Hogan, William J.

Abstract Abstract 3468 Engraftment syndrome (ES) is a complication of hematopoietic stem cell transplantation classically characterized by fever, rash, diarrhea, weight gain and non-cardiogenic pulmonary edema. Renal failure has been observed but is not considered to be a major part of the syndrome. We have noted that acute renal failure (ARF) is common around the time of leukocyte engraftment in light chain amyloidosis (AL) patients after autologous stem cell transplant (ASCT). We suspect this is due to ES and this retrospective review was conducted to further study this entity. Data were collected from 377 AL patients who underwent ASCT from 7/1997 to 10/2009. Patients who experienced an elevation of serum creatinine (Scr) > 0.5 mg/dl within 4 days of leukocyte engraftment were selected. Patients who carried a diagnosis of ES were also included regardless of Scr elevation. Nephrotoxic insults were reviewed. Vitals were collected. Forty-one patients met criteria. Four patients were found not to have ES, 2 sepsis, 1 allergic interstitial nephritis (AIN), 1 acute cellular rejection. ES was noted in 37 (9.8%) patients, 2 presented with mainly pulmonary ES and 8 had both pulmonary and renal involvement. The degree of renal failure varied from mild and self-limited to severe and requiring dialysis. The renal failure is usually preceded by fever, rash, increasing edema, relative hypotension and low urine sodium (Figure 1). Treatment with glucocorticoids (60 mg/d) was successful in reversing the renal failure in most patients but those with pulmonary involvement required higher doses. Our study showed that ES presents more commonly with renal failure than pulmonary involvement in AL patients. Further complications may be prevented by early treatment with corticosteroids once infection is ruled out. Dosing depends on concurrent pulmonary findings. Distinguishing ES with AIN is difficult as presentations are similar but AIN will continue until the offending drug is removed while ES generally responds quickly to steroids alone. Figure 1. Figure 1. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 3572 High dose melphalan and autologous stem cell transplantation (ASCT) is an effective treatment for light chain amyloidosis (AL) but high treatment related mortality (TRM) limits its use. Both cardiac troponin T (cTnT) and N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) are sensitive predictors of high risk patients. Aim of this study is to compare two models of TRM, one using cTnT and the other BNP. Patients who underwent ASCT between 7/1996 and 7/2009 at the Mayo Clinic were analyzed retrospectively. Variables were chosen for ease of measurement and reproducibility thus echocardiographic parameters were excluded. Each additional risk factor must contribute to a significant increase in TRM. Also, since NT-pro-BNP and cTnT are already highly associated with mortality, the other risk factors must be independent predictors. Univariate analysis revealed serum albumin, B-2-microglobulin, cTnT, NT-pro-BNP, and uric acid were associated with TRM while age, sex, alkaline phosphatase, serum creatinine, CRP, proteinuria were not (Table 1). Multivariate analysis showed albumin and uric acid were independent risk factors to cTnT and NT-pro-BNP (Table 2). Of the 412 patients, 347 (8.9% TRM) could be evaluated by the cTnT, albumin and uric acid (TAU) model and 282 (9.2%) TRM could be evaluated by the NT-pro-BNP, albumin, uric acid (BAU) model. Both models showed increasing TRM with additional risk factors beyond 1 risk factor (Table 3 and 4). Albumin and uric acid were found to be significant contributors in both models. Patients with elevated cTnT alone had a 0% TRM vs 23.4% if they had 1 additional risk