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Objectives To apply therapeutic drug monitoring and dose-individualization of intravenous Busulfan to paediatric patients and evaluate the impact of syringe-pump induced Busulfan infusion lag-time after in vitro estimation. Methods 76 children and adolescents were administered 2 h intravenous Busulfan infusion every 6 h (16 doses). Busulfan plasma levels, withdrawn by an optimized sampling scheme and measured by a validated HPLC–PDA method, were used to estimate basic PK parameters, AUC, Cmax, kel, t1/2, applying Non-Compartmental Analysis. In vivo infusion lag-time was simulated in vitro and used to evaluate its impact on AUC estimation. Key findings Mean (%CV) Busulfan AUC, Cmax, clearance and t1/2 for pediatric population were found 962.3 μm × min (33.1), 0.95 mg/L (41.4), 0.27 L/h/kg (33.3), 2.2 h (27.8), respectively. TDM applied to 76 children revealed 6 (7.9%) being above and 25 (32.9%) below therapeutic-range (AUC: 900–1350 μm × min). After dose correction, all patients were measured below toxic levels (AUC < 1500 μm × min), no patient below 900 μm × min. Incorporation of infusion lag-time revealed lower AUCs with 17.1% more patients and 23.1% more younger patients, with body weight Conclusions TDM, applied successfully to 76 children, confirmed the need for Busulfan dose-individualization in paediatric patients. Infusion lag-time was proved clinically significant for younger, low body-weight patients and those close to the lower therapeutic-range limit.

Carbapenem resistance, most notably in Klebsiella pneumonia (KPC), results in infections associated with significant morbidity and mortality. Here we report 2 cases of adolescent patients with KPC infection after high-risk bone marrow transplantation, who eventually succumbed from other causes and review the epidemiology and treatment options for KPC infections in this vulnerable population.

We report the results of an analysis of unrelated allogeneic hematopoietic stem cell transplantations (HSCT) in 71 patients with sickle cell disease (SCD) transplanted in EBMT centers between 2005 and 2017. Median age was 9.3 years; graft type was bone marrow in 79% and peripheral blood in 21%. Recipient-donor HLA match at high resolution typing was 10/10 in 31, 9/10 in 20, and 8/10 in 4 patients; the other patients had intermediate resolution typing. The most frequent conditioning regimens were fludarabine-thiotepa-treosulfan (64%) or busulfan-cyclophosphamide (12%). Cumulative incidence of neutrophil engraftment was 92%; platelet engraftment was 90%. Eleven patients (15%) experienced graft failure. Grade II-IV acute graft-vs.-host disease (GvHD) was 23%; 3-year chronic GvHD was 23%. Three-year overall survival (OS) was 88 +/- 4%. GRFS was 62 +/- 6%. HLA matching was the most significant risk factor for OS: 3-year OS was 96 +/- 4% in 10/10 group vs. 75 +/- 10% in 9-8/10 (p = 0.042); GRFS was 69 +/- 9% vs. 50 +/- 12% (p = 0.114), respectively. In conclusion, unrelated donor HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor, preferably in the context of clinical trials. Using a 10/10 HLA-matched unrelated donor yields better survival indicating that HLA matching is an important donor selection factor in this nonmalignant disease.

Background Bone marrow transplantation is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients, however, will develop graft vs host disease (GVHD), acute or chronic, with serious long-term sequalae. Cases We present 2 cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In 1 girl blunt lysis of the adhesions was performed with the patient under general anesthesia, followed thereafter by local hydrocortisone and estriol treatment. Summary and Conclusion Genital symptoms might not be readily reported by adolescents after bone marrow transplantation. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms, and be acquainted with addressing complications, such as vaginal obstruction.

Toxoplasmosis is a disease of the immunocompetent population. However, cases of toxoplasma infection associated with immunosuppression have been reported, especially the first months after transplantation. Limited data are available about toxoplasma infection, occurring even many months post-transplant in pediatric patients with nonmalignant and malignant diseases. We report the cases of three patients with early and late disseminated toxoplasmosis and review the literature.

Background Antifungal prophylaxis (AFP) is recommended in at-risk hematology-oncology patients. We evaluated the safety of AFP with voriconazole (VRC) in pediatric hematology/oncology patients. Materials and methods A retrospective study of VRC AFP in children with malignancies hospitalized in all 7 Greek pediatric hematology/oncology centers during 2008 to 2012 was conducted. Patients' demographics, outcome, and adverse event (AE) data were recorded. Results Four hundred twenty-nine VRC AFP courses in 249 patients (median age 6 y, 55% boys) were studied. The most common underlying diseases were acute lymphoblastic leukemia (51%), non Hodgkin lymphoma (8.6%), and acute myeloid leukemia (7.7%). The median number of VRC courses per patient was 1.7, whereas the median VRC dose was 7 mg/kg (range, 5 to 7 mg/kg) every 12 hours. During the last 2 weeks before AFP, 51% of the patients had received corticosteroids, 43% suffered from severe neutropenia, and 17.3% from mucositis. The median duration of VRC AFP was 17 days (range, 1 to 31 d). A single breakthrough fungemia due to Candida glabrata was recorded. Only 1 patient died due to the underlying disease. The most common AEs reported in 70/429 (16.3%) courses with ≥1 AE were elevated liver enzymes (50%), hypokalemia (24.3%), and ophthalmological disorders (14.3%). The median time of AE onset was 5 days (range, 1 to 21 d). Among 70 AEs reported, 38.5%, 48.4%, and 12.8% were of grade I, II, and III, respectively. Conclusions VRC prophylaxis in pediatric hematology/oncology patients appears to be well tolerated.

Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed.A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers.Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.

