The optimal choice of salvage therapy for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) or Hodgkin lymphoma (HL) remains unknown. Based on promising results of phase II trials, the preferred salvage regimen in British Columbia since 2002 has been the out-patient regimen, gemcitabine, dexamethasone, and cisplatin (GDP). We conducted a retrospective analysis including all patients with relapsed/refractory DLBCL or HL who received GDP as salvage therapy between September 2002 and June 2010. We identified 235 patients: 152 DLBCL, 83HL. Overall response rates were 49% and 71% for patients with DLBCL and HL, respectively. Within the transplant-eligible population, 52% of patients with DLBCL and 96% of patients with HL proceeded to stem cell transplantation. The 2-year progression-free survival and overall survival were 21% and 28% in the DLBCL cohort, and 58% and 85% in the HL group. GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL.

BACKGROUND:Double-hit lymphoma is characterized by the presence of concurrent MYC (myelocytomatosis oncogene) and BCL2 (B-cell lymphoma 2) gene rearrangements. Prognosis is poor with standard chemoimmunotherapy. Since 2003, the British Columbia Cancer Agency has used CODOX-M/IVAC+R (cyclophosphamide, vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide, and etoposide, combined with rituximab) followed by consolidative hematopoietic cell transplantation as definitive treatment for double-hit lymphoma.PATIENTS AND METHODS:A retrospective review of the survival outcomes of patients with double-hit lymphoma treated at our institution was conducted. Thirty-two patients diagnosed with non-Hodgkin lymphoma with concurrent MYC and BCL2 translocations from 2003 to 2013 were identified. Cases with MYC or BCL2 amplification and those with overexpression in immunohistochemistry analysis were excluded.RESULTS:Median age at diagnosis was 53.0 years (range, 35.5-70.9 years), 23 (72%) were male, and 30 (94%) had stage III to IV disease. CODOX-M/IVAC+R was administered in 25 (78%) patients and 20 (80%) achieved a partial remission or better, of which 9 (36%) had a complete remission. Nineteen of the 32 (59%) patients underwent upfront hematopoietic cell transplantation. At a median follow-up of living patients of 26.4 months, 14 (44%) were alive in remission, 15 (47%) died, and 3 (9%) were alive in relapse. The 2-year progression-free survival (PFS) and overall survival (OS) of all patients were 41% and 53%, respectively. The sixteen patients treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation had a 2-year PFS of 60% and 2-year OS of 82%.CONCLUSION:Patients with double-hit lymphoma treated with CODOX-M/IVAC+R followed by hematopoietic cell transplantation can achieve durable remissions, although disease progression before transplantation remains a significant problem.

Abstract Background Biphenotypic acute leukemia (BAL) is a rare subtype of leukemia accounting for 1% to 4% of all acute leukemias. They are associated with unfavorable outcome especially in adult population when treated with standard chemotherapy alone. Management issues like type of induction therapy, consolidation strategies, and role of high dose chemotherapy with stem cell transplantation remain unclear. Methods A retrospective review of 28 patients (pts) with BAL who were treated in Vancouver between 1984 and 2012 was performed. Diagnoses were confirmed according to WHO 2008 guidelines by two hematopathologists who independently reviewed morphology, immunophenotyping and in few cases immunohistochemistry. Kaplan-Meier estimates were utilized for event free survival (EFS) and overall survival (OAS). Characteristics There were 23 males and 5 females with a median age of 47 (range 17 - 75) years. Median white cell count (WCC) at presentation was 7.7 x 109(range: 0.9 to 192x109)/L. Immunophenotyping revealed “Myeloid + B-lymphoid” pattern in 13 pts (46.4%), “Myeloid + T-lymphoid” pattern in 13 pts (46.4%), “Myeloid + B-lymphoid + T-lymphoid” pattern in 1 pt (3.6%) and “T-lymphoid + B-lymhoid” pattern in 1 pt (3.6%). Cytogenetic studies revealed Normal karyotype in 6 pts (21.43%), complex karyotype in 6 pts (21.43%), Philadelphia chromosome positivity in 3 pts (10.71%), MLL rearrangement in 1 pt (3.57%) and other chromosomal abnormalities in 9 pts (32.14%). Cytogenetic studies failed in 2 pts (7.14%) and no data was available in 1 pt (3.57%). Induction therapy was of AML type in 5 pts (17.9%), ALL type in 8 pts (28.6%), and combination of AML and ALL type in 15 pts (53.6%), and 2 of the 3 pts with Philadelphia positivity also received imatinib (one patient was treated in the pre-Imatinib era) with induction chemotherapy. Twenty (71.43%) pts achieved complete remission (CR), 16 with one cycle and 4 with two cycles. Twelve pts went on to receive high dose chemotherapy with SCT. Stem cell source was autologous in 2 pts (16.7%), related donor in 3 pts (25%), unrelated donor in 6 pts (50%), and unrelated cord blood in 1 pt (8.3%). Eleven of 12 pts were in first CR and one was in second CR before SCT. Conditioning chemotherapy was TBI-based in 7 pts and busulfan based in 5 pts. Results ALL treatment induced a remission in 45%, AML therapy in 0% and 53% responded to combination therapy. EFS and OAS estimates for all 28 patients at 15 years were 29% (95% CI 13% to 48%) and 40% (95% CI 21% to 58%) respectively. Patients receiving high dose chemotherapy and SCT had significantly improved OAS of 63% (95% CI 29% to 85%) vs. 23% (95%CI 6% to 46%) for those receiving only chemotherapy (P = .019). OAS for pts with presenting WCC of <30x109 was significantly better compared to pts with presenting WCC of >60x109 (54% vs. 0%, p = .039).”Myeloid + B lymphoid” group had better OAS estimates compared to “Myeloid + T- lymphoid” group (59% vs. 29% respectively, but not statistically significant, p= 0.1135). Type of induction chemotherapy, and age at diagnosis were not statistically significant outcome predictors. Conclusion Although a small sample size, this study would suggest that adult patients with BAL who achieve a CR with standard chemotherapy should be considered for high dose chemotherapy and stem cell transplantation. This modality of treatment gives them the greatest probability of long term overall survival. Disclosures: Sutherland: Celgene: Honoraria; Janssen : Honoraria; Novartis: Honoraria. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding.

