TRI-SCORE and benefit of intervention in patients with severe tricuspid regurgitation.

BACKGROUND AND AIMS: Benefit of tricuspid regurgitation (TR) correction and timing of intervention are unclear. This study aimed to compare survival rates after surgical or transcatheter intervention to conservative management according to a TR clinical stage as assessed using the TRI-SCORE. METHODS: A total of 2,413 patients with severe isolated functional TR were enrolled in TRIGISTRY (1217 conservatively managed, 551 isolated tricuspid valve surgery, and 645 transcatheter valve repair). The primary endpoint was survival at 2 years. RESULTS: The TRI-SCORE was low (≤3) in 32%, intermediate (4-5) in 33%, and high (≥6) in 35%. A successful correction was achieved in 97% and 65% of patients in the surgical and transcatheter groups, respectively. Survival rates decreased with the TRI-SCORE in the three treatment groups (all P < .0001). In the low TRI-SCORE category, survival rates were higher in the surgical and transcatheter groups than in the conservative management group (93%, 87%, and 79%, respectively, P = .0002). In the intermediate category, no significant difference between groups was observed overall (80%, 71%, and 71%, respectively, P = .13) but benefit of the intervention became significant when the analysis was restricted to patients with successful correction (80%, 81%, and 71%, respectively, P = .009). In the high TRI-SCORE category, survival was not different to conservative management in the surgical and successful repair group (61% and 68% vs 58%, P = .26 and P = .18 respectively). CONCLUSIONS: Survival progressively decreased with the TRI-SCORE irrespective of treatment modality. Compared to conservative management, an early and successful surgical or transcatheter intervention improved 2-year survival in patients at low and, to a lower extent, intermediate TRI-SCORE, while no benefit was observed in the high TRI-SCORE category.

Virtual food exposure with positive mood induction or social support to reduce food anxiety in anorexia nervosa: A feasibility study.

OBJECTIVE: Aversive emotions toward food and the consequences of eating are at the core of anorexia nervosa. Exposure therapy is effective to reduce anxiety and avoidance toward feared stimuli. Based on the inhibitory learning framework, this study examined the feasibility to induce social support or positive mood to enhance the impact of a single session virtual food exposure on food-related anxiety in anorexia nervosa. METHOD: One hundred and forty-five patients were randomized to: (1) virtual food exposure (i.e., baseline condition), (2) virtual food exposure plus positive mood induction (i.e., positive mood condition), or (3) virtual food exposure plus social support (i.e., social support condition). They completed self-report assessments of anxiety toward virtual foods, general anxiety, positive mood, social support, and hunger, before and after virtual food exposure. Number of eye gazes and touches toward foods were recorded during the virtual reality exposure. RESULTS: Patients had lower levels of anxiety toward virtual foods in the positive mood condition, compared to the baseline condition [F(2,141) = 4.36, p = .015; medium effect size]. They also touched food items more often in the baseline condition. No other significant changes were found. DISCUSSION: Virtual food exposure enhanced by positive mood induction seems a feasible approach to strengthen the impact of food exposure in anorexia nervosa. PUBLIC SIGNIFICANCE: This research contributes to the understanding of how patients with anorexia nervosa can be supported to overcome fear and anxiety around food. Virtual reality enables patients to expose themselves to difficult situations (e.g., kitchen with foods of various calorie contents) while experiencing positive stimuli, such as a loving and kind pet or a supportive avatar.

When time worsens framing: a longitudinal analysis of the psychological effects of the COVID-19 pandemic in women with an eating disorder and their healthy sisters.

The COVID-19 pandemic has profoundly affected individuals with eating disorders (ED), leading to an exacerbation of symptoms worldwide in 2020. However, there is a lack of longitudinal analyses of the psychological burdens experienced by this population. This study aims to longitudinally assess the psychological effects of the COVID-19 pandemic in people with ED and their healthy sisters (HS) 1 and 2 years after the onset of the crisis. A sample of 148 individuals, consisting of 73 with ED and 45 HS, was evaluated in spring 2021 and spring 2022 regarding their current psychological and behavioral states. Participants were also asked to reflect on their feelings and behaviors during the 2020 lockdown. General psychopathology, eating disorders, and trauma-related symptoms were evaluated using validated questionnaires. Both groups showed an overall improvement in psychopathological symptoms with time. Individuals with ED exhibited greater improvement compared to their HS, which may be attributed to their initially higher burden. Individuals with ED reported a negative reframe, characterized by internalizing negative emotions and behaviors related to the 2020 lockdown. This longitudinal evaluation revealed two distinct and contrasting effects. Both ED patients and their HS demonstrated psychological improvement over time. However, people with ED experienced a negative reframe that affected their memory of specific life events, subsequently affecting their psychological well-being. These findings shed light on the clinical severity observed in people with ED during these pandemic years.

