ALBERT

Description: Background: 90Y-ibritumomab tiuxetan (Zevamab®; ZEV; Bayer-Schering Pharma- Argentina) has been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Methods: Between Sep. 2005 and Feb. 2008, 45 patients (pts) [22 F & 23 M; median age 62 yrs (45–83)] with refractory/relapsed lymphoma were enrolled. Diagnoses: 37 follicular lymphoma (FL), 5 were mantle cell lymphoma (ML) and 3 transformed lymphoma (TL); 18 pts had bulky disease, 8 had bone marrow involvement and 21 had stage III–IV disease. Median time from diagnosis was 5 yrs (0.5– 29). Twenty two pts had received 1–2 previous treatments, and 23 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. ZEV was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and the same day of the ZEV administration, pts received standard rituximab 250 mg/m2. In 3 pt, ZEV was part of the conditioning regimen of autologous bone marrow transplantation. Results: Forty pts were evaluable for response: 34 (86%) pts responded – 19 CR (48%), 15 PR (38%). Overall survival and PFS for the entire group at 18 months was 63% and 37% respectively, with a median follow-up of 12 months (1–29 months). Of the 45 patients, 5 pts (11%) had died before third month and response was not assessed, 6 pts (13%) did not respond, 3 (7%) died with response from other causes, 14 pts (31%) responded and subsequently relapsed. Finally 17 pts (38%) continue to be in response, 9 (20%) lasting more than twelve months (long lasting responders). Slight differences in duration of response and survival were observed between FL vs ML and TL favouring FL (RR 2.047). Forty six per cent of pts required filgrastim for neutropenia, 24% required platelet transfusions, 22% had neutropenia plus fever and were admitted for complicated pancytopenia, and 20% required red blood cells transfusion. Two patient died 30 & 40 days after treatment with hypoplastic bone marrow complicated with sepsis in the post autologous bone marrow transplantation period. Four pts with previous bone marrow transplantation required filgrastim, transfusions and 2/3 had febrile neutropenia. Conclusion: Our experience with ZEV in relapsed and refractory FL shows 48 % CR. Even heavily treated pts that had previous bone marrow transplantation were able to receive ZEV, although they required extra support. Our experience supports the use of ZEV in relapsed and refractory lymphomas even after autologous bone marrow transplantation.

Description: The radionucleid conjugate with monoclonal antibodies (antiCD20/90Y-ibritumomab tiuxetan) have been approved for the treatment of relapsed, refractory and transformed (high grade) follicular lymphomas. Between September 2005 and August 2007, 41 patients with refractory/relapsed lymphoma were enrolled. Median age was 62 yrs old (45–83). Twenty were women and 21 were men. Thirty three were follicular and 5 were mantle cell lymphoma and 3 transformed lymphoma. Eighteen patients had bulky disease, 8 had bone marrow involvement and 21 had stage III-IV disease. Median time from diagnosis was 5 years (0.5–29). Twenty one had received 1–2 previous treatments, and 20 pts had received 3–5 previous treatments including 5 pts with autologous bone marrow transplantation. All had previously received anti-CD20 monoclonal antibody therapy. Six pts received previous radiotherapy. 90Y-Ibritumomab (Zevamab™ Bayer-Schering Argentina) was administered at 0.3 or 0.4 mCi, based on initial platelet count. Seven days before, and on the same day of the immunoconjugate administration, pts received rituximab 250 mg/m2. Thirty eight were evaluable for response. Thirty four (89%) pts responded: 20 CR (53%) and 14 PR (36%). With a median follow-up of 10 months, 60% of pts were expected to continue in CR at 18 months. Overall survival at the same period for the entire group was 89%. Nineteen pts (46%) required filgrastim administration for neutropenia, Ten pts (24%) required platelet transfusions, 10 pts had neutropenia plus fever and they had to be admitted for complicated pancytopenia, 8 pts required red blood cells transfusion. Two patient died 30 and 40 days after treatment with hypoplastic bone marrow complicated with septicemia and in the post autologous bone marrow transplantation period, respectively. Four pts with previous bone marrow transplantation, required filgrastim, transfusions and 2/3 had febrile neutropenia. Our experience with 90Y-ibritumomab in relapsed and refractory folicullar lymphoma shows 53% CR. Even heavily treated pts, that had previous bone marrow transplantation were able to receive the radioimmunoconjugate, although they required extra support. Our experience favours the use of 90Y-Ibritumomab tiuxetan in relapsed and refractory lymphomas even if they had received previous autologous bone marrow transplantation.

