ALBERT

Description: INTRODUCTION: Recent studies have suggested that tumor microenviroment (TME) may play an important role in lymphomagenesis and tumor progression in non-Hodgkin lymphoma. Tumor-infiltrating lymphocytes and myeloid-derived cells could provide valuable prognostic information independent from tumor characteristics alone. In diffuse large B-cell lymphoma (DLBCL) several attempts have been made to capture prognostic variables associated with TME. Peripheral blood monocytes, lymphocytes and natural killer (NK) cells have been shown to predict outcome in DLBCL patients (pts). Immunohistochemistry and gene-expression profile on tissue biopsies have also been studied as prognostic indicators. In this study we assessed the prognostic significance of the percentage of infiltrating T-lymphocytes (TL) and NK cells measured by flow cytometry (FC) in tissue biopsies of DLCBL. AIMS: -To determine the prognostic impact on survival of the percentage of infiltrating TL and NK cells measured by FC in tissue biopsies. -To evaluate whether this variables can provide additional information when superimposed on the R-IPI. METHODS: We selected pts with DLBCL and available tissue biopsy FC data at the time of diagnosis who received treatment at our institution between 2012 and 2018. Clinical information such as age, gender, stage, serum lactate dehydrogenase levels, R-IPI and cell of origin were collected from medical records. FC analysis was performed with 8-color FC panels according to international Euroflow protocols. Percentage of TL and NK-cells in lymph node biopsy by FC was compared to the normal values determined by Battaglia et al (Immunology 2003). Both parameters were analyzed as dichotomized variables: low vs. normal-high. The survival analysis was estimated with Kaplan-Meier method. The comparison between variables was performed through log-rank test and multivariate analysis with Cox regression. RESULTS: A total of 75 pts were included in this retrospective study. Pts characteristic are summarized in Table 1. All pts were treated with immunochemotherapy regimens. Complete remission rate was 82%. Median PFS and OS were 35.2 and 83.2 months respectively, with a median follow up time of 27.8 months (range: 4.3-177.5). In our cohort, the R-IPI was able to discriminate OS and PFS into poor and good-very good risk (median OS of 27.8 months vs. not reached, and median PFS of 12.8 vs. 82.6 months, p

Description: BACKGROUND Patients with adverse cytogenetic or secondary AML (s-AML) have significantly worse outcomes and lower survival rates. In this high risk subgroup of patients, early consolidation with allogeneic hematopoietic stem cell transplantation (HSCT) in first complete remission (CR1) can improve results, especially in those who achieve negative measurable residual disease (MRD-). More effective treatments than standard 7+3 are needed. CLAG-M is a salvage regimen that has demonstrated high response rates with good tolerance, and seems to be promising in the upfront setting. AIMS To estimate CR and MRD- rates, overall survival (OS) and event free survival (EFS) in transplant eligible patients with high risk AML treated in our center.To compare CR rate and transplant feasibility in CR1 with 7+3 vs. CLAG-M as induction treatment in s-AML. PATIENTS AND METHODS We analyzed adult patients (18-65 years old) with high risk AML (defined by adverse cytogenetic according to ELN2017 or s-AML) who were treated in our institution between 2010 and 2018. All patients were transplant eligible and had an available donor. Clinical information was collected from medical records. We evaluated CR1 and MRD- rates, EFS and OS. We also compared CR rates and HSCT feasibility in s-AML after treatment induction with CLAG-M and 7+3. The survival analysis was estimated with Kaplan-Meier method and the comparison between variables was performed through log-rank test. RESULTS Twenty-one patients were included (13 s-AML and 8 with adverse cytogenetic). The median age at diagnosis was 54 years (21-64); 13 female/8 male. Out of 21 patients, 14 received 7+3 induction and 7 CLAG-M. The median follow-up time was 11 months (0.9-90.8), median EFS and OS for the whole group was 1.05 and 13.5 months, respectively. Two-year OS was 35%. CR1 was achieved in sixteen patients (76%), 10 of them MRD-. The median time to CR1 was 33 