ALBERT

Description: Abstract 1376 Poster Board I-398 Introduction: A relationship between red blood cell (RBC) transfusions and the subsequent development of NHL has been suggested from previous observational reports. The mechanism is unclear but could be related to the known immunomodulatory effect of blood transfusion. This report is a meta-analysis of such observational studies and helps clarifying the strength of such an association, if any. Methods: We searched MEDLINE from January 1966 through June 2009 for observational studies on the association between RBC transfusions and NHL in adults using the keywords “transfusion” and “lymphoma”. Prospective studies and case control studies that reported relative risks (RR), hazard ratios or odds ratios with 95% confidence intervals (CI) were included. One author (SD) gathered the data and another (JC) reviewed the data. A fixed-effect model (FEM) was used to assess the combined outcome of individual studies while a random-effects model (REM) was used, if needed, to account for heterogeneity between studies. Heterogeneity was evaluated using the Cochrane Q and I2 statistics. Publication bias was assessed by direct observation of a funnel plot as well as trim-and-fill statistics. Quality of the studies was assessed independently by another author (SP) using the Newcastle-Ottawa scale. Results: Our initial search rendered 1830 articles. After reviewing the abstracts, 21 papers were selected, from which 5 prospective and 9 case-control studies were included in the final analysis. Based on case-control studies, cases receiving RBC transfusions were associated with an RR of 1.37 (95% CI 0.94-1.87) of developing NHL (p=0.11); a REM was used given the heterogeneity found between studies (I2=90%; Q=90.9, p

Description: Abstract 4790 Introduction Selective ligands of retinoid X receptor (i.e. bexarotene) are used in the treatment of early and advanced stages of cutaneous T-cell lymphoma (CTCL). The objective of this study is to report a Peruvian single-institution experience on 13 cases of relapsed or refractory CTCL who were treated with low-dose bexarotene alone or in combination with phototherapy or interferon alfa-2a. Methods From 2002 to 2008, thirteen patients with relapsed or refractory CTCL were treated with bexarotene at low dose (75-300 mg/day) as monotherapy (BEX; 3 cases) or in combination with interferon alfa-2a (INF) at 3-9 million units subcutaneously three times a week (5 cases) or phototherapy (PT; 4 cases). Therapy was continuously administered until progression of disease or unacceptable toxicity. Eight patients with mycosis fungoides (MF), two patients with aggressive epidermotropic CD8+ cytotoxic lymphoma (AECL), two patients with Sezary Syndrome (SS) and one with smoldering adult T-cell leukemia/lymphoma (ATLL) were included in this study. Results Mean age was 57 years (range 26 to 74 years). In average, patients were exposed to three prior lines of therapy (range 1 to 5). From the 8 cases of MF, 3 cases were treated with BEX monotherapy, achieving 1 complete response (CR), 1 partial response (PR) and 1 progressive disease (PD); 3 cases were treated with BEX and PT, obtaining 1 CR and 2 PR; and 2 cases were treated with BEX and IFN, both showing PD. From the 2 cases with AECL, 1 case received BEX/PT achieving a PR and 1 case received BEX/IFN showing PD. From the 2 cases with SS, both were treated with BEX/IFN achieving a PR. The case of ATLL achieved a PR with BEX/PT. The overall response for the entire group was 69.2% (9/13) with a mean duration of response of 15 months (range 2 to 67 months). From the therapy point of view, BEX alone achieved a 66% overall response rate (ORR), BEX/IFN showed a 40% ORR and BEX/PT showed a 100% ORR with a 20% CR. Most common adverse events were mild, seven patients experienced grade 1–2 hypercholesterolemia, and hypertriglyceridemia grade 1–2 was seen in seven patients and grade 3 in two cases. Four patients developed grade 1–2 hypothyroidism. Conclusions Low-dose BEX alone or in combination with INF or PT is effective in the treatment of patients with relapsed or refractory CTCL and is associated with mild toxicity. Prospective studies, if possible, are needed to further investigate novel therapeutic approaches in these hard-to-treat patients. Disclosures: No relevant conflicts of interest to declare.

