Khera, Nandita

Abstract Background The prognosis for AML or MDS patients (pts) with monosomal karyotype (MK) is dismal. Although a benefit for allogeneic hematopoietic cell transplantation (allo-HCT) compared to chemotherapy or autologous HCT has been demonstrated in young (≤ 60) pts (Cornelissen, 2012), the curative potential of allo-HCT in older (≥ 60) pts with monosomal karyotype AML/MDS is not known. Patients and methods In this retrospective review, we analyzed outcomes for 69 AML (n = 49) or MDS (n = 20) pts ≥ 60 who underwent allo-HCT at Mayo Clinic Arizona between 2005 and 2013, based on cytogenetic grouping as follows: cytogenetically normal (CN, n = 23), cytogenetically abnormal but not MK (CA, n = 32), and MK (n = 14). Monosomal karyotype was defined (Breems, 2008) as a karyotype with at least two autosomal monosomies or a single autosomal monosomy in combination with at least one structural abnormality. Univariate and multivariate statistical analyses were performed to evaluate the impact of these 3 cytogenetic groupings on outcome (primary endpoint progression-free survival). The median age for all pts was 66 (60-76), and median follow-up for surviving pts was 22 months (range 70 days – 7.1 years). Thirty-seven pts had high-risk disease (MDS > 5% blasts or AML not in CR), while 32 were considered standard risk (MDS <5% blasts or AML in CR). The majority of pts had good performance status (KPS ≥ 90% in 66), but 34 pts (49%) had an HCT-CI score of ≥ 3. Conditioning was myeloablative (Bu-Cy) in 4, reduced toxicity FBM (Fludarabine, BCNU, Melphalan) in 36, and RIC/NMA in 29. Donors were matched related in 18, matched unrelated in 36, and mismatched unrelated in 15. GVHD prophylaxis included tacrolimus in all pts combined with mycophenolate mofetil (37) or methotrexate (32); 49 pts received in-vivo T-cell depletion with rabbit anti-thymocyte globulin (rATG, Thymoglobulin, Genzyme, Cambridge, MA). Results The Kaplan-Meier estimate of progression-free survival (PFS) at 2 yrs was 59% (CN), 39% (CA), and 1.5% (MK); P = 0.004 (Fig. 1). The cumulative incidence of relapse at 2 yrs (with death without relapse as a competing risk) was 34% (CN), 25% (CA), and 94% (MK); P= 0.009). In a Cox proportional hazards analysis adjusted for age (≤ 66 vs. > 66), risk status (standard vs. high), conditioning (myeloablative [Bu-Cy + FBM] vs. RIC/NMA), use of ATG (yes/no), donor type (unrelated vs. related), and HCT-CI (0-2 vs. ≥ 3), the only factor predictive for inferior PFS was cytogenetic status (MK vs. CN, HR 4.64 [95% CI, 1.7 – 13]; P = 0.003); (MK vs. CA, HR 2.4 [95% CI 0.97 – 5.9]; P = .057). Conclusions Standard allo-HCT in AML or MDS pts ≥ 60 with a monosomal karyotype appears to have limited curative potential. Although larger studies will be required to confirm our results, novel transplant approaches or post-transplant strategies to prevent relapse should be a focus of future studies in this incurable pt population. Disclosures: Reeder: Novartis: Research Funding; Celgene: Research Funding; Millennium: Research Funding.

