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Background Mycophenolate mofetil (MMF) is frequently combined with cyclosporine-A (CSA) as immunosuppression in unrelated donor CBT. Recent evidence suggests that therapeutic drug monitoring of mycophenolic acid (MPA), the active metabolite of MMF, is advisable based on intra- and inter-patient variability of MMF pharmacokinetics. Moreover, an increased incidence of acute graft-versus-host disease (aGVHD) has been associated with low unbound MPA AUCs in hematopoietic stem cell transplantation. This is highly relevant in cord blood transplantation (CBT) as aGVHD is a leading cause of transplant-related morbidity and mortality. However, as AUCs are cumbersome, a limited pharmacokinetic parameter such as MPA troughs would be ideal. Additionally, the toxicity associated with MPA trough levels is not established and is of concern in CBT especially due to the theoretical risk of myelosuppression from high MPA levels. Methods We evaluated the association between serial (weeks 1-6) total MPA serum trough levels and transplant outcomes in pediatric and adult recipients of double-unit CB grafts. Patients were transplanted between 8/2009 and 11/2012 for hematologic malignancies with 4-6/6 HLA-A,-B antigen, -DRB1 allele donor-recipient matched units and intravenous CSA/MMF was commenced on day -3. To evaluate the association between trough levels and outcomes, the trough levels were dichotomized into < 2 mcg/mL and ≥ 2 mcg/mL for toxicity (neutrophil and platelet engraftment, gastro-intestinal toxicity as measured by TPN duration, and CMV infection) at each time point. For the efficacy (aGVHD prevention) analysis, mean week 1 and 2 trough levels were split at < 0.5 versus ≥ 0.5 mcg/mL. Results Eighty-three patients (median age 44 years, range 1-71) had MPA serum trough levels drawn weekly for the first 6 weeks after CBT. Sixty-nine (83%) received myeloablative (MA) conditioning and 45 (54%) were CMV seropositive. Diagnoses included acute leukemia (n = 51), myeloproliferative disorders/MDS (n = 7), or lymphoma (n = 25). Median trough levels by week were 0.9, 0.9, 0.6, 0.6, 0.9 and 1.3 mcg/mL. The increase in trough levels over time reached significance (p = 0.03). Recipients of MA conditioning had lower MPA troughs than those who received non-myeloablative conditioning (p = 0.02). Younger age (0-15 years old) was associated with lower trough levels (p = 0.002). By time dependent Cox regression analysis, there was no association between trough levels and toxicity as measured by speed and success of neutrophil engraftment, duration of TPN in myeloablative CBT recipients, or time to CMV viremia in seropositive patients. However, MA CBT recipients with a MPA trough ≥ 2 mcg/mL had enhanced platelet recovery (p = 0.005). In a competing risk 2-week landmark efficacy analysis, there were no differences in rates of grade II-IV aGVHD (61% vs 57%, p = 0.52) according to trough level. However, patients with a low MPA trough early post-CBT had nearly triple the incidence of severe (grade III-IV) aGVHD (27.8% vs 9.5%, p = 0.06, Figure 1). Conclusions This analysis suggests that higher total MPA serum trough levels are safe from the standpoint of toxicity and may protect against severe aGVHD. The beneficial effect on platelet engraftment was unexpected but may be explained by a lower incidence of severe aGVHD. Prospective investigation of the utility of MPA trough measurements, and ultimately intervention based on drug monitoring in a larger CBT series is warranted. Disclosures: No relevant conflicts of interest to declare.

