ALBERT

Description: An inherent difficulty in performing allogeneic transplantation in patients (pts) of African American (AA) descent is finding suitably matched 8/8 unrelated donors. In addition for complicated reasons studies have shown that AA have an inferior survival compared to suitable matched patients from different ethnic groups undergoing allogeneic transplantation. Post transplant cyclophosphamide (PTCy) administered on day + 3 and +4 given in combination with tacrolimus and mycophenolate mofetil (MMF) allows for the safe use of more mismatched transplants, including haploidentical transplants. This has created a new approach for patients who lack suitable donors and may allow more AA pts to proceed to transplant. At our institution, we have used PTCy as graft-versus-host-disease (GVHD) prophylaxis in patients undergoing reduced intensity conditioning (RIC) hematopoietic stem cell transplant (HSCT) from mismatched related and unrelated donors, and this group consisted largely of high-risk AA pts. We retrospectively reviewed 16 pts who underwent HLA mismatched HSCT (5/10 to 8/10 HLA matches) at our institution between July 2012 and 2015. All patients received RIC HSCT with PTCy (days +3 and +4) along with tacrolimus and MMF for GVHD prophylaxis. Patients did not routinely receive growth factor support. Primary endpoints included time to neutrophil and platelet engraftment, length of hospital stay, and rates of acute and chronic GVHD. Secondary outcomes included time to relapse, transplant related mortality, and overall survival. Table 1 shows the demographics of the 16 patients who were transplanted. The median age of the patients was 57 years (range: 25-72). Ten pts were of AA descent. Fifteen donors were haploidentical family donors; 6 were 5/10 matches, 4 were 6/10 matches, and 5 were 7/10 matches. One patient received a 8/10 unrelated donor transplant. Five patients had failed previous transplants which included 3 allogeneic and 2 autologous HSCT. Based on published risk stratification (Armand et al. Blood, 2012) of the remaining 11 pts, 7 pts were high risk and 4 were intermediate risk. Neutrophil engraftment (first of 3 days when ANC was ³500 cells/mm3) occurred a median of 19 days post transplant (range:12-22 days); Platelet engraftment (³20,000/µL without platelet transfusion) occurred a median of 21.5 days post-transplant (range: 14-37 days). Median length of hospitalization was 26 days (range: 22-81 days). Two pts failed to engraft after first HSCT. One of these pts had high levels of anti-HLA antibodies directed against her donor. Both pts went on to a second haploidentical transplant and engrafted their neutrophil counts at 13 days and 21 days; respectively. Grade II acute GVHD occurred in 6/16 patients. No patient developed grade III-IV aGVHD. Chronic GVHD was observed in 8/16 patients with severe chronic GVHD seen in one patient. With a median follow up of 160 days (range: 89-778 days) the Kaplan-Meier estimates of overall survival at one year were 81.3% for all transplanted pts (Figure 1) and 80% for the AA pts (Figure 2). Three pts died; 1 patient from an invasive fungal infection and 2 pts from relapse. One additional patient relapsed but continues on treatment. Our experience suggests that the use of PTCy permits HLA mismatched transplantation, with overall survival of 〉 80% and acceptable rates of acute and chronic GVHD. Moreover, the severity of acute GVHD in patients who received PTCy post-transplant was limited, with no reported acute grade III-IV GVHD. In addition, the early outcomes of HLA mismatched transplantation in 10 African-American patients, a population that is often underrepresented in the donor registry, suggests that this approach may preferentially benefit AA pts from an expanded donor pool derived from utilization of partially HLA-matched donors. Figure 1. Figure 1. Figure 2. Figure 2. Figure 3. Figure 3. Disclosures Lum: Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Deol:Bristol meyer squibb: Research Funding.

