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Abstract Abstract 2253 Background: Lenalidomide based combinations are among the most common initial therapies for myeloma. Previous studies have suggested that lenalidomide therapy can result in suboptimal stem cell collection in patients eligible to undergo autologous stem cell transplantation, especially older patients after prolonged exposure to the drug. Many salvage approaches are used when attempting repeat stem cell collection in this patient group. Patients and Methods: Two hundred twenty four patients who underwent stem cell collection following lenalidomide-dexamethasone induction from July 2004 and December 2009 were included in the current analysis. Data pertaining to the duration of lenalidomide therapy, stem cell mobilization regimen, and the collection yields were collected from the medical records. Results: The median age at mobilization was 60.6 years (range; 29, 76) and 136 (60%) were male. There were a total of 245 collection attempts from among 224 patients, 21 (9.8%) patients attempting to remobilize after failing to collect the desired numbers of stem cells at the first attempt. We first analyzed the results of the initial collection attempt. The median duration of lenalidomide therapy prior to stem cell collection was 4 months (range; 1, 26). The mobilization strategies were GCSF (Granulocyte Colony Stimulating Factor) alone in 151 (67%) patients, cyclophosphamide (CTX) followed by GCSF in 29 (13%) patients, and GCSF plus AMD3100 in 44 (20%) patients. Among those receiving AMD3100, it was added either due to peripheral blood CD34 cell count not reaching the threshold for initiation of harvest or for poor first day CD34 cells collection in 34 patients and given in a planned fashion in 10 patients. Overall 15 patients (7%) failed to reach the peripheral CD34 cell counts required to initiate apheresis, and among those starting apheresis 6 patients failed to collect at least 2 million CD34 cells/kg; a cumulative failure rate of 9%. Another 18 (8%) patients failed to collect at least 4 million CD34 cells /kg. The CD34 cells yield on day 1, the total yield, number of collections, the average daily yield and the percentage of the targeted cells collected for each mobilization strategy including failure rates are detailed in the table. Twenty-one patients reattempted stem cell mobilization; including 14 that failed a first attempt and 7 did who not achieve the intended goal even though they collected more than 2 million CD34 cells/kg. The mobilization regimens were GCSF alone, CTX + GCSF, GCSF + GM-CSF (Granulocyte Macrophage Colony Stimulating Factor) and GCSF + AMD in 5, 8, 3, and 4 patients respectively. All patients collected at least 2 million CD34 cells /kg and 14 patients (70%) collected more than 4 million CD34 cells /kg. The median CD34 cells collected with the second attempt was 5.4 million/kg (rang; 2, 19.5) bringing the median total collection for these 21 patients to 9.6 million/kg (2.6-19.6). Overall, of the 224 patients studied, all but the 6 patients who failed initially and did not attempt a second collection collected at least 2 million CD34 cells /kg and 197 (88%) collected at least 4 million CD34 cells/kg. Conclusion: While the overall failure rate of stem cell collection in patients receiving initial therapy with lenalidomide is 10%, a risk adapted approach of adding AMD3100 appear to decrease the risk of failure. However, majority of patients failing a stem cell harvest attempt can be salvaged with a second collection allowing these patients to proceed to a stem cell transplant if desired. Disclosures: Gertz: Celgene: Honoraria; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genzyme: Research Funding. Lacy: Celgene: Research Funding. Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Micallef: Genzyme: Membership on an entity's Board of Directors or advisory committees. Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Background Induction with novel agents, including proteasome inhibitors and immunomodulators, prior to autologous stem cell transplantation (ASCT) is the standard of care frontline treatment of transplant-eligible patients with multiple myeloma (MM). Common novel agent-based induction regimens include three drug combinations with a backbone of bortezomib (V), thalidomide (T) and/or lenalidomide (R). There is limited information on the comparative efficacy of novel regimens used as part of initial therapy prior to an ASCT in terms of overall survival (OS). To address this question, we retrospectively analyzed 1096 consecutive patients undergoing ASCT for MM at Mayo Clinic. Methods Study patients included those who underwent first transplant within 12 months of diagnosis, did not receive more than one induction regimen, did not relapse prior to transplant and did not receive treatment for smoldering MM in the past. Baseline characteristics, response rates and survival data were extracted from an electronic medical record and statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Choice of induction regimen was almost exclusively made by the referring physician. Results Median age at diagnosis was 60.3 years (Interquartile range 53.9-65.9). ISS