ALBERT

Description: Abstract 675 We have previously identified five biomarker proteins that have diagnostic and prognostic value for acute graft-versus-host disease (GVHD) (Blood 113:273-278, Sci Transl Med 2:50-57). In order to determine whether biomarkers can predict GVHD before the appearance of clinical symptoms, we evaluated the three most informative biomarkers of the five (IL2-Receptor-α, TNFR1, elafin) in patient samples prospectively collected between 2000 and 2010 from 513 unrelated (URD) hematopoietic cell transplant (HCT) patients. We focused on URD HCT recipients because they are most likely to develop acute GVHD and could potentially benefit from a predictive laboratory assay and subsequent preemptive intervention. We measured biomarker plasma levels by sequential enzyme-linked immunosorbent assay on samples obtained prior to conditioning (pre-HCT), and at day +7 and day +14 after HCT. In designing the analytical approach, we took into consideration that median time to GVHD onset is delayed after reduced intensity conditioning, that there may be limited opportunity to preemptively intervene in patients on the verge of developing GVHD, and that there have been changes in GVHD prophylaxis agents over the past decade. Therefore, we randomly divided the patients into training (N=342) and validation (N=171) data sets that were balanced for (i) full intensity conditioning, (ii) onset of grade II-IV GVHD earlier than day +21 and (iii) HCT performed after 2005. In order to create a prediction model for acute GVHD, we used the biomarker levels in the training data set to simulate biomarker values for a hypothetical 50,000 patients using the following assumptions: (1) the incidence of GVHD by day 100 is 55%, (2) the median day of GVHD onset after full intensity URD HCT is day 21, with 10% of patients developing GVHD prior to day +7, and 3% developing GVHD after day +56. These assumptions were based on historical URD HCT data at our center. We used logistic regression to compute a predicted probability, p7, of developing grade II-IV GVHD for each of the 50,000 patients based upon the biomarker levels pre-HCT and at day +7. Any patient with p7≥0.64 was categorized as high risk for development of GVHD. For all low risk patients (p7

Description: Pulmonary complications are common following hematopoietic stem cell transplantation (HSCT). The role of fiberoptic bronchoscopy with broncho-alveolar lavage (BAL) in recipients of reduced-intensity (RI) and full intensity (FI) transplants is now reported. Between January 2001-May 2008, 803 allogeneic transplants (212 RI, 591 FI) were performed on 784 patients at the University of Michigan Medical Center. Pulmonary complications, defined as either hypoxia 〉 24 hours, or clinical/radiographic features of pneumonitis, were identified in 313 (39.9%) patients post-transplant. Bronchoscopy was performed on 265 (84.7%) patients with pulmonary complications, including 69 patients undergoing RI transplants (median age 56 yrs, 10–68 yrs) and 196 patients undergoing FI transplants (median age 41 yrs, 1–64 yrs). The time to BAL was similar for recipients of RI when compared to recipients of FI transplant [median: 89 days (0–1854 days) vs. 104 days (7–1533 days)]. Pathogenic organisms were identified in 31.8% (RI) and 25.2% (FI) of BAL procedures. Invasive fungi were the most commonly identified organisms, identified on 48.1% (RI) and 45.2% (FI) of BALs in which pathogens were noted. The incidence of bacterial, viral (including CMV), and mycobacterial pulmonary infections were similar in recipients of RI and FI transplants. The frequency with which pathogens were identified varied with the timing of the bronchoscopy (see Table), with non-infectious pulmonary complications twice as likely to occur in the first 100 days post-transplant in FI than RI transplant recipients (p 〈 0.05). The BAL led to a change in medical management in 54.1% (RI) and 59.3% (FI) of cases respectively, with modifications in antimicrobial therapy in 38.8% (RI) and 42.1% (FI). The bronchoscopy led to modifications in immunosuppressive therapy in 27.1% (RI) and 27.6% (FI) of cases. BAL procedural related complications were rare in both groups, with pulmonary hemorrhage and transient hypoxemia occurring in 〈 2.5% of all patients undergoing a BAL. Conclusion: The incidence of pulmonary complications, as evaluated by bronchoscopy post HSCT, was similar for recipients of RI and FI conditioning regimen. Within the first 100 days post-transplant, non-infectious etiologies for pulmonary dysfunction were significantly more common in FI than RI patients. There were no other significant differences in the timing of pulmonary complications or the type of pathogenic organisms identified following a FI or RI transplant. Broncho-alveolar lavage is a safe procedure in patients following allogeneic transplants, altering medical management in over 50% of cases. Time post-transplant and % BAL with a pathogenic organism identified Day 0–100 * Day 〉 100 Total RI 32.4% 31.3% 31.8% FI 15.8% 31.8% 25.2%

