ALBERT

Description: Background: Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora infection can be difficult because of its scarcity in developed countries, intracellular mode of life, small size of the parasite and its inability to take up routine microscopic stains. However, it is endemic in many countries in Asia, Africa, Central and South America. With the increase in travels to these areas, the number of cases is expected to increase. Moreover, it is found to be associated with numerous food-borne outbreaks.Case presentationWe encountered a patient with human immunodeficiency virus presented with 6 months of diarrhoea. The initial investigation was unrevealing. The diagnosis of Cyclospora infection was finally made on the histological sample obtained by colonoscopy. Moreover, the initial therapy with ciprofloxacin was not effective, while trimethoprim/sulfamethoxazole resulted in final cure of the disease. Conclusion: Travel and food histories are important for the suspicion of Cyclospora infection. Histological examination is more sensitive in making a diagnosis of Cyclospora infection of the gut than fecal microscopic examination. Trimethoprim/sulfamethoxazole is a more reliable therapy for Cyclospora infection in patients with human immunodeficiency virus.

Description: Background: Cyclospora is an uncommon pathogen. The diagnosis of Cyclospora infection can be difficult because of its scarcity in developed countries, intracellular mode of life, small size of the parasite and its inability to take up routine microscopic stains. However, it is endemic in many countries in Asia, Africa, Central and South America. With the increase in travels to these areas, the number of cases is expected to increase. Moreover, it is found to be associated with numerous food-borne outbreaks.Case presentationWe encountered a patient with human immunodeficiency virus presented with 6 months of diarrhoea. The initial investigation was unrevealing. The diagnosis of Cyclospora infection was finally made on the histological sample obtained by colonoscopy. Moreover, the initial therapy with ciprofloxacin was not effective, while trimethoprim/sulfamethoxazole resulted in final cure of the disease. Conclusion: Travel and food histories are important for the suspicion of Cyclospora infection. Histological examination is more sensitive in making a diagnosis of Cyclospora infection of the gut than fecal microscopic examination. Trimethoprim/sulfamethoxazole is a more reliable therapy for Cyclospora infection in patients with human immunodeficiency virus.

Description: Follicular lymphoma arising in an extranodal site is uncommon and its natural history and treatment is poorly characterized in the literature. We retrospectively reviewed a large cohort of patients with stage I and II follicular lymphoma and analyzed the outcomes of patients with extranodal (EN-FL) presentations to identify sites of involvement and treatment outcome, and compared these to patients with nodal follicular lymphoma. From 1967 to 1999, 668 cases of limited stage follicular lymphoma (stage I and II) were treated at the Princess Margaret Hospital. Of these, 157 cases (23.5%) presented in extra-nodal sites. The most common site of presentation was in the head and neck area (42%) followed by gastro-intestinal tract (14.6%) then skin (10.8%). The majority of patients had stage I disease (61.8%). Pathological type was follicular grade I: 22.9%, grade II: 33.1%, and grade III: 43.9%. Treatment consisted of involved field radiation therapy in 72%, combined modality therapy in 22.3% and chemotherapy alone in 3.8%. The treatment changed over time with increased use of combined modality treatment (CMT) [1967–77: 10.5%, vs. 1989–99: 33%] mainly due to the adoption of CMT for follicular grade III lymphoma. Overall complete response rate (CR) to primary treatment was 93%; the CR rate for radiation alone was 97.3%. The cumulative incidence of relapse (RR) was 44% at 10 years. The RR at 10 years was higher for patients age 〉60 (62% vs. 49%; p =0.059) but did not vary according to stage, tumour bulk, gender or histologic grade. For extranodal lymphoma, the 10-year overall survival (OS) rate was 56% and the 10-year disease free survival (DFS) was 42% and was similar for major sites of presentation. Comparison of Stage I–II Nodal and Extra-nodal Follicular Lymphoma Nodal Follicular Lymphoma Extra-nodal Follicular Lymphoma 10 yr Overall Survival 61% 56% (p=0.97) 10 year Disease Free Survival 41% 42% (p=0.27) 10 yr Relapse Rate 50% 44% (p=0.11) In conclusion, a significant number of patients with localized FL present with extra-nodal disease, involving diverse sites. Patients with EN-FL were more likely to have follicular grade III histology. OS, DFS and RR were similar to nodal follicular lymphoma. These results suggest that the clinical management of stage I and II extra-nodal follicular lymphoma should be the same as for nodal, and that a significant proportion of patients have prolonged DFS with radiation-based therapy.

