Academic literature on the topic 'GN 3.5 UL 2002'

During the last 5 years, two new diseases, brown apical necrosis (BAN) and gray necrosis (GN), were observed on English walnut (Juglans regia) and hazelnut (Corylus avellana), respectively (2,3). Both diseases caused severe fruit drop resulting in yield loss often exceeding 30%. Previous work demonstrated that BAN and GN are disease complexes caused by several fungi (Alternaria spp., Fusarium spp., and a Phomopsis sp.) (2,3). In both diseases, preliminary identification of Alternaria spp. revealed they were a complex of small-spored catenulate taxa related to A. alternata. To further characterize these taxa, additional pathogenicity tests and morphological examinations were conducted with isolates obtained from each host. Single-spored isolates were prescreened for pathogenicity by inoculating detached, surface-disinfested hazelnut leaves or walnut leaflets (1). Only isolates that produced foliar lesions after 5 days were used in subsequent fruit inoculations. From this screening, 35 isolates were selected (19 from walnut and 16 from hazelnut). For each isolate, attached fruit of respective hosts were inoculated at bloom by placing 10 μl of a conidial suspension (1 × 106 conidia per ml of H2O + 0.26% agar) onto the stigmas (150 fruit per isolate). Controls (150 fruit) were treated with agar solution only. After 15 days, fruit were examined for development of disease symptoms, and examination continued until fruit maturation (late July). Approximately 20 to 50% of the inoculated fruit displayed discoloration or necrosis of internal tissue, particularly the pericarp and the embryo, although symptoms were more limited than those typically seen in fully expressed BAN and GN. No differences in symptoms were evident among the isolates tested. The controls showed no symptom development initially, although 5% began to develop discoloration at fruit maturity. Fungal isolates used as inoculum were reisolated from all symptomatic fruit by surface disinfesting tissue from the margins of necrotic lesions. For each isolate, the conidial characteristics were described from cultures grown under defined conditions (4). Three distinct groups of isolates were identified. Alternata sp. group isolates produced conidial chains (8 to 20 spores) with numerous secondary and occasionally tertiary chains branching from apical and median cells. Conidia were typically ovate and often possessed a one-celled apical extension. Tenuissima sp. group isolates developed conidial chains (10 to 22 spores) with occasional branching forming secondary chains from apical and median cells. Conidia were ovate to obclavate, often with long apical extensions (10 to 35 μm). Arborescens sp. group isolates developed conidial chains (5 to 12 spores) with numerous secondary, tertiary, and quaternary short chains branching from apical cells. Conidia were typically ovate with minimal apical extensions. Of the walnut isolates, 12, 4, and 3 were from the arborescens, alternata, and tenuissima sp. groups, respectively. Of the hazelnut isolates, 7, 6, and 3 were from the arborescens, alternata, and tenuissima sp. groups, respectively. The finding that Alternaria from several distinct sp. groups can cause similar disease on a single host is consistent with previous work on pistachio, almond, and pear (4). References: (1) A. Belisario et al. Plant Dis. 83:696, 1999. (2) A. Belisario et al. Plant Dis. 86:599, 2002. (3) A. Belisario et al. Inf. Agrario 59:71, 2003. (4) B. M. Pryor et al. Phytopathology 92:406, 2002.