Abstract Background Double-hit (DHIT) lymphoma is a heterogeneous group of non-Hodgkin lymphomas characterized by concurrent translocations involving MYC and BCL2 and typified by aggressive behavior and poor prognosis with only rare long-term survivors. There is no established treatment for DHIT lymphoma. Since 2003, the British Columbia Cancer Agency (BCCA) has adopted the use of intensive chemotherapy CODOX-M/IVAC combined with rituximab (R) followed by high-dose chemotherapy and hematopoietic cell transplantation (HSCT) as definitive treatment for DHIT lymphoma. In younger patients, an ablative matched sibling donor allotransplant (AlloSCT) is preferred over an autotransplant (AutoSCT). For all patients over the age of 60 years only AutoSCT is offered. Total Body Irradiation (TBI) is used as a part of the conditioning regimen for patients younger than 60 years of age. Here we report our provincial experience with this strategy, focusing on the ability to deliver this treatment and survival outcomes. Methods The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with non-Hodgkin lymphomas with concurrent translocation of MYC and BCL2 (DHIT lymphoma) diagnosed between January 2003-September 2012. Results 27 cases of DHIT lymphoma were identified with the following characteristics: median age at diagnosis was 55.8 years (range 35.5-70.9 years); 19 (70%) were male; 26 (96%) patients had stage 3/4 disease; 16 (59%) had bone marrow involvement. All cases were HIV negative. Histological diagnosis based on the WHO 2008 classification were: diffuse large B-cell lymphoma (DLBCL) n=8 (30%); B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCL-U) n=17 (63%); B-cell acute lymphoblastic lymphoma (ALL) n=1; high-grade B-cell lymphoma, not otherwise specified (NOS) n=1. 13 cases (48%) were transformed from an underlying indolent B-cell lymphoma (12 follicular lymphoma, 1 low-grade B-cell lymphoma NOS). CODOX-M/IVAC + R was administered in 20 patients (74%). 7 patients received alternative chemotherapy regimen (5 R-CHOP, 1 R-CVP, 1 R-ICE) due to patient and/or physician preference. 14 patients (52%) underwent HSCT (7 AutoSCT, 7 AlloSCT), including 11 patients treated CODOX-M/IVAC + R pre-transplant, and 3 patients who received other therapy. 13 patients did not undergo HSCT: primary refractory disease n=7; patient preference n=2; deconditioning n=1; age > 65 and poor performance status n=3. The clinical status at time of transplantation was CR in 5 patients (19%), PR in 8 (30%), progressive disease in 1 (4%). The conditioning regimens included: cyclophosphamide/TBI n=6, VP-16/cyclophosphamide/TBI n=4, BEAM n=3, busulfan/cyclophosphamide n=1. At last follow-up, 15 (56%) patients have died, 14 from disease progression and 1 from complications of AlloSCT. 10 (37%) patients are alive and in remission and 2 patients are alive but have relapsed. 8 of 14 HSCT recipients (6 AutoSCT, 2 AlloSCT) remain alive and free of disease compared with 2 of 13 patients who did not receive HSCT; both disease free survivors received CODOX-M/IVAC + R. Median follow-up for living patients was 31 months (range 6.5-67.3 months). 2-year EFS and OS from the diagnosis of all DHIT lymphoma patients were 35% (95% CI 16%-54%) and 45% (95% CI 20%-65%), respectively. For patients who received CODOX-M/IVAC + R, the 2-year EFS was 37%. For patients who received CODOX-M/IVAC + R followed by SCT, the 2-year EFS was 43%. Patients with BCLU/ALL/High-grade lymphoma NOS had a 2-year EFS of 27% and patients with DLBL had a 2 –year EFS of 50%. Conclusion Patients with DHIT lymphoma treated with CODOX-M/IVAC + R followed by SCT can have durable remissions. Regardless, progression during initial therapy prior to SCT remains a significant problem. Patients with DLBCL histology may have a more favorable outcome than those with BCLU. Disclosures: Savage: Eli-Lilly: Consultancy. Toze:Roche Canada: Research Funding; F Hoffmann-La Roche: Research Funding. Sehn:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Gerrie:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Sutherland:Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Villa:Roche: Honoraria, Research Funding; Lundbeck: Honoraria; Celgene: Honoraria. Song:Roche: Research Funding.

Abstract Introduction The only known curative option for relapsed/refractory peripheral T-cell lymphoma (PTCL) is secondary chemotherapy followed by high dose chemotherapy and stem cell transplant (HDC/SCT), if chemosensitivity is demonstrated. The optimal choice of regimen in this setting, as well as in the transplant ineligible population is unknown. Gemcitabine, dexamethasone, and cisplatin (GDP) was developed as an alternative to DHAP with a favorable side effect profile and administration in the outpatient setting. Since 2002, it has been used as the preferred second-line regimen in patients (pts) with relapsed aggressive lymphoma at the BC Cancer Agency (BCCA), including those with PTCL intended for treatment with HDC/SCT, as well as for selected pts treated with palliative intent. Patients and Methods The BCCA Lymphoid Cancer database, provincial cancer pharmacy database, and the Leukemia/BMT Program of BC database were screened to identify all pts who received GDP for relapsed/refractory PTCL, excluding cutaneous ALCL. Clinical factors and whether transplant was planned at the time of relapse/progression were collected. Disease refractory to primary therapy was defined as progressive disease (PD) during primary treatment or relapse within 3 months (m) of treatment completion. All endpoints were calculated from the date of the first cycle of GDP unless stated otherwise. Results 51 pts were identified between 2002 and 2012 with either relapsed (n=31, 61%) or primary refractory (n=20, 39%) PTCL with the following histologic subtypes: PTCL-NOS, n=17 (33%); ALCL, n=16 (31%) [ALK-positive, n=4 (8%); ALK-negative, ALCL n=10 (20%); ALK status unknown, n=2 (4%)]; AILT, n=13 (25%); NK/T cell nasal type, n=4 (8%); hepatosplenic, n=1 (2%); subcutaneous panniculitis-like, n=2 (4%). First-line treatment consisted of a CHOP-like regimen in the majority of pts (n=48) and one patient with NK/TCL received SMILE. Two pts with NK/TCL received radiation alone. The median time to progression or relapse after initial diagnosis was 7.4 m (range 0.8-150.2). At relapse, the median age was 56 years (y) (range 17-86), 43% had an elevated LDH and most had advanced stage disease (stage III/IV, 88%), good performance status (PS 0-1, 69%) and a high or high-intermediate secondary IPI (sIPI >3, 57%). Pts received an average of 3 cycles of GDP (range 1-6). In total, 36 pts (71%) were planned for HDC/SCT, based on age and lack of significant comorbidities, following a response to GDP. Those planned for transplant were more likely to be younger (< 60 y) (p=.050) with a good PS (0-1) at relapse (p=0.049) but had a similar sIPI risk distribution (p=0.195). Of these, 26 ultimately underwent HDC/SCT (transplant rate 72%; auto, n=15; allo, n=11 [non-myeloablative n=2]). Pts who underwent alloSCT (vs autoSCT) were more likely to have disease that was refractory to primary therapy (p=.045). Of the 10 pts planned for SCT who did not undergo transplant, 8 were due to PD, 1 did not have a matched sibling donor, and 1 refused transplant. The overall response rate (ORR) to GDP for all 51 pts was 80% (CR 47%) and with a median follow-up of 10.4 m for living pts, the 2 y progression free survival (PFS) following GDP was 25% and the 2 y overall survival (OS) was 43% with no differences amongst the histologic subtypes. For pts planned for transplant, the ORR was 83% (CR 58%). The 2 y PFS and OS for this group intended for transplant were 30% and 50%, respectively, and those with relapsed disease (n=22) had a superior outcome to those with primary refractory disease (n=14) (2 y PFS 42.5% vs 9%, p=.0027). The 2 y post-transplant OS was 53% and there was no difference observed between the relapsed and refractory pts who were ultimately transplanted (p=.23). For all non-transplanted pts (n=25), the median PFS after GDP was 4.4 m and the median OS was 6.8 m. In responding pts, the median duration of response was 6.8 m. The small group of non-transplanted pts with a good PS (0-1) at the time of GDP, had an improved PFS (7.9 m vs 1.6 m, p=.044) and median OS (3.7 y vs 4.2 m) following GDP with 3 pts alive and without PD. Overall, GDP was well tolerated with no treatment related deaths. Conclusion Our results suggest that GDP is an effective secondary therapy for relapsed PTCL and can lead to long-term survival, especially in those pts who subsequently undergo HDC/SCT. Selected pts with good PS may have durable remissions in the palliative setting. Disclosures: Off Label Use: Off label use of gemcitabine in the treatment of PTCLs. Connors:F Hoffmann-La Roche: Research Funding; Roche Canada: Research Funding. Savage:Eli-Lilly: Consultancy.