Respiratory infections in oncology are both common and potentially severe. However, there is still a gap in the literature, regarding the epidemiology of viral respiratory infections in children with cancer. We prospectively enrolled 224 patients, from September 2012 to August 2015. The cohort included children with hematologic or solid malignancies receiving chemotherapy, or undergoing hemopoietic stem cell transplantation, outpatients/inpatients exhibiting signs/symptoms of febrile/afebrile upper/lower respiratory infection. Viral infection was diagnosed by detection of ≥1 viruses from a sample at time of enrollment, using the CLART

An audit based on a specific questionnaire was attempted, in order to investigate the mycology laboratory diagnostic capacity for invasive fungal diseases (IFDs) in Greek Paediatric Haematology-Oncology departments/units. The study provided the relevant information for the years 2019 and 2020 and included data from all units, concerning culture-based methods and direct microscopy, phenotypic and molecular identification, sensitivity testing, serology and molecular diagnosis, as well as therapeutic drug monitoring. The target was mostly to reveal the level of laboratory coverage for hospitalised paediatric patients, independently of the possibility of performing the tests in the host hospital, or otherwise to refer the specimens elsewhere. In total, the current study demonstrated that the most important facilities and services regarding the IFD diagnostics for paediatric haematology-oncology patients in Greece are available and relatively easily accessible, with a reasonable turnaround time. Acting as an initial registry for further improvements, the audit can serve as a valuable approach to the actual situation and future perspectives. A national clinical mycology network under the auspices of the relevant scientific societies will probably facilitate collaboration between all the departments (clinical and laboratory) involved in invasive fungal infections and provide an easier approach to any necessary test for any hospitalised patient.

Candidemia is an important cause of morbidity and mortality especially in immunocompromised and hospitalized patients. We retrospectively collected data of candidemia cases that occurred in the seven Hematology-Oncology Departments/Units of Greece and the Stem Cell Transplant Unit between 2015 and 2019. In total, 19 episodes of candidemia in 19 patients were recorded. The majority of the patients (78.9%) had at least one risk factor for candidemia. The most frequent risk factors associated with candidemia observed in our patients were prolonged duration of hospitalization (30 days, range 1&ndash, 141), presence of a central venous catheter at diagnosis of candidemia (73.7%) and antibiotics use during the last two weeks (84.2%). Candida parapsilosis was the most common species isolated accounting for 42.1%, followed by C. albicans (26.3%) and C. famata (15.8%). Nearly all of the patients (84.2%) received antifungal monotherapy with liposomal amphotericin B or echinocandins. The central venous catheter was removed in 78.6% of patients and the median time between the first positive blood culture and catheter removal was 3 days (range 1&ndash, 9). Mortality at 28 days was 26.3%. In conclusion, a predominance of non-albicans species was observed in our study in conformity with the global trend.

This paper discusses the implications of Guattari's concept of metamodeling, used to set up an emergent methods design, in a study on neighborhood images and urban development. Related to a theoretical background coming from Deleuzo-Guattarian philosophy, metamodeling is used as a conceptual tool that enables the creation of a flexible and adaptable methods design, which draws on methods that are not completely fixed at the beginning of the research but rather developed in an iterative way. By investigating the questions of how neighborhood images emerge and how they perform citizens’ everyday lives, we developed a methodological dispositive composed of four methods—one based on the use of photography, a second based on drawings, a third based on qualitative geographic information system (GIS), and a fourth that is a quantitative survey—that revealed multiple facets of neighborhood images.

Introduction Lower respiratory tract infections (LRTI) due to parainfluenza (PIF) or respiratory syncytial virus (RSV) represent a major challenge for immunocompromised patients especially those after allogeneic stem cell transplantation (allo-SCT). Evidence-based guidelines for the management of respiratory virus infections in allo-SCT recipients are limited due to the paucity of effective antivirals and the lack of prospective randomized trials. In this study, we report our experience with the use of oral ribavirin with or without the addition of IVIgG in allo-SCT recipients with LTRI due to RSV and PIF. Patients and methods This is a retrospective study performed in 3 BMT centers in Athens, Greece (2 adult and 1 pediatric center). Review of medical records was performed with the aim to identify patients with RTIs who received treatment with oral ribavirin. LRTI was defined according to the European Conference on Infections in Leukaemia (ECIL-4) (Ref 1). Presence of RSV or PIF in specimens from nasopharyngeal wash and/or BAL was documented with the use of a PCR assay. Ribavirin was administered at a dose of 20-30mg/kg divided into 4 daily doses, with appropriate dose adjustment according to creatinine clearance. Treatment with ribavirin was continued until significant symptomatic and radiological improvement. Co-administration of IVIgG was at the discretion of the treating physician and was mostly based on the availability of IVIgG and on the severity of underlying illness. IVIgG was administered at a daily dose of 400mg/kg for a total dose of 2 g/kg. Informed consent was given by patients or their parents. Results Forty-nine episodes of LRTI due to RSV or PIF were reported during a nine-year period in 7 children and 37 adult patients after allo-SCT. Three children and 2 adult patients had a second LRTI due to RSV, 6, 8, 8, 10 and 12 months after the first episode. Patient's characteristics are shown in Table 1. All patients presented with fever and cough. In almost all of the patients auscultation revealed a prolonged expiratory phase, diffuse wheezing, while the presence of crackles was more prominent finding in patients presenting with pneumonia. Arterial blood gas analysis showed moderate to severe hypoxemia. In 32 out of 49 episodes oxygen supplementation was required while 7 patients required mechanical ventilation. All 49 episodes treated with oral ribavirin while in 37 cases ribavirin was administered in combination with IVIgG. High resolution CT-scan was performed in 41 episodes and revealed bilateral abnormalities in all patients examined. Small centrilobular nodules, bronchial wall thickening (32 out of 41 episodes) and ground-glass opacities (21 out of 41 episodes) were common findings, while a pattern of diffuse air-space consolidation was observed in 11 cases. In 43 LRTI episodes a rapid response to treatment in a median of 3 days (range, 2 - 5) was observed. Complete resolution of all symptoms and signs of disease occurred after a median of 9 days (7 - 20) of treatment. One patient with pneumonia due to PIF3 who needed mechanical ventilation had a complete resolution of all symptoms of disease. Six deaths attributable to LRTI were observed among a total of 49 episodes (all 6 patients were in need for mechanical ventilation). Disease relapse confirmed microbiologically occurred in only 1 patient with LRTI due to RSV 10 days after the end of treatment with ribavirin. One children developed bronchiolitis obliterans syndrome (BOS) 9 months after the resolution of RSV infection. Cryptogenic organizing pneumonia (COP) was observed in two patients 1 and 2 months after the complete resolution of LRTI due to PIF. Both patients had an excellent response to treatment with steroids. Conclusions Oral Ribavirin has an excellent efficacy and safety profile. Complete and fast resolution of infection occurred in 88% of cases. From the present study it is not clear if the addition of IVIgG offers any therapeutic benefit. References Fourth European Conference on Infections in Leukaemia (ECIL-4): Guidelines for Diagnosis and Treatment of Human Respiratory Syncytial Virus, Parainfluenza Virus, Metapneumovirus, Rhinovirus, and Coronavirus. Clin Infect Dis 2013;56(2):258-66 Disclosures Tsonis: Gilead: Other: Travel Grant; Astellas: Other: Travel Grants; Innovis: Other: Travel Grant; Pfizer: Other: Travel Grant; Takeda: Other: Travel Grant; Aenorasis: Other: Travel Grant. OffLabel Disclosure: Tabl Ribavirin. Current indication: Treatment of active hepatitis C in combination with interferon-a.