Abstract PBSC mobilization for auto transplantation of NHL pts with multiple regimens of prior chemotherapy is hard to achieve and 25%–30% of patients experience mobilization failure. AMD is a small bicyclam compound which specifically binds to CXCR4 receptor and blocks signaling through SDF-1. Previous studies in normal donors suggested clear dose dependent CD34+ cell mobilization as a single agent as well as additively with G-CSF with little toxicity (ASH meeting, 2002; 2003). Similarly, previous studies with NHL and Myeloma patients resulted with a dose-dependent augmentation of CD34+ cell mobilization in pts receiving G-CSF with little toxicity. The exact mechanism of AMD-induced mobilization of CD34+ cells was not studied in patients and AMD was not used before for PBSC mobilization in hard to mobilize NHL patients. Furthermore, its effect on mobilization of DCs and lymphoma cells was not studied before. On November 2003, we initiated a phase II study of 10, hard to mobilize NHL patients, receiving 16ug/kg of G-CSF for 4 days and G-CSF followed by 240ug/kg of AMD on day 5, 9 hours before apheresis collection. G-CSF and AMD were continued for additional day or 2, as needed, in order to collect the target dose of ≥ 2x106 PBSC/kg. Ten liters of blood were exchanged in ~4hours of apheresis. Median age was 54 years (44 to 63 years). Of the 10 patients enrolled, 6 pts had diffuse large cell lymphoma and 3 had follicular histology with 8/10 received 2 regimens of chemotherapy, 2 of which received also radiation prior to mobilization. At mobilization, 5/9 pts were primary refractory, 3 pts were in 1st relapse, 1 pt in 2nd relapse and 1 pt in 2nd CR. We determined percent CD34+ cells and percent DC1 and DC2 cells as well as percent lymphoma cell mobilization (by Real time DNA-PCR) at baseline (before administration of G-CSF) and before and after AMD, in the blood and in the apheresis product. To date 7 pts were transplanted. Five pts collected in 1 day and 5 pts collected in 2 days. No adverse events were observed during mobilization. All patients collected ≥ 2x106 PBSC/kg and 7 pts have been transplanted with a dose of 2-7x106 PBSC/kg. All transplanted pts engrafted with a mean of 10 days (9 to 12 days) for ≥ 500ANC and with a mean of 13 days (12–14 days for 6/7 pts) to reach 20K of plts. One pt had a delayed plt engraftment and was engrafted on day 27. Addition of AMD to G-CSF, prior to the first or 2nd PBSC collection resulted in a mean increase of percent CD34+ cells from 0.11% to 0.17% ( p=0.017), with a similar mean increase in CD34+ cells/ul (35/ul to 81/ul; p=0.0001) followed by normalization of CD34+ cells/ul within 24 hours. Similarly, addition of AMD to G-CSF resulted in an increase in the mean of DC1 cells from 79/ul to 156/ul (p=0.009) and from a mean of 62/ul to164/ul (p=0.006) for DC2 cells. One pt had 0.08% lymphoma cells at baseline by DNA-PCR for the major breakage point of the Bcl-2 translocation sequence, with no detectable lymphoma cells in the blood or apheresis collection post AMD. All other pts were negative for lymphoma pre and post AMD by this test. Adverse events and sever adverse events related to study were minimal. We conclude that AMD is a safe drug with clinical benefit in increasing PBSC and DC mobilization with no detectable mobilization of lymphoma cells.

Objective: Chronic myeloid leukemia (CML) is a rare disease among children. It comprises 3% of childhood leukemias. CML in children is different from CML in adult. Here we analyzed the clinical features and prognosis of pediatric CML in a single institute from China. Methods: A retrospective study was performed by reviewing clinical records of pediatric CML from 2002 to 2019. Results: A total of 48 pediatric CML cases were included in the study, with 35 males and 13 females (M: F=2.7:1). Four cases were diagnosed during 2002~2007, 12 cases during 2008~2013 and 32 cases during 2014~2019. Two (4.2%) patients were in accelerate phase (AP) and other 46 patients were in chronic phase (CP) at diagnosis. Median age of onset was 9y (range 1~17y). The most common symptoms were fever (21.6%), fatigue (14.9%) and cough (10.8%). Median size of spleen under left costal margin was 5cm (range 0~21cm). Median WBC count was 15.7/ul, hemoglobin 9.5g/dL, platelet count 58/ul, neutrophils percentage 56% (range 21~74%), basophils percentage 3% (range 1~16%) and median eosinophil percentage was 2% (range 0~19%). Thirty-five patients had done karyotype examination, and 28 cases (80%) with classical Philadelphia chromosome (Ph+). Other 13 patients without Ph chromosome but with BCR/ABL1 fusion gene. In our study, there were 4 patients treated by hydroxyurea and α-interferon, other 44 patients have been used imatinib (IM) 240-340mg/m2 per day. Median time from onset to diagnosis was 0.7 months (range 1 day~12 months). Median follow-up time was 52 months (range 1~200 months), while the 5-year overall survival (OS) and event-free survival (EFS) are 100% and 89.1%, respectively. Different gender, age at diagnosis, WBC count, platelet count, karyotype show no difference in OS and EFS. Four patients suffered from blast crisis (BC) (2 patients progressed after using hydroxyurea for 1 and 33 months, 2 patients progressed after using IM for 36 and 6 months, respectively). One patient's BCR/ABL1 transcript level was increased in 36 months after first administration of IM and recovered at 48 months by adding IM dosage from 200mg to 300mg per day. According to the European LeukemiaNet (ELN) criteria, 95.5% patients achieved complete hematologic response (CHR), 90.5% patients achieved complete cytogenetic response (CCyR) and 66.7% patients achieved major molecular response (MMR) at 3, 12, 18 months after IM administration, respectively. There was obvious correlation between WBC count at diagnosis and early molecular response (EMR). Median WBC count was 4.8/ul in patients with EMR and 38.1/ul in patients without EMR. Other clinical features, such as gender, age at diagnosis, hemoglobin count, platelet count and size of spleen, make no difference in EMR. Conclusion: This is a retrospective study on pediatric CML. The median age at diagnosis is 9 years old. Most of all patients are CML-CP. 5y OS and EFS are 100% and 89.1%. The CHR, CCyR, MMR at 3,12,18 months after IM therapy are 95.5%, 90.5% and 66.7% separately. Until now there is no sufficient data on efficiency and safety specific to pediatric CML patients. Further clinical investigations through international collaboration are need to help more and more patients to achieve treatment-free remission. Disclosures No relevant conflicts of interest to declare.

