ALBERT

Description: Introduction: Low dose lenalidomide as a maintenance therapy after the first autologous transplant (autoSCT) has been shown to improve progression free survival (PFS) and possibly overall survival (OS) in standard-risk multiple myeloma (MM). Proteasome inhibitor-based maintenance therapy provides an alternative to lenalidomide and offers PFS and OS advantage in high-risk MM. Most recently oral ixazomib as a maintenance therapy has been shown to reduce the risk of progression by 28%. Despite the advances in maintenance therapy after first autoSCT, no prospective or retrospective studies exist evaluating efficacy of maintenance therapy after second autoSCT. In this retrospective study, we evaluated the impact of maintenance therapy after second autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult MM patients (pts) who received maintenance therapy following second autoSCT. Lenalidomide dose up to 15mg daily and subcutaneous bortezomib 1.3mg/m2 every 2 weeks were considered maintenance therapy. The pts who received higher doses or combinational therapy as maintenance were excluded. We compared outcomes between pts who did and did not receive maintenance therapy following second autoSCT. The objectives were to determine OS, relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) with maintenance therapy following second autoSCT using Cox regression and competing risk models. Results: Between January 2000 and December 2018, 117 pts underwent second autoSCT and met the inclusion criteria. Of these, 39 received maintenance therapy and 78 did not. Median time between first and second autoSCT was 57 months (range, 4.9-124.2) in the maintenance group and 46 months (range, 3.7-193.5) in the no-maintenance group (p=0.32). Disease status at second autoSCT was complete response (CR) (n=7, 6%), very good partial response (VGPR) (n=22, 19%), partial response (PR) (n=30, 26%), stable (n=21, 18%) and progressive disease (n=32, 27%). Melphalan-based preparative regimen was used in 87% of pts, and BEAM was used in 13% of pts. All pts successfully engrafted and median time to neutrophil and platelet engraftment was 11 and 19 days, respectively. Maintenance therapy after second autoSCT was started at a median day of 105 (range, 62-317). Lenalidomide-based maintenance therapy was commonly used in 23 (59%) pts, and bortezomib as maintenance was used in 16 (41%) pts. Sixteen pts received maintenance therapy after both first and second autoSCT, and 23 received second maintenance only. Median duration of second maintenance therapy was 16 months (range, 8.7-26.5). The best response during maintenance was CR (n=8, 21%), VGPR (n=20, 51%), PR (n=9, 23%), and stable disease (n=2, 5%). Median follow-up for OS was 48 and 60 months in the maintenance and no-maintenance group, respectively. Median OS was not reached in the maintenance group and was 40.8 months in the no-maintenance group (HR 2.32, p=0.02). At 3-year, maintenance group had superior RFS (18% vs 12%; HR 1.65, p=0.03), lower relapse rate (69 vs 81%; SHR 0.58, p=0.02). Median time to progression was 24 months in the maintenance group and 14 months in the no-maintenance group (p=0.04). Although limited by small numbers, we did not observe any impact of cytogenetics at diagnosis on OS and RFS after second autoSCT. RFS was superior with lenalidomide-based maintenance compared to bortezomib-based maintenance (HR 2.17, p=0.05). However, OS was not different. The multivariable analysis revealed that maintenance after second autoSCT was associated with significantly superior OS (HR 0.38, p=0.01), RFS (HR 0.59, p=0.03) and lower relapse rate (SHR 0.63, p=0.04). The common reasons for maintenance therapy discontinuation were disease progression (n=20, 51%), side effects (n=7, 18%), and unknown (n=12, 31%). A total of 10/39 pts who received maintenance therapy and 44/77 pts who did not receive maintenance have died. Conclusion: This is the first study showing efficacy of maintenance therapy after second autoSCT. Maintenance therapy after second autoSCT significantly improved overall and relapsed-free survival and should be considered in all pts after second transplant. Our study also reveals real world practice pattern of using variable dose of maintenance therapy among physicians. Disclosures Deol: Novartis: Other: Advisory board; Kite: Other: Advisory board; Agios: Other: Advisory board.

