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Telemonitoring is increasingly used in the management of IBD patients. We investigated the agreement between patients and physicians on scores of disease activity and burden.Consecutive outpatients at one IBD clinic were recruited between February and December 2021. Enrolled patients completed a questionnaire for disease activity (Harvey-Bradshaw Index [HBI] for Crohn's disease or Simple Clinical Colitis Activity Index [SCCAI] for ulcerative colitis) and a test of disease burden (Pictorial Representation of Illness and Self Measure [PRISM]). They did the tests within 5 days of an outpatient visit, working independently on IBD Tool, a new web-based telemonitoring application. Concomitantly, the senior and junior physicians who examined them completed the same tests. The agreement was tested for every pair of scores.Five hundred and sixty patients (289 Crohn's disease; 271 ulcerative colitis) completed disease questionnaires on IBD Tool (in total, 742 times). By Spearman's correlation, the agreement was substantial both for HBI (rho 0.685-0.837) and SCCAI (rho 0.694-0.888) for comparisons between patients, junior and senior physicians. The agreement was moderate-to-substantial for PRISM (rho 0.406-0.725) for the same comparisons. The correlation between disease activity (HBI/SCCAI) and PRISM scores was substantial for senior (rho 0.757-0.788) or junior (rho 0.746-0.753) physicians and moderate for patients (rho 0.458-0.486). The median PRISM score difference was 2.3-1.6 points lower between patients and senior-junior physicians.Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease impact. The inclusion of disease burden scoring in telemonitoring platforms provides important information for the management of IBD patients.Study highlightsWhat IS known•Continuous response to treatments and patient-reported outcomes became an essential goal for IBD patient management.•The use of tele-monitoring and eHealth technologies allows for regular disease assessments and for managing more efficiently IBD patients; disease questionnaires and tests are key to support eHealth tools.What is new here•Agreement between IBD patients and physicians was substantial for disease activity and moderate for disease burden, while agreement among junior and senior physicians was substantial for both.•PRISM performs as well for ulcerative colitis as for Crohn's patients.•The inclusion of disease burden tests might add to eHealth platforms valuable information, complemental to disease activity questionnaires.

Background and Aims Post-surgical recurrence of Crohn's disease (CD) after ileocolonic resection is common. Early identification of features associated with recurrence is a standard procedure of postoperative management, but the prognostic role of such features when detected at later time points is unclear. We compared the predictivity for Crohn's disease recurrence of common clinical–instrumental variables when assessed early ( 36 months) after surgery. Methods This retrospective study considered CD patients who had ileocolonic resection and were followed for a median of 7.6 years. Clinical characteristics, post-surgical therapy, endoscopy recurrence (Rutgeerts’ score ≥i2) and ultrasound features were compared between subgroups who had a early or late post-surgical assessment. Univariate and multivariate analyses were done to identify variables associated with recurrence (clinical and surgical). Results Of 201 patients, 70 (32%) had a early and 39 (19%) had a late post-surgical assessment. The Early and Late subgroups had similar clinical characteristics. Overall, clinical relapse was observed in 131 patients (66%), surgical relapse in 31 (16%), endoscopic recurrence in 149 (75%) and ultrasonographic recurrence in 132 (66%), without significant differences in frequencies between subgroups. By Cox proportional hazard regression, endoscopic recurrence was a significant predictor of clinical recurrence overall (HR=2.31, P = 0.002) and in the Early (HR=3.85, P = 0.002) but not Late subgroup. Discussion The most informative postoperative CD assessment is the one done within the first year of surgery. Later endoscopic evaluations have no prognostic value and should be done only for clinical needs or for research purposes.

