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Introduction: The bone marrow plasma cell (BMPC) clone burden is typically low in light chain (AL) amyloidosis and some patients do not have a detectable serum monoclonal spike (M-spike). Increased BMPC% and serum free light chain (FLC) are associated with poorer outcomes. However, the outcomes of patients with AL amyloidosis based on the presence or an absence of a measurable serum M-spike before autologous stem cell transplantation (ASCT) has not been explored. Methods: This was a retrospective review of patients who had a diagnosis of AL amyloidosis and received ASCT between March 1996 and September 2017. The serum M-spike was recorded before ASCT and patients were divided according to the presence or absence of a measurable serum M-spike. Progression-free survival (PFS) was defined as time from ASCT to disease progression, relapse or death of any cause. Overall survival (OS) was calculated from time of ASCT to death of any cause. Univariate and multivariate analysis for PFS and OS were done using the following variables: age>65 vs. ≤65 years, Mayo 2012 stage 3/4 vs. 1/2, BMPC ≥ 10% vs. <10%, organs involved >2 vs. ≤2, melphalan conditioning 200mg/m2 vs. 140 mg/m2 ,ASCT year >2010 vs. ≤2010, and presence vs. absence of a measurable serum M-spike. Results: Seven-hundred and sixteen patients were identified and 521 (73%) had a measurable serum M-spike. Patients who had a measurable serum M-spike were more likely to have BMPC≥ 10% than patients without a measurable serum M-spike (46% vs. 34%, P=0.002) and they were more likely to have a difference in FLC ≥18 mg/dl (47% vs. 29%, P=0.0001). Overall, PFS and OS were significantly shorter in patients who had a measurable serum M-spike compared to patients without a measurable serum M-spike (Figure 1 A,B). The shorter survival was irrespective of the administration of induction therapy before ASCT. We also evaluated the difference in survival in patients with Mayo 2012 stage 3/4 based on the presence or absence of a measurable serum M-spike. The PFS and OS were also significantly different in these patients (Figure 1 C,D). Predictors for PFS included Mayo 2012 stage 3/4 vs. 1/2 (hazard ratio (HR): 1.5, P=0.003), BMPC ≥ 10% vs. <10% (HR: 1.4,P=0.004), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.6, P=0.001), ASCT year >2010 vs. ≤2010 (HR: 0.8, P=0.03), and the presence vs. absence of a measurable serum M-spike (HR: 1.82, P<0.0001). For OS, Mayo 2012 stage 3/4 vs. 1/2 (HR: 2, P<0.0001), melphalan conditioning 200mg/m2 vs. 140 mg/m2 (HR:0.4, P<0.0001), ASCT year >2010 vs. ≤2010 (HR: 0.6, P=0.002), and the presence vs. absence of a measurable serum M-spike (HR:1.9, P=0.003) were predictive. Conclusion: The presence of a measurable serum M-spike before ASCT is a negative independent predictor for PFS and OS in AL amyloidosis. Figure 1 Disclosures Sidiqi: Amgen: Honoraria; Celgene: Honoraria, Other: Travel grant; Janssen: Honoraria. Dingli:Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Alexion: Consultancy; Janssen: Consultancy; Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Millenium: Consultancy; Sanofi-Genzyme: Consultancy. Kapoor:Amgen: Research Funding; Celgene: Honoraria; Cellectar: Consultancy; Janssen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding; GlaxoSmithKline: Research Funding. Dispenzieri:Intellia: Research Funding; Alnylam: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Kumar:Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Tenebio: Other, Research Funding; Genecentrix: Consultancy; MedImmune: Research Funding; Cellectar: Other; Dr. Reddy's Laboratories: Honoraria; Merck: Consultancy, Research Funding; Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Novartis: Research Funding; Adaptive Biotechnologies: Consultancy; Kite Pharma: Consultancy, Research Funding; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Karyopharm: Consultancy; BMS: Consultancy, Research Funding; Carsgen: Other, Research Funding; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding. Gertz:Proclara: Other; Abbvie: Other; DAVA oncology: Speakers Bureau; Aurora Bio: Other; Prothena: Other: personal fee; Teva: Speakers Bureau; Physicians Education Resource: Other: personal fee; Annexon: Other: personal fee; Ionis/Akcea: Other: personal fee; Sanofi: Other; Appellis: Other: personal fee; Amgen: Other: personal fee; Janssen: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Medscape: Other: personal fee, Speakers Bureau; Research to Practice: Other; Alnylam: Other: personal fee; Johnson and Johnson: Speakers Bureau; Springer Publishing: Patents & Royalties; Celgene: Other.

