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•The major cause of death in patients with ataxia-telangiectasia and hematological malignancies is treatment-related toxicity.•The germ line ATMpathogenic variant functional class is a robust outcome predictor, which can be applied to therapy stratification.

Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of TP53mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.

Introduction Quality of life in childhood cancer survivors is largely affected by survivorship care and transition from treatment to long-term follow-up (LTFU). Referring to evidence-based recommendations, we wanted to evaluate LTFU care for survivors through a survey among the Italian Association for Pediatric Hematology-Oncology (AIEOP) centers. The project aimed to evaluate the availability of services in Italy, investigate strengths and weaknesses, analyze improvements of awareness in the field, and identify the gaps that need to be addressed by different centers.Methods Together with the family representatives, on behalf of AIEOP’s Late Effects Working Group, we developed a questionnaire on assisting childhood cancer survivors. All AIEOP centers received one questionnaire including information on local health system organizations; LTFU for childhood cancer survivors; services for adult survivors of childhood cancer; information provided to survivors/caregivers and care plan delivery.Results Forty-eight AIEOP centers were contacted and 42 replied, with a response rate of 87.5%. The majority of respondents confirmed their interest in assisting patients with a survivorship care plan (95.2%), regardless of a clinic or dedicated staff.Discussion This is the first overview of LTFU in Italy, which provides detailed results at national levels, prompting consideration of improvements in the last decade. Although there is a high level of interest in survivorship care, many centers lack resources to implement such programs. The identification of these challenges is useful for planning future strategies.

Survival of children and adolescents with high-risk, mature B-cell non-Hodgkin lymphoma is improved by the addition of rituximab to chemotherapy. The effect of rituximab on immune reconstitution after therapy has not been well described. Herein, we evaluate the immune effects of the addition of rituximab to intensive chemotherapy, a prespecified secondary aim of the Inter-B-NHL Ritux 2010 trial.

The European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) was established 25 years ago with the goal to facilitate clinical trials and research collaborations in the field both within Europe and worldwide. Since its inception, much progress has been made whereby major improvements in outcomes have been achieved. In this Review, we describe the different diagnostic entities of non-Hodgkin lymphoma in children and young adults describing key features of each entity and outlining clinical achievements made in the context of the EICNHL framework. Furthermore, we provide an overview of advances in biopathology with an emphasis on the role of biological studies and how they have shaped available treatments. Finally, for each entity, we describe future goals, upcoming clinical trials, and highlight areas of research that require our focus going forward.

Rituximab (RTX) is widely employed to treat Epstein-Barr virus reactivation in children undergoing Hematopoietic Cell Transplantation (HCT). The resulting loss of B cells may cause persistent hypogammaglobulinemia. This retrospective cross-sectional study aims to identify flow cytometry biomarkers associated with persistent hypogammaglobulinemia in patients receiving RTX after HCT. We analyzed 5 patients (cases group) requiring immunoglobulin substitution due to low level of IgG (IgG <5 g/L) detected after RTX treatment and 5 patients (controls group) not requiring long-term immunoglobulin (Ig) substitution. We investigated the B cell reconstitution, and in patients group we observed a significantly lower count in B total, IgD+CD27+ marginal B cells and IgD-CD27+ switched-memory B cells, after a median of 5 years from HCT, compared with the control group. Despite the importance limits of our study and the heterogeneity of our data (age of included patients, time of evaluation, interval between RTX dose and assessment) we conclude that RTX given early after HCT might cause a deranged B cell maturation, contributing to the delation in B cell recovery following HCT, and switched memory and marginal zone B cell counts could be a promising biomarker to identify patients requiring long-term Ig substitution.