A novel versatile concept of cardioplegia delivery in cardiac surgery: The ReverseTWO cardioplegia circuit system.

Nowadays, the necessity of having a cardioplegia circuit capable of being adapted in order to administer different types of cardioplegia is strategically fundamental, both for the perfusionist and for the cardiac surgeon. This allows to avoid cutting tubes, guarantees sterility and, most of all, limits the number of cardioplegia circuits for the different strategies of cardiac arrest. The novel "ReverseTWO cardioplegia circuit system" is the development of the precedent "Reverse system" where mainly the 4:1 and crystalloid cardioplegia were used, It has the advantage of allowing immediate change of cardioplegia set-up versus four types of cardioplegia technique, when the strategy is unexpectedly changed before the beginning of cardiopulmonary bypass (CPB), is safe and enables the perfusionist to use one single custom pack of cardioplegia. Two pediatric roller pumps are usually used in our centre for cardioplegia administration; they have a standardized calibration (the leading with » inch and the follower with 1/8 inch) and the circuit consequently has two different tube diameters for the two different pumps. The presence in the circuit of two different shunts coupled with two different coloured clamps allows the immediate set-up for different cardioplegia administration techniques utilizing a colour-coding mechanism The aim of this manuscript is to present the new ReverseTWO Circuit. This novel system allows to administer four different cardioplegic solutions (4:1, 1:4, crystalloid, ematic) based on multiple tubes, which can be selectively clamped, identified through a color-coding method. The specificity of this circuit is the great versatility, which leads to numerous advantages, such as reduced risk of perfusion accident and reduced costs related not only to the purchase of different cardioplegia kits but also to the storage. https://youtu.be/ovJBE4ok2Ds.

Pediatric gray zone lymphoma according to the 2022 WHO classification: An Italian cohort study.

BACKGROUND: The 2022 World Health Organization (WHO) classification redefines the concept of gray zone lymphoma (GZL), restricting it in practice to cases of mediastinal/thymic origin (mediastinal gray zone lymphoma, MGZL) with overlapping features between primary mediastinal B-cell lymphoma (PMBCL) and classical Hodgkin lymphoma (CHL). Cases with histological characteristics of GZL but occurring without mediastinal involvement are better classified as diffuse large B-cell lymphoma, not otherwise specified (DLBCL NOS), with few exceptions. PROCEDURE: We collected clinical and pathological data about all Italian pediatric patients diagnosed with GZL over a 20-year period. RESULTS: We identified only four cases of bona fide MGZL. All patients were adolescent and presented with a mediastinal disease, always associated with other nodal involvement. B symptoms and increased levels of both erythrocyte sedimentation rate (ESR) and lactate dehydrogenase (LDH) were observed. Only two patients achieved a first complete remission, suggesting a more aggressive clinical behavior than either PMBCL or CHL. CONCLUSION: Prospective studies evaluating prognostic factors and establishing the most effective first-line therapy for MGZL are highly needed.

Beyond body image: what body schema and motor imagery can tell us about the way patients with anorexia nervosa experience their body.

AIM: Recent evidence suggests that the body image disturbance often observed in patients with anorexia nervosa also extends to the body schema. According to the embodiment approach, the body schema is not only involved in motor execution, but also in tasks that only require a mental simulation of a movement such as motor imagery, mental rotation of bodies, and visuospatial perspective-taking. The aim of the present study was to assess the ability of patients with anorexia to mentally simulate movements. METHODS: The sample included 52 patients with acute anorexia and 62 healthy controls. All participants completed three tests of explicit motor imagery, a mental rotation test and a test of visuospatial perspective-taking. RESULTS: Patients with anorexia nervosa, with respect to controls, reported greater difficulties in imagining movements according to a first-person perspective, lower accuracy in motor imagery, selective impairment in the mental rotation of human figures, and reduced ability in assuming a different egocentric visuospatial perspective. CONCLUSION: These results are indicative of a specific alteration in motor imagery in patients with anorexia nervosa. Interestingly, patients' difficulties appear to be limited to those tasks which specifically rely on the body schema, while patients and controls performed similarly in the 3D objects mental rotation task.