Abstract Abstract 3094 The HLA class II DRB1 antigen DR15 is an important immunobiologic marker in immune mediated marrow failure states. DR15 has also been reported in small studies to be associated with favorable outcomes (reduction in acute GVHD and reduced relapse resulting in improved overall survival) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on major transplant outcomes, we conducted a retrospective study of 2, 891 recipients of first marrow or mobilized peripheral blood stem cell transplantation for the treatment of acute myeloid leukemia (n=1038), acute lymphoblastic leukemia (n=700), chronic myeloid leukemia (n=948), or myelodysplastic syndrome (n=205) between 1990–2008 and reported to the CIBMTR registry. Selection was confined to HLA-identical sibling transplantation to avoid HLA-disparity as a driving force for observed differences. All patients received conventional myeloablative conditioning, T-replete grafts and cyclosporine plus methotrexate- based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 (25.3%) patients as positive and 2159 (74.7%) patients as negative for DRB1*15 :01 or *15 :02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15-positive and -negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, acute graft-versus-host disease (GvHD) II-IV or III-IV, chronic GVHD, treatment related mortality, relapse, disease-free survival or overall survival. Confining the univariate analysis to myeloid malignancies did not alter these findings. Multivariate analysis models were constructed with DR15 status forced into the models in all steps of model building and the final model regardless of its statistical significance. Other variables tested included: donor/recipient age, CMV status, disease, disease stage, graft source, Karnofsky score, race and year of transplant. Variables that attained a p-value ≤0.05 were held in the final multivariate models. In multivariate analysis, DR15 status showed no significant difference in the primary outcomes of acute GVHD II-IV or III-IV, chronic GVHD, overall survival, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplantation outcomes in this large and homogenous cohort of leukemia and MDS patients. Disclosures: No relevant conflicts of interest to declare.

Introduction Allogeneic hematopoietic stem cell transplant (HCT) patients are at risk for having a low Vitamin D (VD) level. VD level has been correlated with cancer incidence, pulmonary disease and infection. VD also has immunomodulatory properties and reports suggest that a low VD level increases the incidence of chronic GVHD and may impact mortality in HCT. HCT morbidity and mortality is attributed to infection, organ system toxicity, GVHD and recurrent disease. Identifying a correctable factor that would reduce the occurrence or severity of these complications would be beneficial. It is possible that VD may have significant effect on outcome after HCT due to its described properties. Normal VD level may infer better outcome for HCT patients by improving response in or preventing infection, protecting organ function, decreasing risk of relapse and/or decrease incidence or severity of GVHD. We hypothesize that there is a relationship between VD level and morbidity and mortality after HCT. We therefore studied VD levels pre- and post-HCT to determine if there was an impact of VD level on these outcomes. Patients and Methods Two hundred and fifty patients underwent myeloblative or non-myeloablative HCT between 3/12/2009 and 10/29/2012 at our institution. Baseline demographic data, disease characteristics, transplant variables and outcomes data were obtained from the transplant database. These data were supplemented by retrospective chart review for VD levels prior to transplant, at day 100 and 1 year post-HCT. Data were collected through day 100 for occurrence of infection and admissions to the ICU. Categories for VD level included normal (≥30 ng/ml) or abnormal (<30 ng/ml). Patient characteristics were compared using the Chi-square test or Wilcoxon rank sum test. The logrank test was used to compare the survival curves between groups, and the Cox proportional hazard model was used to measure the association between outcomes (mortality, relapse, acute or chronic GVHD) and VD level. Results Of the 250 patients undergoing HCT VD level was performed on 180 (72%) patients pre-HCT, 149 (60%) patients at day 100 post-HCT and 81 (32%) patients at 1 year post-HCT. The rate of acute or chronic GVHD was not significantly associated with VD level pre or post-HCT. Overall infection risk was not significant pre or post-HCT but when sorted by type of infection bacterial infection (p=0.01), radiologic evidence of pulmonary nodules/consolidation (p=0.03), and ICU admissions (p=0.0313) within the first 100 days post-transplant were significantly increased in patients who had a low VD level at day 100 post -HCT. Pre-HCT and 1 year post-HCT VD level did not impact mortality or relapse but there was a significant increase in one year mortality (p=0.02, HR = 5.99) and relapse (p = 0.03, HR=9.47) in patients who had a low VD level at day 100 post-HCT. Discussion This study shows that VD may play a significant role in bacterial infection, pulmonary infection, ICU admission, mortality and relapse after HCT. Those patients with a low VD level at day 100 post-HCT had significantly worse outcomes for relapse and mortality. Those patients with a low VD level at day 100 post-HCT had a higher incidence of lung infection, bacterial infection and admission to the ICU. In contrast to previous studies, we found no correlation between VD level and incidence of acute or chronic GVHD. This study is one of the largest reported and the first to our knowledge that reports decreased risk of certain types of infection (bacterial and lung), mortality and relapse in those with an adequate VD level receiving HCT. It is possible that supplementation of VD to keep levels ≥30 would reduce these complications of HCT. Future prospective study of VD is warranted. Finding a low cost and easy to administer therapy (such as VD replacement) that would reduce morbidity, mortality and relapse in the HCT population is needed. Disclosures: Reeder: Celgene: Research Funding; Novartis: Research Funding; Millenium: Research Funding.

