ALBERT

Description: Bone marrow stromal cells (BMSC, also known as bone marrow-derived “mesenchymal stem cells”) have been used to treat acute graft-versus-host disease (GVHD) and other complications following allogeneic hematopoietic stem cell transplantation (SCT). We conducted a phase I trial using third party, early passage, BMSC for patients with steroid-refractory liver or gastrointestinal GVHD, tissue injury or marrow failure following SCT to investigate safety and clinical responses following BMSC infusion. To identify mechanisms of BMSC immunomodulation and tissue repair, patients were monitored for plasma GVHD biomarkers, cytokines, growth factors, and lymphocyte phenotype before and after BMSC infusion. BMSCs were prepared from marrow aspirates from healthy volunteers with the expansion of 3 passages. Ten subjects were infused a fixed dose of 2 x 106 BMSCs /kg weekly for 3 doses. There was no treatment related toxicity (primary endpoint). Eight subjects were evaluable for response assessment at 4 weeks after the last infusion. Five of the seven patients with steroid-refractory acute GVHD achieved complete remission (CR), two of two patients with tissue injury (pneumomediastinum/ pneumothorax) achieved resolution but there was no response in two subjects with delayed marrow failure. Rapid reductions in inflammatory cytokines occurred after the first BMSC infusion (fig1). Clinical responses correlated with a fall in biomarkers (Reg 3α, CK18, and Elafin) relevant for the site of GVHD, or CK18 for tissue injury. The GVHD complete responders survived significantly longer (〉300 days vs a median of 33 days), had higher baseline absolute lymphocyte and central memory CD4 and CD8 counts but there was no clear difference in natural or induced Tregs. Cytokine changes also segregated with survival. These results confirm that BMSC are associated with rapid clinical responses and biomarker normalization in steroid-refractory GVHD and PM. However BMSC were ineffective in patients with more aggressive GVHD with lower lymphocyte counts, which suggest that effective GVHD control by BMSC, requires a relatively intact immune system. Early detection and BMSC treatment appear important in patients with refractory GVHD. Disclosures: No relevant conflicts of interest to declare.

Description: The advent of imatinib, and subsequently, other tyrosine kinase inhibitors (TKIs) has relegated allogeneic stem cell transplantation (SCT) to second-or third-line therapy for chronic phase-chronic myeloid leukemia (CML). A significant shortcoming of TKIs in the large majority of good-responder patients is the persistent detection of BCR-ABL transcripts despite achievement of complete cytogenetic response (CCyR) or major molecular response (greater than 3-log reduction of BCR-ABL levels below a standardized baseline in minimal residual disease (MRD) measurements from total mononuclear cells). The presence of this MRD, and the demonstration that primitive CD34+ cells from patients in CCyR still harbor BCR-ABL (Bhatia, et al, Blood 2003) strengthens the opinion that TKIs do not eradicate all CML cells. Conversely, SCT has apparently cured some CML patients with more than 20 years follow-up. Of note, MRD is also quite frequently found in CML patients more than 5 years post-SCT, and donor lymphocyte infusions (DLI) are usually given to patients who satisfy criteria for molecular relapse. We compared the level of BCR-ABL transcripts in primitive hematopoietic cells from patients who were treated with T-depleted SCT with scheduled T-cell addback from D+45 to D+100 post-SCT (n=34) with levels in those taking TKIs (n=4). CD34+ progenitor cells were isolated from leukapheresis collections at D+120 post-SCT (n=13), peripheral blood from D+60 – 66 months post-SCT (n=19), bone marrow aspirates in patients on long-term follow-up (4–10 years) post-SCT (n=8) or 15 – 18 months post-TKI treatment alone (n=4); serial post-SCT samples were available in 6 patients. Using fluorescence activated cell sorting, hematopoietic stem cells (HSC, CD34+CD38-Lin-CD90+), common myeloid progenitors (CMP, CD34+CD38+Lin-IL3Rα+CD45RA-) and granulocyte-macrophage progenitors (GMP, CD34+CD38+Lin-IL3Rα+CD45RA+) were collected. BCR-ABL expression in primitive CD34+ subpopulations and total leukocytes from peripheral blood (PB) was measured using real-time quantitative polymerase chain reaction, with the sensitivity to detect one BCR-ABL-positive cell in 106 normal cells. A median of 112 x 106 mononuclear cells (range 16 – 582 x 106) were available per patient sample, with a median of 3 x 106 CD34+ cells (range 1 – 90 x 106) sorted. There was no difference between the number of HSC, CMP or GMP CD34+ cells collected between MRD negative or MRD positive-post-SCT patients, or TKI-treated patients. All patients with negative MRD in PB (n=12 post-SCT, n=1 post-TKI) did not have detectable BCR-ABL transcripts in primitive CD34+ subpopulations. Furthermore, in PB MRD-positive patients, 3/21 (14%) post-SCT and 2/2 (100%) post-TKI did not have detectable BCR-ABL transcripts in HSC, CMP or GMP populations. 