The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.gov: NCT05366569) is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. Of the 14 patients enrolled, 11 were diagnosed with DLBCL, 2 with PMBCL, and 1 with ALL. Five of 11 DLBCL patients met the criteria for “pre-emptive” Lymphocytes-apheresis (being at high risk of second relapse), and 6 were included in the standard-of-care Lymphocytes-apheresis group. Previous autologous stem cell transplantation (ASCT) and age were significantly different between the two groups. At the time of Lymphocyte-apheresis, patients in the “pre-emptive” group had more “fit” lymphocytes (higher CD4+/CD8+ ratio; higher naïve T cells levels) compared with standard group, probably due to the impact of ASCT. At the same time, also being older than 60 years results in a more “exhausted” lymphocyte profile. Overall, “pre-emptive” Ly-apheresis in DLBCL patients at high risk of relapse appears to be feasible and may allow the timely collection of “fit” lymphocytes for CAR-T cell manufacturing.

Real-time quantitative PCR (RT-qPCR) is the gold standard to quantify the BCR-ABL1 transcript for molecular response monitoring in chronic myeloid leukemia (CML) patients, and it plays a pivotal role in clinical decision-making process, even if it presents technical limits. Increasing data suggest that digital PCR (dPCR) is more accurate and reliable than RT-qPCR in CML minimal residual disease monitoring and in patients’ selection for treatment discontinuation. But what about the identification of treatment discontinuation failures? We present the case of a CML patient enrolled both in a study aiming to comparatively assess molecular response by RT-qPCR and dPCR and in the progressive arm of the OPTkIMA trial. This is a phase III trial including CML patients randomized to receive a fixed versus a progressive intermittent tyrosine kinase inhibitor regimen. At 24 months, because of two consecutive detections of MR2.0 by RT-qPCR, the patient resumed daily treatment. Conversely, dPCR revealed a stability of molecular response and even a slight decreasing of transcript over time. An additional specimen was sampled one month after the first MR2.0 detection because of clinical decision: RT-qPCR resulted MR3.0 and dPCR confirmed the transcript’s stability. Nowadays, the resumption of therapy is RT-qPCR-driven despite its limits in detection and robustness. In this case, according to dPCR, the patient could have continued intermittent treatment and the stability of response was then confirmed by RT-qPCR. So, dPCR could be able to better identify peculiar clinical response to therapy.

Exosomes are extracellular vesicles playing a pivotal role in the intercellular communication. They shuttle different cargoes, including nucleic acids from their cell of origin. For this reason, they have been studied as carriers of tumor markers in different liquid biopsy approaches, in particular for solid tumors. Few data are available concerning exosomes as markers of myeloid neoplasia. To better understand their real potential and the best approach to investigate leukemic exosomes, we present the results of a pilot feasibility study evaluating the application of next-generation sequencing analysis of dsDNA derived from exosomes isolated in 14 adult patients affected by acute myeloid leukemias. In particular, leukemia-derived exosome fractions have been analyzed. The concentration of dsDNA co-extracted with exosomes and the number and types of mutations detected were considered and compared with ones identified in the Bone Marrow (BM) and Peripheral Blood (PB) cells. Exosomal DNA concentration, both considering the cargo and the DNA surrounding the lipid membrane resulted in a linear correlation with leukemic burden. Moreover, exosomal DNA mutation status presented 86.5% of homology with BM and 75% with PB. The results of this pilot study confirmed the feasibility of a leukemia-derived exosome enrichment approach followed by exosomal dsDNA NGS analysis for AML biomarker detection. These data point to the use of liquid biopsy in myeloid neoplasia for the detection of active leukemic cells resident in the BM via a painless procedure.