Background Steroid-refractory (SR) acute graft-versus host disease (aGVHD) is a serious complication of allogeneic HCT, for which there is no established standard treatment. Both ECP and cytokine inhibitors such as Infliximab have apparent single agent activity in the therapy of SR aGVHD, but there are no published data that address the efficacy of combination anticytokine therapy and ECP in this setting. We report here results in 18 adult patients (pts) with grade III or IV SR aGVHD who were treated with concurrent Infliximab and ECP. Patients All pts underwent allogeneic HCT (first transplant, n=15, second transplant, n=3) for a hematologic malignancy at Mayo Clinic Arizona between March 2012 and May 2013. The median age was 61 (range 22-70), and the median follow-up of 6 surviving pts is 263 days (range 79-433). Donors were related in 3, matched unrelated in 8, and mismatched unrelated in 7. GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil in 13 pts and tacrolimus/methotrexate in 5; in addition, 17 pts received in vivo T-cell depletion with Thymoglobulin 2.5 – 7.5 mg/kg. All pts developed grades III-IV aGVHD at a median day 27 post-transplant (range 10-107) and failed to respond to a course of high-dose corticosteroids (methylprednisolone or equivalent 2 mg/kg daily) for at least 5 days. Treatment Regimen At diagnosis of SR aGVHD, pts were scheduled to receive weekly Infliximab 10 mg/kg (maximum 4 doses), concurrent with ECP performed twice or thrice weekly for one month, followed by a pre-specified taper schedule (anticipated total treatment duration of 6-9 months). To minimize infectious risk and morbidity, corticosteroids were tapered rapidly after the start of Infliximab/ECP therapy. Results Thirteen pts (72%) responded to the Infliximab/ECP combination; complete response (CR; resolution of all GVHD symptoms for at least 30 days and able to discontinue corticosteroids) was observed in 6 pts (33%), and partial response (PR; improvement in GVHD symptoms, partial taper of corticosteroids, and no additional agent for at least 30 days) in 7 pts (39%). At the time of this report, 6 pts are alive, and the Kaplan-Meier estimate of one-year survival is 22.5 % (95% CI, 8.8%-47%). Only pts who achieved CR had good outcomes (5/6 surviving and clinically well); among 13 pts with PR (7) or no response/progression (6) to Infliximab/ECP, 12 have died and one is day 79 post transplant and remains on ECP and low-dose prednisone. Eleven of the 12 deaths were related to GVHD or complications of its treatment (infection, multi-organ failure). Conclusions In this retrospective study of adult pts with severe (grade III/IV) SR aGVHD, treatment with 4 doses of weekly Infliximab and concurrent ECP resulted in an overall response rate of 72%, with one-third of pts achieving CR; the regimen was well-tolerated and facilitated early taper and rapid discontinuance of corticosteroids. Unfortunately, the overall survival of 22.5% at one year does not appear superior to other single agent or combination therapies reported in the literature, or to historical data from our program. Although a small percentage of pts appear to be long-term survivors, the majority of pts succumb to complications of progressive GVHD or infection. Given poor results with available therapies, and the dismal prognosis of pts with SR aGVHD, future research should focus on better preventative strategies for this devastating complication of allogeneic HCT. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction Although allogeneic hematopoietic cell transplantation (HCT) is an expensive modality of treatment for hematological disorders, very little is known about the financial burden for the patients themselves. We analyzed factors associated with financial burden and its impact on health behaviors of allogeneic HCT recipients. Patients and Methods A questionnaire was mailed to adult patients who were alive after allogeneic HCT performed between 1/06 to 6/12 at Mayo Clinic to collect information regarding financial concerns, household income, employment status, insurance, out-of-pocket expenses and health and functional status. A multivariable logistic regression analysis was performed to determine socio-demographic and clinical factors associated with financial hardship. Results Of 482 patients, 268 responded (response rate 56%). Respondents were more likely to be older and Non-Hispanic Whites. No significant differences were seen in disease or transplant characteristics between the two groups except that respondents were more likely to have received reduced intensity conditioning. Median follow-up after HCT was 2.3 years (range 0.7-6.7 years). All the patients for whom the insurance information was available (missing n=13) were insured. Median physical and mental component score, as derived from the SF-12, were 36.8 [Interquartile range (IQR) 29.3-49.0] and 53.1 (IQR 42.1-57.1) respectively, where the general population score is 50, and lower scores indicate worse functioning. The proportion of patients that reported being on medical disability increased from 8% prior to HCT to 29% after HCT. 73% of the respondents reported that being sick had hurt them financially. 