The objective of this study was to identify prognostic factors for children and adolescents with relapsed or progressive classical Hodgkin’s lymphoma (cHL) to design salvage therapy tailored to them. We analyzed a homogeneous pediatric population, diagnosed with progressive/relapsed cHL previously enrolled in two subsequent protocols of the Italian Association of Pediatric Hematology and Oncology in the period 1996–2016. There were 272 eligible patients, 17.5% of treated patients with cHL. Overall survival (OS) and event-free survival (EFS) after a 10-year follow-up were 65.3% and 53.3%, respectively. Patients with progressive disease (PD), advanced stage at recurrence, and ≥5 involved sites showed a significantly worse OS. PD, advanced stage, and extra-nodal involvement at recurrence were significantly associated with a poorer EFS. Multivariable analysis identified three categories for OS based on the type of recurrence and number of localizations: PD and ≥5 sites: OS 34%; PD and <5 sites: OS 56.5%; relapses: OS 73.6%. Four categories were obtained for EFS based on the type of recurrence and stage: PD and stage 3–4: EFS 25.5%; PD and stage 1–2: EFS 43%; relapse and stage 3–4: EFS 55.4%; relapse and stage 1–2: EFS 72.1%. Patients with PD, in advanced stage, or with ≥5 involved sites had a very poor survival and they should be considered refractory to first- and second-line standard chemotherapy. Probably, they should be considered for more innovative approaches since the first progression. Conversely, patients who relapsed later with localized disease had a better prognosis, and they could be considered for a conservative approach.

Introduction.The presence of iron deposits results in a significant reduction in all magnetic resonance imaging (MRI) relaxation times (T1, T2 and T2*). In the clinical setting the T2* technique is the method of choice for cardiac iron quantification and it has revolutionized the management of patients with hemoglopinopathies. Purpose.To compare myocardial T2 against T2* in patients with thalassemia major (TM) for myocardial iron characterization. Methods.133 TM patients (79 females, 38.4±11.3 years) enrolled in the Extension Myocardial Iron Overload in Thalassemia (eMIOT) Network were considered. T2 and T2* images were acquired, respectively, with multi-echo fast-spin-echo and gradient-echo sequences. Global heart T2 and T2* values were obtained by averaging the values in all 16 myocardial segments. The normal T2 range was established as mean±2 standard deviations on data acquired on 80 healthy volunteers (males: 48-56 ms and females: 50-57 ms). The lower limit of normal for global heart T2*, established on the same healthy population, was 32 ms. Results.A significant correlation was detected between global heart T2 and T2* values (R=0.577; P<0.0001) (Figure). Out of the 113 (84.9%) patients with a normal global heart T2* value, none had a decreased global heart T2 value, while 58 (51.3%) had an increased T2 value. Out of the 20 patents with a decreased global heart T2* value, only 10 (50%) had also a reduced T2 value. Conversely, 9 (45.0%) had a normal global heart T2 value and one (4.5) showed an increased T2 value. The 59 patients with increased global heart T2 value were significantly older than the remaining patients (40.8±10.5 vs 36.4±11.6 years; P=0.019) Conclusion.All patients with decreased T2 value had also a decreased T2* value and in half of the patients iron load was undetected by T2, suggesting that T2 mapping does not offer any advantage in terms of sensitivity for MIO assessment. However, more than half of TM patients had an increased T2 value, thus may be caused by the presence of myocardial inflammation and/or edema. So, T2 mapping could reveal subclinical myocardial involvement in TM patients. Figure Disclosures Pistoia: Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.Meloni:Chiesi Farmaceutici S.p.A.:Other: speakers' honoraria.