staging at diagnosis was available for 49.7% of patients, of which, 34.2%, 39.3% and 26.5% of patients had ISS stage 1, 2 and 3 disease, respectively. Estimated median follow up was 65.6 months (95% CI 58.3-73.3). Baseline characteristics of patients by initial treatment have been summarized in table 1. Major subgroups by induction therapy included patients receiving Cy-Bor-d (n=193, 17.6%), Vd (n=64, 5.83%), Rd (n=253, 23.1%), VRd (n=126, 34.6%), Td (n=157, 14.3%) and VAD or dexamethasone alone as the non-novel agent comparator group (n=229, 20.9%). Median overall survival (OS) was significantly different between novel agent-based and conventional regimens (Log-rank test; p=0.0029), which were 102.7 months (95% CI, 95.2-112.2) and 78.8 months (95% CI, 67.8-92.6) respectively. Median OS with each regimen is shown in table 1. Among novel agent-based regimens, there was no significant difference in median OS, except Td, which was inferior to Rd (HR 1.62; 95% CI 1.17-2.24). Conclusion We cannot demonstrate with overall survival as an endpoint that the doublets of Vd and Rd are inferior to VRd or Cy-bor-d. There were insufficient patients treated with VTd to be included. Our study shows that the choice of novel induction regimen prior to ASCT does not affect survival (with the exception of Td being inferior to Rd), reflecting the wide array of effective salvage options. However, further prospective randomized clinical trials comparing these regimens are required to validate these findings. Table 1. Baseline characteristics and overall survival. Baseline characteristics and survival Cy-Bor-d (n=193) Vd (n=64) Rd (n=253) VRd (n=126) Td (n=157) VAD or Dex (n=229) p-value Median age 61.9 62.15 60.8 60.8 59.3 58.5 0.0041 Sex (percent males) 56.48 57.81 56.92 61.91 57.96 59.82 0.9271 ISS at diagnosis 1:24.82% 2:40.69% 3:34.48% 1:29.73% 2:24.32% 3:45.94% 1:40% 2:43.78% 3:16.22% 1:41.76% 2:34.06% 3:24.18% 1:28% 2:36% 3:36% 1:20% 2:60% 3:20% 0.0005 Median follow-up (95% CI) 20.3 (17.1-22.7) 49.5 (44.7-55.7) 59 (54.5-67) 26.9 (22.8-30.7) 126.7 (120.2-132.9) 143.4 (132.5-152.6) <0.0001 Median OS Not reached (Estimated 5 year OS rate 75%) 97.2 months (95% CI, 66.6-NR) 112 months (95% CI, 97.4-124.3) Not reached (Estimated 5-year OS rate 77%) 81.1 months (95% CI, 59.1-99.1) 78.8 months (95% CI, 67.8-92.6) 0.0019 Figure 1. Figure 1. Disclosures Kumar: Onyx: Consultancy, Research Funding; Novartis: Research Funding; Abbvie: Research Funding; Celgene: Consultancy, Research Funding; Millenium: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Gertz:Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria.

Abstract Background Cytogenetic abnormalities have significant prognostic role in AML at the time of diagnosis. Several prognostic groupings have been recommended including the NCCN and European LeukemiaNet classification. It is still unknown whether cytogenetic abnormalities have any prognostic role at the time of relapse for predicting clinical outcome. In addition, clonal evolution (CE) has been seen in many AML cases, but its prognostic value remains to be identified. Aim To study cytogenetic abnormalities and clonal evolution impact on clinical outcome for patients diagnosed with rAML Method A retrospective, single institution study through chart review of all cases diagnosed with rAML at Mayo Clinic Rochester between 2003 to 2011 was performed. Pts who achieved complete remission and relapsed at our institution were included. Pts with PML-RARA and BCR-ABL rearrangements were excluded from this study. Pts with available cytogenetics data, both at presentation and relapse, were included. Response to treatment was defined as per international working group (IWG) criteria (Cheson JCO 2003). Appropriate IRB approval was obtained in accordance with Helsinki declaration. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V9. Results Out of 192 pts, 74 pts matched our inclusion criteria. The median age at diagnosis is 60 years (range 18-81), 53% were males. At relapse, median white blood cell (WBC) was 3.2 x109, hemoglobin 10.4 g/dL, platelet 59 x109, peripheral blood (PB) blast 2% (range, 0-96), bone marrow (BM) blasts 23% (range, 1-95) and cellularity 60%. Relapse site was mainly in the BM (95%). Flt3 mutation was found in 12/43 (28%), while NPM1 mutation in 2/7 (29%). Upon treatment with salvage therapy, 27 (36%) pts achieved complete remission (CR) and 16 (22%) pts partial remission (PR) for a total overall response (OR) of 58%. Twenty one (28%) pts were able to proceed to allogeneic stem cell transplant (SCT) after achieving remission. Median overall survival (mOS) was 198 days. Pts had a longer mOS if they proceeded to SCT (386 days vs 121 days, p =0.0003). Cytogenetic analysis (CG) were diploid in 32 (43%) of 74 pts at relapse. Five pts had favorable cytogenetics (3 pts with t(8,21) and 2 pts with inv (16)). CG was divided into favorable, intermediate and poor prognosis as per NCCN classification in 5 (7%), 45 (61%), 24 (32%), respectively. As per European LeukemiaNet, there were 4 CG groups divided into: favorable, Intermediate-1, intermediate-2, and adverse in 5 (7%), 33 (45%), 12 (16%), 24 (32%), respectively. Upon comparison of CG at diagnosis and