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The treatment of pediatric patients with refractory or relapsed anaplastic large cell lymphoma (ALCL) is still a major challenge. In addition to conventional chemotherapy and stem cell transplantation, new therapeutic options such as anti-CD30 drugs and anaplastic lymphoma kinase (ALK) inhibitors have been recently introduced in this setting. Among ALK inhibitors, only the first-generation molecule crizotinib is approved for pediatric use, while second-generation molecules, such as brigatinib, are still under investigation. Here we report the case of a 13-year-old boy diagnosed with stage IV ALCL, refractory to first-line conventional chemotherapy and second-line therapy with the anti CD30 antibody–drug conjugate brentuximab-vedotin, who finally achieved remission after a combination of conventional high-dose chemotherapy and the second-generation ALK inhibitor brigatinib. The latter was chosen for its ability to penetrate through the blood–brain barrier, due to the persistent involvement of the patient’s cerebral nervous system. The remission was then consolidated with an allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor using myeloablative conditioning with total body irradiation. At 24 months after HSCT, the patient is in complete remission, alive and well. An updated review regarding the use of ALK inhibitors in ALCL patients is provided.

Objective Preparations with high-titer immunoglobulin-M (HT-IgM) have been used to treat neonatal and adult sepsis as adjuvant to antibiotics. Limited data are available of this use in pediatric oncohematological patients. We retrospectively assessed the characteristics and outcome of febrile episodes treated with broad-spectrum antibiotics and HT-IgM. Methods This study included febrile episodes diagnosed after chemotherapy or hematopoietic stem cell transplantation (HSCT) treated with antibiotics and HT-IgM. Study period was from January 2011 to March 2019. Results Seventy febrile episodes in 63 patients were eligible. In 40% of episodes (n = 28), blood cultures identified a causative organism: Gram-negative (n = 15), Gram-positive (n = 8), polybacterial (n = 4), fungi (n = 1). Twenty-six percent of Gram-negatives were extend spectrum β-lactamase (ESBL)-producers. In 44% of episodes, a deep-organ localization was present, mostly pulmonary. Severe or profound neutropenia, hypotension, and hypoxemia were present in 89, 26, and 21% of episodes, respectively; 20% of episodes required intensive care and 20% of episodes required the use of inotropes. Overall, 90-day mortality was 13% and infection-attributable mortality resulted 8.6%. More than half of the patients received HT-IgM within 24 hours from fever onset. HT-IgM-related allergic reactions occurred in three episodes. Risk factors for 90-day mortality were as follows: hypotension and hypoxemia at fever presentation, admission to intensive care unit (ICU), use of inotropes, presence of deep-organ infection, and escalation of antibiotic therapy within 5 days. Conclusion The combination of broad-spectrum antibiotics and HT-IgM was feasible, tolerated, and promising, being associated with a limited infectious mortality. Further prospective controlled studies are needed to assess the efficacy of this combination over a standard antibiotic approach.

Bloodstream infections (BSIs) after chemotherapy or hematopoietic stem cell transplantation (HSCT) are a leading cause of morbidity and mortality. Data on 154 BSIs that occurred in 111 onco-hematological patients (57 hematological malignancies, 28 solid tumors, and 26 non-malignant hematological diseases) were retrospectively collected and analyzed. Monomicrobial Gram-positive (GP), Gram-negative (GN), and fungal BSIs accounted for 50% (77/154), 38.3% (59/144), and 3.2% (5/154) of all episodes. Polymicrobial infections were 7.8% (12/154), while mixed bacterial–fungal infections were 0.6% (1/154). The most frequent GN isolates were Escherichia coli (46.9%), followed by Pseudomonas aeruginosa (21.9%), Klebsiella species (18.8%), and Enterobacter species (6.3%). Overall, 18.8% (12/64) of GN organisms were multidrug-resistant (seven Escherichia coli, three Klebsiella pneumoniae, and two Enterobacter cloacae), whereas GP resistance to glycopeptides was observed in 1% (1/97). Initial empirical antibiotic therapy was deemed inappropriate in 12.3% of BSIs (19/154). The 30-day mortality was 7.1% (11/154), while the bacteremia-attributable mortality was 3.9% (6/154). In multivariate analysis, septic shock was significantly associated with 30-day mortality (p = 0.0001). Attentive analysis of epidemiology and continuous microbiological surveillance are essential for the appropriate treatment of bacterial infections in pediatric onco-hematological patients.