Description: Abstract 4215 Background: Individuals with hematologic malignancies, are at high risk for Venous thromboembolism (VTE). In patients undergoing hematopoietic stem cell transplantation (HSCT) the incidence and risk of VTE is unclear. Based on this it is difficult to consider prophylaxis in patients who are at potentially high risk for bleeding complications (Gerber, Blood 2008). It is increasingly becoming important to measure the risks of VTE, as the incidence has continued to rise. Different scoring systems have been proposed to assess the risks of VTE in hospitalized patients. In patients who develop VTE during hospitalization their risk of morbidity and mortality is increased. We examined 286 patients who received autologous HSCT transplantation, and 343 patients who underwent allogenic HSCT transplantation at the University of Michigan. We then compared their scores based on the risk assessment score developed by Caprini et al (Ann. Of Surg. 2010). The scoring system was initially validated for patients undergoing surgical procedures, and is currently in use at the University of Michigan to asses risk in bone marrow transplant patients. Risks for the development of VTE range from 10–20% (for moderate risk), 20–40% (higher risk), and 40–80% (highest risk). Objectives: To evaluate the efficacy of Caprinis' risk factor assessment scoring system in patients undergoing autologous and allogenic HSCT and determining the incidence of VTE in the patient cohort. Methods: The medical records of 629 patients between 2005–2008 who received high dose chemotherapy followed by autologous (287) and allogenic (343) stem cell transplants were reviewed. The autologous patient cohort had a mean age of 48.9, and an average BMI of 29.01. The allogenic patient cohort had a mean age of 42.5, with an average BMI of 27.53. HSCT was performed for all of the following conditions: Non-Hodgkin's lymphoma, Neuroblastoma, Multiple myeloma, Leukemia, Myelodysplastic Syndrome, and Hodgkin's lymphoma. The scores were compiled on the day of admission or at the closest date to the actual stem-cell transplant. Based on scoring, the actual incidence of non catheter related VTE in the HSCT patient population was observed. Allogenic patients were observed for VTE incidence from admission to day 30, day 30–100, and 100 days and on. Autologous patients were observed from admission to day 30. Results: 1) Of the 286 patients receiving autologous transplantation the average Caprini risk assessment score was 6.4. The 343 patients receiving allogenic transplantation had an average score of 5.95. Twenty-seven autologous, and fifty-three allogenic patients were at higher risk (3-4 point range) with a 20–40% chance of developing a VTE. 259 autologous patients, and 287 allogenic patients were at the highest risk (5+ point range) with a 40–80% chance of developing a VTE. 2) In both patient cohorts, based on the Caprini risk assessment score HSCT patients were placed in the highest risk category with a 40–80% chance of developing a VTE. 3) Only two patients (0.69%) developed an actual VTE during hospitalization for autologous HSCT. These patients both had a score of 10. Two patients (0.58%) receiving allogenic HSCT developed a VTE from the time of admission to 30 days. These patients had an average score of 7.5. From 30–100 days 5 patients deve loped a VTE, of these patients 1 developed CGVHD, The patients had an average score of 7.6. Twenty patients developed a VTE greater then 100 days, of these patients, 4 of which developed CGVHD. The patients had an average score of 6.55. Conclusion: The Caprini Venous Thromboembolism risk factor a ssessment score is not valid in patients undergoing high dose chemotherapy followed by an autologous or allogenic transplant. HSCT patients are at high risk for bleeding complications and the risk of VTE is relatively low (