Background. A preliminary study involving 59 patients demonstrated that pancreatic iron assessed by magnetic resonance imaging (MRI) was the strongest overall predictor of glucose dysregulation in thalassemia major (TM) patients. Aim. In the present multicenter study we explored systematically the link between pancreatic iron and glucidic metabolism in a large cohort of TM patients. Methods. We considered 705 TM patients (372 F, mean age 37.00±9.95 years) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. The pattern of disturbances of glucose metabolism was assessed by means of the oral glucose tolerance test (OGTT). Results. According to OGTT results, 546 patients (77.4%) had normal glucose tolerance (NGT), 14 (2.0%) had isolated impaired fasting glucose (IFG), 29 (4.1%) had impaired glucose tolerance (IGT), and 116 (16.5%) had diabetes mellitus (DM). None of the 85 patients (12.1%) without pancreatic iron overload (global pancreas T2*≥26 ms) had IGT or DM (Figure 1). The 84.6% of patients with NGT had pancreatic iron overload. The global pancreatic T2* values were significantly higher in patients with NGT than in patients with DM (13.58±11.08 ms versus 8.09±4.72 ms, P<0.0001). Receiver operator characteristic (ROC) analysis showed that a global pancreas T2*<13.73 ms was the optimal cutoff for predicting an abnormal OGTT, with an area under the curve (AUC) of 0.62. Global pancreas T2* values showed a weak significant correlation with insulin values (R=0.160; P=0.002) and homeostasis model assessment-insulin resistance (HOMA-IR) index (R=0.122; P=0.019). Conclusion. A normal global pancreas T2* value has a negative predictive value of 100% for IGT and DM. The low specificity of pancreatic iron overload for glucose dysregulation seems to support the hypothesis that a latency time is need before pancreatic iron burden could give impaired glucose tolerance and overt diabetes mellitus. Figure 1 Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

Background: In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Our aim was to detect if the presence of a β°/β° homozygous genotype is associated to increased iron overload and rate of complications.

Background. Some preliminary data have postulated a correlation between pancreatic iron overload and heart iron and function in thalassemia major (TM) patients. In the present study we explored systematically in a multicenter study the link heart-pancreas in a large cohort of TM patients .

The age at which it is necessary to start Cardiovascular Magnetic Resonance (CMR) T2* screening in thalassaemia major (TM) is still uncertain. To clarify this point, we evaluated the prevalence of myocardial iron overload (MIO), function and fibrosis by CMR in TM patients younger than 10 years. We retrospectively selected 35 TM patients enrolled in the Myocardial Iron Overload in Thalassaemia network. MIO was measured by T2* multislice multiecho technique. Biventricular function parameters were evaluated by cine images. To detect myocardial fibrosis, late gadolinium enhancement images were acquired. Patients' age ranged from 4·2 to 9·7 years. All scans were performed without sedation. Nine patients showed no MIO, 22 patients had heterogeneous MIO with a T2* global value ≥20 ms; two patients had heterogeneous MIO with a T2* global value <20 ms and two patients showed homogeneous MIO. No patient showed myocardial fibrosis. Among the patients with heart T2*<20 ms, the youngest was 6 years old, none showed heart dysfunction and the iron transfused was <35 g in all cases. Cardiac iron loading can occur much earlier than previously described. The first cardiac T2* assessment should be performed as early as feasible without sedation, especially if chelation is started late or if poor compliance is suspected.

Neurological symptoms can represent the first clinical manifestation of central nervous system (CNS) involvement in Hodgkin lymphoma (HL). Because of its rarity, it is often misunderstood for other pathological processes. We report two cases of pediatric CNS HL, presenting with neurological symptoms at diagnosis. We have also reviewed the literature and few cases are reported, only 19 of them concerning children. In both primary and metastatic CNS HL, all patients complained of neurological symptoms at presentation. Despite it being uncommon, physicians should regard the possibility of CNS localization in all children affected by HL presenting with neurological signs and/or symptoms.

Pseudoxanthoma Elasticum (PXE) is an autosomal recessive, multisystem disorder affecting connective tissues. We describe three cases of the acquired PXE-like syndrome that often occurs in association with hemolytic anemias, in particular the hemoglobinopathies, and review the literature on the subject. The pathogenesis of the acquired PXE-like lesions is not yet completely understood. None of the mutations observed in the inherited form has been detected in the syndrome accompanying thalassemia. The cardiovascular complications could be life-threatening. Therefore, an close surveillance of these patients is mandatory.