Abstract Abstract 4132 Allogeneic stem cell transplantation (allo HSCT) is the only modality that may produce long-term disease-free survival/cure for chronic lymphocytic leukemia (CLL). Successful transplant is hindered by relapse (REL), infections (INF), graft versus host disease (GVHD) and rejection of graft (GF). GF may manifest as either lack of initial donor (dn) cell engraftment (primary, P) or loss of donor cells after initial engraftment (secondary, S). To ascertain factors predictive for GF and outcomes thereafter including complete remission (CR), clearance of FISH abnormality (abn), non-relapse mortality (NRM), REL and survival, consecutive patients (pts) proceeding to allo HSCT at the Leukemia/BMT Program of BC with CLL (1991–2011) (n=81 total, 11 GF, 4P, 7S) were studied using prospective databases. HSCT Comorbidity index (Sorror) (CoI) was calculated for all pts, FISH performed pre and post SCT in 67 and 55 pts (10 GF), and chimerism for pts not receiving myeloablative (MA) conditioning (CON). P-values show relationship between non-GF and GF pts. Median (med) pt age (range) at diagnosis (dx) was 49 years (yrs) (26–65) whole cohort; younger at 47 (30–57) yrs in GF pts (p = 0.047). Gender was F in 24 (3 GF): M in 57 (8 GF) pts; 23 F (1 GF): 58 M (10 GF) dn (p = 0.3). Max stage was Rai advanced (III/IV) in 48 pts (59%) (8 GF) (p = 0.3); 17 (6 GF) had B-symptoms prior to HSCT (p = 0.005). Of 77 pts (95%) (11 GF) who received prior fludarabine (flu) (p = 0.4), 47 were refractory (REF) (7 GF) (p = 0.8); 35 (43%) (2 GF) were REF to last therapy (tx) pre-HSCT (p = 0.07). Med number of prior tx was 4 for both groups (range 1–14 whole cohort, 3–7 GF) (p = 0.5). CoI was 0 in 46 (57%) (6 GF), 1–2 in 26 (32%) (5 GF), and 3 or > in 9 pts (11%) (p = 0.3). Med pt age (range) at HSCT, whole cohort vs GF was similar at 57 (32–68) vs 58 (37–63) yrs (p = 0.4); and 45 (19–76) vs 42 (21–58) yrs for dn (p = 0.5). Dn was unrelated (UD) in 38 (47%) (9 GF) (p = 0.01), and HLA-mismatched (MM) in 17 (21%) (4 GF) (p = 0.2); 9 had HLA-C MM (2 GF) (p = 0.9). CON was MA (Cy/TBI) in 23 (28%) (2 GF) (p = 0.4), reduced intensity (RIC) in 41 (51%); flu/bu in 22 (27%), flu/bu + alemtuzumab (A) in 19 (23%) pts, (7 total RIC with GF, 6 post A CON) (p = 0.4), and non-myeloablative (NMA) (flu/cy) in 17 pts (21%) (2 GF) (p = 0.8). Peripheral blood (PB) was used for most pts (69, 85%) (10 GF) (p = 0.6). Cell dose, med (range) was 9.6 (0.4–25.8) TNC x108/kg pt wt (9.9, 2.7–18.4 for GF pts) (p = 0.4). CD34 count was 6.3 (2.4–578.9) x106/kg pt wt (5.9, 3.0–9.5 for GF pts) (p = 0.4). GVHD prophylaxis was CSP/MTX for the majority (79, 98%) (p = 0.1); 2 pts (1 GF) had T-Cell depletion. Pre-HSCT FISH abnormalities (abn) (61, 75% of pts) (10 GF) (p = 0.3) included: del 13q (37, 46%) (10 GF) (p = 0.09); +12 (11, 14%) (2 GF) (p = 0.9); del 11q (24, 30%) (6 GF) (p = 0.09) and del 17p (19, 23%) (3 GF) (p = 0.9). CR was achieved in 48 pts (2 GF) (p = 0.004), a med of 132.5d (28d to 3.5yrs) post HSCT (93d for GF pts, range -30–216 d) (p = 0.2). 42 pts with CR did not REL (2 GF), 6 did; 12 pts without CR have progressive CLL (4 GF), and 21 pts have no CR but no progression (5 GF) (p=0.02). 27 pts cleared FISH abn post HSCT a med of 98d (28d to 2.1yrs) (2 GF) (p = 0.09). AGVHD occurred in 45 pts (2 GF) (p = 0.09) and CGVHD in 55 pts (1 GF) (p = 0.001). KM estimate of OS (whole group vs GF) is similar at 66% vs 71% at 2yr, 57% vs 71% at 5yr and beyond (p = 0.8) At med post-HSCT follow-up (FU) of 3yrs (0.4–17yrs), 48 of 81 pts (60%) survive (7 GF, 64%). 33 are deceased at a med of 1.2yr (39d to 7.1yrs), 10 with NRM (1 GF) and 21 with REL (3 GF). Of the 11 GF pts, 7 required 2nd HSCT (64%, 3 with prior dn, all with different CON; 4 flu+treosulfan+ATG, 1 flu/cy, 1 Cy+ATG and 1 Cy+ATG+TBI); 2 pts (20%) 3rd HSCT. Current status is 7/11 GF pts alive (64%, 4 with CLL, 3 in CR) and 4 deceased (1 NRM, 2 INF, 1 CLL). Factors predictive for GF include (p-value, Odds-Ratio (if applicable)): younger age at dx (0.047), B-symptoms pre-HSCT (0.005, 6.3) (Fig 1), UD (0.01, 5) (Fig 2), alemtuzumab CON (0.008, 5.3) (Fig 3), clonal evolution (CE) by FISH (development of new FISH abn) (0.03, 5.8), and major ABO MM (0.04). GF pts had lower probability of CGVHD (0.001, 0.02), and post HSCT CR (0.004, 0.1), but similar OS to non-GF pts (p= 0.8 log rank). Strategies to decrease GF post allo HSCT for CLL include avoidance of major ABO MM and alemtuzumab in CON. Higher vigilance is required for GF in pts with pre-HSCT B symptoms, CE by FISH, and with use of UD. Of interest, survival for CLL pts with GF is not decreased due to effective rescue tx, but resource utilization is high with extra HSCT procedures required. Disclosures: No relevant conflicts of interest to declare.