Description: Abstract 1216 Poster Board I-238 Background: PD-1 (Program Death-1), an immune inhibitory receptor and its ligands PD-L1 and PD-L2, participate in peripheral tolerance and play a key role in immune suppression and evasion mechanisms in cancer and chronic infectious diseases. PD-1 inhibits activation signals and functions as a pro-apoptotic receptor in effector lymphocytes, and consequently regulates the extent and duration of specific adaptive and innate immune responses. CT-011, a humanized antibody, blocks the function of PD-1, resulting in increased activities of T and NK cells in vitro and in enhanced tumor immunity in experimental tumor models. At the molecular level, the antibody enhances PI3K-mediated survival and trafficking signals, attenuates cell death in effector/memory (CD4+CD45RO+) cells, and enhances trafficking in response to Stromal Cell-derived Factor-1 (SDF-1). We hypothesized that CT-011 would enhance effector/memory cells in patients with DLBCL after AuSCT and delay recurrence. Methods: We treated 41 patients (pts) with DLBCL from 30-90 days after AuSCT with CT-011 and now report data on effector/memory and memory lymphocytes in the first 30 pts. CT-011 was given at a dose of 1.5mg/kg for 3 doses, 6 weeks apart. The primary endpoint was to determine the proportion of patients who have not relapsed or died within 18 months following autologous PBSCT, and it is too early for that analysis. Our secondary endpoint was to measure the number of effector /memory and memory lymphocytes before and after treatment, and those data are the subject of this report. Results: Flow cytometry analyses (Table) on pre (baseline: BL) and post-treatment blood samples from the first 30 pts enrolled show elevated levels of specific effector/memory and memory CD4+ T lymphocytes following treatment with CT-011; the median absolute number (ABS) of effector/memory CD4+CD45RO+CD62L-CCR7- cells was increased by +49% from BL (p

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: More aggressive treatment strategies are needed for women with metastatic breast cancer(mBrCa). Although peripheral blood stem cell transplant (PBSCT) permits the use of high-dose chemotherapy (HDC) that could not otherwise be given, results for PBSCT have not been encouraging. In order to boost tumor kill, we combined a protocol that targets Her2 using activated T cells (ATC) armed with anti-CD3 × anti-Her2 bispecific antibody (Her2Bi) with a second protocol that involves infusions of ATC after PBSCT to boost anti-tumor immunity. In our phase I trial using ATC with Her2Bi to treat women with mBrCA who have Her2 positve or negative disease, we found that multiple infusions of armed ATC induced cytotoxicity directed at BrCa cells in the peripheral blood mononuclear cells (PBMC) of the patients that develop in 2 weeks and last up to 4 mos (Clin Canc Res12:569,2006). Armed ATC lyse tumors that are Her2 low-expressors (0–1+). Targeting leads to specific cytotoxicity, induces cytokine/chemokine release, and proliferation of the armed ATC. In a second study, ATC were infused after PBSCT into 23 women with mBrCa leading to 70% overall survival and 50% progression free survival at 32 mos after PBSCT. Therefore, the combined strategy involved obtaining T cells by another leukopheresis after the boosting with armed ATC, expanding the immune T cells and infusing the expanded ATC after PBSCT to transfer pre-immune anti-BrCa cytotoxicity to reconstitute cytotoxicity after PBSCT. Two patients (one pt was Her2 3+ ; one pt was Her2 0–1+) underwent treatment with this treatment approach. Both patients were given 8 infusions (20 billion/infusion with a total of 160 billion) of ATC armed with Her2Bi in the first protocol and subsequently leukopheresed and ATC were produced for the second protocol. The expanded ATC at an effector:target ratio (E/T) of 25:1, exhibited cytotoxicity at BrCa tumor cells (SK-BR-3) at 71% and 75% for pts 1 and 2, respectively. The cell product for pt 1 contained 68% CD3+, 32% CD4+, 39% CD8+, 29% CD16+56+, 12% CD4+CD25+, and 15% CD8+CD25+ cells and the cell product for pt 2 contained 35% CD3+, 25% CD4+, 8.5% CD8+, 23.3% CD16+56+, 10.4% CD4+CD25+, and 4.7% CD8+CD25+ cells. The protocol involves infusing 15 doses of ATC after PBSCT with 3 doses of ATC/week for 3 weeks and then ATC once/week for six more weeks. The pt1 and pt 2 received total of 114 and 70 billion ATC, respectively. Pt1 developed anti-BrCA cytotoxicity of 9% 2 weeks after PBSCT. Pt2 exhibited anti-BrCa cytotoxicity at an E:T of 25:1 of 38% and 15% at 3 weeks and 6 months after PBSCT, respectively. Phenotyping of peripheral blood at 6 mos after PBSCT showed 61% CD3+, 36% CD4+, 19.5% CD8+, and 15.5% CD56+ cells. There was no cytotoxicity directed at Daudi cells. These data strongly suggest that transfer of pre-immune cells after PBSCT accelerate immune reconstitution of tumor specific cytotoxicity after PBSCT. The preboost strategy with targeted T cells is being combined in a proof of principle trial to assess whether enhanced cytotoxicity can be consistently enhanced after PBSCT.

