ALBERT

Description: Background Therapy-related Myelodysplastic Syndromes (t-MDS) are those MDS occurring after cytotoxic and/or radiation therapy administered for a prior neoplastic or non-neoplastic disorder. Their prognosis is generally very poor. The commonly used risk prognostic models for MDS (IPSS and IPSS-R) are not validated in this entity as they were developed after the exclusion of therapy-related cases (Greenberg et al. Blood 1997; Greenberg et al. Blood 2012). Aims The main aims of this study are: a) to report clinical findings and overall survival on 233 patients with t-MDS, and to compare them with a large series of de novo cases; b) to test if IPSS-R is applicable to t-MDS patients. Patients and methods The study is based on the Spanish Registry for MDS, a retrospective database that includes more than 10000 cases. The investigators were asked to fill in a questionnaire regarding prior disease (PD) and prior therapy in those cases reported to be t-MDS. Herein are described the clinical features and overall survival of the first 233 cases with the required information, and compared with patients with de novo MDS from a single center series (n=725). Log Rank test was applied to asses IPSS-R in t-MDS group. Results The 233 reported patients were diagnosed between January 1993 and February 2014. The series includes 104 women (44,6%) and 129 men (55,4%). One hundred and two patients (43.9%) had a primary hematologic malignancy, 119 (51%) had a solid tumor, and 12 (5.1%) received cytotoxic therapy for autoimmune disorders. Ninety eight patients (42.6%) received only chemotherapy (CT), 45 (19.6%) received only radiotherapy (RT), 44 (19.1%) received combined modality treatment (CMT), and 43 (18.6%) received an autologous stem cell transplantation (ASCT). The median time of latency between PD and diagnosis in t-MDS group was 4.56 years (range: 0.03-29.63) in patients previously treated with CT or CMT, significantly lower than the observed after RT (8.54; range 0.83-23.02) or ASCT (8.64; range 2.87-28.32) groups (p=0.023 and p Disclosures No relevant conflicts of interest to declare.

Description: Ocular adnexal lymphomas (OAL) represent up to 55% of all orbital tumors, being extranodal marginal zone lymphoma (OAMZL) the most frequent histological subtype reported in approximately 50% of patients and its etiology and pathogenesis are still not well understood. There are conflicting reports regarding the association between C. Psittaci infection and ocular adnexal lymphoma (OAMZL), in part because this association may vary between different geographical regions. Herein, we analyzed the clinical features and the presence of C. Psittaci infection in a cohort of 28 patients with OAMZL diagnosed from a single Spanish institution. All tumor samples were centrally reviewed by two pathologists, and C. Psittaci infection was determined in tumor specimens by a Semi-nested PCR method. Between January 1984 and April 2009, 28 patients were diagnosed with primary OAMZL. The median age was 70 years (range: 31- 89) and 40% were male. The great majority of patients (79%) were diagnosed in stage I-extranodal (IE), and six patients (21%) had bilateral ocular involvement. IgH rearrangement was confirmed in 25 out of 28 cases with OAMZL. PCR for C. Psittaci infection was negative in all 28 tumor specimens analyzed. Most patients (82%) were treated with immunochemotherapy combinations, being chlorambucil based regimens the most frequently used. Overall, 18 out of 24 patients (75%) achieved a complete response after first-line treatment. Median PFS was of 79 months (IC 95% 36 - 121). Whereas C. Psittaci infection in OAMZLs has been proved in up to 90% of patients in Northern Italy, in this Spanish cohort OAMZLs were not associated with C. Psittaci infection. These findings confirm that the association between C. Psittacci infection and OAML is highly heterogeneous even between the same geographic regions. In these regions where C. Psittaci infection is not prevalent, the search for alternative antigenic stimuli driving the appearance of this lymphoma is warranted. Disclosures No relevant conflicts of interest to declare.

Description: Cytogenetic abnormalities (CA) are the most important prognostic factor in MDS patients, nevertheless the incidence of CA at diagnosis is not higher than 50% and even less in lower risk patients. The acquisition of CA (ACA) has recently been reported as a frequent and poor prognostic event in patients with normal karyotype at diagnosis (Jabbour et al 2013). The aim of our study was to analyze in a large cohort of patients the incidence, characteristics, and prognosis of the ACA in patients with low and intermediate-1 IPSS risk at diagnosis. We retrospectively reviewed 254 adult patients from the Spanish Registry of MDS with IPSS low or intermediate-1 risk diagnosed between 1995 and 2013. In total 121 patients had at least two consecutive cytogenetic analyses during the follow up. The main end points were overall survival (OS) and AML evolution (TFS). Cytogenetic analyses were conducted on unstimulated bone marrow cells after culture (24–72 hours). The ISCN 2005 criteria were used for identification of abnormal clones. ACA was defined by structural change or gain in at least 2 metaphases and loss in 3 metaphases as proposed in previous reports. Differences among variables were evaluated by non-parametric tests. OS and TFS were analyzed by Kaplan-Meier curve. The median follow-up was 25 months (0-155). The median age at diagnosis was 71 years (26-87) and 28% of the patients were female. The IPSS risk group was low in 43% and intermediate-1 in 57% of the population. Distribution as the IPSS-R was very low 20%, low 42%, Intermediate-1 30%, poor 6%, and there were no cases with very poor risk. At diagnosis, 34.7% of patients had abnormal karyotype. ACA was detected in 16 patients (13,2%) after a median of 30 months (range, 5-165). The most common ACA identified were trisomy 8 as sole abnormality followed by chromosome 7 abnormalities in in 25% and 12.5% of patients, respectively. Of the 42 patients with CA at diagnosis, 12% developed new ACA while among 79 patients with normal karyotype at diagnosis, 14% developed ACA (p=0,7). The presence of ACA changed the IPSS-R risk group in 14 out 16 patients. Compared with patients without ACA, the presence of ACA was significantly associated with a lower hemoglobin level (Table 1). In univariate analysis, ACA was not apparently associated with a higher incidence of AML evolution as there were 2 out of 16 patients (12,5%) with ACA that developed AML while between the 105 patients without ACA, 11 developed AML (11,5%) (P=NS). At last follow-up, 34 (28%) patients died and the median OS for the entire cohort was 67 months (IC 95% 34-99). In Kaplan-Meier curve, the presence of ACA was associated with lower overall survival (median 67 months (95% CI: 34-99) than patients without ACA (median 140 months (95% CI 36,9.243) (P =0.01). In summary, the present analysis shows that, the ACA occurs in around 13% of cases, which is a lower frequency than previously reported in other series, and it may have impact in overall survival. Future studies should address the impact molecular alterations and somatic point mutations; molecular diagnostic may allow identified patients with higher risk to transformation. Table 1. Hematologic parameters at the time for the cytogenetic control. ACA (n= 16) NO ACA (n=105) P Hb g/dL 9,1 (5.8-11.9) 10,3 (5.6-17.7) 0.04 WBC × 109/L 3,15 (0.7-24.1) 4,1 (0.9-32) 0.85 Pla × 109/L 71 (16-127) 93,5 (4-574) 0.38 Blast × 109/L 6 (1-15) 2.4 (0-19) 0.09 Disclosures Valcárcel: Celgene: Honoraria, Speakers Bureau.