18/21 (86%) PB MRD-positive patients who were post-SCT had detectable BCR-ABL transcripts in at least one primitive CD34+ subpopulation. A rise in BCR-ABL levels in GMP populations tended to herald impending relapse. In post-SCT patients on long-term follow-up with persistent PB MRD positivity not fulfilling criteria for molecular relapse, the highest BCR-ABL levels were in HSC populations. In comparable patients with a major molecular response, post-SCT patients appeared to harbor a greater amount of residual leukemia cells in CD34+ subpopulations than TKI-treated patients. Our observations suggest that although SCT is a curative treatment for CML, the graft-versus-leukemia effect may eliminate only more mature leukemic CD34+ subpopulations in some patients who have enduring positive MRD post-SCT, with persistence of the most primitive leukemic HSCs, which are presumably constrained in patients who do not fulfill criteria for relapse. Conversely, TKI appears to reduce the number of BCR-ABL-positive primitive CD34+ subpopulations, especially GMPs and CMPs, more efficiently. Our data support TKI-treatment as an adjunct to DLI to treat CML relapse post-SCT, and concurrent vaccination strategies which are able to target surface proteins on HSC to eradicate disease.

Description: Abstract 2091 Allogeneic hematopoietic stem cell transplantation (HSCT) strategies must serve as platforms for adoptive cellular immunotherapy if the graft-versus-leukemia (GVL) effect is to be fully exploited. In sequential clinical trials at the National Institutes of Health we have used ex-vivo T cell depletion to develop an HSCT with minimal graft versus host disease (GvHD) prophylaxis followed by elective donor lymphocyte infusion on day 90. T-cell depletion creates the lymphodepleted environment for preferential homeostatic expansion of adoptively infused cells, while minimization of post-transplant immunosuppression promotes expansion of the adoptively transfused cells. Since non-engraftment is a limiting complication with extreme T lymphocyte depletion and reduced GvHD prophylaxis, we measured lineage-specific chimerism and clinical outcomes utilizing our optimized approach. Thirty-six patients with hematologic malignancies underwent allogeneic HSCT with a graft from their HLA-identical siblings. The median age was 43 years (range 16–68), 50% were males. Transplant indications were AML(17), ALL (7), MDS (6), CML (2), CLL (2), NHL (1) and CMMoL (1). 50% were standard risk and 50% were high risk. Subjects received myeloablative conditioning regimen with cyclophosphamide (60 mg/kg/dose × 2), fludarabine (25 mg/m2/dose × 5) and total body irradiation (12 Gy divided in 8 fractions, with lung shielding to 6 Gy). Subjects 55 years of age and older received 4 Gy divided in 8 fractions without lung shielding. G-CSF mobilized peripheral blood stem cells from the donor were CD34+ selected by the Miltenyi CliniMacs system, with infusion of a target CD34+ dose of 6 × 106/kg (range 3 to 10 × 106/kg) and a fixed CD3+ dose of 5 × 104/kg. Low-dose cyclosporine till day 21 was the sole GVHD prophylaxis. Delayed lymphocyte add back (5 × 106 CD3+/kg) was given at day 90 in the absence of significant GvHD. CD3+ and myeloid chimerism analysis were performed sequentially on peripheral blood with early lymphocyte add back in cases with falling chimerism. Day 200 overall survival (the primary study endpoint) was 84%. One patient, who was postpartum, failed to engraft and required a second transplant. 34/36 subjects achieved complete donor (〉95%) myeloid chimerism by day 14 and the median time to complete donor CD3+ chimerism was 45 days. The incidence of acute GVHD grade II, III and IV were 23%, 2.9% and 0%, respectively. The incidence of chronic GVHD was 34.3%. At a median follow up of 3.7 years, Kaplan-Meier estimates of relapse, nonrelapse mortality and overall survival were 32%, 31% and 46% respectively. In conclusion, transplants utilizing this approach have acceptable engraftment and clinical outcomes and may serve as an ideal platform for adoptive cellular immunotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3312 Poster Board III-200 Allogeneic hematopoietic stem cell transplantation (SCT) is a curative treatment for some hematological malignancies. The ultimate