ALBERT

Description: Introduction: Allogeneic hematopoietic cell transplantation (HCT) is curative therapy for sickle cell disease (SCD). Good outcomes have spurred an increase in the use of HCT for SCD, including an increasing number of trials using alternative donors. As survival improves, assessment of long-term outcomes and potential late effects (LEs) in this patient population is critical. We evaluated the data reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) to study incidence and risk factors for LEs following HCT for SCD. Methods: Patients reported to the CIBMTR with a diagnosis of SCD who had undergone their first HCT between 1996 and June 2015 were included in this analysis. Patients with graft failure were excluded. We performed a descriptive analysis of patient, disease, donor, and transplant-related factors. The cumulative incidence (CI) of LEs was estimated at 1, 3, and 7 years post-HCT. The number of pre- versus post-HCT SCD-specific disease complications was computed. Overall survival (OS) probabilities were calculated using the Kaplan-Meier method. Multivariable Cox regression analysis was used to evaluate risk factors related to OS and LEs. Results: The study population consisted of 355 patients. The median age at HCT was 10 years (range 15 years of age was associated with significantly inferior OS (mortality HR 7.26, 95% CI 3.57-14.77). Multivariable analysis for LEs demonstrated an increased risk of diabetes (HR 7.29, 95% CI 2.94-18.08) and pulmonary abnormalities (HR 5.90, 95% CI 1.14-30.42) with unrelated donor, while older age at HCT was associated with avascular necrosis (HR 14.19, 95% CI 1.86-108.47), diabetes (HR 3.45, 95% CI 1.69-7.05), and congestive heart failure (HR 8.02, 95% CI 1.13-56.94). SCD-related symptoms overall decreased from pre- to post-HCT (Table 1), most notably acute chest syndrome, vaso-occlusive pain crises, and stroke. Conclusions: Patients with SCD who have undergone HCT for SCD in recent years have excellent OS, confirmed in this CIBMTR multicenter dataset, with diminished SCD-related symptom burden post-HCT. However, they remain at-risk for a myriad of LEs, with risk factors including older age at HCT and unrelated donor, necessitating systemic organ-based follow up post-HCT. Continued follow-up of this patient population is critical to provide appropriate counseling for medical providers, patients, and families considering HCT as a treatment option for SCD. Disclosures Shaw: Therakos: Other: Speaker Engagement.

Description: Although outcomes after allogeneic hematopoietic cell transplantation (alloHCT) for AML have improved, this has mainly been attributed to a reduction in transplant-related mortality rather than reduced leukemia relapse. NK cell alloreactivity is regulated by inhibitory and activating signals mediated through cell-surface receptors including the killer immunoglobulin-like receptors (KIRs). Group A and B KIR haplotypes have distinct centromeric (Cen) and telomeric (Tel) gene-content motifs and donor Cen group B KIR haplotypes have been reported to be associated with decreased relapse and improved survival in AML patients undergoing unrelated donor alloHCT. We hypothesized that donor KIR genotype may also be predictive of outcomes after matched related donor (MRD) alloHCT. We evaluated 93 AML patients in CR1/CR2 who underwent T-cell replete alloHCT using HLA- matched related donors at our institution from 1/2000-3/2013. Sixty-six had myeloablative conditioning (MAC) that that was busulfan/cyclophosphamide-based and 27 had reduced-intensity conditioning (RIC) with fludarabine/total body irradiation or busulfan/fludarabine. Donors were KIR genotyped to assign haplotypes A/A vs. B/X and the distinctive Cen and Tel gene-content motifs of group A and B KIR haplotypes according to the presence or absence of one or more B haplotype-defining KIR genes. KIR B–content score for each KIR genotype was defined as the number of Cen and Tel gene-content motifs containing B haplotype–defining genes (range, 0-4). As compared to those with haplotypes B/X (n=40; B content scores of 1-4) those with haplotype A/A (n=25; B content score of 0) undergoing MAC had significantly lower 100-day, 6-, 12- and 24-month non-relapse mortality (NRM) (8% vs. 0%, 13% vs. 0%, 15% vs. 0%, 25% vs. 0%, respectively, Figure 