e20506 Background: Autologous stem cell transplantation (ASCT) prolongs survival in patients with light chain (AL) amyloidosis. Mayo 2012 stage and increased plasma cell percentage (%PC) are known predictors for survival. Increased beta-2 microglobulin (B2M) predicts survival in patients with multiple myeloma. However, its prognostic effect in patients with AL amyloidosis undergoing ASCT is not known. Methods: We retrospectively reviewed patients who had a diagnosis of AL amyloidosis and were treated with ASCT between July-1996 and September-2017. Patients with creatinine > 1.2 mg/dL were excluded, as that affects B2M levels. The receiver operator curve was used to determine the best cutoff for B2M in predicting survival and was 2.5 mcg/mL. Baseline characteristics were compared between patients with B2M > 2.5 and ≤2.5. Progression-free survival (PFS) was defined as time from ASCT to relapse or death, whichever occurred first. Overall survival (OS) was calculated from ASCT to death of any cause. Univariate and multivariate analysis were done for OS. Results: Five-hundred patients were identified and 222 (44%) had a B2M > 2.5. These patients were more likely to be > 65 years old (32% vs. 17%, P = 0.0001), have Mayo 2012 stage III/IV (33% vs. 8%, P < 0.0001), have ≥3 organs involved (25% vs. 14%, P = 0.001), and have ≥10% PCs (56% vs. 40%, P = 0.0002) compared to patients with B2M ≤2.5. The median PFS and OS were shorter in patients with B2M > 2.5 (median PFS: 64 vs. 80 months, P = 0.03); (median OS: 104.9 vs. 175.5 months, P < 0.0001). On univariate analysis, predictors for OS included age > 65 (HR: 1.6, P = 0.001), Mayo 2012 stage III/IV (HR: 3.3, P < 0.0001), ≥3 organs involved (HR: 1.3, P = 0.06), ≥10% PC (HR: 1.5, P = 0.004), melphalan conditioning 200mg/m2 (HR: 0.28, P < 0.0001), and B2M > 2.5 (HR: 1.8, P < 0.0001). In a multivariate analysis, only Mayo 2012 stage III/IV (HR: 1.8, P = 0.006), melphalan conditioning 200mg/m2 (HR: 0.35, P < 0.0001), and B2M > 2.5 (HR: 1.7, P = 0.01) remained independent predictive of OS. Conclusions: Beta-2 microglobulin > 2.5 is an independent predictor for OS in AL amyloidosis patients undergoing ASCT and should be routinely measured.

