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Introduction In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients. Materials and methods Forty-three PRA-positive and 42 PRA-negative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters. Results There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively. Conclusions Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.

Purpose Patients with heterozygous gain-of-function (GOF) mutations in STAT1 frequently exhibit chronic mucocutaneous candidiasis (CMC), immunodeficiency and autoimmune manifestations. Several treatment options including targeted therapies and hematopoietic stem cell transplantation (HSCT) are available for STAT1 GOF patients but modalities and outcomes are not well established. Herein, we aimed to unravel the effect of ruxolitinib as a bridge therapy in a patient with sporadic STAT1 T385M mutation to manage infections and other disease manifestations. Methods Peripheral blood mononuclear cells were isolated from the patient prior to, during ruxolitinib treatment and 6 months after HSCT. IFN-beta-induced STAT1 phosphorylation/dephosphorylation levels and PMA/ionomycin-stimulated intracellular IL-17A/IFN-gamma production in CD4(+) T cells were evaluated. Differentially expressed genes between healthy controls and the patient prior to, during ruxolitinib treatment and post-transplantation were investigated using Nanostring nCounter Profiling Panel. Results Ruxolitinib provided favorable responses by controlling candidiasis and autoimmune hemolytic anemia in the patient. Dysregulation in STAT1 phosphorylation kinetics improved with ruxolitinib treatment and was completely normalized after transplantation. T(H)17 deficiency persisted after ruxolitinib treatment, but normalized following HSCT. Consistent with the impairment in JAK/STAT signaling, multiple immune related pathways were found to be dysregulated in the patient. At baseline, genes related to type I IFN-related pathways, antigen processing, T-cell and B-cell functions were upregulated, while NK-cell function and cytotoxicity related genes were downregulated. Dysregulated gene expression was partially improved with ruxolitinib treatment and normalized after transplantation. Conclusion Our findings suggest that improved disease management and immune dysregulatory profile can be achieved with ruxolitinib treatment before transplantation and this would be beneficial to reduce the risk of adverse outcome of HSCT.

This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA).Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h.Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p0.05).Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.Geriye dönük çok merkezli bir çalışma düzenleyerek, çocuk hematoloji uzmanlarının sistemik rekombinant doku plazminojen aktivatörü (rtPA) kullanımı ile ilgili deneyimlerinin ortaya konması amaçlandı.Türkiye’deki 13 pediatrik hematoloji merkezinden geriye dönük veriler toplandı. rtPA tedavisinin dozu ve süresi, eşzamanlı antikoagülan tedavi, tam pıhtı erimesi (TPE), kısmi pıhtı erimesi (KPE) ve kanama komplikasyonları değerlendirildi. Düşük doz (DD) rtPA tedavisi 0,01-0,06 mg/kg/saat ve yüksek doz (YD) 0,1-0,5 mg/kg/saat olarak tanımlandı.2005-2019 yılları arasında ortanca yaşı 5 yıl (1 gün-17,75 yıl) olan 54 hastanın 55 trombotik epizodu değerlendirildi. Hastaların tanıları; intrakardiyak tromboz (n=16), derin ven trombozu (DVT) (n=15), inme dışı arteriyel tromboz (n=14), pulmoner tromboemboli (PE) (n=6) ve inme (n=4) idi. Trombüs saptanmasından rtPA başlangıcına kadar geçen süre medyan 12 saat (2 sa-504 sa) idi ve inme, inme olmayan arteriyel tromboz ve intrakardiyak tromboza kıyasla DVT ve PE için anlamlı olarak daha uzundu (p=0,024). Atakların %63,6’sında rtPA tedavisinden önce heparin başlandı. Atakların 22’sine DD ve 33’üne YD rtPA uygulandı. DD ve YD rtPA ataklarının sırasıyla %90’ında ve %36’sında eş zamanlı antikoagülasyon kullanıldı (p=0,0001). DD ve YD rtPA infüzyonlarının medyan toplam süresi sırasıyla 30 sa (2 sa-120 sa) ve 18 sa (2 sa-120 sa) idi (p=0,044). Ölümcül olmayan majör ve minör kanama oranları DD için sırasıyla %12,5, %16,7 ve YD rtPA için %3,2, %25,8 idi. rtPA infüzyonlarının sonunda, atakların sırasıyla %32,7’sinde TPE ve %49’unda KPE elde edildi. Tromboliz için en başarılı bölge intrakardiyak trombozdu. YD’ye karşı DD rtPA uygulaması, TPE/KPE veya kanama ile korele değildi (p0,05).Yüksek riskli trombozlu çocuklarda sistemik trombolitik tedavi, deneyimli hematologlar tarafından rekanalizasyon ve kanamanın yakın takibi altında doğru endikasyon ve doğru zamanda kullanıldığında etkin bir şekilde hayat ve organ kurtarabilir.

Background Haploidentical HSCT is a good option for children with PIDs lacking an HLA-matched donor. Co-transplantation of MSCs during haploidentical HSCT in patients with PIDs may enhance engraftment, decrease the risk of GVHD, and ensure stable donor chimerism. Methods Twenty-seven pediatric patients (median age, 1.4 years; range, .3-10.9) with PIDs undergoing thirty haploidentical HSCT with TCR αβ depletion and co-transplantation of MSCs were enrolled to study. Most patients (73.3%) received myeloablative conditioning consisting of treosulfan or busulfan, fludarabine, and thiotepa. The median duration of follow-up was 14.3 months (range, 1-69 months). Results Acute GVHD occurred in 7 patients (grade I-II n = 5, grade III-IV n = 2). Chronic GVHD was observed in only one patient. Twenty-one patients (70.2%) had 100% donor chimerism in all cell lines including T-cell and B-cell lineages. Primary graft failure was observed in 7 patients (25.9%). The cumulative incidences of TRM were 20% at day 100, and 26.7% at one year and five years. Probabilities of OS were 80% at day 100, and 71.9% at 1 year and 5 years. Infants transplanted younger than 6 months of age had the highest 5-year survival rate (85.7%). Conclusion We conclude that use of TCR αβ depleted haploidentical transplantation with MSCs may ensure a rapid engraftment rate, low incidence of significant acute and chronic GVHD, and acceptable post-transplantation morbidity, especially in patients diagnosed with SCID and may be considered in children with PIDs. In younger patients (≤6 months), survival is comparable between HLA-matched graft and CD3+ TCRαβ depleted HLA-mismatched graft recipients.