1) which was confirmed on multivariable analysis (HR 9.19, p=0.03). There were no differences between these groups regarding patient and transplant-related characteristics, or for acute or chronic GVHD, relapse, or survival. The causes of death in the group with haplotypes B/X were most commonly attributed to infection and then GVHD. However, within the group with B/X haplotypes, the B motif content score (1-4) was not associated with significant differences in NRM (HR 0.79, p=0.56). No difference in outcomes was observed for those undergoing RIC. The number of donor activating KIR genes (2SD1, 2DS2, 2DS3, 2DS4, 2DS5, and 3DS1) was then assessed. As compared to those with 3-6 activating KIR genes (n=20) those with 0-2 (n=41) undergoing MAC had significantly lower 100-day, 6-, 12- and 24-month non-relapse mortality (NRM) (15% vs. 0%, 15% vs. 5%, 15% vs. 5%, 29% vs. 8%, respectively, Figure 2) which was confirmed on multivariable analysis (HR 4.07, p=0.01). There were no differences in other post-transplant outcomes when comparing these groups or when considering those undergoing RIC. An increase of 1 donor activating KIR also was highly associated with NRM (HR 1.37, p=0.008). Overall, these results suggest that in the MRD MAC alloHCT setting donor KIR genotype may be predictive of increased NRM risk, particularly for those with B/X haplotypes and greater numbers donor activating KIRs. No comparable effects were observed in the RIC setting. Future strategies to further enhance immune reconstitution post-transplant may be appropriate to pursue for these higher risk patients. These results may have potential implications to improve donor selection for those AML patients with multiple HLA-matched related donors and need to be validated in larger cohorts. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Background: Recent data have shown that pre-transplant FDG-PET is prognostic in DLBCL patients undergoing autologous stem cell transplantation (ASCT). We retrospectively analyzed data on patients with DLBCL treated with ASCT to assess the impact of pre-transplant FDG-PET on relapse-free survival (RFS) and overall survival (OS). Methods: We reviewed medical records of 32 patients with DLBCL who underwent ASCT using high dose busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP) at Cleveland Clinic from June 2008 to December 2012 and had both a relapse FDG-PET as well as a pre-transplant FDG-PET available for review. All images were interpreted by a staff nuclear medicine radiologist blinded to the outcomes. Visual analysis was performed using the Deauville five-point scale and semiquantitative analysis was done by measuring the maximum standardized uptake value (SUVmax). ΔSUVmax was calculated by determining the difference between the SUVmax at the time of relapse and the SUVmax immediately prior to transplant. Patients were grouped into pre-transplant Deauville score 1-3 or 4-5. Baseline characteristics were compared between groups using the Chi-square test or Wilcoxon rank test. Cox proportional hazards analysis was used to identify prognostic factors. Outcomes were calculated from the date of ASCT. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test Results: The median age of the patients at transplant was 57 and 69% were male. There was no significant difference in baseline characteristics of patients who had a Deauville score 1-3 compared to patients who had a Deauville score 4-5 including mean age, gender, race, Karnofsky performance status, number of prior chemotherapy regimens, prior radiation therapy, and IPI at diagnosis and transplant. There was a trend towards significance in the median SUVmax at relapse in the Deauville 1-3 group compared to the Deauville 4-5 group (11.1 vs. 18.1, p=0.08) and a significant difference in the median pre-transplant SUVmax (2.3 vs. 8.1, p6 vs. 6) prior to transplant is predictive of poor RFS. Pre-transplant PET is a powerful tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 1. OS of DLBCL patients undergoing ASCT based on pre-transplant Deauville score. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Figure 2. RFS of DLBCL patients undergoing ASCT based on pre-transplant SUVmax. Disclosures Smith: celegene, spectrum, genentech: Honoraria. Majhail:Gamida Cell Ltd.: Consultancy; Anthem Inc.: Consultancy.