factor, p = 0.03. Similarly, TRM was 3.7% in patients with elevated NT-pro-BNP alone but 18.0% if they had 1 other risk factor, p = 0.05. NT-pro-BNP and cTnT could not be used in the same model because cTnT becomes non-significant. Both models were superior to visceral organ involvement which had TRM of 5.3% with 1, 9.2% with 2 and 16.7% with 3 organ involvement. Both models were also predictive of overall survival (Figure 1 and Figure 1b). Our results show that these models show that albumin and uric acid with either cTnT or NT-pro-BNP can accurately predict TRM in AL patients undergoing ASCT. Multivariate analysis shows that the NT-pro-BNP containing model may be superior since cTnT loses it significance when added to the model. Our results suggest these models could be very helpful in identifying high risk patients not suitable for ASCT. Figure 1a Overall survival evaluated by Kaplan-Meier method on 347 patients using the TAU model. Mortality increased significantly with the number of risk factors, p < 0.001. Solid line represents patients with 0 risk factors, dotted line represents patients with 1 risk factor, dashed line represents those with 2 risk factors and dotted dashed line represent those with 3 risk factors. Figure 1a. Overall survival evaluated by Kaplan-Meier method on 347 patients using the TAU model. Mortality increased significantly with the number of risk factors, p < 0.001. Solid line represents patients with 0 risk factors, dotted line represents patients with 1 risk factor, dashed line represents those with 2 risk factors and dotted dashed line represent those with 3 risk factors. Figure 1b Overall survival evaluated by Kaplan-Meier method on 282 patients using the BAU model. Overall survival was significantly longer in patients with less risk factors, p < 0.001. Solid line represents patients with 0 risk factors, dotted line represents patients with 1 risk factor, dashed line represents those with 2 risk factors and dotted dashed line represent those with 3 risk factors. Figure 1b. Overall survival evaluated by Kaplan-Meier method on 282 patients using the BAU model. Overall survival was significantly longer in patients with less risk factors, p < 0.001. Solid line represents patients with 0 risk factors, dotted line represents patients with 1 risk factor, dashed line represents those with 2 risk factors and dotted dashed line represent those with 3 risk factors. Table 1. Patient characteristics Control TRM p-value N 318 29 Age 58 (25–73) 55 (35–75) 0.54 Sex (male) 58.2% 72.4% 0.13 Albumin (g/dl) 2.7 (0.8–4.4) 2.2 (0.8–3.7) 0.02 Alkaline phosphatase (U/L) 89 (28–1014) 86 (31–1394) 0.22 b2m (mg/ml) 2.6 (1.0–35.1) 3.2 (1.3–15.2) 0.007 NT-pro-BNP (pg/ml) 564 (12–35000) 1661 (21–35001) 0.03 CRP (mg/L) 0.3 (0.01–16.6) 0.3 (0.05–3.2) 0.34 cTnT (ng/ml) 0.01 (0–1.0) 0.03 (0.01–0.22) <0.001 Scr (mg/dl) 1.1 (0.4–12) 1.2 (0.8–2.3) 0.09 Proteinuria (g/d) 3.4 (0.01–35.4) 5.1 (0.1–20.5) 0.10 Uric acid (mg/dl) 6.2 (1–14.8) 7.5 (3.7–13.2) 0.02 Organ Involvement 1 94.7% 5.3% 0.04 2 90.7% 9.3% 3 83.3% 16.7% Table 2. Multivariate analysis using proportional hazard model cutoffs >Risk Ratio >p-value Model TAU cTnT 0.04 ng/ml 2.78 0.01 Albumin 3.3 g/dl 3.11 0.03 Uric acid 8.5 mg/dl 2.69 0.02 Model BAU NT-pro-BNP 1270 pg/ml 3.77 0.003 Albumin 3.3 g/dl 3.53 0.04 Uric acid 8.5 mg/dl 3.11 0.03 Table 3. Model of cTnT, albumin and uric acid TAU Risk Factors n TRM p-value Risk Ratio 0 69 2.9% 1 205 5.9% 0.33 2 61 16.4% 0.009 2.98 3 12 41.7% 0.05 8.52 Table 4. Model of NT-pro-BNP, albumin and uric acid BAU Risk Factors >n >TRM >p-value >Risk Ratio 0 28 0% 1 161 5.6% 0.20 2 82 14.6% 0.02 2.7 3 11 45.5% 0.01 10.8 Disclosures: Kumar: Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Lacy:Celgene: Research Funding.