relapse; clonal evolution (a change in CG due to gain or loss of chromosomal abnormalities) was found in 42/74 (57%) of pts. CG reverted back to diploid in 8/42 (19%) or gained additional CG abnormalities at relapse in 32 (76%) pts. CR2 was achieved in 80% of favorable CG (NCCN grouping), 40% (intermediate), and 21% in poor risk (p=0.01). Using NCCN CG grouping mOS was: 435 days (favorable), 266 (intermediate), and 104 (poor) (p value = 0.01). However, using European LeukemiaNet grouping mOS was: 435 days (favorable), 174 (intermeidtae-1), 363 (intermediate-2), and 104 (poor) (p=0.004). CE did not affect mOS (p =0.7). On multivariate analysis, response to salvage therapy (p<0.0001), NCCN CG grouping (p =0.03), wbc (p=0.045), and PB blasts (p=0.01) were significant but not age, BM blast, platelet and CE. Conclusion CG were diploid in 43% of relapsed pts. CE (gain or loss of cytogenetic abnormalities) was seen in 57% of CG at relapse compared to diagnosis but did not affect mOS. NCCN (and not European LeukemiaNet) cytogenetic grouping did affect clinical outcome through both achieving second CR and mOS (both on univariate and multivariate analysis). Our results confirm the prognostic value of CG on relapse, and need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.

Abstract Background Tunneled central venous catheters have traditionally been used for administration of chemotherapy (chemo) for acute leukemia treatment. Peripherally inserted central catheters (PICC) are increasingly being used, but there is an increased risk of PICC-associated thrombosis (PAT). There is limited information on management of PAT in this subgroup of patients (pt). Methods In this retrospective cohort study we investigated the primary management of PICC related upper extremity venous thrombosis (TB) in pt with hematologic malignancy undergoing chemo at Mayo Clinic Rochester. Eligible pt were 18 years and older, had documentation of PICC placement at our institution, initiation of chemo within a week of PICC placement, and the TB was objectively documented by compression venous ultrasound (CVU). Superficial venous TB (SVT) was defined as TB of subcutaneous veins (basilic and cephalic) and deep venous TB (DVT) defined as TB of brachial, axillary, subclavian, or innominate superior vena cava and internal jugular veins. We retrospectively stratified initial management (IM) into 1) PICC removal alone (PR), 2) PR and therapeutic anticoagulation (AC), 3) AC alone, and 4) conservative management (CM) consisting of symptomatic care and observation. We also investigated factors influencing IM of PAT. Long term outcomes including incidence of pulmonary embolism (PE), post phlebitic syndrome and recurrence of TB were noted. Results Between 2006 and 2012, 190 pt with AML (n=160), MDS or MDS/MF (n=10), or ALL (n=20) met our study criteria. Overall, 40/190 (21.6%) developed PAT: AML n=38, ALL n=1, MDS/MF n=1. SVT occurred in 16/40 (40%) pt and DVT occurred in 24/40 (60%) pt. IM is shown in Table 1. One pt with SVT received AC for 6 weeks as well as PR. In this pt, IM included AC because of proximity of TB to deep veins. 7 pt had a follow up (f/u) CVU within 3 months demonstrating: TB progression (prog, n=1, IM with PR alone but with prog AC was started); TB stability (stab, n=2, both IM with PR alone) and TB resolution/improvement (R/I, n= 4, 2 IM with PR and 2 IM with CM) In the 5 pt with CM, 2 pt had f/u CVU demonstrating improvement, one pt had charted clinical improvement , and 2 pt had no charted clinical f/u. Of DVT pt on AC (n=14), 5 pt completed at least 2 months of AC. Reasons for early cessation (n=9) of AC included thrombocytopenia (tcp, n=4), hematoma (n=1), hematuria (n=1), subarachnoid hemorrhage (n=1), and unknown (n=1). One pt died 2 days after presence of DVT was noted. Two pt initially treated with PR alone developed a second TB with placement of a new PICC on contralateral arm and AC was subsequently initiated (duration: 3 months (n=1), and 8 days (n=1)). 14 pt with DVT had f/u CVU within 3 months which demonstrated prog (n=2), stab (n= 8), or R/I ( n=4) of TB (Table 2). The 2 pt with TB prog subsequently received longer term AC guided by platelet count. In 5 pt with PICC not initially removed, 3 pt had PR after completion of chemo. (1-4 days), one pt had PR at discharge (27 days from TB), and one pt had PICC in place on discharge. One pt with DVT experienced a PE within one year f/u. This pt had initially completed 3 days of AC which was stopped because of tcp. Conclusion In this cohort of patients with PAT, the most common IM consisted of PR, which appeared to result in a low recurrence rate among pt with SVT. In pt with DVT, the role of AC remains to be defined given the abbreviated course of AC in most pt. Though, the lack of CVU followup in all pt limits conclusions, there appeared to be a low rate of symptomatic prog. Initiation of AC was largely guided by platelet count and degree of occlusive symptoms. Thrombocytopenia was also the most commonly cited reason for discontinuing AC. Close clinical follow up aided by the use of CVU was integral to ensure that PAT did not lead to further adverse events. Disclosures: No relevant conflicts of interest to declare.