Introduction: Allogeneic hematopoietic stem cell transplantation (HSCT) is, to date, the only curative treatment for sickle cell disease (SCD). Because a human leukocyte antigen (HLA) matched sibling donor is not always available, alternative stem cell sources such as unrelated or haploidentical related donors have been explored. The likelihood of finding a 10/10 (HLA-A, B, C, DRB1 and DQB1) matched donor varies among ethnic groups, with the lowest probability among individuals of African descent. To date, few series of SCD patients transplanted with an unrelated donor (UD) have been reported, but the high rates of rejection and chronic graft versus host disease (cGvHD) have limited its widespread application. Patients and methods: We report the results of a retrospective, registry based, survey on 70 UD HSCT performed in patients (pts) with SCD from UD in 22 European Society for Blood and Marrow Transplantation (EBMT) centers between 2005 and 2017. Data were collected from the EBMT database and missing information was updated by the centers. Median follow up was 38 (range 2-154) months. Most pts were HbSS (n=54; 78%), had positive serology for CMV (80%), and a Karnofsky score >80% (98%). Eighteen pts had a major ABO incompatibility. Recurrent vaso-occlusive crisis (n=58), cerebral vasculopathy (n=23) and acute chest syndrome (n=24) were the main indications for HSCT. Red blood cell (RBC) transfusions pre-HSCT were reported in 97% of pts of whom 53% received more than 20 transfusions; 14% of the transfused pts had RBC alloantibodies. Hydroxyurea pre-HSCT was used in 65% of pts. Median age at HSCT was 9.6 years (range 2-43) with 87% of pts being ≤ 16 years. Stem cell source was bone marrow (BM) in 55 pts (79%) and peripheral blood (PBSC) in 15 (21%). The median number of infused TNC /kg was 3.6 x 108 for BM and 7.1 x 108 for PBSC; the median number of infused CD34/kg was 4.4 x 106 for BM and 8.3 x 106 for PBSC. HLA matching at high resolution typing was 10/10 (HLA-A, B, C, DRB1 and DQB1) in 31, 9/10 in 17 and 8/10 in 4 of the patient-donor pairs; intermediate resolution typing was available for 10 (10/10 or 9/10) and the HLA information was missing for the remaining 8 patient-donor pairs. The most frequent conditioning regimens were fludarabine-thiotepa-treosulfan (64%) and busulfan- cyclophosphamide (12%). GvHD prophylaxis was cyclosporine plus methotrexate in 59%. Anti-thymocyte globulin was used in 90% and alemtuzumab in 9% of pts. Results: The cumulative incidence (CI) of neutrophil engraftment at 60 days was 93% (95% CI 76-100), with median time to engraftment of 18 days; platelet engraftment at 180 days was 90% (95% CI 83-98) with a median time of 20 days. Ten pts had graft failure (5 primary and 5 secondary) of whom 6 had a second transplant and were all alive at last FU (median 9.5 months after second HSCT). The CI of grade II-IV aGVHD at 100 days was 23% (95% CI 15-36), and 8 pts (11%) had grade III-IV. Acute GVHD was more frequent in patients who received PBSC (PBSC 42.9%, BM 18.2%, p=0.062). Three-year CI of cGVHD was 23% (95% CI 15-36), 7 pts (10%) had limited and 9 (13%) extensive cGvHD. Three-year overall survival (OS) was 90±4%; three-year event free survival (EFS) (considering death and graft failure as events) was 76±6%; HLA matching between donor and recipient was the most important factor for OS and EFS. Considering only pts-donor pairs with high resolution HLA typing available (n=52), 3-year OS was 96±4% in 10/10 group compared to 77±11% in 9/10 plus 8/10 group (p 0.065), 3-year EFS was 85±7% vs 62±12% (p 0.040), respectively. No significant differences between the groups were observed in CI of neutrophil engraftment, aGVHD and cGVHD. Conclusion: UD HSCT is a valid option for SCD patients who lack an HLA-identical sibling donor. Nevertheless, efforts are still needed to improve outcomes after UD HSCT. Our results indicate that using a 10/10 HLA matched UD improves both OS and EFS compared to donors with 1 or more mismatches; so, when such a matched unrelated donor is not found, using an haplo relative or an unrelated cord blood as donor source should be evaluated. A prospective trial is in preparation to evaluate the use of haploidentical donors for HSCT in SCD (EudraCT number: 2018-002652-33). Disclosures No relevant conflicts of interest to declare.

This article presents the case of the New Acropolis Museum, one of the most important cultural works for contemporary urban development in Greece. We present a comparative study of the briefs and winning projects of the international architectural competition in 1989 and the tender for the architectural, engineering and electromechanical studies in 2000. We use assemblage theory as a theoretical basis for studying the two procurement processes. We illustrate how the diverse changes—changes related with costs, quality, technical complexity, and uncertainty—influenced directly the choice and the organization of the procedures. These different procedural organizations framed, in different ways, the selection of solutions, the project realization and thus the quality of urban space. By studying the links between the selection of procurement processes, their organization and their results, we shed light on the trajectories between the initial problems, the actors, and the priorities and we increase our underst...