Summary The curative potential of allogeneic haematopoietic stem cell transplant (allo HSCT ) in chronic lymphocytic leukaemia CLL is established, with a demonstrated role for graft‐versus‐leukaemia and less certainty for other factors in determining outcome. The first two decades of CLL patients proceeding to allo HSCT at the Leukaemia/Bone Marrow Transplant Program of British Columbia ( n = 49 consecutive, 1991–2009) were studied to clarify factors predicting outcome. The donor was related in 29 (59%) and unrelated in 20 (41%). Conditioning was reduced‐intensity in 27 (55%) and myeloablative in 22 (45%). Thirty‐one of 49 patients survive with median follow‐up of 5 years (0·2–15). Cumulative incidence of non‐relapse mortality; complete remission ( CR ); clearance of fluorescence in situ hybridization ( FISH ) abnormality and progression at 10 years was 36%; 69%; 55% and 22%. Overall survival ( OS ) was 63% at 2 years; 55% at 5 years and beyond. Factors predicting OS ( P value by log rank <0·05) were: comorbidity index <3, FISH rank (Dohner) and 17p deletion, alemtuzumab pre‐ HSCT , achievement of CR post‐ HSCT , donor chimerism >90%, clearance of FISH abnormality post‐ HSCT and absence of high‐grade (3–4) graft‐versus‐host disease. Results from this province‐wide, two‐decade cohort demonstrated that a substantial proportion of patients with high‐risk CLL become long term disease‐free survivors.

Abstract Abstract 1602 Introduction: MCL presents a therapeutic challenge remaining incurable with standard therapy. Most pts exhibit aggressive behaving advanced (adv) stage disease at diagnosis and require multi-agent chemotherapy, while others may have an indolent course. Improved outcomes with rituximab (R) and autologous stem cell transplant (ASCT) have been reported for select pts within the context of small clinical trials. In the province of BC, a new policy was introduced in 2003 recommending upfront ASCT for all eligible pts with adv stage MCL. This largely coincided with the availability of R which was included in the protocol: 6 cycles R-CHOP induction followed by ASCT and 2 cycles R maintenance (R weekly × 4 at 2 and 6 mo). The aim of this study was to review the clinical profile of MCL within a non-selected population of pts and to evaluate outcomes before and after this policy change. Methods: Using the BC Cancer Agency Centre for Lymphoid Cancer database, we identified all pts diagnosed with MCL between Jan 1990 and Dec 2010. Pathology was centrally reviewed and clinical data was retrieved from the database and medical records. Within this grp, we identified a SCT eligible cohort (<66 y with adv stage, excluding pts initially observed) and outcomes were evaluated in the pre and post SCT era, based on the policy initiation date of Jan 2003. Results: In total 535 pts were identified, median age 67 y (range 22–94), 71% male, 88% adv stage, 8% limited (lim) stage (stage I/II, bulk <10 cm, no B-sx), 4% stage unknown. Pathology: 55% diffuse, 25% nodular, 6% mantle zone, 14% blastoid. Primary treatment information was available on 511/535 (96%) pts and was as follows: 335 (66%) various chemo regimens (59% anthracycline-based); 58 (11%) induction chemo followed by SCT (55 auto, 3 allo), 67 (13%) observed, 30 (6%) XRT and/or surgery alone, and 21 (4%) were too frail or refused therapy. Overall, 163/511 (32%) received R as part of initial therapy. With a median f/up for living pts of 53 mo (range 1–251), the median OS and PFS for the entire cohort was 3.1 y and 1.3 y, respectively. Blastoid variant was associated with a poorer outcome compared with other histologies (p<0.001). Lim stage pts (n=45) had a more favorable outcome than adv stage pts (n=469), median OS 7.7 y v 2.9 y (p=0.0001) and median PFS 3.4 y v 1.2 y (p=0.0002). Pts initially observed (n=67) had a similar outcome compared with those receiving any initial treatment (n=423), median OS 4.4 y v 3.2 y (p=0.24). Twenty-nine pts were identified as long-term survivors (OS >10 y), mainly diagnosed prior to SCT policy (where f/up is shorter) and were treated with various regimens. Within this grp, median age was 57 y and 28% had lim stage, but no obvious associated clinical parameters were noted. To evaluate the impact of initial SCT, we compared outcomes in SCT eligible pts (n=179), diagnosed prior to (pre-SCT, n=93) and following its introduction in 2003 (post-SCT, n=86). Clinical characteristics were comparable between the pre-SCT and post-SCT grps; median age 56 y, MIPI score 20% high, 28% intermed, 52% low. Within the pre-SCT grp, initial treatment included CHOP-like chemo (n=46), intensive chemo (n=20), non-anthracycline-based tx (n=20) and SCT (n=3, 1 allo; received prior to policy initiation), median f/up 11 y. Within the post-SCT grp, initial treatment included SCT (n=50, 2 allo), CHOP-like chemo (n=31), non-anthracycline-based tx (n=5), median f/up 4.4 y. Thirty-six post-SCT pts did not undergo SCT (13 co-morbidities, 13 progressive disease during induction, 6 unknown/not offered, 4 declined). R was received by 8/93 (9%) pre-SCT pts and 81/86 (94%) post-SCT pts. Based on era of treatment, outcomes were significantly improved in the post-SCT grp compared with the pre-SCT grp, median OS not reached v 3.4 y, p=0.001 (5-y OS 58% v 34%) and median PFS 3.5 y v 1.3 y, p<0.001 (5-y PFS 38% v 16%). (see figure) An analysis based on actual initial treatment received (SCT v no-SCT), demonstrates favorable outcome associated with SCT (5-y OS 78% v 31%; 5-y PFS 55% v 15%). Conclusion: Outcomes for MCL have significantly improved in the modern era following the introduction of upfront ASCT in BC. Availability of rituximab coincided with this policy change and likely contributed to this improvement. Similar to prior observations, a subset of pts with indolent behaving disease can be observed without impacting OS. Patients with limited stage disease have a more favorable outcome, but no survival plateau was noted. Disclosures: den Brok: F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Song:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. OLeary:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Klasa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Savage:Roche: Research Funding. Shenkier:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Villa:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Slack:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Shepherd:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Gascoyne:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Connors:F Hoffmann-La Roche (Roche Canada): Consultancy, Research Funding. Sehn:F. Hoffmann-La Roche (Roche Canada): Research Funding.

