ALBERT

Description: Background:Allogeneic hematopoietic cell transplantation is a cornerstone of therapy for hematologic malignancies and often a patient's only curative intent treatment. Following development of post-transplant cyclophosphamide (PTCy) regimens, the use of haploidentical hematopoietic cell transplantation (haplo-HCT) has expanded. While overall outcomes for haploidentical transplantation appear to be excellent, its novel approach brings toxicities that are particular to its biological and clinical milieu. We recently described occurrence of severe cytokine release syndrome (CRS) after haplo-HCT. We further reported that severe CRS was associated with poor clinical outcomes, including transplant related mortality (TRM), overall survival (OS), and neutrophil engraftment (Abboud et al, BBMT, 2016). However, the factors predicting the occurrence of and long-term outcomes of patients who develop severe CRS after haplo-HCT is currently not known. Objective: To describe our clinical experience with CRS in an expanded cohort of haplo-HCT patients, its implication on clinical outcomes and elucidation of possible risk factors for the development of severe CRS. Patients and Methods: We performed a retrospective review of patients who had undergone peripheral blood T-Cell replete haplo-HCT with PTCy from July 2009 through March 2016 at our institution. A total of 137 patients were identified, 51% (74) were male, with a median age at transplant of 52 (19-73), a total of 40% (57) had active disease at the time of transplant. The most common diagnosis was AML (93 pts), followed by ALL (16 pts) and MDS (15 pts). Thirty-one percent (44 pts) had undergone prior transplant. In grading CRS, we used our approach modified from by Lee et al (Blood, 2014). Twenty-two patient, donor and disease characteristics were examined to identify predictors for the development of severe CRS. Results:One hundred and twenty-four (90%) of patients met criteria for CRS, and 26 (19%) suffered from severe (grade 3-4) CRS. Virtually all patients (99%) with CRS suffered from fevers. Patients with severe CRS had a significant delay in neutrophil (p 〈 0.0001) and platelet (p 〈 0.0001) engraftment compared to the patients who developed mild or no CRS (Figure 1A and 1B). Severe CRS was also associated with a high early transplant related mortality; the rate of death before post-transplant day 28 was 6.9 times higher for patients with grade 3-4 CRS compared with those with mild CRS (p 〈 0.0001, Figure 1C). Consistent with these findings, the development of severe CRS was associated with extremely poor survival. Median survival was 3 months for grade 3-4 CRS, 15 months for grade 1-2 CRS, and 13 months for no CRS. One-year OS was 4% for grade 3-4 CRS, 55% for grade 1-2 CRS, and 50% for no CRS (Figure 1D). There was no difference in the cumulative incidence of relapse, acute graft versus host disease, and chronic graft versus host disease (data not shown). A total of nine patients received Anti-IL-6 Therapy with tociluzimab (4 mg/kg of actual body weight), 4 of which suffered from severe CRS. In terms of predictive factors, the development of severe CRS was associated with disease risk index (p=0.037), HCT-CI score (p=0.005) and presence of a previous transplant (p=0.026) by univariate analysis. Risk and severity of CRS did not differ by age, ABO mismatch, age, CMV status of donor, donor sex, T-cell or CD34 cell dose. There was no difference in rates of CRS among patients in remission or with active disease at the time of transplant. Conclusions: Severe CRS after peripheral blood haplo-HCT is associated with high early TRM, poor OS and delayed neutrophil and platelet engraftment. Furthermore, patients with high DRI, high HCT-CI and prior HCT are at a higher risk for the development of severe CRS after haplo-HCT. We have previously shown the safety and potential efficacy of using anti-IL-6 therapy in these patients. Our current results suggest potential benefit to targeting this pathway prophylactically in patients at high risk for the development of severe CRS. Table Patient Characteristics Table. Patient Characteristics Figure CRS impacts neutrophil (A) and platelet (B) engraftment and is associated with high TRM (C) and poor OS (D). Figure. CRS impacts neutrophil (A) and platelet (B) engraftment and is associated with high TRM (C) and poor OS (D). Disclosures DiPersio: Incyte Corporation: Research Funding. Abboud:Gerson and Lehman Group: Consultancy; Merck: Research Funding; Teva: Research Funding, Speakers Bureau; Novartis: Research Funding; Pfizer: Research Funding; Seattle Genetics: Research Funding; Alexion: Honoraria; Baxalta: Honoraria; Pharmacyclics: Honoraria; Takeda: Honoraria; Cardinal: Honoraria. Fehniger:Affimed: Consultancy; Celgene: Research Funding; Fortress Biotech: Consultancy.