The aim of the present study was to identify factors associated with the risk of development of gastrointestinal acute graft-versus-host disease (GI-aGVHD), as well as to evaluate the impact of various baseline parameters on response to treatment, nonrelapse mortality (NRM), and overall survival (OS) in pediatric patients with GI-aGVHD after allogeneic hematopoietic stem cell transplantation (allo-SCT). We retrospectively analyzed 300 pediatric patients who underwent allo-SCT from HLA-matched related or volunteer unrelated donors in our institution. GI tract involvement was observed in 46 out of 133 patients with aGVHD grade II-IV. Severe aGVHD (grade III-IV) was more frequently observed among patients with GI-aGVHD in comparison with patients without GI involvement (P < .001). Treatment with steroids resulted in durable responses in 22/46 patients; 14 additional patients responded to salvage therapy, whereas 10 were refractory to all treatments administered. Using Cox regression analysis, we observed that serum albumin level ≥3 mg/dL on day 5 after the initiation of therapy with steroids was statistically significantly associated with decreased hazard of NRM and improved OS (P = .021 and P = .026, respectively). In our study, serum albumin level, early (+ day 5) after the onset of steroids in patients with GI-aGVHD, was a predictor of treatment outcome. Prospective randomized trials need to be performed to verify the predictive significance of serum albumin and the need for early intensification of immunosuppressive treatment.

Directed sibling cord blood banking is indicated in women delivering healthy babies who already have a sibling with a disease that is potentially treatable with an allogeneic cord blood transplant. We evaluated the effectiveness of a national directed cord blood banking program in sibling HLA-identical stem cell transplantation for hematological malignancies and the factors influencing the usage rate of the stored cord blood units. Fifty families were enrolled from which, 48 cord blood units were successfully collected and 2 collections failed due to damaged cord/placenta at delivery. Among enrolled families 4 children needed transplantation; however, only one was successfully transplanted using the collected cord blood unit containing 2 × 107 nucleated cells/kg in conjunction with a small volume of bone marrow from the same HLA-identical donor. Two children received grafts from matched unrelated donors because their sibling cord blood was HLA-haploidentical, while the fourth one received bone marrow from his HLA-identical brother, since cord blood could not be collected due to damaged cord/placenta at delivery. With a median follow-up of 6 years (range, 2–12) for the 9 remaining HLA-matched cord blood units, none from the prospective recipients needed transplantation. The low utilization rate of sibling cord blood in the setting of hematopoietic stem cell transplantation for pediatric hematological malignant diseases necessitates the development of directed cord blood banking programs that limit long-term storage for banked cord blood units with low probability of usage such as non-HLA-identical or identical to patients who are in long-term complete remission.

aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for-profit cord blood-banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107 /kg, and 3.8 × 107 /kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post-transplant immunosuppression with cyclosporine for 12 months. They remain disease-free 6 years post-transplantation.

Background Anti-thymocyte globulin (ATG) has been used to prevent graft failure/rejection in the setting of allogeneic stem cell transplantation (allo-SCT) for hemoglobinopathies; however, epidemiology data for transplant-related infections in this population are scarce. Method We retrospectively analyzed the epidemiology of bacterial, fungal, viral, and parasitic infections in a cohort of 105 children and adolescents with β-thalassemia (n = 100) or sickle cell disease (n = 5) who underwent allo-SCT using human leukocyte antigen (HLA)-identical sibling (n = 96) or HLA-compatible unrelated donors (n = 9) in a single institution. All patients received an ATG-based conditioning regimen. Results The cumulative incidence of cytomegalovirus (CMV) viremia was 45.7% (95% confidence interval [CI] 33–55%), developing at a median of 48 (range 12–142) days without evidence of overt CMV disease. Herpes zoster developed in 8 patients at a median of 12 months post transplant, while 10 patients presented with late onset hemorrhagic cystitis at a median of 35 days post transplant. The cumulative incidence of bacteremia was 17.1% (95% CI 10.6–25%), occurring at a median of 74 (range 24–110) days. No patient developed probable or definite invasive fungal infection. Four deaths were recorded; 2 of them were attributed to infections (toxoplasmosis and Pneumocystis jirovecii pneumonia, respectively). Conclusion The rate of infections after allo-SCT, using an ATG-containing preparative regimen, in our population of pediatric patients with hemoglobinopathies is comparable to that reported elsewhere with the use of non-ATG containing regimens.

ADEM is a rare inflammatory demyelinating disease of the CNS, which usually presents after a viral infection or a vaccination. We report a 15-yr-old boy who was diagnosed with ADEM after an HLA-identical sibling allogeneic BMT for transfusion-dependent PRCA. His course was complicated with GVHD affecting the skin and lungs. Five months post-BMT, he developed neurological symptoms including sudden mental status alteration, dysarthria, facial nerve palsy, and acute paraplegia. The MRI revealed multifocal hyperintense lesions mainly in the subcortical white matter of the cerebrum, the brainstem, the basal ganglia, and the thalami. CSF examination was normal. There was no laboratory evidence of infection. The typical MRI findings and an acute monophasic clinical course were consistent with the diagnosis of ADEM. Clinical and radiological improvement was observed after treatment with high-dose steroids and IVIG. Complete neurologic recovery was achieved six months after the onset of symptoms. We present a rare case of ADEM post-BMT and review of the literature.