One year of COVID-19 pandemic on patients with eating disorders, healthy sisters, and community women: evidence of psychological vulnerabilities.

PURPOSE: The COVID-19 pandemic has been a psychological burden worldwide, especially for individuals with eating disorders (EDs). In addition, the healthy sisters of patients with EDs are known to present specific psychological vulnerabilities. This study evaluates differences between the general population, patients with EDs, and their healthy sisters. METHOD: A group of 233 participants (91 patients with EDs, 57 of their healthy sisters and 85 community women) was enrolled in an online survey on general and specific psychopathology 1 year after the beginning of the COVID-19 pandemic. The survey examined associations between posttraumatic symptoms and depression, anxiety, obsessive-compulsiveness, interpersonal sensitivity, and eating-related concerns. RESULTS: Clinically relevant scores for posttraumatic disorders were found in patients with EDs. Healthy sisters scored similarly to patients for avoidance. Regression analysis showed specific associations between interpersonal sensitivity and posttraumatic symptomatology in patients and healthy sisters, but not in community women. CONCLUSION: The psychological burden in patients with EDs is clinically relevant and linked to interpersonal sensitivity, obsessive-compulsiveness, and global symptom severity. Differences between patients, healthy sisters, and community women are discussed regarding vulnerability factors for EDs. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies.

Fate of mild-to-moderate bicuspid aortic valve disease untreated during ascending aorta replacement.

BACKGROUND: Bicuspid aortic valve (BAV) is the most common congenital heart defect and it is responsible for an increased risk of developing aortic valve and ascending aorta complications. In case of mild to moderate BAV disease in patients undergoing supracoronary ascending aorta replacement, it is unclear whether a concomitant aortic valve replacement should be performed. METHODS: From June 2002 to January 2020, 75 patients with mild-to-moderate BAV regurgitation (±mild-to-moderate stenosis) who underwent isolated supracoronary ascending aorta replacement were retrospectively analyzed. Clinical and echocardiographic follow-up was 100% complete (mean: 7.4 ± 3.9 years, max: 16.4). Kaplan-Meier estimates were employed to analyze long-term survival. Cumulative incidence function (CIF) for time to reoperation, recurrence of aortic regurgitation (AR) ≥3+ and aortic stenosis (AS) greater than moderate, with death as competing risk, were computed. RESULTS: There was no hospital mortality and no cardiac death occurred. Overall survival at 12 years was 97.4 ± 2.5%, 95% confidence interval (CI: 83.16-99.63). At follow-up there were no cases of aortic root surgery whereas three patients underwent AV replacement. At 12 years the CIF of reoperation was 2.6 ± 2.5%, 95% CI [0.20-11.53]. At follow-up, AR 3+/4+ was present in 1 pt and AS greater than moderate in 3. At 12 years the CIF of AR more than 2+/4+ was 5.1 ± 4.98% and of AS more than moderate 6.9 ± 3.8%. CONCLUSIONS: In our study mild to moderate regurgitation of a BAV did not do significantly worse at least up to 10 years after isolated supracoronary ascending aorta replacement.

Complicated postoperative course in isolated tricuspid valve surgery: Looking for predictors.

BACKGROUND: This study aims at better defining the profile of patients with a complicated versus noncomplicated postoperative course following isolated tricuspid valve (TV) surgery to identify predictors of a favorable/unfavorable hospital outcome. METHODS: All patients treated with isolated tricuspid surgery from March 1997 to January 2020 at our institution were retrospectively reviewed. Considering the complexity of most of these patients, a regular postoperative course was arbitrarily defined as a length-of-stay in intensive care unit less than 4 days and/or postoperative length-of-stay less than 10days. Patients were therefore divided accordingly in two groups. RESULTS: One hundred and seventy-two patients were considered, among whom 97 (56.3%) had a regular (REG) and 75 (43.6%) a non-regular (NEG) postoperative course. The latter had worse baseline clinical and echocardiographic characteristics, with higher rate of renal insufficiency, previous heart failure hospitalizations, cardiac operations, and right ventricular dysfunction. NEG patients more frequently needed tricuspid replacement and experienced a greater number of complications (p < .001) and higher in-hospital mortality (13% vs. 0%, p < .001). The majority of these complications were related to more advanced stage of the tricuspid disease. Among most important predictors of a negative outcome univariate analysis identified chronic kidney disease, ascites, previous right heart failure hospitalizations, right ventricular dysfunction, previous cardiac surgeries, TV replacement and higher MELD scores. At multivariate analysis, liver enzymes and diuretics' dose were predictors of complicated postoperative course. CONCLUSION: In isolated TV surgery a complicated postoperative course is observed in patients with more advanced right heart failure and organ damage. Earlier surgical referral is associated to excellent outcomes and should be recommended.

