ALBERT

Description: Background Mantle cell lymphoma (MCL) is an incurable B-cell non-Hodgkin lymphoma associated with poor outcomes. First-line treatment incorporates cytotoxic chemotherapy and rituximab, but there is no single standard of care regimen. In British Columbia (BC), between January 2003 and May 2013, R-CHOP was the preferred induction regimen. Based on results from the STIL-1 trial (Rummel et al, Lancet 2013) demonstrating improved CR rate and prolonged progression-free survival (PFS) of bendamustine and rituximab (BR) compared with R-CHOP, in June 2013, BR became the standard first-line therapy for all patients with MCL regardless of age. In both eras, fit patients generally ≤65 years of age responding to induction were eligible for high-dose BEAM and autologous stem cell transplantation (ASCT). Maintenance rituximab (MR) has been offered to responding patients post ASCT since 2004 and for transplant ineligible patients since 2012. The aim of this study was to assess the efficacy of BR as an induction regimen for MCL. Methods Patients with MCL treated with first-line BR were identified in the BC Cancer clinical and pathology databases as well as the Leukemia/BMT Program of BC transplant database. BR was initiated no later than December 2018. Treatment received was verified using the BC Cancer Provincial Pharmacy database, and clinical characteristics were verified using the BC Cancer Information System. Radiotherapy for localized disease, splenectomy, or a period of observation prior to systemic therapy were permitted. PFS and overall survival (OS) were calculated from the date of initiation of systemic therapy. In the subgroup of patients ≤65 years of age, results were compared to a historical cohort uniformly treated with R-CHOP. Baseline and treatment characteristics associated with PFS or OS (p65 years old, 9 underwent ASCT (age 66-71) and 92 did not. 63/69 patients received MR after ASCT, and 77/121 received MR after BR (without ASCT). Reasons for not receiving MR (6 after ASCT, 44 after BR) were 25 PD, 10 ASCT/BR toxicity, 7 pending, 3 patient preference, 3 early deaths, 2 physician preference. With a median follow-up of 2.4y (range 0.2 - 6.1) in living patients the 3y OS was 69.5% (95% CI 69.4-70.6) and 3y PFS 62.8% (95% CI 62.4-63.6). Baseline characteristics and outcomes were similar between patients ≤65y treated with BR vs. R-CHOP (Table 1, Figure 1A and 1B). 81/140 (58%) patients treated with R-CHOP underwent ASCT. In the subgroup of patients who underwent ASCT, outcomes calculated from the point of ASCT were not statistically different between BR vs. R-CHOP. In univariate analysis, age 〉65y, ECOG performance status 〉1, elevated LDH, blastoid/pleomorphic morphology, no ASCT, and no MR were associated with worse PFS and OS. In multivariate analysis including these variables as well as chemoimmunotherapy regimen, treatment with BR was not associated with PFS or OS. Conclusions In this population-based analysis, BR is an effective induction regimen for both transplant eligible and ineligible patients. ASCT is feasible in patients treated with BR induction. Even though BR was associated with a numerical improvement in PFS compared to R-CHOP in patients ≤65y, differences in PFS and OS were not statistically significant. Longer follow-up is necessary to fully understand the impact of BR in the frontline setting. We observed PD in 12% patients, suggesting that BR may not be an optimal induction regimen across all patients with MCL, particularly in those with aggressive or highly proliferative disease. Disclosures Villa: Roche, Abbvie, Celgene, Seattle Genetics, Lundbeck, AstraZeneca, Nanostring, Janssen, Gilead: Consultancy, Honoraria. Sehn:Morphosys: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Merck: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Apobiologix: Consultancy, Honoraria; Janssen-Ortho: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Acerta: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria. Savage:BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria; Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding. Song:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria.