Description: BACKGROUND: Age-related Epstein Barr virus (EBV)-associated B-cell lymphoproliferative disorder (LPD) is a newly described entity initially reported in Japanese patients with diffuse large B-cell lymphoma (DLBCL) and coinfection with EBV. It usually affects elderly patients and is characterized by poor survival. Immunohistochemical analysis of patients with DLBCL using bcl-6, CD10 and MUM1 can further subclassify DLBCL in germinal center (GC)-like or non-germinal center (non-GC) phenotypes. Non-GC phenotypes have been associated with resistance to conventional therapy and poorer prognosis when compared to GC-like phenotypes, even in the rituximab era. AIM: The goal of this study was to evaluate the immunohistochemical pattern of GC and non-GC markers in patients with diagnosis of age-related EBV-associated B-cell LPD. PATIENTS AND METHODS: Between January 2002 and June 2008, twelve patients with age-related EBV-associated B-cell LPD were identified and included in the analysis. Clinical data were reviewed retrospectively and patient’s biopsies were analyzed for the immunohistochemical expression of bcl-6, CD10, CD30 and MUM-1/IRF4 by tissue microarray technique. Cases were also investigated for EBV-encoded RNA (EBER) using an in-situ hybridization technique. RESULTS: In this cohort, the mean age was 72 years old (range 34–85) at diagnosis; the male to female ratio was 1.4. B symptoms occurred in 5 out of 10 patients. ECOG performance status was higher than 1 in 9 of 10 patients. Advanced stages (III/IV) were observed in 8 of 10 patients. IPI score was higher than 2 in 8 of 10 patients. Extranodal involvement was identified in pleura (n=2), suprarenal gland (n=1), stomach (n=1), cecum (n=1) and bone marrow (n=1). Morphology in all cases was consistent with large cell lymphoma. All cases were positive for EBER and CD20 expression. Two cases had strong positivity to CD30. Ten cases (83%) had non-GC phenotype and 2 cases (17%) had GC-like phenotype. From the non-CG group, five patients (50%) received CHOP regimen. Two had complete response and three had progressive disease. Most of the cases died during the first year with the exception of two patients; one patient had a survival of 42 months and the other is currently receiving treatment with CHOP. From GC-like phenotype group, one patient received CHOP regimen with progressive disease and died 3 month after diagnosis. The other case was lost to follow-up. CONCLUSION: The majority of patients in this report who were diagnosed with the newly described age-related EBV-associated B-cell LPD had a non-GC immunophenotype. This distinct subtype of DLBCL presents with advance stages, high IPI scores, extranodal involvement and short survival. Further research is necessary to elucidate the lymphomagenetic role and the prognostic value of EBV and to improve therapies, which are highly needed in this group of LPD.

Description: BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma. AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis. PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method. RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%. CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

Description: INTRODUCTION: The etiology of Hodgkin lymphoma (HL) is largely unknown. However, certain associations have been noted, such as familial factors and infection with viruses. Smoking has been associated with the development of multiple malignancies and some studies have reported an association between HL and smoking but the relationship of tobacco use with lymphomas in largely unclear. OBJECTIVE: To investigate the potential relationship between tobacco use and the development of HL using a meta-analysis methodology of retrospective, case-control studies. METHODS: An extensive search was conducted using Pubmed/MEDLINE through July 2008. Case-control studies that reported odds ratio (OR) and 95% confidence intervals (CI) or allow for those values to be calculated were included in our analysis. Case reports, editorials, letters to the editor, review articles and prospective studies were excluded. The smoking status was then subdivided in three groups: never smokers, former smokers and current smokers. Meta-analyses were performed comparing the risks of former and current smokers against the risk of never smokers of developing HL. Fixed and random effects models were used to assess for heterogeneity. RESULTS: Seven case-controls studies, accounting for 3201 cases and 15268 controls were included in the analysis. Most of the articles reported OR adjusted for age, sex and educational level. In former smokers, the OR was 0.73 (95% CI, 0.65 – 0.82) when compared to never smokers; no heterogeneity was detected. The current smoker group had an OR of 1.70 (95% CI, 1.36 – 2.13) when compared to the never smoker group; some heterogeneity was detected in this group (p 〈 0.003, I2 = 69.6%). CONCLUSIONS: Despite the heterogeneity observed in the analysis, the current smoker group seems to have a 70% increased risk of developing HL. Although a cause-effect linkage between tobacco use and HL is difficult to prove, further basic and translational research is necessary to clarify the potential etiological role of smoking in HL.

