ALBERT

Description: Background: Oral fludarabine and intravenous rituximab (FR) was the standard first-line therapy for CLL or small lymphocytic lymphoma (SLL) patients (pts) in BC from 2003-2015. Ibrutinib for relapsed/refractory (R/R) CLL was introduced and publicly funded in 2015. Our aim was to review long term outcomes of all CLL/SLL pts treated with FR in BC, including the impact of 2nd line therapy with ibrutinib versus chemoimmunotherapy and to report the risk of secondary malignancies in this population based cohort. Methods: The BC Provincial CLL Database was used to identify all CLL/SLL pts who received first-line FR from 2003-2017. The BC Cancer Registry was used to identify secondary malignancies occurring after FR. Primary outcomes were overall survival (OS) and treatment free survival (TFS), defined as start of FR to next-line therapy or death/last follow-up. Variables examined for impact on OS/TFS included age at FR, gender, primary diagnosis (CLL vs SLL), B symptoms, advanced stage (Rai stage 3-4 CLL, Ann Arbor 1-2 SLL), baseline hemoglobin, lymphocyte count, platelets, LDH and FISH abnormalities. All variables significant on univariate analyses (P

Description: Prognostic factors to predict an aggressive clinical course in chronic lymphocytic leukemia (CLL) such as CD38, ZAP-70 and IgH mutation status have been well described, however, readily available presenting features predictive of long-term stability are less well defined. We performed a retrospective analysis of 335 consecutive patients with CLL seen at St. Paul’s Hospital from January 1969 to July 2005. Patients were identified from the practice data-base and clinical and pathological data abstracted by chart review. Long-term stability was defined as no requirement for treatment for at least 6 years (n=66, group A). Characteristics of group A were compared to all other pts (group B, n=269), and, to avoid follow-up bias, to pts followed for ≥6 y who required treatment (group C, n=62). 65 pts in group A were B-cell in phenotype and 1 was T-cell; group B 268 pts B-cell, 1 T-cell; group C all 62 B-cell. Median age at diagnosis for groups A, B and C were 59.5 (range 33–80) y; 68 (30–94) y; and 60 (30–82) y, respectively (p

Description: BCL-2 expression in diffuse large B cell lymphoma (DLBCL) in HIV-negative patients (pts) is associated with inferior outcome, an effect at least partially overcome by the addition of rituximab (R) to multi-agent chemotherapy (MA-CT). The effect of BCL-2 expression on DLBCL outcome in HIV-positive pts is less well defined. We performed a retrospective clinical-pathological correlation in 141 pts with systemic HIV-associated lymphoma seen at St. Paul’s Hospital between 1982 and 2004; this analysis includes 36 DLBCL since 1992. Clinical DLBCL data were obtained by chart review; HIV-associated data from the data-base of the BC Centre For Excellence in HIV/AIDS. Stored biopsy material diagnostic of DLBCL was sectioned and stained for BCL-2 expression. Median age at DLBCL diagnosis (dx) was 42 (range 20–64)y, DLBCL stage advanced 27; ECOG PS 〉1 n=11; median LDH ratio 1.4 (0.5–8.6); IPI 〉2 n=11; CD4 at DLBCL dx 〉100 n=21; prior AIDS dx n=18; hepatitis B and/or C n=9; on highly active anti-retroviral therapy (HAART) at DLBCL dx n=11; BCL-2+ n=11. HAART with DLBCL treatment (tx) n=17; received CHOP-R n=9, CHOP or ACOP n=18; G-CSF n=10; herpes virus tx n=10; PCP prophylaxis n=35. Significant factors for inferior overall survival (OS) included prior AIDS, median OS (MS) 3.2 vs. 7.4 mo with no AIDS; no HAART use, MS 2.6 vs. 5.2 mo with HAART; BCL-2+, MS 3.2 vs. 5.2 mo for BCL-2 negative; and receiving MA-CT without R, MS 3.8 vs. 7.6 mo for MA-CT + R (p

Description: Acute leukemia, especially acute myeloid leukemia (AML), occurs more frequently in the elderly population. Treatment outcomes for this condition have traditionally been poor and very few patients survive for prolonged periods following diagnosis. We performed a retrospective chart review of all patients sixty years of age and older diagnosed with acute leukemia at St. Paul’s hospital, Vancouver, Canada, from June 1984 to July 2004. One hundred and three patients were diagnosed with acute leukemia [AML- 81; ALL- 15; ALN (acute leukemia not otherwise specified)- 7]. The median age was 72 (range 60–88) years. Fifty-seven (55%) and 46 (45%) patients had de novo and secondary leukemia, respectively. Sixteen patients (28%) had an unfavourable karyotype. Fifty-three patients (51%) received induction chemotherapy (treated) and 50 (49%) were provided with supportive care only (untreated). Treated patients were younger [67 years (60–79)] than untreated patients [76 years (61–88)], (p/= 80 years were treated (n=17). Of the treated patients, 33 (62%) achieved a complete remission (CR), 10 (19%) had resistant disease and 10 (19%) died from complications related to treatment. The median overall survival for the entire group was 103 (1–1229) days, and for treated versus untreated patients was 216 (1–1213) and 38 (2–1229) days, respectively (p=0.0021). The disease free survival in treated patients achieving a CR (n=33) was 262 days (9–722). Less than 5% of patients were alive at 4 years from diagnosis. Univariate variables predictive of prolonged survival included receiving induction chemotherapy (p=0.0027), de novo as opposed to secondary leukemia (p=0.0420), and younger age, with a relative increase in death in older subgroups (60–69, 70–79, 80+), (p=0.0311). Induction chemotherapy was the only independent predictor of prolonged survival in multivariate analysis (p=0.0027). There was no statistically significant difference in the number of treated patients and treatment outcomes between 1984–1993 and 1994–2004. In conclusion, this single-institution series of 103 patients aged sixty years and older with acute leukemia, shows that the prognosis of this disease in older patients is extremely poor. Even though induction chemotherapy seems to prolong survival in patients who are fit to receive treatment, the prognosis remains grim and most patients ultimately die of leukemia, supporting a role for investigational regimens focusing solely on this age group. It is no longer appropriate to follow regimens that have remained largely unsuccessful and unchanged over 20 years.