BACKGROUND Anti-human T-lymphocyte immunoglobulin is commonly used as prophylaxis for graft-versus-host disease after allogeneic hematopoietic stem cell transplantation from unrelated donors. The studies according to optimum dose of ATLG especially in pediatric patients are limited. PATIENTS AND METHODS Outcomes of 99 pediatric patients diagnosed with nonmalignant diseases, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2), and 30 mg/kg (group 3), were analyzed retrospectively. RESULTS The incidences of acute and chronic GVHD were statistically not different between three groups (p = .20 and p = .13), but we did not observe chronic GVHD in group 3 patients. Cox regression analysis showed that ATLG dose of 10 mg/kg (p = .007) and severe acute GVHD (p = .001) were significant prognostic factors for inferior overall survival. Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention, TRM and overall survival were superior in ATLG doses ≥20 mg/kg (p = .04 and p = .037) with no difference between 20 and 30 mg/kg. CONCLUSION Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection, TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 and 30 mg/kg. These observations should be supported with other multicenter prospective studies including larger patient population.

WOS:000614296900001 PMID: 33538100 Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited

Background: Graft versus host disease is a major cause of morbidity and mortality after allogeneic HSCT from unrelated donors. ATLG is commonly used as prophylaxis for GVHD. The studies according to optimum dose of ATLG especially in pediatric patients are limited. Patients and Methods: Outcomes of 158 pediatric patients, who received ATLG as GVHD prophylaxis for matched unrelated donor HSCT at a dose of 10 mg/kg (group 1), 20 mg/kg (group 2) and 30 mg/kg (group 3) were analyzed retrospectively. The median duration of follow-up was 25.25 months (range, 1.1-79.5 months). Results: The incidences of acute and chronic GVHD were statistically not different between three groups (p=0.55 and p=0.45). But TRM at day 100 and OS at the end of follow-up was found significant inferior in patients received ATLG 10 mg/kg (p=0.006, p=0.004). Cox regression analysis showed that ATLG dose of 10 mg/kg (hazard ratio [HR] 0.500 [95% CI 0.301-0.829]; p=0.007), severe acute GVHD (HR 5.512 [2.027-14.993]; p=0.001), and having viral infection (HR 2.510 [1.034-6.089]; p=0.042) were significant prognostic factors for inferior OS. Conclusion: Although ATLG dose of 10 mg/kg is effective in pediatric patients on acute and chronic GVHD prevention and safe from the point of infection; TRM and OS were superior in ATLG doses ≥20 mg/kg with no difference between 20 mg/kg and 30 mg/kg. So, it could be better to choose ATLG dose of 20 mg/kg in conditioning regimen for MUD HSCT in pediatric patients, but these observations should be supported with other multicenter prospective studies including larger patient population.

Background RhD typing has remained of primary importance, as being the leading cause of hemolytic disease of the newborn. Among Rh system’s 55 blood group antigens, RhD is the most immunogenic. We aimed with this study to determine weak D/partial D variant frequency in blood donors who were admitted to our blood center and have serologically designated blood group weak D. Materials and methods We screened blood donors who admitted between 2011 and 2017 to our blood center. Sixty-seven serologically weak D phenotyped donors have participated in the study. These donors' samples were studied further by Polymerase Chain Reaction Sequence- Specific Primers (PCR-SSP) for determining D variants. Results Weak D phenotype was detected in 228(0.12 %) out of 177,554 donors. Sixty-seven of them agreed to take part in the study. The frequency of weak D and partial D was 68.7 % (n = 46), and 22.4 % (n = 15), in order. The most encountered weak D and partial D variant was type 15 and DFR type, respectively. Conclusions The prevalence of serologically weak D phenotypes varies by race and ethnicity. Turkey is a country covering a mixture of European and Asian DNA with different ethnic groups. Thus, our research as giving the overall distribution of RHD variants from the largest city of Turkey, which may reflect the general ethnic background of the country, would help to the establishment of a databank for blood banking. This paper is the first molecular study on RHD variants in Turkey. New molecular research would be more reliable and precise.

IRIS is a phenomenon describing localized inflammatory reactions at BCG vaccination site and development of lymphadenopathy as immune system recovers. It is a rare entity in children following haploidentical HSCT. We represent the successful treatment of a case with fluctuating lymphadenopathy due to BCG vaccine during immune reconstitution period following ex vivo T-cell-depleted haploidentical HSCT.

PURPOSE: Human Signal transducer and activator of transcription 1 (STAT1) gain of function (GOF) mutations present with a broad range of manifestations ranging from chronic mucocutaneous candidiasis and autoimmunity to combined immunodeficiency (CID). So far, there is very limited experience with hematopoietic stem cell transplantation (HSCT), as a therapeutic modality in this disorder. Here we describe two patients with heterozygous STAT1 GOF mutations mimicking CID who were treated with HSCT. METHODS: Data on the HSC sources, conditioning regimen, graft versus host disease (GvHD) and anti-microbial prophylaxis, and the post-transplant course including engraftment, GvHD, transplant related complications, infections, chimerism, and survival were evaluated. Pre- and post-transplant immunological studies included enumeration of circulating interferon gamma (IFN-γ) - and interleukin 17 (IL-17)-expressing CD4(+) T cells and analysis of IFN-β-induced STAT1 phosphorylation in patient 1 (P1)’s T cells. RESULTS: P1 was transplanted with cord blood from an HLA identical sibling, and P2 with bone marrow from a fully matched unrelated donor using a reduced toxicity conditioning regimen. While P1 completely recovered from her disease, P2 suffered from systemic CMV disease and secondary graft failure and died due to severe pulmonary involvement and hemorrhage. The dysregulated IFN-γ production, suppressed IL-17 response and enhanced STAT1 phosphorylation previously found in the CD4(+) T cells of P1 were normalized following transplantation. CONCLUSION: HSCT could be an alternative and curative therapeutic option for selected STAT1 GOF mutant patients with progressive life-threatening disease unresponsive to conventional therapy. Morbidity and mortality-causing complications included secondary graft failure, infections and bleeding.