Description: Introduction: Peri-transplant radiation (XRT) in Hodgkin Lymphoma (HL) patients undergoing autologous stem cell transplant (ASCT) has been associated with improved local control. However, this has not been well established with increased use of novel agents in peri-transplant setting. Methods: This was a retrospective analysis of HL patients who underwent their first ASCT between 2000 and 2018 at Karmanos Cancer Institute in Detroit, Michigan. Peri-transplant radiation was defined as XRT within 3-month window of autologous transplant. Novel agents included brentuximab, check-point inhibitors (CIs), and other targeted agents. The primary endpoint was to compare overall survival (OS) based on utilization of peri-transplant XRT and novel agents with standard salvage chemotherapy. Secondary endpoint was to assess the OS benefit of novel agent use in the post-transplant setting. Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between OS and nine prior chosen predictors (bulky relapse, pulmonary or bone marrow relapse, extranodal disease, CT/PET response [CR vs less than CR], novel salvage [anytime], peri-transplant XRT, site of relapse [local vs systemic], maintenance brentuximab, relapse after initial diagnosis [〉1 year vs ≤1 year]). Results: From 2000-2018, there were total of 220 patients who underwent ASCT for HL. Patients underwent ASCT median of 575 days after initial diagnosis. 65 (30%) patients had XRT during initial treatment and XRT was utilized less frequently in all patients (13% vs 35%) and stage I-II patients (29% vs 46%) who were diagnosed after 2010. Peri-transplant XRT was used in 30 (14%) patients and was utilized similarly in patients who had ASCT before or after 2010 (13% vs 14%) (Figure 1). There was no difference in baseline characteristics (bulky relapse, local vs systemic relapse, etc.) of patients who did or did not receive peri-transplant XRT (Table 1). Novel salvage was used in 32 (15%) patients at any time before transplant (Figure 1). Median OS of all the patients who had ASCT was 11 years [7.6-NR] and PFS was 4.3 years [2.3-7.4]. Median OS of patients who had peri-transplant XRT was not reached [9.4-NR] compared to 7.7 [5.3-NR] years for those without peri-transplant XRT [HR 0.38; 95% CI 0.15-0.96; p=0.033] (Figure 2); on the contrary, there was no difference in PFS between the two groups. Median OS of patients who had novel salvage at any time was not reached [4.3-NR] compared to 11 [7.6-NR] years for those without novel salvage [HR 1.08; 95% CI 0.43-2.72; p=0.877]. Median OS of patients who had either novel salvage (anytime) or peri-transplant XRT was not reached [9.4-NR] compared to 11 years [6.5-NR] for those who had chemotherapy salvage only [HR 0.64; 95% CI 0.32-1.26; p=0.193]. In the multivariable analysis, less than CR to salvage therapy and lack of peri-transplant XRT use were associated with worse OS. There were total of 85 (39%) patients who progressed after ASCT. Median OS for those patients was 3.5 years [2.3-8.8] and PFS was 1 year [0.8-1.5] after relapse from ASCT. The median OS for patients who received novel agents (brentuximab 61%, CI 14%) during first progression after ASCT was 6.9 years [2.3-NR] after relapse from ASCT compared to 2.9 years [2.3-NR] for those that did not [HR 1.47; 95% CI 0.72-3; p=. 288]. In addition, the median OS for patients who received novel agent at any time after transplant was 6.9 years [2.6-NR] after relapse from ASCT compared to 2.5 years [2.2-7] for those who did not [HR 1.96; 95% CI 1-3.86; p=0.048] (Figure 3). Lastly, OS after relapse from ASCT was better if patients progressing on novel agent post-transplant received another novel agent for their successive therapy rather than any other treatment [HR 4.87; 95% CI 1.14-20.8; p=0.018]. Conclusions: We show that there was a lack of standardized patient selection for utilization of peri-transplant XRT and its use was similar before and after the novel agent era. Peri-transplant XRT was possibly used in patients who had residual disease or other high -risk features that could not be identified due to retrospective nature of this study and, despite this, use of peri-transplant XRT was associated with modest survival benefit. Surprisingly, use of novel agent at any time during salvage was not associated with survival benefit. Utilization of novel agents at any time after post-transplant progression was associated with OS benefit. Disclosures Deol: Kite: Other: Advisory board; Novartis: Other: Advisory board; Agios: Other: Advisory board.