Long-term survival for acute lymphoblastic leukemia (ALL) in children improved over the last three decades up to 80–90% of affected patients. Consequently, the quality of life of survivors has become increasingly important. This study analyses the clinical features and outcome of 119 children with ALL, focusing on the quality of long-term survival in a subset of 22 patients over 18 years of age. Among this group, the 10-year event-free survival and overall survival were 83.1% (C.I. 74.0–89.2) and 88.4% (C.I. 80.9–93.1), respectively. Treatment related long-term medical complications were reported only in 2 patients (9.1%). Secondary school was completed successfully in 20 of 22 patients (89.9%). The remaining 2 patients were still attending at the time of the analysis. In conclusion, current treatment for ALL is well tolerated and does not compromise significantly the quality of life of survivors.

Lipopolysaccharide responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency disorder (PID) that can cause a common variable immunodeficiency (CVID)-like disease. The typical features of the disease are autoimmunity, chronic diarrhea, and hypogammaglobulinemia. Neurological complications are also reported in patients affected by LRBA deficiency. We describe a 7-year old female with an acute cervical longitudinally extensive transverse myelitis (LETM) as a feature of LRBA deficiency. This is the first case of LETM associated with LRBA deficiency described in literature.

BACKGROUND, OBJECTIVES The antibody titer of vaccine-preventable disease in 70 patients who underwent chemotherapy or haemopoietic stem cell transplantation (HSCT) was assessed in order to evaluate the seroprotection after treatment and the feasibility and the efficacy of a policy of revaccination. METHODS Serum antibody titers of 70 patients for hepatitis B (HBV), Rubella, Varicella-zoster (VZV), Measles, Mumps, Polio viruses, Clostridium tetani (C. tetani) and Streptococcus pneumoniae (S. Pneumoniae) were analysed. RESULTS After chemotherapy, a lack of protective antibody titers against HBV, Rubella, VZV, Measles, Mumps, Polio viruses, C. tetani and S. Pneumoniae were found in 53%, 45%, 46%, 46%, 43%, 21-26%, 88% and 55% of patients, respectively. In patients who were tested both before and after chemotherapy, the loss of immunity was respectively 39%, 43%, 38%, 42%, 32%, 33%, and 80%. A low number of B-lymphocytes was associated with the loss of immunity against Measles (p=0.04) whereas a high number of CD8+ T-lymphocytes was associated with the loss of immunity against VZV (p=0.03). A single booster of vaccine dose resulted in a seroprotection for HBV, Rubella, VZV, Measles, Mumps, Polio viruses, C. tetani and S. Pneumoniae in 67%, 83%, 80%, 67%, 33%, 100%, 88% and 67% of patients, respectively. After HSCT, the rates of lack and loss of vaccine immunity differ by the infectious disease considered. CONCLUSIONS We confirm that seroprotection for vaccine-preventable disease is affected by treatment for pediatric malignancy. A single booster dose of vaccine might be a practical way to restore vaccine immunity in patients after chemotherapy.

Background/Aim The antibody titer of vaccine-preventable diseases in pediatric patients who underwent chemotherapy was assessed in order to evaluate the seroprotection after treatment and the feasibility and the efficacy of a policy of revaccination. Methods Serum antibody titers of 55 patients for hepatitis B (HBV), rubella, varicella-zoster (VZV), measles, mumps, polio viruses, Clostridium tetani (C. tetani) and Streptococcus pneumoniae (S. pneumoniae) were analysed. Results: After chemotherapy, a lack of protective antibody titers against HBV, rubella, VZV, measles, mumps, polio viruses, C. tetani, and S. pneumoniae was found in 53%, 45%, 46%, 46%, 43%, 21–26%, 88% and 55% of patients, respectively. In 49 of 55 patients who were tested both before and after chemotherapy for at least a pathogen, the loss of immunity for HBV, rubella, VZV, measles, mumps, polio viruses and C. tetani was respectively 39%, 43%, 38%, 42%, 32%, 33%, and 80%. A low number of B-lymphocytes was associated with the loss of immunity against measles (p=0.04) whereas a high number of CD8+ T-lymphocytes was associated with the loss of immunity against VZV (p=0.03). A single booster of vaccine dose resulted in a seroprotection for HBV, rubella, VZV, measles, mumps, polio viruses, C. tetani and S. pneumoniae in 67%, 83%, 80%, 67%, 33%, 100%, 88% and 67% of patients, respectively. Conclusions We confirm that seroprotection for vaccine-preventable diseases is affected by treatment for pediatric malignancy. A single booster dose of vaccine might be a practical way to restore vaccine immunity in patients after chemotherapy.