Description: Proteasome inhibitors (PIs) capitalize on the constitutive activation of NF-KB in AML cells and increase chemosensitivity to anthracyclines and cytarabine. We combined the second generation PI, ixazomib, with the standard AML salvage regimen of MEC (mitoxantrone, etoposide, cytarabine). The primary objectives of this study were to determine the dose limiting toxicity (DLT), maximum tolerated dose (MTD), and phase 2 dose of ixazomib in combination with MEC in relapsed/ refractory (R/R) AML. Secondary objectives included evaluating the efficacy of this combination and correlating response to the gene expression profile and CD74 expression, which may identify a subset of leukemias in which NF-KB is operative with increased sensitivity to PI (Attar et al. CCR 2008; 14: 1446-54). Methods: Patients (pts) were treated at Cleveland Clinic and University Hospitals of Cleveland from Oct 2014 to present. An IND was approved by the FDA, and the protocol was approved by each institutional review board. Eligibility: age 18-70 yrs, R/R AML, and cardiac ejection fraction ≥ 45%. The fraction of blasts positive for CD74 was assessed by flow cytometry. Samples were stored for gene expression profiling pre- and post-treatment (at the time of response assessment). Pts received MEC: mitoxantrone (8 mg/ m2), etoposide (80 mg/m2), and cytarabine (1000 mg/m2) intravenous (IV) Days 1-6. Ixazomib, provided by Takeda, was given orally on Days 1, 4, 8, and 11 and was dose escalated using a standard 3x3 design. Dose levels (DLs): 1 (1.0 mg), 2 (2.0 mg), 3 (3.0 mg), 4 (3.7 mg). An additional 18 pts were to be treated at the MTD. One cycle of treatment was administered. Response was assessed by bone marrow aspirate/ biopsy by Day 45 and complete remission (CR) was defined by IWG criteria (Cheson 2006). Toxicities were graded according to NCI CTCAE v 4.03. Toxicities secondary to neutropenia or sepsis were not considered DLTs. DLTs included: (1) ≥ Grade 4 non-hematologic toxicity (NHT) with the exception of nausea, vomiting/ alopecia and drug-related fevers; (2) any ≥ Grade 3 neurologic toxicity; (3) grade 4 platelet or neutrophil count 50 days beyond the start of chemotherapy and not related to leukemia; (4) any Grade 4 NHT 〉 grade 2 by 45 days beyond the start of chemotherapy. Grade 2, 3, and 4 hyperbilirubinemia were redefined as 1.5-〈 10x upper limits of normal (ULN), 10-20 x ULN, and 〉 20 x ULN. Results: Of 23 pts enrolled, 22 are evaluable. The median age was 58 yrs (range 31-70), 12 (52%) were male and the median baseline WBC was 2.56 K/ uL (range 0.1-62.9). The median time from initial diagnosis to registration was 7.1 months (range 1.4-36.8) and 7 pts (30%) had a history of an antecedent hematologic disorder. Thirteen pts were in 1st relapse and 10 pts were refractory to their last therapy. One pt had received a prior allogeneic hematopoietic cell transplant (AHCT), 7 pts had FLT3 ITD mutations and 7/ 21 pts (33%) had adverse cytogenetics per CALGB 8461 criteria at the time of relapse. At DL1, 1 DLT occurred (grade 4 thrombocytopenia), so this DL was expanded to 6 pts. At DL2, 2 pts developed Grade 4 thrombocytopenia; therefore, the MTD of ixazomib was 1.0 mg. The most common grade 3-5 NHTs in the dose escalation phase were febrile neutropenia (100%), hypoalbuminemia (25%), hypokalemia (42%), hypotension (33%), and respiratory failure (33%). No adverse events in the dose escalation phase were attributed to ixazomib alone. The overall response rate was 55% [CR/ CR with incomplete count recovery (CRi)], and 9 pts proceeded to AHCT. Five of these 9 pts remain alive with a median follow-up of 12.8 months. Five pts had CD74 expression performed. Two pts had high levels of CD74 expression (〉 80%); and both achieved CRi. Myeloid mutation panel data was available in 14 pts. Previous data has demonstrated the number of mutations in DNTMT3A, TP53, ASXL1, and NRAS (0, 1, 〉1) is associated with a worse response to salvage therapy (Advani et al, abstract 3825, ASH 2015). Seven pts had at least one of these mutations and 6 of the 7 achieved CR/ CRi. Conclusions: The combination of MEC and ixazomib was well-tolerated and produced an overall response rate of 55% in patients with relapsed/ refractory AML irrespective of molecular mutation status. The combination is safe with a similar toxicity profile to MEC alone. CD74 expression may represent a biomarker for response to this therapy. Results from gene expression profiling will be complete by the time of the meeting and will be presented. Disclosures