54% experienced adverse financial consequences such as decrease in household income by &gt;50% due to the HCT, need to sell/mortgage home, withdraw money from retirement accounts or having to pay more for medical care than they could afford. 3% declared bankruptcy. 12% had out-of pocket costs for the past 3 months that were&gt; $5000. Median monthly medication copayments were $100 (range $ 0-3000). 36% patients felt that their insurance coverage was poor which was strongly correlated with adverse financial consequences (p=0.0013). Other risk factors for financial burden were poor physical functioning reflected by the physical component score &lt;40 (OR 3.2; p=0.005), lower household income (OR 3.08; p=0.006) and lack of commercial/private insurance (OR 4.2; p&lt;0.001) while adjusting for patient and transplant related characteristics. Time from transplant was a significant predictor (OR 1.2; p=0.03) in the univariate analysis, but lost its significance in the multivariate analysis. 18 to 27% patients reported deleterious health behaviors due to financial constraints such as not taking prescribed medications, not using a recommended medical service or not making physician appointments. Conclusions A significant proportion of allogeneic HCT survivors experience adverse financial consequences with a few reporting severe outcomes like bankruptcy, despite having health insurance coverage. Future research should investigate potential interventions such as early financial counseling and connecting with sources of financial support to help at-risk patients and prevent long-term adverse financial outcomes after this life-saving procedure. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction Older patients undergoing allogeneic stem cell transplantation may experience a higher degree of morbidity and limitations from transplant related complications. Chronic graft-versus –host disease (GVHD) causes a significant reduction in patients’ quality of life (QOL), physical functioning, and functional status. However, it is not known if moderate to severe chronic GVHD has a worse impact on QOL, or survival outcomes for older patients. Methods We analyzed data of patients with moderate or severe chronic GVHD (N=522, 1661 follow-up visits, a total of 2,183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. Moderate or severe chronic GVHD was defined by the National Institutes of Health global severity score at the time of enrollment. We examined the relationship between age group (adolescent and young adult “AYA” 18-40, “middle-aged” 41-59, and “older” ≥ 60 years) and clinical manifestations of chronic GVHD, patient-reported outcomes, functional status, non-relapse mortality and overall survival. Clinical manifestations of chronic GVHD were determined by the clinician-reported individual organ scores. Patient-reported outcomes included (1) QOL as measured by Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the Medical Outcome Short-Form Health Survey (SF-36) (2) chronic GVHD symptom burden as measured by the Lee Symptom Scale; and (3) physical fitness as measured by the Human Activity Profile (HAP). Functional status was assessed using the 2-minute walk test (2MWT). Because of multiple testing, p-values <0.01 were considered significant. Results There were 115 (22%) AYA, 279 (53%) middle-aged and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD included. At study enrollment, older patients (≥60) were similar to younger patients in sex, time from transplant (median 12 months), prior acute GVHD, percentage of severe chronic GVHD, and current co-morbidity scores but differed in disease distribution and conditioning regimen intensity. At enrollment, in unadjusted analyses using all available data, older patients had similar rates and severity of global and organ-specific manifestations of chronic GVHD compared to younger patients, except for genital involvement, which was more prevalent and severe in AYA patients. Although older patients reported