Description: BACKGROUND: Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma (ALK-DLBCL) is a rare lymphoma with several differences from ALK-positive anaplastic large cell lymphoma (ALCL). ALK-DLBCL appears as a defined disease entity characterized by the expression of the ALK protein, usually in a granular cytoplasmic fashion. These cells are usually CD20-negative but express plasma cells markers. The most common chromosomal abnormality is a fusion between the ALK and the clathrin gene. Clinically, ALK-DLBCL presents as lymph node-based disease affecting mostly middle-aged men, frequently showing aggressive behavior, a negative prognosis at advanced stage and a strikingly rare bone marrow involvement. Only 44 cases are currently reported in the English and non-English literature. METHODS: This is a retrospective study with data collected on four patients with ALK-DLBCL between 2002 and 2008 in a general hospital from Peru. Immunohistochemical studies were performed to detect expression of B-cell, T-cell, plasma cell markers and oncoviruses (i.e. EBV and HHV8). FISH cytogenetic studies were attempted but were unsuccessful. Clinical characteristics of the cases included age, sex, primary site of involvement, IPI score, Ann Arbor stage, therapy, survival in months and final outcome. RESULTS: The male:female ratio was 1:1; one 13-year-old girl and three adults of 27, 41, and 70 years of age were identified. Two patients had primary extranodal disease (multifocal bone lesions and right nasal fossa involvement) and the remaining two patients had exclusively nodal disease. Stages were I (n=1), II (n=1), III (n=1) and IV (n=1). Two patients had increased LDH levels and three patients reported B symptoms. IPI scores were 0 (n=1), 2 (n=1) and 3 (n=2). All cases exhibited immunoblastic/plasmablastic morphology. By immunohistochemistry the cases showed positive expression of cytoplasmic ALK-1, CD138, monoclonal cytoplasmic light chain, CD45 and EMA. All cases lacked expression of the CD3, CD20 and CD30 antigens. HHV8 and EBV were not expressed. The survival times ranged from 11 to 72 months; the latter was observed in a patient who presented with stage III disease and is still alive without evidence of lymphoma. CONCLUSIONS: ALK-DLBCL is a distinct subtype of B-cell lymphoma, which does not express CD20 and is characterized by marked plasmacytic differentiation. This lymphoma has clinically aggressive behavior and more effective therapies are warranted. However, some cases can have prolonged survival with intensive regimens. Table 1. Clinical characterisitics of the reported cases Case Age Sex Primary site IPI Stage Therapy Survival (months) Outcome *This regimen is based on induction with vincristine, prednisone, cyclophosphamide, daunorubicin, L-asparaginase and methotrexate, followed by consolidation based on cyclophosphamide, cytarabine, metrotexate, then intensification with vincristine and doxorubicin and manteinance based on metrotexate and mercaptopurine. 1 41 F Nasal fossa 0 IA Radiotherapy 13 Alive, free of disease 2 13 F Cervical lymph node 2 IIB France NHL 96–2002* 62 Alive, free of disease 3 70 M Cervical lymph node 3 IIIB CHOP 72 Alive, free of disease 4 27 M Bone 3 IVB HyperCVAD 11 Alive, with disease