Background: Post transplant lymphoproliferative disorder (PTLD) is a heterogeneous complication of HSCT. It comprises a spectrum of pathogenetic mechanisms and clinical manifestations. It is mostly associated with EBV infection, either as a consequence of reactivation in the post transplant period or less frequently from primary infection. WHO classification defines four major histopathologic subtypes: 1. early plasmacytic hyperplasia and infectious mononucleosis (IM)-like 2. polymorphic lesions which may be polyclonal or focally monoclonal (P-PTLD) 3. monomorphic lesions that fulfill criteria for aggressive B- or T/NL-cell neoplasm (M-PTLD) 4. classic Hodgkin-type Lymphomas (CHL-PTLD). Indistinguishable categories, such as Hodgkin-like P-or M-PTLD might represent laborious diagnostic dilemmas. In literature, PTLD occurs in less than 1% of non T-cell-depleted grafts from matched siblings compared with as high as 25% in unrelated donor (VUD) recipients. There are several risk factors such as the type of conditioning and the use of ATG, the degree of immunosuppression and complications such as concurrent infections and GvHD. Objectives: To present our experience regarding the frequency, presentation and outcome of EBV related PTLD in a paediatric population of allo-HSCT recipients with haematological malignancies, to assess the risk factors and inquire into the heterogeneity in clinical presentation and outcome. Patients-Methods: From January 2004 until December 2014, 177 allo-HSCTs for myeloid and lymphoid malignancies were performed in patients aged 3 months to 19 years. PTLD was recorded in 15 (8 male) with median age of 13.24 yrs (range 5.0-17.9yrs). 11 patients had VUD, 4 patients had an haploidentical related donor and the grafts depleted of T-cells. 12 patients had peripheral blood and 3 had bone marrow as the source of HSCs. 4 were given a fully matched graft, 6 had 1 HLA antigen or allele mismatched donors, 1 patient had a 2 HLA antigen mismatched donor and 4 had 5/10 HLA matched haploidentical donors. All except for 2 patients were EBV IgG positive and the two seronegative patients had an EBV IgG positive donor. The conditioning regimens used were Busulfan or Treosulfan based in 11 patients with the addition of a combination of Cyclophosphamide, Fludarabine, Melphalan, VP16 and ATG. The latter was administered to all patients. GvHD prophylaxis consisted of Cyclosporin A and Methotrexate. Five patients (1 male) are alive and well with a median follow up of 43.1 months (range 8.3-69.2). Results: Neutrophil and platelet engraftment occurred at a median of 20 (range 14-24) and 21 days (range 14-48) respectively. Acute GvHD (stage II-IV) was recorded in 9 patients. Serial quantitative EBV-DNA/ml was employed routinely and the median day of confirmation of a rising level above 1.0x103/ml was day +58 post transplant. Median EBV copies at diagnosis were 2.3x104/ml(range 1.3x103/ml-2.15x105/ml). EBV positivity was immediately recorded post DLI in 3 patients and reactivation occurred post subsequent DLI. Immune reconstitution had not been achieved in any patient at the time of diagnosis. Median WBC count was 4.1x109/lt (1.04X109/lt - 8.78x109/lt) and all patients had absolute lymphopenia. 9 patients had documented other viral and/or bacterial infections. 2 patients developed M-PTLD, consistent unequivocally with DLBCL, 7 patients had P-PTLD and 6 patients had IM-like PTLD with plasmacytic hyperplasia only. All had anti-CD20, two patients had additional chemotherapy. Although responsive to EBV treatment, 3 died of primary disease recurrence while PTLD failed to regress in 7 patients who died of a multitude of complications. With a median follow up of 43,1 months (range 8.3-69.2), 5 patients (1 male) are alive and well. Conclusions: Nearly all HSCT recipients are EBV infected or will be infected eventually, yet only a fraction develop EBV driven PTLD. In our population the incidence was found to be 8.47%. PTLD exhibits a spectrum of features ranging from non specific and reactive to life threatening, indistinguishable from lymphoma. Administration of ATG, the type and extend of HLA mismatch, multiple sites of disease, immune suppression and concurrent infections heighten the risk of systemic manifestation. Rising EBV loads are strongly associated with impending PTLD, which can occur even with an overall modest viral load, thus requiring prompt recognition and early intervention. Disclosures No relevant conflicts of interest to declare.

BU combined with CY, the preferred preparatory regimen for thalassemic patients, is associated with a substantial incidence of graft rejection especially in patients with advanced disease stage. This study retrospectively analyzes the outcome of 75 consecutive pediatric patients with β-thalassemia who underwent HLA-matched sibling transplantation after anti-thymocyte globulin (ATG)-containing myeloablative conditioning regimens. With a median follow-up of 9 years (range 1-15 years), the overall survival (OS) and thalassemia free survival (TFS) rates were 96% and 92%, respectively. Both the estimated TRM and the cumulative incidence of rejection/failure were 4%. The cumulative incidences of acute GVHD grade II-III and grade III were 20% and 5.3%, respectively. No patient developed acute GVHD grade IV. Only two patients developed extensive chronic GVHD. The estimated OS and TFS for patients with Class 1 and 2 disease according to Pesaro criteria were 96.3% and 94.4%, whereas for patients with Class 3 disease they were 94.1% and 88.2%, respectively. In our series, the use of myeloablative conditioning regimens, which include ATG for the transplantation of thalassemic children from matched sibling donors, resulted in excellent outcomes with very low incidences of TRM and rejection.