Abstract Abstract 1878 Poster Board I-900 Autologous stem cell transplant as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, one-third to one-half of patients did not achieve partial response at transplant. Previously published medical literature has showed that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after high-dose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplant. With the introduction of novel agents—immunomodulatory drugs and proteasome inhibitors—response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response after induction therapy with a regimen that contains a novel agent. Unlike patients in reports published previously—before novel agents—patients who do not achieve partial remission have a significantly shorter overall survival from transplant (74.0 vs 43.5 months) and a shorter progression-free survival (22.6 vs 13.1 months; P<.001). Absence of a response to induction therapy with a novel agent predicts a poorer outcome after high-dose therapy.{abstabft}.b CR+VGPR for plateau, P<.001 compared with other 3 categories. Failure to respond to novel-agent induction leads to shorter posttransplant progression-free survival (PFS). Failure to respond to novel-agent induction leads to shorter posttransplant overall survivalDisclosures: Gertz: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Kumar: celgene: Honoraria; millenium: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Lacy: celgene: Honoraria; millenium: Honoraria.TableMultivariable Analysis of Posttransplant Progression-Free SurvivalVariableP ValuePlateau vs relapsed-refractory.003Albumin.86Sex.94b2-Microglobulin.89Bone marrow plasma cells.18Age.75Abnormal cytogenetics.002CTX mobilization.51Labeling index.002

Abstract Background L-asparaginase (LASP) therapy in adults is associated with frequent hepatic and metabolic side effects, often resulting in dose adjustments and omissions. Pegylated asparaginase (PEGASP) substituted for LASP improves convenience of administration with comparable efficacy; however, adverse event (AE) management remains challenging. The incidence and management of LASP- and PEGASP-induced metabolic and hepatic complications in adult ALL patients is not well defined. Methods This single center, retrospective, observational study was approved by the Mayo Clinic Institutional Review Board. Consecutive adult patients with a confirmed diagnosis of ALL receiving LASP or PEGASP containing chemotherapy regimens between January 2000 and October 2012 were evaluated. Patients were followed up to 60 days after the last LASP or PEGASP dose for development of biochemical and clinical pancreatitis, hypertriglyceridemia and hepatotoxicity. Hyperglycemia was not analyzed due to confounding variables, such as concomitant corticosteroid administration. AEs were graded as per the National Cancer Institute Common Terminology Criteria (CTCAE) version 4.03. Analysis was performed using Cox proportional hazard models with odds ratios (with 95% confidence intervals) reported to demonstrate the strength of association between group and AE rate. Results Of 74 adult patients, 54 (73%) met inclusion criteria. History of dyslipidemia, diabetes mellitus, cholelithiasis and coronary artery disease was documented at baseline in 13 (24%), 4 (7%), 4 (7%) and 10 (19%) patients, respectively. Twenty eight (52%) patients received LASP, 22 (41%) received PEGASP and 4 (7%) received both. A total of 399 doses including 335 (84%) LASP and 64 (16%) PEGASP were administered. Distribution based on treatment schedules was as follows; CALGB 9111 (n=20 (37%), Larson et al, 1998), E2993 (n=13 (24%), Goldstone et al, 2008), C10403 (n=9 (17%), NLM: NCT00558519), CCG 1941 (n=7 (13%), Gaynon et al, 2006) and Augmented Hyper-CVAD (n=5 (9%), Faderl et al,2011). Six (11%), 20 (37%), and 53 (98%) patients experienced pancreatic, lipid (hypertriglyceridemia) and hepatic adverse events, respectively. In this group, CTCAE grade 3/4 AEs occurred in 0 (0%), 8 (15%), and 28 (52%) patients, respectively. No deaths were directly related to these complications. Patients receiving PEGASP were more likely to experience AE of any CTCAE grade (OR 11.5, 95% CI 4.4-30.3, p < 0.0001), including grade3/4 AEs (OR 27.9, 95% CI 11.4-68.2, p < 0.0001) in comparison to those receiving LASP. All cases of pancreatitis manifested as biochemical elevation in pancreatic enzymes, and were either grade 1 (n=4, 67%) or grade 2 (n=2, 33%). All patients were managed conservatively. Management of hypertriglyceridemia was heterogeneous across all grades and included observation (n=11, 55%), non-pharmacologic interventions (n=1, 5%), medication management (n=4, 20%) and combined strategies (n=4, 20%). The most common practice was a combination of fibrate derivatives (fenofibrate) and fish oil (n= 5). One patient with a peak triglyceride level of 2285 mg/dL was placed on an insulin/dextrose infusion for 4 days. Hepatic