measure of success of allogeneic SCT for hematological malignancies is its ability to eradicate malignant disease and restore a good quality of life (QOL) in long-term survivors. As numbers of survivors continue to increase, studies systematically examining outcomes in this group of survivors are needed. We studied the clinical and QOL outcomes in a large cohort of patients with hematological malignancies surviving 5 or more years after allogeneic SCT from a single institution. In 2005 we initiated a long term follow up protocol to further study complications in survivors after allogeneic SCT. Patients were enrolled at the third annual visit after transplantation. Annual follow-up visit includes comprehensive clinical evaluation and detailed assessment of QOL, symptom distress, physical and mental health. Measures for QOL included the Functional Assessment of Cancer Therapy-General (FACT-G), the Physical and Mental Component Summary scales (PCS, MCS) of the Medical Outcomes Short-Form 36 (SF-36), and the Rotterdam Symptom Checklist (RSCL). Two hundred sixty two patients with hematological disorder received a SCT from an HLA identical sibling since 1993. One hundred and twenty one patients (46 %) survived 3 or more years and were eligible for participation in the long-term evaluation protocol. Ninety two (35%) survived beyond 5 years from SCT (median follow-up 9.4 years, range 5.1-15.3) and were included in this analysis. Median age at transplantation was 35 years (range 10 - 56). Twenty-two (24%) received a bone marrow transplant, and 70 (76%) received a peripheral blood SCT. We examined chronic graft-versus-host-disease (cGVHD), disease relapse, survival and QOL. Seventeen (18%) of 92 survivors had active cGVHD (limited 9, extensive 8) and were receiving prolonged immunosuppressive treatment 5 years following allogeneic SCT. Four relapsed with leukemia, at a median of 8.5 years (range 6.2 -14.0) post SCT. Four (4.3%) died between 7.4 -13.4 years post SCT (1 relapse, 1 lung cancer, 1 pneumonia, 1 brain hemorrhage). Sixty (65%) completed QOL measures. Most survivors beyond 5 years had an excellent performance status with no difference in the PCS (p =0.89) and MCS (p =0.15) scores and higher FACT-G scores compared with population norms (p =0.02). Although the overall distress for physical and psychological symptoms was low, higher levels of symptom distress were associated with impairments in QOL. In eleven survivors with cGVHD, there was no statistical difference across QOL outcomes although the difference was meaningfully lower (≥5 points). In conclusion, five or more years after SCT for hematological malignancy most individuals survive disease free with an excellent performance status, preserved physical and psychological health, and excellent QOL. However patients with leukemia appear to have a persistent but low chance of disease recurrence. Although cGVHD persists in about 20% of patients it did not appear to affect the excellent QOL that most of our patients experience. The association between cGVHD severity and specific cGVHD manifestations and QOL outcomes requires further study. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4705 We evaluated a photodepletion technique to selectively deplete graft-versus-host disease (GVHD) alloreacting T cells from stem cell transplants. Donor lymphocytes were stimulated with irradiated in-vitro expanded recipient T lymphocytes. Alloactivated T cells preferentially retaining the photosensitizer 4, 5-dibromorhodamine 123 (TH9402) (Kiadis Pharma, NL) were eliminated by light exposure. Twenty-four patients with hematological malignancies (16 high-risk) conditioned with fludarabine, cyclophosphamide and total body, irradiation received a CD34-selected stem cell allograft from an HLA identical sibling and 5×106/kg selectively depleted (SD) donor T cells. Low-dose cyclosporine was used as the only post-transplant immunosuppression. The overall probability of grade III-IV a-GVHD was 13%. Fourteen patients developed chronic GVHD (c-GVHD). Five patients relapsed, 2 of whom remain alive in remission after further treatment. Thirteen patients survive at a median of 22 months. Overall survival and disease free survival probabilities (+/− SEM) were 43 +/− 13% and 35 +/− 13% respectively. The SD technique resulted in a low incidence of relapse (24 +/− 10%), but was complicated by late non-relapse mortality associated with c-GVHD and infection of 50 +/− 14% at 4 years follow up. These results suggest that SD may effectively reduce severe a-GVHD while conserving graft-versus leukemia effects, but the depletion strategy has yet to be optimized. Disclosures: Mielke: Kiadis Pharma: Research Funding.