Description: To describe the demographic and tumor related characteristics and outcomes for patients with primary T-cell central nervous system lymphoma (TPCNSL). A retrospective series of patients with TPCNSL was compiled from twelve cancer centers and seven countries. This study involved 35 male and 10 female patients with a median age of 60 years (range 3–84). Twenty (44%) had Eastern Cooperative Oncology Group performance status (PS) of 0 or 1. Twenty six (58%) had involvement of a cerebral hemisphere and sixteen (36%) had lesions of deeper sites in the brain. Two patients had primary spinal cord lesions and one had meningeal disease only. Serum lactate dehydrogenase (LDH) was elevated in 7 of the 22 cases (32%) and cerebrospinal fluid (CSF) protein was elevated above normal in 19 of the 24 cases (79%) with available data. The median disease specific survival (DSS) for all patients was 25 months (95% confidence interval (CI) 11–38 months). The two and five-year DSS were 51 % (CI 35–66 %) and 17 % (CI 6–34 %) respectively. Univariate and multivariate analyses were conducted for the following factors: age (≤ 60 vs. 〉 60 years), PS (0 or 1 vs. 2, 3 or 4), involvement of deep structures of the central nervous system (no vs. yes), and methotrexate (MTX) use in the primary treatment (yes vs. no). Only PS and MTX use were significantly associated with better outcome with hazard ratios (HR) of 0.2 (CI 0.1–0.4) and 0.4 (CI 0.2–0.8) respectively. This is the largest series ever assembled of TPCNSL. The presentation and outcome appear similar to that of PCNSL of B cell origin. PS 0 or 1 and administration of MTX are associated with better survival. TPCNSL does not appear to require a different therapeutic management approach than B-cell PCNSL.

Description: ASCT results in long-term disease free survival for approximately 40–50% of patients (pts) with relapsed−/− refractory aggressive NHL who respond to second-line chemotherapy. The incidence of second cancers (SC) in long-term survivors and risk factors in this pt population has not been well studied. We performed a retrospective analysis of 372 pts undergoing ASCT at our institution from May 1987 to Dec 2006 for relapsed−/− refractory aggressive NHL after primary therapy. Second-line chemotherapy was given to best response, followed by high dose therapy for pts with chemotherapy-sensitive disease. Intensive therapy was melphalan 180mg/m2 + etoposide 60mg/kg in 86%; regimens including total body irradiation (TBI) 12 Gy were received in 16%. Stem cell source: autologous bone marrow (27%), peripheral blood (63%) or both (10%); 7% received post-ASCT involved field RT to sites of bulky disease. Estimates of SC risk were determined adjusting for competing risks. The incidence of SC was compared to the general population in Ontario from 1987 to 2002. Of 372 pts, 59% had diffuse large B cell lymphoma, 24% transformed from prior indolent NHL, 16% T cell lymphoma, 1% undefined aggressive NHL. Median age at ASCT was 50 years (range 19–70); female 44%. The majority of patients (74%) received 2 chemotherapy regimens prior to ASCT (range 1–8); all pts with de novo DLCL received CHOP or equivalent regimen as primary therapy. For first salvage therapy cytarabine/platinum combinations were used in 205 (55%) pts, miniBEAM (melphalan, etoposide, cytarabine, BCNU) in 40 (11%), gemcitabine/dexamethasone/cisplatinum in 37 (10%); CHOP or equivalent was used in 42 pts (11%). Median follow up is 4.3 years and 27/185 (15%) have been followed more than 10 years. 184 pts (49%) have experienced disease relapse and 32 (9%) have developed a SC (17 MDS/AML, 13 solid tumors, 1 chronic lymphocytic leukemia and 1 acute lymphoblastic leukemia). During the follow up period 187 (50%) patients have died (126 from relapsed lymphoma, 30 from treatment-related toxicity, 14 from second cancer, 5 unrelated medical condition, 7 unknown). The probability of SC is 5% (95% CI: 3%-8%) 3 years post-ASCT and 14% at 10 years (95%CI: 10%-20%). Age at ASCT, sex, receipt of TBI, number of chemotherapy regimens, prior RT, graft source and lymphoma subtype were not associated with development of a second malignancy. Use of miniBEAM as part of salvage therapy was significantly associated with the development of a second cancer (p=0.001). The incidence of malignancy in survivors of ASCT is 32 per 1180 person years of follow-up. When compared to the general population (AML and solid tumors only) the relative risk (RR) for developing AML or a solid tumor is 13.5 (p