Malnutrition is common after allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT), and interventions directed to correct nutritional status are warranted to improve transplant outcomes. In this prospective study, an oral polymeric formulation enriched with TGF-β2 (TE-OPF) was explored to correct malnutrition according to Patient-Generated Subjective Global Assessment (PG-SGA). TE-OPF was proposed to 51 consecutive patients who received transplants at our institution for hematological malignancies, and sufficient dose intake was established per protocol as at least 50% of the prescribed dose of TE-OPF: group A received adequate nutritional support; group B, inadequate. The study met the primary outcomes in terms of safety (no adverse events reported during TE-OPF intake except for its disgusting taste) and malnutrition (PG-SGA C 28 days after transplant): severely malnourished patients (PG-SGA C) accounted for 13% in group A and 88.9% in group B (p = 0.000). At the end of the study, after a median follow-up of 416 days, the estimated median Overall Survival (OS) was 734 days for well or moderately nourished patients (PG-SGA A/B) in comparison to 424 for malnourished patients (p = 0.03). Inadequate TE-OPF intake was associated with an increase in acute gastrointestinal Graft Versus Host Disease (GVHD) cumulative incidence (38% vs. 0% p = 0.006). A higher incidence of pneumonia was reported in group B (p = 0.006). IGF-1 levels at 14 and 28 days after transplant were significantly higher in group A and were associated with a lower incidence of acute GVHD (aGVHD). Higher subsets of B, T, and NK cells were found in group A, and a higher number of CD16+ NK cells was associated with a lower incidence of acute GVHD (p = 0.005) and increased survival at the end of the study (p = 0.023). Artificial neural network analysis suggested that inadequate TE-OPF intake, pneumonia, and sepsis significantly affected malnutrition 28 days after alloHSCT and survival 365 days after alloHSCT (normalized importance 100%, 82%, and 68%, respectively). In this exploratory and preliminary study, the use of TE-OPF appeared to reduce the incidence of malnutrition after alloHSCT, but larger and controlled studies are required.

Colorectal cancer (CRC) is slightly increased in inflammatory bowel disease (IBD) patients, with roughly a 2.5-fold increase compared to the general population. Clinical features associated to CRC risks are extent and severity of colonic involvement, disease duration, concomitant primary sclerosing cholangitis (PSC) and/or familial history of CRC in first-degree relatives. Colonic Crohn’s disease (CD) and ulcerative colitis (UC) share similar risks when similar colonic extent is affected. Risk stratification affects outcomes and surveillance programs.Newer endoscopic techniques substantially ameliorated diagnostic performance of endoscopy, and nowadays the standard for CRC surveillance in IBD patients is high-definition endoscopy, with dye-spray or virtual colonoscopy, oriented at targeted (+ random) colonic biopsies.Visible dysplastic lesions should be considered for endoscopic resection, while invisible dysplasia is still a mandatory proctocolectomy indication.Newer endoscopic interventional techniques (endoscopic mucosa resection, EMR, and endoscopic submucosal dissection, ESD) are appropriate therapeutic techniques to be delivered, but long-term risks of cancer should be balanced towards proctocolectomy.

Context Clinical frailty scale (CFS) is a scale ranging from 1 (very fit) to 9 (terminally ill) for increasing degrees of frailty extensively used in several geriatric contexts. Currently, no study on CFS is available in an allo-HCT setting. Objective To evaluate the prognostic value of CFS on OS and NRM in allo-HCT. Patients and Methods Overall, 234 consecutive patients aged >50 y were transplanted at our center from 2006 to 2020. Median follow-up: 4.03 y (95%CI: 3.54–5.90). CFS was retrospectively calculated by an external physician blind to transplant outcome. Results Cohort characteristics were the following: median age 59 y (range: 50–73), males 147 (63%), AML (44.4%). DRI was high/very-high in 36.8% of cases. Matched related donor was used in 41.5%, unrelated in 46.2%, alternative in 12.3% of cases. Overall, 170 patients (72.6%) received a reduced-intensity conditioning regimen. For the evaluation of patients’ fitness at transplant, the following scores were applied: Karnofsky performance status (≥90 in 91.5%), HCT-CI (≥3 in 43.2%), FIL score (unfit/frail in 6.8%) and CFS (very fit [score 1] in 6.8%, fit [score 2] in 51.3%; managing well [score 3] in 29.9%, and frail [>3] in 12.0%). An increasing CFS score was associated with a higher proportion of FIL frailty and a lower Karnofsky performance status. No significant differences were observed in terms of comorbidities. At last follow-up, 149 (63.7%) patients had died (NRM 41.6%, relapse 58.4%). CFS was strongly associated with OS (2-y-OS of 85.6%, 63.7%, 25.8%, and 7.1% for patients with score 1, 2, 3, and >3, respectively; p Conclusions CFS appears a simple and highly effective tool for transplant outcome prediction among oncohematological patients aged >50 y. These results might suggest the use of this score for improving patient selection.