Description: Background: Autologous hematopoietic stem cell transplantation (AHSCT) is an important modality in the management of many hematologic malignancies. The first step for patients who are candidates for AHSCT is adequate stem cell collection. Recombinant granulocyte-colony stimulating factor (GCSF) is used for stem cell mobilization. Plerixafor has been used to increase the yield of mobilized stem cells, either upfront or pre-emptively when pre-apheresis peripheral blood CD34+ cell count is low. In the last few years, biosimilar G-CSF (Zarxio®) has become available. Although biosimilar G-CSF may reduce mobilization costs when used alone, the effect on use of additional mobilization agents like plerixafor has not been well studied. Therefore, we investigated whether there was a difference in the rate of Plerixafor usage among patients who were mobilized using biosimilar G-CSF (Zarxio®) compared to the original G-CSF (Neupogen®). Methods: This was a retrospective single institution study. We utilized the Karmanos Cancer Insitute's blood and marrow transplantation database to collect data on patients who underwent stem cell mobilization for AHSCT using either Neupogen® (N) or Zarxio® (Z), between January 2015 and June 2017. Per institutional policy, patients received G-CSF 10µg/Kg for 5 days and received Plerixafor if peripheral CD34+ cell count on the first planned day of collection was 〈 20/uL. The target CD34+ stem cell dose for AHSCT was 2 x 106/kg. Kruskal-Wallis tests were used to compare two groups for continuous variables and Chi-squared or Fisher's exact tests for categorical variables. Logistic regression models were used to assess associations between six pre-specified predictors (mobilization, age, radiation therapy, median WBC/ platelet count prior to initiation of mobilization and disease status at time of mobilization) and transplant status. Results: A total of 370 patients underwent stem cell mobilization during the study period. N was used for mobilization in 197 patients while Z was used in 173 patients. Patient characteristics are shown in Table 1. Median age was 61 years (18-78). There were no significant differences in the baseline patient characteristics other than slightly lower median WBC count prior to mobilization, in patients who received N for mobilization. The indication for stem cell mobilization was Multiple myeloma (67%), Non-Hodgkin's lymphoma (21%), Hodgkin Lymphoma (8%) and Amyloidosis (4%). There was no statistically significant difference in plerixafor utilization between the two groups (45% in N group vs 43% in Z group (p-value: 0.794). There was also no difference between the groups in the peripheral CD34+ cell count on firts planned day of collection, number of collected stem cells, total days of apheresis, need for a second mobilization, rate of transplant and duration of transplant hospitalization (Table 2). In MVA, older age and platelet count 〈 100 were the only 2 factors which adversely impacted the possibility for a patient to proceed to transplant (Table 3). Conclusion: There was no difference in plerixafor utilization among the two groups. Previously recognized risk factors like older age and low platelet count were identified as risk factors for not being able to undergo an AHSCT. The cost of biosimilar is about 50% less than the original G-CSF and based on our analysis of a large number of patients at a single institution, biosimilar G-CSF provides significant cost savings for stem cell mobilization. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Description: BACKGROUND: Impact of Plerixafor (P) mobilized stem cells on immune reconstitution of autologous stem cell transplant (ASCT) patients has not been established. Early lymphocyte recovery (Absolute lymphocyte count of 〉 1 K/uL at day 30 after transplant) has been established to predict outcomes in multiple myeloma (MM) patients. The purpose of this study was to evaluate lymphocyte recovery in MM patients who underwent ASCT with stem cells mobilized with G-CSF vs G-CSF+P. Secondary objective was to evaluate the survival outcomes. METHODS: This is a retrospective analysis of MM patients who underwent first ASCT between 2008 and 2016 with either G-CSF or G-CSF+P mobilization at Karmanos Cancer Institute in Detroit, Michigan. Plerixafor was used per institutional guidelines when the peripheral CD-34+ve cell-count was 〈 20/ uL on day 5 of G-CSF mobilization. 610 total patients were identified. Mobilization agents used were G-CSF alone (n= 469) or G-CSF+P (n= 141). All patients underwent transplant after Melphalan (M) conditioning and dose of M was at treating physician's discretion (140 vs 200 mg/m2). The primary endpoint was the Absolute Lymphocyte Count at day 30 (ALC30). Secondary endpoints were PFS and OS Univariable and multivariable Cox proportional hazards regression models were fit to assess associations between ten pre chosen predictors( age, race, stage at diagnosis, doublet vs. triplet therapy, lines of treatment, disease status, mobilization agents, melphalan dose, ALC at day 30, post- transplant maintenance) and survival benefit (PFS and OS). RESULTS: Median age of patients was older in G-CSF+P group (62 vs 60 years, p=. 006) and they were more likely to receive triplet therapy (82 vs 72%, p=. 015) for induction compared to G-CSF group (Table 1). Patients in G-CSF group were more likely to receive greater than one line of treatment before transplant (p=. 006). Disease status at transplant was similar between the two groups. G-CSF patients received higher dose of M (at 200mg/ m2) more frequently (69 vs. 58%, p = 0.010) and median cell dose infused was higher in G-CSF group (3.19 vs 2.88 x106 CD 34+ve-cells/Kg, p= 0.001). Primary endpoint, ALC30, was 1.3 K/uL(.1-4.5) and 1.2 K/uL(.1-5.1) for G-CSF and G-CSF+P, respectively (p=. 608). Median day to neutrophil recovery were similar in both groups (ANC of 500 at Day 12). Post-transplant maintenance use was similar between the two groups. The median PFS was 2.46 years (95% CI, 2.14 to 3.15) and 2.77 years (95% CI, 1.99 to 3.27) for G-CSF and G-CSF+P, respectively (HR: 1.128; 95% CI, (.843-1.509); p=. 417) (Figure 1). The median OS was 6.09 years (95% CI, 4.55 to NR) and 3.73 years (95% CI, 3.20 to NR) for G-CSF and G-CSF+P, respectively (HR: 1.638; 95% CI, (1.118-2.399); p=. 011) (Figure 2) .In MVA, higher stage at diagnosis, less than PR before ASCT, and no post-transplant maintenance therapy were associated with worse PFS and OS. More lines of treatment adversely impacted PFS. Use of G-CSF+P for mobilization and Melphalan dose ≤ 200-mg/ m2 adversely impacted OS. ALC30 did not impact PFS or OS in MVA. There were no significant differences in causes of death among the 2 groups. CONCLUSIONS: In this large, retrospective analysis of MM patients mobilized with G-CSF vs G-CSF + P, there was no significant difference in lymphocyte recovery. Higher Melphalan dose resulted in improved OS in the MVA. There was an overall survival difference favoring the G-CSF group, however, differences in baseline characteristics not accounted for in the MVA may be responsible for this observation. A Prospective study comparing these mobilization regimens including patients with similar baseline characteristics is necessary to confirm this finding. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Description: Introduction: Use of cytoreductive therapy pre-transplant has remained a debatable issue in the management of MDS. Induction chemotherapy has been attempted with no clear advantage. However, the information on pre-transplant hypomethylating agents (HMA) as a debulking/bridging therapy in MDS is unclear. This study evaluates the impact of pre-transplant HMA on post-transplant outcomes in MDS. Methods: We retrospectively evaluated clinical outcomes of adult MDS patients, who underwent allogeneic stem cell transplant (ASCT) at out institute. We divided patients who received pre-transplant HMA into