Background: Chronic graft versus host disease (cGVHD) occurs in 20-30% of paediatric patients receiving haemopoietic stem cell transplantation (HSCT). Neuromuscular disorders such as polymyositis are considered a rare and distinctive but non-diagnostic manifestation of cGVHD and, in absence of other characteristic signs and symptoms, biopsy is highly recommended to exclude other causes. Case report: We report a case of a 17-months-old child affected by hemophagocytic lymphohistiocytosis who underwent a matched unrelated donor haematopoietic stem cell transplantation (HSCT). She developed a severe cGVHD-related polymyositis that was successfully treated with high-dose steroid therapy, rituximab and sirolimus. Conclusions: This is the first case of cGVHD-related-polymyositis described in a pediatric patient which was successfully treated with rituximab.

Background Invasive mucormycosis is a very aggressive fungal disease among immunocompromised pediatric patients caused by saprophytic fungi that belong to the order of the Mucorales. Case Report We describe a case of of Lichtheimia corymbifera infection in a 15-year-old child with B-cell Non-Hodgkin Lymphoma (NHL) involving lung, kidney and thyroid that initially was diagnosed as probable aspergillosis delaying the effective therapy for mucormycosis. Conclusions This case showed that also intensive chemotherapy with rituximab may represent a risk factor for mucormycosis infection. Liposomal amphotericin B and surgery remain key tools for a successful treatment of this aggressive disease.

The polyglandular autoimmune syndrome type I is a rare hereditary autosomal recessive disease. We describe a child with the classic triad of the disease and her sister with pure red cell aplasia and cerebellar hypoplasia. The latter received two haematopoietic stem cell transplantations, complicated by an acute disseminated encephalomyelitis.

Introduction: Rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor frequent in children. Biliary duct localization is extremely rare, but it is the most common cause of malignant obstructive jaundice in pediatric patients. Methods: This report describes a series of 10 patients under 18 years of age with biliary tract rhabdomyosarcoma who were enrolled, from 1979 to 2004, in 3 consecutive Italian pediatric cooperative protocols that had been drawn up by the Soft Tissue Sarcoma Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). Results: Considering initial and delayed surgery, tumor resection was achieved in 7 cases, 3 complete with free margins (2 liver transplants) and 4 with microscopic residual disease. Chemotherapy was given to all patients and radiotherapy to 3. At present, 5 patients survive in complete remission 90-200 months after diagnosis while 4 died of disease progression or relapse and 1 of liver transplant-related complications. Conclusions: Better outcomes in this series were associated with the feasibility of conservative surgery due to the favorable location of the tumor, in particular in the common bile duct. Chemotherapy and radiotherapy might obviate the need for demolitive surgery or liver transplant, which were linked to worse outcomes in our series.

Purpose: The aims of patients’ radiological surveillance are to: ascertain relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if second-line therapy is not standardized/curative; and assess/treat iatrogenic effects. To lessen the emotional and socioeconomic burdens for patients and families, we ideally need to establish whether scheduled radiological surveillance gives patients a better outcome than waiting for symptoms and signs to appear. Methods: We analyzed a prospective series of 160 newly-diagnosed and treated pediatric/adolescent patients with intracranial ependymoma, comparing patients with recurrent disease identified on scheduled MRI (the RECPT group; 34 cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group; 16 cases). The median follow-up was 67 months. Results: No significant differences emerged between the two groups in terms of gender, age, tumor grade/site, shunting, residual disease, or type of relapse (local, distant, or concomitant). The time to relapse (median 19 months; range 5–104) and the MRI follow-up intervals did not differ between the SYMPPT and RECPT groups. The presence of signs/symptoms was an unfavorable factor for overall survival (OS) after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis, an adjusted model confirmed a significantly worse OS in the SYMPPT than in the RECPT patients. Conclusions: Symptomatic relapses carried a significantly worse survival for ependymoma patients than recurrences detected by MRI alone. It would therefore be desirable to identify recurrences before symptoms develop. Radiological follow-up should be retained in ependymoma patient surveillance because there is a chance of salvage treatment for relapses found on MRI