Data on the spectrum of second malignant neoplasms (SMNs) after primary childhood non-Hodgkin’s lymphoma (NHL) are scarce. One-hundred-and-eighty-nine NHL patients diagnosed in a 30 years period of 1980–2010 developing an SMN were retrieved from 19 members of the European Intergroup for Childhood NHL and/or the international Berlin-Frankfurt-Münster Study Group. Five subgroups of SMNs were identified: (1) myeloid neoplasms (n?=?43; 23%), (2) lymphoid neoplasms (n?=?51; 27%), (3) carcinomas (n?=?48; 25%), (4) central nervous system (CNS) tumors (n?=?19; 10%), and (5) “other” SMNs (n?=?28; 15%). In 37 patients (20%) preexisting disorders were reported with 90% having any kind of cancer predisposition syndrome (CPS). For the 189 primary NHL patients, 5-year overall survival (OS) after diagnosis of an SMN was 56?±?4%, being worst for patients with preexisting disorders at 28?±?8%. Five-year OS rates were 38?±?8%, 59?±?7%, 79?±?8%, 34?±?12%, and 62?±?11%, respectively, for patients with myeloid and lymphoid neoplasms, carcinomas, CNS tumors, and “other” SMNs (p?

Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P < .001), lower severity of neutropenia (P = .03), leukopenia (P < .001), lymphopenia (P < .001) with low B+ (P = .001), increased need of granulocyte colony-stimulating factor (P = .04), and increased frequency of autoimmunity over the disease course (P < .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P < .001) and lower white blood cell (P < .001) and lymphocyte (P < .001) values, higher occurrence of apthae (P = .008), and a stronger association with autoimmune diseases/markers (P = .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease.

Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P< .001), lower severity of neutropenia (P= .03), leukopenia (P< .001), lymphopenia (P< .001) with low B+ (P= .001), increased need of granulocyte colony-stimulating factor (P= .04), and increased frequency of autoimmunity over the disease course (P< .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P< .001) and lower white blood cell (P< .001) and lymphocyte (P< .001) values, higher occurrence of apthae (P= .008), and a stronger association with autoimmune diseases/markers (P= .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative procedure in patients with Shwachman–Diamond syndrome (SDS) with bone marrow abnormalities. The results of 74 patients with SDS (6 acute myeloid leukemia, 7 myelodysplastic syndrome, and 61 bone marrow failure) treated with HSCT between 1988 and 2016 are reported. The donor source was: 24% sibling, 8% parent, and 68% unrelated donor. The stem cell source was: 70% bone marrow, 19% peripheral blood stem cells, and 11% cord blood. The conditioning regimen was myeloablative in 54% and reduced intensity in 46%. Neutrophil engraftment was achieved in 84% of patients after a median time of 17.5 days. Graft failure occurred in 15% of HSCTs. Grades I–IV acute and chronic GVHD were observed in 55% and 20% of patients, respectively. After a median follow-up of 7.3 years (95% CI 4.8–10.2), 28 patients died for progression/relapse (7) or toxicity (21). The 5-year overall survival and nonrelapse mortality were 63.3% (95% CI 50.8–73.4) and 19.8% (95% CI 10.8–30.8), respectively. In conclusion, this is the largest series so far reported and confirms that HSCT is a suitable option for patients with SDS. Further efforts are needed to lower transplant-related toxicity and reduce graft failure.

•Children with PCNSL and no immunodeficiency have a good outcome when treated by a histological subtype–driven and radiation-free protocol.•New treatment guidelines are needed for PCNSL in children and adolescents with an underlying immunodeficiency.

IntroductionAtaxia telangiectasia (A-T) is a multisystem disorder caused by biallelic germline pathogenic variants (PV) in the ATM gene. An important feature of A-T is an increased predisposition to cancer with a reported incidence of 25%, primarily attributed to hematological malignancies. Patients with A-T and cancer are usually excluded from therapeutic clinical trials, limited information thus exists concerning their treatment outcomes and toxicity profiles and consequently, optimal management strategies are unclear and an unmet need. In this multinational study, we aimed to investigate the characteristics and outcomes of leukemia and lymphoma in a large cohort of children with A-T and to determine risk factors which impact treatment outcome in order to generate consensus and data-based prospective treatment recommendations.