Karyotype is a key prognostic marker in adult acute lymphoblastic leukemia (ALL) and a Philadelphia chromosome, a breakpoint cluster region/Abelson (BCR/ABL1) gene fusion, is associated with an adverse outcome. In this 5-year study, a proportion of normal karyotype pre-B ALL patients had additional BCR/ABL1 signals on fluorescence in situ hybridization (FISH) analysis. This cohort had a poor outcome and these patients should be offered alternative therapeutic strategies.Background: Diagnostic karyotype and molecular studies represent the most powerful prognostic indicators in acute myeloid leukemia and provide the framework for risk stratification. Risk stratification in ALL has also a vital role in predicting outcome and identifying patients at higher risk of relapse with multiagent chemotherapy, but the role of diagnostic karyotype and molecular markers in adult ALL is limited to few well recognized cytogenetic abnormalities. Patients and Methods: We report a case series of 6 adult ALL patients with a characteristic molecular abnormality that have done poorly with chemotherapy. Between April 2004 and November 2009, 72 adult ALL patients (Pre-B-cell 61; T-cell 11) were referred to and treated at the Leukemia/BMT Program of BC in Vancouver, Canada. FISH for BCR-ABL fusion was positive in 12 of 61 Pre-B cell ALL patients. An additional 6 patients were negative for this typical fusion but had FISH abnormalities related to BCR and/or ABL1. Results: In this report, we describe the clinical and hematopathologic characteristics of these 6 patients and their poor outcome. We review the literature where only 2 similar cases with normal karyotype Pre-B ALL and associated FISH BCR/ABL1 numerical abnormalities were found. Conclusion: We recommend screening all adult pre-B ALL patients with normal karyotype for this clonal abnormality and suggest classifying these ALL patients into the high-risk category. (c) 2013 Published by Elsevier Inc. All rights reserved.

Abstract Abstract 1694 Background: Clonal evolution (CE) and variant Philadelphia (Ph) chromosomal translocations (vPh) are seen in <10% of newly diagnosed CML patients. While the vPh is thought to have no prognostic significance, CE maybe associated with an inferior outcome compared to the presence of a single standard Ph for patients treated with imatinib (IM). This study aims to evaluate the prognostic significance of vPh and clonal evolution in a cohort of CML chronic phase (CP) and accelerated phase (AP) patients treated with IM. Patients and methods: From June 1999 to December 2008, 247 Ph+ CML CP and AP patients treated with IM (300–600 mg daily) were analyzed. Patients having had a prior allogeneic stem cell transplant were excluded. Patients were categorized into 4 groups according to karyotype at diagnosis: Group 1 (CP with CE only, n=28); Group 2 (AP, n=31); Group 3 (CP with vPh, n=20); Group 4 (CP with standard Ph, n=168). Cytogenetic response, treatment failure, event free survival (EFS) and overall survival (OS) were calculated for each group and multivariate analysis was performed to determine potential variables predictive of response and survival. Results: Groups 1 and 2 had lower complete cytogenetic responses (CCR) to IM and higher rates of treatment failure compared to Group 4. (Table1). At a median follow up 4.2 years, Groups 1 and 2 had lower median OS and EFS compared to Groups 3 and 4 (Table1). The 5 year probabilities of OS and EFS were 79 % and 53 % (Group 1), 77 % and 73 % (Group 2), 94 % and 87 % (Group 3), and 90 % and 83 % (Group 4). (Figures 1 and 2). In multivariate analysis, the only significant factors predictive of CCR were Sokal score (p=.01), CE at diagnosis (p=.03) and dose of IM (p=.03). When the analysis was restricted to EFS and OS, the presence of CE at diagnosis (p<0.0001), prior treatment before IM (p=0.04), the dose of IM (p=0.01) and the response to IM (p<0.0001) were the factors associated with significant EFS and the presence of CE at diagnosis (p=0.004), the dose of IM (p=0.05) and the response to IM (p<0.0001) were predictive of OS. The presence of a vPh had no effect on EFS and OS. Conclusion: The presence of CE at diagnosis and/or features of AP in patients with CML treated with IM are associated with an inferior prognosis, but the presence of the vPh does not appear to have any prognostic significance. It remains to be determined whether the second generation TKI's can overcome the negative influence of CE on EFS and OS. Disclosures: No relevant conflicts of interest to declare.

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.

The treatment of multiple myeloma (MM) has changed with the advent of thalidomide, bortezomib, and lenalidomide, the so-called novel agents (NAs). Given the complexity of MM therapy in the NA era we pursued a population based study to assess for improvements in survival as well as to characterize the relevance of early relapse (within 12 months) and the International Staging System in this clinical setting. We reviewed our experience with 460 patients with MM treated with autologous stem cell transplant (ASCT) between 1988 and 2008, of whom 306 had relapsed. The cohort was divided into two groups based upon relapse pre-2004 and relapse during/after 2004 (2004+), which correlated to availability of bortezomib and lenalidomide. Improvements in both overall survival (OS) (median 32.0 months vs. 71.8 months; p < 0.001) and post-relapse survival (PRS) (median 15.2 months vs. 42.8 months; p < 0.001) correlated with the NA era. Exposure to NAs conferred a better PRS (median 35.7 months vs. 9.1 months; p < 0.001). Although all patients had improvements in survival, those who relapsed late continued to do better. Lastly, in the NA era, the ISS remains an important prognostic tool in relapse, but only in the late relapsing cohort.

Sudden blast phase (SBP) is a rare event that occurs in an unpredictable fashion amongst patients with chronic myeloid leukemia (CML) who otherwise appear to be responding satisfactorily to imatinib (IM) treatment. We investigated the incidence, clinical characteristics, treatment outcome and long-term follow-up of 213 patients with chronic phase CML treated with IM according to the European LeukemiaNet guidelines. Nine patients, eight of whom received IM as first-line therapy, developed SBP (4.2% of the total). They tended to have low or intermediate risk Sokal scores at diagnosis, a predominance of the lymphoid phenotype and a short interval from "optimal" response to the development of BP. Five of the nine patients with SBP are alive in complete molecular remission; however, all of them underwent allogeneic hematopoietic stem cell transplant. The cumulative incidence of SBP for the patients who received IM as first-line therapy was 5.9% and the 2-year overall survival of the nine patients who developed SBP was 56%. Despite the improved outcome for patients with SBP receiving tyrosine kinase inhibitors (TKIs) and transplant, many of these patients are not salvaged with these therapies. This illustrates the need to develop predictive models to identify patients early whose response to TKI therapy will not be durable and hopefully prevent the transformation to advanced disease.