Abstract Background: With improved treatment modalities, longevity for sickle cell disease (SCD) is increasing. Yet there is still a subgroup of adult patients whose survival rate has not improved. These patients, if well defined by evidence based decisions, might be those for whom more aggressive disease modifying therapy would be appropriate. Methods: We identified all patients with SS/Sβ0 seen at our medical center in 2002 whom we were still following in 2012 as well as those who had died between 2002 and 2012. Patients with SC and Sβ+ thalassemia were excluded. ED, clinic, and inpatient admissions over the entire years 2002 and 2012 were obtained. All 2002 and 2012 steady state parameters for a given laboratory test for a given patient were averaged. “Steady State” was defined as those values not within one day of an ED visit or within one week of a hospital admission. Data were assessed for normality; parametric and non-parametric bivariate tests were performed as appropriate. Data from 2002 and 2012 was compared with paired-T tests. Mortality data were analyzed using Kaplan-Meier curves and Cox proportional hazard models. Results: We identified 289 SS/Sβ0 patients in 2012 (ages 18-87, 54% female) who had been present in our system in 2002 (survival cohort). We also identified 70 patients present in 2002 (ages 19-88 at death, 47% female) who had died between 2002 and 2012, inclusive (mortality cohort). Average age at death was 42.1±14.0 years, median survival was 58.3 years (95% CI: 54.5 – 63.0). Survivors had, in 2002, higher HbF, Hb, higher MCHC, lower white blood cell (WBC) counts and creatinine (Cr) levels, and fewer admissions than those who did not survive past 2012 (Table 1). Absolute Reticulocyte count (Retic), MCV, LDH, liver function tests, ED and clinic use were not significantly different between survivor and mortality groups. Cox proportional hazards model showed increased hazard ratios with lower HbF, higher WBC, Cr and increased admissions. When the survivors from 2002 were compared to themselves in 2012, they were shown to decrease HbF, Hb, MCHC, WBC, alkphos, and total bilirubin over time and to increase admissions, ED visits, Retic, MCV, Cr, and weight. Clinic visits, direct bilirubin and LDH were not significantly different. Conclusions: As therapeutic alternatives increase, it may be important to tailor therapy, and the need for better prognostic markers becomes ever more important. We observed here that several known mortality predictors evolve over time. As the “survivor” population ages, they may begin to resemble those with a poorer prognosis with decreased Hb and HbF levels but increased admissions and ED visits. However in our sample, WBC, a recognized factor in mortality and morbidity, decreased further over time in those who survived. Similarly, absolute reticulocyte count increased further over time in the survivors, suggesting an ability of the marrow to respond to the increased anemia. Further studies should be done to distinguish which biomarkers, at what level and in what age groups, are truly predictive of severity in sickle cell disease. Abstract 1388. Table 1: Comparison of 2002 SCD cohort who survived until 2012 with those who did not (left panel) and of a subset of this survivor population with themselves in 2012 2002 All Patient Data Matched Data 2002&2012 Survivor 2002 Mortality 2002 Cox Hazard Survivor 2002 Survivor 2012 N 289 70 359 134 134 Hb (g/dL) 8.5±1.4 7.8±1.4* .82(.65-1.02) 1g/dL 8.4±1.4 8.1±1.5* MCHC (g/dL) 35.2±1.2 34.5±1.8* .85(.69-1.04)1g/dL 35.1±1.2 34.2±1.3# Retic (x10^9/L) 181.3(131.9/237.8) 183.4(128.5/218.2) 1.00(1.00-1.01) 1k/uL 185.9(144.0/236.8) 247.4(168.1/341.2)# WBC (x10^9/L) 11.6±3.6 12.4±4.5 1.11(1.02-1.21)* 1 k/Ul 11.6±3.5 10.8±4.1* Cr (mg/dL) 0.5(0.6/0.7) 0.8(0.6/1.5)# 1.25(1.00-1.55)* 1mg/dL 0.6(0.5/0.7) 0.7(0.6/0.9)# Alb (g/dL) 4.3±.3 4.1±.4# .72(.33-1.57) 1g/dL 4.3±.3 4.2±.5 AlkPhos (U/L) 103.0(86.8/159.8) 121.0(99.6/166.8) 1.3(.91-1.99) 