Objectives Shwachman–Diamond syndrome is a rare disorder characterized by exocrine pancreatic insufficiency, skeletal abnormalities, and bone marrow failure, with high risk of leukemic evolution. The aim of the study was the immunophenotypic characterization of bone marrow cells from patients with Shwachman–Diamond syndrome to assess the maturation pathway of blood progenitor cells and to identify the presence of recurrent abnormalities. Methods Bone marrow samples from nineteen patients and eleven controls were analyzed by multiparameter flow cytometry. Results We found a low frequency of CD34+ cells (P = 0.0179) and myeloid progenitors (P = 0.025), in the bone marrow of patients with Shwachman–Diamond syndrome as compared to the controls. A significant reduction in the percentage of granulocytes (P = 0.002) and an increase of monocytes (P

We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement. PAI-1 warrants study as a diagnostic marker for SOS in ALL.

Pearson syndrome (PS) is a rare mitochondrial disorder that usually presents with transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction, and lactic acidosis. Typical bone marrow (BM) features are vacuolization in hematopoietic progenitors, hypocellularity, and ringed sideroblasts. At the neonatal age, PS may have a variable clinical onset. Moreover, there is little information about BM features at this age and the timing of their presentation. We report a neonatal case of PS that presented with refractory anemia and atypical BM features. We reviewed the BM findings in neonatal-onset PS cases to stress the importance and limitations of BM evaluation at this age.

Aims of patient follow-up are: discovering relapse to apply second-line therapy for possible cure, accruing patients in phase 1/2 protocols if second-line therapy is not standardized/curative, evaluating/treating iatrogenic effects. To lessen the patient/family emotional and social economic burdens, we should ideally understand if scheduled radiological follow-up has a better rationale/outcome than the symptomatic relapse. We analyzed the Italian series of 2016 (doi:10.1093/neuonc/now108) comprehending 160 newly diagnosed pediatric/adolescent patients with intracranial ependymoma (EPD) according to relapse status (recurrence at scheduled exam [RECPT]/sign-symptomatic recurring [SYMPPT]). RECPT and SYMPPT were assessed in Cox model as time-dependent variables for overall survival (OS). Differences in characteristics between RECPT and SYMPPT subgroups were assessed by Wilcoxon-Mann-Whitney or Fisher Exact tests. Kaplan-Meier curves depicted event-free survival (EFS) and OS after recurrence according to signs/symptoms. There were 16 SYMPPT /34 RECPT, at a median follow-up of 55 months. No significant differences were found between SYMPPT/RECPT for gender, age, tumor grade/site, shunt, residual disease, radiation boost, type of relapse (local/distant/combined). Time-to-relapse (median:19 months, range 5–104) and treatment adoption did not differ between SYMPPT/RECPT while signs/symptoms depicted an unfavorable factor for OS after relapse (5-year OS: 8% vs 37%). Adjusted model in multivariate analysis confirmed that presence of signs/symptoms was prognostically unfavorable. In order to improve the OS in symptomatic patients, their early identification-in the first two/three years after diagnosis- would be desirable. Perhaps, this could be obtained paying attention to “heuristically detected” subgroup of patients, not just describing general prognostic variables but discovering possible biology differences according to signs/symptoms.