Abstract Abstract 3557 Introduction: Autologous stem cell transplantation for patients with amyloidosis results in high reported hematologic and organ response rates compared with conventional chemotherapy. Patients: Four-hundred and thirty-four patients have undergone transplantation between March 8, 1996, and April 13, 2010 Table 1. Clinical parameters seen in patients with amyloid are given in Table 2. The overall day-100 mortality seen in this group of patients is 44 of 434 patients (10%). Results: The most important determinant of outcome is stage defined by BNP and troponin levels. Figure 1 demonstrates the survival for patients for all 3 cardiac stages. Troponin <.035; NT-proBNP <332. Stage 1 both low, Stage 3 both elevated. The survival of all patients based on whether they achieved a complete response, a partial response (>50%), or no response was analyzed. Median survival has not been reached for the complete response group, is 107 months for the partial response group, and is 32 months for the no response group (p<0.0001). Figure 2, divides the patients at the median dFLC level of 13.5 mg/dL demonstrating that for patients with a higher level of free light chain, the median survival is 87.6 months and has not been reached for those with a lower level of free light chain. A proportional hazards model for variables that impact on survival was done in all patients, and the only relevant predictor of outcome was stage (p<0.0001). When the same analysis was performed using a landmark of 6 months, the only predictor of outcome was stage (p=0.0005). When best response was incorporated into the landmark model, it was the strongest predictor of survival. The amyloid stage predicted survival (p= 0.0005), and the best response to therapy (p <0.0001). When the same analysis was performed in the entire group of 434, stage and best response each remained significant (p<0.0001). Discussion: There is a high response rate associated with high-dose therapy that was not observed in the melphalan and prednisone era. For eligible patients who can be transplanted safely, high-dose melphalan is an effective therapy for many patients with amyloidosis. Best response and stage at diagnosis are the best predictors of overall survival. Disclosures: Lacy: Celgene: Research Funding. Dispenzieri:Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding.

Abstract Abstract 5226 Background Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder with overlapping features between myelodysplastic syndromes and myeloproliferative neoplasms. Allogeneic stem-cell transplant (SCT) is considered to be a potentially curative option (Eur J Haematol. 2013; 90:355); with karyotype and comorbidity index (CI) being independent prognostic factors. The role of newer CMML prognostic models remains to be elucidated. We carried out this study to analyze the predictive value of the Mayo model (Leukemia 2013; 27:1504) in assessing transplant outcomes for patients with CMML. Methods After due IRB approval, 25 patients with WHO-defined CMML that underwent allo-SCT at Mayo Clinic from 1992 through 2013 were identified. All patients underwent bone marrow examination and cytogenetic evaluation at diagnosis. Clinical features including status at transplant, graft-versus-host disease (GVHD) prophylaxis, donor-recipient HLA-matching, donor-recipient blood types and CMV status were documented. Patients were evaluated for development of GVHD, disease relapse, remission status, and death from all causes. We evaluated the prognostic relevance of clinical and laboratory parameters including those previously identified by the MDAPS (Blood 2002;99:840), Spanish cytogenetic stratification (Haematologica 2011;96:375), and the recently described Mayo model Results Among 25 study patients, 14 (56%) were males and 15 (60%) had WHO defined CMML-1 (6-symptomatic/transfusion dependent, 3-monosomy 7). The median age at transplant was 51 years (range, 18-66 years). Graft sources included: 19 (76%) peripheral blood, 5 (20%) bone marrow, and 1 (4%) double umbilical cord blood. Ten (40%) patients received a reduced intensity conditioning. At last follow up, 15 (60%) deaths were documented while the remainders are alive and disease free. There were six (25%) post-transplant relapses all resulting in mortality. The 5-year OS was 42% and the 5-year non relapse mortality was 35%. Based on the Mayo model, 15 (60%) patients received a high-risk prognostication, 6 (24%) were intermediate and 3 (12%) were low. In an univariate analysis that included: demographics, blood counts at diagnosis and transplant, WHO classification (p=0.19), Spanish karyotypic stratification (p=0.67), prognostication according to the MDAPS (p=0.35) and Mayo model, disease status at transplant, SCT comorbidity index (p=0.06), graft sources, transplant conditioning regimens (p=0.08), development of acute (p=0.64) and chronic GVHD (p=0.06); thrombocytopenia at diagnosis (p=0.04), disease status at transplant (p=0.02), and a high risk prognostication using the Mayo model (p=0.01) were statistically significant. On a multivariable analysis only high risk prognostication by the Mayo model (p=0.02) retained its negative prognostic impact. In an univariate analysis for relapse-free survival, risk stratification by the Spanish cytogenetic system (p=0.04) and the Mayo model were prognostic (p=0.01), with the high risk prognostication by the Mayo model retaining its negative prognostic impact (p=0.01). Conclusions Allogeneic SCT remains a viable treatment option for patients with CMML. The Mayo model serves as a valuable tool, helping with the identification of high risk CMML patients. These patients seem to benefit from allo-SCT in comparison to non-transplant therapeutic options. Given the smaller sample size, validation in a larger patient cohort is needed. Disclosures: No relevant conflicts of interest to declare.

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.