100 U/KL 111.0(86.8/165.0) 91.3(70.0/125.1)# Weight (KG) 58.3±21.3 64.1±15.7* 1.00(.98-1.02) 1 KG 58.4±21.1 66.0±13.9# HbF (%) 15.7(8.4/20.1) 5.5(1.9/12.4)# .94(.90-.98)# 1% 15.9(7.4/20.5) 6.4(4.1/11.8)# ED (per year) 2.6±3.9 1.9±3.3 .96(.88-1.04) 1/year 2.6±3.9 5.2±10.7# Clinic (per year) 6.8±8.3 8.3±11.5 1.01(.99-1.04) 1/year 6.8±8.3 7.3±10.5 Admits (per year) 0.3±0.8 2±2.5# 1.28(1.18-1.38)# 1/year 0.3±0.8 2.1±3.2# *=p<.05, #=p<.01 Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 4863 Introduction: Cytogenetic studies are an important prognostic tool in the management of hematologic malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). While a nonrandom structural gain of 1q may be seen in MDS and AML, it is most commonly due to an unbalanced translocation usually in association with other chromosomal abnormalities. Duplication of the long arm of chromosome 1 [dup(1)(q21q32)] as the sole abnormality in nonlymphoid hematologic malignancies has only rarely been reported. As a result, very little is known about the clinical significance of this chromosomal abnormality. However, it has been suggested that this single aberration is predictive of an increased risk of clonal evolution and poor overall prognosis. Case Presentation: A then 55 year old male presented in June, 2002 with a CBC showing: WBC 36,300/ul (74% blasts with Auer rods), Hgb 7.0 gm/dl, MCV 98fl, platelets 61,000/ul. Bone marrow biopsy was 90% cellular with sheets of blasts. The blasts were positive for CD34, CD117, HLA-DR, CD13, MPO, CD56, and Tdt. A diagnosis of AML M2 was made. Cytogenetics showed 45,X,-Y, t(8;21)(q22;q22). He underwent successful standard induction with “7+3” followed by consolidation with “5+2” and 4 cycles of high dose cytarabine. Subsequent bone marrows after induction and during consolidation showed no evidence of AML. The karyotype was 46,XY with no evidence of t(8;21) by FISH. He has had complete recovery of his blood counts, except for intermittent neutropenia. In May, 2004, G-banding of his bone marrow revealed the presence of a dup(1)(q21q32) as an isolated cytogenetic aberration for the first time. This finding was again seen on follow up studies in 2006, 2007, and 2009. His most recent evaluation in May 2010 showed WBC 5,500/ul (neutrophils 2,200/ul), Hgb 14.0 gm/dl, MCV 92fl, platelets 299,000/ul. Bone marrow biopsy was 40% cellular with trilineage hematopoiesis. The aspirate showed erythroid hyperplasia with megaloblastoid features. No dysplastic RBC or ring sideroblasts were seen. Cytogenetics showed 46,XY,dup(1)(q21q32)[15]/46,XY[5]. FISH for AML1/ETO t(8;21) and for abnormalities of chromosomes 5, 7, 8, and 20 were negative. Discussion: Dup(1q) has been reported as an isolated cytogenetic abnormality in a variety of MDS subtypes. It may be either a primary or secondary chromosomal aberration. It has been suggested that isolated dup(1q) in MDS is a harbinger of disease progression. Recent reports of MDS with either inverted dup(1)(q32 q21) or dup(1)(q21q32) of both chromosome 1 homologs showed no disease progression but had very short follow-up. Conclusion: To our knowledge, this case is the first report of an acquired duplication dup(1)(q21q32) as the sole abnormality in a patient previously treated for AML. This duplication developed approximately 2 years after induction and consolidation chemotherapy. The involved clone is not the original leukemic clone since there is no evidence for t(8;21) or -Y. Six years later, there has been no evidence of progression to MDS or sAML. It is not known why our patient has shown such long survivorship after discovery of dup(1)(q21q32), nor is it known if this chromosomal finding is a treatment related phenomenon. This case suggests that dup(1q) may not be exclusively associated with a poor prognosis. FISH analysis with a 1q21 probe is planned to confirm our G-banding observation. Disclosures: Lachant: sanofi-aventis: Speakers Bureau; glaxosmithkline: Speakers Bureau.

