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Autoimmune systemic diseases (ASD) may show impaired immunogenicity to COVID-19 vaccines. Our prospective observational multicenter study aimed to evaluate the seroconversion after the vaccination cycle and at 6-12-month follow-up, as well the safety and efficacy of vaccines in preventing COVID-19. The study included 478 unselected ASD patients (mean age 59 ± 15 years), namely 101 rheumatoid arthritis (RA), 38 systemic lupus erythematosus (SLE), 265 systemic sclerosis (SSc), 61 cryoglobulinemic vasculitis (CV), and a miscellanea of 13 systemic vasculitis. The control group included 502 individuals from the general population (mean age 59 ± 14SD years). The immunogenicity of mRNA COVID-19 vaccines (BNT162b2 and mRNA-1273) was evaluated by measuring serum IgG-neutralizing antibody (NAb) (SARS-CoV-2 IgG II Quant antibody test kit; Abbott Laboratories, Chicago, IL) on samples obtained within 3 weeks after vaccination cycle. The short-term results of our prospective study revealed significantly lower NAb levels in ASD series compared to controls [286 (53-1203) vs 825 (451-1542) BAU/mL, p < 0.0001], as well as between single ASD subgroups and controls. More interestingly, higher percentage of non-responders to vaccine was recorded in ASD patients compared to controls [13.2% (63/478), vs 2.8% (14/502); p < 0.0001]. Increased prevalence of non-response to vaccine was also observed in different ASD subgroups, in patients with ASD-related interstitial lung disease (p = 0.009), and in those treated with glucocorticoids (p = 0.002), mycophenolate-mofetil (p < 0.0001), or rituximab (p < 0.0001). Comparable percentages of vaccine-related adverse effects were recorded among responder and non-responder ASD patients. Patients with weak/absent seroconversion, believed to be immune to SARS-CoV-2 infection, are at high risk to develop COVID-19. Early determination of serum NAb after vaccination cycle may allow to identify three main groups of ASD patients: responders, subjects with suboptimal response, non-responders. Patients with suboptimal response should be prioritized for a booster-dose of vaccine, while a different type of vaccine could be administered to non-responder individuals., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Covid-19 infection poses a serious challenge for immune-compromised patients with inflammatory autoimmune systemic diseases. We investigated the clinical-epidemiological findings of 1641 autoimmune systemic disease Italian patients during the Covid-19 pandemic., Method: This observational multicenter study included 1641 unselected patients with autoimmune systemic diseases from three Italian geographical areas with different prevalence of Covid-19 [high in north (Emilia Romagna), medium in central (Tuscany), and low in south (Calabria)] by means of telephone 6-week survey. Covid-19 was classified as (1) definite diagnosis of Covid-19 disease: presence of symptomatic Covid-19 infection, confirmed by positive oral/nasopharyngeal swabs; (2) highly suspected Covid-19 disease: presence of highly suggestive symptoms, in absence of a swab test., Results: A significantly higher prevalence of patients with definite diagnosis of Covid-19 disease, or with highly suspected Covid-19 disease, or both the conditions together, was observed in the whole autoimmune systemic disease series, compared to "Italian general population" (p = .030, p = .001, p = .000, respectively); and for definite + highly suspected diagnosis of Covid-19 disease, in patients with autoimmune systemic diseases of the three regions (p = .000, for all comparisons with the respective regional general population). Moreover, significantly higher prevalence of definite + highly suspected diagnosis of Covid-19 disease was found either in patients with various "connective tissue diseases" compared to "inflammatory arthritis group" (p < .000), or in patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs treatments (p = .011)., Conclusions: The finding of a higher prevalence of Covid-19 in patients with autoimmune systemic diseases is particularly important, suggesting the need to develop valuable prevention/management strategies, and stimulates in-depth investigations to verify the possible interactions between Covid-19 infection and impaired immune-system of autoimmune systemic diseases. Key Points • Significantly higher prevalence of Covid-19 is observed in a large series of patients with autoimmune systemic diseases compared to the Italian general population, mainly due to patients' increased susceptibility to infections and favored by the high exposure to the virus at medical facilities before the restriction measures on individual movement. • The actual prevalence of Covid-19 in autoimmune systemic diseases may be underestimated, possibly due to the wide clinical overlapping between the two conditions, the generally mild Covid-19 disease manifestations, and the limited availability of virological testing. • Patients with "connective tissue diseases" show a significantly higher prevalence of Covid-19, possibly due to deeper immune-system impairment, with respect to "inflammatory arthritis group". • Covid-19 is more frequent in the subgroup of autoimmune systemic diseases patients without ongoing conventional synthetic disease-modifying anti-rheumatic drugs, mainly hydroxyl-chloroquine and methotrexate, which might play some protective role against the most harmful manifestations of Covid-19.