toxicity manifested as CTCAE grade 3/4 transaminitis in 13 (24%) patients, hyperbilirubinemia in 4 (7%) patients and both in 11 (20%) patients. Temporal correlation was used to best distinguish confounding variables including possible hepatoxicity from azole antifungals and other drugs. Management of hepatic toxicity included delay in dosing, subsequent LASP or PEGASP dose reduction and laboratory monitoring until resolution. Overall, deviations in LASP or PEGASP administration were documented in 18 (33%) patients due to metabolic or hepatic AEs. Eight (15%) patients required omission of at least 1 dose, 7 (13%) experienced delays of administration and 7 (13%) needed a dose reduction. Conclusion PEGASP administration resulted in significantly higher AE rates in comparison to LASP and this significance was retained when comparing AEs of CTCAE grade 3 and 4. Given the growing trend of using PEGASP combination chemotherapy in adults with ALL, a detailed analysis looking at the increase in side effects, their consequences (delayed tereatment and dose reductions) and the impact of these factors on disease remission and survival is needed. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: Allogeneic Hematopoietic cell transplantation (HCT) is potentially curative therapy for MDS and AML. Although the median age at presentation is >65 years, most patients receiving HCT for these disorders are young (<60years). With the availability of Reduced Intensity Conditioning (RIC) many older patients are able to undergo HCT. The older age group is the most rapidly increasing cohort in CIBMTR registry. We analyzed the outcomes of AML and MDS patients' ≥ 60 years who received allogeneic sibling or unrelated donor HCT at our institution between 2009 and 2014. We also evaluated the influence of patient-, disease-, and transplant related factors on outcomes. Methods: Prospectively collected data available in the BMT databases at Mayo Clinic Florida, Arizona and Rochester as well as individual patient charts were reviewed after IRB approval. Patients with MDS or AML in complete remission at the time of transplant were included; those with active disease, induction failure, or prior transplant were excluded. HCT-specific comorbidity index (HCT-CI) and the disease risk index (DRI- Armand et al. Blood 2012) was noted. Survival estimates were calculated using the Kaplan Meier method. Associations with survival were explored using single variable Cox-regression modeling and log-rank tests. Results: 80 patients were included; 68 AML and 12 MDS. 31 (39%) were male. Median age 66 years (range 60-75). 33%, 52%, and 13% patients had ECOG status of 0, 1, >2, respectively. Thirty-seven patients (46%) had low or intermediate DRI and 43(54%) had high DRI. Twenty-two (28%), 24 (30%), and 34 (43%) patients had HCT-CI of 0, 1, or >2. There were equal number of sibling and unrelated donors; 85% were full HLA match and 15% with 1 or 2 mismatches; mean age of the donors was 52years (range18-74). Transplant conditioning was fludarabine-containing reduced intensity regimens in 78 (97%), 2 patients received myeloablative conditioning. The source of stem cells was peripheral blood in all patients. A median of 5.87 x10^6 CD34/kg donor cells were infused (range 1.58-10.92 X10^6). All patients received calcineurin inhibitor based GVHD prophylaxis (tacrolimus 56%, cyclosporine 44%); 6 patients also received ATG. The median follow up of survivors was 13 months. Kaplan Meier estimate of overall survival at 100 days, 1 year, and 2 years was 90%, 64%, and 55%. Cumulative incidence of relapse at 6 months, 1 year, and 2 years was 19.5%, 22.3%, and 27.1%. Relapse free survival at 2 years was 50%. The non-relapse/ treatment related mortality at 6 months, 1 year and 2 years was 11.7%, 15.9% and 15.9%. The rate of acute grade 2-4 GVHD was 30% and chronic GVHD was 39%. Univariate analysis identified secondary disease (compared to de novo) and high DRI(compared to low/intermediate) to be associated with worse mortality - HR 2.54 (1.31-4.93; P = 0.006), and 2.31 (1.13-4.73; P = 0.021), respectively. Probability of overall survival at 6 months, 1 year, and 2 years for patients with de novo disease (n=57) vs. secondary disease (n=23) was 87.1% vs. 64.5%, 71.1 vs. 45.6%, and 63.2 vs. 32.6%, respectively; P= 0.006. There was no effect of donor age, donor type or degree of mis-match on the survival. Conclusion: Allogeneic HCT is feasible in older patients with MDS and AML utilizing reduced intensity conditioning regimens with acceptable outcomes that are comparable to published results in younger patients. Patients with high DRI and secondary disease have poorer overall survival as compared to those with de novo disease and low/intermediate disease risk index. These data support other studies that age alone does not negatively influence transplant outcomes. Disclosures No relevant conflicts of interest to declare.