Description: Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease 〉 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

Description: Background: fludarabine (F) is licensed for the management of indolent non Hodgkin’s lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (M) in low grade NHL even in refractory relapsed (RR) patients (pts). The Latin American Cooperative Oncology Hematology Group (LACOHG) proposed a multicenter study in Latin American countries in 2002 to use FM in RR B-cell low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FM in RR B-cell low grade NHL during (2003–2006). Methods: Forty-eight patients in the period of January 2003 to February 2006 were evaluated. Forty-four pts. had follicular lymphoma and 4 small lymphocytic lymphoma. Median age 63.5 years old (range: 24–83). Gender: female 56% and male 44%. Inclusion criteria for low grade NHL-LG was: any previous treatment excluding autologous transplantation, Ann Arbor stage II to IV, age 〉 18 years old, ECOG performance status 0–2 and written informed consent. ECOG performance status 0: 2%, 1: 71% and 2: 27%. Ann Arbor staging: II: 2%, III: 29% and IV: 69%. International Prognostic Index (IPI): 0–1: 19%, 2–3: 71% and 4–5: 10%. Median previous treatment was 1 (range: 1–3). FM treatment consisted of F 25 mg/m2 i.v. (day 1–3) and M 10 mg/m m2 i.v. (day 1) each 28 days for 6–8 cycles. Results: on this low grade NHL cohort the overall response rate (ORR was 81%; progressive disease and non-response 19%. With a median follow up of 17 months, OS at 24 months was 86% (DE 5.2%) and DFS at 24 months 57.1% (DE 11.3%). LDH in serum was not an adverse prognostic factor for DFS and OS. Safety: on the 286 cycles in 48 pts, the toxicity was: 18 episodes of grade 3-4 neutropenias, 15 episodes of grade 3-4 thrombocytopenia, 7 episodes of grade 1–2 nausea/vomiting, grade 1–2 diarrhea in 4 pts, 8 pts were admitted to the clinic, 11 fever episodes, 2 allopecia, 4 pts developed grade 1–2 peripheral neuropathy and infections 7%: one case herpes zoster. Mortality rate: 12,5% (6/48 patients), 5 of them because progressive disease. No cardiac toxicity was reported. Conclusions: FM is an effective and safe treatment for RR low grade NHL. A longer follow up and a larger trial, might be needed to confirm these results in a multicenter, randomized study. DFS with FM in RR low grade NHL : LACOHG DFS with FM in RR low grade NHL : LACOHG

Description: Background. In our experience, in Argentina, the use of rituximab + chemotherapy in relapsed/refractory CD20+ follicular (FL) non-Hodgkin’s lymphoma results in 100,000/mm3 and bone marrow involvement 5 cm). Three pts were Ann Arbor stage I or II and 7 pts were stage IV. Three pts had received 1–2 cycles of rituximab + chemotherapy and 7 pts had received 3–5 previous cycles. Three pts had undergone autologous transplant. Pts received rituximab 250 mg/m2 IV on days 0 and 7. After the second dose of rituximab, pts received 11 MBq (0.3 mCi) 90Y-Zevalin per kg or 15 MBq (0.4 mCi) 90Y-Zevalin per kg based on platelet counts, with a maximum dose of 32 mCi. Blood counts were monitored weekly until week 10 post-treatment and monthly thereafter. Patient tumor response was reevaluated 3 and 6 months after treatment according to standard criteria. Results. Five pts received a complete dose of 0.4 mCi 90Y-Zevalin per kg and 5 received a reduced dose of 0.3 mCi 90Y-Zevalin per kg. The overall response rate was 60% (CR = 5, PR = 1). Table 1 summarizes the responses. The 5 pts with a CR remained disease-free 8 months later. The pt with a PR progressed with adenopathies and visceromegaly 7 months after treatment. Seven of 10 pts experienced hematologic toxicity: 5 of these 7 pts required G-CSF because of grade 3/4 neutropenia and 3 of these pts developed neutropenic fever. Four of the 7 pts required platelet transfusions and 2 of them required red blood cell transfusions. All 3 pts with previous autologous transplant were in the group with hematologic toxicity. All of these pts required G-CSF and transfusion support, and 2 of these 3 pts were admitted to the clinic for this treatment; hematologic recovery occurred by week 9 post-treatment. Conclusion. The use of 90Y-Zevalin in the relapsed/refractory NHL setting resulted in better response rates and longer disease-free survival than with standard chemoimmunotherapy. Our finding with 50% CR in a heavily pretreated cohort, including 42.8% CR in stage IV pts and 33% CR after autologous transplantation, is encouraging. We are continuing to follow these patients. Table CR PR NR/PD Previous transplant (n=3) 1 1 1 Mantle cell (n=1) 0 0 1 Follicular (n=9) 5 1 3 Tumor volume 〉 5cm (n=4) 1 0 3 Tumor volume