Abstract Abstract 2561 Introduction. AML in patients above age 60 is associated with adverse outcomes compared to younger patients. This is due to the higher incidence of adverse risk cytogenetic changes, poor performance status and end organ function that precludes patients from receiving intensive chemotherapy. Large population based studies have reported 5yr survival rates of 5–8% even in patients receiving standard ‘3+7’ induction chemotherapy. Our study looks at the effect of disease and patient characteristics on outcomes in elderly AML patients who received remission induction chemotherapy in the hope of predicting which individuals would benefit most from this treatment. Patients and Methods. Retrospective data was collected from 381 patients > age 60 who underwent conventional cytarabine and daunorubicin (7+3) induction and consolidation chemotherapy after clinical evaluation suggesting they were fit for such treatment, from Jan 1990 to Sept 2009. The follow up duration ranged from 6m–19.5 years. The data collected were age, ECOG performance status,Haematopoetic stem cell transplant comorbidity Index (HCI) (Sorror et al Blood 2005;106:2912),WBC at presentation, bone marrow blast percentage, antecedent hematologic disease (AHD), Cytogenetic risk group by MRC(UK) criteria, remission status, date of relapse, mortality and overall survival (OS). Statistical analysis was performed to determine variables affecting OS using Cox regression analysis. Multivariate Cox regression coefficients were used to generate a nomogram to predict OS based on Akaike's information criterion. Results. The CR rates in the 3 MRC risk groups were 95%,75% and 40% respectively. The 8 week mortalities in the 3 risk groups 10%,8%and 29% respectively. The 3 month survival was 85%, 1year 50% and 5yr 16% for the patients as a whole. Multivariate analysis showed that age at diagnosis, WBC, cytogenetic risk group and AHD affect OS while sex, ECOG, HCI and BM blast count do not. Using the 4 variable significantly predicting OS a nomogram was developed. Its ability to predict OS of individual patients was evaluated using bootstrapping of a set of 200 resamples. To use the nomogram, draw a line straight upwards to the points axis to determine the number of points received for each of the 4 variables. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the survival axes to determine the likelihood of 1-, 3- or 5-year OS Discussion. AML in patients > age 60 is typically associated with a poor outcome after intensive chemotherapy. However, even among this high risk group results are heterogeneous. This is illustrated in our study where the CR rate and induction mortality varied substantially across cytogenetic risk groups. In addition to the cytogenetic risk group we found age, WBC at diagnosis and the present of AHD to have prognostic value in this elderly group. However, the HCI was not predictive of survival in these AML patients > age 60 receiving standard induction and consolidation chemotherapy. The prognostic patient factors identified in multivariate analysis are easily available in newly-diagnosed AML patients, usually before decisions regarding initial therapy must be made. If confirmed in a larger prospective study, the nomogram we have developed will help clinicians predict the expected survival following intensive chemotherapy, thus helping the patient to make an informed choice regarding risk vs benefit. Disclosures: Sutherland: Centocor Ortho Biotech research & Development: Research Funding.