Description: Background: Over the past two decades, peripheral blood stem cells (PBSC) have surpassed bone marrow as the preferred graft source for adult allogeneic transplantation due to its more rapid engraftment and potentially better graft-vs-tumor effects, and because PBSC collection is much less invasive for the donor. The optimal CD34+ PBSC dose is ≥ 4.0x106cells/kg, but doses ≥ 8.0x106cells/kg are suggested by some for reduced-intensity conditioning and haploidentical transplants. There is no established minimum CD34+ PBSC dose, but doses below 2.0x106cells/kg have been associated with a higher risk of engraftment delay and failure. There is significant inter-donor variability in the ability to mobilize PBSCs. Several factors have been identified as predictors of PBSC mobilization in healthy donors including: gender, age, weight, body mass index (BMI), and blood counts before and after mobilization. The impact of the donor’s comorbidities on mobilization is currently unknown. Patients/Methods: We performed retrospective chart review of 488 consecutive adult patients who underwent apheresis for allogeneic stem cell donation at Washington University School of Medicine from 2006 through 2013. Patients who received any collection regimen other than 10mcg/kg of G-CSF daily with 20 liters (+/-10%) apheresis on Day 5 were excluded. Patients who had undergone a previous apheresis for stem cell donation were excluded. Univariate analysis was performed to identify predictors of CD34+ PBSC collection in a single apheresis. Variables analyzed were: gender; age; weight; BMI; donor-to-recipient weight ratio; pre and post-mobilization blood counts (white blood count [WBC], hematocrit, platelets, neutrophils, lymphocytes, and monocytes); pre-mobilization glucose and triglyceride levels; post-mobilization peripheral blood (PB) CD34+count; and medical history significant for hypertension, hyperlipidemia, or diabetes mellitus. Subsequently, a linear regression multivariate analysis was performed with all variables found to be significant in the univariate analysis. 2-tailed tests for significance were used throughout the analysis. Results: 304 patients met the eligibility criteria for analysis. The median age was 53 years (range 18-76), 90% were Caucasian, and 50% were male. The median number of CD34+ cells collected was 7.4 x106/kg (range 0.8-27.1). 97% (295) collected ≥ 2.0x106 CD34+cells/kg, 81% (247) collected ≥ 4.0x106 CD34+cells/kg, and 44% (134) collected ≥ 8.0x106 CD34+ cells/kg. Post-mobilization PB CD34+ count (r= 0.841, p

Description: Tumor lysis syndrome (TLS) is a potentially lethal metabolic complication of chemotherapy or cytolytic antibody therapy usually seen in patients with hematologic malignancies, especially those malignancies with a high proliferative rate, large cellular burden and/or sensitivity to chemotherapy. The prevention and management of TLS includes hydration and reduction of serum uric acid (SUA) levels. Although Allopurinol (ALLO) has had longstanding use for TLS prophylaxis, its efficacy in controlling SUA is limited, especially due of its lack of action on pre-existing hyperuricemia. Rasburicase (RAS), a recombinant urate oxidase, effectively reduces SUA due to conversion of UA into allantoin, a readily excretable and soluble substance. RAS has significant activity in the initial management of TLS-associated acute hyperuricemia in pediatric populations, and is currently indicated in the US for this condition in children and adolescents. A prospective, randomized, controlled phase III study was conducted in adult pts to compare the efficacy in SUA control of RAS (0.20 mg/kg/d, IV) days 1–5, versus RAS+ALLO (RAS 0.20 mg/kg/d, IV days 1–3 plus oral ALLO 300 mg/day days 3–5) versus ALLO alone (300 mg/d) days 1–5. 280 pts (275 evaluable) with hematological malignancies at high or potential risk for TLS were enrolled. 