ALBERT

Beschreibung: Abstract 4956 Introduction. Patients with Myelodysplastic Syndrome (MDS) are susceptible to developing iron overload as a response to the red blood cell (RBC) transfusions and ineffective hematopoiesis. This iron overload (IOL) is characterized by an increase in oxygen-reactive species accompanied by a decrease in antioxidants, and results in hepatic, cardiac and endocrine disorders, as well as an increased risk of infection. Ineffective hematopoiesis promotes iron absorption at intestinal level. This process is enhanced by the presence of mutations in the hereditary hemochromatosis gene (HFE). This study aims to define the features that accompany patients with iron overload, comparing them to a MDS population at diagnosis. Patients and methods. 34 low/int-1 MDS patients (International Prognostic Score System, IPSS) were assessed, 22 of them at diagnosis and 12 patients when IOL was developed. Peripheral blood samples were drawn after informed consent was obtained from the patient or the patient′s guardians in accordance with the Declaration of Helsinki. The analyzed parameters were: WHO classification, sex, age, blood count, number of RBC units received, iron metabolism, and mutations of the HFE gene. Liver damage was estimated by measuring Alanine transaminase (ALT) levels, and liver iron concentration (LIC) detected by Magnetic Resonance (MR). Likewise, levels of labile plasmatic iron (LPI) (eLPI Assay Kit, Aferrix) were quantified by spectrofluorimetric determination. Oxidative damage was assessed by quantifying the modified base 8-oxo-2-hydroxi-deoxiguanosine (8-oxo-dG) by means of High-Performance Liquid Chromatography (HPLC) and the O2− anion levels by flow cytometry. Results. According to the WHO classification, 72. 2% of cases with MDS and IOL assessed belonged to Refractory Sideroblastic Anemia (RSA) group, unlike 27. 3% of patients at diagnosis (p=0. 0265). In comparison to diagnosis patients, IOL subjects presented lower mean age (76 vs. 81 years; p=0. 0172), hemoglobin levels (7. 5 ± 0. 4 vs. 10. 3 ± 0. 3 g/dl; p

Beschreibung: Abstract 2452 Background. Clinical trials have shown an improved response rate and progression free survival (PFS) among the different treatment options used in the last two decades, specially with rituximab in combination with fludarabine and cyclophosphamide. We wished to analyze, in an unselected community based population, the clinical characteristics and efficacy of first line therapy with several treatment options used throughout a ten-year period. Patients and methods. We included 307 patients diagnosed of CLL and requiring first-line treatment between January 2000 and September 2009. Patients were treated at 20 hospitals placed in the Community of Valencia and Murcia and received first-line therapy according to the clinical guidelines of each hospital. PFS was calculated from date of first treatment to date of progression/relapse. We performed a descriptive analysis of clinical and biological features. The survival curves were built with Kaplan-Meier method and compared with the log rank test. Multivariate analysis for response and PFS were performed by logistic and Cox regression methods respectively, using the statistical package SPSS (v15). Results. Median age at treatment was 67 years (range 28–94) with 58% (n=179) men. 39% (120/305) were in Binet A, 38% (117) in Binet B and 22% (68) in Binet C. 27% (84) were Rai III-IV. B symptoms were present in 25% (77) and fever was a rare symptom 3%. Patients were asymptomatic in 59% (181) of the cases with ECOG performance status 0–1 in 83% (256). Splenomegaly was present in 41% (127) and hepatomegaly only in 8% (24). 42% of the patients (129) had at least three lymph-node areas affected with bulky disease (diameter higher than 〉5cm) in 10% (32). Median haemoglobin level was 126gr/L (46–169), lymphocyte count 49 x109/L (0,5–613) with lymphocyte doubling time (LDT)