ispartof: HAEMATOLOGICA vol:104 issue:8 pages:E335-E339 ispartof: location:Italy status: published

Baris, Safa/0000-0002-4730-9422; kiykim, ayca/0000-0001-5821-3963; FIRTINA, Sinem/0000-0002-3370-8545; Ozen, Ahmet/0000-0002-9065-1901; NG, YUK YIN/0000-0001-9755-6045 Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiencies (PIDs) caused by gene variants that lead to a failure of functional T cell development, with or without accompanying defects in the production of B and/or NK cells Istanbul University Research FundIstanbul University [52575, 20499] This project is supported by Istanbul University Research Fund (No: 52575 and 20499) and Istanbul Bilgi University [Y.Y Ng, 2017)]. WOS: 000463216500006 30903456 Q1

EgeUn###, Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P =.011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P =.012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P =.014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P =.007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P =.063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%. The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Cytomegalovirus (CMV) infection is one of the most common complications after allogeneic hematopoietic stem cell transplantations (HSCT). Valganciclovir (VGC) has increasingly been used as prophylaxis against CMV infection after solid organ transplantation, but data on the efficacy and safety of VGC in pediatric HSCT patients are limited. We present our experience with VGC following ganciclovir (GCV) as preemptive therapy in pediatric HSCT patients. A total of 46 patients (38% patients) were found to be positive for CMV reactivation. Patients were treated with GCV (group I, n: 22) or GCV followed by VGC (GCV+VGC, group II, n: 24). VGC was preferred in the treatment of outpatients, whereas inpatients were treated with GCV. There was no significant difference in CMV clearance (P=0.78), treatment duration (P=0.087), and second CMV infection (P=0.3) between the 2 groups. The length of hospital stay was 21 days in GCV group, 14 days in VGC following GCV group (P=0.07). There were no treatment-related side effect in both groups. In conclusion, oral administration of VGC as preemptive therapy was found to be safe and effective. It is also a more suitable application for pediatric patients instead of an intravenous route. It could reduce the duration of inpatient stay and cost of hospitalization.

The MN1 (Meningioma 1) gene is overexpressed in certain subtypes of acute myeloid leukemia (AML) and high levels of MN1 expression in mouse bone marrow cells results in myeloid leukemia. We showed that compared with control bone marrow (BM) MN1 expression was increased (2-fold or more) in 29 out of 73 (40%) pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient BM. Additional analysis of MN1 expression in sub-groups within our cohort carrying different chromosome translocations showed that carriers of the good prognostic marker t (12;21)(TEL–AML1) ( n = 27) expressed significantly more MN1 than both healthy controls ( n = 9) ( P = 0.02) and the group carrying the t (9;22)(BCR–ABL) ( n = 9) ( P = 0.001). In addition, AML1 expression was also upregulated in 31 out of 45 (68%) B-ALL patient BM compared with control and there was a significant correlation between MN1 and AML1 expression ( r = 0.3552, P = 0.0167). Retroviral MN1 overexpression increased the colony forming activity of mouse Pro-B/Pre-B cells in vitro . Our results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. Further investigation into the clinical and biological significance of elevated MN1 expression in TEL–AML1 positive leukemia might provide insight into additional molecular mechanisms contributing to B-ALL and may lead to improved treatment options for patients.

KILIC, SUAR CAKI/0000-0001-7489-2054; Emir, Levent/0000-0003-2424-3763; Hazar, Volkan/0000-0002-1407-2334 WOS: 000412118800010 PubMed: 28571522 We examined outcomes of 62 pediatric patients with relapsed or refractory non-Hodgkin lymphoma (rr-NHL) who underwent hematopoietic stem cell transplantation (HSCT). The overall survival (OS) and event-free survival (EFS) rates were 65% and 48%, respectively. Survival rates for patients with chemosensitive disease at the time of HSCT were significantly higher than those of patients with chemosensitive disease (69% vs. 37%, p = .019 for OS; 54% vs. 12%, p

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.

To study the risk factors for hemangioma-related complications, treatment indications and analyze the outcome of patients with infantile hemangioma. Retrospective. University hospital. Fifty-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). The surgical treatment included total excision whereas medical treatment was carried out by interferon and /or corticosteroids. Data 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. Thirty-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. Although 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.

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.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.The mean granulocyte content per concentrate was 27.4×10⁹ (min: 4.2×10⁹ to max: 68.4×10⁹) depending on donor's 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.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.

Received/Gelis tarihi : September 3, 2013 Accepted/Kabul tarihi : November 16, 2013 To the Editor, Although clofarabine is known as an effective novel agent in relapsed acute leukemia [1,2,3,4,5], determining the optimum combination with other agents and the optimum time to use remains a challenge. Clofarabine is recommended to be used after 2 protocol regimens in patients with relapsed leukemia [1]. We want to add our experience with clofarabine in children with multi-relapsed acute lymphoblastic and myeloblastic leukemia. We analyzed the data of 12 children (1-13 years old) treated with the CLOVE protocol [clofarabine (4 mg/m2), cyclophosphamide (440 mg/m2), and etoposide (100 mg/m2) for 5 days] [2,3,4] for relapsed or refractory acute leukemia between 2009 and 2013. We used this therapy in a third or more of cases of relapsed acute leukemia. Bone marrow relapses were eligible for the treatment protocol. Seven of 12 patients had acute lymphoblastic leukemia (ALL) and 5 had acute myeloid leukemia (AML) (Table 1). Patients with relapsed ALL were treated with 1 or 2 cycles of FLAG after applying the BFM-95 REZ protocol. Patients with no response were administered clofarabine. Patients with relapsed AML were treated with 2 cycles of FLAG after applying the MRC protocol. Patients without response were given clofarabine in 1 or 2 cycles. The required permission for all patients was received from the Ministry of Health.