We report successful bone marrow transplantation in an 11-year-old male with chronic myeloid leukemia from his HLA-identical sibling selected by preimplantation HLA testing. Because collection of cord blood failed, the transplantation was performed when the donor reached the age of 19 months, and sufficient bone marrow could be harvested safely. The patient was BCR/ABL negative at the time of transplantation after complete molecular response to imatinib. Currently, 16 months post-transplantation he is well and in complete molecular remission. This report describes preimplantation HLA-genotyping to deliver a matched sibling donor for successful transplantation of a malignant disorder.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for many children with various genetic or malignant diseases. However not all children in need for HSCT have a suitable donor available. For such cases in vitro fertilization (IVF) with pre-implantation genetic diagnosis (PGD) combined with human leukocyte antigen (HLA) tissue typing has been used to select an IVF healthy and HLA-matched embryo in order to give birth to a child who may serve as a stem cell donor. We report our experience with five children transplanted from HLA-matched siblings selected after IVF and PGD in our center. Methods and Patients: The clinical protocol was approved by the center’s Institutional Research and Ethics Committee. Written informed consent was obtained from parents. Hormonal stimulation for IVF, culture techniques, PGD and HLA-typing were performed according to standard protocols. Detection of the genetic disease mutation was performed by using mini-sequencing. Embryos genotyping was performed by using multiplex polymerase chain reaction (PCR) analysis of informative polymorphic short tandem repeat (STR) markers. Healthy and HLA-identical embryos were transferred 6 days after fertilization to the uterus of the respective mothers. Confirmatory genetic testing and HLA-typing were performed during the first trimester of pregnancy by using chorionic villus sampling. Patient’s characteristics are shown in Table 1. None of our patients had an available matched sibling donor. All patients underwent myeloablative conditioning consisting of busulfan, cyclophosphamide and antithymocytic globulin. GVHD prophylaxis consisted of CyA plus Methotrexate. Stem cell graft consisted of bone marrow plus cord blood in 4 out of 5 patients, while one patient received bone marrow only. Results: All couples underwent a single cycle of IVF resulting into the generation of 78 embryos. Fourteen embryos were healthy and HLA-identical with their sibling and 10 of them were transferred to the uterus of the respective mother giving birth to a total of 6 healthy children. Results of IVF, PGD and HLA-typing are shown in more detail in Table 2. The median age of the donor at the time of HSCT was 16 months. The median total nucleated cell (TNC) concentration of cord blood grafts was 2.3x107/kg, while the median CD34+ cell was 0.47x105/kg. The median TNC and CD34 cell concentration of bone marrow grafts was 1,97x108/kg and 5,09x106/kg respectively. All patients achieved sustained engraftment of donor cells. Mild acute GVHD of the skin was observed in one out of 5 patients. As of today, with a median follow up period of 4 years, all patients are alive with complete donor chimerism, without chronic GVHD and free of disease. Conclusions: IVF and PGD/HLA typing methodology should be considered and discussed with parents in cases where no HLA-matched donor is available. The procedure can be applied only in cases requiring non-urgent HSCT, and in parents of reproductive age. | Patient | Sex | Age (years) | Disease | Previous treatments | Date of transplant | | ------- | ------ | ----------- | ----------------------------- | ----------------------------------------- | ------------------ | | 1 | Male | 4,5 | Chronic granulomatous disease | Interferon-gamma, antibiotics | 2/10/2007 | | 2 | Male | 4 | Chronic granulomatous disease | antibiotics | 1/7/2008 | | 3 | Male | 11 | Chronic myeloid leukemia | Hydroxyurea, imatinib | 21/7/2009 | | 4 | Male | 4 | Thalassemia major | RBC transfusions | 4/5/2010 | | 5 | Female | 4,5 | Diamond-Blackfan anemia | Corticosteroids, RBC transfusions | 30/4/2013 | Table 1: Patient’s characteristics | Patients | IVF (cycles) | Number of embryos after IVF | Number of healthy and HLA-identical embryos | Number of healthy and HLA-identical transferred embryos | Number of healthy and HLA-identical borned children | | -------- | ------------ | --------------------------- | ------------------------------------------- | ------------------------------------------------------- | --------------------------------------------------- | | 1 | 1 | 37 | 6 | 2 | 1 | | 2 | 1 | 11 | 2 | 2 | 1 | | 3 | 1 | 10 | 2 | 2 | 1 | | 4 | 1 | 10 | 1 | 1 | 1 | | 5 | 1 | 10 | 3 | 3 | 2 | Table 2: Results of IVF, PGD and HLA-typing Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: Treatment results for pediatric non-Hodgkin's lymphoma (NHL) continue to improve internationally. OBJECTIVE: Our goal was to evaluate patient characteristics in our series of patients with NHL and outcomes for the last 16 years (1990–2006). METHODS: Our patients included 52 newly diagnosed children (11 girls) with a median age of 8.40 years (range: 0.33–14.5 years). Histology results included B-lymphocyte NHL, T-lymphocyte NHL, and Ki-1 in 35, 12, and 5 patients, respectively. In each 5-year period, 14 (3), 17 (3), and 21 (5) patients (girls) were diagnosed, respectively. Common presenting sites were the mediastinum (16), neck area (14), and abdomen (10). Disease was at stage I, II, III, and IV in 3, 14, 23, and 7 patients, respectively. Treatment varied over time. Berlin-Frankfurt-Munich (BFM) protocols had been applied since 1995 (BFM-NHL-90), and since 1997 the BFM-NHL-95 protocol had been applied. Irradiation was given to 5 patients (2 with B-NHL, 3 with T-NHL), and autologous stem cell transplantation was performed on 4 patients, all with B-NHL (1 with central nervous system disease, 1 with residual disease at the end of treatment, and 2 at relapse). RESULTS: At this writing, 41 patients are alive; 39, 2, and 1 are in first, second, and third remission, respectively. In total, 9 have succumbed (2 died soon after admission in other hospitals as a result of acute-phase complications), and 5 patients died during the first decade of our retrospective study (with T-histology and extensive disease). The event-free survival rate is 74.4% (39 of 52 patients), and the overall survival rate is 80.9% (41 of 52 patients), for a median follow-up time of 6.1 years (range: 0.01–14.7 years) for all patients. For the 39 patients treated with the BFM-95 protocol since 1997, event-free survival and overall survival rates are 79.4% and 88.2%, respectively, for a median follow-up time of 4.8 years. CONCLUSIONS: Overall and event-free survival rates and outcome of our patients with NHL treated during the last 16 years are standing high. There has been limited use of irradiation and stem cell transplantation.

