Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most frequent type of non-Hodgkin lymphoma. Although PET/CT has allowed a better diagnostic evaluation in these patients, none metabolic index has been incorporated into prognostic scores, neither molecular markers have been associated with PET/CT findings. Aim: To define the association between PET/CT findings and EZH2 mutations, and their impact on survival of patients with DLBCL. Methods: Patients: A cohort study of newly diagnosed DLBCL patients. Cohorts were defined according to the presence of EZH2 (Y641N/Y641F/Y641H/Y641S) mutations. Clinical variables were: age, comorbidities, IPI score, bulky disease, clinical stage, serum albumin, LDH and B2-microglobulin levels, and ECOG. Histopathologic variables were GC (Germinal center) versus no-GC by Hans nomogram, BCL2, BLC6, & MYC expression, as well as double-hit. All patients were treated with six cycles of standard RCHOP. PET/CT assessed parameters were: Total metabolic tumor volume (TMV), Total lesion glycolysis (TLG) and SUV max. Clinical response was evaluated by PET/CT, using Deauville's criteria. All 18F-FDG PET/CT scans were performed using the Biograph 16 PET/CT scanner (Siemens AG, Munich, Germany). Patients fasted for at least 6 h prior to intravenous (IV) administration of 18F-FDG (5.5 MBq/kg body weight) to ensure a serum glucose level of <10 mmol/l. Methods: DNA was extracted from paraffin-embedded tissue. PCR analysis was carried out in a 2700 Thermalcycler (Applied Biosystems) to detect mutations in Exon 16 of EZH2; the sequencing and electrophoresis of PCR products was performed using ABI3100 genetic analyser. Sequences were compared with the EZH2 reference sequence (GenBank NG_032043.1). The protocol was approved by IRB (Approval number CEI/966/15). Statistics: After descriptive analysis, mean metabolic indexes were compared by ANOVA between patients with wt and any of the EZH2 mutations . Kaplan-Meier method was used to construct Disease-free survival (DFS) curves and the Log-rank test was used for comparisons. COR curves were used to evaluate metabolic indexes as risk factors infuencing on DFS. Results: Results: 230 patients (120 male), were included. Median age was 58.3 years (SD 14.25; range: 21-91); 169 of them (73.4%) had advanced disease and 224 (97.3%) had ECOG <2. Absence of B symptoms or bulky disease was documented in 154 (67%) and 136 cases (59.1%), respectively. GC-type was found in 65%. Although sixty cases (26%) were considered to be DLBCL double expressor (MYC +BLC2 overexpression), only 15% were double-hit DLBCL. Mutations at codon 641, exon 16 of EZH2 were described in 15% of cases, as follows: Tyr 641 Asn (Y641N) [6 %],Tyr 641 Phe(Y641F) [6%], Tyr 641 His (Y641H) [3%] and Tyr 641Ser (Y641S) [1%]. Any clinical parameter was different between wt and any EZH2 mutations. However, regarding metabolic indexes by PET/CT, TLG was higher in EZH2 mutated patients (mean: 8314.02g [95 %CI: 5623-11004g]), in comparsion with wt patients (mean: 5228.99g, [ 95 % CI: 4114-6316g], p=0.02). Response was classified as complete in 75% of cases, partial in 3.5%, and progressive disease in 11%. The association of these mutations on DFS is shown in table 1. In addition, mean TLG and TMV indexes were lower in patients without relapse. (Table 2) Summary/Conclusion: These preliminary results suggest that patients with any of EZH2 (Y641F) mutations have a higher TLG by PET/CT at diagnosis, and both values have a negative impact on DFS of patients with DLBCL. Our results need to be confirmed on a larger sample and a longer follow-up. Disclosures No relevant conflicts of interest to declare.
Background: The increasing survival rate of patients with non-Hodgkin lymphoma has allowed the diagnosis of long-term complications including therapy related myeloid malignancies (t-MDS/t-AML). Methods: To determine the frequency of late-onset cytopenias, as well as t-MDS/t-AML in patients with lymphoproliferative malignancies, a cohort followed from Jan 2011-Dec 2016 including patients with either Follicular Lymphoma (FL) or Diffuse Large B Cell Lymphoma (DLBCL) was reviewed. Inclusion criteria: patients that received full treatment at Instituto Nacional de Cancerología (INCAN), who achieved full hematologic recovery at the end of treatment, and thereafter developed any degree of cytopenia (according to the CTCAE v4.0). Exclusion criteria: Follow-up less than 6 months and previous treatment before receiving medical care at INCAN. Initially peripheral causes (vitamin deficiencies, viral infections, liver autoimmune diseases, among others) were discarded. Thereafter, bone marrow aspiration was performed for morphologic analysis (including cellularity), karyotype and FISH panel. Baseline data was compared between groups with cytopenias and without it, with X2 method. A Cox-regression model evaluated the factors involved in the development of cytopenias. Survival was estimated with Kaplan-Meier method. Results: Of 840 patients enrolled, 35 developed cytopenias (4.16%) (23-DLBCL & 12-FL). Causes of cytopenia were: medullar hypoplasia (n=4, 11.4%), transitory cytopenia (n=4, 11.4%), t-MDS (n=8, 22.8%), t-AML (n=2, 5.7%) among others. In patients with FL, only hemoglobin <12 g/dL (p=0.032) and >6 nodal areas (p=0.037) at diagnosis were statistically significant factors for the development of cytopenia; no factor was significant in patients with DLBCL. It is of interest that 80% of patients developing t-MDS also received radiotherapy. Anemia was the most frequent cytopenia in patients with DLBCL (22.8%) and pancytopenia was the most frequent in FL (54.5%). For patients with t-MDS or t-AML (table 1), there was a gender predominance in women (66.7%). Patients with complex karyotype were associated with progression to t-AML, those with t(11q23) and -7 had aggressive clinical course and shorter survival. Treatment details and outcomes are summarized in table 1. Conclusions: The incidence of t-MN is increasing as more patients survive their primary cancers. It is quite important to get further knowledge on the molecular biology of the group of therapy-related disorders not only for a better diagnostic and classification criteria, which may help in selecting individualized treatments, but also to investigate potential chemopreventive strategies. Disclosures No relevant conflicts of interest to declare.
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