Description: We report here the long-term outcome of 95 patients with myelodysplastic syndromes (MDS) who underwent allogeneic stem cell transplantation (SCT) following busulfan-containing regimens. The median age was 43 (range:3–62) and 55 patients were male. Eighty-four patients had primary MDS, 11 had secondary MDS. Twenty patients received induction therapy for leukemic transformation prior to SCT. Pre-transplantation cytogenetic studies were available in 82 patients, and were categorized according to the international prognostic scoring system (IPSS) karyotype groups. The bone marrow biopsies/aspirates were reviewed and classified according to WHO classification (Table 1). Sixty one patients received related donor transplant (54 patients were 6/6 HLA-matched), and 34 patients received unrelated donor transplant (26 patients were 6/6 HLA-matched). Ninty patients received consecutive administration of busulfan 4 mg/kg/day orally for 4 days, cytosine arabinoside 2 g/m2 IV every 12 hours for 4 doses, and cyclophosphamide 60 mg/kg IV daily for 2 days (BAC); and 5 received other busulfan-containing regimens. GHVD prophylaxes were either cyclosporine (75 patients) or tacrolimus (12 patients) regimens, and 8 patients received other regimens. The median duration of transplant hospitalization was 34 days (range:13–121 days). Grade I–IV regimen-related toxicities (RRT) included GI (diarrhea, 32; stomatitis, 38), liver (28), cardiac (19), kidney (15), lung (25), neurological (7) and skin (5). Acute and chronic GHVD occurred in 48 (50%) and 21 (22%) patients, respectively. With a median follow up of survivors of 6.7 years, the Kaplan-Meier estimates for overall survival were 45%±5% (±SE), 35%±6% and 34%±6% at five, ten and fifteen years, respectively (Figure 1). Fifty-four patients died. The causes of death were GHVD (14 patients), relapse (12), infection (11), pulmonary toxicity (3), multiorgan failure (3), hepatic (2), renal (1), cardiac (1) and other causes (7). Non-relapse mortality at 100 days and three years was 22% and 40% respectively. The long-term follow up of patients receiving high-dose busulfan-based regimens for allogeneic SCT in this study indicated durable overall survival with acceptable toxicity. Patient Characteristics BAC: Busulfan/Ara-C/Cyclophosphamide, BU: Busulfan, CY: Cyclophosphamide, TLI: Total lymphoid irradiation, FLU: Fludarabine, ATG: Antithymocyte globulin, CS: Cyclosporin # of Patients 95 Median Age (range) 43 (3–62) Male/Female 55/40 Cytogenetic risk (IPSS)     Good/Intermediate/Poor 38/14/30     Not available 13 Disease Duration Median (range) 182 (40–1944) Etiology     Denovo/Secondary 84/11 Donor     HLA-identical sibling 54     HLA-nonidentical sibling 7     Unrelated HLA-identical 26     Unrelated HLA-nonidentical 6 WHO Classification     RA 5     RARS 2     RAEB-1 4     RAEB-2 16     RCMD 14     CMML 4     AML 20     MDS-U 6     Not available 24 Source of stem cells     BM/PBSC 69/26 GVHD prophylaxis     CSA/Methylprednisolone 32     CSA/Methotrexate 43     Tacrolimus/Mycelophenolate 7     Tacrolimus/Methotrexate 5 Busulfan regimen     BAC 90     BU/ATG/CS/TLI 2     BU/CY 1     BU/FLU/TLI 2 Figure Figure

Description: Introduction: Pleural effusions are common clinical finding in patients undergoing hematopoietic stem cell transplantation (HSCT). It can be a manifestation of underlying lung injury or a part of a systemic process. This study will investigate the incidence, risk factors, and clinical outcomes associated with pleural effusion in allogeneic HSCT. Methods: We conducted a retrospective study of 618 consecutive adult patients who underwent allogeneic HSCT for hematological disorders, between January 2008 and December 2013. Results: The baseline characteristics of the groups with and without pleural effusions are shown in table 1. The only significant difference was