Abstract Abstract 3231 Poster Board III-168 Background Peripheral blood stem cells (PBSC) are the preferred graft type for autologous stem cell transplantation (ASCT) and mobilization is typically done using growth factor (GF) alone or a combination of chemotherapy (CTX) and GF. The success of mobilization is influenced by several factors such as prior therapy and mobilization strategy. Patients (Pts) failing to mobilize successfully often have GF dose increased and if unsuccessful, mobilization reattempted with chemotherapy + GF or G-CSF (Granulocyte Colony-Stimulating Factor) + GM-CSF (Granulocyte-Macrophage Colony-Stimulating Factor). More recently, plerixafor, a CXCR4 inhibitor, has been found to enhance G-CSF based collection allowing potential early intervention in poor mobilizers. However, this approach requires valid cut-points for peripheral CD34 counts (pCD34) for cost efficient use. Methods We studied 910 first time, G-CSF based PBSC mobilizers with MM (565; 62%), or light chain amyloidosis (345; 38%). Salvage attempts were excluded, as were first attempts using CTX+GCSF, plerixafor or GF combinations. Sensitivity-specificity analysis (ROC) was used to define ideal cut-points for predefined outcomes. We used a CD34 yield of 2 million/kg as the minimum required collection and 4 million/kg as the ideal collection for this analysis. Our current practice is to initiate collection at a pCD34 of 10/uL. Results We first determined the best day 1 pCD34 cutoff for being able to collect at least 2 million/kg PBSC to be 9.2/uL. Among those with ≥9.2/uL, only 1.6% failed to collect at least 2 million compared to 27% among the rest (P < 0.001). These numbers were 1.7% and 25% respectively using the traditional cutoff of 10/uL. We then examined how the pCD34 on day 2 predicted collection, among those failing to reach the current threshold of 10/uL. Among this group, a pCD34 on day 2 of 8/uL was the best cutoff to predict a collection of 2 million/kg. Among those with >8/uL, only 9% failed to collect at least 2 million compared to 48% among the rest (P < 0.001). Among those with day 1 pCD34 < 10, 65% achieved a count of 8/uL on day 2. We then examined what pCD34 on day 1 can best predict a pCD34 ≥ 8 on day 2 and found this to be 5/uL. Among those with day 1 pCD34 ≥ 5/uL, 92% reached day 2 pCD34 ≥ 8 compared to 36% among the rest (P < 0.001).We then determined cutoffs based on ideal targets using only those patients achieving pCD34 count > 10/uL by day 2, since these patients would have started collection without any change in the mobilization technique. We used a maximum of 5 collections to achieve the goal as being ideal, taking into account the most commonly used practice of collecting during weekdays. We examined cutoffs both for a target of 4, 8 and 12 million/kg for one, two or three transplants respectively. Among those with a day 1 or day 2 pCD34 > 10/uL 98% collected 4 million/kg in 5 collections. The best day 1 or day 2 pCD34 predicting a 8 million/kg yield in 5 collections was 21.4/uL and a 12 million/kg yield was 27.9/uL. Among those with day 1or 2 pCD34 ≥ 21.4/uL, 90% collected 8 million compared to 54% among those with pCD34 < 21.4/uL. Similarly, among those with day 1 or 2 pCD34 ≥ 27.9/uL, 79% reached 12 million in ≤ 5 days compared to 17% among those with pCD34 < 27.9/uL (P < 0.001).Finally we examined if poor collection on first day, despite a pCD34 > 10 predicts for poor overall yield. A ratio of day 1 collection (million/kg) to pCD34 day 1 or 2 < 5×104 was highly predictive of failure to get eventual yield of 2 million/kg, with 38% below the cutoff failing to reach the goal compared to 2% for those above the cutoff. Conclusions This study provides an estimate of optimal pCD34 count thresholds for early identification of patients at high risk of collection failure. It is reasonable to use the first or second day pCD34 count, since a substantial proportion of patients will achieve the threshold value by day 2 and have similar outcome as those reaching the threshold by day 1. Based on the results here, interventions such as plerixafor can be considered if pCD34 count is < 5/uL on day 1 or < 9/uL by day 2, to achieve the minimum collection of 2 million/kg. However, in order to achieve the ideal targets, a higher threshold should be considered and the recommendation would be 17/uL, and 28/uL for target of 8 or 12 million respectively. Finally, identification of poor mobilizers after start of collection potentially provides another time point for early intervention, and this needs to be prospectively studied. Disclosures Micallef: Genzyme: Research Funding. Gertz:Genzyme: Research Funding. Kumar:Celgene,Genzyme,Millenium,Novartis,Bayer,: Honoraria, Research Funding.

