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Several guidelines have been published about management of chronic GvHD (cGvHD), but the clinical practice still remains demanding. The Gruppo Italiano Trapianto di Midollo Osseo (GITMO) has planned a prospective observational study on cGvHD, supported by a dedicated software, including the updated recommendations. In view of this study, two surveys have been conducted, focusing the management of cGvHD and ancillary therapy in cGvHD, to address the current ‘real life’ situation. The two surveys were sent to all 57 GITMO centers, performing allografting in Italy; the response rate was 57% and 66% of the interviewed centers, respectively. The first survey showed a great disparity especially regarding steroid-refractory cGvHD, although extracorporeal photo-apheresis resulted as the most indicated treatment in this setting. Another challenging issue was the strategy for tapering steroid: our survey showed a great variance, and this disagreement could be a real bias in evaluating outcomes in prospective studies. As for the second survey, the results suggest that the ancillary treatments are not standardized in many centers. All responding centers reported a strong need to standardize management of cGvHD and to participate in prospective trials. Before starting observational and/or interventional studies, a detailed knowledge of current practice should be encouraged.

Chemotherapy and irradiation can affect the gonads, leading to impairment of pubertal development and/or infertility. Fertility preservation (FP) is therefore a crucial endeavor in hematopoietic stem cell transplantation (HSCT) because of the severe impact of infertility on the quality of life of long-term survivors. Despite the existence of different international guidelines, FP counseling and procedures are not routinely implemented as part of patient care. We present herein a survey conducted by the Pediatric Working Party of the European Society for Blood and Marrow Transplantation (EBMT), which aims to analyze and compare different FP practices for children and adolescents across EBMT centers in 2013. A total of 177 pediatric centers reporting to the EBMT were contacted; of this number, 38 centers (21%) located in 16 different countries responded. These centers reported 834 patients receiving HSCT in 2013 (73% prepubertal), corresponding to 22% of all children (n=3789) undergoing HSCT in EBMT reporting centers. Overall, 39% of the reported patients received counseling and 29% received an FP procedure. The increased need for FP programs, extended education for patient-care teams, and more personal resources and funding emerged from this survey as pivotal factors necessary to support and implement such programs.

Younger children are considered to be more vulnerable to late effects (LE), which prompted us to study LE in patients after haematopoietic stem cell transplantation (HSCT) for a haematological malignancy before the age of 3. In this multicentre EBMT study, cumulative incidence (CI) and severity of endocrine LE, central nervous system complications and secondary malignancies at 5, 10, 15 and 20 years of follow-up were assessed. Risk factors (RF) like gender, diagnosis, age at and year of HSCT, TBI- or chemo-conditioning and GVHD were analysed. CI of any LE was 0.30, 0.52, 0.66 and 0.72 at 5, 10, 15 and 20 years after HSCT, respectively. In 25% of the patients, LE were severe at a median follow-up of 10.4 years. In multivariate analysis, only TBI was a RF for having any LE and for thyroid dysfunction and growth disturbance. Female gender was a RF for delayed pubertal development. Some more insight could be gained by descriptive analysis regarding the role of TBI and GVHD on the severity of LE. Although only five selected LE have been studied and median follow-up is relatively short, the incidence and severity of these LE are considerable but not different from what has been found in older children and TBI is the main RF.

Hemolymphoproliferative diseases (HLD) are among the most common causes of morbidity and mortality in children. In the past few years, the increased effectiveness of treatment modalities has significantly increased overall survival, but has also disclosed new aspects of the natural history of these disorders, among which central nervous system (CNS) involvement. CNS complications of HLD can basically be categorized into direct localization of primary disease, indirect effects of malignancy such as cerebrovascular or infectious complications, and iatrogenic side effects. Magnetic resonance imaging plays an important, often crucial role in the diagnosis of several of these disorders. Close interdisciplinary collaboration between hemato-oncologists and neuroradiologists is of paramount importance to provide affected children with an early diagnosis and proper treatment.

To describe and evaluate the incidence and risk factors of severe neurologic events (SNE) in pediatric recipients of allogeneic or autologous hematopoietic stem cell transplantation (HSCT) for hematologic or nonhematologic diseases.

We report on five patients from three families with neurogenic arthrogryposis, cholestasis and tubular renal dysfunction. Despite a similar clinical picture the liver histology showed a broad pathological spectrum, ranging from pigment storage to parenchymal giant cell transformation and ductopenia. The findings are compared with those of other cases from the literature in search of a correct nosology of the syndrome characterized by arthrogryposis, renal and liver disease.

Although peracetic acid (PAA) is used widely for cold sterilization and disinfection, its mechanisms of sporicidal action are poorly understood. PAA at high concentrations (5–10%) can cause major loss of optical absorbance and microscopically-visible damage to bacterial spores. Spores killed by lower levels of PAA (0.02–0.05%) showed no visible damage and remained refractile. Treatment of spores ofBacillus megaterium ATCC 19213 with PAA at concentrations close to the lethal level sensitized the cells to subsequent heat killing. In addition, PAA was found to act in concert with hypochlorite and iodine to kill spores. Antioxidant sulfhydryl compounds or ascorbate protected spores against PAA killing. Trolox, a water-soluble form of a-tocopherol, was somewhat protective, while other antioxidants, including a-tocopherol, urate, bilirubin, ampicillin and ethanol were not protective. Chelators, including dipicolinate, were not protective, but transition metal ions, especially the reduced forms (Co2+, Cu+ and Fe2+) were highly protective. The net conclusions are that organic radicals formed from PAA are sporicidal and that they may act as reducing agents for spores that are normally in a highly oxidized state, in addition to their well known actions as oxidizing agents in causing damage to vegetative cells.

