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Abstract Background: Acute myeloid leukemia (AML) is an aggressive blood cancer with a wide range of response and relapse rates using standard chemotherapy combining anthracycline plus cytarabine (7+3). The stem cell receptor tyrosine kinase KIT is expressed on more than 10% of blasts in 95% of relapsed AML cases and mediates leukemic proliferation and has anti-apoptotic effects (Domen and Weissman 2000). AML with high KIT expression is associated with poorer outcome (Del Poeta, Venditti et al 2003). Goals: To study the efficacy and safety of combination 7+3 and nilotinib in patients (pts) with AML and KIT expression. Primary goal is to determine the complete response (CR) rate; while secondary goals include 2-year overall survival (OS) and disease free survival (DFS) in addition to safety. Methods: A single arm, Phase II study, enrolled pts at Mayo Clinic (MN and AZ). Appropriate IRB was obtained and study was registered (NCT 01806571). Pts were enrolled if they were newly diagnosed with AML with KIT (CD117) expression of ≥ 20% on myeloblasts by flow cytometry. KIT mutations were allowed. Nilotinib 300 mg twice daily was given on days 4-14 of induction and consolidation; and continuous daily maintenance therapy for up to 2 years. Cytarabine 100 mg/m2/day continuous IV x7 days plus daunorubicin 60 mg/m2 IV daily x3 days were used for induction, while consolidation used standard cytarabine 3 gm/m2 twice daily days 1, 3, 5 for a total of 4 cycles. This is a Simon 1-stage design with a safety analysis after enrolling 12 pts, and an interim analysis after enrolling 18 out of 43 pts (Al-Kali, ASH 2015) recommended to continue study accrual. Results: i)- Demographics: Thirty four pts were enrolled from July 2013 to June 2017. Median age was 59 years (range 24-69) with 71% being male. Median laboratory findings include hemoglobin of 8.8 gm/dL, platelets of 56 x109/L, white blood count of 3.3 x109/L (0.4-125), and peripheral blood blasts 17 %(0-94%). Cytogenetics were normal in 43% of the pts and favorable cytogenetics were seen in 6%(inv 16). FLT3 gene testing was done on 26 pts and was positive in 13%. KIT gene sequencing (exon 8, 9, 10, 11, 17) revealed pathogenic mutation in 1/28 cases (4%). ii)- Clinical outcome Out of all 34 pts enrolled on the study, 18 (53%) achieved CR (or CR with incomplete platelet recovery) with a median CR duration of 21.8 months. Of 26 evaluable pts, the overall CR rate was 69%. 4 of the 18 pts (22%) who achieved remission needed a second induction. One pt died due to liver failure (had only one dose of nilotinib and toxicity was attributed to daunorubicin). 13 (38%) pts proceeded to allogeneic stem cell transplant (HSCT), 12 of whom are alive and none were able to initiate nilotinib maintenance. Only 6 (1 had HSCT) out of 34 (18%) pts relapsed after achieving CR. Median DFS was 45.8 months, while median OS was 42.4 months. 2-year DFS and OS were 58% and 72%, respectively. iii)- Safety Thirty four pts were evaluated for adverse events (AE). Fourteen pts had G4 non-hematological AEs, including fourteen G4 AEs related to infection, 2 with electrolyte imbalances, 1 heart failure, 1 elevated bilirubin, 1 elevated lipase, and 1 jejunal hemorrhage. One patient had G5 liver failure. Most common (>20%) G3 non-hematological AEs were febrile neutropenia (56%), hypophosphatemia (21%), elevated ALT (21%) and hypertension (21%). Conclusion: Combination daunorubicin and cytarabine with nilotinib (DATA) appears to be safe and effective. Final results show an acceptable safety profile with most common AE being infection. Thirty day mortality was low (3%). DATA regimen has comparable CR rates of 53% (intent to treat) and 69% in evaluable pts. Relapse rates were very low at 18% with durable responses and encouraging survival rates. Figure. Figure. Disclosures Al-Kali: Novartis: Research Funding. Tibes:Novartis: Research Funding. Palmer:Novartis: Research Funding.

