Duygu Uçkan Çetinkaya

The effect of poly(3-hydroxybutyrate-co-3- hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cell (hMSC) on axonal regeneration in experimental sciatic nerve damage

This study is designed to evaluate the treatment effect of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and human mesenchymal stem cells (hMSC) on axonal regeneration in experimental rat sciatic nerve damage, and compare the results of this modality with autologous nerve grafting. In Spraque–Dawley albino rats, 10-mm-long experimental nerve gaps were created. Three groups were constituted, the gap was repaired with autologous nerve graft (autograft group), PHBHHx nerve graft alone (PHBHHx alone group), and PHBHHx nerve graft with hMSCs inside (PHBHHx with hMSC group), respectively. The results were evaluated with functional recovery, electrophysiological evaluation, and histological evaluation either with light microscopy and transmission electron microscopy for axonal regeneration and myelin formation. In functional evaluation, autograft and PHBHHx with hMSC groups showed functional improvement with time, whereas PHBHHx alone group did not. Electrophysiological evaluation showed better results in autograft and PHBHHx with hMSC groups when compared to PHBHHx alone group. There was no statistical difference between autograft and PHBHHx with hMSC groups. Histological evaluation showed regenerated axons in each group. Autograft group was better than the others, and PHBHHx with hMSC group was better than PHBHHx alone group both for axonal regeneration and myelin formation. This study showed that the nerve grafts which were prepared from PHBHHx with oriented nanofiber three-dimensional surfaces aided to nerve regeneration, either used alone or with hMSC. PHBHHx provided better nerve regeneration when used with hMSCs inside than alone, and reached the same statistical treatment effect in functional evaluation and electrophysiological evaluation when compared to autografting.

Oxidative protein damage with carbonyl levels and nitrotyrosine expression after chemotherapy in bone marrow transplantation patients.

Protein oxidation is defined as the covalent modification of a protein, induced either directly by reactive oxygen species/reactive nitrogen species or indirectly by reaction with secondary by-products of oxidative stress. Protein carbonyls are the most commonly measured products of protein oxidation. Additionally, nitrotyrosine is a product of tyrosine nitration mediated by reactive nitrogen species such as peroxynitrite anion and nitrogen dioxide. Samples were collected before the preparative regimen (10 days before transplantation; day –10), on transplantation day (day 0), and after transplantation (days 7, 14, and 28) from 16 pediatric allogeneic hematopoietic stem cell transplantation (HSCT) patients. The erythrocyte 3-nitrotyrosine expression was shown to be significantly increased after chemotherapy. In accordance, the mean plasma carbonyl levels on days 14 and 28 were significantly higher than on the other days. High-dose chemotherapy applied in the preparative regimen of HSCT may be responsible for this long-term oxidation of plasma proteins. These results show that high-dose chemotherapy resulted in protein oxidation both in plasma and in erythrocytes in HSCT patients.

Successful hematopoietic stem cell transplantation in a patient with congenital dyserythropoietic anemia type II

CDA are a group of inherited, rare diseases that are characterized by dyserythropoiesis and ineffective erythropoiesis associated with transfusion dependency in approximately 10% of cases. For these latter patients, the only curative treatment is HSCT. There are very limited data on HSCT experience in this rare disease. Herein, we report a five‐yr six‐month‐old girl with compound heterozygous mutations in SEC23B gene, who was diagnosed to have CDA type II and underwent successful HSCT from her matched sibling donor.

Hematopoietic stem cell transplantation from a donor with Klinefelter syndrome for Wiskott–Aldrich syndrome

Abstract:  WAS is a rare X‐linked recessive disorder characterized by primary progressive T cell immunodeficiency, impaired antipolysaccharide antibody response, thrombocytopenia with small platelet, and eczematoid dermatitis. Untreated patients with typical WAS have poor prognosis with the major causes of death being infection, bleeding, lymphoproliferative disorders, and malignancy. Due to the increased risk of infectious and hemorrhagic episodes the best results with HSCT are achieved in patients less than five yr of age and are recommended as early as possible. Here, we report a three‐yr‐old boy with WAS who underwent UCB and BMT from his genotypically identical brother with Klinefelter syndrome.