Abstract Abstract 2911 Poster Board II-887 BACKGROUND: Pomalidomide (POM) is an immune modulatory drug (IMiD® Immunomodulatory compound) recently shown to improve anemia in subjects with myelofibrosis (MF) in an adaptive phase-2 trial (0.5 mg or 2.0 mg/d with or without prednisone; Tefferi et. al. JCO 2009)). There were no dose limiting toxicities (DLT) observed. No other MF-features (splenomegaly, fibrosis) were identified/improved even at the highest dose. We performed a subsequent dose-escalation trial to determine whether higher doses of POM are effective and well tolerated. METHODS: The trial was classic 3 × 3 design on pts with symptomatic MF (anemia and/or symptomatic splenomegaly). POM was started at dose of 2.5 mg/days (d) for 21 d every 28 d. Dose increased in cohorts by 0.5 mg/d were done if no subject had a DLT (≥grade-4 hematologic toxicity, ≥grade-3 febrile neutropenia or ≥grade-3 non-hematologic toxicity) in cycle-1. Subsequent cohorts were enrolled until the maximum tolerated dose (MTD) was reached (dose level before that resulting in DLT in >1 of 6 subjects). In the phase 2 portion, subjects were treated at the MTD, those without response at the MTD after 3 cycles were lowered to the minimal effective dose (MED) of 0.5mg/d. RESULTS: Subjects: 19 subjects with MF were enrolled 06/2008-03/2009. 14 had primary MF, 3 post-polycythemia vera MF, and 2 post-essential thrombocythemia MF. Median age was 67 y (range, 43-83 y), 11 were female (58%). 16 had a JAK2-V617F mutation. 11 were RBC-transfusion–dependent (58%). 16 subjects had palpable splenomegaly, median 12.5 cm below the LCM (range, 1-26 cm). Median time since diagnosis was 24 mo (range, 1-173 mo). 15 were considered intermediate-high risk by IWG-MRT IPSS (Cervantes et al, Blood, 2009). Phase-1: 3 subjects each were enrolled at the 2.5 mg/d, 3.0 g/d, and 3.5 g/d mg dose cohorts. A DLT (bone marrow suppression) was seen at the 3.5 mg/d level. 3 additional subjects received 3.0 mg/d level cohort confirming this dose as the MTD. Phase-2: 10 additional subjects were enrolled at the MTD of 3.0mg/d. No improvement in anemia was seen, possibly because of bone marrow suppression. Consequently, the dose was decreased to 0.5mg/d in 7 subjects (2 remain on 3.0mg). 9 subjects remain on POM (all but 2 at 0.5mg/d. 104 cycles have been given (median, 4/ subject; range, 2-11). 10 subjects, all at ≥2.5mg/d discontinued because of lack of response/ withdrawal of consent (N=5), progression (N=4) or unrelated worsening co-morbidities (N=1). Toxicity: Dose-related bone marrow suppression was the main toxicity. 10/19 subjects had grade-3/-4 neutropenia (N=8) and/or thrombocytopenia (=3) and was only observed at doses ≥2.5mg/d. No substantial bone marrow suppression at 0.5m/d. Non-hematologic toxicity was uncommon at any dose level with grade-3 fatigue at 3.0mg/d in 1 subject. Efficacy: There was clinical benefit in 9 subjects. 7 subjects achieved an IWG-MRT response (Tefferi et al, Blood, 2006) including clinical improvement (CI) in anemia (N=6; rbc-transfusion-independence or hemoglobin increase >2g/dL for ≥2 mo) and/or splenomegaly (N=2; ≥50% reduction of palpable component for ≥2 months). 2 subjects had improved anemia below the IWG-MRT CI-threshold. Clinical benefit occurred after a median of 3.8 mo (range, 2.1-9.2 mo), and only after reduction to 0.5mg/d in 7 responders including both with spleen responses. There were 2 responses amongst 11 subjects receiving ≥2.5 mg/d compared to 7 of 8 subjects receiving '1.0mg/d. These responses occurred a median of 1 cycle after dose reduction (1-3 months). Responses were durable: 8 of 9 responders continue on-study. CONCLUSIONS: In subjects with myelofibrosis, POM doses ≥2 mg/d are associated with moderate to severe bone marrow suppression. Response occurred at doses ≥2 mg/d primarily after dose reduction to 0.5 mg/d where bone marrow suppression was infrequent. The authors suggest 0.5 mg/d as the preferred doses for a phase-3 trial. Disclosures: Litzow: Enzon: Honoraria, Research Funding.