worse physical functioning [SF-36 Physical Functioning (p=0.01)], shorter 2MWT (p=0.002), and lower HAP scores (p=0.001) than AYA and middle-aged patients suggesting they have more physical limitations, older patients had better QOL [FACT-BMT (p=0.01)] scores compared to middle-aged patients and similar to AYA patients. Older patients had better psychological [Lee Psychological Scale (p<0.001), SF-36 Mental Health (p=0.01)] and emotional functioning [FACT-Emotional Well-being (p=0.001)] and less pain [SF-36 Bodily Pain (p=0.006)] than AYA and middle-aged patients but similar chronic GVHD symptom burden [Lee Symptom Scale (p=0.47)]. In multivariable linear mixed models utilizing all visit data and adjusted for clinical covariates, older patients had QOL (FACT-BMT) that was comparable to AYA patients (estimate -0.04, p=0.99) and better than middle-aged patients (estimate 5.7, p=0.004), while the SF36 physical and mental component scores and symptom burden were not different between the groups. Non-relapse mortality and overall survival were similar between the age groups in unadjusted analyses (p=0.23, p=0.17) and after adjusting for clinical covariates (p=0.17, p=0.15) in Cox models. In a subgroup analysis, we found that there were no differences in overall and organ-specific chronic GVHD manifestations, QOL and survival between patients in the 60-64 (n=73), 65-70 (n=39), and >70 (n=16) age groups, except for more moderate-severe skin involvement in the 65-70 year olds. Conclusion Despite higher physical and functional limitations, older patients with moderate or severe chronic GVHD have preserved QOL, comparable disease manifestations and symptom burden, and similar overall survival and non-relapse mortality when compared to younger patients. Therefore we did not find evidence that older age itself is associated with worse QOL or survival in patients with moderate or severe chronic GVHD. Disclosures: No relevant conflicts of interest to declare.

Abstract Introduction: Depression is associated with increased mortality among healthy individuals and patients with various medical conditions including cardiovascular disease and cancer. The impact of an existing diagnosis of depression prior to autologous and allogeneic hematopoietic stem cell transplantation (HCT) on clinical outcomes including overall survival has not been studied. Methods: We analyzed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to compare overall survival and hospital-length-of-stay during the first 100 days after autologous (n= 3786) or allogeneic (n = 7433) HCT for adult (≥ 18 years) patients with hematologic malignancies with an existing diagnosis of pre-transplant depression requiring treatment vs. those without pre-transplant depression. Data regarding an existing diagnosis of pre-transplant depression requiring treatment were collected from medical chart reviews and reported to the CIBMTR. Data for autologous and allogeneic HCT were analyzed separately. Using Cox proportional hazards regression models adjusting for patient-, disease-(including the disease risk index for allogeneic HCT), donor-(for allogeneic HCT), and transplant-related variables, we compared overall survival between patients with or without pre-transplant depression. To account for early deaths, we compared the number of days alive and out of the hospital in the first 100 days post-transplantation using Poisson models adjusting for patient-, disease-, and transplant-related variables. Among patients undergoing allogeneic HCT, we also compared the risk of grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD among patients with or without pre-transplant depression using Cox proportional hazard regression analyses controlling for significant confounders. Results: We included 1116 (15%) patients with pre-transplant depression and 6317 (85%) patients without pre-transplant depression who underwent allogeneic HCT between 2008 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to age, disease distribution, disease risk index, time from diagnosis to transplant, conditioning regimen, receipt of total body irradiation, graft type, donor type, and donor source, but they were more likely to be female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. In multivariable analyses, pre-transplant depression was associated with higher overall mortality (HR 1.13, 95% CI 1.04-1.23, p = 0.004) and higher risk of grade II-IV acute GVHD (HR 1.25, 95%CI 1.14-1.37, p < 0.0001), but similar risk of chronic GVHD (HR 1.06, 95% CI 0.96-1.16, p = 0.26). Pre-transplant depression was associated with fewer