Description: Abstract 1930 Poster Board I-953 Background: Lymphopenia is an independent prognostic factor for survival for different hematological malignancies like follicular lymphoma, Hodgkin lymphoma and diffuse large B-cell lymphoma. The role of lymphopenia at diagnosis on survival in peripheral T-cell lymphoma, unspecified (PTCLU) is not known. Methods: Eighty seven patients with a diagnosis of PTCLU were evaluated at the Edgardo Rebagliati Martins Hospital in Lima, Peru from October 1997 until April 2008. The primary objective of the study was to assess the role of lymphopenia at diagnosis in survival in cases with PTCLU. Lymphocyte count at diagnosis was obtained from the standard complete blood cell count (CBC). Lymphopenia was defined as a lymphocyte count of less than 1 × 109/L. Kaplan-Meier survival estimates and the log-rank test were performed for univariate survival analyses and Cox proportion-hazard regression test was performed for the multivariate analysis. Results: Eighty four patients with a histological diagnosis of PTCLU were included in this study. The median follow-up was 13.4 months (range 1–68 months). The sample population included 54% males and 46% females with a median age of 57 years (range 18–87 years). The median number of lymphocytes at diagnosis was 1.3 × 109/L (range 0.06–5.2 × 109/L). Lymphopenia was present in 37% of cases. In the univariate analysis, lymphopenia was identified as a poor factor for survival (median OS 59 vs. 1 month; p

Description: Background: Alemtuzumab (Campath®/Mabcampath®, anti-CD52 humanized monoclonal antibody) has recently been shown to be effective in the treatment of diverse hematological malignancies. Mycosis fungoides (MF) and Sezary Syndrome (SS) are low grade cutaneous T-cell lymphoma with indolent course and multiple relapsed. Aim: We describe our experience from three centers in South America with refractory/relapsed MF/SS patients treated with Alemtuzumab as monotherapy. Methods: From July 2005 to April 2006 a total of 13 patients were recruited from 2 centers in Lima-Perú and one center in Caracas-Venezuela with histopathology diagnosed of advanced refractory/relapsed MF (10pts) or SS (3pts); median age 60 years old (range: 36–72); 9 pts. were male. Median number of previous therapies 2.5 (range: 2–7). Treatment scheduled was planned as follow: Alemtuzumab 30 mg i.v. tiw per 8 weeks with a gradually escalated doses during the first week (3,10, 30 mg). Trimethoprim/sulphamethoxazole and acyclovir as prophylaxis were given. Median Alemtuzumab total dose was 429 mg (range: 123–706) over a median time of treatment of 6.2 weeks (range:3–15). The first nine pts. received the planned schedule dose; 2 pts. received Alemtuzumab 30 mg i.v. tiw for 4 weeks and then 30 mg i.v. weekly and the last 2 recruited pts. received Alemtuzumab 10 mg iv. tiw for 4 weeks them after 10 mg i.v. biw and finally 10 mg i.v. weekly. CMV monitoring with pp65 was performed in the first five pts. and qualitative PCR in 3 pts. Results: Twelve patients were evaluable for response. Overall response rate (ORR) was 75% (9/12), with three patients achieving complete remission (CR) and six patients with partial response (PR); three patients with progressive disease (PD) during treatment. Responses were seen in 6/9 (75%) MF pts. and 3/3(100%) SS pts. Regarding clinical presentation: 4 over 4 (100%) eritrodermic forms responded and 5 over 8 (62%) tumoral forms responded. Response duration and CMV reactivation were described in table 1. Hematological toxicity was grade 1–2 neutropenia in three pts. and grade 1–2 thrombocytopenia in three pts. One pt. developed urosepsis caused by E. Coli. and 1 pt. had genital herpes. No cardiac toxicity was reported. Kaposi sarcoma progression was discovered in one pt. One pt. died with CMV pneumonitis, three months after treatment, 1 pt. died at two months during treatment for a neurology event Conclusion: Alemtuzumab as monotherapy shows promising clinical activity with sustained response in patients with advanced MF and SS. New studies should be address the Alemtuzumab impact in these malignancies with reduced doses or even combined therapies. Table 1. Outcomes, follow-up and CMV status Alemtuzumab (TD, mg) Response Follow-up (m) CMV Status TD=total dose, NE=no evaluable, AD=active disease, m=months, R=reactivation, F=fever, P=Pneumonitis 123 NE AD, 14 m R with F 313 PD Died, 8 m 706 PD AD, 8 m 403 CR Relapse at 6 m R with F 253 CR Relapse at 3 m. R with F 493 PR PR at 8 m, and death 123 PR Relapse at 3 m R no F 163 PD AD, 3 m R no F 673 CR Relapse at 30 m 673 PR Relapse at 14 m 673 PR Death at 2 m 673 PR PR, 30 m 673 PR PR, 3 m and death R with P