Abstract Introduction: The Bone Marrow Transplant Program at Mayo Clinic (Rochester, Minnesota) developed a multidisciplinary approach (involving physicians, nurses, pharmacists, dietitians, and financial specialists) for outpatient management of patients undergoing stem cell transplantation. This approach uses an electronic ordering system for diagnostic tests and chemotherapy to minimize medical errors. Table. Patient Characteristics (N=716) Characteristic Value Male, no. of patients (%) 426 (59) Age, median (IQR), y 59 (53–65) Creatinine, median (IQR), mg/dL 1.0 (0.9–1.2) b2-Microglobulin, median (IQR), mcg/mL 2.5 (1.9–3.7) Gammopathies, no. of patients (%) Measured by serum immunofixation or immunoelectrophoresis IgA 148 (21) IgG 414 (58) IgM 6 (1) IgD 12 (2) Light chain 83 (12) Biclonal 6 (1) None 47 (7) Measured by urine immunofixation or immunoelectrophoresis k light chain 402 (56) l light chain 226 (32) Biclonal 1 (0) None 79 (11) Not performed (anuric) 8 (1) Status at stem cell transplant, no. of patients (%) Untreated 4 (1) Plateau 436 (61) Primary refractory 113 (16) Relapse after therapy 93 (13) Relapse during therapy 70 (10) Characteristic Value CD34+ cells, median (IQR), ×106/kg Collected, no. 10.0 (7.6–12.6) Infused, no. 4.7 (3.9–6.2) Sessions of apheresis, median (IQR) 3 (2–5) Engraftment, median (IQR), days after transplantation Neutrophils, 0.5×109/L 13 (12–15) Platelets, 50×109/L 16 (14–22) Duration of hospitalization, median (IQR), d 4 (0–10) Abbreviation: IQR, interquartile range. Results: During a 45-month period after implementation of the program (2005-Sept 2007), the day-100 survival rate was 99.5% for low-risk myeloma patients (transplantation during first plateau; n=202) and 97% for high-risk myeloma patients (refractory, relapsing or second or greater plateau; n=71). The overall day-100 survival rate was 99%(270/273). Analysis of hospitalization trends since inception of the program showed that 39% of patients completed the transplant procedure as outpatients. The median duration of hospitalization for all patients was 4 days; age and serum creatinine levels were predictive of the need for and duration of hospitalization Conclusion: Outpatient stem cell transplantation is feasible for patients with multiple myeloma with a therapy mortality of 1%. Nearly 40% of our patients completed the procedure without hospitalization. Age and serum creatinine levels predicted a higher likelihood of hospitalization. Implementation of out patient transplant requires affordable housing in the community since many third party payers do not support hotel costs despite the reduction of hospital days. The hospital physical plant and patient registration process has to support use of designated hospital rooms for purely out patient practice. The transplant team must have process owners to standardize across all disease categories collection protocols, conditioning regimens, infusion SOP’s and post infusion supportive care guidelines for standard antibiotics, narcotics, laboratory work and transfusion thresholds. A care team meeting between physicians, nursing, dietary, pharmacy, business office, data base and appointment coordinators is essential to coordinate all the multidisciplinary efforts. Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of age greater than or less than or equal to 65 years Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL Kaplan-Meier curve shows the percentage of patients remaining in the hospital through time t, stratified on the basis of creatinine greater than or equal to or less than 1.5mg/dL