Purpose: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy., Methods: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice., Results: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns., Conclusion: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.

Forty-five consecutive patients submitted to a bone marrow transplant (BMT) were followed up weekly in order to evaluate the incidence of cytomegalovirus (CMV) infections on the basis of CMV antigenemia and polymerase chain reaction. All but one transplanted patients engrafted; fourteen patients out of these were CMV antigenemia positive after 16-184 days (median 32.5, mean 43.4) with an 31.8% incidence. CMV infections were associated with graft-versus-host disease and immunogenetic relationship between the donor and the recipient. No CMV infection was detectable in autologous transplants while antigenemia was demonstrated in 3/11 and 6/7 patients with BMT from respectively mismatched related and matched unrelated donors.

This study reports a large cooperative experience in myeloablative therapy and bone marrow rescue undertaken to define better the outcome of children with disseminated neuroblastoma after megatherapy. Between 1984 and 1993, 135 children underwent myeloablative therapy with bone marrow transplantation (BMT) in nine Italian Centres. One hundred and seventeen children received unpurged autologous BMT, five allogeneic BMT and 13 peripheral blood progenitor cells as rescue. Of these 135 children, 57 were in 1st CR, 11 in 2nd or subsequent CR, 42 in 1st PR, and 25 had more advanced disease. Twelve children (9%) died of toxicity, 86 relapsed or progressed at 1-68 months (median 7 months) and 80 of these subsequently died of progressive disease. Forty-three children are still alive with 37 in continuous remission at a median of 65 months (30-123 months) after BMT. Overall and disease-free survival at 8 years are 28.5% (s.e. 4.3) and 26% (s.e. 4), respectively. Disease-free survival is 34.6% (s.e. 6.7) for the patients grafted in 1st complete remission, 23.6% (s.e. 6.6) for patients grafted in 1st partial remission, 36.4% (s.e. 14.5) for patients grafted in 2nd or subsequent CR, and 8% (5.4) for patients with advanced disease. We conclude these data confirm that early toxicity of myeloablative therapy is manageable and that myeloablative therapy with bone marrow rescue may contribute to an improved long-term survival of children with disseminated neuroblastoma but the objective of cure of all patients remains distant.

We retrospectively analyzed the data base of the Italian Association of Pediatric Hematology/Oncology BMT Group on the incidence and severity of GVHD in children given allogeneic BMT from HLA-identical sibling and receiving cyclosporin A (CsA) alone as GVHD prophylaxis. The study population included 145 patients for acute GVHD and 114 children at risk for chronic GVHD. Twelve patients had non-malignant diseases and 133 patients were affected by malignant disorders. Among the 145 patients (50 females, 95 males), 107 (74%) presented acute GVHD and 38 (26%) had no sign of disease. In the group of patients with acute GVHD, 38 children (26% of the whole study population) were found to have grade II disease, 9 (6% of the whole) grade III, 4 (3%) grade IV. Donor-recipient sex pairs had no significant influence on incidence of acute GVHD neither did donor-recipient age class stratification. Of the 114 patients evaluated for chronic GVHD, 86 (76%) developed no disease while 23 patients (20%) presented secondary chronic GVHD and 5 (4%) had de novo chronic GVHD. The incidence of chronic GVHD was higher in F-M than in M-M donor-recipient sex pairs (33% vs 11%, p < 0.05), with no difference between F-F and M-F. In patients of > 10 years, a higher incidence of chronic GVHD was observed in both female donors and recipients compared with male donors and recipients (48% vs 20% and 47% vs 19%, respectively, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