Abstract Backgrounds and Aims Hepatic veno-occlusive disease (VOD) associated with hematopoietic stem cell transplantation (HSCT) is characterized by a clinical triad of jaundice (total bilirubin, >2 mg/mL), hepatomegaly with right upper quadrant pain, and ascites and/or unexplained body weight gain (>5% of baseline) within 30 days after operation. Although the pathogenesis of hepatic VOD has not been fully elucidated, the common pathological features are thrombi formed in hepatic central vein. We previously reported that a significant decrease of plasma ADAMTS13 activity was noted in patients undergoing HSCT, who subsequently developed VOD (Park et al, BMT 2002). Then, we showed that plasma antigen levels of von Willebrand factor (VWF) has been kept higher in HSCT-patients with VOD than in those without, and in fact prophylactic infusions of fresh frozen plasma (FFP) with a dose of 10 ml/kg body weight 3 times per week were effective to reduce the frequency of VOD occurrence in high risk patients (Matsumoto et al, BMT 2007). However, more recent studies by ours indicate that FFP infusion alone is not enough to totally eliminate the occurrence (unpublished). Recently, it has been shown that the treatment with recombinant soluble thrombomodulin (rTM) is sometimes highly efficient to reverse VOD progression. But its pharmacokinetics and regimen for the treatment has not been established. As a first step to elucidate a possible combination regimen of FFP and rTM to VOD patients, here we have analyzed the transitional changes of unusually large VWF multimers (UL-VWFMs). The UL-VWFMs are released from damaged endothelial cells and induce platelet hyperagglutination under high shear stress generated in microvasculatures, and are often observed in patient plasmas undergoing HSCT. Patients and Methods During 2011-2012, 45 patients were received allogenic HSCT in the second internal medicine department of our university hospital. None of these patients ,however, were received planned prophylactic FFP infusions, and as a result six patients undergoing allogenic cord blood transplantation (CBT) developed VOD. Clinical features of these 6 patients are shown in Table 1. Under approval of Ethics Committee of Nara Medical University, we consecutively collected patient's citrated plasmas (ca 2.5 ml) and stored at -80°C until use. Using these deep-frozen plasma samples, we here extensively analyzed plasma levels of ADAMTS13 activity (ADAMTS13:AC), VWF antigen (VWF:Ag), and VWF collagen binding activity (VWF: CBA), together with VWF multimer analysis. More importantly, we also measured the corrected platelet count increment (CCI) to evaluate the efficiency of Platelet trsnsfusions. Then, we comprehensively evaluated these data with routine clinical and laboratory findings. Results and Discussion 1) Plasma levels of ADAMTS13:AC were moderately but consistently decreased during two months after HSCT, whereas those of VWF:Ag were kept high, usually more than 200% and often 500% of the normal. 2) The UL-VWFMs appeared soon after HSCT, and continued at least until absolute neutrophil count (ANC) increased to >500 (usually 20-30 days after HSCT). 3) Until platelet engraftment (usually 40-60 days after HSCT), platelet transfusions (every 2-3 days interval) are usually performed to prevent the bleeding complications. During that period, the CCI values were consistently low, but those values were significantly increased during the administration of rTM. 4) Excess platelet transfusions before platelet engraftment induced the consumption of larger VWFMs in patient's plasmas, and often almost simultaneously hepatic VOD developed. Thus, platelet transfusions during the appearance of UL-VWFMs in patient's plasmas may induce platelet clumping in microvasculatures, and lead to the development of thrombotic complications including hepatic VOD. 5) The measurement of plasma levels of VWF:CB activity appeared to well predict the presence of UL-VWFMs. A representative case is shown in Figure. Thus, a combination regimen of FFP and rTM might be advisable when the patients show the early clinical signs of hepatic VOD and the laboratory data such as VWF:CBA suggest the presence of UL-VWFMs in patient's plasmas. Disclosures: Matsumoto: Alexion Pharma: Membership on an entity’s Board of Directors or advisory committees. Fujimura:Alexion Pharma: Membership on an entity’s Board of Directors or advisory committees; Baxter International Inc: Membership on an entity’s Board of Directors or advisory committees.