Abstract Abstract 3100 The advent of reduced intensity (RI) conditioning for allogeneic stem cell transplant (HSCT) has brought the question of safe application of this therapy (tx) to older patients. This is of particular importance in CLL where the median age at diagnosis (dx) is 65 yrs. This study compares outcome post RI HSCT in those aged 60 and older (older group, n=23 pts) to those less than age 60 (younger group, n=35 pts) who received RI HSCT at the Leukemia/BMT Program of BC 2001 - June 2011 (total group n=58). Forty-two of 58 (73%) were male. Racial origin was mostly white with only 2/58 (3%) Asian pts. Max stage (Rai) pre-HSCT was advanced (III + IV) in most (31/58, 53%); 13 pts (22%) had B symptoms. Characteristics of the entire group (n=58) include (med, range): interval from dx to HSCT 7.4 yrs (0.4–29); number of prior tx 4 (1–14) and % lymphocytes in pre-HSCT marrow 71 (3–98). 22% (13/58) had bulky nodes (>5cm). Six (10%) had Richter's transformation. HSCT comorbidity index (Sorror) was 0 in 33 (57%), 1–2 in 18 (31%) and >= 3 in 7 pts (12%). Most received prior nucleoside analog (57/58, 99%) and rituxan (47/58, 81%) tx. Twenty-five (43%) were resistant (RES) to last tx given; 30 of 56 pts (54%) were fludarabine (flu) RES. The younger and older group were similar apart from age at dx and HSCT (med, range) which were 47 (26–57) vs 54 (36–55) yrs and 56 (42–59) vs 63 (60–68) yrs respectively. Med donor age was 46 yrs (19–76); 39 (67%) were male; 83% of female donors were parous; 27 (47%) were unrelated (UD); and 12 (21%) mismatched. Stem cells were peripheral blood. Conditioning was non-myeloablative (flu/cy) in 14 pts (24%), and reduced intensity (fludarabine/busulfan) in the remainder (44 pts, 76%). For UD HSCT campath was added to flu/bu in 19 and thymoglobulin in 8 pts. Gvhd prophylaxis was cyclosporine and methotrexate. Count recovery occurred in 97%; 2 pts did not recover (both <60yrs); 1 died (H1N1) and 1 is > 1 year post 2nd RI UD HSCT. Graft failure (GF) occurred in 8 pts (14%) predominantly related to campath; 1 pt died (H1N1), 1 is well with autologous recovery 3 yrs post GF and 6 of 8 required further HSCT (including 2 older pts who survive > 1 yr post 2nd HSCT). Acute graft vs host disease (gvhd) grades 2–4 occurred in 83% of pts and chronic gvhd in 54% and was neither more severe nor prevalent in older pts. CR post HSCT has occurred in 26 /58 pts (45%), a med (range) of +108 days (0 days -5.4 yrs). DLI was given to 11 pts (4 older pts). At median (range) follow up of 20 months (0.3–120) post HSCT and 10.1 yrs (0.7–37) post dx 44 / 58 pts (75%) survive in the whole group, including 25/35 pts (71%) younger group and 19/23 pts (83%) older group. Death in CR occurred in only 2/14(14%) deaths or 2/58 pts (3%), both of whom were younger pts. Time of death post HSCT was similar in the younger and older groups. Pre-HSCT FISH was performed in 52 /58 pts; results were abn in 47/52 pts (90%); 28/29 (97%) younger and 19/23 (83%) older group and included: del 17p in 15 pts (26%); del 11q in 15 (26%); trisomy 12 in 11 (19%); del 13q in 29 (50%) and bi-allelic del 13q in 11 (19%). Abn FISH normalized pre-HSCT in 8 /52 (15%) and post-HSCT in 18/40 pts (45%), leaving only 22/54 (40%) with currently abnormal FISH tests. Donor chimerism >=90% was achieved to date in 43/50 assessable pts (86%) and occurred with similar frequency in younger and older age groups. Survival analysis for the whole group demonstrated the following had a positive impact on OS (p value): achievement of donor chimerism > 90% (0.006); CR post HSCT (0.010) and normal FISH or clearance of previously abn FISH (0.007). Non-significant factors included FISH (Dohner ranking); 17p del; acute gvhd gr 2–4; cgvhd; and patient age. KM estimate for OS at 1, 2, and 5 years is: whole group 85%, 73%, 73%; younger 82%, 73%, 73; older 90%, 72%; 72%. There is no difference in OS for the younger vs older group (p= 0.7). In conclusion advances have now made it possible to safely and successfully perform RI HSCT for fit older pts with CLL and obtain similar outcome and overall survival to younger pts. This allows application of this potentially curative therapy to this important patient population. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 3465 Multiple studies have demonstrated the curative potential of allogeneic hematopoietic stem cell transplantation (allo HSCT) for CLL, with a clear and strong role for graft vs. leukemia and a less certain role for other factors including dose intensity. It is also known that FISH abnormalities (abn) are prognostic for CLL. The ability and timing of SCT to eradicate CLL in specific FISH categories, and the relationship of this clearance to onset of gvhd has not been clarified. In order to ascertain factors related to outcomes including achievement of CR, clearance of FISH abN, NRM, relapse/progression (REL) and survival, patients (pts) proceeding to allo HSCT at the Leukemia/BMT Program of BC with CLL (n=49 consecutive, 1991–2009) were studied with the use of prospective databases. HSCT Comorbidity index (Sorror) (CoI) was calculated for all pts. FISH was performed pre and post SCT in 35 and 33 pts respectively. Chimerism was performed for all pts not receiving myeloablative (MA) regimens. Gender was F:M 16:33 for pts, 15:34 donor (dn). Median (med) age at SCT was 54 yrs (32-68) for pts; 45 (19-76) yrs for dn. Max stage was Rai advanced (III/IV) in 32 (65%). 30 of 45 pts (67%) who had received prior fludarabine (flu) were flu refractory (REF); 26 (53%) were REF to their last pre-SCT therapy (tx). Med number of prior tx was 3 (1-14). CoI was 0 in 25 (50%), 1 or 2 in 17 (35%), and 3 or more in 7 pts (15%). Conditioning was MA (Cy/TBI) in 22 (45%), and reduced-intensity (RIC) in 27 (55%), consisting of flu/cy in 16 (33%), and flu/bu +/− campath (for UD only, n=9) in 11 (22%) pts. Dn was UD in 20 (41%), and HLA-mismatched (mm) in 12 (25%). PB was used for most pts (38, 78%). GVHD prophylaxis was CSP/MTX for the majority (47, 96%). With med post SCT follow-up (FU) of 5 yrs (0.2-15) 31 of 49 pts are alive. Med FU (range) from dx is 11.6 yrs (3 - 35). 18 are deceased at a med of 292 days (39 days - 5.7 yrs) post SCT, 9 with NRM and 9 with REL. All pts who died with REL had either del 17p or 11q, as did 3 of 9 pts with NRM. CR has been achieved in 33 pts, a med of 103 days (range 28 days to 5.4 yrs) post SCT, and 69 days post earliest onset of gvhd. 30 pts with CR did not REL, 3 did; 3 pts without CR have progressed, and 13 pts have not achieved CR to date but do not have progressive CLL. DLI was administered in 8 pts, a med of 154 days post SCT (86-710), resulting in CR for 6 of these 8 pts. Pre-SCT FISH abN (n, % of pts) included: del 13q (20, 57%); +12 (7, 20%); del 11q (16, 46%) and del 17p (10, 29%). 2 of 32 pt with FISH abN cleared these pre and 17 post SCT at a med of 149 days (36 days to 3.7 yrs). All pts who failed to clear FISH abN had del 17p (n=8) or 11q (n=4) with the exception of 1 pt who had del 13q and graft failure. KM estimate of OS is 63% at 2 yr, 55% at 5 yr and beyond. Factors predictive for OS include (p value): CoI <3 (0.02), FISH rank (Dohner) (0.004), achievement of CR post SCT (0.002), chimerism >90% on all tests (0.01) and clearance of FISH abN post SCT (0.04). Importantly, age of pt and dn, UD, MA vs RIC, HLA mm, sensitivity to fludarabine and last tx did not affect OS. AGVHD gr 3–4 (but not gr 0–2 or CGVHD) had negative impact on OS (0.004). Studies are ongoing to evaluate the role of HSCT timing, intensity of conditioning and gvhd in the eradication of CLL in the FISH subgroups. Specific tailoring of transplant intensity and manipulation of graft vs leukemia effects may be required for individual patients in particular to improve outcomes for poor risk patients with del 17p, and to minimize risk for patients with better prognosis. Disclosures: Toze: Hoffman La Roche: Consultancy, Honoraria, Research Funding; Genzyme: Honoraria, Research Funding; Glaxo Smith Kline: Honoraria. Sutherland:Celgene: Honoraria; Orthobiotech: Honoraria.

Age remains probably the most important prognostic factor in acute lymphoblastic leukemia (ALL). Adults with ALL have poor outcome with chemotherapy when compared to children; as age increases overall survival (OS) continuously declines. Elderly ALL (EALL) patients (pts) have the worst outcome with chemotherapy. Despite good initial response to induction chemotherapy, relapse rate (RR) is high and most pts will succumb to their disease. Few studies have addressed the outcome of EALL with chemotherapy.