BACKGROUND

Diffuse large B-cell Lymphoma (DLBCL) secondary to a chronic severe Epstein-Barr virus (EBV) infection has not been previously described in a patient with trisomy 21. Here we report the case of a 14-year-old girl with trisomy 21 with impaired control of EBV and DLBCL. She was cured with dose-adapted chemotherapy and hematopoietic stem cell transplantation without severe treatment-related toxicity. We describe the first case of EBV-positive DLBCL in a patient with trisomy 21 and we propose a treatment modality for this rare entity.

Anaplastic large cell lymphoma (ALCL) accounts for approximately 15 of all pediatric non-Hodgkin lymphomas. It has distinct clinical features, including frequent involvement of extranodal sites and rare localization to the central nervous system. As some presenting features of ALCL are in common with the hemophagocytic syndrome, we previously analyzed a small series of patients with ALCL for PRF1mutations and found that 27 of them carried mutations. We now expanded our preliminary study by increasing the cohort of ALCL patients to a total of 84 consecutive cases, in whom we extended mutation analysis to the genes SH2D1A, PRF1 e UNC13D, all related to familial HLH. Furthermore, perforin expression in tumor cells was investigated on paraffin-embedded tissues by immunohistochemical analysis. Mutations were observed in 2384 patients (27.4). Twenty-one patients (25) carried a total of 10 different mutations of PRF1; they were monoallelic in 20 patients, biallelic in 1. No mutations were found in the gene SH2D1A. Two additional patients had missense mutations of the UNC13Dgene. These data show that monoallelic germline mutations of PRF1are frequent in patients with childhood ALCL, suggesting that partially impaired cytotoxic machinery may represent a predisposing factor for ALCL. Involvement is less frequent for UNC13Dand absent for SH2D1A.

Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALK during treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK–positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALK transcripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P < .001). Five-year survival of MDD-negative and MDD-positive/MRD-negative patients was 91% ± 3% and 92% ± 5%, respectively, compared with 65% ± 9% of MDD-positive/MRD-positive patients (P < .001). Early evaluation of MRD in NPM-ALK–positive ALCL identifies patients with a very high relapse risk and inferior survival.

Detection of minimal disseminated disease (MDD) at diagnosis correlates with relapse risk in children with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL). We investigated whether minimal residual disease (MRD) positivity by qualitative reverse-transcriptase polymerase chain reaction (RT-PCR) for Nucleophosmin (NPM)-ALKduring treatment identifies patients at the highest relapse risk. Blood and/or bone marrow of 180 patients with NPM-ALK–positive ALCL treated with Berlin-Frankfurt-Münster-type protocols were screened for NPM-ALKtranscripts at diagnosis; 103 were found to be MDD-positive. MRD before the second therapy course could be evaluated in 52 MDD-positive patients. MRD positivity correlated with uncommon histology. The cumulative incidence of relapses (CIR) of 26 MDD-positive/MRD-positive patients (81% ± 8%) was significantly higher than the CIR of 26 MDD-positive/MRD-negative (31% ± 9%) and 77 MDD-negative patients (15% ± 5%) (P< .001). Five-year survival of MDD-negative and MDD-positive/MRD-negative patients was 91% ± 3% and 92% ± 5%, respectively, compared with 65% ± 9% of MDD-positive/MRD-positive patients (P< .001). Early evaluation of MRD in NPM-ALK–positive ALCL identifies patients with a very high relapse risk and inferior survival.

Temporal bone squamous cell carcinoma (SCC) accounts for less than 0.2 of all head and neck tumors. Although some progress has been made in treating this aggressive tumor, the prognosis in advanced cases remains poor. More effective therapeutic strategies need to be considered, including receptor-mediated carcinoma-targeted therapy. Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti-apoptosis, invasion, angiogenesis, and immune surveillance evasion. The aim of the present study was to preliminarily investigate the potential prognostic role of pSTAT3 expression in temporal bone SCC.