Description: Introduction: Little is known about the lethality of acute GVHD (aGVHD) in T -cell depleted (TCD) allogeneic hematopoietic stem cell transplantation (HSCT). We examined the incidence of aGVHD and its relative contribution to non relapse mortality (NRM) in a cohort of consecutive TCD HSCT at a single institute. Methods: We report 132 consecutive subjects who had undergone TCD HLA-identical sibling HSCT between 2006 and 2016 for hematologic malignancies. All subjects received conditioning with Fludarabine 125mg/m2, Cytoxan 120 mg/kg and 1200 cGy total body irradiation (TBI) ( 31 days) achievement of complete donor lymphoid chimerism. Significantly improved outcomes were noted for those transplanted beyond 2012: OS, NRM and CIR being 82%,6.2% and 20% at one year, and 68%, 6.2% and 41% at 3 years. Cox proportionate hazard modeling identified steroid refractory aGVHD (HR 4.0, P=0.007) and transplant prior to 2012 (HR 6.7, P=0.001) as significant factors impacting NRM. Conclusions: T cell addback after ex vivo TCD HSCT was associated with a significant burden of aGVHD. Steroid refractory aGVHD impacted NRM, but slow lymphoid engraftment, disease risk, CMV reactivation and age did not. Significant improvements in NRM in the current era suggest greatly improved salvage of steroid refractory aGVHD. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: High rates of cervical HPV disease in women after allogeneic stem cell transplantation (SCT) have been reported, but risk factors related to severe, multifocal, including vaginal and vulvar, HPV disease are not defined. Objective: To determine rates and risk factors for multifocal and severe HPV disease in post-transplant women. Methods: In a prospective long-term study after SCT, gynecologic history and assessment, cervical cytology and HPV testing were obtained with follow-up colposcopy and surgery as indicated for abnormal results. Prior HPV disease, genital graft-versus-host-disease (gGVHD), chronic GVHD (cGVHD) and immunosuppression treatment (IST) 〉3years were assessed for their association with extent and severity of genital HPV disease. Logistic regressions were used for multivariate analysis. Results: Sixty five long term (〉3 year) SCT survivors were studied prospectively on protocol. Patients received allogeneic transplantation from HLA-identical sibling donors with most undergoing myeloablative total body irradiation (94%) and T lymphocyte-depleted peripheral blood stem cells in 91% Of 65 women, 62 had gynecologic assessment with 8 (13%) having prior history of HPV disease; 16 (26%) had gGVHD. 20 women (32%) had acute GVHD, 46 (74%) had cGVHD; extent was limited in 23(37%) and extensive in 23(37%). 26(42%) had cGVHD requiring IST 〉3years. Of 21(34%) women with HPV disease after transplant, 12 required surgery and 7 had multifocal disease. Extensive chronic GVHD (but not acute GVHD) was found to significantly impact occurrence (OR=3.5, p=0.038), high-grade severity (OR=7.1, p=0.024) or multifocal HPV disease (OR=14.6, p=0.017). Conclusion: Women who have undergone SCT have an increased risk of genital HPV disease, with highest rates in women with extensive cGVHD. Likely as a result of chronic immune dysregulation and the temporal nature of HPV, these women are at high risk of severe, multifocal disease, which if untreated may progress to genital cancer. Thus, gynecologic assessment as well as possible post-transplant HPV vaccination are critical aspects of care for women with significant GVHD post-transplant. Support: Intramural programs of NHLBI, Clinical Center and NICHD, NCT00106925 Disclosures Stratton: Allergan: Research Funding.

