Gulyuz Ozturk

Successful haematopoietic stem cell transplantation in 44 children from healthy siblings conceived after preimplantation HLA matching

Haematopoietic stem cell transplantation (HSCT) remains the best therapeutic option for many acquired and inherited paediatric haematological disorders. Unfortunately, the probability of finding an HLA matched donor is limited. An alternative technique is PGD combined with HLA matching, which offers the possibility of selecting unaffected embryos that are HLA compatible with the sick child, with the aim of possible use of stem cells from the resulting baby in future. Since the first successful report for Fanconi anaemia a decade ago, the therapeutic success of this technique was reported in a few cases and for a limited number of disorders. Here, we report full recovery of 44 sick children who received HSCT from healthy infants conceived after pre-implantation HLA matching for the following 10 indications; beta-thalassaemia, Wiskott-Aldrich syndrome, Fanconi anaemia, sickle cell anaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, Glanzmanns thrombasthaenia, Diamond-Blackfan anaemia, X-linked adrenoleukodystrophy and mucopolysaccharidosis type I. No serious complications were observed among recipients and donors. Graft failure occurred in four children with beta-thalassaemia where a second HSCT was planned. Preimplantation HLA matching is a reliable technique and provides a realistic option for couples seeking treatment for an affected child when no HLA-matched donor is available.

Respiratory syncytial virus infection outbreak among pediatric patients with oncologic diseases and/or BMT

Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy with or without autologous/allogeneic hematopoetic stem cell transplantation (HSCT). There have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients.

Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken.

Effect and safety of granulocyte transfusions in pediatric patients with febrile neutropenia or defective granulocyte functions.

Background Despite the introduction of new broad-spectrum antibiotics and antifungal therapies over the past decade, infections remains the most frequent cause of death in patients with neutropenia. The aim of this study is to assess the effect and safety of granulocyte transfusions (GTX) for the treatment of severe life-threatening infections in pediatric patients with febrile neutropenia or defective granulocyte functions. Methods In this study, 35 pediatric patients with high-risk febrile neutropenia or defective granulocyte functions, who received 111 GTX, were included. GTX were used for 3 consecutive days during infections not responding to antimicrobial therapy. Results The mean granulocyte content per concentrate was 27.4×109 (min: 4.2×109 to max: 68.4×109) depending on donors white blood cell count before harvest. GTX were well tolerated in all patients. The infection-related survival rate was 82.4% and overall survival rate was 77.1% at day 30. The overall survival rate was 65.7% and 52% at 3 and 48 months, respectively. Conclusions GTX is safe and effective in controlling the life-threatening infections. Further randomized controlled studies with long-term follow-up are needed to assess the exact role of GTX in the outcome of patients with neutropenia and patients with defective granulocyte functions.

Trends in hepatitis B and hepatitis C virus seropositivity among blood donors over 15 years screened in the blood bank of a university hospital

Blood transfusion carries well defined risks including hepatitis B and hepatitis C virus transmission. In this study, records of blood donation candidates between the years 1996-2010 were retrospectively reviewed. A total of 220 841 apparently healthy adult donors were screened for hepatitis B surface antigen, anti-HCV with enzyme linked immunosorbent assay (ELISA) method. The overall prevalence of HbsAg and HCV were 1.07% and 0.39%, respectively. HBV seroprevelance decreased through years 1996-2010 but HCV seroprevelance showed a fluctuant course decreasing from 1996 to 2002. In order to decrease transfusion transmitted infections there should be centralized blood collection systems having qualified staff, equipment and non-remunerated voluntary blood donations must be strongly encouraged.

Human herpes virus type 8-associated Kaposi sarcoma in a pediatric liver transplant recipient

Çeltik C, Ünüvar A, Aydoğan A, Gökçe S, Öztürk G, Güllüoğlu M, Yılmaz G, Türkoğlu S, Anak S, Sökücü S, Durmaz Ö. Human herpes virus type 8‐associated Kaposi sarcoma in a pediatric liver transplant recipient.
Pediatr Transplantation 2011: 15: E100–E104.

Mesenchymal Stem Cell Treatment for Steroid Refractory Graft-versus-Host Disease in Children: A Pilot and First Study from Turkey.

This study evaluated the efficacy of mesenchymal stem cells (MSCs) from bone marrow of a third-party donor for refractory aGVHD. We report the first experience using MSCs to treat refractory aGVHD in 33 pediatric patients undergoing allogeneic HSCT from Turkey. Totally, 68 doses of bone marrow derived MSCs were infused. The median dose of MSC was 1.18 × 106 cells per kg body weight. Overall, complete response (CR) was documented in 18 patients, partial response (PR) was documented in 7 patients, and no response (NR) was documented in 8 patients. The 2-year estimated probability of overall survival (OS) for patients achieving CR and PR/NR was 63.8% and 29.4%, respectively (p = 0.0002). While the cumulative incidence of transplant related mortality (TRM) at day 100 after first MSC infusion was 46.6% in PR/NR patients, there was no any TRM at day 100 after first MSC infusion in CR patients (p = 0.001). Twelve patients developed chronic GVHD (cGVHD); eight of them were alive, with five having extensive disease and three having limited disease. In conclusion, MSCs appear to be safe and effective treatment option for pediatric patients with steroid refractory aGVHD. But the efficacy of MSCs on cGVHD in aGVHD patients treated with MSCs seems to be limited.