Allogeneic hematopoietic stem cell transplantation in pediatric chronic myelogenous leukemia cases: Hacettepe experience

Abstract: Recently, there are emerging reports on the beneficial effect of imatinib mesylate for pediatric CML patients; however, the general recommendation is that high‐risk CML patients with a human leukocyte antigen‐identical donor should be transplanted within the first 12 months after diagnosis. Herein, the data of 16 allogeneic HSCT in 14 children with CML were analyzed retrospectively. In the present study, three‐yr EFS was 54.1 ± 10.8% and three‐yr OS was found as 80.7 ± 12.5%.

Investigation of the Effects of an Exercise Program on Physical Functions and Activities of Daily Life in Pediatric Hematopoietic Stem Cell Transplantation.

The aim of this study was to determine the effectiveness of an implemented exercise program for children throughout the hematopoietic stem cell transplantation (HSCT) process.

ADA Deficiency: Evaluation of the Clinical and Laboratory Features and the Outcome

IntroductionAdenosine deaminase (ADA) deficiency is an autosomal recessive primary immunodeficiency. It results in the intracellular accumulation of toxic metabolites which have effects particularly on lymphocytes and the brain. The aim of this study was to evaluate the outcome of 13 ADA-deficient patients. We planned to evaluate their clinical and laboratory findings before and after enzyme replacement therapy (ERT), allogeneic hematopoietic stem cell transplantation (aHSCT), and hematopoietic stem cell gene therapy (HSCGT).MethodsMeasurement of ADA enzyme activity and metabolites and sequencing of the ADA gene were performed in most of the patients with ADA deficiency. One of the patients with late-onset ADA deficiency was diagnosed by the help of primary immunodeficiency panel screening.ResultsTen out of 13 patients were diagnosed as SCID, while 3 out of 13 were diagnosed as delayed-/late-onset ADA deficiency. Late-onset ADA deficiency patients had clinical and laboratory findings of combined immunodeficiency (CID). Eight patients with ADA-SCID were found to have higher levels of ADA metabolite (dAXP%) (62.1% (34.6–71.9)) than 3 patients with delayed-/late-onset ADA deficiency (6.9% (2.1–8.9). All but one patient with SCID had T-B-NK− phenotype, one had T-B-NK+ phenotype. Genetic defect was documented in 11 patients. Four out of 11 patients had compound heterozygous defects. Three out of 4 patients with compound heterozygous defects had delayed-onset/late-onset ADA deficiency. Seven out of 11 patients with SCID had homozygous defects. Five out of 7 had the same homozygous indel frameshift mutation (c.955-959delGAAGA) showing a founder effect. There were two novel splice site defects: one (IVS10+2T>C) was heterozygous in a patient with late-onset ADA deficiency, and the other was homozygous (IVS2delT+2) in a SCID patient. Other defects were missense defects. Nine out of 13 patients were put on pegylated ADA ERT. Four out of six patients were transplanted without using a conditioning regimen. HSCGT was performed to one of the patients.ConclusionThe genetic diagnosis of SCID is utmost important. There is a chance to give ERT before the definitive therapy if the patient with SCID/CID has ADA deficiency. Although ERT was insufficient to restore a normal immune function in ADA-SCID patients, it was useful to improve and stabilize the clinical status before curative therapy (aHSCT/HSCGT). Enzyme replacement therapy was successful in patients with late-/delayed-onset ADA deficiency who presented with the features of combined immunodeficiency. Gastrointestinal polyposis in a patient with late-onset ADA deficiency may be an association or a coincidental finding. Intermittent neurodevelopmental evaluation especially for hearing impairment should be performed in most of the ADA-deficient patients. This may alleviate the speech delay and cognitive abnormalities which may be observed in the follow-up.

Successful Outcome With Fludarabine-Based Conditioning Regimen for Hematopoietic Stem Cell Transplantation From Related Donor in Fanconi Anemia: A Single Center Experience From Turkey.

Fanconi anemia (FA) is a heterogeneous autosomal recessive (and rarely X linked) disorder, which is characterized by congenital malformations, progressive bone marrow failure, and predisposition to malignancies. Hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for the hematological manifestations in FA.