Description: INTRODUCTION: Ex-vivo T cell depletion strategies have been widely used to reduce the incidence of graft versus host disease (GVHD) in allogeneic stem cell transplantation (allo-SCT). Although several options of ex-vivo graft manipulation strategy are available, direct comparison between strategies along with relevant biomarkers has been lacking. Here we evaluated cellular and plasma biomarkers in two separate graft manipulation strategies, CD3-CD19 depletion versus CD34+ selection using the Miltenyi CliniMACS and their association with clinical outcomes. METHODS: Forty two subjects with hematological malignancies underwent HLA matched sibling allo-SCT at a single center between 2012 and 2015 and received either an ex-vivo CD3-CD19 depleted, CD34+ negatively selected graft (CD3/19D, n=20) or an ex-vivo CD34+ cell positively selected graft (CD34S, n=22). Both cohorts were treated with the same conditioning regimen of cyclophosphamide, fludarabine, and total body irradiation (600-1200 cGy) and GVHD prophylaxis of low dose cyclosporine. Peripheral blood mononuclear cells and plasma samples were collected at days 14 or 30, 60, 100 post-transplant. Post-transplant cellular immune reconstitution was evaluated by multi-color flow cytometry immunophenotyping, characterizing the subsets of memory T cells, regulatory T cells (Tregs), natural killer (NK) cells, and B cells with various functional markers. The plasma levels of ST2, Reg3α, and sTNFR1 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at transplant was 48 years (range 17-70) in CD3/19D and 45 years (11-73) in CD34S. At a median follow up of 37 months in CD3/19D and 22 months in CD34S, the major clinical outcomes were similar between two groups; the overall survival (70% and 86%), non-relapse mortality (5% and 4.5%), and cumulative incidence of relapse (35% and 39%) at 2 years, respectively. Two subjects in CD3/19D developed late engraftment failure before day 100 but all other subjects achieved primary neutrophil and platelet recovery. Unexpectedly, the cumulative incidence of grade II-IV acute GVHD was higher in CD3/19D (61%) in comparison to the incidence in CD34S (32%, P=0.07, Figure). The cumulative incidence of extensive chronic GVHD was 33% in CD3/19S and 24% in CD34S. The fraction of Helios negative Tregs post-transplant was significantly lower in CD3/19D (median [interquartile range]: 10.4% [7.1-16.4] at day 30; 4.9% [3.0-8.3] at day 60) compared to CD34S (23.8% [10.7-35.8], P=0.03 at day 30; 8.8% [6.8-18.4], P=0.01 at day 60, Figure). Plasma ST2 levels were significantly higher in CD3/19D (45ng/mL [27-67] at day 14; 33ng/mL [27-62] at day 28) in comparison to CD34S (29ng/mL [19-40], P=0.03 at day 14; 25ng/mL [14-33], P=0.03 at day 28, Figure). In addition, significantly higher CD4 naive T cells, lower effector memory and PD-1 bright CD4 T cells were observed in CD3/19D in comparison to CD34S. NK and B cell profiles were not significantly different between the two groups. CONCLUSION: Both methods of ex vivo TCD were associated with extremely low NRM rates (~5%).We observed a higher cumulative incidence of acute GVHD in the recipients of CD3/19 depleted grafts, accompanied with the distinct biomarker profiles of poor Treg reconstitution and high level of ST2. CD3/19 depletion may have disproportionately depleted Tregs in the graft, leading to uncontrolled tissue damage and GVHD evidenced by higher ST2 levels. Further validation is required to confirm the utility of monitoring Treg reconstitution and ST2 level as biomarkers to predict the outcomes of T cell depleted allo-SCT. Figure 1. Figure 1. Disclosures Battiwalla: NIH/NHLBI: Employment.