Description: Introduction: T-cell lymphomas (T-NHL) represent rarer entities compared to B-NHL, accounting for 5% -10% of NHL in Western countries and 15%-20% in Asia. They are divided into clinico-pathologic subtypes based on etiology, morphology, and clinical behavior. Because of the rarity and the lack of specific histologic features for the different subtypes, the diagnosis is difficult and clinical picture is usually very helpful to establish the diagnosis. We conducted a retrospective analysis of patients (pts) with T-NHL treated at our Centre, with the purpose of studying overall outcome and possible prognostic factors, including histologic subtypes, from our database. Patients and methods: Consecutive T-NHL pts (excluding Adult T-cell leukemia/lymphoma, NK/T NHL, and primary cutaneous T-NHL), receiving primary treatment at the Princess Margaret Cancer Centre (PMCC) between 2001-2014 were included. Data were extracted from a prospective patient database and the medical record regarding baseline characteristics, treatment, response and outcome. Response assessment was with CT imaging as per 1999 Working Group criteria. Results: Of a total of 2155 pts with aggressive histology NHL treated at PMCC between 2001-2014, 2031 pts had B-NHL and 124 (5.7%) T-NHL. Median age was 56 years (18-90), male/female ratio: 2.4; 63% presented with advanced stage (III-IV) disease, 22% had bone marrow involvement; 63% had elevated LDH and 44% had B symptoms. Observed subtypes were: Peripheral T-cell lymphoma, NOS 58 pts (PTCL NOS, 47%), Anaplastic large cell lymphoma, ALK-negative 16 pts (ALCL-ALK-, 13%), ALCL, ALK-positive 22 pts (ALCL-ALK+, 18%), Angioimmunoblastic T-cell lymphoma 13 pts (AITL, 10.5%), Enteropathy-associated T-cell lymphoma 7 pts (EATL, 5.6%), Hepatosplenic T-cell lymphoma 8 pts (HSTCL, 6%). 105/124 pts (85%) received induction chemotherapy; CHOP-like regimens were used in 94 pts (90%), and involved field radiation therapy (RT) was included in primary treatment in 24 pts (19%). Nineteen pts were treated palliatively, 5 pts with RT alone, 14 pts received palliative chemotherapy or supportive care only. Complete response (CR) was obtained in 63/105 pts (60%; Table 2), PR in 2 pts (1.9%) and 40 pts had no response or progressive disease (SD and PD; 38%). Considering together the most common subtypes (ALCL-ALK+/-, AITL, PTCL NOS), CR rate was 84% in limited stage vs 52% in advanced stage disease. Among patients with CR, 24 relapsed (38%). Fourteen pts received autologous stem cell transplant (8 at relapse, 6 for PD); 7/14 (50%) were alive at last follow-up. At a median follow-up of 5.3 years, 57/124 (46%) pts are alive. Cause of death was T-NHL in 50/124 (40%) pts. Two pts died of second malignancy (1.6%). Median overall survival (OS) and progression-free survival (PFS) were 4.57 years (95%CI: 2.23-9.53; 5yOS: 48%) and 1.5 years (0.87-3.17; 5yPFS: 37%), respectively (Table 2). For pts with limited stage disease median PFS was 4.57 years (5yPFS: 49%) and median OS 10.0 years (5yOS: 62%), while for pts with stage III/IV, median PFS was 0.82 years (5yPFS: 31%) and OS 1.81 years (5yOS: 38%). Median OS for pts who did not experience relapse (39/63; 62%) was 13.38 years (95%CI: 9.53-NA; 5yOS: 93%) vs 3.12 years (95%CI: 1.69-4.07 years; 5yOS: 25%) in pts who had relapse after CR1 (p

