ALBERT

Description: The Cape Verde Frontal Zone (CVFZ) is a highly dynamic region located in the southern boundary of the Canary Current Eastern Boundary Upwelling Ecosystem. Due to the interaction of the Cape Verde Front with the Mauritanian coastal upwelling, the area features large vertical and horizontal export fluxes of organic matter. Full-depth profiles were recorded during FLUXES I cruise, with four consecutive transects defining a box embracing the giant filament of Cape Blanc and the Cape Verde front. Fifteen levels were sampled in medium and long stations (down to 4000 dbar) and 10 levels in short stations (down to 2000 dbar) where inorganic nutrients (NO3, NO2, Si(OH)4 and PO4), dissolved organic carbon/total dissolved nitrogen (DOC/TDN), and suspended particulate organic carbon and nitrogen (POC and PON) were sampled. Micromolar concentrations of nutrient salts were determined simultaneously by segmented flow analysis in an Alliance Futura autoanalyser. The determination of suspended POC and PON was carried out by high temperature catalytic oxidation at 900 °C in a Perkin Elmer 2400 elemental analyser. DOC and TDN were analysed by high temperature catalytic oxidation at 680 °C with a Shimadzu TOC-V analyser connected in line with a TNM1 measuring unit. Alongside with water samples conductivity, temperature and depth (CTD; SeaBird SBE911 plus), and dissolved oxygen (SeaBird SBE43), fluorescence of chlorophyll (SeaPoint SCF), and turbidity (SeaPoint STM) were measured. CTD conductivity was calibrated with water samples taken from the rosette and analysed on board with a Guildline 8410-A Portasal salinometer. Samples for dissolved oxygen (O2) determination were analysed on board by the Winkler potentiometric method. The chlorophyll (Chl) fluorescence sensor was calibrated with water samples taken at 4 depths in the photic layer which were estimated fluorometrically by means of a Turner Designs bench fluorometer 10-AU.

Description: INTRODUCTION Follicular lymphoma (FL) may, over time, transform into an aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). Transformed follicular lymphomas (tFL) have a worse prognosis due to poorer response to treatment than primary DLBCL. The incidence of transformation is estimated in ~3% per year, although it varies largely between different studies (24%-70% overall). These differences are mainly due to different criteria to define tFL, to lack of evidence of tFL by biopsy, absence of clonality studies discarding secondary de novo NHL, studies performed in the pre-Rituximab era, or different follow-up times among studies. With all this pitfalls, the actual incidence of transformation remains an open question. The aim of the present study is to analyse the incidence and prognostic impact of transformation in patients with FL in a large retrospective series of the Spanish group of Lymphomas (GELTAMO). PATIENTS&METHODS A total of 1763 patients from 19 Spanish centres diagnosed of FL between 2000 and 2011 were recruited in the study. Data were obtained from the database of centres willing to participate in this study. True tFL (FL to DLBCL) were recorded. From the original cohort, FL IIIb, composite FL+DLBCL, discordant FL (FL in bone marrow and DLBCL in adenopathy or viceversa), and downgrading tFL (DLBCL at diagnosis and relapse of FL) were excluded. Patients with inadequate follow-up were not considered. Therefore, 1611 patients (grade I, II, and IIIa) were finally included. This study was approved by the Salamanca University Hospital Ethic Committee. RESULTS One hundred and ten patients (median follow up of 6 years) were transformed to DLBCL. Cumulative incidence of transformation at 5, 10, and 15 years was of 5%, 9%, and 14%, respectively. With a median follow up of 75.9 months (2 to 179), median time to transformation was 66 months, ranged 1-179. Considering survival from diagnosis of FL, tFL patients had a shorter OS than non-transformed (19% vs. 69%, p