Abstract Background: Fludarabine plus busulfan (FB) and fludarabine plus melphalan (FM) are two commonly used reduced intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (SCT). A recent analysis showed that both regimens had similar overall survival (OS) but relapse incidence (RI) was significantly higher with FB with a trend towards higher non-relapse mortality (NRM) in FM (Baron et al., Cancer 2015). However, that cohort included patients treated with oral and intravenous busulfan without pharmakokinetic targeting of intravenous which may impact anti-leukemic activity. Aim: Compare transplant related outcomes of FB vs. FM using intravenous (IV) busulfan targeted to the area under the curve (AUC). Methods: After due IRB approval, patients with acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) receiving RIC-SCT from 2008-2014 were identified. All baseline and laboratory features were retrospectively extracted. Busulfan dose in FB was 0.8 mg/kg IV for 10 doses with therapeutic AUC target of 900-1500 mcmol/L (min). All patients received T-cell replete grafts. Categorical and continuous variables were compared using Pearson's chi-squared and Wilcoxon/Kruskal-Wallis, respectively. Survival estimates were calculated using the Kaplan-Meier method and curves were compared using the log-rank test. Cumulative incidence was computed as competing events using Grey's model. Univariate and multivariate analyses were performed using Cox regression modeling. Results: A. Baseline characteristics and AUC monitoring: 134 pts were identified (47 FB and 87 FM). Median follow up of the entire cohort was 40 months (0-63.3) and at last follow up, 60% and 29% have died or relapsed, respectively. Baseline characteristics stratified according to conditioning regimen are shown in table 1. Younger age (60 yrs FB vs. 61 yrs FM, p = 0.015) and a trend towards a higher CMV R-/D- status (28% FB vs. 14% FM p = 0.064) were the only significant differences identified. All patients in the FB group received intravenous busulfan and 46/47 patients had evaluable AUC data with a range of 732-1354 mcmol/L (min). A total of 19 patients were outside of range, all <900 mcmol/L (min) and required a median dose increase of 28.1% (3.3-50.2%) B. Engraftment and toxicity data: The median time for platelet engraftment was 19 days (0-48) for FB vs. 16 days (14-183) for FM (p = 0.0023) whereas the median time to absolute neutrophil count (ANC) engraftment was 18 days (7-30) for FB and 15 days (11-40) for FM (p = 0.077). Cumulative incidence of grade II-IV, III-IV acute GVHD and chronic GVHD at 2-yr was 57.3%, 11% and 52.8% for FB and 48.6%, 17% and 63.4% for FM (p = 0.73, 0.4 and 0.21, respectively). Two patients in the FM group died of cardiac causes (heart failure and sudden cardiac arrest). No cases of sinusoidal obstructive syndrome were observed in either arm C. Transplant outcomes: A significantly higher 2-yr relapse incidence (RI) was associated with FB vs. FM at 35.6% vs 17.3%, respectively (p = 0.0058). 2-yr progression free survival (PFS) was also significantly lower in the FB vs. FM at 51.2% vs. 65.1%, respectively (p 0.031). However, 2-yr OS and NRM was similar for FB vs. FM (53.1% and 22.9% vs 63.9% and 21.9%, respectively p = 0.26 and 0.89). Necessitating a dose adjustment based on AUC did not increase the risk for relapse or affect NRM. In multivariate analysis, FB was associated with increased RI with hazard ratio (HR) 2.29 (1.07-4.88; p = 0.033). Other factors significantly associated with RI on multivariate analysis were secondary/therapy related disease with HR 2.84 (1.34-6.02; p = 0.0067) and CR1 vs. other with HR 0.39 (0.17-5.32; p = 0.019). The significance of the results remained unchanged after exclusion of MDS patients (data not shown) Conclusion: Despite AUC dose adjustment, FB compared to FM was associated with increased RI with a similar OS and NRM. AUC dose adjustment did not impact transplant outcomes and its routine use in RIC should be further evaluated. Given the wide use of FB as a conditioning regimen, these important observations should be prospectively studied in a randomized fashion. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Novartis: Research Funding. Wolf:Janssen Scientific Affairs, LLC: Consultancy.