Abstract Chakravarti, (Blood, 2002, p1071) and others have described the use of alemtuzamab, a monoclonal antibody that binds to CD52 on T cells, B cells, monocytes and dendritic cells in vivo for control of graft vs host disease in reduced intensity or fully-ablative matched related and unrelated transplant regimens for hematologic malignancies. Control of GVHD has been good, but high relapse rates and infectious complications have been seen. We report our experience with 42 pts who underwent matched related (27) or unrelated (15) bone marrow (8), blood stem cell (33), or both (1) transplants for hematologic malignancies. There were 16 women and 26 men, median age 48, and median f/u is 9 months. All AML pts had high-risk disease defined as beyond CR1 (11), CR1 with high risk cytogenetics (5), AML with tri-lineage dysplasia (6), or failed prior autologous transplant (1) Three had >10% marrow blasts at time of transplant. All other pts had advanced and multiply recurrent disease. All pts received alemtuzamab either at 20 mg/m2/d x 5 (17), or 30 mg/m2/d x 3 (25) between days -8 through -4. The conditioning regimens also included 12.8 mg/kg IV busulfan, (27), 6.4 mg/kg IV busulfan (8), melphalan 140 mg/m2 (6), or Cy/TBI (1). All non-TBI patients received 30 mg/m2/d x 5 of fludaribine. Median recovery of ANC to >500/ul and platelets > 20,000/ul w/o transfusion were 13 and 14 days, respectively. TRM included 1 pt each with intracranial hemorrhage at day 8, multi-organ failure/sepsis at day 28, and IPS/ARDS at day 119. Two of the 3 deaths were in MRD transplants; no serious episodes of VOD were observed. Grade 2–4 GVHD was seen in 4/14 evaluable MUD pts and 1 (sex mismatched) of 26 evaluable MRD pts. CMV reactivation has been seen in nearly all CMV sero+ pts, and bk reactivation was seen in 25 pts with hemorrhagic cystitis in 10. One case of PTLD, 3 graft failures, and one severe case of disseminated adenovirus infection resulting in nephritis, cystitis and transient cardiomyopathy were also seen. Relapse/# evaluable for different diseases are as follows: AML 12/22, Gleevec-resistant CML 3/3, MDS 0/4, MM 3/3, NHL 0/3, ALL 0/3, CLL 0/2. Relapse rates in evaluable MRD pts, 15/26 (58%), were statistically higher compared to MUD pts, 3/14 (21%) (p = 0.05). RR in marrow, 2/8, vs BSC, 16/32, were comparable. Alemtuzamab use has been effective at controlling GVHD and infectious complications can be reduced with early and pre-emptive use of ganciclovir. Nevertheless, high relapse rates remain a significant problem and preclude routine use of this approach in MRD patients with advanced myeloid diseases. Current use of this agent has been individualized for donor (MRD vs MUD) and disease (myeloid vs other) status.〉

Abstract Abstract 1588 Background: EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification of Lymphomas. Diagnostic criteria include age >50 years, DLBCL morphology and EBV expression in lymphomatous cells. However, these criteria are evolving as several patients are <50 years and a specific cut-off for the percentage of EBV expression has not been defined. The goal of this retrospective study is to evaluate clinical and pathological characteristics of EBV+ DLBCL from Peruvian patients. Methods: Between January 2002 and January 2012, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases re positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immuno-histochemistry. Clinical data were reviewed retrospectively and patient's biopsies were analyzed for the expression of BCL6, CD10, CD30 and MUM-1/IRF4 using a tissue microarray (TMA) technique. The overall survival (OS) curves were calculated using the Kaplan-Meier method, and compared using the log-rank test. Results: A total of 43 EBV+ DLBCL patients are included in this study. The median age was 73 years (range 25–95 years). Four patients (9% ) were <50 years. The male:female ratio was 2.2:1. B symptoms occurred in 59%, ECOG >21 in 60%, advanced stage (III/IV) in 58%, elevated LDH levels in 44%, and lymphocyte count <1000/uL in 35%. The International Prognostic Index (IPI) score was 0–2 in 39% and 3–5 in 61% of the patients. Extranodal disease occurred in 20 patients (46%): stomach (n=3), tonsil (n=3), pleura (n=2), palate (n=2), cecum (n=2), bone marrow (n=2), ileum (n=1), bone (n=1), skin (n=1), lung (n=1), meninges (n=1), breast (n=1) and peritoneum (n=1). Three patients had central nervous system involvement (7%), one at presentation and two at relapse. Based on