Monitoring of Epstein-Barr virus (EBV) load and pre-emptive rituximab is an appropriate approach to prevent post-transplant lymphoproliferative disease (PTLD) occurring after hematopoietic stem cell transplantation (HSCT). This pre-emptive approach, based on EBV-DNA monitoring through a quantitative polymerase chain reaction, was applied to 101 consecutive patients who underwent allo HSCT at our Institute (median age 50). A single infusion of rituximab was administered to 11 of 16 patients who were at high risk for progression to PTLD, defined as a DNA value >10 000 copies/mL. All patients cleared EBV DNAemia, without any recurrences. Main factors significantly associated with high risk for PTLD were as follows: (i) unrelated vs. sibling (26% vs. 7%; p = 0.011); (ii) T-cell depletion (29% vs. 6%; p = 0.001); (iii) graft versus host disease (GVHD; 30% vs. 7%; p = 0.002); and (iv) cytomegalovirus (CMV) reactivation (29% vs. 4%; p = 0.001). Multivariate analysis showed that CMV reactivation was the only independent variable associated with EBV reactivation. We conclude that: (i) a single infusion of rituximab is able to prevent the risk of progression into EBV-related PTLD; and (ii) CMV reactivation is strongly associated with EBV reactivation; therefore, an intensive EBV monitoring strategy could be advisable only in case of CMV reactivation.

3807 Background: The prognostic role of serum ferritin (SF) evaluation at baseline in patients (pts) affected by myelodysplastic syndrome (MDS) is still controversial. In fact, increased SF mainly due to transfusion requirement during disease history has a clear negative impact on overall survival (OS) (Malcovati et al., 2006) and also on leukemic evolution (LE) (Sanz, ASH 2008, de Swart ASH 2010) while contrasting data about its role at baseline on OS has been published. Park and colleagues (ASH 2010) failed to identify a negative prognostic impact of SF higher than 300 ng/mL in a cohort of low risk untransfused MDS patients while data from the European LeukemiaNet MDS registry identified SF as an independent prognostic factor for OS and progression-free survival in low- and int-1 MDS (de Swart, Edimburgh 2011). SF can be a marker of iron overload but also of inflammation and little is known about the impact on survival of other iron parameters such as transferrin saturation (TS) or inflammation such as C reactive protein (CRP) in MDS pts at diagnosis. Aim: Aim of our study was to evaluate the prognostic role of iron parameters and inflammation at diagnosis in MDS patients analyzing data collected in the MDS Piedmont Registry. Materials and methods: 1360 patients enrolled in the MDS Piedmont Registry (1999–2010) were analyzed. Patients with information on OS and LE and available baseline SF (n=670), TS (n=299), CRP (n=287) were included in the analysis. Survival analysis was performed using Kaplan-Meier method. Patients were stratified according to a cut off value of 800 ng/mL for SF, 40% for TS and values within or higher the normal range (0,8 mg/dL) for CRP. In order to compare survival curves, log-rank test was used. Cumulative incidence of LE, according to SF, TS and CRP levels, was calculated accounting for death from any causes as a competing event. Results: In the population with SF baseline values, 3-years OS in pts with SF < 800 ng/mL was 80.7 (95%CI: 75.8–84.8) and in pts with SF >800 ng/mL was 66.1 (95%CI: 46.7–79.8) (p= 0,006). The result seems to be confirmed in the low risk MDS subgroup in toto (n=226) and considering only the untransfused pts (136 cases) (p=0,0073 and p=0,0038 respectively) but no statistically significance in OS of high risk pts (n=108) has been observed. In subjects with available data on TS, 3-years OS for pts with TS lower than 40% was 75.0 (95% CI: 64.2–83.0) while in pts higher than 40% was 72.1 (95%CI: 59.5–81.4) (p=0,1). Finally, in pts with CRP values 3-years OS was 80.8 (95%CI: 69.7–88.2) for patients < 0,8 mg/dL and 47.2 (95%CI: 34.5–58.9) for pts > 0,8 mg/dL. Also 3-year cumulative incidence of LE was higher in pts with SF > 800 ng/mL [35.8 (95%CI: 20.3–51.2) vs 18.5 (95%CI: 14.4–22.5); p=0,002 ] and in those with CPR > 0,8 mg/dL [35.3 (95%CI: 23.9–46.7) vs 12.7 (95%CI: 5.7–19.7); p<0,001]. In TS subgroups no difference was observed [13.5 (95%CI: 7.0–20.0) for TS<40% vs 20.8 (95%CI: 11.8–29.8) for TS>40%; p=0.172]. Conclusions: although the limits of missing data, our results suggest that high levels of SF and CRP above the normal range at baseline should have a prognostic role in MDS pts, while TS seems to have little impact on OS. Moreover SF and CRP seem to have both a negative impact on LE. Our data suggest a more important prognostic role of chronic inflammation parameters than iron overload or oxidative stress in MDS patients at diagnosis. Further prospective evaluation of more specific parameter of oxidative stress and inflammation need to be analyzed in order to confirm our preliminary observation. Disclosures: No relevant conflicts of interest to declare.