EPN-02. FINAL RESULTS OF THE 2ND AIEOP PROTOCOL FOR INTRACRANIAL EPENDYMOMA (EPD) Maura Massimino1, Rosalba Miceli1, Felice Giangaspero2,3, Luna Boschetti1, Paolo Ferroli4, Paola Peretta5, Emilia Pecori1, Laura Valentini4, Veronica Biassoni1, Maria Luisa Garre6, Elisabetta Schiavello1, Iacopo Sardi7, Armando Cama6, Silvia Scoccianti8, Maurizio Mascarin9, Lorenzo Genitori7, Daniele Bertin5, Anna Mussano10, Elisabetta Viscardi11, Piergiorgio Modena12, GiuseppinaCalareso1, Salvina Barra13, Giovanni Scarzello14, LuciaQuaglietta15, Giuseppe Cinalli15, Angela Mastronuzzi16, Carlo Giussani17, Carlo Marras16, Rita Balter18, Patrizia Bertolini19, Ermanno Giombelli19, Francesca Buttarelli2, Manila Antonelli2, and Lorenza Gandola1; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; Universita Sapienza Roma, Roma, Italy; Neuromed Pozzilli, Pozzilli, Italy; Fond IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; Ospedale Infantile Regina Margherita, Torino, Italy; Istituto Giannina Gaslini, Genova, Italy; Ospedale Pediatrico Meyer, Firenze, Italy; OspedaleCareggi,Firenze, Italy;CRO,Aviano, Italy;OspedaleS.Anna, Torino, Italy; Clinica di Oncoematologia Pediatrica, Padova, Italy; Genetica, Osp S. Anna, Como, Italy; Istituto dei Tumori, Genova, Italy; Istituto Oncologico del Veneto, Padova, Italy; Ospedale Pausillipon, Napoli, Italy; Ospedale Bambino Gesu, Roma, Italy; Ospedale S. Gerardo, Monza, Italy; Ospedale Borgo Roma, Verona, Italy; Ospedale, Parma, Italy This study stratified patients after surgical resection (complete 1⁄4 NED vs incomplete 1⁄4 ED) and centrally reviewed histology(gr.2 vs gr. 3). Gr2 tumors/NEDpts were focally irradiated with a 3D-conformal technique 1.8Gy/d up to 59.4 Gy, gr3/NED received also 4 VEC(Cyclo,VP16,VCR) after irradiation. EDpts received 1-4 VEC, second-look surgery whenever possible,59.4 Gy followed by 8 Gy boost into 2 fractions on still measurable residue. Children aged 1-3 yrs received the same treatment but for those gr2/NED who could receive only 6 VEC. Between January 2002/December 2014, 160 consecutive children, median age 4.9 years, entered the protocol; follow-up was a median 67 months. M/F was 100/60, infratentorial origin in 110(2 plus metastasis). After surgery, NEDpts were 110,grade 3 was assessed in 84. 100 resections were performed in 46/160 children with another 12 rendered NED after first excision,10 after 1-4 VEC,2 after radiation. Boost was applied to 24/40 still ED patients after surgery/ies and VEC obtaining PFS/OS of 58.1%/68.7% in this severe prognosis subgroup. For the whole series,5-year PFS/OS were 65.4%/81.1% with no toxic deaths. In univariable analysis, female gender, supratentorial origin, NED status before RT, grade 2, shunt absence were favourable for OS, in multivariable NED status and grade 2 were. For PFS, female gender, NED status before RT, grade 2 were significant in univariable, only grade in multivariable. In a multicentric collaboration this trial accrued the highest patient number so far published with comparable results to best monoinstitutional series. Radiation boost was feasible and efficacious in improving local control. Complete surgery, also through multiple excisions, still confirmed its prognostic strength as well as grade. Further biological parameter definition on this series will be the object of next coming studies. Neuro-Oncology 18:iii30–iii39, 2016. doi:10.1093/neuonc/now070.2 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

In patients undergoing hematopoietic stem cell transplantation (HSCT), refractoriness to platelet transfusion has been associated with graft failure, delayed engraftment, early mortality and decreased overall survival. Therapeutic strategies include plasma exchange, immunoglobulins, rituximab, and splenectomy. We describe here three patients with refractoriness to platelet transfusion due to anti-human leukocyte antibodies who were splenectomized before HSCT (two cases) and after HSCT (one case) due to the lack of efficacy of other therapies. Splenectomy was uneventful. All three patients achieved a full donor engraftment. We suggest that splenectomy is feasible and effective in HSCT patients to reduce the risk of graft failure or delayed engraftment.