Malnutrition is a common problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and could impair immune function. Immune dysfunction after allo-HSCT may be linked with infections, GVHD, and relapse and negatively affect the outcome. Aim of this review was to identify malnutrition biomarkers, potentially useful for immune-system monitoring, in the setting of allo-HSCT. After a systematic search, no satisfying biomarker was found, except for citrulline. Citrulline could be useful in monitoring gastrointestinal function after allo-HSCT and its role in the complex relationship with immune-system function ought to be better explored. A multi-omics approach, including biomarkers and PRO (patient reported outcomes) is, in our opinion, the optimal way to study the relationship between malnutrition and transplant outcomes.

CMV infection is a major challenge in allogeneic stem cell transplantation (allo-SCT). The changing landscape in CMV management includes the introduction of letermovir in prophylaxis of high-risk patients and the source of CMV DNA monitoring (plasma—PL vs. whole blood—WB), for pre-emptive therapy (PET) initiation. We report here how our real-life experience in CMV management evolved, following letermovir registration. We focus on: (i) the effects of systematic use of letermovir for CMV prophylaxis in high-risk patients, (ii) the results of a longitudinal comparison of CMV DNAemia monitoring in PL and WB. From December 2018 to April 2020, 60 allo-SCTs have been performed in our center (LET ERA), of whom 45 received letermovir in prophylaxis from day 0 to day + 100, because of recipient positivity of anti CMV IgG. These patients were compared with a cohort of 41 allo-SCTs performed between November 2017 and November 2018 (NO LET ERA). Firstly, the incidence of CMV clinically significant infections, CMV disease, bacterial infections, proven/probable fungal infections, hospital re-admissions after allo-SCT by day + 100 in the two ERA were 8 vs. 44% (p = 0.0006), 2 vs. 12% (p = 0.02), 37 vs. 56% (p = 0.05), 8 vs. 19% (p = 0.09), and 23 vs. 39% (p = 0.09), respectively. By day + 180 these differences were 17 vs. 68% (p < 0.00001), 2 vs. 12% (p = 0.02), 45 vs. 78% (p = 0.09), 8 vs. 22% (p = 0.05), and 40 vs. 66% (p = 0.01), respectively. Secondly, from February to May 2019, we comparatively measured CMV DNA from WB and PL and we confirmed that there is a linear correlation between CMV DNA level in WB and PL (Spearman’s test r = 0.86). Moreover, CMV DNAemia at the time of PET in the 12 patients with a clinically significant CMV infection was higher in WB vs. PL (5.202 vs. 4.981 copies/ml, p = 0.1). Our real-life experience confirms that: (i) letermovir is highly effective, leading to a significant drop in CMV clinically significant infections and CMV-related complications by day + 100 and + 180 after allo-SCT; (ii) WB may be an effective alternative to PL as a source for CMV DNA monitoring, as a linear correlation of DNAemia was confirmed between WB and PL, even if the CMV DNAemia at PET initiation was comparable in the two sources.

Background Myelodysplastic syndromes and acute leukemias after allogeneic stem cell transplantation (allo-SCT) are mainly caused by recurrence of the primitive leukemic clones. More rarely, they originate from donor hematopoietic stem cells, developing the so-called donor cell leukemia (DCL) or myelodysplastic syndromes (DC-MDSs). DCL and DC-MDS can be considered as an in vivo model of leukemogenesis, and even if the pathogenetic mechanisms remain speculative, a genetic predisposition of donor progenitor cells, an altered host microenvironment, and the impairment of immune surveillance are considered the main causes. Case presentation We report a case of DC-MDS diagnosed 5 years after an allo-SCT from a matched related donor (patient's sister) in a patient with Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL). The sex-mismatch allowed us to identify the donor cell origin. At the onset, the DC-MDS was characterized by chromosome seven monosomy and NRAS, RUNX1, and BCOR mutations. Because of a familiar history of colorectal neoplasia and the variant allele frequency (VAF) of NRAS mutation at the onset, this mutation was searched on germline DNA in both the donor and the recipient, but the result was negative. Moreover, after transplant (+4 months), the patient developed severe and long-lasting chronic graft-versus-host disease (cGVHD), requiring multiple lines of treatments. Because of the severe immunosuppression, recurrent infections occurred and, lately, the patient died due to septic shock. Conclusion This case report highlights the need, whenever possible, to evaluate the donor origin of the posttransplant myelodysplasia and acute leukemias. The potential key role of the impaired immune surveillance and of long-lasting immunosuppression appears to be emerging in the development of this case of DC-MDS. Finally, this case reminds the importance to investigate the familiar genetic predisposition in donors with a familiar history of neoplasia.