Successful hematopoietic stem cell transplantation after myeloablative conditioning in three patients with dedicator of cytokinesis 8 deficiency (DOCK8) related Hyper IgE syndrome

Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal-recessive form of hyperimmunoglobulin E syndrome which is a primary immunodeficiency (PID), also classified in the group of combined immunodeficiencies [1]. DOCK8 is a protein within the family of Rho-GTPases which is expressed in lymphocytes, affects cell signaling and reorganization of the cytoskeleton [2]. Clinical features of this disease include recurrent upper and lower respiratory tract infections, elevated IgE levels, eosinophilia, severe atopic dermatitis, asthma, and food allergies. Patients with DOCK8 deficiency have increased incidence of viral cutaneous infection; herpes simplex virus, human papilloma virus, and molluscum contagiosum virus. A high risk of malignancy, which is typically hematologic or epithelial, are reported in 8–17% of patients with DOCK8 deficiency [3]. The only definitive treatment option is allogeneic hematopoietic stem cell transplantation (HSCT) and experience about HSCT in DOCK8 deficiency is limited [4, 5]. Here we report three cases with DOCK8 deficiency who underwent HSCT after myeloablative conditioning in our center. The patients presented characteristic manifestations of DOCK8 deficiency including eczema (all patients), recurrent sinopulmonary infection (all patients), food allergy (Case 1, 3). In case 1 IgE specific for food allergens were as follows; egg white: 33.4 Ku/L (class 4), milk: 37.6 Ku/L (class 4) and nuts: 22.8 Ku/L (class 4). In case 3 food mix test showed 24.4 Ku/L (class 4). Case 3 also had molluscum contagiosum. Additionally, case 2 had resistant giardiasis, sclerosing cholangitis and colitis and case 3 had sclerosing cholangitis. Cryptosporidium was not isolated in the patients with sclerosing cholangitis. Case 3 also had bronchiectasis before HSCT. All three cases were given monthly intravenous immunoglobulin therapy and trimethoprim-sulfomethaxozole prophylaxis. In addition to the clinical features compatible with DOCK8 deficiency, diagnosis was also confirmed with mutational analysis. The details of the mutations are given in the table as given in Table 2. The donors were human leukocyte antigen (HLA) identical siblings in all patients. Busulfan based myeloablative conditioning regimen was used (Table 1). Cyclosporine A and short-course methotrexate on days +1, +3, +6 were used as graft versus host disease prophylaxis in all patients (Table 1). Engraftment was achieved in all patients. The chimerism analysis showed 93% donor profile in case 1 (with full donor chimerism at follow up) and full donor chimerism (donor chimerism>%95) in other two cases at +1 month after HSCT. None of the patients developed acute or chronic GVHD. After HSCT case 2 developed hyperbilirubinemia [5.28 mg/dl (0.3–1.2 mg/dl))], high transaminase levels [ALT: 544 U/L (<39 U/L), AST: 337 (<51 U/L)], hypoalbuminemia [3.1 g/dL (3.5–5.2 g/dL)], painful hepatomegaly, edema, oliguria, and weight gain (>5% from baseline). Although a late finding, a decreased or reversed portal venous flow was not shown on Doppler ultrasound. With these clinical and laboratory findings case 2 was diagnosed with VOD (moderate) which improved with defibrotide therapy. Eczema resolved in all patients. Food allergy resolved clinically in both case 1 and case 3. In case 1 specific Ig E * Barış Kuşkonmaz bkuskonmaz@gmail.com

Hematopoietic stem cell transplantation in children with Griscelli syndrome: A single‐center experience

GS2 is a rare autosomal recessive disease characterized by hypopigmentation, variable immunodeficiency with HLH. HSCT is the only curative treatment for GS2. We analyzed the outcome of 10 children with GS2 who underwent HSCT at our center between October 1997 and September 2013. The median age of the patients at transplant was 13.5 months (range, 6‐58 months). All of the patients developed HLH before HSCT and received HLH 94 or HLH 2004 protocols. Donors were HLA‐identical relatives in 8 patients, HLA‐mismatched relatives in 2 patients. Engraftment was achieved in all except one patient. None of the patients developed acute GVHD. Chronic GVHD occurred in one and veno‐occlusive disease occurred in four patients. Eight of the patients are under remission without any neurologic sequelae—median time of disease‐free survival is 92.4 months. The present study shows successful transplant outcome without long‐term neurologic sequelae in patients with GS2 who underwent HSCT from HLA‐related donors.