Description: Introduction: Peripheral T-cell Lymphoma represents a heterogeneous group of lymphoid malignancies characterized by poor prognosis with 5-year overall survival (OS) about 25% with conventional chemotherapy. Autologous stem cell transplant (Auto-SCT), as consolidation, is often considered in first complete remission (CR), providing between 30 to 40% long term disease-free survival. However, patients receiving Auto-SCT in second CR or with refractory disease have poor outcomes with progression-free survival ranging from 15-20% to 0%, respectively. In such cases, allogeneic stem cell transplant (Allo-SCT) may provide long term disease control. We intended to study outcomes of Allo-SCT in peripheral T-cell lymphoma patients. Methods: We have retrospectively evaluated long-term outcomes of adult peripheral T-cell lymphoma patients at Karmanos Cancer Institute. The objectives were to determine GVHD rate, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following Allo-SCT. Results: Between January 2005 and December 2017, 39 patients underwent Allo-SCT. The different diagnoses included peripheral T-cell lymphoma, not-otherwise-specified (n=16), angioimmunoblastic T-cell lymphoma (n=8), anaplastic T-cell lymphoma (n=8), hepatosplenic T-cell lymphoma (n=2), cutaneous T-cell (n=3) and NK cell lymphoma (n=2). The median age at transplant was 50 years (range, 21-67). The median number of prior therapies was 2 (range, 1-5) and 12 patients (31%) had failed prior Auto-SCT. Sixteen patients (41%) were in CR and 2 (5%) were in partial remission at the time of Allo-SCT, whereas 12 (31%) patients had relapsed disease and 9 (23%) had refractory disease. Twenty-one patients (54%) received matched related and 18 patients (46%) had unrelated Allo-SCT. Myeloablative conditioning regimen was used in 22 patients (56%), whereas reduced intensity regimen was used in 17 (44%) patients. Grade III-IV acute GVHD occurred in 25.6% (95% CI, 13.2-40.1%) and chronic GVHD occurred in 41% (95% CI, 25.1-56.3%). After a median follow-up of 3.08 years (95% CI, 2.49-7.28) among surviving patients, the estimated probabilities of 3-year OS and PFS were 35.9% (95% CI, 22.4-57.6%) and 32.5% (95% CI, 19.9-53%), respectively. The 3-year relapse rate was 23.9% (95% CI, 11.5-38.7%), whereas NRM was 35.9% (95% CI, 21.1-50.9%). No difference in OS and PFS was noticed in patients receiving Allo-SCT in first CR compared with patients receiving Allo-SCT beyond first CR (p=0.81; p=0.94). Similarly, no difference in OS and PFS was noted in patients with Allo-SCT followed by failed prior Auto-SCT compared with patients with upfront Allo-SCT (p=0.31; p=0.47). Seventeen of 39 patients were alive and 22 were deceased (n=7 disease relapse; n=15 NRM). Out of 39 patients, 13 (33%) alive patients are free of relapse and GVHD as of data analysis. Conclusion: Our study suggests that Allo-SCT is a viable treatment option for peripheral T-cell lymphoma and appears to provide cure in these highly selected patients. The survival advantage was noted in patients beyond first remission; therefore, it should be considered in all transplant eligible patients. In addition, certain proportion of patients who failed prior Auto-SCT benefited from Allo-SCT, which points towards potential role of graft-versus-lymphoma effect. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.