Context Evaluation of elderly patients' eligibility for allogeneic stem cell transplantation (allo-SCT) is crucial. A comprehensive geriatric assessment (CGA) has demonstrated important prognostic value in hematology. However, its role in allo-SCT transplant setting has still to be defined. Objective To evaluate the feasibility and efficacy of the Fondazione Italiana Linfomi (FIL)-score, a combined comorbidity (CIRS-G) and functionality (ADL/IADL) score, on allo-SCT outcome. Patients and methods This is a retrospective study involving 228 elderly (>60y) patients consecutively submitted to allo-SCT at our centers from 2008 to 2018. Median follow-up 36 months (range, 1-118). Results The median age was 64 years (range, 60-76), and 155 (68%) were male. AML was the most common indication for transplant (53%), DRI was high/very-high in 42% of cases. A matched unrelated, sibling or alternative donor was utilized in 41%, 30%, and 29% of cases, respectively. Stem cell source was derived from peripheral blood in 82% of patients. Myeloablative conditioning regimen was reserved for only 20% of patients. Based on FIL score, available in 215 patients, 125 (58%) patients were classified as “fit” and 90 as “unfit/frail.” According to FIL score, fit patients were more frequently diagnosed with AML (p Conclusions A comprehensive geriatric assessment with FIL score seems to add significant prognostic information in elderly patients submitted to allo-SCT. The pre-transplant adoption of this easy-to-use tool could help the patients' selection and management.

Nowadays, the evaluation of elderly patients' eligibility for allogeneic stem cell transplantation (allo-SCT) is crucial. We evaluated the feasibility and efficacy of a multidimensional geriatric assessment, the Fondazione Italiana Linfomi (FIL) score, on a cohort of 228 patients older than 60 years submitted to allo-SCT in Italy and France from 2008 to 2018. Based on FIL score, available in 215 patients, 125 (58%) patients were classified as “fit” and 90 as “unfit/frail.” The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was measured in 222 patients (97%); 71 (32%) patients had HCT-CI 0, 75 (34%) patients scored 1–2, and 76 (34%) ≥3. A total of 121 (53%) patients died after a median follow-up of 36 months. FIL score was found to highly predict survival, due to an excess of NRM in unfit/frail group, and confirmed its independent prognostic role on OS (HR: 0.37; 95% CI: 0.25–0.55; p

Due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia characterized by the break-point cluster region-proto-oncogene 1 tyrosine-protein kinase (BCR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BCR-ABL1 protein and induce major or deep molecular responses in the majority of patients. Despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render CML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (CP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PCR (dPCR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BCR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in CML.

We present a case of a patient with a three-month history of peripheral blood cytopenia without a confirmed diagnosis of myelodysplastic syndrome, who developed a favourable-risk acute myeloid leukemia (AML), according to the European Leukemia Net (ELN) criteria. The patient achieved a complete remission with incomplete platelet recovery (CRi) after induction. The patient achieved the morphological CR after the first consolidation and completed the first-line treatment with a syngeneic stem cell transplantation (SCT). A disease relapse occurred after one year of CR (blast cell count in the bone marrow 15%), and the patient was offered a haplo-SCT, which he refused due to personal reasons. In this paper, we discuss the interplay between clinical and biological risk factors in non-high-risk AML patients and speculate that some old clinical risk factors (e.g., age of the patient, achievement of CR after induction, and previous history of myelodysplastic syndrome) may still impact on the treatment decision algorithm of some of these patients.