the Hans classification, 76% had non-germinal center profile. Ki67 expression was >80% in 53% of the patients. Eleven evaluated patients had a c-myc-negative status. Chemotherapy was received in 75% of the cases due to poor performance status. The overall response rate with conventional chemotherapy was 46%, with complete response in 39%, partial response in 7%, and no response in 54%. The median survival was 7.5 months. The Oyama score was: 0 factors (13%), 1 factor (47%), and 2 factors (40%) with median OS of 41, 11 and 1.5 months respectively (p=0.07). A lymphocyte count <1000/uL was a prognostic factor for OS (p=0.001). Conclusions: Based on our study, which is the largest cohort in Latin-America, EBV+ DLBCL is an aggressive entity with frequent extranodal disease and poor response to conventional chemotherapy. The overall survival remains poor. Lymphopenia, as defined as lymphocyte count <1000/uL, appears as a prognostic factor for OS. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3681 Background: Pediatric Immune Thrombocytopenia (ITP) has an incidence of 4–6/100,000 with 1/3 of cases becoming chronic. Treatment choice is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies (Neunert CE, et al. Pediatr Blood Cancer 2008; 51(4):513). Previous studies in ITP have not examined predictors of response to rituximab or whether response to prior treatments predicts response. Objective: To evaluate univariate and multivariable predictors of platelet count response to rituximab. Methods: After local IRB approval, 550 patients with chronic ITP enrolled in the longitudinal, North American Chronic ITP Registry (NACIR) between January 2004 and June 2010. Eligibility included: ages 6 months-18 years at ITP diagnosis, clinical diagnosis of ITP, and ITP duration >6 months. Primary ITP was defined as isolated thrombocytopenia without associated conditions. Secondary ITP included those patients with immune thrombocytopenia associated with other immune-mediated medical conditions, including Evans Syndrome. Treatment response was defined as a post-treatment platelet count ≥50,000/uL within 16 weeks of rituximab and within 14 days of steroids. Steroids were prescribed as 1–4 mg/kg prednisone or adult equivalent over 4–14 days with or without taper. The NACIR captured treatment responses both retrospectively prior to enrollment and then prospectively, and both periods were included in this analysis. The multivariable logistic regression modeling process utilized SAS 9.1 using binary variables which were either significant in the univariate analysis or clinically important. A backwards elimination procedure was used to select the final model. Results: Seventy-six (13.8%) patients were treated with rituximab. Demographics of the patients treated with rituximab include: 42% male; 81% Caucasian, 17% Black, and 2% Asian. The mean age at diagnosis of ITP was 8.4 ± SD 5.1 years. The median platelet count at diagnosis of acute ITP was 10,000/uL (IQR 5,000-20,000/uL). 19 (25%) patients had secondary ITP or Evans syndrome. Treatment with rituximab had an overall response rate of 63.2% (48/76). Univariate predictors of response to rituximab are shown in Table I. The strongest univariate predictor of response to rituximab was response to steroids. Gender, ethnicity, and race were not predictive of response to rituximab. Furthermore, other variables which did not predict rituximab response include: history of a bleeding score ≥3 (Buchanan and Adix, J Pediatr 2002; 141: 683), symptoms ≥1 month prior to ITP diagnosis, older age (age >5 years), platelets ≥20,000/uL at acute ITP diagnosis, and a positive ANA. In multivariable analysis, response to steroids remained a strong predictor of response to rituximab with an OR 6.2 (95% CI 1.8–21.3, p=0.004). Secondary ITP also remained a strong a predictor of a positive response to rituximab with an OR 5.9 (95% CI 1.2–33.3, p=0.03). Conclusion: In the NACIR, response to steroids and secondary ITP were strong predictors of response to rituximab, a finding not previously reported in children or adults. Although this finding requires further validation, this result may provide evidence that rituximab should be most considered in patients previously responsive to steroids. Disclosures: Off Label Use: Rituximab for chronic ITP. Lambert:Cangene: Membership on an entity's Board of Directors or advisory committees. Klaassen:Novartis: Research Funding; Cangene: Research Funding. Neufeld:Novartis, Inc: Research Funding.