Several new drugs are progressively improving the life span of patients with B-cell chronic lymphocytic leukemia (CLL). However, the rapidly evolving standard of care precludes robust assessments of the incremental clinical value of further innovative drugs. Therefore, we systematically reviewed comparative evidence on newly authorized CLL drugs, as reported by standard and network meta-analyses (MA) published since 2016. Overall, 17 MAs addressed the relative survival or safety of naïve and/or refractory/relapsed (R/R) CLL patients. In R/R patients, therapies including BTK- and BCL2-inhibitors reported progression free survival (PFS) hazard ratios ranging from 0.08 to 0.24 (versus chemotherapy) and a significant advantage in overall survival (OS). In naïve patients, the PFS hazard ratios associated with four recent chemo-free therapies (obinutuzumab- and/or acalabrutinib-based) ranged from 0.11 to 0.61 versus current standard treatments (STs), without a significant OS advantage. Ten MAs addressed the risk of cardiovascular, bleeding, and infective events associated with BTK inhibitors, with some reporting a different relative safety in naïve and R/R patients. In conclusion, last-generation therapies for CLL consistently increase PFS, but not OS, and minimally decrease safety, as compared with STs. Based on available evidence, the patient-customized adoption of new therapies, rather than universal recommendations, seems desirable in CLL patients.

No abstract

4028 BACKGROUND. The corner stone of the WHO classification and prognostic scores of myelodysplastic syndromes (MDS) is the blast count in bone marrow. The standard cytology evaluation of at least 500 bone marrow cells is easy to perform, but some concerns arise about reproducibility of this method. Nowadays bone marrow trephine biopsy and flow cytometry are frequently considered for the diagnosis of MDS. However there is so far paucity of data comparing cytology, histology and flow cytometry in quantifying bone marrow blasts in order to differentiate non RAEB from BAEB-I and RAEB-II cases. AIM OF THE WORK. The Aim of the work was to analyse the differences and the prognostic impact of cytology, histology and flow cytometry in differentiating non RAEB from BAEB-I and RAEB-II. PATIENTS AND METHODS. Since 1999, clinical and laboratory data from 1256 new cases of MDS were prospectively recorded into the Piemonte MDS Registry. Blast count could be performed with the three different methods: BMC (bone marrow cytology) has been performed in 844 cases, BMH (bone marrow histology) in 874 cases, and BMF (bone marrow flow cytometry) in 636. In order to quantify blasts, immune-histochemistry evaluation of CD34+ cells was used in BMH, while both CD34+ and CD117+ cells were considered in BMF. Out of the total of the 636 patients analysed by BMF only 420 had an accurate and complete registration of CD34 and CD117 positivity and were considered for the present analysis. In two hundred and thirty six cases all three evaluations were contemporary available. The concordance of each diagnostic method with the others and their prognostic value were evaluated in both univariate and multivariate analyses. A comparison between BMC and BMH was available in 571 cases, between BMC and BMF in 228 cases, and between BMH and BMF in 279 cases. RESULTS. The disagreement in classifying patients as non-RAEB or RAEB-I or RAEB-II between BMC and BMH was 156/571 (27%), with BMH over-evaluating blasts in 114/571 cases (20%) and under-evaluating blasts in 42/571 cases (7%). The disagreement between BMC and BMF was 80/228 (35%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMC in 53/228 (23%) and in 27/228 (12%) cases respectively. The disagreement between BMH and BMF was present in 113/279 (41%), with BMF over-evaluating and under-evaluating blast percentage in comparison to BMH in 44/279 (16%) and in 69/279 (25%) cases respectively. In univariate analysis all three methods of quantifing blasts and differentiating non-RAEB from RAEB-I and RAEB-II retained an important prognostic value for both leukemic evolution and survival. However when the three models were tested in multivariate analysis in order to define the best predictor of leukemic evolution, BMC retained the best predictive value. CONCLUSIONS. When BMH or BMF are used instead of BMC in order differentiate non-RAEB from RAEB-I and RAEB-II, the shift to a different WHO category is evident in at least 30% of patients and BMH and BMF do not play the same role as BMC. BMC still remain the standard method to quantify blasts for classification and prognostic evaluation of MDS. Disclosures: Off Label Use: Lenalidomide in Mantle Cell Lymphoma. Boccadoro:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Saglio:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.