T-cell-depleted HAPLO HSCT is an option to treat children with high-risk acute leukemia lacking an HLA-identical donor. We reviewed the outcome of children with acute leukemia after HAPLO (n = 21) and HLA-MUD (n = 32) transplantation. The proportion of patients with ≥CR2 was significantly higher in HAPLO transplantation than MUD transplantation. Patients with MUD transplantation were significantly higher ABO incompatible than patients with HAPLO transplantation. There was no difference between the 2 groups in terms of engraftment, aGvHD and cGvHD, VOD, hemorrhagic cystitis, infections, and relapse. The 5-year OS of MUD transplantation and HAPLO transplantation groups was found 65.8% and 71.1%, respectively (log-rank 0.51). The 5-year RFS was 80.7% for MUD transplantation group and 86.9% for HAPLO transplantation group (log-rank 0.48). There was no statistically significant difference between 2 groups according to TRM (25% MUD transplantation vs 16.3% HAPLO transplantation, log-rank 0.48). These data suggest that survival for patients with high-risk acute leukemia after HAPLO transplantation with ex vivo ɑβ+ T-cell depletion is comparable with MUD transplantation.

Development of KS in pediatric liver transplant recipients is a rare entity and has dismal prognosis. Latent HHV-8 infection, immunosuppression, and genetic predisposition are possible etiological factors. Decreasing the dose or cessation of immunosuppressive drugs, switching to sirolimus with antiproliferative and antitumor properties, and different chemotherapeutic regimens are the current therapeutic strategies. We herein report a pediatric liver transplant recipient who developed generalized KS at post-transplant fifth month. The disease had an aggressive course despite the highly toxic chemotherapy. On the other hand, a prompt and durable response was provided by paclitaxel with tolerable side effects. The patient is now free of disease for at least 24 months and healthy with good graft function under sirolimus therapy as maintenance immunosuppression. Instead of highly toxic chemotherapy, paclitaxel can be used as therapeutic option in cases with generalized disease and in those who are unresponsive to conventional chemotherapy. However, new studies are needed to assess the efficacy of the paclitaxel therapy in KS in the liver transplant recipients.

Background 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. Methods Two RSV infection outbreaks developed between February–April 2006 and January–March 2009 in hospitalized pediatric patients for various hemato-oncological diseases ± HSCT. A survey of respiratory viruses was done using direct immunofluorescent antibody assay from nasopharyngeal washing aspirate. Results In two RSV infection outbreaks (2006 and 2009), RSV antigen was detected in 6/30 patients. Five of six patients with RSV antigen were all treated with 0.2–0.4 g/kg intravenous immune globulin (IVIG) and specific antiviral therapy, oral ribavirin (20–25 mg/kg/day in three doses). Five patients recovered fully, although two were retreated due to recurrent (+) RSV antigen and respiratory symptoms within 2 weeks. We did not give oral ribavirin to one patient with (+) RSV antigen due to mild symptoms. All patients are alive and well. Conclusions In contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in post bone marrow transplantation (BMT) period, is low when diagnosed and treated early enough. Oral ribavirin might be an option together with IVIG in the treatment of RSV especially when other forms of antivirals could not be obtained. This approach will make it possible to give the scheduled anti-neoplastic therapy on time. Pediatr Pulmonol. 2010; 45:307–311. © 2010 Wiley-Liss, Inc.

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 was1.18×106cells 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%, respectivelyp=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 patientsp=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.

A 15-year-old Iraqi male patient with acute lymphoblastic leukemia received an allogeneic bone marrow transplant from his brother. On the 18th day after the transplant, the patient developed grade II acute graft-versus-host disease, and treatment included methylprednisolone. On day 140, the patient was diagnosed with leukoderma. On day 150, the patient was admitted to hospital because of numbness and muscle weakness in the extremities and a disturbance of the gait. Neurologic examination showed muscle weakness in the upper and lower extremities and there were no deep tendon reflexes. Nerve conduction studies showed reduced conduction speeds of the motor nerves with demyelinating features. The patient was diagnosed as having a chronic inflammatory demyelinating polyradiculoneuropathy (CIDB) based on clinical and electrophysiological findings. Treatment included methylprednisolone and intravenous immunoglobulin. The neurologic function improved but the skin lesions persisted. This case shows that graft-versus-host disease can act as a triggering factor for the appearance of autoimmune diseases. Keywords : Leukemia, Graft-versus-host disease, Leukoderma, Chronic inflammatory demyelinating polyneuropathy

This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU+etoposide+ara-C+melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39months, 46 patients were alive. At fiveyr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at fiveyr was 72.3% and 19%, respectively (p, This study evaluates the outcome of 66 pediatric patients with rrHL who underwent autoHSCT. Twenty-nine patients experienced early relapse, and 19 patients experienced late relapse. Of 18 newly diagnosed with HL, 13 were primary refractory disease and five had late responsive disease. At the time of transplantation, only 68% of the patients were chemosensitive. The majority of patients received BCNU + etoposide + ara-C + melphalan for conditioning (45/66), and peripheral blood (56/66) was used as a source of stem cells. After a median follow-up period of 39 months, 46 patients were alive. At five yr, the probabilities of OS, EFS, the relapse rate, and the non-relapse mortality rate were 63.1%, 54.3%, 36.4%, and 9.1%, respectively. The probability of EFS in chemosensitive and chemoresistant patients at five yr was 72.3% and 19%, respectively (p < 0.001). Multivariate analysis showed that chemoresistant disease at the time of transplantation was the only factor predicting limited both OS (hazard ratio = 4.073) and EFS (hazard ratio = 4.599). AutoHSCT plays an important role for the treatment of rrHL in children and adolescents, and survival rates are better for patients with chemosensitive disease at the time of transplantation.