Abstract Background: Adult T-cell acute lymphoblastic leukemia / lymphoma (T-ALL) is an rare and aggressive hematological malignancy with overall survival (OS) according to the UKALL XII/E2993 of 48% at 5 years (Marks et al, Blood 2009). Over the last decade, the incorporation of L-asparaginase, dose intensification (similar to pediatric protocols), availability of newer agents such as clofarabine (Dec 2004) and nelarabine (Oct 2005) have been shown to improve outcomes. We carried out this study to see if the above mentioned changes in treatment have translated to an OS benefit. Methods: After due IRB approval, adults diagnosed with T-ALL from 1990-2014 at Mayo Clinic were identified. All clinical and pathologic data was retrospectively reviewed Comparative analysis was performed based on year of diagnosis before and after 2005 (Group 1, diagnosis prior to 2005, and Group 2, diagnosis post 2005). Survival was estimated using the Kaplan-Meier Method and log-rank test. Chi-square test was used to compare variables. Results: A. Patient Characteristics: Between 1990 and 2014, a total of 92 consecutive patients (pts) with T-ALL were identified. Median age at diagnosis was 33 years (range; 18-88 years) with 72% males. Distribution of pts by year of diagnosis was as follows: Group 1(n= 47) (51%), and Group 2 (n=45) (49%). Median overall survival was 97.2 months. Median follow up for Group 1 was 50 months, during which time 23 (39%) deaths were documented, and 22.8 months (0.9 - 115.4) for Group 2 at which time19 deaths (42%) were documented (p= 0.04). Pts in Group 2 were older than Group1 (median age 41 vs 27 years (p= 0.004). Apart from age, the two groups were similar in other characteristics (Table 1). B. Therapy received by patient groups: We observed a high use of L-asparaginase containing regimens in Group 1 vs Group 2 [35(74%) pts vs 19 (42%), p=0.0013]. In contrast there was an increase in use of Hyper-CVAD in Group 2; 23(51%) vs. 3 (6%) (p<0.0001). There was no difference in the use of intensive pediatric protocols (p=0.11). There was a trend of increased use of nelarabine in Group 2, however clofarabine usage was not different (p=0.09, and p=0.6 respectively) (Table1). Allogenic stem cell transplant was offered more in Group 2 compared to Group 1, 16 (36%) patients vs. 10 (21%) patients (p=0.0009). In contrast, 7 (19%) patients underwent autologous transplantation in group 1 vs. none in group 2 (p=0.0009). C. Overall outcome by patient groups: We did not observe any difference in CR, or relapse rates among the two groups. The median OS and time to relapse were also not statistically different among Group 1 and 2 [102.6 vs 61.8 months Figure A, and 7.1 vs 14.1 months respectively]. Furthermore, age adjusted survival analysis was also not statistically significant. Conclusion: In this large cohort of adult T-ALL patients, in spite of significant advances in treatment strategies over the last two decades, we observed no difference in overall and relapse free survival prior to and after 2005. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Celgene: Research Funding. Thompson:Kite Pharma: Research Funding. Witzig:Spectrum: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Valeant Pharma: Equity Ownership.

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: Myelodysplastic syndromes (MDS) are clonal hematological diseases which present with cytopenias. Hematopoietic cell transplantation is usually limited to fit patients with higher risk MDS and donor availability. Hypomethylating agents (azacitidine and decitabine) have been the mainstay option for the management of MDS with different clinical efficacy in low versus high risk MDS trials. No trials have compared the two agents. Aim: To conduct a systematic review and network analysis comparing the efficacy of azacitidine to decitabine. Methods: The protocol of the systematic review was developed a priori. A comprehensive search of several databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Scopus) was conducted from each database's earliest inception through November 20th, 2014 without language restrictions. Trials enrolling adults diagnosed with MDS who received hypomethylating agents (azacitidine or decitabine) therapy were included. Studies were screened by two independent reviewers and differences were resolved by consensus. The Cochrane Risk of bias tool was used to appraise the trials. Random effects model was used to pool relative risks (RR) of outcomes (overall survival, overall response rate, hematologic improvement and grade 3 or 4 toxicity). Adjusted indirect comparisons were used to estimate RR for indirect comparisons (Glenny AM, et al. Health Technol Assess. 