Description: Introduction: Gemcitabine, dexamethasone and cisplatin (GDP) has become a standard salvage chemotherapy (SC) regimen for relapsed/refractory (RR) lymphoma prior to autologous stem cell transplantation (ASCT) (Crump JCO 2014). Response to SC is now evaluated using 18-Fluoro-deoxyglucose positron-emission-tomography (FDG-PET) scans based on the recent Lugano classification (Cheson JCO 2014). We evaluated the response of patients (pts) with Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL) to GDP by PET-CT scans and attempted to determine whether PET was predictive of outcome. Methods: We performed a retrospective chart review of consecutive HL and DLBCL (diffuse large B-cell lymphoma) pts who underwent ASCT following GDP SC at our centre between January 2014 and July 2016. All pts previously received anthracycline-based chemotherapy (typically ABVD for HL or R-CHOP for NHL) for primary treatment. Pts underwent FDG-PET scans after 3 cycles of SC and scans were retrospectively reported with the Deauville Criteria Scale with Deauville scores of 1-3 considered negative, whereas scores of 4 or 5 represented a positive result. Response to GDP was documented with CT scans using 1999 Working group Criteria (JCO 1999). Pts proceeded to ASCT if they had a PR by CT imaging and no signs of PD on PET-CT. Post-PET radiation or additional chemotherapy could be given at the discretion of the treating physician. Progression free survival (PFS) and overall survival (OS) were calculated by the Kaplan-Meier method from the date of progression or date of ASCT. Statistical analysis to determine the significance of PET result on outcome was performed using the long rank test. Results: 45 pts with DLBCL and 29 pts with HL were identified: median age was 45 (range: 23-69) and 29 (range: 19-58) years respectively. Baseline patient characteristics are listed in Table 1. Following GDP SC, PET Deauville scores of 1-3 were reported in 55% of HL and 29% of DLBCL pts. Overall response rate to GDP by CT was 72% for HL pts and 64% for DLBCL pts (Table 2). For HL, 100% (16/16) of pts with a PET(-) scan and 91% (10/11) with a PET(+) result proceeded to ASCT. 85% (11/13) of DLBCL pts who had a PET(-) scan and 48% (15/31) with a PET(+) scan underwent ASCT. Additional therapy post PET scan included involved field radiation, additional chemotherapy (mini-BEAM) or novel therapy (brentuximab and bendamustine for HL patients). Median follow-up time was 14.2 months (HL) and 13.4 months (DLBCL) from relapse/progression after initial chemotherapy; and 9.6 months (HL) and 10.9 months (DLBCL) from ASCT. There was a statistically significant difference between PET(+) and PET(-) DLBCL patients from the time of initial disease progression for PFS (26% versus 69%, p=0.011) that did not reach statistical significance for OS (p=0.072). However, there was no significant difference for PFS and OS in DLCBL from ASCT when stratified by PET result (p= 0.154 and p=0.723 respectively). In HL pts, no statistically significant differences for PFS and OS from progression (p=0.480 and p=0.387 respectively) or from ASCT (p=0.579 and p=0.450 respectively) were found when stratified by PET result (see Tables 3 and 4). Conclusion: Deauville 4-5 PET scores appear to be predictive of PFS for RR-DLBCL pts. The lack of a significant difference between PET results for OS in DLBCL is likely due to sample size and the need for longer follow-up. For RR-HL pts, PFS and OS rates were both high but did not seem to noticeably differ by PET result. Additional therapy employed for Deauville 4-5 patients peri-ASCT could influence outcome. Overall, PET response assessment post GDP appears to stratify outcome in patients with DLBCL and PET adapted therapy in HL patients may improve outcome in Deauville 4-5 patients. Review of pending cases and subsequent follow-up is ongoing. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Primary mediastinal B-cell lymphoma (PMBCL) is a rare clinical entity representing less than 2-4% of Non-Hodgkin lymphomas. PMBCL typically occurs in young adults, more often in females, with early stage disease usually limited to the antero-superior mediastinum. PMBCL tends to have a more locally aggressive clinical course with a substantial percentage of patients with primary refractory disease or early relapse. Patients with primary refractory or relapsed disease have a lower probability response to second-line therapy and proceeding to autologous stem cell transplant (ASCT). The optimum chemotherapy regimen and role of radiation are currently the subject of debate; for this reason we evaluated our experience using a uniform treatment policy of combined modality therapy (CMT), including factors that influence patient outcomes. Methods: We analysed 88 patients (median age 35, range 15-64) diagnosed with PMBCL, treated at Princess Margaret Cancer Centre from 1994-2012. Data on stage, clinical prognostic factors, pathologic characteristics (including presence of sclerosis) treatment and outcome were retrieved from a prospective lymphoma database and pathology reports. Statistical analysis was performed to assess the overall survival (OS) and progression free survival (PFS) at 5 years; PFS events were progressive disease (PD), relapse or death from any cause. Patient characteristics are shown in Table 1 Results: All patients received treatment with curative intent. In the majority of patients first-line chemotherapy was cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP, 47 patients) or CHOP + rituximab (R-CHOP, 38 patients) (average number of cycles = 6); standard involved field consolidative radiation was given to 68/83 patients (82%), with a median dose of 35 Gy, usually in 20 fractions. Following the first line treatment, 38 patients achieved CR (complete response), 33 patients had PR (partial response), PD occurred in 18 patients, 10 patients with initial response relapsed. 28/88 patients with PD or relapse received second line chemotherapy (cisplatin-based or Mini-BEAM) and 6/28 went on to ASCT. Twenty one of 88 (24 %) patients died from progressive lymphoma, 2/88 died of other causes. Overall survival (OS) at five years was 72.4%, and five year PFS in was 67.7%. We observed significantly inferior five year-OS and PFS in men by univariate analysis (p=0.019; OS= 51.9% vs 80.2% in women and p=0.022; PFS= 47.6 % vs 75.2% in women, respectively); The presence of sclerosis on tumor biopsy also resulted in inferior OS and PFS (OS= 60.4% vs 89.3 %, p=0.0045; PFS= 56.1% vs 81.7%, p=0.013, respectively);PFS and OS in patients treated with R-CHOP was superior to patients who received chemotherapy without Rituximab( PFS of 84.2% vs 55.8%, p= 0.0099 and OS of 89.2% vs 61.9%, p= 0.012). In multivariate analysis, male gender and tumor pathology (PMBCL with sclerosis) were predictive of inferior OS (p=0.018 and p= 0.022, respectively) and also, inferior PFS (p= 0.0499 and p= 0.024, respectively); age at diagnosis, stage and bulk did not have independent impact on OS or PFS. Conclusions: Current therapy with R-CHOP and radiation result in excellent PFS and OS. The reasons for adverse outcomes in males in our cohort and pathological correlates of extensive sclerosis are being explored. Table 1. Patient characteristics at presentation (n=88) Variable N (%) Females 62(70.4) Stage I 39(44.3) Stage II 42(47.7) Stage III-IV 8(9.1) B symptoms 27(30.7) Elevated LDH 44(50) Bulk 〉 10 cm 60 (68.2) Extranodal disease 37 (42) Disclosures Kukreti: Celgene: Honoraria. Porwit:Beckman-Coulter: Speakers Bureau.

Description: Introduction Adolescents and young adults with hematologic malignancies have distinct tumor biology, treatment outcomes and psychosocial consequences from cancer diagnosis and its treatment. Follicular lymphoma (FL) is generally considered to be a disease of the elderly, with a median age at diagnosis of 67 years and 65% of patients 60 years or older. FL is rare among young adults (age