Beschreibung: Abstract 2448 Introduction. Combination of Rituximab (R) with fludarabine (F) and cyclophosphamide (C) as first line treatment of B-CLL, results in a high complete response rate, improved progression free and overall survival compared with FC in randomised trials (Hallek et al, Blood 2009). However, more than 30% of patients relapse or show disease progression at 3–4 years after FR or FCR treatment (Byrd et al., Blood 2005; Keating et al., J Clin Oncol 2005). We report on the efficacy and safety results of an interim analysis after one year of Rituximab maintenance (Rm) following FCR in previously untreated CLL patients (pts). Methods and Patients. Between October 2007 and June 2009, a cohort of 84 physically fit pts with CD20 positive CLL received treatment with 6 cycles of FCR (R:375mg/m2 iv cycle-1 and 500mg/m2 iv, cycles 2–6; F:25mg/m2 iv, days 1–3; and C:250mg/m2 iv days 1–3; every 28 days). After 3 months of clinical response evaluation, pts achieving a response were treated with R: 375mg/m2 iv every 2 months for 3 years. Anti-infective prophylaxis included trimethoprim-sulfamethoxazole and acyclovir during treatment and until CD4 positive lymphocyte reached 0.3×109/L. Pts achieving a complete response (CR) and negative minimal residual disease (MRD) in peripheral blood (PB) and bone marrow (BM) after 4 courses of FCR, were allowed to stop FC and complete 2 courses of R and continue with Rm. The median age was 59.5 (range 37–70), 32% were females, 6% were Rai low risk, 69% intermediate risk and 25% high risk stage. IGHV status was unmutated in 64.4%, CD38 positive (〉30%) in 47.6% and ZAP-70 positive (〉20%) in 57.3% of pts. The incidence of genetic abnormalities by FISH for del 6q, del 11q (ATM), trisomy 12, del 13q and del 17p (p53) was 3.5%, 26.1%,15,4%, 50% and 4.7% respectively. MRD was evaluated by multicolor flow cytometry (sensitivity: 1 CLL cell positive in 10000 leukocytes). The primary end point was to evaluate the response rates and adverse events (AEs) profile of FCR and Rm treatments. Secondary endpoints included progression free and overall survival, correlation of response with MRD after FCR and Rm treatments. The mean number of FCR cycles was 5.3, and the complete treatment was administered in 80% of pts. Results. We present the results of a planned interim analysis after 1 year (6 cycles) of Rm following FCR as induction treatment. Of 90 pts screened from 29 centres, 84 were assigned (6 failed eligible criteria) to FCR and were evaluable for response. On an intent to treat analysis, overall response, CR, partial response (PR), non response and progression rates were 95.2%, 73.8%, 21.4%, 3.6% and 1.2% respectively. Of 79 pts evaluable for BM-MRD status, MRD-negative CR, MRD-positive CR, MRD-negative PR and MRD-positive PR rates were 57%, 21.5%, 7.6% and 13.9% respectively. The most common AEs after FCR were rituximab infusion (65.1%), myelotoxicity (33.7%) in 29 pts and infections (34%) with 1 serious AEs (SAEs)(1 exitus by viral myocarditis). In addition, there were 12 non hematological SAEs. Seventy five out of 84 pts continued with Rm treatment, 9 were withdrawn by progression (1), toxicity (5) and investigator decision (3). As of June 2010, 70 out 75 eligible pts had initiated Rm and 37 (49.3%) had completed 1 year of Rm (6 cycles) and were evaluable for response. Of them, 24 (64.8%) pts were in MRD-negative CR and only 1 pts converted to MRD-positive CR; 8 (21, 6%) pts were in MRD-positive CR and 3 converted to MRD-Negative CR, while 5 (13.5%) continued in MRD-positive CR with a sustained decreasing number of CLL cells in BM. Five pts were in MRD-positive PR and of them, 4 were in sustained PR with BM-MRD response and one pts presented clinical progression. In summary, 70.2% reached MRD-negative CR and 97.3% were in sustained response. The most common AEs after Rm were grade 3/4 neutropenia between cycles in 6 (16.7%) pts, infections in 15 (41.7%) pts and there were 2 (5.6%) SAEs (2 pneumonia) reported in this population. Conclusion: Based on these preliminary results, the addition of rituximab maintenance following FCR is feasible and effective in untreated CLL pts and increases the quality of clinical responses by obtaining a higher number of MRD-negative CR cases with an acceptable safety profile. Disclosures: Garcia-Marco: ROCHE: Consultancy, Honoraria, Research Funding. Off Label Use: Rituximab is not approved as maintenance therapy. Leon: ROCHE: Employment.