Description: Abstract 35 Patients with hematologic malignancies who are not in remission prior to allogeneic hematopoietic stem cell transplantation (HSCT) have a poor prognosis. In an effort to improve the anti-tumor activity of conditioning without added toxicity, we combined clofarabine, which is known to have a significant anti-leukemia activity, with myeloablative doses of busulfan in a phase I/II study in non-remission hematologic malignancies. Busulfan was administered as a single daily dose of 3.2 mg/kg IV × 4d (days -5 to -2) and clofarabine as a single daily dose of 20, 30 or 40 mg/m2 IV × 5d (days -6 to -2) with the specific dose determined by the Time to Event-Continuous Reassessment Method (TITE-CRM). All pts received dexamethasone 12 mg IV on the days of clofarabine to prevent capillary leak syndrome. Graft-versus-host-disease (GVHD) prophylaxis was tacrolimus/MMF in all but one patient (tacrolimus/methotrexate). Forty six pts were enrolled. Characteristics of pts are shown in table 1. Prior to HSCT, pts failed an average of 3 regimens (range: 1–5), none were in remission, and 68% of leukemic pts had peripheral blasts. The majority received unrelated and / or HLA mismatched grafts. CloBu4 was generally well tolerated. Grade 3–4 non-hematological toxicities observed from initiation of conditioning to day +30 include: transient transaminitis (50%), mucositis (26%), hand-foot syndrome (13%), transient hypoxia (13%), nausea/vomiting (11%), diarrhea (11%), hypertension (7%), veno-occlusive disease (4%), hyperbilirubinemia (4%), hypersensitivity (2%), joint pain (2%) and seizure (2%). There were no cases of renal insufficiency and all cases of transaminitis resolved to ≤grade 1 within 14 days. All patients engrafted (median 11 days for neutrophils [range: 9–16]; 10 days for platelets [range: 1–20]. Lineage specific chimerism was analyzed at day 30, 100, 180, and 365. Full donor chimerism in CD3 lineage was achieved in 54%, 75%, 94% and 100% of pts on days 30, 100, 180 and 365, respectively. Absolute CD4 counts were 228±170, 238±147 307±151, and 341±184 cells/μ l on days 30, 100, 180, and 365, respectively. Acute GVHD (≥ grade 2) occurred in 48% of pts and resulted in five deaths. Overall, 80% of pts achieved CR by day +30 (AML = 94%, Others = 53%, AML without prior allo HSCT = 100%). Cumulative incidence of relapse in AML patients was 38%. The median duration of remission for AML pts was 15.4 months (range 2–34 m). Non-AML pts experienced a higher incidence of relapse/progression (67%, p=0.008) and shorter remissions (8.6 m, range 2–29 m). At a median follow up of 18 months, overall survival for the entire cohort was 42% at 18 months post-transplant (50% for AML, n=31). In conclusion, these data suggest that clofarabine combined with myeloablative doses of busulfan is well tolerated, facilitates engraftment, and has significant anti-tumor activity, particularly in patients with non-remission AML at HSCT. Given that CloBu4 reliably led to remissions that lasted a median of 15.4 months in non-remission AML pts, this regimen may provide a platform for further interventions such as maintenance therapy for this population of pts. Disclosures: Mineishi: Genzyme: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding. Off Label Use: Clofarabine use for transplant conditioning regimen. Erba:Genzyme: Consultancy, Honoraria, Research Funding.

Description: Abstract 3119 Hematopoietic stem cell transplants (HCT) for older patients with acute myelogenous leukemia (AML) have increased significantly over the past decade, associated with the use of reduced intensity conditioning (RIC) regimen. In the unrelated donor (URD) setting, anti-thymocyte globulin (ATG) has routinely been used to improve engraftment and decrease the incidence and severity of graft versus host disease (GVHD). We hypothesized that replacing ATG with low dose total body irradiation (TBI) during conditioning would provide sufficient immunosuppression to permit engraftment in older patients undergoing unrelated donor transplants for AML. Outcome data, including engraftment and GVHD rates were then compared to similar patients undergoing matched related donor (MRD) HCT for AML. Methods: Between 2007–2012, 50 patients (55–70 years, median 61 years) with AML in CR1 (n=41) or 〉CR1 (n=9) were prospectively enrolled on an IRB-approved clinical trial using a RIC regimen. Donors were either MRD (n=23), or URD (n=27) if a suitable MRD was not available. HLA matched donors were available in 39 of the 50 patients, with single antigen mismatched donors used in 11 (41%) URD cases. All patients were conditioned with fludarabine (160 mg/m2) + busulfan (6.4 mg/m2) [FluBu2]; URD recipients additionally received 200cGy TBI on day -1 pre-transplant. GVHD prophylaxis was tacrolimus and