GVHD prophylaxis (p =0.002). A total 71 patients developed pleural effusions with the cumulative incidence of 12.6 % (95% CI, 10.0% to 15.6%) in five years. The median time of onset of pleural effusion from HSCT was 40 days (range, 1, 869). The onset of pleural effusion had a bimodal distribution with the first peak at 23 days (range 17, 29) and second peak at 362 days (range 277, 450). Based on chest CT criteria, the effusions were judged as large, moderate and small in size in 15%, 51% and 34% of patients respectively. Twenty five (35%) patients with pleural effusions underwent thoracentesis for respiratory difficulty and had a median of 800cc (range, 250 to 13500cc) of pleural fluid removed. Fourteen patients (56%) had exudative and 9 (36%) had transudative pleural effusions. Pleurx catheter was placed in 2 (3%), and chest tube in 3 (4%) patients. Causes of effusion listed in order of frequency are infection (38%), volume overload (23%), chronic GVHD (20%), heart failure (6%), engraftment syndrome (4%), veno-occlusive disease (4%), malignant pleural effusion (3%), hypersensitivity pneumonitis (1%) and iatrogenic (1%). Time of onset is different among various etiologies (p=0.006). Although thoracentesis was performed in 25 patients, the specific etiology by pleural fluid analysis was identified in only 2 patients. Pleural effusion secondary to infections, hypersensitivity pneumonitis, and engraftment syndrome occurred in the first 100 days after transplant, whereas pleural effusion due to chronic GVHD/polyserositis, bronchiolitis obliterans occurred 200 days after transplant.Fifty seven patients (80%) with pleural effusions had evidence of GVHD however; fourteen (20%) patients with pleural effusion had no evidence of acute or chronic GVHD. Twenty three (32%) patients had both pleural effusion and ascites, 27 (38%) had both pleural and pericardial effusion and 29 patients had pleural effusion alone. Multivariate cox regression analysis showed age, African American race, higher comorbidity index, unrelated donor, HLA-match 7/8, intermediate to high risk disease to be associated with worse survival among patients who developed pleural effusion after HSCT. There was no significant difference in overall survival between patients with or without pleural effusion (p=0.257). Conclusion: Majority of the patients who developed pleural effusions responded well with the treatment of the underlying disease. Although thoracentesis was often done for therapeutic reasons, it was a weak diagnostic tool. We did not identify any adverse impact of development of post HSCT pleural effusions on overall survival. Table 1. Characteristics Pleural Effusion (N=71) No Pleural Effusion (N=547) Signif Age - Median (range) year 55(25,73) 58(22,78) 0.514 Sex - no. (%) 0.522 Male/Female 43(61)/28(39) 305(56)/242(44) Diagnosis - no. (%) 0.490 AML 25(35) 213 (39) ALL 9(13) 53 (10) CLL 4(6) 27 (5) CML 2 (3) 16 (3) NHL 13 (18) 94 (17) Multiple Myeloma 3 (4) 16 (3) MDS 9 (13) 74 (14) Myelofibrosis 1 (1) 18 (3) Hodgkin's Lymphoma 1 (1) 8 (1) PLL 4 (6) 7 (1) Aplastic Anemia 0 (0) 17 (3) CMML 0 (0) 4 (1) Comorbidity-Median (range) 3 (0,8) 3 (0,9) 0.055 Disease risk status - no. (%) 0.389 Low 4 (6) 48 (9) Intermediate 32 (45) 284 (52) High 31 (44) 193 (35) Very High 4 (6) 22 (4) HLA - no. (%) 0.566 8/8 56 (79) 413 (76) 7/8 12 (17) 117 (21) 0.99 Matched related 25 (35) 197 (36) Matched unrelated 46 (65) 350 (64) Conditioning regimen - no. (%) 0.761 Full intensity 45 (63) 361 (66) Reduced intensity 26 (37) 186 (34) GVHD prophylaxis - no. (%) 0.002 Mycophenolate-Tacrolimus 41 (58) 328 (60) Mycophenolate-Tacrolimus-Thymoglobulin 26 (37) 131 (24) Tacrolimus- Thymoglobulin 3 (4) 17 (3) Thymoglobulin-Tacrolimus-Sirolimus 0 (0) 64 (12) Others 0 (0) 5 (1) Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Deol: Bristol meyer squibb: Research Funding.