Several studies proved that virus-specific T-cells play a pivotal role in controlling cytomegalovirus (CMV) infection in adult allogeneic hematopoietic stem-cell transplant (HSCT) patients. Fewer data are available in pediatric HSCT settings, when immature and inexperienced immune system may affect antiviral immune reconstitution.

Posttransplant lymphoproliferative disease caused by Epstein-Barr virus (EBV-PTLD) is a severe complication after allogeneic hematopoietic stem-cell transplantation (HSCT). We evaluated whether the modulation of immunosuppression (IS) guided by quantitative polymerase chain reaction for EBV (EBV-PCR) was effective as a first-line therapeutic approach for EBV reactivation.

Childhood anaplastic large cell lymphoma (ALCL) is a well defined entity with a rather poor prognosis. Different approaches have been adopted in the treatment of ALCL in various cooperative trials, including short high‐dose intensive therapy and leukemia‐like protocols. In the early 1990s, the Italian Association of Pediatric Hematology and Oncology (AIEOP) initiated a multicenter trial for the treatment of ALCL based on a modified LSA2‐L2 protocol.Thirty‐four consecutive eligible children with newly diagnosed ALCL were enrolled in the AIEOP LNH‐92 protocol. Treatment was comprised of an induction of remission phase, followed by consolidation and maintenance for a total duration of 24 months, independently of disease stage.Thirty of 34 patients (88%) achieved complete disease remission and 8 patients experienced disease recurrence. With a median follow‐up of 8.4 years, the probabilities of survival and event‐free survival were 85% (range, 79–91%) and 65% (range, 57–73%), respectively. Therapy was well tolerated and hematologic toxicity was the most frequent toxicity.The leukemia‐like protocol AIEOP LNH‐92 was found to be an effective treatment for childhood ALCL. Its long duration may be beneficial to specific patient subgroups, but optimal treatment duration in ALCL remains to be elucidated. Cancer 2005. © 2005 American Cancer Society.

Abstract

To evaluate the effect of chemotherapy on humoral immunity to vaccine‐preventable disease, the authors investigated the persistence of protective antibody titers in a group of patients who were alive and well after they were treated for pediatric malignancies.Serum antibody levels were evaluated for polio, tetanus, hepatitis B, rubella, mumps, and measles in 192 children. The terms lack of immunity and loss of immunity, respectively, were used to describe the absence of immunity in patients who were tested only after chemotherapy and in patients who were tested both before and after chemotherapy and determined to have immunity before chemotherapy.Overall, the absence of a protective serum antibody titer for hepatitis B, measles, mumps, rubella, tetanus, and polio was detected in 46%, 25%, 26%, 24%, 14%, and 7% of patients, respectively. On univariate analysis, loss of antibodies against rubella, mumps, and tetanus was associated significantly with younger age (P < 0.001, P = 0.02, and P = 0.001, respectively), and loss of antibodies against measles was significantly associated with younger age and female gender (P = 0.0003 and P = 0.008, respectively). The administration of 59 booster vaccinations to 51 patients who had lost ≥ 1 protective antibody titer resulted in an overall response rate of 93%.Chemotherapy induced different rates of loss of protective antibody titers depending on the type of vaccination administered. This finding may be responsible for the failure of vaccination programs for patients who have undergone chemotherapy. The administration of a booster dose after the completion of chemotherapy is a simple and cost‐effective way to restore humoral immunity against most vaccine‐preventable diseases. Cancer 2004. © 2004 American Cancer Society.