92 pts received RAS, 92 pts received RAS+ALLO, and 91 received ALLO. Treatment arms were well balanced in terms of demographics, baseline characteristics, TLS risk, and percentage of pts with baseline hyperuricemia. The SUA response rate - defined as normalization of SUA (≤ 7.5mg/dl) at days 3–7 was 87.0% in the RAS arm, 78.3% in the RAS+ALLO arm and 65.9% in the ALLO arm. RAS was superior over ALLO (p=0.0009) in the overall study population as well as in pts at high risk TLS (89.0% vs. 62.8%, p=0.0012), and in pts with baseline hyperuricemia (89.5% vs. 52.9%, p=0.0151). The time to control SUA in hyperuricemic pts was 4.1 h in the RAS arm and 27 h in the ALLO arm. The mean SUA area under the curve (AUC) results indicated that there was an 8.4-fold increase in UA exposure in the ALLO arm compared to the RAS arm. There were no significant differences in the incidence or severity of adverse events, serious adverse events or deaths. The majority of RAS and/or ALLO-related adverse events were grade 1 and 2, and most of these events were hypersensitivity-related reactions. No cases of anaphylaxis, methemoglobinemia or hemolysis were observed with RAS treatment. In conclusion, RAS is superior to ALLO in normalization of SUA, with a faster effect, in adult pts at risk for TLS. RAS alone or followed by ALLO are two valid options for this patient population.

Description: Introduction: Gemtuzumab ozogamicin (GO; MylotargTM) is an antibody-drug conjugate composed of an anti-CD33 monoclonal antibody covalently linked to the potent antibiotic calicheamicin. Previous studies have shown GO is generally well tolerated and can induce durable second remissions when administered as monotherapy or in combination with chemotherapy in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). We report safety data from an expanded-access protocol (EAP) that allowed compassionate use of GO in patients with R/R AML or acute promyelocytic leukemia (APL) and no access to comparable or alternative therapy. Methods: Conducted in the United States, the GO EAP (NCT02312037) was an open-label study in patients aged ≥3 months with R/R AML (including myelodysplastic syndrome) or APL who were considered to have the potential to derive clinical benefit and had exhausted other treatment options. The protocol allowed for treatment regimens tested in clinical trial settings and reported in the Mylotarg Investigators Brochure or peer-reviewed journals. Data from these trials indicated these regimens could potentially benefit a patient with R/R AML or APL. For R/R AML patients, the regimens included GO as monotherapy or in combination with anthracyclines and/or nucleoside-analogue containing regimens or hypomethylating agents. For patients with APL, these included GO as monotherapy or in combination with all-trans retinoic acid and/or arsenic trioxide. Patients were permitted to re-enroll in treatment, and their data are summarized according to each enrollment treatment. Results: A total of 331 patients received GO either as monotherapy for R/R AML (adult [aged ≥18 years]: n=118; pediatric [aged

Description: Background In a randomized study of single-agent eltrombopag (EPAG; n=64) versus placebo (PBO; n=34) in thrombocytopenic patients with advanced myelodysplastic syndromes or acute myeloid leukemia (AML), median overall survival (OS) was 27 weeks for EPAG versus 15.7 weeks for PBO (hazard ratio [HR]: 0.73). In addition to standard supportive care, disease-modifying treatments were generally permitted at any time at the investigator's discretion. To explore the role of concomitant anticancer therapy in this study population, a post hoc subgroup analysis was conducted in patients in each treatment group who received anticancer treatment. Methods Anticancer treatment was grouped post hoc into the following categories: palliative treatment (eg, hydroxyurea, low-dose cytarabine), hypomethylating agents (HMAs; eg, azacitidine and decitabine), induction chemotherapy (eg, 7 + 3; mitoxantrone, etoposide, and cytarabine, etc), and other (eg, lenalidomide). Baseline characteristics and safety/efficacy parameters were examined in this subgroup of patients. Results While on study treatment, a similar proportion of patients in both treatment arms of the trial received anticancer therapy (EPAG, n=28 [44%]; PBO, n=13 [38%]). The majority of patients receiving anticancer therapy in both the EPAG (64%) and PBO (54%) arms received palliative treatments (primarily hydroxyurea and low-dose cytarabine) followed by HMAs (Table). Induction chemotherapy was received by 11% of patients in the EPAG subgroup, compared with no patients in the PBO subgroup. For the subgroup of patients who received anticancer therapy, EPAG patients had higher baseline median platelet counts and absolute neutrophil counts, and a lower incidence of poor prognosis karyotype (Table). The percentage of patients with AML and those who were platelet transfusion dependent were similar between treatment arms at baseline (Table). All patients in both treatment groups experienced ≥1 adverse event (AE) while on study treatment. A lower proportion of EPAG patients experienced a serious AE (SAE) on therapy compared with PBO patients, and proportionately fewer infection-related SAEs were reported in EPAG versus PBO patients (Table). Pyrexia SAEs were higher in the EPAG (5 [18%]) arm versus the PBO (1 [8%]) arm. In the subgroup of patients receiving anticancer therapy, a similar proportion of EPAG and PBO patients experienced Grade ≥3 hepatobiliary events (3 [11%] vs 1 [8%]). Three (11%) EPAG patients experienced Grade ≥3 renal and 2 (7%) thromboembolic events on study drug, whereas no PBO patients experienced these events. A lower proportion of patients on EPAG (18%) experienced AEs that led to discontinuation of study treatment compared with those on PBO (46%). A lower proportion of EPAG patients (32%) died on therapy compared with PBO (69%); the primary cause of death in both arms was the underlying disease. Median platelet counts for EPAG patients receiving anticancer treatment increased above baseline, whereas median platelet counts remained stable at baseline levels for PBO patients. A higher proportion of EPAG patients than PBO patients achieved platelet (50% vs 31%) and red blood cell (RBC; 29% vs 8%) transfusion independence for ≥8 weeks (Table). Bleeding events (Grade ≥3) were reported in fewer EPAG patients (11%) versus PBO patients (38%). When censoring patients at the start of anticancer treatment, no apparent difference in OS was observed between treatment arms (HR: 0.97). Summary/conclusion In the subgroup who received anticancer therapy, EPAG patients had higher incidences of platelet and RBC transfusion independence, higher median platelet counts, and lower incidences of bleeding and infectious complications compared with PBO patients, with selected SAEs occurring at higher rates. These results support the safety profile of EPAG in combination with a variety of anticancer agents. In addition, these data suggest a possible beneficial supportive care effect in patients receiving concomitant therapy with EPAG and anticancer treatment. Further studies of EPAG in combination with anticancer therapy are warranted to confirm these hypotheses. Disclosures: Platzbecker: GlaxoSmithKline: Honoraria. Off Label Use: Eltrombopag is a TPO receptor agonist that is used for the treatment of thrombocytopenia due to various diseases. It is approved in cITP and now being evaluated for the correction of thrombocytopenia in subjects with MDS/AML. Wong:GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau. Verma:GlaxoSmithKline: Research Funding. Abboud:Alexion: Honoraria; Ariad: Honoraria; Novartis: Honoraria; Teva: Speakers Bureau. Greenberg:Amgen: Research Funding; GlaxoSmithKline: Research Funding; KaloBios: Research Funding; Novartis: Research Funding; Onconova: Research Funding. Lyons:Novartis: Research Funding; GlaxoSmithKline: Research Funding; Amgen: Honoraria, Research Funding. Santini:Novartis: Honoraria; Janssen: Honoraria; GlaxoSmithKline: Honoraria; Celgene: Honoraria. Cheng:GlaxoSmithKline: Speakers Bureau. Dougherty: GlaxoSmithKline: Employment. Mannino:GlaxoSmithKline: Employment. Mostafa Kamel:GlaxoSmithKline: Employment, Equity Ownership. Chan:GlaxoSmithKline: Employment. Stone:GlaxoSmithKline: Employment. Giagounidis:GlaxoSmithKline: Honoraria.