Description: Abstract 1968 Background: Recent advances in HSCT have resulted in improved overall and relapse-free survival and decreased incidence of serious complications. Improved survival has prompted an increased focus on enhancing HRQoL. There is an accumulating body of evidence emphasizing that physical activity (PA) may be one modifiable lifestyle factor associated with decreased negative side effects related to HSCT and improved HRQoL. We sought to summarize the available evidence related to the effects of PA participation and HRQoL in HSCT recipients. Methods: We searched electronic databases including Pubmed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and conference proceedings from American Society of Hematology and American Society of Clinical Oncology to April 1, 2012. No language or publication date limits were used. Studies were eligible for inclusion if they were randomized controlled trials (RCTs) or quasi-experimental trials with a control group comparing exercise interventions with placebo-control or standard of care in adult HSCT recipients. Exercise was defined as any form of PA that was performed on a repeated basis for a fixed time frame over a fixed time interval. Included studies were required to have a HRQoL measure as a primary (1o) or secondary (2o) outcome. Change in global HRQoL from pre to post-intervention for intervention and control groups were compared using a DerSimonian and Laird random effects model. Heterogeneity was assessed by calculating the Q- and I2 statistics. Meta-regression was performed for the following study characteristics: total number (no.) of study participants; mean age; % female; average body mass index (BMI); mean exercise duration in minutes per session; intervention length in weeks; % adherence; type of transplant (allo- or combination of allo- and auto-transplants); and whether HRQoL was a 1o or 2o outcome. Sensitivity analysis assessed the cumulative effect of studies by publication year and no. of participants. Influential analysis was conducted to determine change in pooled effect estimate by removing one study at a time. Publication bias was assessed the Begg's rank correlation and Egger's regression test and plot. Results: Of the 1606 studies originally identified, 7 studies involving 420 patients who underwent HSCT (of which 208 were assigned to exercise or PA intervention) met all inclusion criteria. One study was excluded from the final analysis as it was identified as an extreme outlier. All 6 remaining studies used the European Organization of Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) measurement tool thus weighted mean differences (WMD) were calculated for ease of interpretation. Participation in an exercise intervention resulted in an increase in global HRQoL with a WMD of 4.72 points (95% CI: −0.04, 9.47; P = 0.05). The proportion of variability in WMD attributed to intra-study heterogeneity was 65% (95% CI: 15%, 85%; P = 0.02) and was due primarily to variation in exercise intervention protocols and study quality. Meta-regression identified that whether HRQoL was a 1o or 2o outcome significantly affected the pooled effect estimate (P=0.02). Sensitivity analysis did not reveal any important trends. Influential analysis demonstrated that the study with the most influence when removed was Baumann A, where WMD decreased to 2.86 points (95% CI: −1.25, 8.57). There was no statistical evidence of publication bias by assessment with the Egger's regression test (coefficient for bias 2.35, 95% CI −1.90 to, 6.59, P = 0.20) and Begg's rank correlation test (Z-score 0.75 with continuity correction, P = 0.45). Conclusions: This analysis summarizes the best available evidence regarding effect of exercise participation on overall self-reported HRQoL in adult HSCT recipients. The pooled estimate, after excluding outliers, showed that exercise participation resulted in a 4.72 point increase in the global HRQoL score on the EORTC QLQ-C30 measure, which was borderline statistically significant (P =0.05). This effect estimate is similar in magnitude to pivotal meta-analyses of exercise interventions in breast cancer survivors. Substantial heterogeneity existed among included trials. Larger RCTs with a strong focus on study quality and long-term effects of exercise participation should be conducted. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2022 Background: HDT/ASCT is the preferred treatment for relapsed and refractory HL patients (pts) with chemosensitive disease, with cure rates approximating 40–60%. The role for HDT/ASCT in chemoresistant HL is less well defined and many centers do not offer this treatment to such patients. Since 1985, HDT/ASCT has been recommended in British Columbia (BC) for all HL pts with progressive disease despite primary ABVD-type therapy, irrespective of response to salvage therapy. We sought to evaluate the long-term outcomes of HL pts whose disease was resistant to chemotherapy preceding HDT/ASCT. Methods: We reviewed all HL pts who underwent HDT/ASCT for primary progression (PP) or first relapse (1REL) after initial treatment with chemotherapy +/− radiation. Primary progression (PP) was defined as progression during or within 3 months of completion of initial therapy. Pts were considered to have: chemoresistant (R) disease = stable disease or progression on chemotherapy preceding HDT/ASCT; chemosensitive (S) disease = clinical and/or radiographic response to chemotherapy preceding HDT/ASCT; or untested (U) if no salvage chemotherapy was given. Clinical and laboratory data were obtained from the BC Cancer Agency Lymphoid Cancer Database, the Leukemia/BMT Program of BC Database and from hospital, clinic, and physician records. Results: 251 pts underwent HDT/ASCT for PP (n=90 36%) or 1REL (n=161 64%) between 1985–2011: male 53%; median age at diagnosis 28 y (range 16–59 y), at HDT/ASCT 31 y (range 31–62 y). Characteristics at diagnosis were: advanced stage(stage IIB, II bulky, III or IV) 94%; stage 3–4 60%; B symptoms 57%; bulk (≥10 cm) 42%; primary therapy: ABVD/ABVD-like, 95%; MOPP-like 5%; combined modality therapy 31%. Salvage therapy prior to HDT/ASCT included MVPP (28%); COP/COPP (22%); GDP (27%); no chemotherapy (13%); other (11%). RT was given with salvage therapy in 19%: alone, 27%; with chemotherapy, 73%. Conditioning regimen was with CBV/CBVP in the majority of cases (88%); BEAM (11%); other (1%). At a median follow-up for living pts of 8 y (range 0.2 – 25 y), 136 pts (54%) were alive free of HL; 89 pts (35%) have relapsed. For all pts, median overall (OS) and progression free survivals (PFS) were 21.7 y (95% CI 16.0–27.5) and 17.3 y (95% CI 9.8–24.8), respectively. 13 pts (5%) died of complications related to or within 1 month of HDT/ASCT, 6 (2%) from secondary malignancies, 7 (3%) from unrelated causes. 199 pts (56 PP, 143 1REL) had information available regarding response to salvage therapy. Of the 56 PP pts, 14 (25%) had chemoresistant disease (PP/R); 21 (38%) did not receive salvage therapy and thus were untested (PP/U); 21 (38%) had chemosensitive disease (PP/S). 10-y PFS for PP/R, PP/U, and PP/S groups were 27%, 24%, and 40%, respectively; 10-y OS were 53%, 27%, and 53%, respectively. Of the 143 1REL pts, 26 (18%) had chemoresistant disease (1REL/R); 12 (8%) did not receive salvage therapy (1REL/U); 105 (73%) had chemosensitive disease (1REL/S). 10-y PFS for 1REL/R, 1REL/U, and 1REL/S groups were 49%, 57%, and 58%, respectively; 10-y OS were 55%, 65%, 69%, respectively. OS and PFS for the chemoresistant groups (PP/R, PP/U, 1REL/R) and 1REL/U are shown in Figures 1A and 1B respectively. To evaluate impact of chemoresistance on outcomes, PP/R (pts resistant to both primary and salvage therapy, “double-resistant”) and PP/U pts (resistant to primary therapy, “single-resistant”) were grouped together (n=35) and compared to PP/S pts. There was a significant difference in OS (P =.05) but not PFS (P =.12). When pts with 1REL/R were compared to 1REL/S, there was no significant difference in OS (P =.25) or PFS (P =.26). Conclusion: In this large uniformly treated cohort of HL pts with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor, particularly for PP pts; however, this poor prognostic factor could be partially overcome by HDT/ASCT, resulting in cure in 25–50% of pts across all chemoresistant groups. Importantly, even pts who were double-resistant to both primary and salvage therapy were cured in 27% of cases. HDT/ASCT should therefore be considered in all transplant eligible pts, regardless of responsiveness to salvage chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Background: The myelodysplastic syndromes (MDS) encompass a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic and ineffective blood cell production leading to cytopenia and a variable risk of transformation to acute myeloid leukemia. The natural history of patients (pts) with MDS is variable and several prognostic scoring systems have been developed to guide treatment decisions. The revised IPSS (IPSS-R) score is commonly used in practice to predict outcome in newly diagnosed pts as well as in predicting their transplant outcomes. It remains unclear however whether improving IPSS-R pre allogeneic transplant (allo-SCT), using different therapeutic strategies, is associated with better clinical outcomes post-transplant. Methods: The Leukemia/BMT Program of British Columbia database was queried to