Description: Abstract 5001 Background Adult T-cell leukemia/lymphoma (ATLL) is an aggressive disease associated with the human T-lymphotropic virus type-I (HTLV-I). ATLL has heterogeneous clinical presentations and outcomes. Shimoyama's ATLL classification includes acute, lymphomatous, chronic and smoldering subtypes. The objective of this study is to define prognostic factors for survival in patients with ATLL. Methods 102 ATLL cases were collected in our center between January 1997 and September 2008. A diagnosis of ATLL was made according to the following criteria: a clinical history consistent with ATLL, a positive HTLV-1 antibody by ELISA and Western Blot or evidence of HTLV-1 proviral integration by PCR, and histological findings compatible with ATLL. Descriptive statistics were used to assess categorical and continuous variables. Survival curves for OS were estimated using the Kaplan-Meier method and compared using the log-rank test. For the multivariate analysis, the Cox Proportional-hazard regression test was used. Results The median age at diagnosis was 60.5 years (range 23–92 years), with a female-to-male ratio of 1.2:1. Forty nine cases (48%) had a performance status ≥ 2. Clinical types were acute (n=45), lymphomatous (n=43), smoldering (n=3), cutaneous (n=10) and chronic (n=1). Median hemoglobin was 12.0 g/dl (range 5.2–17.4 g/dl), median albumin was 3.3 g/dl (range 1.8–4.6 g/dl), median beta-2 microglobulin was 4.4 g/dl (range 1.1–16.9 g/dl), and LDH was 808 UI/ml (range 298–13000 IU/ml). Twenty nine patients with acute ATLL were treated with chemotherapy obtaining an overall response rate (ORR) of 14% (4/29), 3 complete responses (CR) and 1 partial response (PR), while in 38 patients with lymphomatous ATLL, an ORR of 32% (12/38) was obtained, 8 CR and 4 PR. Smoldering and cutaneous ATL types received mainly topic treatments. Median overall survival (OS) was 2.4 months for the acute type, 11.4 months for the lymphomatous type, 17.2 months for the smoldering type and 39.4 months for the cutaneous type (p

Description: Background: Association between osteonecrosis of the jaw (ONJ) and aminobisphosphonate treatment in patients (pts.) with multiple myeloma, breast cancer and prostate cancer has been increasingly reported in the literature. Risk factors for this complication include presence of infection, recent dental extraction and any oral surgical procedure with bone exposure. Patients and Methods: All patients with myeloma multiple or prostate cancer diagnosis treated at two institutions from Lima with either IV zoledronic acid or pamidronate from 2005–2007 were evaluated using outpatient records. Patients with ONJ were identified and their characteristics were compared to all patients receiving bisphosphonate therapy. Results: One hundred eighty three patients were evaluated. One hundred three had metastatic prostate cancer, and eighty myeloma multiple. All patients with myeloma multiple received pamidronate and all patients with prostate cancer received zoledronic acid. Six patients developed ONJ (3.2%). Five pts. were male and one female; a median age of 62 (range 50–74) and 5 had metastatic prostate cancer and 1 myeloma multiple. Zoledronic acid and pamidronate were involved in 5 and 1 cases respectively. The median number of bisphosphonate infusions prior to the development of ONJ was 16 (range 12–20). No patient had dental extraction or oral surgical procedure before ONJ. Bone exposition occurred in four cases. Treatment was antibiotics in all cases and surgery in two. Conclusions: ONJ is a serious complication of bisphosphonate therapy and it affected a significant proportion of our Latino american patients.