Childhood B‐cell lymphomas (B‐NHLs) represent a group of aggressive malignancies that are amenable to high‐intensity chemotherapy regimens. In 1992, the Italian Association of Pediatric Hematology and Oncology (AIEOP) initiated a prospective clinical trial involving the diagnosis and treatment of childhood B‐NHL based on a well established strategy developed by the Berlin–Frankfurt–Munster Group.Between November 1992 and October 1997, 163 children who had B‐NHL were treated prospectively in the first national AIEOP trial. Disease staging was performed according to the St. Jude staging system, and treatment was assigned on the basis of risk group (R1, R2, or R3), which took into account disease stage and resectability and serum lactate dehydrogenase (LDH) levels.Of the 144 evaluable patients, 11 had Stage I disease, 35 had Stage II disease, 76 had Stage III disease, and 22 had Stage IV disease. Thirteen, 54, and 77 patients were included in risk groups R1, R2, and R3, respectively. The 10‐year overall survival (OS) and event‐free survival (EFS) rates for the overall population were 89.4% and 81.8%, respectively; the EFS rates for patients in risk groups R1, R2, and R3 were 100%, 86.9%, and 75.1%, respectively. Multivariate analysis indicated that age ≥ 10 years, disease histology other than Burkitt or Burkitt‐like lymphoma, and LDH levels ≥ 1000 international units per liter had negative prognostic value. Analysis of the toxicity (according to the World Health Organization grading system) associated with 710 of the 748 chemotherapy cycles administered revealed 855 cases of Grade 3 or 4 toxicity, with 73% being cases of hematologic toxicity. Toxic episodes were most common after the first chemotherapy cycle and were equally common in the R2 and R3 risk groups. To date, the development of a second malignancy has not been observed in any patient in the study cohort.Long‐term follow‐up of the current study (AIEOP LNH92) confirms the observation of a favorable outcome for patients with B‐NHL treated with short, intensive chemotherapy regimens and raises the possibility that non‐Burkitt or non‐Burkitt‐like histology and age ≥ 10 years may have negative prognostic value for patients with childhood B‐NHL. Cancer 2004. © 2004 American Cancer Society.

Voriconazole is a new triazole active orally and parenterally that recently proved effective in the treatment of invasive aspergillosis and in empirical antifungal therapy for persistently febrile neutropenic patients. Limited data are available for pediatric patients. We report our experience with voriconazole in seven children with invasive aspergillosis, i.e., four girls and three boys with a median age of 5 (range 2–13) years affected by acute lymphoblastic leukemia (3), acute myeloid leukemia (2), refractory anemia with excess of blasts (1), and severe aplastic anemia (1). First-line therapy in all patients was liposomal amphotericin B (AmBisome) administered at a dosage of 3–5 mg/kg day. Voriconazole was administered for a median 8 (range 2–15) weeks. Response was complete and partial in two patients, respectively, stable in one, and there was no response (failure) in two. The voriconazole treatment was well tolerated. Four patients died—two of progressive aspergillosis. Three patients are alive and well 6, 5, and 4 months after the diagnosis of aspergillosis. Voriconazole appears to be an effective salvage treatment for invasive aspergillosis in pediatric patients, with good responses in patients who recover from neutropenia or are not relapsing.

Diencephalic syndrome (DS) is a complex of signs and symptoms related to hypothalamic dysfunction; its main features are emaciation, despite a normal or slightly diminished caloric intake, and an alert appearance. DS has been almost exclusively described in association with space-occupying lesions of the hypothalamic-optic chiasm region, mainly juvenile pilocytic astrocytoma (JPA). A systematic diagnostic approach, including contrast-enhanced magnetic resonance imaging (MRI) of the child's head, is rapidly expanding our knowledge of this syndrome. The MRI findings for three children affected by DS associated with biopsy-proven JPA, consecutively referred to the Pediatric Neuro-Oncology Program of the Department of Pediatrics at the University of Padua between September 1991 and January 1996, are presented in this article. The children were boys, ages 6, 7, and 18 months, respectively. In all three patients, the initial contrast-enhancing MRIs of the head showed evidence of tumor dissemination. This finding prompted a study of the spine, which in turn showed tumor deposits in all three subjects. Among the 43 patients younger than 16 years with low grade astroctyoma who consecutively entered the Neuro-Oncology Program during the study period, these 3 patients were the only ones who had disseminated tumors. In this study, the hypothesis was formulated that DS and disseminated hypothalamic-optic chiasm JPA tend to be more commonly associated than previously stated. This study suggests that the initial contrast-enhanced MRI of the head of a child affected by DS and hypothalamic JPA must be looked at carefully for evidence of tumor dissemination, and that the spine must also be examined if the findings are positive. Cancer 1997; 80:142-6. ©; 1997 American Cancer Society.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