Abstract Background: High dose melphalan & autologous peripheral blood stem cell (PBSC) transplantation is increasingly utilized for primary systemic amyloidosis (AL). PBSC mobilization with filgrastim is safe in various patient & normal donor populations. While there is a case report of filgrastim-induced fatal pulmonary edema in an AL patient undergoing PBSC mobilization, we elucidate the incidence & magnitude of fluid-related complications in this patient population, describe the management & outcomes, & identify features predictive of risk. Methods: IRB approval & patient consent were obtained prior to review of medical records for all adult Mayo Clinic AL patients who underwent PBSC mobilization with filgrastim 10 mcg/kg once daily from 7/98 – 8/03. Three patient episodes were excluded: 1 refused consent & 2 had a 2nd PBSC mobilization & were included once. A fluid-related complication was defined as documented increased fluid retention (peripheral edema, pleural effusion or ascites) or use of additional therapy (diuretics, albumin or dopamine) to facilitate diuresis. Results: Sixty-three of 123 patients (51%) developed a fluid-related complication. Significant interventions were needed during mobilization & prior to PBSC transplant, including admission to ICU (n=3), hemodialysis to manage fluid status (n=3), paracentesis (n=2), & thoracentesis (n=3), including one requiring chest tube placement & pleurodesis. Patients with complications had more hospitalizations during PBSC mobilization compared to those that did not (24 vs 6; p=0.001); with 20 of 24 directly related to fluid status. While not statistically significant, the complications group was more likely to fail to collect adequate PBSC or have mobilization prematurely discontinued (6 vs 2; p=0.32). One patient in each group died suddenly during mobilization. Characteristics Predictive of Fluid-related Complications Patients with Fluid-Related Complications N (%) p-value AL Organ Involvement 1 vs 2 vs 3 23/58 (40%) 26/45 (58%) 14/20 (70%) 0.01 Kidney: yes vs no 48/85 (57%) 15/38 (40%) 0.08 Heart: yes vs no 41/61 (67%) 22/62 (35%) 0.0004 Baseline edema: yes vs no 47/77 (61%) 16/46 (35%) 0.005 Diuretic: 0 vs 1 vs &gt;1 15/52 (29%) 37/59 (63%) 11/12 (92%) &lt;0.0001 Albumin: ≤ 2 vs &gt; 2 mg/dL 18/24 (75%) 45/99 (45%) 0.009 On univariate analysis patients with complications had increased septal wall thickness (median 13 vs 12 mm, p=0.05), increased total urinary protein (median 3.698 vs 2.9575 g/day, p=0.04), & lower serum albumin (median 2.8 vs 3.3 mg/dL, p=0.005). Via multivariate regression patients with albumin &lt; 2 mg/dL had an OR=3.8 (CI 1.2 – 13.6), those with cardiac AL had an OR=5.5 (CI 2.2 – 15.4), & patients utilizing diuretics at baseline had an OR=12.1 (CI 2.8 – 61.2) for the likelihood of complications. Patients with fluid-related complications during mobilization had a lower survival rate at 100 days (78 vs 92%, p=0.003) & 1 year after PBSC transplantation (65 vs 91%, p=0.003). Conclusions: Over 50% of AL patients who undergo PBSC mobilization with filgrastim 10 mcg/kg once daily develop clinically significant fluid retention & subsequent complications. Cardiac AL, hypoalbuminemia, & diuretic use prior to filgrastim administration were more likely to develop complications. Fluid-related complications during PBSC mobilization are associated with poorer survival after transplantation for AL.

Abstract Background: In childhood acute lymphoblastic leukemia (ALL), a rapid decline of circulating blasts in response to induction chemotherapy or prednisone is one of the most important prognostic factors for achieving remission and for relapse-free survival (RFS). However, in AML parameters of chemosensitivity have been restricted to the assessment of residual bone marrow (BM) blasts during aplasia. We hypothesized that time to peripheral blood (PB) blast clearance would have prognostic relevance with respect to RFS in AML. Methods: From 1994 to 2006 outcomes of 86 adults (47 males; median age 52 y) with previously untreated AML (non- acute promyelocytic leukemia) achieving CR and receiving high-dose cytarabine (HDAC)-based consolidation have been included in this retrospective analysis. The median and range of white blood cell count (WBC), platelet count and PB blast percent were 5.3 × 109/L (0.9–267), 59 ×109/L (5–361) 22.5% (0–97), respectively. A 100 cell manual slide differential count was done in all with PB blasts unless the WBC was less than 0.5 ×109/L. Karyotype was classified as favorable, intermediate and unfavorable in 10, 63 and 12 cases, respectively and failed in one. Induction consisted of idarubicin at 12 mg/m2/ d (n=70) or