2005). All statistical analyses were conducted using STATA, version 13 (StataCorp LP, College Station, TX). Results: Only four trials met the eligibility criteria (Figure 1). Two trials compared Azacitidine (75mg/m²/day SC x 7 days) to the best suppurative care (BSC) and included 549 patients (278 azacitidine and 271 BSC, age average: 69; range: 31-92), and the other 2 compared decitabine (15 mg/m² IV q 8 hours x9) to BSC and included 403 patients (208 Decitabine and 195 BSC, age average: 69.7; range: 60-90) (Table 1). The proportion of patients with intermediate-2 and high-risk myelodysplastic syndrome (based on International Prognostic Scoring System (IPSS)) in trials comparing decitabine to BSC was 82.21% and 83.08%; respectively, and in trials comparing azacitidine to BSC was 62.59% and 61.26%; respectively. The risk of bias was moderate overall. Compared to BSC, azacitidine was significantly associated with lower risk of death (RR=0.83, 95% CI: 0.74-0.94, p=0.002) whereas the effect of decitabine did not reach statistical significance (RR=0.88, 95% CI: 0.77-1.001, p=0.053). Both drugs were superior to BSC in terms of partial and complete response. Head to head comparisons were not statistically significant (except for the outcome of complete response where low certainty evidence suggested that azacitidine treated patients were less likely to have complete response compared to decitabine (RR=0.11, 95% CI= 0.01, 0.86, p=0.04). (Table 2). Conclusion: Azacitidine and decitabine are both superior to BSC. The available indirect evidence comparing the two agents warrants low certainty and cannot reliably confirm superiority of either agent. Head-to-head trials are needed. In the meantime, the choice of agent should be driven by patients' preferences, drug availability and cost. Table 2. Results of meta-analysis Outcome Azacitidine VS. Decitabine Azacitidine VS. BSC Decitabine VS. BSC RR LCI HCI P value RR LCI HCI P value RR LCI HCI P value Death 0.95 0.79 1.13 0.54 0.83 0.74 0.94 0.002 0.88 0.77 1.001 0.05 Complete response 0.11 0.01 0.86 0.04* 2.56 1.44 4.58 0.001 23.46 3.22 170.84 0.002 Partial response 0.35 0.04 3.03 0.34 4.91 2.27 10.63 <0.0001 14.02 1.87 105.08 0.01 Major erythroid improvement 0.47 0.03 8.37 0.60 6.37 3.93 10.33 <0.0001 13.67 0.79 235.57 0.07 Major platelet improvement 1.51 0.30 7.56 0.62 4.80 2.98 7.70 <0.0001 3.19 0.68 14.89 0.14 Major neutrophil improvement 2.89 0.56 14.82 0.20 2.63 1.68 4.12 <0.0001 0.91 0.19 4.38 0.907 Hematologic improvement 0.25 0.06 1.09 0.07 2.18 1.67 2.85 <0.0001 8.62 2.05 36.32 0.003 Anemia 1.18 0.53 2.63 0.69 0.89 0.75 1.06 0.198 0.76 0.35 1.66 0.49 Neutropenia 0.99 0.75 1.30 0.92 1.87 1.63 2.14 <0.0001 1.90 1.49 2.42 <0.0001 Thrombocytopenia 0.87 0.64 1.18 0.37 1.63 1.43 1.86 <0.0001 1.87 1.43 2.45 <0.0001 Infection 1.13 0.52 2.43 0.76 1.25 0.60 2.60 0.55 1.11 0.87 1.42 0.41 *These results warrant low certainty due to imprecision (very small number of events) and are driven by 14 patients achieving complete response in BSC arm in one trial. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background Chronic myelomonocytic leukemia (CMML) is a clonal hematologic disorder that was classified by the World Health Organization (WHO) as a myelodysplastic/ myeloproliferative overlap disease. Cytogenetic abnormalities have a significant prognostic role in many hematologic neoplasms, but their prognostic value in CMML has been debatable. Recently, monosomal karyotype (MK) has been reported to be a marker of poor prognosis in patients with myelodysplastic syndromes (MDS) and primary myelofibrosis, but its value in CMML is unknown. Aim To study MK effect on clinical outcome for patients diagnosed with CMML Method A retrospective study of all cases diagnosed with CMML at Mayo Clinic Rochester between 1994 to 2011 was performed. Only pts with complete cytogenetic analysis at presentation to our institution were included. MK was defined as the presence of ≥ 2 autosomal monosomies or one autosomal monosomy with at least one structural abnormality (Breems et al, JCO 2008). CK was defined as the presence of at least 3 chromosomal abnormalities. 