Mukherjee: Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Caimi:Genentech: Speakers Bureau; Gilead: Consultancy; Roche: Research Funding; Novartis: Consultancy. Maciejewski:Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Speakers Bureau; Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Speakers Bureau. Sekeres:Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Description: Acute undifferentiated leukemia (AUL) and mixed phenotype acute leukemia (MPAL) are acute leukemias of ambiguous lineage representing less than 5% of all adult leukemias. Ontogenetically, they are thought to be caused by precursor lesions in early pluripotent hematopoietic progenitor cells having the ability to differentiate into both lymphoid and myeloid lineages. In contrast, common lymphoid and myeloid leukemias are likely derived from precursor lesions in committed progenitor cells. The molecular characteristics of the cell of origin of these leukemias have not been fully characterized. Given the ambiguous classification of these disorders, we used NGS to evaluate the molecular profiles of this unique subset of leukemias. Our panel tested for the 60 most commonly mutated genes in myeloid malignancies (MM), which can be used to further elucidate driver mutations that play a role in the pathogenesis of this unique entity. Molecular data was available for 18 of 35 patients (pts) (51%), of whom 8 were T/myeloid, 7 were B/myeloid, and 3 were AUL. 14 pts out of the 18 had samples at the time of initial diagnosis, 3 AUL cases harbored mutations commonly seen in MM, including one patient with DNMT3A and a germ line JAK3 mutation, another with U2AF1 and PHF6 mutations, and one pt with SF3B1 and MECOM mutations. Of the 5 B/myeloid cases, 4 had only one mutation detected by the sequencing panel, including TET2, PTPN11, KDM6A, and PHF6, and one had no mutations, but did have complex cytogenetics. Of interest, we identified four patients with T/myeloid MPAL that harbored a FLT3-ITD mutation. Notably, one of these cases had additional DNMT3A and TET2 mutations while another case had a WT1 mutation. We assert that the mutational data for MPAL supports that T-myeloid MPAL encompasses a borderland between early T precursor (ETP)-ALL/AML in addition to more typical cases of T-ALL/AML given its similar immunophenotype to ETP ALL (CD117, CD13 and CD33 positive). The overlap between these two entities is illustrated in the figure below. With this immunophenotyping and molecular profiling we propose a new provisional entity, ETP-myeloid MPAL in addition to already existing ETP ALL. Of 1250 pts with acute leukemia diagnosed from 1997-2016 at Cleveland Clinic, 35 had immunophenotypic characteristics of ambiguous leukemia based on WHO criteria. The median age at diagnosis was 50 years, and 22 (63%) were male. There were 31 MPAL (16 T/myeloid, 15 B/myeloid) and 4 AUL cases. Among the 31 MPAL patients, 2 were mixed lineage chimera (subclones), and 29 had true biphenotypic features. 48% of the cohort had normal cytogenetics at diagnosis, 23% had other cytogenetic abnormalities, 14% had complex karyotype, 9% had MLL gene rearrangement, and 6% had t(9;22). 62% of pts were treated with acute lymphoblastic leukemia (ALL) directed induction chemotherapy (IC), while 38% were treated with acute myelogenous leukemia (AML) directed IC. Rates of complete remission (CR) were significantly higher in pats treated with ALL-IC regimen (82%) versus AML-IC regimen (23%) (p=.003). In our study, two cases with the recurrent lymphoid mutations WT1 and KDM6A, that achieved CR with upfront ALL-IC, while one case with FLT3-ITD, DNMT3A, and TET2 mutations achieved CR with AML-IC treatment. Pts

Description: Abstract 312 Prognosis in myelodysplastic syndromes (MDS) is heavily influenced by cytogenetics. Trisomy 8 (+8) is reported in 15–20% of MDS patients (pts) and is one of the most commonly identified karyotypes in this disease. Sole +8 is an intermediate-risk karyotype in MDS by the International Prognostic Scoring System (IPSS). However, pts with +8 myeloid malignancies exhibit wide clinical heterogeneity. In chronic myelomonocytic leukemia (CMML), +8 is considered high-risk, while in MDS functional data suggests an “immunopathologic” cause that is responsive to immunosuppressive agents and confers a good prognosis. Single nucleotide polymorphism array (SNP-A) and molecular technologies (next generation sequencing) have led to further refinement of prognosis in MDS, and subsequent discovery of molecular mutations with distinct effects on outcomes. We