemotherapy in recurrent and/or chemotherapy resistant hodgkin lymphoma cases: A single center experience

Giriş: Standart tedavi alan Hodgkin Lymphoma (HL) hastalarının yaklaşık %20’sinde hastalık dirençli seyredebilir veya tekrar edebilir. Tekrar eden/ dirençli HL’da standart tedavi yüksek doz kemoterapi ve takip eden otolog kök hücre naklidir (OKHN). Otolog KHN sonrası tekrar eden hastalarda ise allojeneik kök hücre nakli (AKHN) önemli bir kurtarma tedavisi olarak görülmektedir. Amaç: Medipol Üniversitesi Tıp Fakültesi çocuk kemik iliği nakil ünitesinde OKHN ve AKHN yapılan hastalarda sonuçları değerlendirmek. Yöntem: Tekrar eden/dirençli HL nedeniyle 2014 Kasım ile Temmuz 2019 tarihleri arasında merkezimizde OKHN yapılan 18 olgu retrospektif olarak değerlendirilmiştir. Otolog KHN sonrası hastalığı tekrar eden ve AKHN yapılan hastalarda ayrıca değerlendirilmiştir. Bulgular: Onaltı hasta halen hayattadır. Onbir hastada OKHN sonrası has talık tekrar etmiştir. Relaps eden hastalardan 10’una AKHN yapılmıştır. Bu hastalardan üçünde tekrar görülmüş olup, sekizi nakil sonrası hayattadır lar.Background: Nearly 20% of patients with Hodgkin Lymphoma (HL) who receive standard treatment will relapse or have a refractory disease. Standard treatment for the Relapsed/Refractory (RR) HL is salvage high dose chemotherapy followed by autologous stem cell transplantation (AuSCT). Management of RR HL after AuSCT with allogeneic stem cell transplantation (ASCT) is also considered as an important salvage therapy. Objective: To describe the outcome in pediatric patients with RR HL who underwent AuHSCT and ASCT in Medipol University hematopoietic stem cell transplantation center. Method: We retrospectively evaluated 18 pediatric patients with RR HL who underwent AHSCT between November 2014 and July 2019. The evaluation of ASCT after RR HL AuSCT is also done. Results: Sixteen patients are still alive. Eleven of them relapsed after AuHSCT. AllogeneicHSCT was performed on 10 patients who relapsed. Relapse was seen in three patients after AHSCT. Eight of them are still alive

A fast Monte Carlo algorithm for studying bottle-brush polymers

Obtaining reliable estimates of the statistical properties of complex macromolecules by computer simulation is a task that requires high computational effort as well as the development of highly efficient simulation algorithms. We present here an algorithm combining local moves, the pivot algorithm, and an adjustable simulation lattice box for simulating dilute systems of bottle-brush polymers with a flexible backbone and flexible side chains under good solvent conditions. Applying this algorithm to the bond fluctuation model, very precise estimates of the mean square end-to-end distances and gyration radii of the backbone and side chains are obtained, and the conformational properties of such a complex macromolecule are studied. Varying the backbone length (from $N_b=67$ to $N_b=1027$), side chain length (from N=0 to N=24 or 48), the scaling predictions for the backbone behavior as well as the side chain behavior are checked. We are also able to give a direct comparison of the structure factor between experimental data and the simulation results.Comment: 9 pages, 10 figure

Diagnosis and management of pseudohypoparathyroidism and related disorders : first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders.Peer reviewe

Recommendations for Diagnosis and Treatment of Pseudohypoparathyroidism and Related Disorders : An Updated Practical Tool for Physicians and Patients

Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.Peer reviewe

Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement

This Consensus Statement covers recommendations for the diagnosis and management of patients with pseudohypoparathyroidism (PHP) and related disorders, which comprise metabolic disorders characterized by physical findings that variably include short bones, short stature, a stocky build, early-onset obesity and ectopic ossifications, as well as endocrine defects that often include resistance to parathyroid hormone (PTH) and TSH. The presentation and severity of PHP and its related disorders vary between affected individuals with considerable clinical and molecular overlap between the different types. A specific diagnosis is often delayed owing to lack of recognition of the syndrome and associated features. The participants in this Consensus Statement agreed that the diagnosis of PHP should be based on major criteria, including resistance to PTH, ectopic ossifications, brachydactyly and early-onset obesity. The clinical and laboratory diagnosis should be confirmed by a molecular genetic analysis. Patients should be screened at diagnosis and during follow-up for specific features, such as PTH resistance, TSH resistance, growth hormone deficiency, hypogonadism, skeletal deformities, oral health, weight gain, glucose intolerance or type 2 diabetes mellitus, and hypertension, as well as subcutaneous and/or deeper ectopic ossifications and neurocognitive impairment. Overall, a coordinated and multidisciplinary approach from infancy through adulthood, including a transition programme, should help us to improve the care of patients affected by these disorders

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Çocukluk çağı malignitelerinde 18Flor-florodeoksiglukoz PET/BT görüntüleme