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 A total of 262 pts diagnosed with CMML had available cytogenetic data at diagnosis. Median age was 72 years, 176 (67%) were male. Median hemoglobin 10.5 g/dL, white blood cells (wbc) 12 x109/L, platelet 89 x109/L, peripheral blood (PB) blast 0, and bone marrow (BM) blast 4%. CMML2 was seen in 9% while 47% were proliferative (wbc >13). Leukemic transformation was documented in 34 pts (13%). Median overall survival was 513 days. Cytogenetic (CG) analysis was diploid in 167 pts (64%). Trisomy 8 was the most frequent cytogenetic abnormality at 8% (22), followed by complex karyotype (CK) 5% (14), then -7 at 4% (10) and MK 3% (7, six of which were also CK). Comparing pts with diploid CG to other categories indicates: to abnormal CG pts had lower wbc (0.001), PB blasts (p<0.0001), and BM blasts (p=0.0001); to CK pts had lower PB blasts (p=0.003) and higher platelets (p=0.03); to -7 pts had lower wbc (p=0.005), PB blast (p=0.0004), BM blasts (p=0.03) and higher platelets (p=0.03); to +8 pts had lower PB blast (p=0.02) and BM blasts (p= 0.01); no difference was noted when compared to MK. Median OS was statistically significantly worse in MK+ vs MK- (24 vs 527 days, p= 0.002), but not in other comparisons: -7 vs others (250 vs 527 days, p=0.2), CK+ vs CK- (256 vs 527 days, p=0.05), diploid vs others (570 vs 365 days, p=0.1), +8 vs others (312 vs 527 days, p=0.1). Pts with MK+ only or MK+CK+ did worse than CK+ only or other groups (4, 63, 304, 527 days, respectively, p<0.0001). On a multivariate analysis, MK+ (in addition to platelet, BM blast, hemoglobin, and wbc) did have an impact on OS (p=0.0004), while CK+, -7, +8, diploid CG, age, PB blast did not. Conclusion Cytogenetic abnormalities were not frequent findings in pts diagnosed with CMML (36%), but did affect wbc, PB and BM blasts. The most common cytogenetic abnormality was +8 while MK was present at 3% (less than published data in MDS). Only MK predicted statistically significant shorter mOS between all other cytogenetic categories on both univariate and multivariate analysis. This finding needs to be validated by larger cohorts of pts due to its rare occurrence in CMML. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction: Disease relapse remains one of the major causes of treatment failure in hematopoietic stem cell transplant (HSCT) following reduced-intensity conditioning (RIC) regimens. Donor chimerism assessment early after HSCT may help identify patients at risk for relapse who may benefit from additional therapeutic interventions but its precise role in this setting is unclear. In addition, the differential impact of conditioning regimen is not well studied. Aim: 1. Study the impact of early full T-lymphocyte chimerism (T-lymphocyte chimerism ≥ 90% on day 30 to 60) on relapse incidence (RI) and acute graft versus host disease (aGVHD) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following RIC-HSCT. 2. Looking at the tempo of achievement of complete donor T-lymphocyte chimerism based on the two most common RIC regimens, Fludarabine/Melphalan (FM) and Fludarabine/Busulfan (FB). Method: After IRB approval, patients with AML or MDS who underwent RIC-HSCT with FB or FM between 2008 and 2014 at our institution were identified. Post-transplantation CD3 (lymphocyte) and CD33 (myeloid) donor chimerism were measured per protocol using PCR-based analysis of short tandem repeats. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon / Kruskal-Wallis, respectively. Survival estimates were calculated using the Kaplan-Meier and log-rank test. RI was estimated accounting NRM on a competing event analysis using Grey's model. Cox proportional regression was used to compute hazard ratios (HR). Results: Baseline characteristics: Out of 134 patients who received FM or FB, 75 patients had evaluable early sorted chimerism data. 42 and 33 patients received FB and FM, respectively. Patient, disease and transplant variables were balanced in both FM and FB (Table 1). The median follow up of the cohort was 37 months (2.4-43) and at last follow up 29.1% of patients relapsed and 59% died. All patients achieved early complete myeloid chimerism whereas T-lymphocyte chimerism was complete in 50 patients and mixed in 25 patients. Characteristics of early lymphocyte chimerism by status are shown in table 1. Notably, likelihood