Description: Introduction: 30% of Hodgkin Lymphoma (HL) patients are refractory or relapse (RR) after first line therapy. Salvage chemotherapy followed by high-dose chemotherapy and with Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) can cure many patients, but those who are transplanted with active disease detectable by PET-CT have a very poor prognosis. Therefore, the current challenge in HL is to improve the results of the pre-transplant chemotherapy. We and others have demonstrated that the addition of Brentuximab Vedotin (BV) to chemotherapy can produce very good results. Objectives: We conducted a phase II trial to assess response rate with combined Brentuximab vedotin and ESHAP chemotherapy [BRESHAP] as 2nd line therapy for RRHL prior to APBSCT (ClinicalTrials.gov #NCT02243436). Methods: Primary efficacy endpoint was the proportion of complete responses (CR) pre-APBSCT. A prior phase I step was carried out to establish the appropriate dosis. Final treatment consisted of Brentuximab Vedotin (1.8 mg/m2/day IV, D1), Etoposide (40 mg/m2/day IV, D1-4), Solumedrol (250 mg/day IV, D1-4), High dose AraC (2 g/m2 IV, D5) and cisPlatin (25 mg/m2/day IV, D1-4). Results: Patients with relapsed or refractory classical HL (cHL) after one prior line of therapy were eligible. 66 patients were included in the trial. There were 35 females and 31 males, with a median age of 36 years (18-66). At inclusion, 40 patients were considered primary refractory, 16 as early relapses (complete remission -CR- shorter than 1 year) and 10 as late relapses. Currently, all patients have completed the pre-transplant therapy. During that period, there were 22 Severe Adverse Events (SAEs) reported in 15 patients: Fever in 13 occasions (neutropenic in seven, and non-neutropenic in six), hypomagnesemia and gastrointestinal alterations (n=2) and pneumothorax, skin lesions, left ventricular function reduction and pulmonary embolism [PE](n=1). There were 2 deaths: non-neutropenic abdominal sepsis and PE. Grade 3-4 hematologic toxicity presented in 22 cases: neutropenia (n=18), thrombocytopenia (n=12), and anemia (n=5). Grade 3-4 extrahematologic adverse events present in ≥5% of cases were non-neutropenic fever (n=8) and hypomagnesemia (n=3). All patients except three underwent stem cell mobilization after the 1st (n=15), 2nd (n=36) or 3rd (n=12) cycle using subcutaneous G-CSF 5 mcg/Kg/12 h. for 5 days. All patients collected 〉2·10e6/Kg peripheral blood CD34+ cells in all cases (median 5.75, range 2.12-33.4). The number of harvesting procedures was one in 47 patients, two in 13, three in 2 and four in 1. The transplant has been done in 61 patients, with data are available from 47: all engrafted with a median of 9&10 days for neutrophil and platelet recovery, respectively. No major events were registered during transplant period, except for one patient who died at day +110 due to pneumonia. Overall pre-transplant response was 96%, including a 70% and 26% complete and partial remission rates, respectively. Of these forty-seven patients, 37 (80%) were in metabolic CR after transplant and 3 (7%) in PR; six patients were considered as non-responders (13%) and went out of the trial. At a mean follow-up of 11 months, 7 patients have progressed, rendering a projected progression free survival of 87% at one year. Six patients have already died: three due to progression, and the three already mentioned above (PE, abdominal sepsis and pneumonia). With a mean follow-up of 11 months, the projected overall survival was 90% at one year (cause specific, 96%). Conclusions: BRESHAP is a highly effective regimen for remission induction prior to transplant in patients with refractory or relapsed Hodgkin lymphoma. The addition of BV to the conventional chemotherapy did not resulted in a higher toxicity for the pre- and post-transplant periods and it did not hamper the collection of PBSC. Disclosures No relevant conflicts of interest to declare.

Description: Key Points Increased levels of sCD19 protein in the CSF are associated with CNS disease in DLBCL and BL patients at risk of CNS lymphoma. Presence of lymphoma cells by FCM and/or increased CSF sCD19 levels are related with a poorer EFS and/or OS in DLBCL and BL patients.

Description: Background and objective Fludarabine in combination with cyclophosphamide (FC) plus rituximab (R) is an effective treatment for newly diagnosed as well as relapsed follicular lymphoma (Tam 2004; Keating 2005; Sacchi 2007). Maintenance treatment with R, after different induction treatments, improves overall and progression-free survival (Forstpointner 2006; van Oers 2006). Therefore, we aimed to evaluate the efficacy and safety of the FC-R regime followed by maintenance doses of R. Patients and Methods We present an intermediate report of the one-arm study in which 75 previously untreated patients with a diagnosis of follicular non-Hodgkin’s lymphoma in Ann Arbor stage II–IV were included between October 2004–2006. Seventy four were assessed for safety after receiving at least one FC-R dose (F: 3x25 mg/m2 and C: 1 g/m2; R: 375mg/m2), and 72 for response to treatment. Patients aged 53.4 years in average, one in five showed bulky disease and 72.2% Ann Arbor IV staging. FLIPI index determined 23.9% patients with low (0–1) score, 38% with intermediate (2) and 38% with poor score (3). A total of 47 patients presented some molecular alteration in PB or BM. Results Induction therapy was delivered throughout 4–6 courses, resulting in 91% complete responses (CR) and 9% partial responses (PR) (Table 1). From the patients who presented monoclonal population at diagnosis, 40 were evaluated for molecular response after induction and only 1 remained MDR positive for bcl2/IgH. Overall survival (OS) at 24 months was 87.5%, and two patients presented progressive disease within this period. The median OS has not been reached at this evaluation. To the date, 262 adverse effects grade 3–4 (32.6%) have been documented (80.9% neutropenias) and 80 infectious complications were recorded (23.8% grade 3–4). Three patients died from respiratory diseases, two from acute leukemia, and six from other causes. Table 1 EVOLUTION OF RESPONSE Evaluated Response at End of Induction Therapy Evaluated Response Post-Course 3 Assesable End Ind. (n=67) Missing End Ind. (n=5) CR: complete response; uCR: unconfirmed CR; PR: partial response; NE: not evaluated; WD: withdrawn; EX: exitus. Assesable PC3 (n=70) CRITERIA CR PR NE WD EX 14 CR 12 - 1 1 - 32 uCR 31 - 1 - - 24 PR 16 6 - - 2 2 Missing PC3 (NE) 2 - - - - 72 Total 61 6 2 1 2 Conclusions The FC-R has proven a potent antitumoral activity in untreated follicular lymphoma patients, rendering very high clinical and molecular responses. However, as reported in similar studies (Hochster 2007 ASCO), the high incidence of prolonged neutropenias and lymphopenias developed as consequence of the chemotherapy regime, questions the safety of the induction treatment.