hypothesized that the differential outcomes noted in +8 MDS are primarily influenced by both clinicomorphologic features and the acquisition of new cytogenetic (isolated, +1, ≥2) and molecular defects. To further characterize the clinical and molecular behavior of +8 myeloid neoplasms, we analyzed 68 pts seen at the Cleveland Clinic with a +8 clone. Hematologic, bone marrow (BM), cytogenetic (metaphase cytogenetic [MC]/SNP-A) and survival data were collected. Survival comparisons were made by Kaplan-Meier analyses. Cox-proportional hazard ratio was used to determine factors predictive of outcomes. Response was evaluated per International Working Group 2006 criteria. Most (69%) pts were male; median age 69 years (38–89), and median follow-up 15 months. 69% (47/68) had MDS, 10% (7/68) MDS/MPN, 3% (2/68) MPN and 18% (12/68) AML. 41% of pts had an isolated +8 abnormality (+8 (i)), 16% had one additional abnormality (+8plus1), and 43% had ≥2 additional abnormalities defined as +8complex. By IPSS, Int-1=34%, Int-2=25%, high=42%. SNP-A data were available in 51% of the cases and detected new lesions in 60% of them (gains[46%], losses[43%], UPD[23%]). Clinically, pts with +8complex had higher median peripheral blood blasts (PB) compared to +8plus1 and +8(i) (3.5 vs 0 vs 0%,p=.04). By treatment, pts received high intensity (BMT±high dose chemo=35%), low intensity (hypomethylating agents [HMA]± lenalidomide=37%) or supportive therapies=28%). Overall response rate was 47%, with 14% CR. By cytogenetic grouping, +8complex had lower response rates compared to +8 with additional karyotype (30 vs 60 vs 52%; p=.06). Median overall survival (OS) was 15 months, and median event free survival (EFS) was 8 months, with worse OS noted in +8 complex compared to +8 plus1 and +8(i) (OS=11 vs 22 vs 29 months, p=.02; EFS=5 vs 10 vs 12 months; p=.04). To investigate the biologic rationale of these observations, we performing direct sequencing for poor prognostic genes in myeloid malignancies, such as ASXL1, IDH1/2, EZH2, K/NRAS, CBL and TP53 and for predictors of good outcomes/response like SF3B1/TET2. Molecular mutations were identified in 9/24 (38%) pts, with mutational frequencies within +8(i) (12 pts) of TET2 (42%), ASXL1 (42%), K-/NRAS (17%), SF3B1 (17%), and TP53 (0%). None of these mutations were detected in the +8plus1 or +8complex cohorts except for TP53 in one +8complex pt. No IDH1/2/EZH2/CBL mutations were found in the entire +8 cohort. Interestingly, mutations in TET2 conferred a better OS (88 vs 12 mos; p=.01). In +8 myeloid malignancies, ASXL1 mutations did not impact OS. We are currently performing whole exome sequencing and other immunogenetic studies in +8 pts to help identify factors that contribute to these group outcomes. To further define factors predictive of worse outcomes in +8 pts, univariate and multivariate analyses were performed and a predictive model of OS was designed. Using a simple scoring system, one point each was assigned to LDH ≥240, platelets 5%, and 2 points to an ANC 2], median OS=4.6 months; p

Description: Abstract 3072 In the 1990s, the most common indication for high dose chemotherapy (HDC) and autologous hematopoietic cell transplantation (AHCT) was breast cancer. Several randomized controlled trials for metastatic breast cancer (MBC), performed to address the role of HDC and AHCT, found no survival benefit over conventional therapy. A recently published meta-analysis confirmed a lack of significant survival benefit and failed to identify any subset of patients that benefited from this approach. Many trials of HDC for MBC, however, demonstrate better than expected 10–15 year progression free and overall survival occurring in 5–15% of patients. These data prompted us to evaluate the long term results of treatment with HDC and AHCT in MBC at our institution. Two-hundred eighty five patients underwent HDC followed by AHCT for metastatic breast cancer from 1984–2000. Preparative regimens included STAMP V (cyclophosphamide [Cy], carboplatin, thiotepa [TT]), n=98; CBT (Cy, carmustine, TT), n=79; busulfan and Cy, n=54; TT, n=27; STAMP I (Cisplatin, Cy, BCNU), n=26; and BCNU, n=1. With a median follow up of 169 months (range 77–283 months) in survivors, 34 (12%) of these patients remain alive. Of the 251 patients who died, 218 (87%) died of relapsed/metastatic disease. Other causes of death included infectious or cardiopulmonary etiologies. Incidence of death from secondary malignancies was less than 1%. Her2 status was unavailable in the majority of the patients, but comparison by age (50) and hormonal status did not demonstrate any significant differences in relapse (p=0.33 and p=0.32 respectively) or survival (p=0.13 and p=0.42). Using Cox analysis, we identified three prognostic factors for survival in multivariable analysis: number of prior chemotherapy regimens (HR 1.48 per 1 regimen increase, p