Background This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). Methods WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. Results From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. Conclusions In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

Background: Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumour of the infancy and of the first decade of life. It is locally aggressive and potentially life threatening when associated to consumptive coagulopathy, known as Kasabach-Merritt syndrome (KMS). No consensus or guideline for the therapy has been reached because of the lack of prospective trials and the different standard care suggestions are based on retrospective case series. Case report: We report the case of a 9-month-old male with KHE and KMS in which the initial response, obtained with prednisone and vincristine, was subsequently consolidated and strengthened by long-term treatment with sirolimus, an mTOR inhibitor. A summary of the published data is presented as well. Conclusions: The inhibition of mTOR pathway represents the most important therapeutic innovation introduced in the last few years for KHE. Our case shows the effectiveness and good tolerance of long-term therapy with sirolimus. Keywords: Kaposiform Hemangioendothelioma, Kasabach-Merrit syndrome, sirolimus, prednisone, vincristine

UNLABELLED We describe a premature twin born at 30 wk of gestational age, affected with familial haemophagocytic lymphohistiocytosis. Two different mutations were identified in his DNA: one inherited from the mother and one from the father. Haemophagocytosis had been confirmed in his twin brother, who died soon after birth, as well as in the re-evaluation of the autopsy of his older sister, who died 1 y earlier. At 26 d of age, chemotherapy and immune-suppressive treatment were started according to the HLH-94 protocol. At 6 mo of age, a bone marrow transplant from an HLA-identical, unrelated volunteer was performed. Now at 32 mo of age, the infant is healthy and without signs of graft-versus-host disease. CONCLUSION This case report shows that immuno-chemotherapy and allogenic bone marrow transplant are feasible even in premature infants affected with familial haemophagocytic lymphohistiocytosis, which should be ruled out in unknown bleeding disorders of neonates.

Purpose A postsurgical "stage-based" protocol for ependymoma was designed. Methods and materials Children were given: ( 1 ) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or ( 2 ) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.4 Gy (1.1 Gy/fraction b.i.d.); VEC consisted of VCR 1.5 mg/m 2 1/w, VP16 100 mg/m 2 /day × 3, CTX 3 g/m 2 d 1. When feasible, second-look surgery was recommended. Results Sixty-three consecutive children were enrolled: 46 NED, 17 ED; the tumor was infratentorial in 47 and supratentorial in 16, with spinal metastasis in 1. Of NED patients, 35 of 46 have been treated with HFRT; 8 received conventionally fractionated radiotherapy, and 3 received no treatment. Of the 17 ED patients, 9 received VEC + HFRT; violations due to postsurgical morbidity were as follows: HFRT only (2), conventionally fractionated radiotherapy (3) + VEC (2), and no therapy (1). Objective responses to VEC were seen in 54%; objective responses to RT were seen in 75%. Overall survival and progression-free survival at 5 years for all 63 children were 75% and 56%, respectively; for the NED subgroup, 82% and 65%; and for the ED subgroup, 61% and 35%, respectively. All histologies were centrally reviewed. At multivariate analysis, grading, age, and site proved significant for prognosis. Conclusions HFRT, despite the high total dose adopted, did not change the prognosis of childhood ependymoma as compared to historical series: New radiotherapeutic approaches are needed to improve local control. Future ependymoma strategies should consider grading when stratifying treatment indications.

PurposeTo assess the non-inferiority of pegfilgrastim versus filgrastim in speeding the recovery of polymorphonuclear cells (PMN) in pediatric patients who underwent autologous peripheral blood stem cell transplant (PBSCT).MethodsThe sample size of this randomized, multicenter, phase III study, was calculated assuming that a single dose of pegfilgrastim of 100 ug/kg was not inferior to 9 doses of filgrastim of 5 ug/kg/day. Randomization was performed by a computer-generated list and stored by sequentially numbered sealed envelopes.ResultsSixty-one patients, with a median age of 11.5 years, were recruited: 29 in the filgrastim arm and 32 in the pegfilgrastim arm. Twenty percent were affected by lymphoma/leukaemia and eighty percent by solid tumors. The mean time to PMN engraftment was 10.48 days (standard deviation [SD] 1.57) and 10.44 days (SD 2.44) in the filgrastim and pegfilgrastim arms, respectively. Having fixed a non-inferiority margin Delta of 3, the primary endpoint of non-inferiority was reached. No differences were observed for other secondary endpoints: platelet engraftment, mean time to platelet recovery (28 days vs. 33 days), fever of unknown origin (79% vs. 78%), proven infection (34% vs. 28%), mucositis (76% vs. 59%). After a median follow-up of 2.3 years (95% C.I.: 1.5, 3.3), 20 deaths were observed due to disease progression.ConclusionsWe conclude that pegfilgrastim was not inferior to daily filgrastim in pediatric patients who underwent PBSCT. EU CLINICAL TRIAL REGISTER NUMBER: 2007-001430-14.