Description: Introduction: On August 2002 an international multicentric trial on Fludarabine monophosphate (FAMP) plus Cyclophsphamyde (Cy) among previously untreated B-cell CLL, was activated. Our aim is to evaluate efficacy and toxicity of FAMP plus Cy in previously untreated B-cell CLL patients (pts). This is the second interim analysis after a fourth-year period. Material and Methods: Treatment consists in three consecutive days of oral FAMP 40 mg/m2 (n=84) or i.v. FAMP 25 mg/m2 (n=13) plus i.v. Cy 600 mg/m2 on day 1 or Cy 250 mg/m2 from day 1 to 3, every 28 days × 6 cycles. Responses were assessed according to the National Cancer Institute working group criteria after cycle 3 and again after cycle 6. Since August 2002 to March 2006, 109 CLL pts from Argentina (n=95), Perú (n=11) and Uruguay (n=3) were enrolled for this protocol; eighty-nine were evaluated for response and toxicity. Median age: 64 years old (range: 44–81); male = 47, female = 42; Binet staging: A=14, B=45, C=30; median beta-2 microglobuline = 4.00 mg/dL (range: 1.3–9.2); median LDH = 341 UI/L (range: 101–762); among patients with available data the CD 38 expression more than 10% was 38% (22 of 58 pts). Blood counts at inclusion: median values (range); Lymphocytes: 32 ×109/L (2,7–137), Hb: 120 g/L (50–164), platelets: 175×109/L (10–364). Renal and hepatic parameters within normal range limits. Cytogenetic by banding was available in 27 cases: no alterations (n=17), +12 (n=1), del (6), del (12) (n=1), lost Y (n=1). Results: At the time of this second interim analysis (March 2006), 56.2% (50 pts) had completed 6 cycles and 97.8% (87 pts) had undergone at least 3 cycles. Overall responses: 92% = 81 pts (CR: 39% = 35 pts; PR: 52% = 46 pts); treatment failure: 9% = 7 pts. Evaluation for toxicity: 89 episodes of haematological toxicity and 7 episodes of infection grade 3–4 were reported after 436 cycles. Thirteen pts died: seven due infectious complications because of prolonged hematologic toxicity; one due to tumoral lysis syndrome, one due hemoptysis associated with lung cancer and the remaining four due disease progression. At 24 months, estimated DFS was 70% (figure 1, SE 7.6%) and estimated Overall Survival was 76% (figure 2, SE 7.4%). The median survival was not achieved in responders (PR and CR). Conclusion: FAMP plus Cy combination as front-line treatment is effective in B-cell CLL. Haematologic toxicity is the most severe adverse events. The response rates to this therapy is quite similar to those reported for other multicentric trials and better than others GATLA protocols. Figure 1 Figure 1. Figure 2 Figure 2.

Description: There is a general agreement that extensive remuneration gaps may cause pressing environmental, social, and economic problems. Thus, a critical question to be answered is what is the effect of being at the forefront of corporate sustainability on the CEO–employee pay gap. This paper addresses the question by examining empirical evidence from 415 constituents of the S&P 1500 index over the years 2006–2016. For the above period, we found a positive relationship between a strong commitment to sustainable development at the firm level and the CEO–employee pay differential. Additionally, firms characterized by higher performance, growth potential, and financial robustness constituted more dispersed salary distribution environments. The findings also suggest that CEO gender has a significant effect on the pay gap with a moderating influence of female CEOs. The paper contributes to the literature by shedding additional light on the urgent need for the implementation of a limit capping the CEO–worker pay ratio at a certain, responsible level as one of screening criteria used by sustainability ranking providers. Furthermore, it also shows that leading corporations in the area of sustainability do not implement any serious solutions in the above area on their own accord.

Description: Integrated reporting is a key instrument used to inform stakeholders about the sustainability issues of a company. Only an assured report can effectively instill confidence in its users regarding the sustainability of the company. Based on the International Integrated Reporting Framework issued by the International Integrated Reporting Council (IIRC), the authors solicited perceptions from auditors and audit report users about several aspects of integrated reporting assurance. An analysis of the responses suggests that integrated reporting assurance is important, but there are many challenges (both methodological and related to the characteristics of non-financial information) for auditors to overcome. Reporting companies and auditors must work to overcome these problems. The former ones must improve the quality of non-financial information and the later must adapt their audit procedures. This paper provides valuable insights into preferences regarding the form and content of the audit report on integrated reporting. This study is useful to regulators of audit activity, auditors’ corporations, the IIRC, and other international associations, academics, and audit report users, and contributes to the current integrated reporting literature by examining the perceptions of auditors and users regarding the assurance of integrated reporting. Integrated reporting assurance is still an under-explored field of research.