Description: Reduced intensity conditioning for allogeneic hematopoietic cell transplantation (alloHCT) has become a standard approach for older patients and for those with co-morbidities that prohibit myeloablative conditioning. The optimal conditioning regimen for patients with AML or MDS undergoing such transplants is not clear. Therefore we performed a single center, retrospective analysis comparing busulfan (100 mg/m2/day on days -5, -4, -3, -2) and fludarabine (40 mg/m2/day on days -5, -4, -3, -2) (BuFlu) versus fludarabine (30 m2/day on days -5, -4, -3) and 400 cGy total body irradiation (200 cGy on days -1 and 0) (FluTBI) conditioning. All of the BuFlu transplants were performed as inpatient hospitalizations while all of those with FluTBI were performed as an outpatient. A total of 71 patients in two cohorts were included. The first study cohort consisted of 38 patients (23 AML, 15 MDS) who received FluTBI from 3/2004-4/2010, and the second included 33 (20 AML, 13 MDS) patients conditioned with FluBu from 6/2010-12/2013. The groups had similar disease risk and HCT comorbidity index scores. The BuFlu patients were older (median age 65 [range, 34-73] vs. 61[range, 44-70] years, P=0.03), but there were no other differences in patient or disease characteristics. All patients received peripheral blood stem cells as the graft source. The donor sources were 53% matched related (MRD) and 47% matched unrelated (MUD) for FluTBI patients and 58% MRD and 42% MUD for BuFlu patients. The BuFlu group received more red blood cell (RBC) transfusions (median 4 vs. 2, P=0.02), but there were no differences in platelet transfusion requirements. Platelet recovery was longer for patients receiving BuFlu than FluTBI (median 16 vs. 12 days, P=0.004), but there was no difference in cumulative incidence of neutrophil recovery. The respective median number of days hospitalized in the first 100 days post-transplant was 22 vs. 10 days (P

Description: INTRODUCTION: High dose busulfan (Bu) is an integral component of many commonly-used preparative regimens for both allogeneic and autologous transplantation. Data on the efficacy and toxicity of q6 vs. q24 hour dosing are of significant clinical interest. In order to facilitate a therapeutic dose-monitoring protocol, we transitioned from q6 to q24 Bu dosing as part of our standard Bu/Cy/VP ASCT preparative regimen for patients with Hodgkin (HL) and Non-Hodgkin Lymphoma (NHL) in July 2012. We present comparative outcomes of q24 Bu dosing vs historical controls receiving q6 Bu. METHODS We retrospectively reviewed 400 consecutive eligible lymphoma patients who underwent ASCT from 2007-2013 with Bu/Cy/VP. All patients received Cy 60 mg/kg IV over 4 hours on days -3 and -2 and VP 60 mg/kg as continuous infusion on days -5 and -4. Bu was given at a dose of either 0.8 mg/kg q6 (N = 307) x 14 doses for patients transplanted between 2007-July, 2012 or 2.8 mg/kg q 24 hours (N = 93) on days -9 through -6 for subsequent patients. Outcomes assessed from date of transplant were: relapse, non-relapse mortality (NRM), relapse-free survival (RFS) and overall survival (OS). Toxicity was assessed using pulmonary and liver function tests (PFTs and LFTs) at specified time-points before and after ASCT. In addition, for a subset of 22 patients receiving q24 Bu, we measured serial Bu serum levels after the first dose of Bu with an in-house liquid chromatography-tandem mass spectrometry assay using turbulent flow online extraction technology (Bunch, et al. J Chromatogr B Analyt Technol Biomed Life Sci, 2010. 878(31): p. 3255-8) and subsequently determined the cumulative Bu area-under the curve (AUC). RESULTS Baseline patient and disease characteristics of patients dosed with q6 and q24 Bu were similar. The median age was 55 (range 20-78) years; 63% were males. 18% had HL and 82% had NHL with a comparable distribution of subtypes in both groups. Patients in both groups had comparable rates of prior chemotherapy regimens and of complete/partial remission at the time of ASCT. Due to a change in institutional guidelines, plerixafor was more commonly incorporated in peripheral blood stem cell mobilization regimen in the q24 group compared to q6 cohort (70% vs. 39%, P