Objectives: The aim of the study was to evaluate the utility of (18)fluorine-fluorodeoxyglucose (F-18-FDG) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, restaging, and treatment response of childhood malignancies.Methods: This study included 52 patients (32 boys, 20 girls) who were referred to our clinic between November 2008 and December 2018 with the diagnosis of malignancy. The patients were evaluated retrospectively. Median age of the patients was 13 years (range 2-17). F-18-FDG was given to the patients intravenously, and time of flight with PET/16 slice CT was performed 1 hour thereafter. The lowest dose was 2 mCi (74 MBq) and the highest dose was 10 mCi (370 MBq). Fasting blood sugars of all patients were found below 200 mg/dL (11.1 mmol/L).Results: F-18-FDG PET/CT was performed to evaluate the response to treatment in 38 of 52 children, staging in 11 patients (staging and evaluation of the response to treatment in nine of them), restaging in 2 patients, restaging, and evaluation of the response to treatment in 1 patient. F-18-FDG PET/CT examination was reported as normal in 13 patients (5 girls, 8 boys). The pathological F-18-FDG uptake was detected in 39 patients (14 girls, 25 boys), which indicated metastasis and/or recurrence of the primary disease. Total number of deaths was 30 (13 girls, 17 boys).Conclusion: F-18-FDG PET/CT has a significant role for staging, restaging, treatment response, and detection of metastatic disease but it is limited for the early diagnosis of childhood cancers.Amaç: Çalışmamızın amacı, çocukluk çağı malignitelerinin tanı, evreleme, yeniden evreleme ve tedaviye cevabın değerlendirilmesinde 18florflorodeoksiglukoz (18F-FDG) pozitron emisyon tomografisi/bilgisayarlı tomografinin (PET/BT) yararını göstermektir. Yöntem: Kasım 2008 ve Aralık 2018 tarihleri arasında, malignensi tanılı 52 hastanın (32 erkek, 20 kız) dosyaları ve görüntüleri geriye dönük olarak incelendi. Ortalama yaş 13 (2-17) idi. 18F-FDG’nin intravenöz enjeksiyonundan 1 saat sonra, time of flight/16 kesit BT yapıldı. Çalışmamızda en düşük doz 2 mCi (74 MBq), en yüksek doz 10 mCi (370 MBq). Tüm hastaların açlık kan şekerleri 200 mg/dL’nin (11,1 mmol/L) altındaydı. Bulgular: 18F-FDG PET/BT, 52 hastanın 38’ine tedaviye yanıt değerlendirilmesi, 11 hastaya evreleme (9 hasta evreleme ve aynı zamanda tedaviye yanıt değerlendirilmesi), 2 hastaya yeniden evreleme, 1 hastaya yeniden evreleme ve tedaviye yanıt değerlendirilmesi amacıyla yapıldı. 18F-FDG PET/ BT çalışması 13 hastada (5 kız, 8 erkek) normaldi. Otuz dokuz hastada (14 kız, 25 erkek) çalışma, metastaz ve/veya primer hastalığın nüksü ile uyumlu bulundu. Toplam ölüm sayısı 30 (13 kız, 17 erkek) idi. Sonuç: 18F-FDG PET/BT çocukluk çağı malignensilerinin tanı, evreleme, yeniden evreleme ve tedaviye yanıt değerlendirilmesi açısından çok faydalıdır ancak erken tanıda yararı sınırlıdır

Evaluation of the demographic and clinical findings of pediatric patients that developed acute graft-versus-host disease after allogeneic hematopoietic stem cell

Aim: Acute graft-versus-host disease (GVHD) is an complication after allogeneic hematopoietic stem cell transplantation (alloHSCT), manifesting with an erythematous maculopapular rash followed by liver disease and dysfunctions of the gastrointestinal tract. This study aimed to retrospectively investigate the demographic and clinical characteristics of pediatric patients diagnosed with acute GVHD after undergoing allo-HSCT due to various hematological diseases. Material and Methods: The study included 33 pediatric patients that underwent their first allogeneic bone marrow transplantation in the Pediatric Bone Marrow Transplant Unit between 2015 and 2018 and were consecutively diagnosed with acute GVHD in consultation with the department of dermatology. The demographic characteristics, clinical findings, donor characteristics, treatments, and survival status of each patient were recorded. Results: Between 2015 and 2018, bone marrow transplantation was performed in 150 pediatric patients, of whom 33 (22%) developed acute GVHD. Of the 33 pediatric patients, 19 (57.6%) were boys and 14 (42.4%) were girls. At the time of transplantation, the mean age of the patients was 8.5 years, and the median age was 7 years. Twenty patients (60.6%) had only skin GVHD while 13 (39.4%) had skin and gastrointestinal and/or hepatic GVHD. It was found that the rashes had appeared on average 27.4 days after allo-HSCT. Palmoplantar involvement was detected in 13 patients (39.4%), painful erosion in the oral mucosa in 11 (33%), and conjunctivitis in seven (21.2%). The factors of being a male patient, being a female donor, transplantation from unrelated donors, liver involvement, and palmoplantar involvement were found to create risk of mortality, but not significantly (respectively p=0,753;p=0,145,0,66). Five patients (15%) progressed from acute to chronic GVHD. In patients that progressed from acute to chronic had, the mean donor age was higher, the mean time from transplantation to rash was longer, and oral involvement was higher, but not significantly (respectively; p=0,596;p=0,980;p=0,193. Conclusion: In acute GVHD, the skin is the first and most involved organ; therefore, dermatologists play an important role in its diagnosis. This study is important for determining the factors affecting the decrease in progression to chronic GVHD and prolonging survival