identify all pts with MDS who had undergone an allo-SCT between Feb 1997 and April 2013. Pertinent information on clinical features and outcomes were then retrospectively reviewed. IPSS-R was calculated at MDS diagnosis (dx) and then re calculated prior to transplant. Outcomes of pts who had improvement in IPSS-R were then compared to those with no improvement or worsened IPSS-R score. Overall survival (OS) and Event free survival (EFS) were estimated using the Kaplan-Meier method and a competing risk analysis was used to calculate relapse and non-relapse mortality (NRM). Univariate and multivariate analyses were conducted. Log-Rank test was used to determine the p value. Results: We identified 138 pts who have undergone allo-SCT with the following characteristics: median age at transplant was 49 years (yrs) (range 17-66); 76 (55%) were male; 121 pts (88%) underwent myeloablative (MA) conditioning, 68 (49%) related donor and 70 (51%) unrelated donors out of which 43 (61%) were matched and 27 (39%) were mismatched. The source of stem cells were: peripheral blood n=101 (73%), bone marrow n=35 (25%) and cord blood n=2 (1%). The median interval from dx to transplant was 128 days. The median follow up (FU) of live pts was 7.3 yrs (range 1.5-17.4). Acute graft vs. host disease (aGVHD) grade 2 or higher was present in 74 (54%), chronic graft vs. host disease (cGVHD) was present in 94 (68%). During the time of FU 83 (60%) of pts had died. Relapse occurred in 41 (30%). Causes of death were: relapse n=39; GVHD n=20; regimen related n=11; infection n=5 and other causes, n=9. Baseline characteristics of all pts are shown in table 1. In 12 (9%) pts, the IPSS-R could not be calculated either because cytogenetics failed or bone marrow biopsy pre transplant was not done. At the time of transplant 85 (62%) pts had blasts 20% and blasts count was unknown in 5 pts. IPSS-R improved in 62 (45%), worsened in 23 (17%), no change 41 (30%) and unknown in 12 (9%). Type of treatment was chemotherapy in 55 (40%), best supportive care in 80 (58%) and immunosuppressive therapy (IST) in 3 (2%). The OS and EFS for all pts were 34% and 33%, respectively. There was no difference in outcome between pts who have undergone MA vs non-MA, OS 34% and 39% (p=0.63) and EFS 34% and 32% (p=0.86), respectively. OS was not statistically different between pts with improved IPSS-R vs worsened vs unchanged, 30% vs 22% vs 40%, p= 0.63 (see figure 1). EFS was 30% vs 21% vs 40%, p=0.53, respectively. Relapse was 36% vs 53% vs 31%, p=0.35 and non-relapse mortality was 54% vs 57% vs 42%, p=0.75, respectively. There was no difference in OS and EFS between pts treated with chemotherapy vs supportive care with OS of 40% vs 41%, p=0.63 and EFS of 33% vs 32%, p=0.46, respectively. OS and EFS for grade 2 or higher aGVHD were 34% vs 32%, p=0.13 and 32% vs 32%, p=0.22, respectively. Figure 2 shows OS for Pts with blast 20% at transplant. Relapse of pts with blasts 20 at the time of transplant was 23% vs 69% vs 66%, p=0.0004, respectively. On multivariate analysis, only three factors were associated with worse OS and EFS which were: cytogenetics at dx, blast count at transplant and absence of cGVHD. Conclusion: Improving IPSS-R before allogeneic transplant does not translate into better clinical outcome. The IPSS-R cytogenetic risk group at the time of diagnosis and blast count at transplant are highly predictive of post-transplant outcomes. Patient characteristics Patient characteristics Disclosures Gerrie: Roche Canada: Research Funding. Toze:Roche Canada: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding. Nevill:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: 2454 Background: Purine nucleoside analogs have been shown to produce high remission rates of 75–90% when used as first-line monotherapy for HCL. Long-term studies have shown that remissions may be lasting but are not durable. Median progression-free survival is approximately 8 years. Fludarabine (F) is an attractive option for treatment of relapsed HCL due to its similar mechanism of action, the ability to administer multiple courses for repeated exposure and its oral bioavailability. Rituximab (R) has shown single-agent activity in HCL as well as synergy with fludarabine in vivo. In addition, clinical trials have demonstrated that FR is effective in other indolent B-cell lymphoproliferative disorders. We assessed the tolerability and efficacy of FR for relapsed or refractory HCL. Patients and Methods: The British Columbia Cancer Agency (BCCA) Lymphoid Cancer Database was searched to identify patients treated with FR for relapsed or refractory HCL (F 40 mg/m2/d orally d 1–5 [adjusted for renal function] and R 375 mg/m2 IV d 1, every 28 days for 4 cycles). All cases were centrally reviewed to exclude variant HCL and splenic marginal zone lymphoma. Results: 252 patients with HCL were identified, of whom 90 developed progressive disease after initial therapy (36%). 