days alive and out-of-the hospital (Means Ratio (MR) = 0.97, 95% CI 0.95-0.99, P = 0.004). Among patients undergoing autologous HCT, we included 512 (13.5%) patients with pre-transplant depression and 3274 (86.5%) patients without pre-transplant depression between 2007 and 2012. Patients with pre-transplant depression were similar to those without pre-transplant depression with regards to disease distribution, disease status prior to HCT, time from diagnosis to transplant, conditioning regimen, and year of transplant, but they were slightly younger, more likely be to female, white, divorced, less educated, not working full-time, and had lower performance status and higher number of comorbid conditions. Pre-transplant depression in autologous HCT recipients was not associated with overall survival in multivariable analyses (HR 1.15, 95% CI 0.98-1.34, p = 0.096), but was significantly associated with fewer days alive and out of the hospital (MR = 0.98, 95% CI 0.97-0.99, p = 0.002). Conclusion: Pre-transplant depression was associated with higher mortality and higher risk of acute GVHD among patients undergoing allogeneic HCT. Moreover, pre-transplant depression is associated with a longer hospital-length-of stay during the first 100 days after autologous and allogeneic HCT. Therefore patients with pre-transplant depression represent a highly vulnerable population at risk for post-transplant mortality and complications, and they may benefit from more intensive interventions to mitigate the risk of depression on their post-transplant outcomes. Disclosures Chen: Bayer: Consultancy, Research Funding. Lee:Bristol-Myers Squibb: Consultancy; Kadmon: Consultancy. Hahn:Novartis: Equity Ownership; NIH/NHLBI: Research Funding.

Abstract Abstract 2850 Myelofibrosis (MF), both primary myelofibrosis (PMF) and post essential thrombocytosis/polycythemia vera myelofibrosis (post ET/PV-MF), are chronic myeloproliferative neoplasms characterized by a progressive clinical course that leads to shortened survival. The heterogeneous nature of MF lends itself to a variable clinical course that commonly includes hepatosplenomegaly, constitutional symptoms, and progressive cytopenias. Medical therapy for myelofibrosis has been effective in palliation of common symptoms related to anemia, splenomegaly but allogeneic stem cell transplantation (ASCT) remains the only potentially curative therapeutic modality. The timing of ASCT, choice of conditioning regimen, patient selection and the impact of co-morbidities are critical to optimal use of this modality. We have retrospectively analyzed our experience for patients undergoing ASCT for primary and post ET/PV myelofibrosis at Mayo Clinic across all 3 sites: Scottsdale Arizona; Rochester, Minnesota; and Jacksonville, Florida. Methods: We conducted a retrospective review of all patients from 1992 to 2012 with PMF or post ET/PV-MF who underwent an ASCT at Mayo Clinic. This retrospective review included a waiver of informed consent and was approved by the Mayo Clinic Institutional Review Board. Patients that transformed to the MPN blast phase and individuals who underwent a second transplant for either relapse or graft failure were also included. Overall survival was estimated using Kaplan-Meier. Associations between prognostic factors and overall survival were assessed using Cox regression. Results: Baseline Patient Characteristics: Forty-eight patients (29 male) with a median age of 57 yrs (range 31–73) underwent ASCT. DIPSS-plus risk score was low in 2, intermediate 1 in 2, intermediate 2 in 9 and high in 35 patients. Disease type was PMF in 24, PV-MF in 10, ET-MF in 10, and MPN/MDS overlap in 4 pts. Eight patients evolved to the MPN-blast phase prior to transplant. JAK-2 mutation was positive in 27 patients and negative in 12 patients with JAK-2 status unknown in 9 patients. The median time from PV/ET to MF was 136 months (83–189 months) and from MF diagnosis to transplant was 59 months (3–144 months). All but 2 patients were red cell transfusion dependent prior to transplant (96%). Eight patients underwent splenectomy prior to transplant. Transplantation Characteristics: Patients who underwent ASCT received either myeloablative (MA, 13 pts) or reduced-intensity conditioning (RIC, 35 pts) regimen. The graft was from an unrelated donor in 22 pts and related donor in 26 pts with 44 being matched and 4 being mismatched. The myeloablative regimens included Bu/Cy, TBI/Cy, and Bu/Flu. The RIC regimens included flu/mel, Bu/Flu, FBM, and TBI/Flu. GVHD prophylaxis was with tacrolimus/MTX, CSA/MTX, and tacrolimus/MMF. Nineteen