Comparing traditional aortic valve surgery and transapical approach to transcatheter aortic valve implant.

During the last 15 years, transcatheter aortic valve implant (TAVI) has become a valid alternative to surgical aortic valve replacement in symptomatic patients with severe aortic stenosis, and high or intermediate operative risk. Transcatheter aortic valve implant could be approached through various access sites, among which the transapical has long been one of the most popular. Through the years, this procedure has shown results similar to the standard surgical approach, but not as good as the same procedure via the transfemoral approach. For this reason, along with continuous technological advances, the transfemoral approach is used, presently, in 90% of the patient, while the transapical route has been limited, progressively, to a minority of patients. Currently the Heart Team should decide, in every single patient, between conventional surgery and TAVI. In clinical practice, TAVI is favoured in high-risk patients, and in the elderly at intermediate surgical risk with favourable anatomical features. In patients in whom TAVI is preferable to surgery, but have 'non-usable' femoral approach, alternative routes, such as transaxillary or transapical, could be considered.

Proteomic Profiles and Biological Processes of Relapsed vs. Non-Relapsed Pediatric Hodgkin Lymphoma.

The identification of circulating proteins associated with relapse in pediatric Hodgkin lymphoma (HL) may help develop predictive biomarkers. We previously identified a set of predictive biomarkers by difference gel electrophoresis. Here we used label-free quantitative liquid chromatography-mass spectrometry (LC-MS/MS) on plasma collected at diagnosis from 12 children (age 12-16 years) with nodular sclerosis HL, including six in whom the disease relapsed within 5 years of treatment in the LH2004 trial. Plasma proteins were pooled in groups of three, separately for non-relapsing and relapsing HL, and differentially abundant proteins between the two disease states were identified by LC-MS/MS in an explorative and validation design. Proteins with a fold change in abundance >1.2 or ≤0.8 were considered "differentially abundant". LC-MS/MS identified 60 and 32 proteins that were more abundant in non-relapsing and relapsing HL plasma, respectively, in the explorative phase; these numbers were 39 and 34 in the validation phase. In both analyses, 11 proteins were more abundant in non-relapsing HL (e.g., angiotensinogen, serum paraoxonase/arylesterase 1, transthyretin), including two previously identified by difference gel electrophoresis (antithrombin III and α-1-antitrypsin); seven proteins were more abundant in relapsing HL (e.g., fibronectin and thrombospondin-1), including two previously identified proteins (fibrinogen ß and γ chains). The differentially abundant proteins participated in numerous biological processes, which were manually grouped into 10 biological classes and 11 biological regulatory subclasses. The biological class Lipid metabolism, and its regulatory subclass, included angiotensinogen and serum paraoxonase/arylesterase 1 (more abundant in non-relapsing HL). The biological classes Immune system and Cell and extracellular matrix architecture included fibronectin and thrombospondin-1 (more abundant in relapsing HL). These findings deepen our understanding of the molecular scenario underlying responses to therapy and provide new evidence about these proteins as possible biomarkers of relapse in pediatric HL.

FDG PET in response evaluation of bulky masses in paediatric Hodgkin's lymphoma (HL) patients enrolled in the Italian AIEOP-LH2004 trial.