mycophenolate. Patients exhibited high risk (n=21) or intermediate risk (n=29) disease at initial diagnosis, as defined by cytogenetic and molecular criteria. High risk (HR) patients included those with either a FLT3 mutation, monosomy 5 or 7, 5q-, 7q-, t(6:9) or complex cytogenetics (〉 3 abnormalities). Patients with t(8:21), t(16:16) or inv 16 were excluded from analysis. Stem cell sources included peripheral stem cells (n=49) or marrow (n=1). Results: For the entire cohort, the 1y and 3y relapse free survival (RFS) was 56% (95% CI: 43–69) and 43% (95% CI: 28–58) respectively, with 1y and 3y overall survival (OS) rates 58% (95% CI:46–74) and 44% (95% CI: 27–62%). There was no significant difference in 1y RFS between URD and MRD recipients [62±9.5% vs 48±11%] or 3y RFS [44±11% vs 40±12%], p = 0.42 (Figure). There was no difference in outcome by age, with 3y RFS 42.5±11% for patients 55–59 yrs (n=20) and 40±12% for patients 60–70 yrs (n=30), p =0.54. The median donor age was 37 yrs (range 19–50) for URD and 58 yrs (range 42–70) for MRD recipients. The median CD34 cell dose infused was 5.0 × 10(6)/kg in both cohorts [range URD: 1.2 –8.3 × 10(6), MRD: 1.9 –9.8 × 10(6)]. There was no difference in time to neutrophil engraftment, with both cohorts engrafting a median 12 days post-transplant. Primary graft failure occurred in 1 (3.4%) URD recipient, who received an HLA mismatched graft. No cases of secondary graft failure occurred in either cohort. Day 100 CD33 chimerism was all donor in all URD cases, and in 75% of MRD recipients. Grade 2–4 acute GVHD developed in 44% URD and 30% MRD respectively, with grade 3–4 acute GVHD in 7% URD and 10% MRD. Patients with intermediate risk disease experienced 1y and 3y RFS of 74±8.5% and 3-year RFS 62±10.5%, respectively. By comparison, transplant outcomes were poor for patients with high risk disease, with 1y and 3y RFS only 31±10% and 13±10% (Figure). Conclusion: Replacing ATG with low dose TBI in older AML patients undergoing RIC URD does not appear to compromise engraftment or increase GVHD rates. Survival is similar to that experienced by MRD recipients who are transplanted without either ATG or TBI. RFS for patients with high risk AML was poor, but patients with intermediate risk AML may benefit from this strategy when compared to historical results with non-transplant approaches for this patient population. Disclosures: Talpaz: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; B.M.S.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Teva: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Couriel:Therakos: Speakers Bureau; Merck: Speakers Bureau.

Description: Background: The combination of fludarabine with a myeloablative dose of busulfan (FluBu4) has been shown to be well tolerated with reduced toxicity compared to other myeloablative regimens. Clofarabine is a second generation purine antimetabolite with potent anti-leukemia properties. We replaced fludarabine with clofarabine in a phase I/ II trial of Clofarabine-Busulfan x 4 (CloBu4) in an attempt to develop a pre-transplant conditioning regimen suitable for pts with refractory, non-remission hematologic malignancies at the time of transplant. Methods: All pts had a hematologic malignancy not in remission at the time of transplant. Busulfan was administered as a single daily dose of 3.2 mg/kg IV x 4d (days -5 to -2) and clofarabine as a single daily dose of 20, 30 or 40 mg/m2 IV x 5d (days -6 to -2) with the specific dose per pt determined by the Time to Event-Continuous Reassessment Method (TITE-CRM). All pts received dexamethasone 12 mg IV on the days of clofarabine to avoid capillary leak syndrome. GVHD prophylaxis was tacrolimus/MMF in19 pts and tacrolimus/methotrexate in 1. Results: To date, 20 pts are evaluable for toxicity, 19 for engraftment, and 16 for response. Diseases were AML (including 2 myeloid blast crisis of CML) (n=13), ALL (n=2), CLL (n=2), NHL (n=2), and multiple myeloma (n=1). Six pts had received previous stem cell transplantation (SCT), 2 auto SCT (range between SCT 295-1066 d) and 4 allo (range 75–1002 d). The clofarabine dose levels were: 20 mg/m2 (n=6), 30 mg/m2 (n=13) and 40 mg/ m2 (n=1). The median age of patients was 51 years (range 13–68). Donors were siblings (n=8) or unrelated volunteers (n=12). All 19 evaluable pts engrafted at a mean of 11 days for both neutrophils and platelets. Busulfan kinetics were evaluated in 14 patients with an average steady state level of 803 ng/ml (605–1132). Dose increase was required in 2 cases and decrease in 2 cases to maintain target range of 