of achieving complete T-lymphocyte chimerism ≥ 90% at 60 days was 100% versus 47% in FM and FB respectively (p <0.0001). Acute graft versus host disease: There was no significant difference in incidence of grade II-IV aGVHD between patients with full early donor T-lymphocyte chimerism in comparison to those with early mixed donor chimerism (46% vs. 48%, p =0.87). Impact of full chimerism and conditioning regimen on RI and overall survival (OS): Among the entire cohort, patients achieving early full T-lymphocyte chimerism had a significantly lower RI compared to those with mixed chimerism with a HR of 0.38 (CI 0.14-0.97; p=0.044) but OS was not significantly different with HR 0.69 (CI 0.33-1.51; p=0.34). In patients conditioned with FB, there was no difference in 2-year RI between complete or mixed early T-lymphocyte chimerism at 38.2% and 40.7% respectively (p = 0.9). After FM conditioning, all patients achieved early T-lymphocyte chimerism and the 2-year RI was 6.9%. Achievement of early complete lymphocyte chimerism post FB in comparison to FM was associated with significantly higher risk of relapse (HR 8.6 CI 2.07-57, p=0.0025). Furthermore, there was a trend towards worse OS with FB vs. FM with a median of 23 vs. 44 months, respectively (p = 0.058). Conclusion: Similar to prior reports, we observed that full T-lymphocyte chimerism is associated with decreased relapse risk without an increase in aGVHD. Our findings also suggest that RIC with FM yields a higher incidence of early complete T-lymphocyte chimerism and is significantly associated with decreased risk of relapse compared to FB. There was a greater risk of relapse in the FB group, even among those achieving early complete donor lymphoid chimerism. This needs further validation given the small sample size. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Abstract Background The impact of cytomegalovirus (CMV) infection on the risk of relapse after Hematopoietic Cell Transplantation (HCT) remains controversial, with some studies demonstrating lower risk (Green et al, Blood 2013), while others demonstrating no impact (Schmidt-Hieber et al, Blood 2013), or lower relapse risk only in myeloablative (MA) (Manjappa et al, BBMT, 2014) or in reduced intensity conditioning (RIC) (Cichocki et al, ASH 2014) HCT. Furthermore, the majority of studies have used antigenemia for CMV monitoring, while there is limited data with the use of Quantitative Nucleic Acid Testing (QNAT). Aim To determine the impact of CMV infection, as detected by QNAT, on transplant-related outcomes for patients with acute myeloid leukemia (AML), stratified by MA or RIC HCT. Methods After IRB approval, consecutive adults with AML who underwent allogenic HCT from HLA-matched peripheral blood (PB) grafts at our institution between 2006 and 2014 were retrospectively reviewed. All grafts were T-cell replete. Early CMV infection was defined as any positive CMV result by PCR assay during the first 100 days post HCT. Relapse incidence (RI), non-relapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) were compared between patients with and without CMV infection, and stratified according to MA or RIC. DFS and OS were estimated using the Kaplan-Meier method, and compared with log-rank test. Cumulative incidence of relapse and NRM were analyzed as competing events, using Gray's test. Multivariable analyses adjusting for patient's age, disease status at transplant, cytogenetic risk, and ABO incompatibility were performed using Cox's proportional hazards regression, and the Fine and Gray approach. Results A total of 190 consecutive patients, including 94 (49%) MA and 96 (51%) RIC HCT were analyzed. Patients, disease, and transplant characteristics are shown in table 1. Of the 94 MA HCT (median age 45 y, 50% male), 66 (70%) received total body irradiation. After a median follow up of 18 m, 36 (38%) CMV infection, 16 (17%) relapses, 22 (23%) NRM and 35 (37%) deaths occurred in the MA group. Median time to CMV infection and to relapse in this group was 38 (range 8-241) and 140 (29-1690) days, respectively. Among the recipients of MA HCT, patients with early CMV infection showed no difference in the RI (figure 1), but had a significant trend towards higher NRM and significantly lower DFS and OS in both univariate and multivariable analysis (figure 2) (P values shown in table 2). Among 96 RIC HCT (median age 59 y, 