Description: Long term allogeneic stem cell transplantation (allo-SCT) survivors face a 2.3 fold increase risk of premature cardiovascular (CV) related death compared to the general population. A reliable screening strategy to identify allo-SCT survivors at risk for CV-related disease is therefore warranted to minimize future events. Cardiac CT is an emerging non-invasive imaging technology with high sensitivity for detecting coronary artery disease (CAD) and high negative predictive value to exclude the presence of CAD. We conducted the first prospective non-randomized single institution study to evaluate Agatston coronary calcium scoring by CT with concomitant coronary CT angiograms as a tool to identify the survivors at risk for CV disease. Sixteen asymptomatic post allo-SCT survivors (11 males; 5 females) with median age of 45 years (range 22-66) at transplant underwent coronary calcium scoring and contrast enhanced coronary CT angiograms at a median follow up of 5 years post transplant. 10-year Framingham cardiovascular risk scores (incorporating age, sex, total cholesterol, HDL cholesterol, systolic BP, HTN, smoking status) were also calculated at time of screening. Two were classified as high risk, 1 intermediate and 13 as low risk. Iodinated IV contrast was administered for coronary artery visualization and IV hydration given to patients with decreased creatinine clearance. Non-obstructive CAD was detected in seven (44%) patients. Additionally, four (25%) of these subjects had aortic root calcification. Lesion distributions by arterial territory were: left main 5.8%, left anterior descending 35.3%, left circumflex 29.4% and right coronary artery 29.4%. Characteristics of coronary plaques were: 47% calcified, 47% mixed calcified / non-calcified, and 6% non-calcified. In those with CAD, the median coronary calcium score was 55 (range: 0-992) (p

Description: INTRODUCTION: Premature vascular disease is a leading cause of late mortality in allogeneic stem cell transplantation (SCT) survivors but the underlying mechanism is not understood. Dyslipidemia is a strong and targetable risk factor for coronary artery disease (CAD) in the general population and its relevance (higher prevalence and high attributable risk in epidemiologic studies of arterial disease) has also been recognized in SCT survivors over the last decade. However, we have previously shown that Framingham risk scores, which rely upon traditional lipid cholesterol measures, are insensitive in determining the presence of CAD. Here, we present the first comprehensive lipoprotein analysis in well-annotated asymptomatic SCT survivors, simultaneously assessed for vascular health using cardiac CT to identify CAD. PATIENTS & METHODS: We performed a cross-sectional analysis of 67 survivors who underwent allo-SCT between 1993 and 2012 for hematologic malignancies and survived for at least three years. All subjects received total body irradiation (TBI) based conditioning followed by a 3-4 log ex vivo T cell depleted graft. The median age at transplant was 39 years (range 17-69). The median duration of follow up was 11 years (range 3-22). Sixty percent were male. Seventy percent had some chronic GVHD, but only 23% required immunosuppression at 3 years post transplant. All subjects had a cardiac CT performed and CAD was defined by the presence of either luminal stenosis by angiography or coronary calcification. Cardiovascular clinical data (hypertension, diabetes, dyslipidemia, smoking, CRP, body mass index) and 10- year Framingham risk scores were also collected. Comprehensive lipoprotein analysis was performed on fasting plasma samples using nuclear magnetic resonance (NMR) with the Vantera clinical analyzer (LipoScience Inc., Raleigh, NC). Digitized spectral data signals undergo algorithmic processing to identify and quantify concentrations of lipoproteins and, potentially, small molecule metabolites from a single sample. 13 subjects with history of lipid lowering therapy or absence of plasma sample were excluded. 24 lipoprotein metabolites were measured including particle cholesterol content (_C), particle count (_P), size [small (S_), medium (M_), large (L_), large + medium (LM_)] and average size (_Z). Due to natural variability in the amount of cholesterol per particle, HDL_C/LDL_C and HDL_P/LDL_P levels often are discordant. HDL_P/LDL_P provides a more clinically reliable measure of HDL/LDL quantity than HDL_C/LDL_C. RESULTS: CAD was confirmed in 45% of survivors; 89% of lesions were non-obstructive and 28% of plaques were non-calcified. Lipoprotein analysis on 54 subjects showed no significant association between HDL or LDL particle cholesterol content, particle count or size distribution. Interestingly, measures of Triglyceride and VLDL were significantly higher in survivors with CAD vs no CAD [VLDL_P median 90.4 vs 54.0 nmol/L (p= 0.009), M_VLDL_P 40.2 vs 23.1 nmol/L (p= 0.03), LM_VLDL_P 44.5 vs 26.1 nmol/L (p= 0.04), and total triglycerides (TG) 172 vs 133 mg/dL (p= 0.03)] (Figure 1). CONCLUSION: In allo-SCT long term survivors, elevated triglyceride and VLDL counts were associated with early CAD even when traditional targetable measures of dyslipidemia (HDL and LDL) were normal. Future efforts will integrate traditional cardiac risk factors with metabolic markers (lipoproteins, insulin resistance and growth hormone deficiency) to better understand premature coronary artery disease in SCT recipients. Figure 1 Figure 1. Disclosures Battiwalla: NIH/NHLBI: Employment.