Description: Introduction: About 40-45% of relapsed chemo-sensitive diffuse large B cell lymphoma (DLBCL) patients achieve long term survival with autologous transplant (autoSCT). However, the outcomes of patients who fail autoSCT are extremely poor. In addition, patients with high risk DLBCL and refractory disease have lower chances of response to autoSCT. Allogeneic stem cell transplant (alloSCT) could be a viable option in these circumstances, in part due to cytoreductive effect of conditioning regimen and graft-versus-lymphoma effect. Here we report outcomes of DLBCL patients who received alloSCT in upfront settings or following failed autoSCT. Methods: We retrospectively evaluated clinical outcomes of adult DLBCL patients at Karmanos Cancer institute. The objectives were to determine rate of GVHD, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following alloSCT. Results: Between January 2005 and December 2017, 81 patients underwent alloSCT. Of these, 73 patients had de novo, 7 had transformed DLBCL and one had testicular involvement. The median age at transplant was 52 years (range, 21-68). The median number of treatments prior to alloSCT was 3 (range, 1-6). Twenty-four patients (30%) had prior failed autoSCT, and 57 (70%) had upfront alloSCT. Disease status at transplant were: complete remission in 22 patients (27%), partial remission in 6 (7%), relapse in 31 (38%) and refractory in 22 (27%). Thirty-three patients (41%) underwent matched related and 48 (59%) had matched unrelated alloSCT. CNS and bone marrow involvement at the time of transplant were noted in 10% and 47% of patients, respectively. Patients received following conditioning regimens: R-BEAM (58%), BU-FLU-TBI (27%), BU-FLU (2%), CY-TBI (2%), BU-CY (2%), CY-FLU-TBI (2%), and others (5%). With a median follow-up of 5 years (95% CI, 4.01-9.89), the cumulative incidences of grade III-IV acute GVHD at 6-month and chronic GVHD at 1-year were 27.2% (95% CI, 18-37.2%) and 37% (95% CI, 26.5-47.6%), respectively. At 1-year, OS was 48% (95% CI, 38.4-60.3%), PFS was 43.2% (95% CI, 33.6-55.4%) and GRFS was 13.5% (95% CI, 7.8-23.5%). One-year relapse rate was 24.7% (95% CI, 15.9-34.5%), and NRM was 32.1% (95% CI, 22.2-42.4%). Sixteen patients (20%) patients were alive without chronic GVHD and relapse. Relapse disease at the time of transplant was associated with higher post-transplant relapse rate, and poor performance status was adversely associated with OS and PFS. No effect of prior autoSCT, conditioning regimen or type of donor was found in multivariable analysis on OS, PFS, relapse and NRM. Twenty-seven out of 81 patients (33%) were alive at the time of data analysis. Causes of death included relapse (37%), infection (31%), acute GVHD (13%) and multiorgan failure (11%). Conclusion: Our study indicates that alloSCT provides long-term survival in these high-risk patients with low relapse rate; although non-relapse mortality was high in this group where about a third had failed prior autoSCT. Disclosures Deol: Kite Pharmaceuticals: Consultancy; Novartis: Consultancy.