13 patients were treated with FR between 2004–2009 for relapsed or refractory disease after first-line cladribine (n=2) or after multiple lines of therapy (n=11). Median age at FR was 59 years (range, 46–82 years); 85% of patients were male. Patients were heavily pre-treated with a median of 2 prior systemic treatments (range, 1–5). All patients had received at least 1 course of cladribine; 5 had received 2 courses (38%). Additional systemic treatments included interferon (n= 5, 38%) and deoxycoformycin (n= 4, 31%). A purine analogue was the therapy immediately prior to FR in all patients with cladribine in 11 (85%) and fludarabine alone in 2 (15%). 11 patients had a response to their last course of purine analog therapy, while 2 patients had refractory disease. FR therapy was administered at a median of 12.9 years from diagnosis (range, 3.4 –27.5) and at a median of 58 months from the last therapy (range, 2–155). Prior to FR therapy, the average interval between therapies was 46 months (range, 15–165). Median counts at time of FR were (data missing on 2 patients): hemoglobin 115 g/L (range, 79–145), white blood cell count 2.2 × 109/L (range, 0.9–8.6), lymphocyte count 1.0 × 109/L (range, 0.4–7.14), neutrophil count 1.09 × 109/L (range, 0.3–1.6), and platelets 98 × 109/L (range, 29–203). Patients underwent a median of 4 cycles of FR (range, 2–4) with oral fludarabine well tolerated in all cycles. Treatment was discontinued in 1 patient after 2 cycles due to a hypersensitivity reaction to rituximab and fludarabine was discontinued in 1 patient after 3 cycles due to the development of interstitial lung disease. The latter patient went on to receive a total of 6 rituximab infusions. Herpes zoster occurred in 2 patients, during and 6 months after completion of FR therapy, respectively. No patients required hospitalization during therapy. Information regarding response was available in 10 patients. All 10 patients had complete normalization of peripheral blood counts, absence of abnormal circulating lymphocytes and resolution of splenomegaly if present at initiation of FR. 3 patients had bone marrow biopsies at completion of therapy and all showed an absence of minimal residual disease by immunophenotyping. Currently, 12 patients (92%) remain in remission without further therapy while 1 patient has developed recurrent disease, 31 months after FR. With a median follow-up of 26 months from FR (range, 5–72), progression-free survival is 80% and overall survival 100%. Conclusion: In this multiply relapsed and heavily pre-treated group of patients with HCL, including patients previously exposed to purine analog therapy, the combination of oral fludarabine and rituximab was well tolerated, safe and effective. FR is a reasonable treatment option for patients with relapsed or refractory HCL. Disclosures: Off Label Use: Rituximab is being included because of previously documented phase II clinical trial activity against hairy cell leukemia.

Description: Background: Patients with follicular lymphoma (FL) who achieve a complete (CR) or partial (PR) response to rituximab-containing chemotherapy followed by maintenance rituximab (MR) experience improved progression-free survival (PFS). In contrast, MR does not improve outcomes in chemo-sensitive patients with diffuse large B-cell lymphoma (DLBCL). There are no published data describing the impact of MR in patients presenting with indolent and aggressive histology lymphoma simultaneously in the same biopsy (composite, COM) or two separate sites (discordant, DIS). Methods: Patients with newly-diagnosed COM/DIS lymphomas composed of an indolent B-cell non-Hodgkin lymphoma (excluding CLL/SLL, mantle cell lymphoma, and grade 3B FL) and DLBCL were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. All patients received first-line chemotherapy with R-CHOP. In early 2006, a treatment policy was introduced recommending MR 375 mg/m2 IV every 3 months for 2 years in patients with COM/DIS lymphomas achieving a CR/PR to R-CHOP induction. PFS, time to progression (TTP) and overall survival (OS) were calculated from the time of diagnosis and compared between treatment groups. Results: 98 patients with COM/DIS lymphomas were identified between January 2001 and December 2013: median age 64 y (range 22 - 86), 56% male, 48% elevated LDH, 30% performance status ≥ 2, 87% stage III/IV, and 51% high-intermediate or high IPI. 58 (59%) and 40 (41%) patients had COM and DIS lymphoma, respectively. FL was the indolent component in 65% of all cases. 