PURPOSE: We present the results of an investigation of the role of FDG PET in response evaluation of bulky masses in paediatric patients with Hodgkin's lymphoma (HL) enrolled in the Italian AIEOP-LH2004 trial. METHODS: We analysed data derived from 703 patients (388 male, 315 female; mean age 13 years) with HL and enrolled in 41 different Italian centres from March 2004 to September 2012, all treated with the AIEOP-LH2004 protocol. The cohort comprised 309 patients with a bulky mass, of whom 263 were evaluated with FDG PET at baseline and after four cycles of chemotherapy. Responses were determined according to combined functional and morphological criteria. Patients were followed up for a mean period of 43 months and for each child we calculated time-to-progression (TTP) and relapse rates considering clinical monitoring, and instrumental and histological data as the reference standard. Statistical analyses were performed for FDG PET and morphological responses with respect to TTP. Multivariate analysis was used to define independent predictive factors. RESULTS: Overall, response evaluation revealed 238 PET-negative patients (90.5%) and 25 PET-positive patients (9.5%), with a significant difference in TTP between these groups (mean TTP: 32.67 months for negative scans, 23.8 months for positive scans; p < 0.0001, log-rank test). In the same cohort, computed tomography showed a complete response (CR) in 85 patients (32.3%), progressive disease (PD) in 6 patients (2.3%), and a partial response (PR) in 165 patients (62.7%), with a significant difference in TTP between patients with CR and patients with PD (31.1 months and 7.9 months, respectively; p < 0.001, log-rank test). Similarly, there was a significant difference in relapse rates between PET-positive and PET-negative patients (p = 0000). In patients with PR, there was also a significant difference in TTP between PET-positive and PET-negative patients (24.6 months and 34.9 months, respectively; p < 0.0001). In the multivariate analysis with correction for multiple testing, only the PET result was an independent predictive factor in both the entire cohort of patients and the subgroup showing PR on CT (p < 0.01). CONCLUSION: After four cycles of chemotherapy, FDG PET response assessment in paediatric HL patients with a bulky mass is a good predictor of TTP and disease outcome. Moreover, in patients with a PR on CT, PET was able to differentiate those with a longer TTP. In paediatric HL patients with a bulky mass and in patients with a PR on CT, response on FDG PET was an independent predictive factor.

Acute Normovolemic Hemodilution Reduces Allogeneic Red Blood Cell Transfusion in Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: To better understand the role of acute normovolemic hemodilution (ANH) in a surgical setting with high risk of bleeding, we analyzed all randomized controlled trials (RCTs) in the setting of cardiac surgery that compared ANH with standard intraoperative care. The aim was to assess the incidence of ANH-related number of allogeneic red blood cell units (RBCu) transfused. Secondary outcomes included the rate of allogeneic blood transfusion and estimated total blood loss. METHODS: Twenty-nine RCTs for a total of 2439 patients (1252 patients in the ANH group and 1187 in the control group) were included in our meta-analysis using PubMed/MEDLINE, Cochrane Controlled Trials Register, and EMBASE. RESULTS: Patients in the ANH group received fewer allogeneic RBCu transfusions (mean difference = -0.79; 95% confidence interval [CI], -1.25 to -0.34; P = .001; I = 95.1%). Patients in the ANH group were overall transfused less with allogeneic blood when compared with controls (356/845 [42.1%] in the ANH group versus 491/876 [56.1%] in controls; risk ratio = 0.74; 95% CI, 0.62 to 0.87; P < .0001; I = 72.5%), and they experienced less postoperative blood loss (388 mL in ANH versus 450 mL in control; mean difference = -0.64; 95% CI, -0.97 to -0.31; P < .0001; I = 91.8%). CONCLUSIONS: ANH reduces the number of allogeneic RBCu transfused in the cardiac surgery setting together with a reduction in the rate of patients transfused with allogeneic blood and with a reduction of bleeding.

Detection of prognostic factors in children and adolescents with Burkitt and Diffuse Large B-Cell Lymphoma treated with the AIEOP LNH-97 protocol.

Burkitt lymphoma (BL) and Diffuse Large B-Cell Lymphoma (DLBCL) account for most cases of non-Hodgkin lymphoma (NHL) in childhood. We report the clinical characteristics, outcome and prognostic factors in children with BL or DLBCL treated according to the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) LNH-97 protocol. Patients aged up to 18 years that were newly diagnosed with BL/DLBCL were included in the study. Therapy consisted of pre-phase followed by 2-6 high-dose chemotherapy courses tailored according to lactate dehydrogenase (LDH) value and disease stage. A total of 442 patients (379 BL, 63 DLBCL) were enrolled between 1997 and 2014, of whom 18 failed to achieve remission, 6 experienced treatment-related death, 2 developed second malignancy and 20 relapsed. At a median follow-up time of 5 years, overall survival was 93% (±1%) and event-free survival was 90% (±1%). LDH value above the median value had an independently negative prognostic value (P < 0·0001). However, in the subgroup of 128 patients in which minimal disseminated disease (MDD) was analysed, MDD-positivity became the only unfavourable prognostic factor for progression-free survival. Tailored chemotherapy could be extremely effective with limited toxicity. Identification of MDD as a hallmark of a higher risk of treatment failure may provide a target population for treatment intensification by anti-CD20.