Description: We sought to determine whether bexarotene can be combined with decitabine in elderly and relapsed AML patients. Both drugs have been shown to be well tolerated in acute myeloid leukemia (AML) patients as single agents, and these agents have non-overlapping mechanisms and side-effect profiles; bexarotene activates transcriptional effects of RXRA through hetero- and homodimers, while decitabine is thought to act through DNA hypomethylation. Furthermore, through Affymetrix expression array profiling of 111 AML patients and Nanostring analysis of 7 MDS and AML patients, we observed consistently elevated levels of RXRA relative to RARA, suggesting that a ligand specific for RXR may be more effective to induce AML differentiation than the RARA ligand ATRA. We treated 18 elderly (≥ 60 years old) or relapsed AML patients in 3+3 dose escalating bexarotene cohorts: 100 mg/m2/day, 200 mg/m2/day, 300 mg/m2/day. All patients were treated with decitabine 20 mg/m2IV on days 1-5 of 28 day cycles. All patients were monitored for hypertriglyceridemia and hypothyroidism, and treated accordingly. The average age was 73, the average performance status was 1, an adverse karyotype was observed in 9 patients, and 12 patients had relapsed after prior therapy. Only one patient experienced a dose limiting toxicity (grade 3 fatigue) and 8 patients were treated with the maximum dose (myelosuppression, infection, differentiation syndrome, hypertriglyceridemia, hyperlipidemia, hypothyroidism, nausea, weight loss and reversible electrolyte abnormalities were not considered dose limiting). The overall response rate was 22%: 1 patient achieved complete remission with incomplete count recovery (CRi) and 3 patients achieved blast reduction greater than 50% (partial response, PR). In addition, six patients achieved stable disease (SD). Patients with CRi, PR, or SD completed an average of 4.25 cycles, while other patients completed an average of 1.2 cycles. Of note, 3 patients successfully transitioned to allogeneic transplant following therapy (average age 68). We correlated ex vivo bexarotene sensitivity with clinical response. Bone marrow cells were collected on day 0 and day 3 of bexarotene therapy (during cycle 1, decitabine was administered on day 3 after bone marrow collection) and co-cultured with irradiated MS5 murine stromal cells for 72hrs with or without further bexarotene treatment. We used flow cytometry to compare CD11b expression in cells treated with and without bexarotene ex vivo, and compared expression between samples collected on day 0 vs day 3 (in vivo treatment). Bexarotene increased CD11b expression greater in the 4 responding patients vs non-responders (fold increase in CD11b: ex vivo average 2.1 ± 0.3 vs 1.1 ± 0.1 fold, p 〈 0.003; and in vivo 1.6 ± 0.3 vs 0.7 ± 0.2 fold, p 〈 0.03; increase in absolute percentage of CD11b+ cells: ex vivo average 24% ± 2.6% vs 0.7% ± 1%, p 〈 0.001; and in vivo 13.6% ± 4% vs -3.6% ± 2.2%, p 〈 0.002). Furthermore, all 4 responding patients demonstrated an equivalent or increased induction of CD11b when treated ex vivo with ATRA compared with bexarotene. These results show that bexarotene, a retinoid which selectively binds to and activates RXRs, but not RARs, can be safely combined with decitabine in relapsed and refractory AML patients. This combination leads to partial response in a subset of patients, is well tolerated, and can bridge elderly patients to allogeneic transplant. Because ex vivo bexarotene treatment identified all patients achieving a PR, further studies should focus on patients who display ex vivo sensitivity. Finally, the mechanism of RXRA-activated differentiation is likely to be through the RXRA/RARA heterodimer, as all 4 patients who responded to bexarotene also responded to ATRA when tested ex vivo. Disclosures: Welch: Eisai: Research Funding. Off Label Use: Bexarotene for the treatment of AML. Abboud:Ariad, Alexion, Novartis, Teva: Honoraria, Speakers Bureau. Stockerl-Goldstein:Celgene : Speakers Bureau; Millennium: Speakers Bureau.