56% male), fludarabine plus melphalan was used in 62 (65%) and fludarabine plus busulfan in 34 (35%) patients. In this group, early CMV infection occurred in 33 (34%), relapse in 25 (26%), NRM in 25 (26%), and deaths in 46 (48%) patients after a median follow up of 21 m (1-91 m). Among the recipients of RIC HCT, median time to CMV infection and to relapse was 40 (17-175) and 291 (19-1971) days, respectively. In the RIC group, early CMV infection was associated with a significant trend towards lower RI (figure 1) and higher NRM in both univariable and multivariable analysis, but no difference in DFS and OS (figure 2). Conclusion Our study of a large homogenous group of AML patients who underwent a uniform HLA-matched PB HCT demonstrates a significantly lower risk of relapse associated with early CMV infection detected by QNAT following RIC, but not MA HCT. Early CMV infection in MA HCT is associated with higher NRM and therefore inferior survival, whereas in the RIC HCT, there is no impact on survival as the benefit of lower relapse is offset by the higher NRM. Table 1. Patients, disease and transplant characteristics according to CMV infection All Patients Patients with CMV Viremia Patients without CMV Viremia P value Patients, no (%) 190 (100) 69 (36) 121 (64) - Median age, y (range) 54 (18-72) 54 (26-70) 54 (18-72) 0.75 Male Patients, no (%) 104 (55) 30 (43) 74 (61) 0.02 D/R CMV Serostatus, no (%) <0.0001 -/- 29 (15) 1 (1) 28 (23) +/+ 64 (34) 35 (51) 29 (24) +/- 13 (7) 1 (1) 12 (10) -/+ 84 (44) 32 (47) 52 (43) Conditioning 0.65 MA 96 (51) 33 (48) 63 (52) RIC 94 (49) 36 (52) 58 (48) Disease status at Transplant 0.96 CR1 129 (68) 46 (67) 83 (69) CR2 34 (18) 13 (19) 21 (17) Other 27 (14) 10 (14) 17 (14) Cytogenetic 0.65 Favorable 8 (4) 2 (3) 6 (5) Intermediate 130 (68) 46 (67) 84 (69) Unfavorable 52 (28) 21 (30) 31 (26) Disclosures Al-Kali: Novartis: Research Funding.

Background: Hematopoietic stem cell transplantation (HCT) remains the most effective postremission therapy for high-risk acute myeloid leukemia (AML). FMS-like tyrosine kinase3 (FLT3) mutations occur in about 30% of patients with cytogenetically normal AML. FLT3-ITD (internal tandem duplications) mutations are associated with short-lived remissions and poor outcomes. These adverse effects can be offset by allogeneic HCT in first complete remission (CR1). We carried out this study to get a real world perspective on feasibility of allogeneic HCT in CR1 for FLT3-ITD mutant AML patients. Methods: The Mayo Clinic AML database was queried for all patients that had tested positive for the FLT3 ITD, from January 2003 to December 2014. 75 patients were identified, of which 28 (37%) underwent allogeneic HCT in CR1. 12 were excluded as they were transplant ineligible from an age standpoint, 6 patients actually had MDS and 2 were excluded for primary induction failure. Clinical and outcomes data were abstracted retrospectively. Results: 29 patients were included in the final analysis, with a median age of 57 years (range 21-68), 38% males. Median time from diagnosis to last follow up was 339 days. 24(83%) had normal cytogenetics. 26(90%) received treatment with anthracycline + cytarabine based therapy, 3(10%) were enrolled on a clinical trial. 25(87%) patients went on to receive consolidation therapy. 22 (75%) of the patients relapsed after achieving a CR1, with a median time to relapse of 134 days (range 27-1710 days). Only 8 (26%) of the 22 patients were able to achieve a CR2 with salvage chemotherapy, of which 6 (75 %) successfully underwent allogeneic HCT.2 (25%) out of 8 patients received FLT3 inhibitor in 1st relapse. We then assessed the reasons why relapsed patients did not undergo HCT in CR1. The most common being; relapse during evaluation/work up for HCT in 8(27%) patients, 5 (17%) had comorbidities that precluded HCT, 3 (10%) were never referred for HCT due to personal preferences. At last follow up 19(65%) patients were dead. Conclusion: While allogeneic HCT is an effective consolidative strategy for FLT3 ITD mutant AML patients, in the real world, a large number are not transplanted in CR1 due to delays in donor search and transplant scheduling strategies resulting in disease relapse. Effective strategies to avoid delays in scheduling, rapid donor searches and the use of alternative donor sources are much needed for these patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.