Background Ewing Sarcoma Family Tumours (ESFT) are rare in early childhood. The aim of this study was to report the clinical characteristics and outcome of children under 6 years of age affected by ESFT of the bone in Italy. Methods The records of all the children diagnosed with osseous ESFT in centres members of the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) from 1990 to 2008 were reviewed. The Kaplan–Meier method was used for estimating overall and progression-free survival (OS, PFS) curves; multivariate analyses were performed using Cox proportional hazards regression model. Results This study includes 62 patients. An axial primary localization was present in 66% of patients, with the primary site in the chest wall in 34%. Fourteen (23%) patients presented metastatic disease. The 5-year OS and PFS were 73% (95% confidence interval, CI, 58–83%) and 72% (95% CI 57–83%) for patients with localized disease and 38% (95% CI 17–60%) and 21% (95% CI 5–45%) for patients with metastatic disease. Metastatic spread, skull/pelvis/spine primary localization, progression during treatment and no surgery predicted worse survival (P

A full-term male was born after a pregnancy complicated between 22 and 31 weeks of gestation by non-immune hydrops fetalis (NIH). At 48 h of life, the physical examination revealed jaundice, which was treated successfully with conventional phototherapy for 24 h, and mild hepatomegaly, which was not promptly investigated. At 20 days of life, the patient presented with a clinical picture of failure to thrive and significant abdominal distension (figure 1). Liver and spleen were palpable at 7 and 8 cm below the costal margin, respectively. The patient was dystrophic without dysmorphic features or signs of neurological involvement. Liver enzyme levels and cholestasis indices were significantly altered (aspartate aminotransferase 126 U/L gamma glutamyl transferase 283 U/L, alkaline phosphatase 533 U/L, total bilirubin 58 mmol/L, conjugated bilirubin 41 mmol/L), while leucocyte count, haemoglobin level, coagulation parameters, albumin and serum glucose level were …

The optimal treatment of advanced sporadic Burkitt lymphoma in adults is still a matter of debate. The salutary results of pediatric therapies did open the road for improving the adult outcome. Between May 1988 and March 2009, 71 consecutive patients—46 adults, 25 children—affected by Burkitt lymphoma/leukemia were treated with the same intensive pediatric protocol alternating vincristine, adriamycine and fractionated ciclophosphamide (phase A) with high dose methotrexate and high dose cytarabine (phase B) in four Italian institutions. Eighty-nine per cent of patients were in Stage III–IV or had L3 leukemia. Complete remissions were 67/71 (94.4%), 24/25 (96%) in children, and 43/46 (93.5%) in adults. Toxic deaths were 3/71 (4.2%), all in adults. There were nine relapses (one in children, eight in adults), all but one observed early. After a median observation of 94 months (range 23–275), the Event–Free Survival rate is 92% in children and 71.7% in adults (P = 0.067). The 23 more recent adults received also rituximab, without differences in outcome as compared to patients who did not. Our experience confirms that such an intensive pediatric-derived chemotherapy is feasible and improves the long-term outcome of adults with advanced Burkitt lymphoma. Am. J. Hematol., 2012. © 2011 Wiley Periodicals, Inc.

The objective of this study was to evaluate whether electroneurography could help in differentiating between vincristine-induced neuropathy and acute inflammatory demyelinating polyradiculoneuropathy. We performed electroneurography in 7 children from September 2006 to March 2009 admitted to receive chemotherapy including vincristine for acute lymphoblastic leukemia, in whom severe acute limb weakness developed, suggesting vincristine-induced neuropathy. Three of 7 patients had electroneurography, suggesting acute inflammatory demyelinating polyradiculoneuropathy. They received intravenous immunoglobulins without discontinuing chemotherapy, and within 10 days their electroclinical conditions improved. Although electroneurography showed only absent F waves, preventing us from reaching a definitive neurophysiological diagnosis of acute inflammatory demyelinating polyradiculoneuropathy, children’s presenting clinical manifestations, their disease course, and rapid and complete recovery after intravenous immunoglobulins argued strongly in its favor. A prompt, correct differential diagnosis of vincristine neuropathy and acute inflammatory demyelinating polyradiculoneuropathy in patients with acute lymphoblastic leukemia receiving vincristine is essential to improve disease outcome and prolong life expectancy.