The ABO incompatibility between donor and recipient is not considered a barrier to successful allogeneic HSCT. Nevertheless, conflicting data still exist about the influence of ABO incompatibility on transplant outcome in pediatric patients with thalassemia. Fifty-one children with beta-thalassemia major who underwent allogeneic HSCT were enrolled this study. Twenty-three of them (45%) received an ABO-incompatible transplant [minor ABO mismatch: six (26%), major ABO mismatch: fourteen (61%), and bidirectional mismatch: three (13%)]. In this study, ABO incompatibility did not significantly impair GVHD, VOD, neutrophil and platelet engraftment, TRM, OS and TFS. Particularly in major and bidirectional ABO-mismatched patients, a delayed erythroid recovery was recorded as compared to the group receiving an ABO-compatible graft (median time, 31 and 38 days vs. 19.5 days; p: 0.02 and p: 0.03). Median time to red cell transfusion independence was significantly longer in major ABO-incompatible patients (median time, 87 days vs. 32 days; p: 0.001). Therefore, whenever feasible, major ABO-mismatched donors should be avoided in HSCT recipients, to prevent delayed erythroid recovery with prolonged RBC transfusion needs and impaired quality of life.

Çakan M, Aktay-Ayaz N, Gemici H, Annayev A, Çıtak A, Akçay A, Öztürk G. Sustained hyperferritinemia in a child with macrophage activation syndrome secondary to systemic juvenile idiopathic arthritis - perforinopathy: case based review. Turk J Pediatr 2018; 60: 598-603. Systemic juvenile idiopathic arthritis is a subtype of juvenile idiopathic arthritis and characterized by arthritis and many systemic features like fever, rash, hepatosplenomegaly, lymphadenopathy and serositis. Macrophage activation syndrome is the most dreadful complication of systemic juvenile idiopathic arthritis and can cause mortality and morbidity if not recognized and treated early and aggressively. Hemophagocytic lymphohistiocytosis (HLH) is characterized by diminished or absent activities of natural killer cells and cytotoxic T lymphocytes leading to cytokine storm and uncontrolled activation of T cells and macrophages. Primary (familial) HLH is a group of autosomal recessive disorders caused by mutations in the perforin and other related genes and distinctive for onset during early infancy and high rate of mortality. Secondary HLH may be caused by infectious, oncologic and rheumatologic disorders. The term Perforinopathy is used to describe cases with classical familial HLH and also for cases with familial HLH gene mutations but not following a classical familial HLH course. Herein we report a case of chronic perforinopathy in which clinical symptoms started with systemic juvenile idiopathic arthritis and severe macrophage activation syndrome that needed plasma exchange and extracorporeal membrane oxygenation during acute period and ongoing interleukin-1 blockage for sustained hyperferritinemia.

A 4-year-old boy with acute lymphoblastic leukemia receiving maintenance treatment developed quadriparesis, facial palsy, difficulty in swallowing, and hypertension following a respiratory infection and candida septicemia. Examination of the cerebrospinal fluid was normal initially but later showed albuminoncytologic dissociation, the characteristic finding of Guillain-Barre syndrome. Complete recovery occurred after treatment with intravenous immunoglobulin. Differential diagnosis of Guillain-Barre syndrome from vincristine toxicity in patients with leukemia and possible association with the infections are discussed.

The Turkish Apheresis Group has maintained a national registry for apheresis activities since 1997. The hemapheresis practice of Turkey in 1998 is summarized in brief detail in this article. A total of 30,136 apheresis procedures were performed at 31 different apheresis centers. At 10 centers, 145 peripheral blood stem cell (PBSC) apheresis were performed on 82 patients in allogeneic setting and at 17 centers, 981 PBSC apheresis were performed on 271 patients in autologous setting. Frequently observed adverse effects during PBSC apheresis were mild tremor and chills, paresthesia and nausea in 15% of the patients and donors. Vascular access complications, particularly observed in autologous setting due to central venous catheters were encountered in 10% of the procedures. Eight hundred and sixty-nine therapeutic plasma exchange procedures were performed at 21 centers on 172 patients, most commonly for neurological disorders and thrombotic thrombocytopenic purpura (TTP)/hemolyic uremic syndrome (HUS). Therapeutic cytapheresis procedures like leukapheresis, plateletapheresis and erythrocyte apheresis were performed especially for cytoreduction in myeloproliferative disorders. A total of 204 cytapheresis procedures (66% leukapheresis, 33% plateletapheresis and 1% erythrocytapheresis) were performed on 134 patients in 15 centers. Donor plateletapheresis was the most used apheresis procedure, reaching a total of 28.016 in 1998. Many university hospitals and a few state hospitals are performing above-mentioned apheresis procedures with great success and acceptable side effects. According to these data we are planning prospective trials and will establish National Standards of Practice.

WOS: 000341378500012, PubMed ID: 25066893, 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, Glanzmann's 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. (C) 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

To determine outcome of neuroblastoma (NBL) in children under 18 mo of age who had been treated with national protocols. The characteristics and treatment outcomes of 27 children were evaluated retrospectively. The event-free survival (EFS) at 60 and 108 mo were 84.7 % ± 7.7 and 72.6 % ± 7.7, respectively. The overall survival (OS) was 91.7 % ± 8 at 108 mo. The only significant risk factor for OS in children with neuroblastoma was the treatment response at the end of therapy (p = 0.001). “Wait and see” policy was applied to two infants with low risk NBL and one infant with stage 4S neuroblastoma and all 3 of these infants have been in remission at last followup. Four of the five patients with MYCN-amplified neuroblastoma were alive at a median follow-up time of 54 mo (range: 5–108 mo). The EFS and OS of the present group were similar to that of the previous series which included children under 18 mo of age with neuroblastoma. Well known prognostic factors did not affect EFS and OS significantly; this may be related to the retrospective design of the present study and the small number of patients reviewed. High survival rate in infants with MYCN-amplified tumors suggests the difference in the biology of infant neuroblastoma.

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. (C) 2012 Elsevier Ltd. All rights reserved.