patients received ATG. Infectious disease prophylaxis, CMV monitoring, and additional supportive care measures were according to institutional guidelines. A majority of patients received peripheral blood stem cells with only 1 patient receiving bone marrow as the source of stem cells. Outcomes: The median time to neutrophil engraftment was 17.2 days. Two patients received a second transplant for relapsed disease. The incidence of graft failure was 10%. Graft versus host disease both acute and chronic occurred in 33 patients and 15 patients respectively. Day 100 overall survival was 92% and 2 year survival was 62% (95% CI 45–75%). There were no statistically significant associations between individual prognostic factors (DIPSS-plus classification, age, and HLA match) and survival. Conclusions: The Mayo Clinic national experience of ASCT for MF across our geographically diverse Cancer Center is encouraging. Our centers have transplanted 48 patients over the past 10 years with very favorable outcomes. Our results from a multi center practice are consistent with regards to survival, graft versus host disease, and types of transplants being performed compared to currently available published data from large single location transplant centers. This data helps confirm the prevailing knowledge that ASCT is a useful treatment. Disclosures: Mesa: Incyte: Research Funding; Lilly: Research Funding; Sanofi: Research Funding; NS Pharma: Research Funding; YM Bioscience: Research Funding.

Abstract Background: Donor cell chimerisms are tested at frequent intervals after allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the predictive value of this testing in patients with myelofibrosis (MF) is not well-defined. In this study, our primary objective is to evaluate the correlation of day 30 and day 100 donor cell chimerism and overall survival (OS) in patients (pts) who undergo alloHSCT for MF. Methods: Charts were reviewed for pts who underwent alloHSCT for MF at Mayo Clinic in Arizona, Minnesota and Florida between January 2005 and December 2015. Patients who died within 30 days of alloHSCT were excluded. Chimerism studies were evaluated in the peripheral blood for CD3 and CD33 fractions at day +30 (D30) and day +100 (D100). Cut-off value of 100% and less than 100% was used because of limited variability below 100%. Standard statistical methods were used to compare continuous and categorical variables. The Kaplan-Meier method was used to provide survival curves. Results: Baseline characteristics: Sixty three consecutive patients who underwent alloHSCT for MF since January 2005 until December 2015, and had D30 and/or D100 chimerism studies available were included in the study. Of these, 24 (38%) were female. Median age at diagnosis was 56 years (range, 19 - 73 years) and median age at AHSCT was 58 years (range, 19 - 73 years). Dynamic International Prognostic Scoring System-Plus (DIPSS-Plus) risk category at the time of alloHSCT was high in 31 (49%), intermediate-2 in 30 (48%) and intermediate-1 in 2 (3%) pts. JAK2 V617F mutation status was available in 61 pts and was positive in 35 (57%) pts. Nineteen (30%) pts had been treated with a JAK2 inhibitor prior to alloHSCT. Fifty-two (83%) pts had at least grade-2 fibrosis in bone marrow at the time of HCT. Transplantation: Median time from diagnosis to AHSCT was 12.9 months (range, 2.3 - 248.2 months). Fifty-five (87%) received a reduced intensity conditioning (RIC) regimen while 8 (13%) received myeloablative conditioning regimen. Of these 55 pts, RIC regimens used were busulfan fludarabine based regimen in 15 (27%), fludarabine melphalan based regimen in 18 (33%) and fludarabine melphalan carmustine in 22 (40%) pts. Donor source was matched related in 30 (48 %), matched unrelated in 28 (44%), single-antigen mismatched related in 4 (6%) and mismatched unrelated in 1 (2%). Peripheral blood stem cells were used in all AHSCTs. Outcomes: Median follow-up was 24.4 months (range, 1.5 - 83.6 months). Amongst pts who had <100% donor chimerism at D30 in CD33 fraction, 2 had 90%, 1 had 80% and 2 had zero% donor chimerism. At D100, 1 pt had 95%, 1 had 90%, 1 had 60%, 2 had 5% and 1 had zero% donor chimerism. Eighteen out of 57 (32%) pts who had 100% donor chimerism in CD33 fraction at D30 had died at the time of analysis compared to 4 out of 5 (80%) patients with less than 100% (p=0.03). Eight out of 38 pts (21%) who had 100% donor chimerism in CD33 fraction at D100 died versus 3 out of 6 (50%) with less than 100% (p=0.12). There was no significant survival effect of CD3 chimerism (p values=0.68, 