Description: Introduction Disease recurrence is the major cause of treatment failure after allogeneic hematopoietic stem cell transplantation (alloHSCT) for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Graft-versus-host disease (GVHD) is the major cause of non-relapse morbidity and mortality after alloHSCT. Decitabine (DAC) is a hypomethylating agent that irreversibly binds to and inhibits DNA methyltransferase-1, leading to loss of DNA methylation. DAC maintenance may help eradicate minimal residual disease and facilitate a graft-versus-leukemia effect. Lower DAC doses are expected to be better tolerated after alloHSCT and equally effective in promoting hypomethylation. Additionally, DAC maintenance may have a favorable effect on the incidence of GVHD by enhancing the effect of T-regulatory lymphocytes (Choi et al, Blood, 2012). Methods Patients (pts) with AML/MDS in complete remission (CR) after alloHSCT, with ANC〉 1,500/mm3, platelets〉 50,000/mm3, and without grade III-IV acute GVHD were eligible to receive DAC, starting between day +50 and +100 after alloHSCT. We investigated 4 DAC doses: 5, 7.5, 10 and 15 mg/m2/day IV x 5 days of a 6-week cycle, for a total of 8 cycles. Each cohort contained 4-8 evaluable patients. The Maximum Tolerated Dose (MTD) was defined as the maximum dose at which〈 20% of patients experience hematologic or non-hematologic dose limiting toxicities (DLT) during the 1st cycle of treatment. GVHD prophylaxis was at the physician discretion. Results 19 pts were enrolled to date; the median age was 60 y (22-66); 14 pts had AML and 5 MDS. All conditioning regimens were myeloablative; 14 donors were unrelated and 5 related. 3 cohorts have been completed and a final 4th cohort is currently enrolling. Median follow-up from alloHSCT is 24 mo (7-36). 8 pts (44%) completed all 8 cycles: 7 pts remain in CR with stable counts and full donor chimerism and 1 pt developed CNS-only relapse 26 mo after alloHSCT. 9 pts went off study before cycle 6: 1 pt for poor compliance after 6 cycles, 3 pts for relapsed disease (after 1, 2 and 5 cycles, respectively), 2 pts for sepsis, and 2 pts after physician decision. 6 pts have died: 3 from relapse, 2 from sepsis after 3 cycles of DAC (they were not neutropenic at a time), and 1 form sepsis 〉1 y after getting off study. 2 pts are still on study passed 3rd cycle. DAC maintenance was well tolerated. Associated hematological toxicities were mostly grade I/II leukopenia and thrombocytopenia. There was one occurrence of hematological DLT. No MTD has been reached. Non-hematological toxicities were grade I/II nausea, fatigue, neuropathy, and transaminase elevation. 2 pts had grade I-II acute GVHD prior to starting DAC and both resolved while on DAC; 1 pt developed grade IV gut GVHD coinciding with first cycle of DAC that completely resolved on DAC; 1 pt developed late acute GVHD of skin and liver around 6th cycle of DAC that resolved after few wks. 2/8 pts who completed 8 cycles of DAC developed very mild skin and oral chronic GVHD not requiring any systemic therapy, 1/8 pt developed late acute GVHD responding to therapy, and 1 pt developed overlap GVHD syndrome. 4/7 pts who went off study prior cycle 6, and did not have an early relapse, developed severe chronic GVHD requiring intensive immunosuppressive therapy. Conclusion To our knowledge this is the first report of DAC as maintenance therapy after alloHSCT. DAC at the dose of 15 mg/m2 for 5 days every 6 weeks is safe and can be administered in heavily pretreated pts in the post-alloHSCT setting. Approximately 43% of pts were able to receive all 8 cycles. The lack of toxicities and low incidence of GVHD indicate that a longer period of administration should be investigated. Although there is a trend of increased FOXP3 expression, results were not statistically significant. Further correlative studies, including genome-wide methylation studies, are ongoing. Disclosures: Off Label Use: Decitabine maintenance after alloHSCT.