Description: Abstract 2363 Poster Board II-340 Background: Clinical trials report that FR as initial therapy in symptomatic CLL produces an overall response rate of 90% and significantly improves progression-free survival (PFS) and overall survival (OS) compared retrospectively to F alone [Byrd Blood 2003, 2005] and that FCR (F, cyclophosphamide and R) improves response rates and PFS compared to FC alone [Hallek ASH 2008]. FR has been the standard initial therapy for CLL/SLL in British Columbia (BC) (population = 4.2 × 106) since 2004. We wished to determine if, in an unselected community based population, the same results could be achieved with FR therapy as those seen in highly selected clinical trial populations. Patients and Methods: The BC Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify pts who received FR as initial therapy for CLL/SLL as per BCCA guidelines (F 40mg/m2/day orally D1-5 or 25mg/m2/day IV D1-5 [adjusted for renal function] and R 375mg/m2 IV D1, q 28 days for 4-8 cycles). Pts were excluded if they had more than one hematologic malignancy (n=2). OS was calculated from date of FR to date of death or last follow-up. Treatment-free survival (TFS) was calculated from date of FR to date of next treatment or death from toxicity. Factors present at initiation of treatment were analyzed for impact on outcomes. Results: 98 pts were identified who received FR from 2004-2009 as initial therapy for CLL (83%) or SLL (17%). Median age at FR was 62 y (range, 42 – 86 y). 36% had Rai stage 3 or 4 and 13% had ECOG performance status 2-3. Median lymphocyte count was 30 × 109/L (range 0.6-282 × 109/L) and LDH was elevated in 34% (29/86 with available levels). Nearly half of all pts tested were positive for CD38 (34 of 69 pts, 49%) and ZAP 70 expression (10 of 22 pts, 45%). FISH was performed in 35 pts: 13q deletion, 21 (60%); 11q deletion, 5 (14%); 17p deletion, 10 (29%); trisomy 12, 11 (31%). Most pts (65%) were observed prior to FR for a median of 28 months (range, 3 – 172 mos). Common indications for treatment included symptomatic lymphadenopathy (n=36), cytopenias (n=28), fatigue (n=23), and constitutional symptoms (n=19). Pts underwent a median of 6 cycles of FR (range, 1-8). Treatment was discontinued due to toxicity in 13 pts (13%) (cytopenias, 5; febrile neutropenia, 3; infection, 2; pulmonary disease, 1; ITP, 1; AIHA, 1) and due to progression in 4 pts (4%). Hospitalization during therapy was required in 13 pts (13%) (febrile neutropenia, 5; documented infection, 2; elective splenectomy, 2; pulmonary disease, 2; ITP, 1; rituximab administration, 1). At a median follow up of living pts of 2.4 y, 31 pts (32%) have received additional therapy after FR including CVP in 11 pts (+R, 8); chlorambucil, 7 (+ R, 1; +prednisone, 1); FR, 5; cyclophosphamide, 5 (+prednisone, 3; +vincristine, 1); CHOP, 3 (+R, 2). At time of analysis (June 2009), 86 pts were alive; 14 died, 12 from progressive CLL and 2 from toxicity of FR (severe infection, 1; interstitial lung disease, 1). For the entire 98 pts, the 2 and 4 y OS were 90% and 72%, respectively (median not reached); 2 and 4 y TFS were 69% and 54%, respectively (median 4.0 y). Factors at treatment contributing to OS in univariate analysis included elevated LDH (P=0.004), Hb 15% of CD19+ cells) by immunophenotyping (P=0.04). TFS was significantly worse in those with Hb 150 × 109/L (P=0.0013) while cytogenetic abnormalities and immunophenotyping had no effect on TFS. Age ≥ 60 y (n=60) or age ≥ 70 y (n=26) had no effect on either OS or TFS. Conclusions: In this non-selected community based population of pts with CLL/SLL, including many over 60 y (61%) and 70 y (27%) of age, our results show that initial treatment with FR leads to excellent OS and TFS, consistent with clinical trial results: 2 y OS, this study 90%; FR Byrd [Blood 2005] 93%; FCR Hallek [ASH 2008] 91%; 2 y TFS, this study 69%; FR Byrd, 2 y PFS 67%; FCR Hallek 2 y PFS 77%. FR can be safely and successfully given to community based pts, irrespective of age, for first-line therapy for CLL/SLL with OS and TFS similar to that achieved in clinical trial settings. Disclosures: Connors: Roche Canada: Research Funding.