Abstract Background: EBV-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is a provisional entity included in the 2008 WHO Classification of Lymphomas. Diagnostic criteria include age >50 years, DLBCL morphology and EBV expression in lymphomatous cells. However, these criteria are evolving as several patients younger than 50 years of age without immunodeficiency have been diagnosed. Also, a specific cut-off for the percentage of EBV expression has not been defined. Lymphopenia, monocytosis, neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte-to-monocyte ratio (LMR) have been reported prognostic in patients with DLBCL and other lymphomas. The goal of this retrospective study is to evaluate these novel prognostic factors in a cohort of EBV+ DLBCL patients. Methods: Between January 2002 and January 2014, all patients meeting criteria for EBV+ DLBCL were included in the analysis. Patients with evidence of immunosuppression were excluded. All cases were positive for the presence of EBV-encoded RNA (EBER) by in situ hybridization, and CD20 and/or PAX-5 expression by immunohistochemistry. Clinical and pathological data were reviewed retrospectively. Lymphopenia was defined as an absolute lymphocyte count <1000/uL, and monocytosis as an absolute monocyte count >600/uL. NLR was defined as the division of the absolute neutrophil count over the absolute lymphocyte count. LMR was defined as the division of the absolute lymphocyte count over the absolute monocyte count. Patient's biopsies were analyzed for the expression of BCL6, CD10, CD30 and MUM-1/IRF4. Overall survival (OS) curves were calculated using the Kaplan-Meier method, and compared using the log-rank test. Results: A total of 45 EBV+ DLBCL patients are included in this study. The median age was 68.9 years (range 25-95 years). Four patients (9%) were younger than 50 years. The male:female ratio was 2.2:1. B symptoms occurred in 60%, ECOG >1 in 55%, advanced stage (III/IV) in 58%, and elevated LDH levels in 44%. The International Prognostic Index (IPI) score was 0-2 in 39% and 3-5 in 61% of the patients. Lymphopenia was seen in 35%, and monocytosis in 69% of patients. Extranodal disease occurred in 23 patients (51%): stomach (n=3), tonsil (n=3), pleura (n=2), palate (n=2), cecum (n=2), bone marrow (n=2), ileum (n=1), bone (n=1), skin (n=1), lung (n=1), meninges (n=1), soft tisue (n=1) and peritoneum (n=1). Based on the Hans classification, 76% had non-germinal center origin. Ki67 expression was >80% in 53% of the patients. Chemotherapy was not received in 25% of the cases due to poor performance status. The Oyama score was: 0 factors (13%), 1 factor (47%), and 2 factors (40%) with 2-year OS of 86%, 49% and 27%, respectively (p=0.016). Lymphopenia was an adverse prognostic factor for OS (HR 3.23, 95% CI 1.24-8.43; p=0.017) in the univariate analysis. The 2-year OS for EBV+ DLBCL patients with lymphopenia was 24%, and 55% for patients without lymphopenia. Monocytosis, NLR and LMR were not significantly associated with OS in our cohort of EBV+ DLBCL patients. Conclusions: Lymphopenia, defined as an absolute lymphocyte count <1000/uL, appears as a prognostic factor for OS in EBV+ DLBCL. Disclosures No relevant conflicts of interest to declare.