Description: BACKGROUND: For more than 20 years, CHOP has been the gold standard treatment for patients with aggressive NHL. The addition of rituximab to this regimen has been shown to improve outcomes in elderly patients with advanced (Coiffier et al NEJM2002; 346:235–42). However, CHOP is often poorly tolerated by elderly patients resulting in dose reductions and consequently lower response and cure rates compared to younger patients. Myocet™ (non-pegylated liposomal doxorubicin) has an improved pharmacokinetic profile with less myelosuppression and GI toxicity and has a reduced risk of cardiotoxicity at dose levels equivalent to standard formulations of doxorubicin. METHODS: In this phase II, open label, 2-stage study, we replaced the conventional doxorubicin with Myocet™ to evaluate the response rate and safety of the R-COMP regimen (rituximab, cyclophosphamide, vincristine, Myocet™, prednisone). Previously untreated, elderly patients (≥60 yrs) with CD20+ newly diagnosed, advanced DLBCL were treated every 3 weeks with: Myocet™ 50mg/m2, cyclophosphamide 750mg/m2, vincristine 1.4 mg/m2 (max. 2mg), rituximab 375 mg/m2 (day 3 on cycle 1, day 1 thereafter) and prednisone 100mg/d d1–5 for 8 cycles. Response was assessed after 3 and 8 cycles. RESULTS: Thirty patients were enrolled in stage 1 of the study with a median age of 72 (range 61–82). At baseline 17 (56%) patients had stage III–IV disease; 60% had an intermediate or high risk (2+) International Prognostic Index score and the median LVEF was 59% (range 50–75). A total of 198 cycles of chemotherapy were given, with a median of 8 cycles (range 1–8). Of the 198 cycles administered 15 (8%) were delayed by haematological or hepatic toxicity for a median of 7 days (range 0 to 25). The relative dose intensity for the regimen was 87%, for Myocet™ it was 84%. Toxicity was mainly haematological with grade 3 or 4 neutropenia in 29% of cycles and febrile neutropenia in 4%. There was no grade 3 or 4 vomiting and a low incidence of grade 1 or 2 vomiting (3%). At the last observation the median LVEF was 55% (range 40–76), 16 patients had no change or an improved LVEF and 13 patients had a reduced LVEF. In the cohort of 24 patients evaluable for response, 15 (63%) had a complete response and an additional 7 (29%) achieved a partial response. CONCLUSIONS: These interim results suggest R-COMP is a well tolerated regimen with promising response rates in elderly patients with advanced DLBCL. Patient recruitment continues in stage 2 of the study with the aim of enrolling a total of 75 patients with a 2-year follow-up.

Description: Introduction: Diffuse large B-cell lymphoma (DLBCL) is one of the most common malignant neoplasms in elderly patients, potentially curable when optimum treatment is administered. The combination of rituximab with CHOP chemotherapy (R-CHOP) is considered standard for these patients, but randomized studies published to date are limited to the range of age from 60 to 80 years, so that in patients over this age treatment election is not so clear, usually opting for palliative treatment or a "full" treatment at a reduced dose. This retrospective study is primarily aimed to analyze the influence of the type of treatment and comorbidity scales in overall survival (OS) of a large series of patients 〉80 years with aggressive B-cell lymphoma. Methods: Eligible patients were aged ≥ 80 years, diagnosed of DLBCL, follicular lymphoma grade 3B or transformed lymphoma. The main patient characteristics were obtained retrospectively from the medical records, including a complete geriatric assessment (CGA, "comprehensive geriatric assessment") and the Charlson comorbidity index. The Ethics Committee of the University Hospital of Salamanca approved the study. Results: 288 patients from 19 GELTAMO hospitals were registered in the study, of which 234 (60% women) were evaluable and have been included in this preliminary analysis. The median age was 84 years (80-94) and the vast majority (94%) were DLBCL. According to the Charlson index, 65% of patients were low-intermediate risk, and according to CGA, 63% of patients were considered "fit". A higher proportion (60% v 44%, p = 0.03) of patients with low or intermediate comorbidity index were treated with a curative intent (CHOP +/- rituximab), as compared with patients with high or very high index. With a median follow up of 41 (range 9-142) months, the median OS was 11.5 months (33% estimated at 3 years). The median OS for patients treated with R-CHOP-like (N=96) was 35.3 months, significantly better (p