Abstract 3547 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukaemia (ALL) has been most commonly performed using a myeloablative, total body irradiation (TBI)-based preparative regimen; however, there are emerging concerns about long-term sequelae of TBI in pediatric patients. The availability of intravenous (i.v.) busulfan (Bu) prompted us to evaluate the effectiveness of i.v. Bu-based preparative regimens on pediatric patients who underwent allo-SCT for ALL. We retrospectively evaluated the outcomes of 31 children with ALL transplanted with i.v. Bu-based preparative regimens at our institution between January 2005 and May 2010. Twenty-one patients were in first complete remission (CR1), 8 in CR2, 1 in CR3, and 1 in advanced disease. The donors were HLA-matched siblings (n=9), matched unrelated (n=20), or 1-antigen mismatched related donors (n=2). The median age of the patients was 4.8 years (range, 2 months-16.7 years). Twenty patients received bone marrow, 8 peripheral blood stem cells, and 3 cord blood. Busulfan was administered as a 2 h IV infusion every 6 h over 4 days (16 administrations). Five dose levels were defined on body weight as follows: 1.0 mg/kg for 23-34 kg; 0.80 mg/kg for >34 kg. Busulfan administration was followed by Cyclophosphamide and VP-16 in 21 patients, Cyclophosphamide and Thiotepa in 6, Cyclophosphamide and Melphalan in 2 and Cyclophosphamide and Fludarabine in 2 patients. Graft versus host disease (GVHD) prophylaxis consisted of Cyclosporine A and Methotrexate in all patients transplanted with blood or marrow stem cells, while Methotrexate was omitted in those patients who underwent cord blood allo-HSCT. Anti-thymocyte globulin was added in patients transplanted from an unrelated donor. All patients but one achieved sustained engraftment. Median time to ANC>500, and platelets>20.000 was 19 days (range14-29), and 21.5 days (range 12–44) respectively. One patient died on day 10 and another patient relapsed on day 22; both were considered invaluable for engraftment. There were 6 cases of mild veno-occlusive disease, and 5 cases of hemorrhagic cystitis. Grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD (cGVHD) occurred in 15/31 and 5/31 patients, respectively. At median follow-up of 27 months, 23 patients are alive and diseases free. Four patients died of relapse and 4 died of transplant-related mortality (TRM). The overall survival (OS) rate, relapse rate, and TRM rate were 67 %, 24%, and 10%, respectively. These results are comparable to those reported with TBI-based preparative regimens and suggest that it is time to re-evaluate the use of TBI in ALL patients. Disclosures: No relevant conflicts of interest to declare.

In this article we analyse how knowledge is generated in the design field of knowledge-based urban development (KBUD). Planners and urban designers, governments on various levels, or construction industry are dealing with complex urban realities in which places, discourses, but also specific spatio-temporal dynamics of economic, juridical and political systems come together. We approach the issue of planning by studying decision-making within juries of design competitions. Here knowledge is produced between actors from different professional and economic backgrounds, between global discourses and local specificities. In order to trace how knowledge creation takes place in decision-making – between various and heterogeneous types of knowledge, between global tendencies for innovation and local prerequisites and settings – we apply Amin and Roberts' concept of 'knowing in action'. We will elaborate on this model using ethnographic data on the work of a jury board in a design competition. As a result we prop...

Acute myeloid leukemia (AML) accounting for approximately 17% of all childhood acute leukemias, arises either de novo or from a backround of myelodysplasia or previous chemotherapy. Cytogenetics is considered one of the most valuable prognostic determinants in AML while current risk–group classification in the limited cases of pediatric AML, is mainly based on cytogenetics and early treatment response. We reviewed the clinical and cytogenetic characteristics and the outcomes of 33 cases of childhood AML between 1997 and 2007 in order to investigate the incidence of the main FAB subtypes, the incidence of primary AML compared to secondary AML (s-AML) and the correlation between specific chromosome abnormalities and outcome in greek pediatric AML patients. Chromosome studies were performed on unstimulated bone marrow cells, derived from 33 pediatric AML patients, who were

Clinical patient observations led to the hypothesis of increased ALL blast resistance in hyperglycemia (HG) states in pediatric ALL patients, either with preexisting diabetes mellitus (DM) or with steroid induced diabetes (SID). To evaluate the above, the chromometric MTT (methyl thiazole tetrazolium) assay was used Kaspers GJ et al, Leuk Res1995;19:175–81.Ficoll separated nucleated bone marrow cells from newly diagnosed pediatric ALL patients were cultured in usual conditions (NL) and in higher glucose levels (233–295 mg/dl), with the addition of titrated prednisolone (PDN) concentrations. The PDN concentration that lyses 50 % of the cultured blast cells (LD50) is the measure of PDN drug sensitivity. PDN concentrations of 0.02–2.0, 2.1–150, above 150 μg/uL indicate high, intermediate and low blast sensitivity to PDN, respectively. Hence, patient blasts with LD50 at >150 μg/uL are resistant to PDN. The MTT assay results have been related to patient outcome (remission induction and event free survival, Pieters R et al Pediatr Oncol1994;22:299–308). Twelve newly diagnosed pediatric patients, with median age 6.4 years (range, 1.7 to 16.5 years) with common/CD10+ (N=8), pre-B (N=2), early pro-B (N=1) and maturing B (N=1) ALL were studied. All patients exhibited >80% ALL blast BM infiltration. Sensitivity (LD50 < 150 μg/uL) in both NL and HG conditions was evident for 2 patients, while resistance to both conditions was seen in 3 patients. Patients resistant at NL conditions were resistant in HG, too. In contrast, 7 of 12 patients sensitive to PDN in NL conditions proved resistant in HG conditions (glucose 233–295 mg/dL). All 9 sensitive in NL conditions patients (in HG conditions 2 sensitive and 7 resistant) exhibited a median ×800 fold increase of the MTT LD50 measured (range 6–29.000 fold). For all patients (N=12) median MTT LD50 under NL conditions was 0.15 μg/uL and in HG conditions 167.5 μg/uL (× 116.6 fold increase). This change was statistically significant (Mc Nemar’s test, p=0,016) and this change was not simply related to the change in glucose concentration. These findings of greatly increased ALL blast resistance in hyperglycemia environment, can support the notions given earlier (Weiser MA et al, Cancer2004;100:1179–85, Pieter’s R EHA 2008) that hyperglycemia by itself can promote PDN resistance. Given that steroids is a mainstay in ALL treatment and that steroid induced hyperglycemia is a common occurrence, blood glucose monitoring and hyperglycemia correction appears to be of paramount significance in delivering an effective ALL treatment.