Twenty children with acute idiopathic thrombocytopenic purpura (ITP) were randomized to receive either oral megadose methylprednisolone (MDMP) or intravenous immunoglobulin G (IV IgG). Normal platelet counts (or = 150 x 10(9)/l) were obtained in 6 patients of each group in 3 days and in 8 and 9 patients treated with oral MDMP and with IV IgG within 1 week, respectively. It is concluded that oral MDMP could easily be used for the early elevation of platelet counts, which is important for ITP treatment.

A 6-month-old male infant with hereditary spherocytosis (HS) who was the first child of a cousin marriage is presented. The patient had splenomegaly and severe anaemia. Examination of the peripheral blood smear revealed spherocytes and the osmotic fragility of red blood cells was greatly increased. Physical examination of the parents revealed that both parents had mild anaemia, jaundice and splenomegaly. Their peripheral blood smears showed spherocytes and a few acanthocytes. Osmotic fragility of red blood cells of both parents were increased. Red cell membrane electrophoresis indicated a deficiency of ankyrin in the propositus; mild deficiency was also detected in both parents. Electrophoretic patterns of red cell membrane proteins suggested that the child was homozygous for the dominant form of HS associated with ankyrin deficiency, while both parents had the simple dominant form of the disease. Red blood cell transfusions were given to the patient starting at the age of 1 month until splenectomy was performed at the age of 1 year that resulted in complete haematological response. This observation indicates that homozygosity for dominant type of HS associated with ankyrin deficiency is life compatible and splenectomy may cure the anaemia.

Objective: In pediatric patients treated for malignancies with chemotherapy or bone marrow transplantation (BMT), the disease and the treatment lead to impaired immunity and loss of immunity continues for a time period after the completion of therapy. Therefore, revaccination of these children is necessary. The aim of this study was to examine the differences between different treatment groups, namely solid tumors, leukemias and BMT patients, for their response to inactivated or subunit or live attenuated vaccines at least 6 months after the cessation of the of treatment. Materials and Method: The study was performed prospectivly in 35 patients with solid tumors (Group I), 32 patients with leukemia (28 ALL, 4 AML) (Group II) and 13 patients after BMT (Group III). Inactivated (Diphtheria, tetanus), subunit (acellular pertussis, hepatitis B, hepatitis A) and live attenuated (measles-mumps-rubella (MMR), varicella) vaccines were applied to patients. Blood samples taken from the all patients before vaccination and 1 month after vaccination. IgG antibodies against measles-mumps-rubella and varicella were evaluated in vitro. Results: For inactivated vaccines, the level of anti diphteria antigen was highly positive in Group I and II, 80% and 71.8% respectively, but only 53.8% of Group III patients were positive before vaccination. After one dose all of these levels became 100%. For tetanus it was the same pattern (84.4% 88.6% and 46.2%, low in Group III). They all reached 100% after vaccination with one dose. Anti pertussis IgGs were low in all 3 groups, 54.3%, 46.9%, 38.5% respectively. These levels were 66.7%, 66.7%, 50% after the vaccination and the differences were meaningful for Groups I and II (p : 0.02 and 0.002), but not for Group III (p : 0.068). In subunit (purified antigen) vaccines, for Hapatitis B, Anti HBs levels were low in all groups (60%, 37.5%, 46.2%) before vaccination. After one dose, 55.6%, 64.3%, 50% became positive, but only after the second dosage 100% of the patients were positive. For Hepatitis A, positive levels of antiHAV IgG before vaccination were 28.6%, 37.5%, 53.8% for the 3 groups. Except for one patient in the BMT group 100% became positive with one dose. Among live, attenuated viruses, measles, rubella, mumps vaccinations were applied. Anti-rubeola IgG levels were positive in 45.7%, 34.4% 15.4% of patients in 3 groups before vaccination. After one dose they all became positive except for one patient in each group, who responded after one more dose. For rubella, 85.7%, 78.1% and 61.5% of patients were positive for anti-rubella IgG before vaccination in respective groups and they all became 100% positive after one dose. Before mumps vaccination, 82.9%, 71.9% and 46.2% of patients were positive for anti-mumps IgG before first dose. 83.3%, 100% and 50% became also positive after one dose, but after the second dosage 100% were positive. 65.7%, 59.4% and 53.8% of the patients were seropositive for antiVZV IgG respectively before vaccination. Except for four cases in Group I, the rest achieved seropositivity after one dose. Conclusion: In our study, after one booster dose of vaccine, all patients had very good antibody response against to diphtheria, tetanus, hepatitis A, rubella vaccines at least 6 months after the cessation of therapy for leukemia and solid tumors and 12 months after BMT. Protection after mumps vaccine was in moderate levels in leukemia and solid tumor groups, but not in BMT group. All groups responded moderately for measles, varicella, pertussis, hepatitis B, some needing one more booster. BMT group seems to be the maximum looser and the least responder after vaccination. The groups showed differences in antibody responses to vaccines, according to age, the time passed after the cessation of treatment and their primary vaccination status. To evaluate the response obtained, following antibody levels for response to vaccination is necessary and a booster should be considered when there is a decrease or loss in these levels. Disclosures Karakas: Novartis: Research Funding.

Chemotherapy of the central nervous system may cause neurotoxicity in children with acute lymphocytic leukemia. We evaluated regional blood flow in a 6-year-old child presenting with akinetic mutism, using Tc-99m-HMPAO single photon emission tomography (SPECT) following high-dose intravenous methotrexate therapy. While findings in X-ray computerized tomography were decreased density in bilateral basal ganglia and thalamic nuclei with diffusely decreased attenuation of the periventricular white matter, a global, frontal dominant profoundly abnormal perfusion pattern involving both gray and white matter was observed in the SPECT study. Treatment of the central nervous system with high dose intravenous chemotherapy may cause profound abnormalities in white and gray matter blood flow and early assessment of the neurotoxicity may be identified by Tc-99m-HMPAO SPECT in the pediatric age group.