Description: Myeloablative transplant has been investigated in poor prognosis indolent lymphoma; although recurrence rate is low it is associated with high mortality; the use of non-myeloablative conditioning regimens could reduce TRM maintaining the GVH effect. Up to May 2006, 35 patients with follicular NHL received a Non Myeloablative related allogeneic according to two prospective multicenter trials; conditioning regimen consisted of Fludarabine 150 mg and Melphalan 70–140 mg. GVHD prophylaxis consisted of CSA plus short-course MTX. All patients received filgrastim-stimulated peripheral blood stem cells from a HLA related identical donor. Median age at transplant was 50 years (34–62) and 16 (46%) had received a previous autologous transplant. At transplant, 5 patients (14%) were in CR1 (after several lines of chemotherapy), 9 (25%) in 〉CR1, 12 (34%) in PR, 1 (3%) had stable disease (after 3 chemotherapy lines) and 8 (23%) progressive disease. All patients engrafted. Acute GVHD developed in patients 19 (54%) (17patients (48%) grade II-IV). Chronic GVHD developed in 18 out of 27 patients at risk (67%), being extensive in 11 (41%). Disease was evaluated at day +100 and at that moment 23 patients were in CR, (85%) 1 (4%) in PR, two (7%) had stable disease and 9 patients ( 26%) have died. With a median follow up of 60 months (range: 32–80 months), 20 patients (57%) are alive disease free, and 14 (43%) have died, 12 of them (37%) due to transplant toxicity and 2 patients (6%) due to progression. Overall Survival (OS) and Event Free Survival (EFS) are 57 and 54 % respectively. Analysing variables which influence on OS and EFS, patients 55 years have a OS significantly shorter than those

Description: Background: Nodal aggressive PTCL have a poor prognosis with conventional chemotherapy regimens for aggressive non-Hodgkin lymphomas. Therefore innovative approaches are needed. Among them, strategies including consolidation with high-dose chemotherapy and autologous stem cell transplantation in front line therapy may improve the outcome of these diseases. Aim: To report the experience of a national cooperative group in 26 patients with aggressive nodal PTCL who underwent treatment including ASCT as consolidation of front line therapy. Patients and Methods: Twenty-six patients Gallium scan positive with nodal PTCL entered into the study: 11 cases of PTCL-unspecified (42%), 8 ALCL (31%) and 7 AIL (27%). Patients received three courses of MegaCHOP and subsequently were evaluated by CT scan and Gallium scan. Those patients Gallium scan negative received another course of MegaCHOP and then the transplant. Those patients Gallium scan positive after 3 courses of MegaCHOP received 2 courses of the IFE regimen (Ifosfamide 3.3g/m2 days 1–3 and Etoposide 300 mg/m2 days 1–3) and if at least achieved a partial response received the transplant otherwise they are out of the study. Median age was 44 years, 96% of the patients presented Ann Arbor stage III or IV; 54% presented B symptoms; 31% bone marrow involvement and 72% of the patients presented 2–3 factors of the a-IPI. Results: Thirteen patients (50%) achieved a CR after 3 courses of MegaCHOP and 12 patients received IFE as salvage therapy. Twenty patients out of the 26 initial patients were able to proceed to the transplant. After the transplant 85% of patients achieved a CR. The 6 patients who did not received the transplant was due to progression of the disease in 4 cases, lethal toxicity in one case and refusal in another case. With a median follow up of 35 months for alive patients, the overall survival (OS) and progression-free survival (PFS) at 3 years were 73% and 53%, respectively. OS, PFS and disease-free survival for the 20 patients who underwent the ASCT consolidation was 84%, 53% and 63%, respectively. Conclusion: Early salvage therapy for patients not in CR after 3 courses of chemotherapy and ASCT consolidation for chemosensitive patients may improve the outcome of patients with nodal aggressive PTCL. Larger series and longer follow up are needed to confirm this promising approach.