Description: Abstract 787 The interaction between leukemic blasts and the bone marrow microenvironment is postulated to be an important mediator of chemoresistance in AML. Although many candidate receptor/ligand pairs have been implicated, the CXCR4 / SDF-1 axis functions as the principal regulator of homing and retention of both normal and malignant hematopoietic cells in the marrow. We hypothesized that disruption of the CXCR4 / SDF-1 axis with plerixafor (Mozobil®), a small molecule inhibitor of CXCR4, may sensitize AML to the effects of chemotherapy. We conducted an open label, phase I/II study in patients with relapsed or refractory AML in which plerixafor was administered prior to salvage chemotherapy. A test dose of plerixafor was administered SQ followed by a 24 hour observation period to analyze its effects on AML blasts in the absence of chemotherapy. Plerixafor was then given 4 hours prior to MEC chemotherapy (mitoxantrone 8 mg/m2/d, etoposide 100 mg/m2/d and cytarabine 1,000 mg/m2/d) daily for 5 days. Forty pts have been enrolled in the study with median age of 49 yrs (range 19-71). Baseline characteristics include 6 pts (15%) with secondary AML, 4 (10%) with prior transplant, 24 (60%) with intermediate and 10 (25%) with poor risk cytogenetics. Thirty-six pts (90%) received plerixafor + MEC as their 1st salvage regimen for relapsed disease with 21 (53%) having a CR1 duration of 〈 12 months and 9 pts (6%) for primary refractory disease. The remaining four pts (10%) received the regimen as their 2nd salvage regimen. Three dose levels of plerixafor: 80 mcg/kg, 160 mcg/kg and 240 mcg/kg were tested in the phase I dose escalation. In the phase II, a total of 34 patients have been treated at the 240 mcg/kg dose level. Common grade ≥ 3 adverse events consisted primarily of cytopenias and infections. No evidence of hyperleukocytosis or significant delays in neutrophil recovery (ANC 〉500/mm3, median 27d, range 21-37) or platelet recovery (plt 〉50k/mm3, median 26d, range 20-40d) were observed. Of the 32 pts currently evaluable for response at the 240 mcg/kg dose level, a complete remission (CR+CRi) has been achieved in 50% of pts (CR=13, CRi=3) which compares favorably to historical CR rates of 25-35%. Treatment failure was due to persistent disease in 14 pts (44%) and early death due to complications from infection in 2 pts (6%). One year KM estimate of overall survival is currently 56%. Correlative studies demonstrate that plerixafor mobilizes AML blasts (mean 2.5-fold increase, range 0.9-7.3 fold) into the peripheral circulation peaking at 6-8 hours after administration. FISH performed in pts with informative cytogenetic abnormalities indicates that mobilization occurs equally in both non-leukemic and leukemic populations. Higher baseline surface CXCR4 expression correlated with increased mobilization of AML blasts (Pearson's r=0.53, p=0.023) into the PB at 6 hrs post-plerixafor. In addition, a strong correlation was also observed between baseline CXCR4 expression and % SDF-1 migration in transwell assays (r=0.84, p=0.0013). Furthermore analysis of AML PB blasts at 6 hrs post-plerixafor demonstrate increased CXCR4 expression as well as increased chemotaxis in response to an SDF-1 gradient in transwell assays compared to baseline (64% vs 38%, p=0.0006). We conclude that plerixafor can be safely administered in combination with cytotoxic chemotherapy in patients with AML. Based on encouraging preliminary evidence of efficacy and in vivo evidence of CXCR4/SDF-1 blockade, confirmatory randomized studies of plerixafor for chemosensitization in AML are being planned. Disclosures: Uy: Genzyme: Consultancy, Speakers Bureau. Off Label Use: Plerixafor for AML. Abboud:Genzyme: Consultancy. Vij:Genzyme: Consultancy. DiPersio:Genzyme: Consultancy, Honoraria.