Maura Faraci

Impact of cumulative anthracycline dose, preparative regimen and chronic graft-versus-host disease on pulmonary and cardiac function in children 5 years after allogeneic hematopoietic stem cell transplantation: a prospective evaluation on behalf of the EBMT Pediatric Diseases and Late Effects Working Parties

This prospective study focused on risk factors and clinical outcome of pulmonary and cardiac late effects after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We prospectively evaluated 162 children by pulmonary function tests (PFTs) and cardiac shortening fraction (SF) before allo-HSCT and yearly up to the 5th year of follow-up. The 5-year cumulative incidence of lung and cardiac impairment was 35 (hazard rate=0.03) and 26% (hazard rate=0.06), respectively. Patients presenting abnormal PFTs and SF at last follow-up were 19 and 13%, respectively, with a median Lansky performance status of 90% (70–100). Chronic graft-versus-host disease (c-GVHD) was the major risk factor for reduced lung function in univariate (P=0.02) and multivariate analysis (P=0.02). Total body irradiation (TBI) alone and TBI together with pre-transplant anthracycline administration were significant risk factors for reduced cardiac function in univariate analysis, only (P=0.04 and 0.004, respectively). In conclusion, our prospective study demonstrates an asymptomatic post-allo-HSCT deterioration of pulmonary and cardiac function in some long-term survivors, who had been transplanted in childhood, and thus emphasizes the need for lifelong cardiopulmonary monitoring and the development of new strategies both to reduce pre-transplant cardiotoxic regimens and to treat more efficiently c-GVHD.

Prevention and treatment of acute GvHD.

GvHD remains a source of significant morbidity and mortality in the setting of allogeneic haematopoietic SCT. Improving outcomes in stem cell transplant recipients requires additional therapeutic modalities for GvHD, especially for patients who fail to respond to initial therapy with steroids. Moreover, while the absence of acute GvHD (aGvHD) is associated with a higher risk of relapse of the underlying malignant disease, severe aGvHD usually induces the occurrence of life-threatening complications such as severe infections. This article summarizes the current state of aGvHD prophylaxis and treatment.

Neuroradiologic findings and follow‐up with magnetic resonance imaging of the genetic forms of haemophagocytic lymphohistiocytosis with CNS involvement

Haemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome caused by deficient down‐regulation of the immune response. Presence of central nervous system (CNS) involvement at diagnosis is a poor prognostic sign, and should be carefully investigated. Herein, we describe the neuroradiological findings, clinical data, and treatment outcome in 12 patients with genetic HLH and CNS complications. Neuroimaging was important in identifying CNS involvement, monitoring treatment responses, and detecting treatment complications. Pediatr Blood Cancer 2012; 58: 810–814.

Role of active follow-up for early diagnosis of relapse after elective end of therapies

To evaluate the role of active follow‐up for the detection of relapses occurring after completion of therapy in children with cancer.

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

A retrospective study was conducted among Italian children treated with hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk factors in the development of osteochondroma (OC). OC occurred in 27 patients who received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis of cumulative risk stratified by the various risk factors revealed that male sex (P=.026), autologous HSCT (P=.001), age at HSCT (< or =3 years) (P < .0001), and total body irradiation (TBI) (P <.0001) significantly affected the risk of OC. Multivariate analysis, restricted only to tumor types with at least 1 case of OC, showed that earlier age at HSCT (P =.0004) and TBI (P < .0001) were the only factors that were significantly associated with OC.

Magnetic resonance imaging in childhood leukemia survivors treated with cranial radiotherapy: a cross sectional, single center study.

Children treated with cranial radiotherapy (CRT) for leukemia are at risk of developing central nervous system injuries. Magnetic resonance imaging (MRI) represents the examination method of choice for evaluating radiation‐induced brain complications. The purpose of this report is to describe the spectrum of MRI abnormalities detected in a group of survivors of leukemia treated with cranial irradiation.

Invasive mould infections in newborns and children

Invasive mould infections represent important complications of different pediatric conditions. Epidemiology and clinical features vary according to the type of underlying conditions that determine the risk of invasive mycosis. No pediatric study has specifically evaluated the efficacy of prophylaxis or therapy invasive moulds infections, while pediatric dosages for the treatment of invasive aspergillosis are available for drugs that produced positive results in clinical trials undertaken in adults.

Neuroradiology of Pediatric Hemolymphoproliferative Disease

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.

A retrospective EBMT survey on the use of cidofovir for BK-related haemorrhagic cystitis after allogeneic haematopoietic stem cell transplant

83 Inhibitory KIR-ligand mismatching is associated with decreased incidence of relapse and improved diseasefree survival after unrelated cord blood stem cell transplantation for patients with acute leukaemia R. Willemze*, C. Arrais Rodrigues, M. Labopin, I. Ionescu, K. Boudjedir, G. Sanz, G. Michel, G. Socié, B. Rio, J. Garcia, G. Kögler, L. Lecchi, P. Loiseau, E. Gluckman, V. Rocha on behalf of Eurocord-Netcord* and Acute Leukaemia Working Party of the EBMT, Paris

1. Severe neurological events (SNE) after bone marrow Transplantation (BMT) in children

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-Barre syndrome in the remainning one. Preliminary analysis shows that type of BMT (p