Introduction. A multidimensional geriatric assessment has been shown to predict therapy-related toxicities in elderly hematology patients. No data are yet available on the use of combined functional and comorbidity scores in the allogeneic stem cell transplant (alloSCT) setting. The Lymphoma Italian Foundation (FIL) score, a multidimensional approach, combines the geriatric comorbidity score using the cumulative illness rating scale-geriatric (CIRS-G) with the activities of daily living (ADL) score, instrumental activity of daily living (IADL) score, and older age. Aims. The aim of the present study was to evaluate the role of the multidimensional FIL score in predicting alloSCT outcome, in terms of transplant-related mortality (TRM), relapse incidence (RI) and overall survival (OS). Patients and methods. Overall, 228 patients older than 60 years were submitted for alloSCT in Italy and France, during the last 10 years (2009-2018). Patients' characteristics are detailed in Table 1. The median age of the study population was 64 years (range, 60-76), and 155 (68%) were male. Acute myeloid leukemia was the most common indication for transplant (53%) and complete remission status was recorded in 54% of cases at transplantation. A matched unrelated donor, sibling donor or alternative donor was utilized in 41%, 31%, and 28% of cases, respectively. Stem cell source was derived from peripheral blood in 82%, bone marrow in 8%, and cord blood in 10% of cases. Utilization of a myeloablative conditioning regimen was reserved for only 20% of patients. Median number of CD34+ x10^6/Kg infused cells was 5 (range, 0,01-12,9), and of CD3+ x10^7/Kg cells 18 (range, 0,2-47,8). The median follow-up period of the cohort was 36 months (range, 12-138). Overall survival was estimated by the Kaplan-Meier method from the date of transplant to the date of last follow-up or death; the log-rank test was used to detect differences between subgroups. The Fine and Gray competing risk regression model was used for calculation of TRM and RI. Univariate and multivariate analyses were carried out using the Cox proportional-hazards regression model. Results. A total of 121 (53%) patients died at last follow-up. The cause of death was related to TRM in 60 (49%) cases comprising infection (31), toxicity (13), acute GVHD (9), and chronic GVHD (7); disease relapse was the ultimate cause of death in 61 (51%) cases . The 2-year expected TRM, RI and OS were 25%, 36% and 49%, respectively. The FIL score was measured in 215 patients and classified patients as 'fit' in 125 (58%) casesa nd 'unfit/frail' in 90 (42%). According to the FIL score, fit patients were more frequently in complete remission (CR) at alloSCT compared with unfit/frail patients (78% vs 21%, p2 (34%). Interestingly, the HCI-CI (HR 1.06, 95%CI 0.96-1.16, p=0.27) failed to predict alloSCT outcome. In contrast , FIL score, predicted fit patients to have a better 2- and 5-year OS of 66% and 59% compared to 32% and 30% in unfit/frail patients (p 80 (0.53, 95%CI 0.36-0.78, p=0.0013) and FIL frail/unfit status (2.83, 95%CI 1.93-4.17, p80 (HR 0,56, 95%CI 0,37-0,85, p=0.0066) and FIL score (HR 2,20, 95%CI 1,27-3,78, p=0.0046) maintained significant associations with OS (Figure 2). Conclusions. In a fairly large cohort of elderly patients (≥60 years) undergoing alloSCT at two European transplant centers, a multidimensional geriatric approach appears to be more accurate compared to a sole comorbidity assessment, in predicting alloSCT outcome and identifying patients at high risk of TRM. This simple tool could easily be applied before transplant for better patient selection and tailoring of treatment. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding.