35/40 patients with DIS had low-grade histology in the bone marrow. Following R-CHOP, 77 (79%) and 21 (21%) patients achieved CR and PR, respectively. 43 patients were treated with R-CHOP alone before the MR policy introduction, and 55 were treated with R-CHOP+MR; the latter group received a median of 8 (range 1 - 8) MR doses. There were no significant differences in baseline characteristics or response rates between the two groups with the exception of a higher proportion of patients with poor performance status in the group not given MR. With a median follow-up of 10y (range 1.5 - 13.6) in living patients treated with R-CHOP and 6y (range 0.9-9.5) in patients treated with R-CHOP+MR, there were 20 (47%) and 15 (27%) relapses, respectively (p=0.26). Of these, 11 relapsed with indolent histology, 11 relapsed with DLBCL, 3 relapsed in the central nervous system (CNS), and 10 had no biopsy at relapse (8 had aggressive and 2 indolent clinical behavior on review of medical records). There were 6 (30%) indolent and 14 (70%) aggressive relapses in patients treated with R-CHOP, while there were 7 (47%) indolent and 8 (53%) aggressive relapses in patients treated with R-CHOP+MR (p=0.31). 19 patients eventually died from lymphoma (8 with DLBCL relapse, 5 without a biopsy at relapse, and all 3 with CNS recurrence). The 6-y PFS was 60% (standard error [SE] 5%) with no difference between patients treated with or without MR (Hazard ratio (HR) 0.74, 95% CI 0.39 - 1.37, p= 0.33). The 6-year TTP was 64% (SE 5%), again with no differences between the two groups (HR 0.68, 95% CI 0.34 - 1.33, p= 0.25). The 6-year OS was similar between the two groups (p= 0.89). In the subgroup of patients with FL (21 R-CHOP and 43 R-CHOP+MR) the addition of MR did not impact PFS (p= 0.90), TTP (p= 0.99), or OS (p=0.55). An additional 52 patients were diagnosed after the treatment policy introduction in 2006, but did not receive MR for several reasons including physician non-adherence, progressive disease on R-CHOP, toxicity from R-CHOP or patient refusal. In an intent-to-treat analysis (43 pre-policy and 107 post-policy) there were no differences in outcomes. In a per-protocol analysis (95 R-CHOP and 55 R-CHOP+MR), there were no significant differences in outcomes. Conclusion: The addition of MR does not appear to improve PFS, TTP or OS in patients with COM/DIS lymphomas achieving CR/PR to R-CHOP, although comparisons are likely underpowered and 6-year median length of follow-up in the MR group may not be sufficient. However, the majority (63%) of relapses are aggressive and unlikely to be impacted by MR. The role of MR in these uncommon lymphomas requires further exploration. Disclosures Connors: Roche: Research Funding; Seattle Genetics: Research Funding. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding. Scott:Celgene: Consultancy, Honoraria; NanoString: Patents & Royalties: Inventor on a patent that NanoString has licensed. Gerrie:Roche: Honoraria, Other: Advisory board, Research Funding; Lundbeck: Honoraria, Other: Advisory board, Research Funding; Janssen: Other: Advisory board. Villa:Roche: Research Funding.

Description: Tyrosine kinase inhibitor (TKI) therapy has revolutionized the treatment of patients (pts) with chronic myeloid leukemia (CML). While allogeneic hematopoietic stem cell transplantation (HSCT) remains the only known curative therapy for CML, it is now rarely utilized given the excellent long-term results with TKI treatment. Therefore, only a few reports are available detailing HSCT outcome for this pt population. The purpose of this study is to examine HSCT outcome for pts with CML who received TKI therapy and identify predictors of survival, relapse and non-relapse mortality (NRM). Between January 2002 and April 2012, 55 pts with CML underwent HSCT at the Leukemia/BMT Program of BC. Transplant indications were advanced disease at diagnosis (15), TKI resistance as defined by the ELN treatment guidelines (30), TKI intolerance (2), physician preferance (4). Four pts had not received TKI therapy during this time period and were excluded from further analysis. Of the 51 pts examined in this study there were 34 males and 17 females. The median age at HSCT was 45 years and the Sokal score at diagnosis was low risk or intermediate risk (22), high risk (28) and unknown (1). The median time from diagnosis to HSCT was 307 days. Therapy prior to HSCT was imatinib (IM) only (22); IM with chemotherapy (19); IM followed by dasatinib and/or nilotinib (10). Disease status at HSCT was first chronic phase (CP1) (19), accelerated phase (9), CP2 (19), CP3 (3), BP (1). Four pts had kinase domain mutations identified at HSCT. EBMT score was 