Congenital mesoblastic nephroma is a relatively rare infantile renal tumor. It comprises 3–6% of renal masses in childhood and 50% during the neonatal period. Most mesoblastic nephroma occur in the newborn period, with 80% of the cases being reported within the first month of life. Macroscopically the tumor is composed of a solid mass of different sizes tending to invade the surrounding structures and renal parenchyma. The authors report a case of cystic mesoblastic nephroma of the cellular subtype, with diffuse areas of hemorrhage and necrosis. The tumor was treated by surgical excision with radical nephrectomy and the child is doing well 4 years after the operation.

We describe a premature twin born at 30 wk of gestational age, affected with familial haemophagocytic lymphohistiocytosis. Two different mutations were identified in his DNA: one inherited from the mother and one from the father. Haemophagocytosis had been confirmed in his twin brother, who died soon after birth, as well as in the re-evaluation of the autopsy of his older sister, who died 1 y earlier. At 26 d of age, chemotherapy and immune-suppressive treatment were started according to the HLH-94 protocol. At 6 mo of age, a bone marrow transplant from an HLA-identical, unrelated volunteer was performed. Now at 32 mo of age, the infant is healthy and without signs of graft-versus-host disease.This case report shows that immuno-chemotherapy and allogenic bone marrow transplant are feasible even in premature infants affected with familial haemophagocytic lymphohistiocytosis, which should be ruled out in unknown bleeding disorders of neonates.

Two children affected by severe aplastic anaemia and sickle cell anaemia rejected the allogeneic bone marrow transplantation from an HLA-matched unrelated volunteer and an HLA-identical sibling, respectively. In both cases a second transplant using granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) was performed. Donors were the HLA-haploidentical mother and the same HLA-identical sibling who was employed for the first marrow allograft, respectively. Treatment with G-CSF and PBSC collection were well tolerated. Both patients had engraftment of donor haemopoiesis and did not experience severe graft-versus-host disease. These cases confirm that PBSC transplant should be considered as a feasible treatment to reverse graft failure in paediatric patients.

Background: Advanced Burkitt's lymphoma (BL) has an extremely poor prognosis in adults. With a previous protocol including CNS prophylaxis, 40% of our adult patients achieved CR and only 13% became long survivors. In 1988, following this poor experience, we adopted a very intensive pediatric-derived protocol. Patients and methods: Twenty-one consecutive patients, 8 adults (median age 35, stage III: 1; IV: 7; leukemias: 6) and 13 children (median age 10, stage III: 8; IV: 5; leukemias: 4) were treated with the same protocol (POG 8617), based on alternate two-phase cycles with sequential high-dose CTX,VCR, ADM + CNS chemoprophylaxis (phase A) and HD MTX + HiDAC (phase B). Adults received 6 cycles. children 8; i.t. prophylaxis in phase B was omitted in adults. Results: Twenty of 21 (95%) patients achieved CR (adults 100%, children 92%). Two patients died early; 2 relapsed at 4 and 9 months. With a median follow-up of 28 months (4-96), 17 patients (81%) are event free (adults 75%, children 85%). Severe infections affected 62% of adults and 15% of children. Conclusions: (I) The prognosis of adult advanced BL definitely improved with this intensive protocol. (2) There were no differences in outcome between adults and children. (3) Outcome of lymphoma and leukemia was similar. (4) Severe infections occurred frequently in adults. This intensive pediatric protocol requires a careful supportive therapy.

A very rare case of mesenteric teratoma, detected by routine ultrasound screening at 20 weeks' gestation, is reported. The patient, a male newborn delivered at 40 weeks' gestation in good condition, was successfully operated on at birth. The post-operative course was regular and the baby is currently doing well.

We report the first case of a thymic cyst appearing in the course of treatment for non-Hodgkin lymphoma of the anterior mediastinum. The patient was a 9-year-old child in whom an abnormal contour of the left cardiac border persisted after chemotherapy, suggesting residual disease. The mass was found at thoracotomy to be a benign thymic cyst. The lesion was not present 2 years previously, and most likely represented cystic degeneration of the thymus, secondary to lymphomatous involvement. CT scan was not helpful in distinguishing the cystic lesion from residual lymphoma.