600–900 ng/ml. One pt who developed hypersensitivity to clofarabine with fever and joint pain after the first dose, received an additional 20 mg of dexamethasone with subsequent doses and finished all five doses of clofarabine. Other grade 3–4 toxicities attributable to the conditioning regimen include transient liver enzyme abnormalities (8/20), hypoxia (5/20), hypertension (2/20), seizure (1/20), and ascites (2/20). Neither case of ascites had elevated bilirubin, but one case showed pathologic findings compatible with veno-occlusive disease on liver biopsy. Both of these pts had pre-existing conditions including pretransplant liver damage (1) and enlarged spleen before SCT due to preceding myelofibrosis (1). Acute GVHD developed in 2/20 and proved fatal in one case. Peripheral blood CD3+ cell chimerism was evaluable in 10 pts on day 30; 1 pt had 100% donor CD3+ cells, whereas 9 pts had in mixed chimerism (

Description: Abstract 740 Introduction: Graft-versus-host disease (GVHD) precludes an effective utilization of allogeneic hematopoietic stem cell transplantation (HSCT). Histone deacetylase inhibitors (HDACi) are an important class of anti-cancer agent and have recently been shown by us and others to attenuate experimental GVHD in multiple murine models. They suppress proinflammatory cytokine production, modulate antigen presenting cells (APCs), and enhance T regulatory cell (Treg) numbers and functions. We have translated our experimental observations from murine models in a first-in-human clinical trial to test the hypothesis that HDAC inhibition will be safe and reduce the severity of GVHD in patients undergoing matched related donor (MRD) reduced intensity conditioning (RIC) allogeneic HSCT. Methods: From March 2009 through June 2012, we enrolled 45 patients at two centers, the University of Michigan and Washington University, in a phase I/II trial that combined the HDACi, vorinostat, with standard GVHD prophylaxis regimen consisting of tacrolimus and mycophenolate mofetil (MMF) and compared them with historical controls. The primary endpoint was the cumulative incidence of grade 2–4 acute GVHD (aGVHD) with a target risk of 25%, which would represent a statistically significant improvement over the 42% risk experienced by historical controls, assuming a type I error rate of 5%. The controls comprised of patients who underwent MRD RIC allogeneic HSCT and received standard GVHD prophylaxis with tacrolimus and MMF. Study eligibility included adult patients with a hematological malignancy for which RIC HSCT was considered appropriate and had an available 7/8 or 8/8-HLA-MRD. Specifically, patients with CLL and lymphoma must have been in CR, PR or had stable disease. Patients with myelodysplasia, acute leukemia or CML must have had 〈 20% blasts on the bone marrow examination. Study subjects received fludarabine 40 mg/m2 for 4 days, busulfan 3.2 mg/kg for 2 days, MMF for 29 days, and tacrolimus levels were maintained between 8–12 ng/mL through day (D) 56, and then tapered off by D180 (in the absence of GVHD). The investigational agent, vorinostat, was administered orally from D-10 to D100. Results: The median age of the study patients (vorinostat-treated) was 58 years (range, 43–69 years). There have been no cases of graft failure or excessive toxicity or death attributable to vorinostat. The median time to neutrophil and platelet engraftment was similar between study and controls (12 vs 11 days, respectively, for both groups). Bone marrow chimerism analyses for study patients showed the percent of myeloid (CD33+) engraftment to be 94%, 100% and 100%, and whole T cell (CD3+) engraftment to be 74.5%, 75%, and 100% at D30, D100 and D365, respectively. In the 45 study patients, the cumulative incidence of D100 grade 2–4 aGVHD was significantly lower compared to controls (22% vs 42%, respectively, P=0.04). Severe grade 3–4 aGVHD at D100 (4% vs 19% controls) and transplant-related mortality at 1 year (13% vs 19% controls) were also reduced. The incidence of aGVHD was globally diminished in all target organs, and all but one patient responded rapidly to standard steroid therapy. The incidence of relapse was similar between the study and controls (17% vs 20%, respectively). Infectious complications were not different between the groups. We performed several correlative analyses with patient samples to understand the putative mechanisms based on murine studies. Peripheral blood mononuclear cells (PBMCs) from study patients demonstrated enhanced histone (H3) acetylation at D30 compared with PMBCs from controls (P