Description: Introduction: Clostridium difficile (C.diff) colitis (CDI) continues to be a common complication in recipients of allogeneic stem cell transplantation (AlloSCT). Multiple risk factors were associated with CDI in this patient population including prior CDI, antibiotic prophylaxis and therapy, acute graft versus host disease (aGVHD), etc. Our aim in this study was to evaluate the effect of thymoglobulin used in GVHD prophylaxis on the incidence of CDI in patients undergoing AlloSCT. Methods: We studied 3 consecutive cohorts of AlloSCT recipients. Group1- related donor AlloSCT without thymoglobulin (N=100, transplanted 3/2010-12/2013); group 2 - unrelated donor AlloSCT with thymoglobulin (N=110, transplanted 4/2012-12/2013); and group 3 - unrelated AlloSCT without thymoglobulin (N=100, transplanted 12/2009-12/2011). Majority of patients except three in group 3 were diagnosed with CDI with a PCR based test. Results: All 3 groups were similar with respect to the baseline characteristics (Table 1). The median follow up for the 3 groups was 2 years. At a median follow up of 2 years the incidence of CDI in the three groups were 19%, 26%, 28% respectively, p=0.2 (table 2). The incidence of CDI prior to aGVHD was similar in three groups (18/100, 25/110 and 19/100 in groups 1, 2 and 3 respectively). The incidence of CDI after development of aGVHD was higher in group 3 (1/100, 4/110 and 9/100 p=0.06 in groups 1, 2 and 3 respectively). The incidence of Grade II-IV aGVHD was significantly higher in group 3 (63%) as compared to groups 1 and 2 (49 and 41%) p=0.006 (Table 2). Similarly the incidence of any grade GI GVHD was higher in group 3 (44% Vs 23% and 24%) p=0.0009. The median time to development of aGVHD was similar in all three groups (28 days in groups 1, 31 days in group 2 and 26 days in group 2). Multivariable analysis revealed that none of the factors examined (age, sex, diagnosis, intensity of conditioning, type of transplant, use of thymoglobulin, acute GVHD) was related to development of CDI. Development of GI GVHD tended to increase the risk of subsequent CDI (40% vs 27%, p=0.06). Development of CDI did not increase the risk of development of subsequent GI GVHD (30% vs. 26%). Use of thymoglobulin improved two year overall survival in patients undergoing unrelated transplant (p=0.006). Conclusion: Thymoglobulin use did not affect the overall incidence of CDI in recipients of Allo-SCT. There is a trend towards increased incidence of late onset CDI in patients undergoing unrelated Allo-SCT and not recieving thymoglobulin probably because of higher incidence of GVHD and steroid use. There was no difference in the incidence of CDI in related vs. unrelated transplant recipients. Use of thymoglobulin improved survival in recipients of unrelated Allo-SCT. Table 1. Baseline Characteristics: Related (N=100) unrelated with Thymo (N=110) Allo unrelated without Thymo (N=100) P-value Age Median 54 58 52 NS Gender F 42 47 51 NS M 58 63 49 Race Caucasian 83 99 91 NS Other 17 11 9 Conditioning regimen Myeloablative 76 59 63 NS RIC 24 51 37 Diagnosis Leukemia 47 61 56 NS Lymphoma 30 21 20 MDS 12 20 11 Other 11 8 13 Source of stem cells BM 9 6 10 NS PBSC 91 104 90 HLA match 10/10 94 71 71 NS* 9/10 2 26 21 8/10 13 8 Haploidentical 4 GVHD** Prophylaxis Tac/MMF 97 100 Tac/MMF/Thymo 101 Tac/Sirolimus/Thymo 9 *No difference in HLA match between the groups 2 and 3. **Tac (Tacrolimus); MMF (Mycophenolate Mofetil); THYMO (Thymoglobulin). Table 2. Results: Groups 1. Related 2. Unrelated with Thymo 3. unrelated without Thymo P value Incidence of aGVHD II-IV 48% 41% 63% p=0.006 Incidence of GI GVHD 23% 23.6% 44% p=0.0009 Use of systemic steroids 38% 32% 61% p=0.0001 Overall Incidence of CDI 19/100 (19%) 29/110 (26%) 28/100 (28%) p=0.20 Incidence of CDI prior to GVHD 18/100 (18%) 25/110 (22%) 19/100 (19%) NS Incidence of CDI after onset of GVHD 1/100 (1%) 4/110 (3.6)% 9/100 (9%) p=0.06 Median Overall survival at 2 year f/u 68% 52% 46% p=0.0057 Disclosures Deol: Bristol meyer squibb: Research Funding. Lum:Karyopharm Therapeutics Inc: Equity Ownership; Transtarget.Inc: Equity Ownership. Revankar:Actelion, Merck, Gilead, Astellas: Research Funding; Dara biosciences: Consultancy. Chandrasekar:Merck, Glaxo, Chimerix,: Research Funding.