Description: Aberrant expression of the cell surface marker CD30 in systemic B-cell HIV-related NHL other than anaplastic large cell lymphoma (ALCL) has been reported. CD30 is a member of the tumor necrosis factor (TNF) family of receptors, and activation of CD30 mediates cell cycle regulation in preclinical models. The outcome of AIDS-related lymphoma (ARL) patients (pts) has improved dramatically in recent years with good control of HIV infection and the ability to intensify chemotherapy appropriate to the lymphoma. To determine whether CD30+ systemic ARL might have different clinical outcome and require a tailored approach to therapy, we performed a retrospective clinical-pathological correlation in pts seen at St. Paul’s Hospital in Vancouver, Canada (SPH) and focused on 39 B-cell lymphoma (BCL) pts since 1992. Clinical and HIV-related data were abstracted by chart review and from the CFE data-base. Stored biopsy material diagnostic of BCL was sectioned and stained for CD30 expression by immunohistochemistry. Median age was 41 (range 20–64) years and 37 pts were male. 16 pts had diffuse large B-cell lymphoma (DLBCL), 17 other B-cell NHL excluding ALCL, and 6 Hodgkin’s Lymphoma (HL); 29 were advanced stage. HIV risk was sexual in 31 and injection drug use (IDU) in 8. Median CD4 at diagnosis was 140 (10–770) cells/ul and 20 pts received HAART. Lymphoma therapy was administered according to era and histology: CHOP-like ± Rituximab (R) n=28; ABVD-like n= 6; CODOX-M/IVAC-R n=1; HAART alone n=1; resection n=1; declined therapy n= 2. 8 pts received added R and 4 added radiation therapy. 20 were CD30+ and 19 CD30−; the only baseline characteristic that differed significantly according to CD30 status was histology p

Description: Monoclonal Lymphocytosis of Undetermined Significance (MLUS) is a clonal lymphoproliferation, usually of B-cells. MLUS has the immunophenotype of Chronic Lymphocytic Leukemia (CLL) but an absolute lymphocyte count of 10 X 109/L or less and no lymphadenopathy, organomegaly, cytopenias, or symptoms attributable to the lymphoproliferation. There is little published information as to whether the clinical course of MLUS differs significantly from that of CLL. We performed a retrospective analysis of 335 consecutive patients with clonal lymphocytosis seen at St. Paul’s Hospital diagnosed between January 1969 and July 2005. Patients were identified by a search of the practice database and clinical and pathological data were abstracted by chart review. MLUS was present in 106 patients and CLL in 229. All MLUS were of B-cell phenotype and 227 patients had B-CLL. Median age at diagnosis was 64.5 (range 33–86) y for MLUS and 65 (30–94) y for CLL (p

Description: EBV infection of B-lymphocytes is known to promote cell proliferation and survival. In contrast to NHL in HIV-negative patients (pts), in whom ≤5% are EBV-positive (EBV+), up to 50% are EBV+ in systemic HIV-related NHL. Highly active antiretroviral therapy (HAART) has improved the outcome of AIDS-related lymphoma (ARL) pts and allows intensification of lymphoma therapy. To determine whether EBV+ systemic ARL might behave more aggressively and require intensification of therapy, we performed a retrospective clinical-pathological correlation in pts seen at St. Paul’s Hospital in Vancouver, Canada, and focused on 39 B-cell lymphoma (BCL) since 1992. Clinical and HIV-related data were abstracted by chart review and from the CFE data-base. Stored biopsy material diagnostic of BCL was sectioned and stained for EBV by EBER. Median age was 40 (range 20–64) years and 37 pts were male. 16 pts had diffuse large B-cell lymphoma (DLBCL), 17 other B-cell NHL and 6 Hodgkin’s Lymphoma (HL); 29 were advanced stage. HIV risk was sexual in 25 and injection drug use (IDU) in 14. Median CD4 count at diagnosis was 140 (10–770) cells/ul and 23 pts received HAART. Lymphoma therapy was administered according to era and histology: CHOP-like ± Rituximab (R) n=28; ABVD-like n=6; CODOX-M/IVAC-R n=1; HAART alone n=1; resection n=1; declined therapy n=2. 9 pts received added R and 3 added radiation therapy. 11 received therapy directed against other herpes viruses (HVT) at some point in ARL treatment. 25 were EBV+ and 14 EBV−; no baseline HIV or lymphoma related characteristics differed significantly according to EBV status nor did receipt of HVT. In a Kaplan-Meier analysis, EBV expression was significant for overall survival (OS); median survival (MS) for pts with EBV+ ARL was 38 (2.5–74.3) months (mo) vs. 6.1 (0–18.5) mo for EBV− (p