Aim: The aim of this study was the prospective evaluation of MRD during childhood ALL therapy and its correlation with specific prognostic criteria of ALL-BFM 95 protocol and with patient outcome. Patients/Methods: 127 children (49 girls) with ALL were studied during the period 1999–2008. The median age at diagnosis was 9,32 years (range, 0,6–16,48). All patients were diagnosed in the same center and treated uniformly with the ALL-BFM 95 protocol, modified in two therapeutic branches, medium and high risk, as we have published previously. We used three or five colours’ flow cytometric panels for MRD quantification at sequential standardized treatment time-points: at day 15 of induction (T1), at day 33 (T2) of induction, before consolidation (T3), before re-induction (T4), before maintenance (T5), at maintenance completion (T6). Additionally for the high risk patients, 6 more determinations before each consolidation treatment cycle were performed. The median follow-up time was 48,4 months (range, 1,7–110,3). For statistical analysis, descriptive statistics and Kaplan-Meier were used. Results: Immunophenotypical analysis resulted in 119 patients with ALL of B-origin and 8 of T-origin. Median WBC at diagnosis was 10×109/lt, while extra-BM infiltration was found in 9 children. According to ALL-BFM 95 protocol’s criteria: 40 patients were fulfilling the criteria of the standard risk (SR), 61 of medium (MR) and 26 of high risk (HR), respectively, and therapeutically were divided into two groups: A (101 patients, SR+MR) and B (26 patients, HR). MRD was detected in: 59/123 patients at treatment time-point (T1) (39/59 from group A, of which 26/39 with high MRD levels, and 20/59 from group B, all with high MRD levels). In time-point (T2), disease was detected in 19/124: 5/19 from group A (3/5 high MRD levels), 14/19 from group B (11/14 high MRD levels). At treatment-point (T3), 3/127 had detectable disease (all from group B). None of the patients of group A had minimal residual disease at the following time-points, while only 2 patients of group B had persistent presence of MRD. In total, 14/127 children relapsed (4/SR, 2/MR, 8/HR), with significant levels of MRD in 7 (6/7 HR) and 4 (all HR) patients, at time-point (T1) and (T2), respectively. Among all, 114 children survived (CR1: 110, CR2: 4), while 13 children died (9/disease, 4/therapy-related toxicity). Conclusions: Our results suggest that MRD detection in continuous standardized treatment time-points of childhood ALL correlates with shorter disease free (DFS) and overall survival (OS), however in our cohort there was no sufficient evidence of MRD independency as prognostic factor (cox-regression analysis) compared to the classical prognostic criteria of the ALL-BFM 95. The enlargement of the group of patients and the expansion of the follow-up period will lead to more reliable conclusions.

INTRODUCTION: Although prevention remains the cornerstone for the management of thalassemia, hematopoietic stem cell transplantation (HSCT) is the only curative approach. OBJECTIVE: Our goal was to assess our experience with HSCTs for the treatment of patients with thalassemia. METHODS: From 1994 to 2006, 96 HSCTs have been performed in 84 thalassemic children from Greece, 3 with sickle cell/thalassemia and 1 with sickle cell disease. According to Pesaro classification, of these 84 children, 20 were in class I, 35 were in class II, and 29 were in class III. Donors were 84 histocompatible siblings and 4 unrelated volunteers. The graft was of bone marrow in 85, cord blood in 3, bone marrow and cord blood in 4, and peripheral blood stem cells in 4. The conditioning regimen consisted of busulfan, cyclophosphamide, and antilymphocyte globulin. RESULTS: All except 1 patient received engraftments. Ten patients rejected the graft. Eight received another transplant from the same donor, 7 of which were successful. Four patients died; causes of death were graft-versus-host disease (GVHD) (2), disseminated toxoplasmosis (1), and brain hemorrhage (1). At a median follow-up time of 6.5 years, 84 of 88 children survived, 81 were cured and free from transfusions, and 3 remained transfusion-dependent. Severe acute GVHD developed in 18 children, and chronic GVHD developed in 8 patients. The overall survival rate, event-free survival rate, rejection rate, and transplant-related mortality rate were 95%, 94%, 11%, and 5%, respectively. Event-free survival was 100% for class I, 95% for class II, and 87% for class III. Eleven children had mixed chimera (residual recipient hematopoiesis) with normal levels of hemoglobin. CONCLUSIONS: HSCT is a highly effective treatment for thalassemic patients who have a fully matched donor (related or unrelated). Younger age at transplant secures excellent results with reduced morbidity and mortality rates.

The extensive use of etoposide has been implicated in the development of secondary acute myelogenous leukemia (AML) with unfavorable prognostic characteristics and most often involvement of the 11q23 locus. The case herein being presented exhibits favorable characteristics and poses the question whether it represents a secondary malignancy or a second primary event. A five year old boy was diagnosed with a mass of the posterior fossa representing anaplastic ependymoma of the brain stem (medulla oblongata) without CNS nor distant metastases. After partial resection of the tumor, the patient received 53 Gy to the tumor bed and 30 Gy to the neuroaxis followed by temozolamide p.o. for 4 cycles. Following this treatment, symptoms improved, he was ambulatory and back to school. Two years later he relapsed with unresectable tumor and received etoposide (VP-16) at 100 mg/m2/day for 21 days of 28 cycles, with a palliative intent. The treatment proved efficacious to him and he continued to receive VP-16 for 3 years in total. Six years after initial diagnosis and 3 years on VP-16, he developed ecchymoses, with thrombocytopenia (PLT: 15 k/uL) and leukocytosis (WBC: 25.8 k/uL). Bone marrow evaluation revealed infiltration with AML M2 blasts (>80%), MPO+ (93%), CD 34+ (58%), CD15+ (19%), CD71+ (33%), CD38+ (87%), CD33+ (47%) and CD123+ (52%), karyotype with detection of t(8;21). Bone marrow RT-PCR confirmed the presence of AML1-ETO hybrid gene, the absence of the MLL-AF4 product, and the absence of 11q23 involvement. Results were also confirmed by FISH technique. The patient was started on chemotherapy according to the AML-BFM 98 protocol. Disease remission was rapidly achieved (day +15 BM with no blasts) and treatment schedule was prompt, for the first 4 months of treatment. Severe, long-lasting marrow aplasia followed and pulmonary Aspergillosis was evident (compatible findings on CT and detection of Aspergillus specific proteins in the plasma by PCR), requiring assisted ventilation. However the patient succumbed 5 months following the diagnosis of AML. Childhood ependymomas have a dismal prognosis despite intensive treatment. This child exhibited a similarly good treatment response either to the ependymoma or to the later evolved AML. This AML1-ETO positive AML either representing a second primary malignancy or a rare type of secondary, therapy induced leukemia, is not a common and well described event and it certainly did not present, in our case, the usual dismal course of a secondary AML. Of importance our patient achieved and remained in remission with minimal treatment, for over 5 months, verifying the good prognosis of AML1-ETO positive AML either as a primary or a secondary event.