ALBERT

Beschreibung: To achieve CR is an important goal in the treatment of most Hematological malignancies. In Multiple Myeloma (MM) although there is evidence demonstrating an association between CR and long-terms outcomes, some trials have failed to find such a correlation. In addition, it is not clear whether different responses categories, such as CR, near-CR (nCR) o Very Good Partial Response represent different prognostic subgroups or include an homogeneous group of patients with similar outcomes. Therefore, the confirmation of a possible association between different responses categories and long-term outcomes is required. We evaluated the prognostic influence on EFS and OS of pre- and post-transplant responses in newly diagnosed MM patients. Patients and Methods: We analyzed 632 patients who had been included in the prospective GEM2000 trial. All were uniformly treated with VBCMP/VBAD induction followed by high-dose therapy and autologous stem cell transplant and maintenance therapy with interpheron plus prednisone. Disease response was assessed post-induction and post-transplant using EBMT criteria, modified to include nCR. CR required at least 6 weeks of negative immunofixation (IFx) in serum and urine plus less than 5% plasma cells in BM. nCR was defined as electrophoresis-negative but IFx-positive. Partial response (PR) required greater than 50% reduction in M-protein and Stable disease (SD) included patients with minimal response and no change by EBMT criteria. Results: Probability of achieving CR post-transplant was significantly higher among patients achieving nCR versus PR (p= 0.004) versus SD or PD (p= 0.0003) pre-transplant. Patients achieving nCR or PR post-induction had similar outcomes, and both response categories showed a trend to have inferior EFS and OS as compared to patients in CR. After transplant, only borderline differences in EFS were detected upon comparing nCR with PR (nCR: median 40 months; PR median 34 months, p=0.07), by contrast the EFS of CR patients (median 61 months) was significantly longer than that of nCR or PR categories (both comparisons p

Beschreibung: Abstract 5022 Krüppel-like factor 4 (KLF-4) is highly expressed in epithelial tissues such as the gut and skin. Several studies based on clinical evidence suggest that KLF-4 functions as a tumor suppressor in cancers of the colon, bladder, stomach and in leukemia. In contrast, KLF-4 expression is increased in primary breast ductal carcinomas and in oral dermal squamous cell carcinomas, suggesting that KLF-4 is important in tumor development and progression. However, KLF-4 expression in lymphomas has not been investigated. Our preliminary studies have examined KLF-4 expression in lymphoma cell lines and a TMA containing fresh tissues derived from patients with several types of lymphoma. There was a significantly higher expression of KLF-4 in Burkitt's lymphoma compared with other lymphomas such as follicular or DLBCL. These findings suggest that KLF-4 may be considered as a new biomarker in Non-Hodgkin's lymphoma (NHL). Further analyses based on the clinical outcome revealed that KLF-4 protein expression was significantly associated with poor patient's survival. The increased KLF-4 expression was associated with an inferior survival duration (P= 0.002). The survival for 12 patients who had a tumor with weak KLF-4 expression and 13 patients with negative KLF-4 expression was significantly longer than that for the 30 patients with strong KLF-4 expression (P〈 0.001). Other variables that affected survival in univariate analyses included stages and completeness of resection were shown to have a statistically significant effect on survival (P=0.001), however age or sex did not have a statistically significant effect on survival. These data provide the first clinical and causal evidences that alterations of KLF-4 expression can play a critical role in the development and progression of NHL. Disclosures No relevant conflicts of interest to declare.

Beschreibung: Objectives: To identify a clonal population by molecular techniques in patients treated with Fluradabine, Cyclophosphamide, Rituximab (CF+R) and included in the LNF-03 clinical trial. To relate these alterations to the clinical variables at diagnosis and response to treatment. Patients and Methods: Patients: 71 patients from the LNF-03 clinical trial. Their treatment consisted of CF+ Rx6 and posterior maintenance with Rituximab. Peripheral Blood (PB) and Bone Marrow (BM) were studied at diagnosis. Methods: bcl2/IgH rearrangements were studied by real-time PCR (Olsson et al, Mod Pathol 1999). Ig rearrangement of VDJ IgH, Igs IgL KVJ, Kdel and LVJ was studied according to BIOMED II protocols. Results: 43 of the 71 patients (60.56%) presented some molecular alteration in PB or BM. 33% of the patients in the study presented t(14;18) in some of its majority forms, bcl2/IgH mayor 19 (26.4%) and minor 3 (4.22%). 13 patients were positive for bcl-2/IgH, both in BM and in PB. The median amount of blc2/IgH in BM was 8.315% (62.9–0.04), Whereas in pb it was 4.775% (92.6–0.06), with no significant differences observed. Nevertheless, monoclonality was detected in BM in eight cases but not in PB, and to the inverse, one it happened in three patients. Of 71 patients, 38 (53.52%), presented displayed monoclonality in at least one of the Ig genes. Of these patients, 38% presented the clonal rearrangement in IG-L KVJ, 26% in IG-H CDR1, 23% in IG-L KDEL, and 13% rearranged in IG-L LAMBDA. There were 57 patients whose BM was available. 28 of them presented pathological infiltration, and monoclonality was detected in 23 cases; in 29 patients who were not pathologically infiltrated, monoclonality was detected in 12 cases. 83% (6/37) of the patients presented a complete response (CR), 8.1% (3/37) uncertain CR (uCR) and 8.1% (3/37) partial response (PR), after the induction treatment. No relation was found between the presence of molecular alterations in BM/PB and the achievement of a CR. Conclusions: The study of the rearrangements of Ig and bcl2/IgH is a good strategy for identifying lymphomatosus disease at diagnosis; bone marrow is more informative than peripheral blood. The presence of molecular alterations in PB and/or BM is not related to a poorer answer to induction treatment. Partially funded by Roche Farma SA.

Beschreibung: Abstract 1811 Poster Board I-837 The prognostic significance of achieving complete remission (CR) in Multiple Myeloma (MM) has finally been accepted. However, available studies have been based on series with a median follow-up around 5 years. This time period is insufficient according to the current life expectation of MM. Aim To establish the real effect of prognosis of the different response categories in a cohort of MM patients treated with autologous stem cell transplantation (ASCT) after long term follow up. Patients and methods Follow-up from diagnosis of 344 MM patients transplanted between 1989 and 1998 has been updated. These patients were previously included in a study aimed at establishing the post-ASCT response significance in MM and to validate the EBMT classification (Br J Haemat 2000;109:438-46). It was possible to update the follow up of 322 patients as at April 2009. At this date 99 patients were alive with a median follow-up form diagnosis of 12.5 years. Response categories and evaluated cases were: i) Complete Response (IF-) (CR), n= 84 ii) near Complete Response (EF-/IF+) (nCR), n= 66 iii) Very good partial response (VGPR) (