Forty years have passed since the publication of the "Patients' Rights Charter" (included in a separate section at the end of the work: "Patients' rights: a critical guide to understanding and usage of civil hospital facilities"), but it still remains remarkably topical. We here provide an analysis of the original Charter (1975) taking into consideration the changes that have occurred in sensitivity to gender, cultural as well as socioeconomic differences, the right to body privacy and to continuity of care, the key role of general practitioners, the reciprocal relations in the information and decision-making processes with shared diagnostic and therapeutic pathways and active patient participation, which mandates that adequate education in communication and care strategies be provided to all caregivers.

Risk stratification in acute myeloid leukemia (AML) patients using prognostic parameters at diagnosis is effective, but may be significantly improved by the use of on treatment parameters which better define the actual sensitivity to therapy in the single patient. Minimal residual disease (MRD) monitoring has been demonstrated crucial for the identification of AML patients at high risk of relapse, but the best method and timing of MRD detection are still discussed. Thus, we retrospectively analyzed 104 newly diagnosed AML patients, consecutively treated and monitored by quantitative polymerase chain reactions (Q-PCR) on WT1 and by multiparametric flow cytometry (MFC) on leukemia-associated immunophenotypes (LAIPs) at baseline, after induction, after 1st consolidation and after 1st intensification. By multivariate analysis, the factors independently associated with adverse relapse-free survival (RFS) were: bone marrow (BM)-WT1 ≥ 121/10(4) ABL copies (P = 0.02) and LAIP ≥ 0.2% (P = 0.0001) (after 1st consolidation) (RFS at the median follow up of 12.5 months: 51% vs. 82% [P

CMV represents one of the most serious life-threatening complications of allogeneic stem cell transplantaion (allo-SCT). Pre-emptive treatment with anti-CMV drugs is highly effective, but toxicity and repetitive reactivation of CMV represent a major challenge in the clinical practice. The use of anti-CMV specific immunoglobulins (Megalotect) is controversial. We retrospectively collected data on 539 patients with hematological malignancies submitted to allo-SCT in 6 Italian Bone Marrow Transplant Units between 2016 and 2017. Two hundred and forty two of the 539 patients (45%) developed at least one CMV reactivation. In 94/242 cases (39%) Megalotect was used according to internal guidelines. This report focuses on this group of 94 patient. Megalotect was used as prophylaxis in 15/94 cases (16%) and as pre-emptive therapy together with a specific anti-CMV drug in 79/94 cases (84%). Fifty-six out of 94 cases (60%) received 50 UI/Kg weekly, 33/94 cases (35%) received 50 U/Kg every 2-3 weeks (the remaining patients received different doses and schedule according to the Center policy). Megalotect was used because all the 94 patients were considered at high risk of developing repetitive CMV reactivation. In the prophylaxis setting these risk factors were: haploidentical and cord blood transplantation in 5 cases and unfavorable CMV sireology combiation in 14 cases. In the pre-emptive setting, the risk factors were: haploidentical transplantation in 30 cases, aGVHD requiring high-dose steroids in 37 cases and unfavourable CMV serology combination (D-/R- in 44 cases, D+/R- in 1 case). In the pre-emptive setting the following anti-CMV drugs were used first-line: gancyclovir (31 cases), foscarnet (19 cases), valgancyclovir (14 cases), different combinations (15 cases). Overall, the treatment was well tolerated, with no reported infusion reactions nor other adverse events. Megalotect was administered for a median of 2 doses (range 1-9) and 3 doses (range 1-33) in patients treated prophylactically or pre-emptively. None of the 15 cases treated with Megalotect as prophylaxis developed CMV reactivation. Focusing on the 79 cases treated with Megalotect pre-emptively, 59 patients (75%) achieved at least one CMV viremia negativity during tratment. Median time to first negativity was 19 days (range 3-190). In 30/79 cases (38%) a subsequent CMV reactivation was observed during the follow up, which was treated with a second-line anti-CMV specific drug. Interestingly, only 6/94 cases (6%) developed CMV disease: gut localization in 4 cases and other site in 2 cases.Overall 24/94 patients died (25%) and no death was CMV-related Our preliminary experience with Megalotect suggests that it is safe and well tolerated both in the pre-emptive and prophylaxis setting. We have no conclusive data regarding the efficacy of this treatment in reducing the cumulative dose of anti-CMV specific drugs. Interestingly, when used as prophylaxis, no CMV reactivation was recorded. In the pre-emptive setting, the combination of Megalotect and anti-CMV specific drug was able to induce negativity of CMV viremia in a relatively short time (median 19 days) and 38% of these high-risk patients only developed further CMV reactivation during follow up. Further prospective trials are warrented to address the most appropriate use of Megalotec (preophylaxis vs pre-emptive) and to identify the best setting of patients who can benefit from Megalotect alone or in addition to anti-CMV specific drugs. Disclosures Foà: ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.