Description: Abstract 2401 Background: Melphalan (M) 200 mg/m2 is a standard conditioning regimen for myeloma patients (pts) with normal renal function (NRF) undergoing ASCT. M exhibits a steep, log-linear dose effect with a potential for dose escalation (DE) to overcome M resistance. However, severe oral mucositis (OM) at M ≥ 200 mg/m2 precludes DE due to significant morbidity. Palifermin (P) as a cytoprotective agent has demonstrated efficacy in reducing intensity and duration of OM in pts receiving intensive chemo-radiotherapy. We designed a phase I study to determine the MTD of M in pts with NRF when used with P. Study Design: We enrolled 19 pts from 07/2007 to 09/2009. Data is reported on 18 evaluable pts as 1 pt was removed due to the inability to receive all 6 doses of P. DE was done (3 pt cohorts) in 20 mg/m2 increments, depending on the dose limiting toxicities (DLT). Level (L) 1 began at M 200 mg/m2 with P 60 mcg/kg/d, given as I.V. bolus on Day -5, -4, -3 and Day +1, +2 and +3 (PBSCs infused on Day 0). M was given on D-2 up to and including 280 mg/m2 (n = 6). If no symptomatic grade ≥ 3 DLTs were noted by day +30, an additional cohort of 3 pts were entered at the next dose level. Dose escalations were to stop if ≥ 2 DLTs occurred at M dose; with that dose declared as the MTD. Grade 3/ 4 diarrhea and ≥ grade 3 cardiac toxicity was considered DLT; grade 3/4 hematological toxicity was acceptable. The grade of OM was assessed daily according to the WHO oral-toxicity scale (grade 0–4). Key Eligibility Criteria: age 18–74 years, stage 2/3, ECOG performance status 〈 2, CrCl 〉 60, total bilirubin ≤ 1.5 × IULN, ALT/AST ≤ 3 × IULN, eligible for ASCT per institutional criteria and at least 2.0 × 106 CD34+ cells/kg cryopreserved for ASCT. Calculation of M dose: M dose was calculated using the actual body weight except when the actual body weight was 〉 40% above the ideal body weight; in that case, adjusted body weight was used. Results: Med age 48.5 y (33-65). Med # of prior Rx: 2 (1-5). Median CD34 cells dose 4.77 × 10(6) [2.18-11.36]; median day of neutrophil recovery +10 (10-13) and median day of platelet engraftment 19.5 (0 to 29). The overall incidence of OM ≥ grade 3 was 44% (8/18) with a median duration of OM 10 days (4 -20 d). Only 1 pt in L 1 group developed grade 4 OM. Two out of 6 pts given M 280 mg/m2 did not develop any OM. Atrial fibrillation occurred in 1/6 pts treated with M 280 mg/m2. The most common adverse events included rash (18 events, no grade 3), elevation of amylase (10, 4 grade 3-asymptomatic) and lipase (5, 2 grade 3 -asymptomatic) and edema (11, no grade 3). 11 pts (61%) required IV opioid analgesics; none needed TPN/NG feeding. All 18 pts were evaluable for response at D+100 and there were no treatment-related deaths. Median duration of follow up is 17.5 months (5.6-36.5). At D+100, all 18 patients were progression free. At D+365, 13 pts are free of progression, 2 have PD, and 2 have expired while 1 pt has not reached D+ 365 yet. First expired pt on L5 relapsed at 5 months post ASCT and no further details are available on two other expired patient. Conclusions: Palifermin permits dose escalation of M up to 280 mg/m2 with acceptable toxicity. A phase 2 trial is planned to better delineate the anti-myeloma efficacy of this regimen. Disclosures: Abidi: Millennium: Speakers Bureau. Off Label Use: Bortezomib is currently not approved for maintenance therapy after Autologous stem cells transplant. Lum: Transtarget Inc: Equity Ownership.