daunorubicin at 45 mg/m2/d (n=16) on days 1–3 with infusional cytarabine at 100 mg/m2/ d on days 1–7 and repeated in those with persistent BM blasts on day 14 (n=17). The first consolidation was the same as that used to achieve CR. Thereafter, 3 courses of HDAC at 3g/m2 (1.5 g/m2 if ≥ 60 y) q12 h on days 1, 3 and 5 were planned. Results: At the time of analyses, 43% had died, primarily of relapse (97%). Median overall survival (OS) and RFS were 30.2 m (5.5–133) and 14 m (2–131.5), respectively. The median time to PB blast clearance was five days (range: 2–10). For this analysis, only those with PB blasts at initiation of induction (n=73) were included. We defined the day of PB blast clearance as the first day after commencing induction that PB blasts were absent. Separation according to blast clearance on or before day 5 resulted in the most balanced distribution and strongest significant difference between each subgroup of 45 and 28 patients, with significantly different rates of relapse of 33% and 79%, respectively (p&lt;0.0001). We also defined three “blast risk groups” as good, intermediate and poor, according to PB blast clearance on or before day 3, on days 4 or 5, or on day 6 or beyond, respectively. This provided 3 well-balanced groups (good, intermediate and poor) of 16, 30 and 27 patients with significantly different and escalating relapse rates of 12.5%, 47% and 78%, respectively (Fig 1). Univariate analysis of several variables identified PB blast clearance day (p&lt;0.0001), number of inductions to CR (p =0.0043) and cytogenetic risk group (p=0.028) as being significantly associated with RFS. On multivariable analysis, only the first sustained its significance. The results were similar for OS. Conclusion: In adults who achieve CR after induction chemotherapy for non-APL AML, early PB blast clearance predicts superior RFS and OS. Figure Figure

2058 Background: We present a tertiary center experience with high-dose methotrexate, rituximab and temozolomide (MRT) chemotherapy in both primary and secondary CNS lymphoma. Methods: A retrospective analysis was performed for a total of 27 patients (20 male, 7 female) who underwent treatment at Mayo Clinic, Rochester between November 2010 and October 2012. The median age was 63 years (range 23-73). Of these, 12 patients were diagnosed with primary CNS lymphoma, while 15 patients had secondary CNS lymphoma. All patients received at least 1 cycle of MRT. The most common histological subtype was diffuse large cell lymphoma (23 of 27 patients). Other histological subtypes were high grade lymphoma (2 patients), Burkitt’s lymphoma (1 patient) and Mantle cell lymphoma (1 patient). Results: Of 26 patients, who underwent imaging studies for response assessment after MRT, 14 patients achieved complete response (CR), 4 patients achieved partial response (PR), 2 patients had stable disease, while 6 patients had evidence of disease progression. Overall, the median number of chemotherapy cycles with MRT was 3 (range 1-6). For patients, who achieved CR, the median number of MRT cycles was 4 (range 2-6). MRT was well tolerated. Of 27 patients, who underwent their entire treatment at Mayo Clinic, grade 3 or higher treatment related toxicity were noted to be as follows – neutropenia (9/27), thrombocytopenia (4/27), anemia (7/29), and transaminitis (10/27). 16 of 27 patients proceeded to high dose chemotherapy and autologous stem cell transplant. Out of 16 patients, 14 received BCNU/Thiotepa as conditioning regimen, while 2 patients underwent BEAM conditioning. All 16 patients who underwent transplantation remain in CR at this time. Of the remaining 11 patients, 4 are being planned for autologous transplantation, 2 received and responded to salvage chemotherapy, while 5 patients died of progressive disease. Conclusions: Overall, the MRT regimen was well tolerated. Overall response rate was noted to be 67% (18 of 27 patients) and achieved CR in 54% patients (14 of 26 patients). Patients who underwent autologous stem cell transplantation as consolidation therapy continue to do well at a median followup of 12.5 months (range 2-20 months).