Two different rabbit anti-thymocyte globulin (ATG) formulations, thymoglobulin-ATG (tATG) and fresenius-ATG (fATG) are usually employed as prophylaxis for graft-versus-host-disease (GVHD), one of t...

Background : Blood stream infections (BSIs) represent a major complication of allo-SCT and are a major cause of morbidity and mortality during and after bone marrow aplasia. Objectives: The objective of this study was to describe the incidence and outcome of BSIs in a cohort of patients submitted to allo-SCT, in order to track changes of the epidemiology and bacteria resistance. Methods : We retrospectively analyzed the microbiological data of 162 patients allotransplanted in Brescia University Hospital, over a period of 6 years. Results : Eighty patients experienced a BSIs for a total of 119 isolates. In 77 cases (65%) a Gram positive bacteria was isolated, being coagulase negative Staphilococci the most frequent species (77% of the cases). In 42 cases (35%) a Gram negative bacteria was isolated (E. coli 57% and P. aeruginosa 24%). Fluoroquinolones resistance was frequent (90% for S. epidermidis , 92% for E. coli , 90% for P. aeruginosa ). Methycillin resistance of S. epidermidis was 100%, 76% of E. coli were ESBL positive and among P. aeruginosa resistance to carbapenems was 40%. The 2 years overall survival of patients with BSIs vs patients without BSIs was 46% vs 60% (HR1,48, p=0,07). P. areuginosa and E. coli were the species with the highest mortality (50% and 33%, respectively). Conclusions : These data confirms that BSIs, mainly sustained by Gram positive bacteria, are frequent in allotransplanted patients (50% of the cases) and may influence the outcome of allotransplanted patients, being antibiotics resistance highly frequent among these bacteria.

Autologous stem cell transplantation (ASCT) is a potentially curative treatment of lymphoma, but peripheral blood stem cell (PBSC) mobilization fails in some patients. PBSC mobilizing agents have recently been proved to improve the PBSC yield after a prior mobilization failure. Predictive parameters of mobilization failure allowing for a preemptive, more cost-effective use of such agents during the first mobilization attempt are still poorly defined, particularly during mobilization with chemotherapy + granulocyte colony-stimulating factor (G-CSF). We performed a retrospective analysis of a series of lymphoma patients who were candidates for ASCT, to identify factors influencing PBSC mobilization outcome. Premobilization parameters-age, histology, disease status, mobilizing protocol, and previous treatments-as well as white blood cell (WBC) and PBSC kinetics, markers potentially able to predict failure during the ongoing mobilization attempt, were analyzed in 415 consecutive mobilization procedures in 388 patients. We used chemotherapy + G-CSF in 411 (99%) of mobilization attempts and PBSC collection failed (

Favourable/intermediate ELN-risk acute myeloid leukemias (AMLs) (e.g. those harboring t(8;21) or inv(16) or NPM1A mutations or CEBP-alpha bi-allelic mutations) account for 30% to 50% of all newly diagnosed AMLs [1,2]. In this setting, conventional induction treatments may induce complete remission (CR) in up to 70% to 80%, but relapses still occur in 40% to 50% of cases and, at the end, no more than 30% to 40% of patients can be cured. Therefore, the optimization of post- remission therapy represents the greatest challenge in the treatment of favourable/intermediate-I ELN-risk AML.