A multicenter cooperative group has been activated in Italy in 1986, with the aim of focusing on the following issues: to standardize perspectively the approach to bone marrow transplantation (BMT) in pediatric centers granting the recommendations of the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP); to study effects and toxicity of preparative regimens to BMT; to evaluate the special features of BMT in children, such as clinical management, care and late effects, as peculiar issues of a pediatric setting. Indeed, one of the major aims of the group is to attempt to address in the most appropriate ways, such as in children only and at a nation-wide level, the most crucial questions about the real role of BMT, taking advantage from the fact that most of the children with cancer undergoing BMT in Italy have been treated homogeneously before transplant, i.e. according to AIEOP protocols (70%). Accordingly, specific information were recorded by means of problem oriented forms, aimed to generate a full registry. The registry has been collecting the experiences of 10 pediatric hematology and oncology centers where children eligible for BMT were registered and/or where BMT was performed. This paper was meant both to summarize the 4 years activity of the registry and to analyze what we have learnt so far, as well as what may be suggested to design our future strategies by presently available although retrospective data. It is concluded that the pediatric BMT registry we set up appears useful and of growing interest and potential relevance.

This study was performed in 5 pediatric centers. It considered a group of children affected by acute lymphoblastic leukemia (ALL) treated with ABMT. 56 patients were considered, 35 males and 21 females, with a median age of 11 years. The children were transplanted in 2nd (36) or subsequent (20) complete remission. The mean of 1st remission duration was 32 months. Analysis of the sites of relapse before transplantation showed that 39 patients had bone marrow relapses, 17 patients had CNS and/or testicular isolated relapses only. 32 harvests were purged in vitro by 1 mcgr/ml Vincristine and 30 mcgr/ml Prednisone, 16 by 100 mcgr/ml Mafosfamide, 8 were not cleaned. 29 patients received high dose Vincristine (4 mg/m2), TBI (1200 cGy), Cyclophosphamide (3600 mg/m2) as standard conditioning regimen before transplant. 27 patients received other conditioning treatments with (14) or without (13) TBI. Of the 56 children 25 relapsed from 1 to 42 months after ABMT, 7 toxicity related deaths were registered and 1 death for second tumor was observed. 23 children remained in continuous complete remission from 1 to 49 months after transplantation. The probability of EFS at 4 years was 21%. High dose Vincristine did not statistically improve the EFS, but a trend was observed (44% versus 0%). Vincristine, Asta-Z or none purging did not show any significant effect on EFS (37% vs 32% vs 0%). On the contrary when the EFS was related to the site of relapse, isolated or sistemic, the difference was almost statistically significant (46% vs 18%). The analysis of our results indicates the isolated relapse as good prognostic factor in ABMT for ALL and high dose Vincristine associated to conditioning regimen as worthy of further investigations.

We report data from an Italian survey on ABMT in 93 AML children less than 14 years in 1st or 2nd remission performed in 15 Centers. Different conditioning regimens have been employed: BAVC, an original schedule of chemotherapy; TBI plus Cy and/or other drugs (TBI + CHT); other high dose chemotherapy schedules (HD CHT). 62 patients have been transplanted in 1st CR; 38 have been conditioned with BAVC, 16 with TBI + CHT and 8 with HD CHT. Relapses were 21 in the BAVC group (DFS = 35% at 66 months), 5 in the TBI group (DFS = 61% at 48 months) and 5 in the HD CHT group; overall DFS is 39% at 66 months. 31 patients have been transplanted in 2nd CR; 14 were conditioned with BAVC and 16 with TBI + CHT; 6 patients relapsed in the first group, DFS is 56% at 50 months; in the second group 2 early deaths and 3 relapses occurred, DFS is 65% at 65 months. 1 patient in 2nd CR, conditioned with HD CHT, died during aplasia. Overall DFS is 59% at 65 months. Although no final conclusions concerning ABMT in AML children may be drawn from this retrospective study because of heterogeneity of population and methods, results obtained in 2nd CR are clearly better to those obtained with standard chemotherapy alone, confirming the role of ABMT in this high risk category of patients.