0.59). Of the 23 deaths that had occurred at the time of analysis, cause of death was disease progression or relapse in 8 (35%), graft versus host disease in 6 (26%), transplant related (sepsis / engraftment failure) in 5 (22%) and unrelated causes in 4 (17%). Survival analysis: As depicted in the Kaplan Meier curve (figure 1), median overall survival (OS) for pts with 100% donor chimerism in CD33 fraction at day 30 was not reached while for <100% donor chimerism was 16 months (p=0.04). Survival at 3 years for patients with 100% CD33 donor chimerism at D30 was 65% while it was 40% for pts with less than 100%. Also, survival at 3 years for patients with 100% CD33 donor chimerism at day 100 was 75% compared to 50% for patients with less than 100%. Conclusions: In our study, 100% donor chimerism in CD33 fraction is associated with improved survival after alloHSCT for MF compared to pts with less than 100%. Further understanding regarding the reason for this relationship is critical. Larger studies to replicate these results would be imperative to validate these findings. Disclosures Mesa: Incyte: Research Funding; Ariad: Consultancy; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; Gilead: Research Funding; CTI Biopharma: Research Funding; Galena: Consultancy.

Abstract Introduction: Allogeneic stem cell transplant is an intensive procedure, offered in a limited number of medical centres. We sought to describe how sociodemographic variables impacted access to transplant across the United States, and if disadvantaged populations had inferior access to transplant. Methods: Data from the Surveillance, Epidemiology and End Results Program (SEER) and the Center for International Blood and Marrow Transplant Research (CIBMTR) was integrated to determine the rate of unrelated donor transplantation between 2000 and 2010 in each of the 612 counties included in the SEER registry. Patients under the age of 65 with AML, ALL, and MDS were included, and the analysis was restricted to unrelated donors due to limited availability of ZIP code in CIBMTR data. New incident cases were determined from SEER, and the number of transplants was determined from CIBMTR. The transplant rate was calculated (transplants performed divided by incident cases) for each county. County attributes (percent minority, rural/urban status, percentage below the poverty line, and median family size) were obtained from US Census data. Poisson regression was used to describe how county attributes impacted transplant rates. Transplant rates were calculated separately for AML, White residents, and pediatric ALL. Results: 3147 patients were identified in the CIBMTR dataset that met inclusion criteria. The estimated ZIP code completeness was 75%. There were 30,468 new incident diagnoses of ALL, AML, and MDS. For AML, patients from rural areas (less than 20,000 residents) and patients from areas with higher poverty levels had lower transplant rates (Table 1). Minority status and family size did not impact transplant rate. In regression models, higher levels of poverty remained associated with lower transplant rates, while rurality did not (Table 2). The results were similar among White residents. In contrast, in pediatric ALL, no county attributes (poverty, rurality, percent minority, and family size) were significantly associated with a difference in transplant rate (Table 1). However, numbers of transplants were smaller, limiting power. Discussion: Patients with AML from disadvantaged areas had lower rates of unrelated donor transplant. While patients from disadvantaged areas were also more likely to be non-White, and non-White Americans are less likely to have an available unrelated donor, this difference was also seen in White Americans from disadvantaged areas. This suggests the lower transplant rate is due impaired access to transplant. Poverty rate was the most important predictor of transplant rate. The results of this study suggest that improving access to transplant in disadvantaged populations should be a priority for health care administrators. Based on these results, approximately 2500 Americans do not undergo allogeneic transplant annually due to inferior access associated with higher poverty rates. Table 1 Univariate Analysis Table 1. Univariate Analysis Table 2 Acute Myeloid Leukemia, Regression Model * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Table 2. Acute Myeloid Leukemia, Regression Model. / * Metropolitan = county > 50,000 people, micropolitan = county > 20,000, rural county < 20,000. Disclosures Hahn: Novartis: Equity Ownership; NIH: Research Funding.