Abstract 113 Introduction: DLBCL and HL represent highly curable lymphoid malignancies. Patients (pts) whose lymphoma is refractory to or relapses following initial therapy pose a significant therapeutic challenge. The goal of therapy is to proceed to a non-cross-resistant salvage regimen followed by high dose chemotherapy (HDC) and stem cell transplantation (SCT) for transplant eligible pts. The optimal choice of salvage therapy remains unknown. The combination of gemcitabine, dexamethasone and cisplatin (GDP) has been shown in phase II studies to induce high response rates with minimal toxicity (Baetz T, Ann Oncol, 2003; Crump M, Cancer, 2004). Based on these promising results, British Columbia Cancer Agency (BCCA) policy has recommended GDP as the preferred salvage regimen for pts with relapsed/refractory DLBCL and HL since 2002. Patients and Methods: We conducted a retrospective analysis using the BCCA Lymphoid Cancer Database and included all pts with relapsed/refractory DLBCL and HL who received GDP as salvage therapy between September 2002 and June 2010. Pts were treated with gemcitabine 1000 mg/m2 IV day 1,8; dexamethasone 40 mg PO days 1–4 and cisplatin 75 mg/m2 IV day 1, administered at 3 week intervals (2-3 cycles for transplant eligible patients and up to 6 cycles for non-transplant candidates). Primary endpoints were response rate, PFS (defined as the interval from the beginning of GDP to first progression, relapse or death from any cause) and OS. Results: 235 pts treated with GDP were identified; 152 and 83 pts with relapsed/refractory DLBCL and HL, respectively. Clinical characteristics at time of diagnosis for patients with DLBCL were: 68% male, 65% stage III/IV, 42% bulky disease ≥ 10 cm, 43% B-symptoms, 59% IPI 0–2, 41% IPI 3–5. Median age at time of GDP was 57 y (range 20–79 y). 57 pts (37%) had primary refractory disease to first-line R-CHOP; 144 (95%) were treated with GDP at first relapse/progression; median time from diagnosis to relapse after R-CHOP (excluding primary refractory pts) was 21 m (range 7–139 m). 30 pts (20%) received rituximab with GDP. Detailed radiologic response assessment following GDP(+/−R) was available for 82% pts with response rates as follows: 16% CR/CRu, 33% PR, 17% SD, 34% PD. 9 pts (6%) underwent HDC followed by allogeneic SCT and 57 pts (38%) underwent HDC followed by autologous SCT. With median follow-up of 24 m from start of GDP (range 0–84 m), 51 pts (34%) were alive and 101 pts (66%) have died (99 from lymphoma, 1 treatment toxicity during allogeneic SCT, 1 unrelated cause). 2-y PFS and OS were 21% and 28%, respectively. The 2-y PFS and OS for the subset of patients who underwent HDC/SCT were 36% and 47%, respectively. Clinical characteristics at diagnosis for the 83 pts with relapsed/refractory HL were: 55% male, 59% stage III/IV, 39% bulky disease ≥ 10 cm, 55% B-symptoms, 80% nodular sclerosis, 4% mixed cellularity, 2% nodular lymphocyte predominant, 2% lymphocyte depleted and 12% HL NOS. IPS variables were retrievable on 66% patients: 82% IPS ≤ 3 and 18% IPS ≥ 4. Median age at time of GDP was 31 y (range 17–73 y). 30 pts (36%) had primary refractory HL and 73 (88%) received GDP at first relapse/progression. Median time from diagnosis to relapse following ABVD-like therapy (excluding primary refractory pts) was 20 m (range 9–186 m). Detailed radiologic response assessment following GDP was available in 67% pts with response rates as follows: 7% CR/CRu, 64% PR, 13% SD, 16% PD. In total, 1 pt underwent HDC followed by allogeneic SCT and 69 pts (83%) proceeded to HDC and autologous SCT. With a median follow-up of 30 m from start of GDP (range 0–86 m), 70 pts (84%) were alive and 13 (16%) have died (all from HL). 2-y PFS and OS were 58% and 85%, respectively, and for the subset of pts who underwent HDC/SCT were 57% and 86%, respectively. Hospitalization rates due to complications during GDP were higher in patients with DLBCL than HL (20% vs 7%), likely reflecting differences in age and co-morbidities between the 2 cohorts. No failures of stem cell mobilization were recorded and the only toxic death was a consequence of HDC and allogeneic SCT. Conclusions: GDP is an effective and well-tolerated out-patient salvage regimen for relapsed/refractory DLBCL and HL. Outcomes appear to be comparable to those reported with more aggressive regimens. Results from an ongoing Canadian prospective trial comparing R-GDP to R-DHAP will help clarify the role of GDP in the treatment of relapsed/refractory DLBCL. Disclosures: Connors: Hoffmann-La Roche: Research Funding.

Abstract Abstract 4597 Introduction: Light chain deposition disease (LCDD) and light and heavy chain deposition disease (LHCDD) are plasma cell disorders characterized by pathologic aggregation and deposition of immunoglobulin components in tissues leading to organ dysfunction. Reported outcomes with conventional chemotherapy include high rates of end stage renal disease and death. High dose melphalan followed by autologous stem cell transplantation (ASCT) has been employed in an attempt to improve outcomes, but few published data are available to support this practice. Methods: We conducted a retrospective review of all patients within our institutional database treated with ASCT for LCDD or LHCDD. Diagnosis was based in all cases upon renal biopsy. Associated multiple myeloma (MM) was diagnosed if bone marrow plasma cells were > 10% with concomitant anemia, hypercalcemia or lytic bone disease. Filgrastim was used for peripheral blood stem cell mobilization. All patients received melphalan conditioning at a reduced dose of 140 mg/m2 (due to renal dysfunction) with the exception of one patient who received melphalan 200 mg/m2. Response to treatment was adapted from the International Consensus Criteria (Gertz et al. 2005) designed for use in AL amyloidosis except that bone marrow biopsies were not performed to confirm complete hematologic remission. A renal response was considered to have been reached if proteinura decreased from 50% of baseline with stable creatinine or if creatinine decreased by 50% from its peak value. Results: We identified eight patients (7 LCDD, 1 LHCDD) treated with ASCT between August 2006 and November 2009. The median age at diagnosis was 48 years (range 40–62). Two patients had associated MM. All patients had come to medical attention as a consequence of renal dysfunction. The median serum creatinine at presentation was 192 μ mol/L (119-444) with two patients meeting criteria for nephrotic syndrome and a third having anasarca with nephritic syndrome. No patients were found to have associated AL amyloidosis, myeloma cast nephropathy, or extrarenal LCDD. Left ventricular ejection fraction was normal in all patients and none had evidence of cardiac infiltration. Kappa light chain restriction was present in seven patients with lambda light chain restriction in the eighth. Median kappa FLC level at diagnosis was 528 mg/L (range 42–1290, normal 3.3–19.4). Induction therapy consisted of dexamethasone in five patients and dexamethasone with bortezomib in two patients; one patient proceeded directly to ASCT without induction therapy. At the time of ASCT, the median serum creatinine was 183 μ mol/L (122-298). Stem cell mobilization was uncomplicated and ASCT was tolerated with no treatment related deaths or requirement for ICU admission. Significant toxicities included engraftment syndrome requiring steroids (2), bacteremia (2), sepsis with hypotension (1), pneumonia (1), grade 3 mucositis (1) and edema requiring ultrafiltration (1). One patient with a pre-ASCT creatinine of 298 μ mol/L went on to develop end stage renal disease and dialysis dependence two months after ASCT. Hematologic response was CR in two, PR in four, and not assessable in two patients due to insufficiently elevated baseline M-protein quantity for response determination. Seven patients had a renal response. After a median follow up from ASCT of 18 months (1-39 months), only one patient had experienced disease progression with increasing kappa FLC level. With the exception of the one dialysis dependent patient, no patients had symptoms related to renal disease at last follow up. Conclusion: In selected patients with LCDD and LHCDD, high dose melphalan with ASCT produced a high rate of hematologic and renal response with acceptable toxicity. Longer follow up is needed to assess the durability of response. Disclosures: No relevant conflicts of interest to declare.