Background Acute graft-versus-host disease (aGVHD) is common after double-unit cord blood transplantation (CBT) with an incidence of grade II-IV aGVHD as high as 55% by day 180 in patients transplanted without ATG. aGVHD is associated with increased morbidity and transplant-related mortality (TRM). Mycophenolate mofetil (MMF) combined with a calcineurin-inhibitor is commonly used to prevent GVHD after CBT. However, unlike the 1 gram (gm) every 8 hours dosing that is now standard in adult donor allografts, MMF dosing in CBT has traditionally been every 12 hours. Our center has increased MMF dose from 1 gm every 12 (q12) to 1 gm every 8 (q8) hours in an effort to reduce severe aGVHD after double-unit CBT. However, the efficacy of this intervention is not established and a theoretical concern is that intensified MMF dosing could result in an increased risk of delayed engraftment or graft failure. Methods We evaluated 171 double-unit CBT recipients (median age 39 years, range 0.9-71) transplanted with either myeloablative (MA, n = 133) or non-myeloablative (NMA, n = 38) conditioning for high-risk hematologic malignancies between 10/2005 and 4/2013. CB units were 4-6/6 HLA-A, -B antigen, -DRB1 allele matched to the recipient (16 6/6, 171 5/6, 155 4/6). All patients received GVHD prophylaxis with intravenous calcineurin-inhibitor (predominantly CSA) and MMF from day -3 without ATG. Prior to 9/2009, 80 patients (47%) received MMF 1 gm IV q12 (and those 12 years and ≥50 kg (or 15 mg/kg/dose if >12 years but Results Patient characteristics and infused viable CD34+ cell doses were similar in the q12 and q8 MMF groups. A comparison of transplant outcomes by MMF dosing is shown (Table). There were no differences in the time to neutrophil or platelet engraftment and the median time to count recovery was also similar. The incidences of grade II-IV aGVHD at day 100 were similar in the groups (46% vs 52%). However, there was a suggestion of decreased grade III-IV aGVHD at day 100 in the q8 MMF group (12%) versus the q12 group (21%), although this comparison did not reach significance. With a median follow-up of 41 months (range 3-94), the PFS in each dosing group was not significantly different. Conclusions We demonstrated that intensified q8 MMF dosing is safe from the standpoint of engraftment and toxicity. There was a suggestion of decreased severe grade III-IV aGVHD in recipients of 1 gm IV every 8 hours. While a larger analysis is needed to further investigate these findings, the results are encouraging. They suggest that, as with adult donor allografts, intensified q8 hour MMF dosing should be the dose investigated for the prevention of aGVHD in CBT recipients transplanted with CSA/ MMF prophylaxis without ATG. Finally, aGVHD prophylaxis could be further optimized in CSA/ MMF-based CBT by mycophenolic acid trough level drug monitoring, early post-transplant biomarker measurements such as ST2, and delayed taper post-transplant. Disclosures: No relevant conflicts of interest to declare.

Abstract 2263 Background: Autologous stem cell transplantation (ASCT) remains the only curative option for many lymphoma patients and it is an integral component of treatment for patients with multiple myeloma (MM). Stem cell mobilization has most commonly been performed using either chemotherapy and colony-stimulating factors or colony stimulating factors alone. This approach was challenged by the inability to collect enough CD 34 cell count to perform an ASCT. Plerixafor (Mozobil ®) previously known as AMD3100, a selective antagonist of CXCR4, has recently been approved for ASCT mobilization in combination with granulocyte- colony stimulating factor (G-CSF) for both multiple myeloma and lymphoma patients and is effective for patients who failed to mobilize enough CD34 cells with other modalities. Patients and Methods: This retrospective study examines all adult patients with MM and lymphoma who received plerixafor as a mobilization agent for ASCT at Memorial Sloan- Kettering Cancer Center between January 1st, 2009 and August 1st, 2010. Patient's information was obtained from the pharmacy data base and electronic medical records. Data included demographics, diagnosis, first line mobilization regimen, second and third line regimens, doses of plerixafor received, number of pheresis sessions and CD34 cells per kg collected per each session. The primary objective was to determine how many patients failed stem cell collection following mobilization at our center. Results: Fifty-six adult patients with lymphoma (N=23) and MM (N=33) were identified. Patients were excluded if they were treated for a pediatric malignancy or an alternate diagnosis. The average number of pheresis and CD34 cells/kg collected in each group are shown Table 1. Forty-three percent (10/23) patients with lymphoma received plerixafor and G-CSF as the first line option for mobilization and 57% (13/23) received plerixafor and G-CSF after failing other regimens. A total of 5 (22%) patients with lymphoma failed collection following mobilization with plerixafor, 1 as a primary mobilization failure and 4 having failed other mobilization strategies. Thirty-nine percent (13/33) of patients with MM received plerixafor and G-CSF as the first line option for mobilization and 61% (20/33)after failing other regimens, including cyclophosphamide (N=15) and G-CSF alone (N=5). Among the patients mobilized with plerixafor, 6% (2/33) failed collection, 1 who received plerixafor and G-CSF for primary mobilization and only 1 after failing other regimens. Conclusion: In lymphoma and MM patients plerixafor in combination with G-CSF is effective for stem cell mobilization and in this study we report higher success rates than in previously published data. The few number of failures with plerixafor plus G-CSF given as a primary mobilization regimen, supports its use in this setting and is attractive considering that it can reduce patient's exposure to chemotherapy. Disclosures: Matasar: Genzyme Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.