Introduction Despite more robust attempts to deliver chemotherapy in the outpatient setting, certain regimens for hematologic malignancies require inpatient hospitalization for treatment and monitoring clinical status. Increased length of stay (LOS) for planned chemotherapy admissions leads to increased healthcare utilization and decreased patient satisfaction. We sought to identify potentially modifiable risk factors for increased LOS. Methods Planned chemotherapy admissions to the inpatient hematology services at Mayo Clinic (Rochester, MN) from October 2018 through March 2019 were reviewed. We included patients who had treatment plans based on four pre-specified common regimens for acute myeloid leukemia, relapsed non-Hodgkins lymphoma and multiple myeloma. Patients who remained in the hospital for lack of caregiver support were excluded. Patient characteristics, including age, malignancy type, and chemotherapy regimen were recorded. Encounter characteristics included day of week of admission, time of admission, time chemotherapy plan initiated, and whether or not all necessary procedures (labs, vascular access, chemo orders) were completed prior to admission. Primary outcome was LOS. Secondary outcome was time to treatment initiation (TTI) after admission. Results There were 100 planned admissions for patients receiving four regimens: cytarabine consolidation, EPOCH, ICE, VDT-PACE, during the six month review period. Thirty-six admissions did not occur as planned (regimen changed, rescheduled, or disease progression). Of the remaining 66 admissions, 11 outliers were excluded from primary analysis. Baseline characteristics are summarized in Table 1. Univariate analysis with independent t-test found no difference in LOS for patients who had physician chemotherapy orders in place prior to admission. To the contrary, we detected a non-significant trend toward longer mean length of stay for patients that were not seen in clinic on day of admission (Table 2). On ANOVA, there was a statistically significant difference in LOS when comparing Monday admissions 3.93 days (95% CI 3.07 to 4.79) vs Friday 5.25 days (95% CI, 4.86 to 5.64), but not between any other days. There were no statistically significant differences in TTI when comparing by day of week, physician order status, or chemotherapy regimen. Again, a non-significant trend toward increased TTI was observed for patients not seen in clinic on the same day as admission. Conclusions This study serves as a starting point towards identifying modifiable factors that are essential to delivery of safe, satisfying inpatient care to our hematological malignancy patients.Our noteworthy finding regarding patients who were admitted on Friday having a longer LOS than those admitted on Monday requires further exploration. This study is ongoing with mature data to be presented at the meeting. Disclosures No relevant conflicts of interest to declare.

Abstract Background Voriconazole is a common antifungal medication used in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients. In solid organ transplantation, multiple studies have associated the use of voriconazole with the development of squamous cell carcinoma (SCC) post-transplant, but its association with SCC in allo-HSCT patients is unknown. We sought to determine this association. Methods After IRB approval, Mayo Clinic’s transplant database (2007-2012) was accessed and electronic charts of allo-HSCT patients were retrospectively reviewed. Voriconazole exposure was defined as exposure to voriconazole at any time during treatment of primary disease, prior to or following HSCT. Cumulative voriconazole exposure was defined as total days of voriconazole use following HSCT; days were not required to be consecutive. Two time-dependent voriconazole exposure variables were defined: (1) history of voriconazole exposure (yes/no) over time, and (2) cumulative days on voriconazole over time. Results 404 patients underwent allo-HSCT during this timeframe, and 381 patients (table 1) were included in the final analysis. 23 patients were excluded (8 patients received multiple transplants, 9 patients were treated under pediatric protocols, 6 patients lacked research consent). 312/381 received voriconazole; other antifungal therapy included fluconazole (n=40), posaconazole (n=23), anidulafungin (n=1), and caspofungin (n=5). Median duration of cumulative days of voriconazole was 214 (range 2 -1553). SCC developed in 26/312 exposed to voriconazole and in 1/69 who received alternative antifungals. Cumulative incidence of SCC at 1 year was 3%, 2 years was 8%, 3 years was 13%, 4 years was 14%, and at 5 years was 19% (figure 1). Cumulative days of voriconazole use was found to be a risk factor for the development of SCC, and this relationship persisted in a multivariate model using previously identified risk factors (gender, age at transplant, TBI conditioning regimen, skin cancer pre-HSCT, chronic GVHD) as covariates (HR 1.859 for each 180 days of use, p<0.001). History of prior voriconazole exposure was not associated with an increased risk of SCC after covariate adjustment (HR 2.436, p=0.2369). Conclusion This is the first study to establish cumulative days of voriconazole use as a risk factor for SCC development following allo-HSCT, and may help guide appropriate antifungal prophylaxis in this patient population which is already at an increased risk of developing skin cancers. Disclosures: No relevant conflicts of interest to declare.

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.