Description: Abstract 2241 Poster Board II-218 Introduction: T-LGL has the phenotype characteristics of a post-thymus mature T cell. Expansion of T-LGL has been reported to occur in association with viral infections, autoimmune diseases, lymphoproliferative malignancy and HSCT. The clinical significance of finding T-LGL expansion post HSCT is unclear. We recently reviewed the incidence of T-LGL expansion in patients who underwent allogeneic HSCT in our institution. We specifically asked whether T-LGL expansion was associated with increased viral infections, stable chimerism, graft-versus-host disease (GvHD), recurrence of primary disease, and overall survival. Patients and Methods: A retrospective analysis was done on all adult patients who underwent allogeneic HSCT at the Karmanos Cancer Institute between January 1, 2004 to June 30, 2009. In patients with persistent lymphocytosis (〉3000 cells/mm3) post HSCT, expansion of T-LGL phenotype was identified by flow cytometry (CD2, CD3, CD5, CD7, CD8 and CD57 positive) and clonality was confirmed by T cell receptor beta and/or gamma gene rearrangement (TCR-GR) using southern blot analysis and polymerase chain reaction (PCR). Results: A total of 547 patients underwent allogeneic HSCT during the study period. We identified T-LGL expansion in 24 patients with persistent lymphocytosis using flow cytometry. Median age of patients with T-LGL expansion was 50 years (range 24-68 years). Median time to diagnosis was 275 days post HSCT (range 69-1454 days) and median duration of follow-up was 811 days (range 85-1701 days). All 24 patients achieved full donor chimerism post transplantation by STR analysis. Fourteen out of 24 patients with T-LGL expansion had positive TCR-GR, in 2 patients TCR-GR was not done and the remainder was negative. Twenty out of 24 patients had cytomegalovirus (CMV) viremia confirmed by PCR before the onset of T-LGL expansion; the remainder had no CMV viremia. In all patients with T-LGL expansion there was no subsequent recurrence of CMV viremia or infection. All 24 patients had documented graft versus host disease (GvHD). In the group with T-LGL expansion only 2 patients relapsed with primary disease and only one patient died (due to a cardiac event). The cumulative incidence of T-LGL expansion was 4.4% at the end of the study period. Conclusion: To our knowledge, this is the largest reported series of T-LGL expansion post allogeneic HSCT. T-LGL expansion was associated with an interesting sequence of CMV viremia preceding T-LGL expansion and subsequent lack of recurrence of CMV viremia or infection. We also observed a very low number of relapse of primary disease or death in patients with T-LGL expansion. One hypothesis is that T-LGL expansion may be a result of specific stimulation with CMV antigens post allogeneic HSCT. An alternate hypothesis is that T-LGL expansion is a surrogate marker for accelerated immune reconstitution. At present, it is also unclear if T-LGL expansion is a marker of ‘graft-versus-leukemia' effect with respect to relapse of primary disease warranting further research. Disclosures: Lum: Transtarget Corporation: Founder