Ophthalmic examination of a girl admitted with the complaint of growth failure revealed retinal hard drusen. It was surprising to observe drusen in a child because they represent an age-related degenerative change in normal individuals. After further evaluation, she was diagnosed to have Bloom syndrome, a premature aging syndrome. To the authors' knowledge, this is the first case of Bloom syndrome associated with drusen. It is probable that not only aging but also other fundamental cell processes, especially uncontrolled cell proliferation, might be similarly affected and might follow a more rapid course in this inherited condition presenting with drusen. The authors suggest paying extra attention to drusen during the ophthalmic assessment in the diagnosis of all Bloom syndrome patients; it may be prudent to watch more carefully for the development of cancer in patients with drusen than those without drusen.

Editor,—Protein C is a plasma inhibitor protein that, once activated, inhibits clot formation and enhances fibrinolysis. Protein C deficiency has two forms. The homogeneous form presents in the neonatal period with ecchymotic-necrotic skin lesions and widespread thrombosis in major blood vessels with very low or undetectable protein C activity. Heterozygote individuals have protein C levels of approximately 50% and usually remain asymptomatic until adolescence.1 We present a neonate with homozygous protein C deficiency whose initial finding was leucocoria. ### CASE REPORT A 2 day old female infant was referred to Gazi University Hospital Division of Newborn Medicine with bullous …

WOS: 000085501700008 PubMed: 10734661 Acute promyelocytic leukemia (APL) is often associated with a severe hemostatic disorder, caused bg the release of procoagulant and fibrinolytic substances from leukemic blasts. The coagulation profile may exhibit disseminated intravascular coagulation and fibrinolysis or proteolysis. Therefore, heparin and antifibrinolytic agents alone or in combination have been used to prevent severe bleedings. Remission induction with all-trans-retinoic acid (ATRA) is accompanied with rapid correction of hemostatic abnormalities. Thrombosis is a rare complication of APL and may be due to the alterations in hemostasis caused by the disease itself as well as ATRA and antifibrinolytics. Here, the occurrence of thrombosis during induction treatment with ATRA combined with aprotinin and chemotherapy is described in a patient who is homozygous for factor VQ 506 mutation.

This prospective study evaluated 382 pediatric patients with peripheral lymphadenopathy (LA) presenting at the Pediatric Oncology and Hematology Departments of Social Security Children's Hospital and Gazi University Medical Faculty Hospital. The ages of the patients ranged between 2 months and 16 years (median 7 years); 72% of the patients were male. Of the 382 patients, 138 had localized LA (a single anatomic area involved), 171 had limited LA (two or three areas involved), and 73 had generalized LA (four or more anatomic areas involved). The specific etiology (either benign or malign) was defined in 79% of patients with generalized LA. However, in patients with localized LA and limited LA, specific etiology could be identified only in 43 and 53% of patients, respectively. Based on this study, BCG-LA and pyogenic infections are more frequently manifested by localized LA; LA of unknown origin, Hodgkin's disease, tuberculosis, nasopharyngeal carcinoma, and toxoplasmosis are frequently manifested by localized or limited LA; and cytomegalovirus infection (CMV), infectious mononucleous, rubella, acute leukemia, non-Hodgkin's lymphoma are frequently manifested by limited or generalized LA. Out of 382 patients, 196 patients had a maximum lymph node diameter of less than 2 cm. A benign etiology was shown in 159/196 of these patients. In 37/196 of these patients LA was due to a malignancy, and these cases almost invariably had some apparent additional diagnostic clinical and laboratory findings. Based on this observation a maximum lymph node size of 2 cm was considered an appropriate limit to distinguish malignant disease from benign causes except when there is other evidence of an underlying malignant disease. However, lymphadenopathies located at supraclavicular region (27 patients) either localized or as part of generalized LA had a specific benign or malignant disease in etiology (malignancy in 20, tuberculosis in 3, CMV in 2, sarcoidosis in 1, and lipoma in 1) even though they were less than 2 cm in diameter.

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 donor's 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.

Abstract 4365 Fibrinolytic system plays a role in tumor growth, invasion and metastasis in cancer. High levels of plasminogen activator inhibitor-1 (PAI-1) which is a part of fibrinolytic system is a sign of poor prognosis in a number of cancer types. Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease of childhood. Risk groups of ALL are used to determine treatment strategies in childhood ALL. In this study, we aimed to ascertain the prognostic and predictive roles of PAI-1 and vitronectin in children with ALL, and their relationship with risk groups of ALL. In the literature, there are few studies with PAI-1, but no study with vitronectin and ALL in children. In this study, we analyzed the plasma PAI-1 and vitronectin levels of 37 recently diagnosed ALL patients (age range: 9 months–17 years), and 25 age-matched healthy children as a control group by using the ELISA technique. The mean PAI-1 levels was 27.36±16.53 ng/ml, vitronectin levels 97.54±29.82% in the ALL group; and, 23.60±10.44 ng/ml, 85.50±20.85% in the control group, respectively. It was found that the plasma vitronectin levels of ALL group was high as nearly statistically significant (p=0.06). Although, the PAI-1 levels of ALL group was higher than the control group, there was no statistically significance (p=0.27). The ALL group was divided into three risk groups (standard, moderate, and high) according to the BFM protocol. When the standard and moderate-high risk groups are compared with control group, the vitronectin levels of standard risk group was higher than the control group (p=0.048), but no difference was found for PAI-1 levels (p=1.00). There was no significant difference for vitronectin levels (p=0.76), and PAI-1 levels (p=0.25) between moderate-high risk groups and the control group, although PAI-1 levels were higher in moderate-high risk groups. In conclusion, we could not find any relationship between the parameters of fibrinolytic system and ALL risk groups except the vitronectin levels of standard risk group, new studies are needed. Disclosures: No relevant conflicts of interest to declare.