Wilms’ tumour (WT) is the most common primary genitourinary tumour of childhood with the annual incidence of approximately 8 per million children younger than 15 years of age. Genetic plays an important role in this cancer. WT1 located on chromosome 11p13, WT2 on 11p15, loci at 1p, 7p, 16q, 17p (the p53 tumor suppressor gene), and 19q (the putative familial WT gene FWT2) are believed to harbor genes involved in the biology of WT. The majority of these children are surviving into adult life and due to the combination of genetic susceptibility, irradiation and antineoplastic treatment, are at increased risk for second malignant neoplasms (SMNs). We report the case of a young man with a parotid carcinoma occurring thirteen years after diagnosis of WT. The patient was initially treated according to the SIOP 6 Nephroblastoma protocol, comprising a 4-week two-drug (Actinomycin D, Vincristine) presurgical treatment, nephrectomy and 22-week treatment with biweekly Actinomycin D and Vincristine. No radiation therapy was given. Nine months after the end of therapy he experienced an isolated hepatic relapse, treated with Peptichemio (450 mg/m2), two courses of Cisplatin (40 mg/m2/day for 5 days) and Etoposide (100 mg/m2/day for 5 days) and two cycles of the combination Ifosfamide (2 gr/m2/day for 5 days), Doxorubicin (40 mg/m2/day for 2 days), Vincristine (1.5 mg/m2). Resection of a complete necrotic lesion at the fourth hepatic segment was subsequently performed. Treatment was completed with high dose association of Melphalan (200 mg/M2) and Vincristine (4 mg/M2) followed by autologous bone marrow transplantation (BMT). After 13 years since WT diagnosis and 11 years after BMT the patient presented a right non tender, homogeneous and mobile parotideal mass. After the total parotidectomy the diagnosis was consistent with a low-grade mucoepidermoidal carcinoma. In the National WT Study Group review regarding 43 SMNs out of 5278 patients enrolled between 1969 and 1991 the relevant risk factor for developing a SMN were radiation therapy (RT), the association of Doxo-rubicin and RT and utilization of chemo-therapy for the treatment of the relapse. All these risk factors were present in the only reported case of parotideal carcinoma in these series. In the SIOP survey RT was related to secondary bone cancer and the use of epipodophyllotoxin with leukemia occurrence. On these basis in our patient a clear pathogenetic mechanism is lacking, then we can also attribute the secondary parotid carcinoma simply to the chance. Physician needto be aware that even unusual SMNs, can develop also in subjects that for their primary malignancy and related treatment are at low risk.

To evaluate incidence, risk factors and outcome of SNE after BMT, we retrospectively evaluated 272 (169 M, 103 F) consecutive children that between June 1985 and January 2001 underwent BMT at the “G. Gaslini” Institute. Subjects with solid tumor were excluded. Their median age at transplant was 8 years (range 2 mos. – I 9 yr.), and the source of stem cells was autologous (A), related donor (RD)., and unrelated donor (UD) in 87, 115 and 70 subjects, respectively. 166 children received total body irradiation (TBI) as part of the conditioning regimen; 63 received Busulfan while 43 were treated with other drugs; finally, 54 children received cranial prophylactic irradiation (CPI) (1800 cGy) during front line treatment before BMT.A total of 41 SNE were observed in 37 children (18 M, 19 F); their median age at BMT was 10 years (range 2–16 yr.). Neurological symptoms occurred after a median time of 92 days (range 5–3203) The source of HSCT was UD-BM, RD-BM, and A-BM in 19, 16, and 2 cases respectively.). Ten of them received CPI before BMT. Neuralogical symptoms were: seizures (n=20), changes of mental status and coma (n=12), motor or sensitive defects (n=6), progressive loss of cognitive functions (n=3), clonus and myoclonus (n=2) and visual impairment (n=1). Causes of neurological symptoms were attributed to CSA toxicity (CSA-t) in 21 pt. (77%), to irradiation or chemotherapy injury (IC-i) in 7 (2.6%), to CNS infections (CNS-I) in 7 (2.6%), to CNS hemorrhages in 3 pt. (1.1%) and to immunomediated pathogenesis in the remaining 3 (1.1%). CSA-t occurred in 21 out of 185 patients receiving immunosuppressive therapy. Onset of symptoms was after a median of 96 days (range 20–370 days) after BMT. When CSA was discontinued, a complete resolution of SNE was observed in all cases. The 7 IC-i occurred between 1 month and 7 years after BMT. Mental deterioration and/or coma were observed in 5, clonus and dysarthria in one and visual impairment in another. CNS-I were observed in 7 pt. and were mostly of viral origin (2 cases of EBV, and 1 of CMV, HHV6 and adenovirus, respectively), whereas the 2 remaining cases had neuratoxoplasmosis and aspergillosis. The 3 CNS hemorrhages occurred 30, 50 and 250 days fram BMT, respectively. Finally the 3 immunomedia-ted SNE were due to a demyelinating leucoencephalopathy in the context of ex-tensive chranic GvHD in 2 cases; and to a Guillain-Barré syndrome in the remainning one.Preliminary analysis shows that type of BMT (p<0.01) and TBI (p<0.05) are risk factors for SNE; gender, age at BMT, and CPI were not associated with an increased risk of SNE. Risk factors for the 5 different types of SNE will be presented and discussed.