days, the median OS of these patients was 26.7 months (figure 1). Eleven patients (52%) were refractory to first induction, 10/14 in the 7+3 subgroup, and only 1/7 patients treated with CLAG-M. Six of them converted to CR after reinduction (5 with CLAG-M). Fourteen (67%) underwent HSCT in CR1. The median time to HSCT consolidation was 106 days. The median relapse free survival in transplanted patients has not been reached (Table 1). Considering only s-AML, 6 patients received 7+3 and 7 CLAG-M. Median age in 7+3 subgroup was 41 vs. 57 years in CLAG-M. The median OS was 13.5 months. In the 7+3 cohort, only 1 achieved CR (16%); the other five received reinduction with CLAG-M, and 4 converted to CR1. The median time to CR1, EFS and OS were 82 days, 1 month and 26 months respectively. In contrast, 4 of the 7 patients (57%) that received CLAG-M achieved CR1, but only 1 of the 3 that were refractory could convert to CR. The median time to CR1 in patients treated with CLAG-M was 27 days, median EFS 7.5 months and median OS has not been reached (Figure 2). There were no statistically significant differences between the two treatment groups. Eight patients (62%) could be bridged to HSCT, 4 of each subgroup (Table 2). CONCLUSIONS Our results in this real life small cohort of high risk AML were similar to historical controls. In the s-AML subgroup, differences between 7+3 and CLAG-M were not statistically significant probably due to the low number of patients analyzed. However, patients who received CLAG-M required less cycles of treatment to achieved CR1, allowing HSCT rapidly in this selected population. Since most of the refractory patients to 7+3 responded to reinduction with CLAG-M, both groups had similar transplant rates. According to our experience CLAG-M might be an attractive treatment option with high CR rates and acceptable safety profile. In this high risk AML population, two thirds of the patients were effectively "bridged" to HSCT with a 2-year OS rate of 35%. Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION: Several studies have disclosed the predictive role of tumor microenvironment (ME) in diffuse large B cell lymphoma (DLBCL). However, there is limited data regarding the prognostic impact of immune cells (IC) in the bone marrow (BM) of DLBCL patients (pts). Regulatory molecules secreted from primary tumor sites may induce a pro-tumorigenic ME within BM, resulting in an impaired systemic immune response that could promote lymphoma survival. AIMS: -To determine the prognostic impact on survival and risk of early relapse (ER) of the % of T lymphocytes (TL), monocytes (Mo), neutrophils, NK cells and polyclonal B lymphocytes (BL) measured by flow cytometry (FC) in pre-treatment BM aspirates of DLBCL pts. METHODS: We selected pts with DLBCL and available BM aspiration FC data at the time of diagnosis who received treatment at our institution between 2012 and 2019. Clinical information was collected from medical records. FC analysis was performed with 8-color FC panels according to international Euroflow protocols. % of TL, Mo, neutrophils, NK cells and polyclonal BL by FC were compared to the normal values determined by Matarraz et al. (Cytometry part B, 2010). All parameters were analyzed as ordinal variables in 3 categories: low, normal and high. Odds ratio for ER (relapse within a year) was calculated using logistic regression. The survival analysis was estimated with Kaplan-Meier method. The comparison between variables was performed through log-rank test and multivariate analysis with Cox regression. RESULTS: A total of 119 pts were included in this retrospective study. Pts characteristics are summarized in Table 1. All pts were treated with immunochemotherapy regimens. Median PFS and OS were not reached, 75th percentile of 12.7 and 27.8 months (m), respectively; with a median follow up time of 30.7 m (range: 3.4-60). ER was documented in 25 pts. Regarding BM IC, pts with normal TL, polyclonal BL and Mo % were significantly associated with superior PFS and OS (figure 1A and table 2). No correlation between BM NK cells or neutrophils levels and outcome was observed. Moreover, BM IC levels did not statistically differ in involved vs not involved BM. In our cohort, the R-IPI was able to discriminate outcomes in poor and good-very good (G-VG) risk (median OS of 48 m vs. not reached, p