Hodgkin lymphoma in a patient with mosaic trisomy 18: First clinical observation.

We report the case of a 17-year-old boy with a mosaic trisomy 18, who was diagnosed with Hodgkin lymphoma. The patient showed only poor growth and two muscular ventricular septal defects; no facial dysmorphims were present. He was admitted to our hospital because of asthenia and weight loss; a mediastinal enlargement was found and an histological diagnosis of nodular sclerosis Hodgkin lymphoma on mediastinal biopsy was performed. Contextually, a chromosomal analysis on bone marrow aspirate and on peripheral blood revealed a mosaic trisomy 18. This result was confirmed also with cytogenetic analysis on skin fibroblasts. While there is a well-documented association between trisomy 18 and solid cell tumors, this is, to our knowledge, the first reported case of Hodgkin lymphoma in a patient with a mosaic trisomy 18, enlarging the spectrum of possible oncologic manifestations of the disease.

Tigecycline Lock Therapy for Catheter-Related Bloodstream Infection Caused by KPC-Producing Klebsiella pneumoniae in Two Pediatric Hematological Patients.

Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.

Non-Hodgkin lymphoma in children with an associated inherited condition: A retrospective analysis of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

BACKGROUND: Inherited conditions affecting genetic aberration, viral oncogenesis, reduced immune surveillance, and long-lasting antigen stimulation may build the way to lymphomagenesis in humans. METHODS: We extracted from the database of 4 consecutive trials for pediatric non-Hodgkin lymphoma (NHL) all cases with an associated genetic disease. RESULTS: Among 1,430 patients, 34 (2.4%) had an associated inherited condition and a mature B-lineage (n = 28), anaplastic large cell lymphoma (n = 4), or T-lineage (n = 2) NHL. Their median age at the diagnosis was 9.3 years (range, 2.6-17.8 years). In 14 cases (41%) the underlying condition was considered to be a potential cause for undue toxicity if the expected therapy was applied. Thus, treatment modification had been planned in advance. The overall survival was 89% (standard error [SE] 1%), 73% (SE 10%), and 73% (SE 23%) at 3 years for registered patients with no inherited condition associated, with genetic abnormalities and with underlying condition causing an immune deficiency, respectively (P = 0.003). CONCLUSION: In our cohort, patients with NHL with an underlying constitutional condition represent the 2.4% of the cases. In the subset of patients with primary immune deficiency, which may have contributed to lymphomagenesis, allogeneic hematopoietic stem cell transplantation may be required. In the remaining patients, the association with lymphoma remains apparently unexplained and could be not causative. Detailed reporting of such cases may contribute to disclose even rare and fully unexpected association, which may have implications for research in the field of lymphomagenesis.

Long-term results of the AIEOP LNH-97 protocol for childhood lymphoblastic lymphoma.

BACKGROUND: Treatment intensification was considered a suitable strategy to increase the cure rate of lymphoblastic lymphoma (LBL) in children. PROCEDURE: The AIEOP LNH-97 trial was run between 1997 and 2007 for newly diagnosed LBL in patients aged less than 18 years. Treatment schedule was based on the previous, LSA2-L2 derived, AIEOP LNH-92 protocol. Modifications included: increased dose of upfront cyclophosphamide and methotrexate, use of l-Asparaginase during induction therapy, intensive block therapy for slow responders, and late intensification ("Reinduction") for patients with advanced stage disease. Total therapy duration was 12 months for stage I and II, and 24 months for stage III and IV. Central nervous system prophylaxis did not include cranial irradiation. RESULTS: 114 eligible patients were enrolled, 84 males and 30 females; median age was 9 years. Complete remission was obtained in 98% of patients. After a median follow-up time of seven years, 29 patients failed due to progression of disease (n = 2), relapse (n = 25), or second malignancy (n = 2). The 7-year overall survival was 82% (standard error [SE] 4%) and the 7-year event-free survival was 74% (SE 4%). No subgroup showed significantly different event free survival. None of the patients died of front line chemotherapy-related toxicity. CONCLUSIONS: Treatment intensification was associated with good outcome in children and adolescents with LBL, with limited toxicity. Prognosis after relapse was better for patients who underwent allogeneic hematopoietic stem cell transplantation. Measurements of biological markers and treatment response are necessary for achieving further improvement through more accurate identification and stratification of patients at risk of disease relapse.