Abstract Abstract 3211 Poster Board III-148 Although autologous stem cell transplantation (ASCT) has become standard of care for many patients with hematologic malignancies, many patients fail to collect a minimum number of CD34 + stem cells to support high dose chemotherapy and ASCT. Recently, plerixafor, a CXCR4 antagonist, was FDA approved for use in combination with G-CSF for autologous peripheral blood stem cell mobilization in patients with NHL or Multiple Myeloma. In February 2009, we commenced a risk adapted approach to the utilization of plerixafor. The study was restricted to patients mobilized with GCSF alone and patients undergoing chemotherapy primed PBSC mobilization were excluded. Peripheral blood stem cell mobilization was commenced with G-CSF at 10 mcg/kg/day. On day 4, a peripheral blood (PB) CD34 count was measured. For patients whose PB CD34 was ≥10/μL, apheresis was commenced the following morning. For patients whose PB CD34 was <10/μL, it was measured again on day 5; if ≥10/μL then apheresis was commenced the following morning. If PB CD34 was <10/μL on day 5, plerixafor (0.24 mg/kg sc) was administered on the evening of day 5 and apheresis was commenced the following day (Group A). In addition, during apheresis, for patients whose collection yield was < 0.5 × 106 CD34/kg, in the absence of instrument failure or problems with the collection procedure, plerixafor was added (Group B). Morning administration of G-CSF and evening dosing of plerixafor continued daily until apheresis was complete. From February to July 2009, 174 mobilization attempts occurred; 27 with chemotherapy and 147 with cytokines alone. The 147 pts who underwent mobilization with cytokines alone are presented here. The underlying diagnosis was as follows: Myeloma 61 pts, NHL 54 pts, Amyloid 17 pts, Hodgkin 10 pts, POEMS 4 pts and 1 pt with a solid tumor. For the entire group the median number of CD34 cells collected was 5.5 × 106 CD34/kg (range 0.1-17). The median number of apheresis was 3 (range 1-12). 67 patients (46%) received plerixafor; 37 patients started plerixafor during mobilization (Group A) and 30 patients during collections due to a poor yield (Group B). 12 pts of the 37 received plerixafor on day 4 because of prior mobilization failure or high risk of mobilization failure and are included in Group A. Table 1 outlines the details of mobilization and collection by groups. By disease category, of the 61 patients with MM, 28 (46%) received plerixafor (8 Group A and 20 Group B). Median apheresis in all the MM pts was 2 (range 1-12) with a total of 6.8 × 106 CD34/kg (2.2-16.7). In the 54 NHL pts, 32 (59%) received plerixafor (24 Group A and 8 Group B). Median apheresis for all pts with NHL was 3 (range 1-7) with a total of 4.6 × 106 CD34/kg (range 0-11.4). Overall, only 7 of 147 (5%) mobilization attempts failed to achieve a minimum of 2 × 106 CD34/kg. This compares to a 22% failure rate prior to institution of this risk adapted approach. In conclusion, implementing this risk adapted approach allows poor mobilizers to be identified promptly and for plerixafor to be initiated during mobilization and collection, thereby reducing the number of mobilization failures. In patients who predictably would not have successful collection based on a PB CD34 <10/μL, addition of plerixafor results in a majority of patients achieving an adequate collection. This risk adapted approach may be more cost effective than reattempting mobilization after a prior failure or utilizing combination G-CSF and plerixafor for upfront mobilization. Table 1. Mobilization and Collection data. All patients N=147 Group A1 N=37 Group B2 N=30 No Plerixafor N=80 PB CD34 day 4 Median 11 0 7 19 Range 0-331 0-7 0-32 0-331 PB CD34 day 5 Median 10 4.5 12 15 Range 0-51 2-9 11-23 9-51 Apheresis Yield Median 5.5 4.4 6.0 6.2 Range 0.1-17 3.1-12.7 3.0-12.2 2-17 Number of Apheresis Median 3 3 5 2 Range 1-12 1-7 4-12 1-8 Days of Plerixafor Median n/a 3 2 n/a Rang 1-7 1-8 1 Group A – Plerixafor initiated prior to apheresis 2 Group B – Plerixafor initiated during apheresis Disclosures No relevant conflicts of interest to declare.