Abstract 4903 Anaplastic large cell lymphoma (ALCL) accounts for approximately 10% of the childhood lymphomas. ALCL is characterized by peripheral, mediastinal or intra-abdominal lymph node involvement or extranodal involvement. We report a child with ALCL with unusual localization. An eleven-year-old boy had been admitted to the another university hospital with left knee pain and swelling for 15 days. The left knee joint punction had been done, and osteomyelitis had been diagnosed, and treated with antibiotics. However, there had been no recovery from his complaints, and left knee synoviectomy had been done. This operation had revealed anaplastic large cell lymphoma in the intraarticular soft tissue of the left knee. Then, he was referred to our hematology and oncology clinic for advanced therapy. There was nothing significant in the background and family history. Physical examination showed a 3 cm mass arising from the left knee joint with lobulated contours. PET-CT showed the left inguinal lymph node involvement, only. Chemotherapy according to ALCL 99 protocol was started because of the tumor was not resectable. After the first course of therapy, tumor mass was reduced apparently. By the end of his second chemotherapy course, tumor was not detectable. Now, he completed his therapy, and he is on follow-up without any complaint or recurrence for 18 months. In conclusion, to the best of our knowledge, this is the first reported case with ALCL originating from the intraarticular soft tissue which was treated successfully. Disclosures: No relevant conflicts of interest to declare.

Pediatric patients with malignancy are at high risk of thromboembolic complications due to complex interactions of a variety of factors such as the malignancy, chemotherapy, central venous catheters (CVCs), infections, dehydration, and hereditary thrombophilia. In this study, deficiencies of protein C (PC), protein S (PS), and antithrombin (AT), activated protein C resistance (APCR), the factor V G1691A mutation, the prothrombin G20210A mutation, and increased factor VIII, IX, fasting homocysteine levels were assessed at the diagnosis of leukemia, retrospectively. The aim was to evaluate the role of the thrombophilic risk factors on vascular events during treatment period. Thirty children (11 F, 19 M) with leukemia (24 patients with ALL, 4 AML, one biphenotypic leukemia, one infant leukemia) were enrolled in this study. The median age of the patients was 56 months (range 7–215 months). All patients had CVCs, and thromboprophylaxis was not given to the any patients. We detected main prothrombotic risk factors at the diagnosis of leukemia as following: low PC (8/30), PS (11/30), AT activity (3/25), APCR (5/22), increased FVIII (5/22), FIX (2/22), and homocysteine levels (2/8), and FV Leiden mutation (1/24; heterozygous). The prothrombin G20210A mutation was not detected in any patient. The parents of these patients with abnormal test results were also evaluated to discriminate congenital or acquired deficiencies. In addition; PC, PS, AT levels were followed-up, and MTHFR genotype for the patients with high homocysteine levels was studied, also. In spite of, 24 of these 30 patients had at least one abnormal laboratory test result at the diagnosis of leukemia, venous thrombosis (7 with CVC-related venous thrombosis, one CVC-related jugular vein thrombosis and VOD, one vena saphena parva thrombosis) developed in 9 of 24 patients. In conclusion, leukemic children with at least one prothrombotic risk factor have high venous thrombosis risk. Further trials are needed to clarify the necessarity of screening program for thrombophilia and thromboprophylaxis in children with leukemia and CVCs, and, especially for the patients carrying hereditary prothrombotic risk factors.

Respiratory syncytial virus (RSV) has been reported to cause severe morbidity and mortality among cancer patients receiving chemotherapy together with or without autologous/allogeneic stem cell transplantation (APBSCT), but there have been few reports describing the outcome of RSV infection specifically among pediatric oncology patients. Between February 20 – April 15, 2006, among 15 pediatric patients hospitalized for various oncologic diseases and post-BMT problems, 7 patients developed progressive cough and/or dyspnea. A survey of respiratory viruses was done using direct immunofluorescent antibody assay. Three patients (two high-risk patients with acute lymphoblastic leukemia receiving induction or consolidation chemotherapy, one under treatment for chronic GvHD postBMT) were found positive for RSV (20%). The remaining patients with respiratory symptoms were followed-up for RSV infection, but remained negative during all surveys. Three patients and the sister of the boy with hyper-IgM syndrome, who was also transplanted for hyper-IgM syndrome and under treatment for chronic GvHD and pneumonia, in the same room with her brother, were all treated with IVIG and specific antiviral therapy, oral Ribavirin (20–25 mg/kg/day in three doses). All patients recovered fully, although two were retreated due to recurrent RSV positivity and respiratory symptoms within two weeks. In striking contrast with the outcome of RSV infection in adult oncology patients, the mortality associated with RSV infection in pediatric oncology patients even in postBMT period, is very low and can easily be treated with IVIG and oral Ribavirin, used effectively because of unavailability of other forms (iv or nebulized forms) in our country, if diagnosed and treated early enough. It is even possible to give the scheduled anti-neoplastic therapy for not being delayed.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with the survival rates up to 80–90%, but in high-risk patients the survival rate is still unsatisfactory. The aim of this study is to analyze the pediatric ALL data of a single pediatric university center between 1987–2005 retrospectively to identify risk factors effecting the event free survival (EFS). In order to determine the risk factors possibly effecting the survival, we analyzed gender, age, physical examination findings, blood cell count, FAB morphology, immunophenotyping results, translocations and extramedullary involvement. During the same period, chemotherapy regimens used and response to these protocols were also analyzed. A total of 372 cases [220 male (60%) and 151 female (41%)] were diagnosed and treated in our center between 1987–2005. The age distribution was as follows: 7% patients under 2 years, 68% between 2–10 years, 25% above 10 years of age. At diagnosis, 76% patients had a hemoglobin level 10.000/mm3, 74% platelet 2cm., white blood cell >50.000/mm3 and platelet count 2cm. and ≥M2 bone marrow status at day 14 and CD 45 negativity. After a follow up of 72±59 months (1–300 months) 58% of patients are alive & well, 28% were lost to follow up and 14% patients succumbed to death. Overall survival (OS) for 60&120 months follow up were 83%, 83% and event free survival (EFS) 72%, 70% respectively. In conclusion, in ALL patients risk assessment is very important to conduct appropriate therapy. Identifying such factors and implementing risk adapted therapy will improve our treatment results decreasing the toxicity rates in pediatric ALL. Therefore treatment of all ALL patients still remains a challenge.