Description: Abstract 4391 Background: High dose chemotherapy followed by autologous transplantation of peripheral blood stem cells plays an important role in the management of intermediate- and advanced-stage multiple myeloma. In order for successful engraftment to occur, adequate numbers of high quality peripheral stem cells must be harvested prior to transplantation. Mobilization of PBSC in patients treated with lenalidomide has been associated with poor apheresis collections after G-CSF mobilization. The purpose of this study is to present our institution’s experience utilizing an intermediate-dose cyclophosphamide-based mobilization regimen. Methods: We retrospectively analyzed data for patients with multiple myeloma who underwent autologous stem cell transplant at UCLA between 2006 and 2010. Data were obtained from the database of the UCLA Heme Malignancy/Stem Cell Transplant Unit, the electronic health record system and stem cell processing laboratory. All patients underwent mobilization with a regimen of cyclophosphamide 2.5g/m2 IVPB, G-CSF 10 mcg/kg/day for 4 days SQ, and prednisone 2mg/kg/day for 4 days po. The number of CD 34+ cells was used as a marker for the number of peripheral stem cells collected. Minimum dose collected to ensure adequate engraftment was 2×106/kg CD34+ cells. Patients were conditioned with melphalan 100mg/m2/d x2 (unless there was evidence of renal failure, in which case the dose was reduced to 100mg/m2) with subsequent infusion of stem cells. Neutrophil engraftment was defined as the first day of absolute neutrophil count greater than 500×106/L ≥ 7 days after transplant. Results: Autologous stem cell transplant was performed in 103 patients with multiple myeloma at UCLA between 2006 and 2010. Median number of apheresis procedures was 1 (1–12) with a median of 4.4×106/kg (1.4–33.5) CD34+ cells collected. Median time to engraftment was 10 (8–18) days. Thirty-five patients received lenalidomide at some point in their pretransplant treatment. Median number of apheresis procedures was 1 in both lenalidomide and non lenalidomide treated groups. In the lenalidomide treated group 54% required only one collection versus 75% in the non lenalidomide treated group (p=0.033). In the lenalidomide treated group 31% required 3 more or more collections versus 10% in non lenalidomide treated group (p=0.0075). Three patients in the lenalidomide group had subsequent mobilization with plerixafor with one of these requiring bone marrow harvesting. Median CD34+ cells collected was 3.5×106/kg and 4.9×106/kg (p=0.246) in the lenalidomide and non-lenalidomide groups respectively. Both groups had a median time to neutrophil engraftment of 10 days with a similar range. Conclusion: Pre-transplant use of lenalidomide adversely affected the number of stem cell apheresis procedures required to procure adequate stem cell dose as evidenced by a greater percentage requiring 3 or more collections. However, despite prior lenalidomide exposure, the use of our mobilization regimen permitted adequate collection, with the majority of patients requiring only one apheresis procedure, and led to an equivalent time to neutrophil recovery. Disclosures: Off Label Use: Cyclophosphamide and G-CSF for mobilization of stem cells.

Description: Introduction: Post-transplant relapse and GVHD are two major barriers of success of allogeneic hematopoietic stem cell transplantation (AHSCT) for AML. These outcomes are often dependent on the complex interaction between the post-transplant immunosuppression and the conditioning regimen. We as well as others have used rabbit thymoglobulin for the reduction of both acute and chronic GVHD in unrelated transplant in AML. The interaction between different conditioning regimens and thymoglobulin may play an important role in the outcomes, but it has not been fully investigated. In this study, we compared outcomes of patients undergoing unrelated donor AHSCT for AML using thymoglobulin with either a myeloablative or reduced intensity conditioning regimen. Patients received busulfan/fludarabine (Bu/Flu)-based myeloablative conditioning (MAC) regimen with 4 days of busulfan or reduced intensity conditioning (RIC) regimen using 2 days of busulfan with fludarabine. Since 2 days of busulfan as RIC may have a higher relapse rate, we added low dose TBI (200cGY) to the RIC regimen (Bu/Flu/TBI). Methods: We retrospectively evaluated outcomes of adult AML patients who underwent unrelated donor AHSCT utilizing tacrolimus, mycophenolate (MMF) and thymoglobulin as GVHD prophylaxis. All patients received either a Bu/Flu/TBI-based RIC or a Bu/Fu-based MAC regimen. Thymoglobulin was administered at a total dose of 4.5mg/kg in divided fashion (0.5mg/kg on day-3, 1.5mg/kg on day -2, 2.5mg/kg on day -1). Tacrolimus and MMF were started on day -3. The objectives were to determine the rates of acute and chronic GVHD, overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM) using Cox proportional hazard regression and competing risk models. Results: One hundred twenty-two patients with AML received unrelated donor AHSCT between January 2005 and December 2017. Of these, 88 (72%) patients had de-novo and 34 (28%) had secondary AML. Sixty-four patients received Bu/Flu/TBI-based RIC, and 58 received Bu/Flu as MAC regimen. All patients received peripheral blood stem cells. The patients receiving RIC regimen were older (median age 66 vs 53 years, p

Description: Introduction: Rabbit thymoglobulin, an in-vivo T-cell depleting agent, is widely used as a part of GVHD prophylaxis regimen. Current dosing of thymoglobulin is often weight based and does not consider patient related factors. This results in highly variable exposure of thymoglobulin. Although higher doses (〉7mg/kg) of thymoglobulin have shown to reduce the risk of GVHD, it is associated with increased rate of opportunistic infections and disease recurrence. Conversely, lower dose (2.5mg/kg) of thymoglobulin is associated with increased risk of GVHD. Thus, optimum dosing of thymoglobulin remains undefined. We hypothesized that recipient peripheral blood ALC on the first day of thymoglobulin infusion would interact with the dose of thymoglobulin administered and predict post-transplant outcomes. We plan to identify association of thymoglobulin dose with the ALC on the first day of thymoglobulin. Methods: We retrospectively evaluated clinical outcomes of adult patients (pts) who underwent matched unrelated donor AHSCT and received tacrolimus, mycophenolate (cellcept) and thymoglobulin as GVHD prophylaxis. Thymoglobulin was given at a total dose of 4.5mg/kg in divided fashion (0.5mg/kg on day -3, 1.5mg/kg on day -2 and 2.5mg/kg on day -1). The objectives were to determine rate of GVHD, overall survival (OS), relapse-free survival (RFS), relapse rate and non-relapse mortality (NRM) following AHSCT using Cox proportional hazard regression and competing risk models. Results: Between January 2005 and December 2017, 217 pts underwent AHSCT. The most common indications for AHSCT were AML (n=95, 44%), MDS (n=57, 26%), non-Hodgkin's lymphoma (n=23, 11%), and ALL (n=22, 10%). Median age of pts was 60 years (range, 18-79). All pts received peripheral blood stem cells. Ninety-eight pts (45%) received full intensity conditioning regimen and 119 pts (55%) received reduced intensity regimen. The median ALC on the first day of thymoglobulin administration was 200 K/cubic millimeter. The 6-month cumulative incidence rate (CIR) of grade III-IV acute GVHD was 14.8% and the 2-year CIR of chronic extensive GVHD was 35.4%. With a median follow up of 3.82 years for surviving patients, the 2-year RFS, OS, relapse and NRM were 50%, 57.1, 20.1%, and 30.2%, respectively. CMV and EBV reactivation rates were 37% and 11%, respectively. Four pts developed CMV disease. By our lowest ALC cutoff of 100 K/cubic millimeter, pts were divided into two groups (ALC ≤ 100 vs. ALC 〉 100). Multivariable analysis revealed that ALC 〉 100 was associated with significantly superior OS (HR 0.51, 95% CI 0.33-0.79, p=0.002), RFS (HR 0.49, 95% CI 0.33-0.74, p=0.001) and lower NRM (SHR 0.57, 95% CI 0.34-0.97, p=0.038) and marginally lower relapse rate (SHR 0.57, 95% CI 0.31-1.05, p=0.070). In addition, higher infused total nucleated cells was associated with higher NRM (SHR 1.70, 95% CI 1.02-2.83, p=0.041). No impact of disease risk index, KPS, conditioning regimen, infused CD34 cells on NRM, relapse, RFS or OS was observed. Conclusion: Our study indicates that ALC ≤ 100 is associated with adverse post-transplant outcomes when thymoglobulin dose of 4.5mg/kg is used for in-vivo T cell depletion. This finding may indicate that in pts with lower ALC, thymoglobulin dose may need to be adjusted to optimize its efficacy and avoid toxicities. In the future prospective studies, which evaluate dose reduction of thymoglobulin in pts with low ALC need to be planned to confirm these results. Disclosures Deol: Agios: Other: Advisory board; Novartis: Other: Advisory board; Kite: Other: Advisory board.