1-4 (33), and 5-7 (18). HSCT was myeloablative in 48 pts [TBI-based (25); BuCY (23)] and reduced intensity in 3 pts. Stem cell source was bone marrow (8) or PBSC (43) from a HLA matched sibling (24), HLA matched unrelated donor (UD) (18) or mismatched UD (9). At a median follow-up of 5.9 years, 18 pts have relapsed [molecular (7), cytogenetic (1), hematologic (10)] and 16 pts have died [relapse (8), GVHD (3), infection (2) regimen related toxicity (2), cerebral hemorrhage (1)]. The overall survival (OS), event-free survival (EFS), relapse and NRM at 8 years was 68%, 46%, 41% and 23% respectively. The corresponding results for the 32 pts transplanted for TKI resistance/intolerance were 75% (OS), 52% (EFS), 39% (relapse) and 15% (NRM). In univariate analysis, disease status at HSCT (p=.0005), lower EBMT score (p=.04), complete molecular response (CMR) to HSCT (p

Description: Introduction In recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger. The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger. We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity. Methods A retrospective analysis was performed on patients treated for ALL on a pediatric-based protocol. These protocols (ALL 08-01 and ALL 13-01) were modifications of the Donna Farber Cancer Institute 01-175 protocol. The format included induction with high dose methotrexate, followed by central nervous system (CNS) therapy including cranial irradiation. A single cycle of etoposide and high-dose cytarabine was given. Consolidation and continuation cycles included doxorubicin, asparaginase, vincristine and dexamethasone. Patients were included if they were aged 18-40 years and had standard risk, Philadelphia chromosome negative ALL. Between February 2008 and November 2014, 25 eligible patients were identified. These were compared with the 23 consecutive standard risk patients most recently treated with ALL 89-1. They had been diagnosed between February 2003 and July 2008. Exclusion criteria were age greater than 40 and non-standard risk ALL. Demographic and clinical data were collected on all patients from the Leukemia Program databases. Overall survival (OS) was calculated from time of diagnosis until death. Event free survival (EFS) was calculated from diagnosis until death, induction failure or relapse. Estimation of OS and EFS was performed using the Kaplan-Meier method. Patient characteristics were compared using Chi-squared test or Fisher's exact test. Ethics approval was obtained from the University of British Columbia ethics board. Results The median age of the combined patient group was 24.5 years. There were no statistically significant differences pre-treatment between groups. Combined median follow up was 28.7 months All 25 patients receiving a pediatric protocol achieved a CR, compared to 19 of 22 with the adult protocol. Despite the more intense chemotherapy dosing regimen in the pediatric protocol, there was no increase in hospitalizations, invasive fungal infections or deaths from treatment toxicity (Table 1). There was a trend towards increased thrombotic events in the pediatric-treated group, at 32% versus 9%. These included deep vein thrombosis in 4 patients, pulmonary emboli in 2, and cerebral sinus thrombosis in 2. Relapse occurred in 24% of the pediatric-treated patients and 45% of the adult-treated ones (p=0.215). Allogeneic stem cell transplantation was performed in 4 patients in the former group and 7 in the latter. Nine of these were carried out in CR2 or later, with two patients going into transplant with active disease. Overall survival following transplant was 44%. Two year event free survival was significantly improved in the group treated on the pediatric protocol (Figure 1), at 79% versus 36% (p=0.011). There was a trend towards improved overall survival in this small cohort, at 83% versus 49% (Figure 2). Conclusions A pediatric-based ALL treatment protocol was tolerated in patients up to the age of 40 years. In our centre, this is associated with an increase in EFS, and a trend towards increased OS, even considering the small cohort. We await with interest the results of larger studies investigating the ideal upfront therapy for young patients with ALL. Table 1. Results All Patients N=47 Adult N=22 Pediatric N=25 P Number % Number % Number % CR after induction 44 of 47 94 19 of 22 86 25 of 25 100 .095 Severe infection 20 of 47 43 9 of 22 41 11 of 25 44 .831 Thrombosis 10 of 47 21 2 of 22 9 8 of 25 32 .079 Pancreatitis 2 of 47 4 0 of 22 0 2 of 25 8 .491 Toxicity deaths 3 of 47 6 2 of 22 9 1 of 25 4 .593 Relapse 16 of 47 34 10 of 22 45 6 of 25 24 .215 AlloHSCT 11 of 47 23 7 of 22 32 4 of 25 16 .303 Disclosures No relevant conflicts of interest to declare.