This particular case highlights the importance of a multidisciplinary team expertise in the differential diagnostic process of acute abdominal pain. The case involves a 10-year old Chinese boy who presented with intermittent abdominal pain; the clinical and radiologic picture narrowed the differential diagnosis between an acute appendicitis and an intestinal lymphoma. Diagnosis of a high grade - B lymphoma was made by performing a colonoscopy; this procedure was deemed the best option to obtain a quick diagnosis with low invasiveness.

No relevant conflicts of interest to declare.

BackgroundAutoimmune neutropenia is a chronic reduction of absolute neutrophil below the threshold for age, due to peripheral destruction by specific antibodies (AaN). “Primary autoimmune neutropenia” (pAN) usually appears in early infancy and generally resolve within 18-24 months, while “Secondary autoimmune Neutropenia” (sAN) rises later in life and is usually accompanied by autoimmune features. Very few descriptions on the topic are available in the literature. Aim of the study:to describe from a clinical and immunological point of view a cohort of subjects affected with sAN included registered in the Italian Neutropenia Registry (INR) and to compare these data with those from subjects diagnosed with pAN still in the INR .

Background

INTRODUCTION:

Bader: Servier: Consultancy, Honoraria; Neovii Biotech: Research Funding; Riemser: Research Funding; Medac: Consultancy, Research Funding; Novartis: Consultancy, Honoraria.

No relevant conflicts of interest to declare.

Introduction: Fertility preservation is crucial in the setting of hematopoietic stem cell transplantation (HSCT) due to the severe impact of infertility on quality of life in long term survivors. Many chemotherapy agents as well as CNS or pelvic irradiation can affect gonads leading to impairment of pubertal development and/or infertility. In the last years different fertility preservation guidelines especially for cancer patients have been published. Despite these recommendations options for fertility preservation are not well established in children, it's discussed only in about 42% (Terenziani et al. PBC 2014)of all eligible patients. We present here a survey conducted by the Pediatric WP of the EBMT.

Background:No stratification criteria have been established so far for treatment of childhood lymphoblastic T-cell lymphoma (T-LBL). Probability of event-free survival is about 75%, however survival in relapsed patients is very poor. Activating NOTCH1mutations were reported to be associated with favorable prognosis and it has been demonstrated that in T-cell acute lymphoblastic leukemia miR-223 up-regulates NOTCH1 through negative modulation of FBXW7. We recently identified a miRNA expression profile specific for pediatric T-LBL [Mussolin et al, Leukemia 2014], suggesting that few miRNAs, including miR-223, may play a major role in T-LBL pathogenesis. The prognostic relevance of miR-223 and its correlation with NOTCH1/FBXW7 mutational status and protein expression is still unknown in T-LBL.

No relevant conflicts of interest to declare.

No relevant conflicts of interest to declare.

Introduction. Hypofibrinogenemia and its correlation with hemorrhagic risk is usually detected by serum fibrinogen level with Clauss test. Recently the role FIBTEM test of rotational thromboelastometry (ROTEM) has been evaluated for prevention and management of acute bleeding in intesive care and surgical settings. We applied it for monitoring fibrinogen deficiency for the first time in children affected by acute lymphoblastic leukemia (ALL) treated with Peg-asparaginase (PEG-Asp). Antithrombin levels (AT) were measured as parameter for thrombotic risk. This drug impairs protein synthesis and causes severe coagulative deficiencies, with both hemorrhagic and thrombotic complications. Guidelines for the management of coagulation abnormalities being missing, we tried to identify parameters for management and prevention.