Infantile Hemangiomas: Complications and follow-up

ObjectiveTo study the risk factors for hemangioma-related complications, treatment indications and analyze the outcome of patients with infantile hemangioma.DesignRetrospective.SettingUniversity hospital.PatientsFifty-five patients (1–69 months; median: 12 months) with infantile hemangioma with mean follow-up 19 months. The eligibility was based on the criteria of the International Society for the Study of Vascular Anomalies (ISSVA).InterventionThe surgical treatment included total excision whereas medical treatment was carried out by interferon and /or corticosteroids.Main outcome measuresData was collected including sex, age, prematurity, age at onset, number, anatomic location and size of hemangioma, age at treatment, cause of treatment decision, family history, presence of extra malformations, involvement of internal organs, presence of life altering or life threatening complications, response to treatment, dose and duration of medications, complications associated with treatment, follow-up period, and final outcome.ResultsThirty-four (62%) patients were followed-up without treatment, whereas 21 others underwent treatment including steroids, interferon, and surgery. The size of hemangioma was a major factor that predicted hemangioma-related complications (P=0.002). Patients with hemangioma related complications had bigger lesions (size ≥40cm2 or the longest size on a single plane ≥5 cm). Nineteen patients (34%) had complications, but only 8 (14.5%) out of them had life or function-threatening complications.ConclusionAlthough dosing and treatment protocol is still debatable, steroids and interferon are good options for hemangioma treatment. The management strategy should be individualized for each case.

Effects of rhG-CSF Plus Dexamethasone on Hemostatic Parameters in Healthy Granulocyte Donors: Role of u-PA and Nitric Oxide

Granulocyte colony-stimulating factor (G-CSF) is widely used to reduce the risk of infection resulting from neutropenias and to mobilize and collect CD34+ hematopoetic progenitor cells (HPCs) for autologous and allogenic transplantation. The safety of recombinant human G-CSF (rhG-CSF) administration in healthy donors has been investigated in several studies. However, there are limited cumulative data about the effects of rhG-CSF on hemostasis. Hemostatic parameters, including urokinase-type plasminogen activator antigen (u-PA:Ag) and nitric oxide in 17 healthy granulocyte apheresis donors who donated for neutropenic patients were evaluated. rhG-CSF (single dose, 10 μg/kg subcutaneously) and dexamethasone (8 mg, single dose oral) were given to donors 12 hours before granulocyte apheresis. Two blood samples were drawn at time 0 (T0) before rhG-CSF and dexamethasone administration and at time 1 (T1), immediately before the apheresis. A statistically significant rise in coagulant factor VIII (FVIII) and von Willebrand factor (vWF), and slightly rise in u-PA:Ag were observed after G-CSF plus dexamethasone administration. In addition, there were positive correlations between vWF-D-dimer and FVIII-D-dimer. A significant decrease in mean total nitric oxide (NOx), nitrite, and nitrate levels was also found after G-CSF plus dexamethasone administration. Moreover, there was a strong negative correlation between nitrite and D-dimer levels (r = −0.611; P = .009). Even if partially compensated with u-PA and protein C, increased FVIII and vWF activity, and decreased nitric oxide levels may still partially contribute to progress of thrombosis risk in rhG-CSF plus dexamethasone administered healthy granulocyte donors. Large numbers of healthy donors exposed to G-CSF plus dexamethasone will be needed to evaluate the risk of thrombosis in this population.

Reduction of hepatitis B seroprevalence in blood banking units by combined utilization of self-exclusion forms and clinical evaluation of blood donation candidates in Turkey

SUMMARY In this retrospectively designed study, we evaluate the influence of the permanence and qualifications of health-care professionals on blood disposal rates due to hepatitis seropositivity. We observed a decrease of 44.2% in the number of blood units being rejected due to the donors hepatitis B seropositivity in the second study period in which self-exclusion forms and where blood donation candidates were evaluated by a family physician. However, a similar decrease of the disposal rate due to hepatitis C seropositivity was not observed. This is especially important in countries which cannot afford many of the expensive modern laboratory tests. A comprehensive evaluation of self-exclusion forms and a brief examination prior to donation will greatly increase transfusion safety. Unfortunately, there are blood banks in Turkey which employ no physicians at all.