Description: Abstract 1713 Genomic aberrations like 17p and 11q deletions and mutations in p53 affect survival outcome in CLL. To further our understanding of the anatomy and clinical importance of various acquired genomic copy number aberrations (aCNA) in CLL, we have generated SNP 6.0 array-based genomic profiling data of DNA from sorted CD19+/CD3+ cells from 256 CLL patients, of which 201 were untreated and 55 relapsed (median number of prior therapies 1) at study enrollment. Acquired CNAs were detected using visual inspection of paired (CD19+: tumor/CD3+: normal reference DNA) genomic copy number heatmap displays using the validated software tool dChipSNP. This analytical approach is conservative and has been previously externally validated using FISH for other tumor types and lesions 〉 0.2 Mb. The range of aCNA for all cases was 0–22 lesions, most of which were sub-chromosomal deletions. We did not detect a sub-chromosomal aCNA in 72/256=28% of the cases even at this ultra-high resolution, suggesting that sub- chromosomal aCNA are not involved in the pathogenesis of this CLL subset. Three or more sub-chromosomal lesions were found in 50/256=20% of all cases analyzed; this is likely a low estimate of the true frequency of this genomic CLL type given the aggressive clinical behavior. Of the 50 cases with ≥3 sub-chromosomal lesions, 26 harbored somatically acquired p53 exon 2–10 mutations (26/50=52%). Next we determined the prognostic importance of various established and novel biomarkers on the clinical endpoint overall survival (OS; alternatively computed using either the CLL diagnosis date or the trial enrollment date as the reference date). For previously untreated patients (N=201) and for the OS analysis based on the diagnosis date and the date of death, OS was 84 months for p53 mutated cases (N=24), 94 months for 17p cases (N=16), 116 months for 11q cases (N=14), 237 months for ZAP70+ cases (N=85), 174 months for IgVH unmutated cases (N=82) and 167, 90 and 52 months for ≥2 (N=68), ≥3 (N=31) or ≥4 (N=19) aCNA based on SNP 6.0 array profiling, respectively. For all patients (N=256) and for the OS analysis based on the diagnosis date and date of death, OS was 96 months for p53 mutated cases (N=36), 91 months for 17p cases (N=25), 123 months for 11q cases (N=25), 139 months for ZAP70+ cases (N=123), 123 months for IgVH unmutated cases (N=116) and 144, 108 and 77 months for ≥2 (N=100), ≥3 (N=50) or ≥4 (N=33) aCNA based on SNP 6.0 array profiling, respectively. Furthermore, CLL patients with wild type p53 exons 2–10 and SNP 6.0 array-based genomic lesion loads of 2 lesions or more had significantly (all p

Description: Abstract 43 We have previously shown that TNF Receptor 1 (TNFR1) levels early after myeloablative hematopoietic cell transplant (HCT), especially following unrelated donor (URD) HCT, predict later graft-versus-host disease (GVHD), non-relapse mortality (NRM), and overall survival (OS). Given this data we hypothesized that augmenting standard GVHD prophylaxis with the TNF-inhibitor etanercept would protect against GVHD and NRM while improving survival. We therefore conducted an IRB-approved Phase II trial at two centers to determine whether prophylactic TNF blockade with etanercept decreases the rates of acute GVHD and day 100 NRM seen after high-risk allogeneic matched (n=68, 71%) or single antigen mismatched URD (n=25, 26%) or single antigen mismatched related donor (RD) (n=3, 3%) HCT. Follow-up data are available for 96/100 patients (pts) enrolled between 2005 and 2009. HLA matching used high-resolution DNA-based techniques for HLA-A, B, C, and DR. Patients received tacrolimus, methotrexate (5 mg/m2 on days 1, 3, 6, 11) and etanercept (0.4 mg/kg, max 25 mg) twice weekly from the start of conditioning to day 56. All pts received myeloablative regimens; either TBI/cyclophosphamide (TBI, n=29), fludarabine and 12.8 mg/kg IV busulfan (FluBu4, n=31) or other myeloablative chemotherapy regimens, either BCNU/etoposide/cyclophosphamide or busulfan/cyclophosphamide (BCNU/Busulfan, n=36). The median age of the pts was 45y (range 2-61y). To determine whether the administration of etanercept effectively reduced post-transplant TNFR1 levels we compared day 7 post-transplant TNFR1 levels in the 96 study pts to 132 control pts who received standard GVHD prophylaxis of tacrolimus/methotrexate and were matched for age, conditioning regimen, degree of HLA-match, and disease status. The median day 7 TNFR1 levels in study pts was 2518 pg/ml, significantly lower than the median day 7 level of 3529 pg/ml in control pts (p