ALBERT

Description: Abstract 1180 Background: Although peripheral blood stem cell (PBSC) donation has been considered safe and less stressful, certain fetal or life-threatening acute (within 30 days of post donation) adverse events as well as late occurrence of hematological malignancies have been reported among donors. Since the Japan Marrow Donor Program requires the confirmation of safety and risk of PBSC donation at family donors prior to applying this technique for volunteer donors, the Japan Society for Hematopoietic Cell Transplantation (JSHCT) performed nation-wide consecutive pre-registration and follow up for PBSC family donors from 2000 to 2010. This time, we report the comprehensive outcome of this project. Methods: The JSHCT mandated the registration of every PBSC family donor at the donor registration center then, issued donor identification number to each donor. The society required every harvest center to observe the JSHCT standards for donor eligibility, stem cell mobilization and harvest. The society also required to notify it of any severe adverse events, the results of the day30 clinical and laboratory check and of the annual health check for five years. Findings: Among 3,264 pre-registered donors, 47 emergency reports were submitted for 5 years and it was revealed that acute unexpectedly severe adverse events such as interstitial pneumonitis or anginal attack occurred at 0.58 % of donors although no mortality cases within 30 days of post donation were found. The relationship between donors' basic information such as age or gender and clinical and laboratory abnormalities obtained from 2,882 day 30 reports was studied and it revealed the followings; the risk factor for fatigue, headache, insomunia, anorexia and nausea was female, the risk factors for prolongation of hospitalized period were older age, low body weight, high total dose of granulocyte colony stimulating factor (G-CSF), the presence of past or current health problems and the episode of past stem cell donation, the risk factors for thrombocytopenia were older age and high total dose of G-CSF, the risk factors for splenomegary were older age and high total dose of G-CSF, the risk factors for poor CD34+ cell mobilization were older age, female and the episode of past stem cell donation, the risk factor for over CD34+ stem cell mobilization was younger age. The information from 6,233 annual health checks from 1,708 donors for 5 years showed the followings; the incidence of non-malignant but significant health problems was 1.5%, the incidence of non hematological malignancies was 0.7%, the incidence of hematological malignancy was 0.06%. It was also confirmed that the incidence of hematological malignancies among PBSC donors was not high compared with that among retrospectively surveyed bone marrow family donors. Interpretation: The consecutive donor pre-registration and annual follow up system that sets strict standards for donor eligibility, cell mobilization and harvest is effective in preventing real life-threatening acute adverse events and also is useful to know the real figures on PBSC donors and to assure donor safety. Such a system should be applied to all hematopoietic stem cell (family and volunteer, bone marrow and peripheral blood) donors. Disclosures: No relevant conflicts of interest to declare.

Description: Key Points First therapeutic application that targets Robo4 on the tumor blood vasculature High-throughput screening system to isolate cell-internalizing monoclonal antibodies useful to develop effective antibody-drug conjugates

Description: Background The safety and the risk in normal healthy BM/PB donors are serious concerns. Several retrospective surveys reported adverse events in healthy donors, but the real incidence of these events may be underestimated in related donors while it has been fully monitored in unrelated donors by BM/PB donor registries. Methods JSHCT has conducted a nation-wide consecutive pre-registration of related donors in Japan, for PB since April 2000 and for BM since April 2005. JSHCT mandatory requires all members to register every related donors and to report any severe adverse events in donors in the first 30 days and then annually for 5 years after donation. These early and late severe events were categorized into definitely severe; life-threatening, treatment-required or long-lasting and relatively severe to mild; transient and not treatment-required. Pre-registration to the JSHCT as a BM/PB donor is made into the conditions of personal-accident-insurance subscription. Results 1. The preceding retrospective survey on related BM donors by a governmental research committee in 2005 reported four A-events (0.07%) including one death and 21 B-events (0.35%) in 5921 donors. 2. 3975 PB donors (3264 before and 711 after April 2005) and 999 BM donors (after April 2005) have been registered to this prospective registration by the end of July 2007. 3. There has been no death in PB /BM donors. 4. 64 events (1.6%) have been reported in PB donors as early events. 11 A-events include interstitial pneumonitis(2), hypoxemia(2), ascites, SAH, retroperitoneal hematoma, anginal attack, precordial discomfort, vein thrombosis and cholangitis. 5. Four-B events (0.4%) have been reported in BM donors as early events. 6. Relatively severe early (acute) adverse events occurred in 1.39% of those donors who fulfilled donor eligibility standards of the JSHCT guideline (N=3097), and 3.85% of those with one or more exclusion criteria (N=78) (P=0.09) 7. 35 late adverse events were reported in 3167 PB in the five year observation period. Although these late events were not proved to be related to G-CSF administration or apheresis, the relationship could not be completely denied. These occurred in 1.10% of those fulfilled the JSHCT donor eligibility standards (N=3097) and in 1.28% of those with exclusion criteria (N=78)(P=0.88). 8. Late adverse events have not been reported in BM donors because of short observation period. Conclusion Both BM and PB collection in related donors were shown to be safe in general. But several serious adverse events were reported. Prospective donor registration has enabled us to accurately monitor the real incidence of adverse events and has been useful for transplant physicians to observe the safety guideline for BM /PB collection by JSHCT, which results in lowering the rate of avoidable adverse events in related donors with known risk factors. Our seven year experience suggests the importance and usefulness of the prospective registration system of related PB /BM donors, and international collaboration is required to clarify and to improve the safety and the risk of PB /BM donation both in related and in unrelated donors.

Description: In April 2000, we created a system, which was cooperatively steered by The Japan Society for Hematopoietic Cell Transplantation (JSHCT) and G-CSF producing and/or selling companies, to catch up the types and the frequencies of acute and late severe adverse events (SAE) of peripheral blood stem cell (PBSC) donors among relatives in Japan. Every PBSC donor was registered to JSHCT and was given unique donor number before the PBSC donation. Every harvest center was mandatory required to observe the JSHCT Guideline for donor’s criteria and to submit the day 30 report as well as the immediate report of any severe SAE, and also to ask donors’ receiving annual health check for 5 years. This time, we report the acute SAE observed among 3,262 consecutive donors in 233 institutes and the late SAE reported through annual health check by the forth year of post PBSC harvest among 1,370 donors (2,849 times) who agreed with this work of the society. As of March 2005, 50 acute SAE out of 3,262 cases (1.5%) were reported, including anginal attack, vain thrombosis, retroperitoneal hematoma, subarachnoid hemorrhage, interstitial pneumonitis and others. Twenty-eight (2.0%) of late SAE were reported from 1,370 cases, including 1 hematological malignancy (acute myelogenous leukemia ), 8 other malignancies and others. To compare these acute and late SAE of PBSC donors to those of bone marrow (BM) donors, the questionnaires, a part of which was shared with The European Group of Blood and Marrow Transplantation (EBMT) were sent to 286 institutes of JSHCT and 191 institutes (67%) answered about 5,921 cases of bone marrow harvest from relatives and the comparative results were as followings: PBSC donors: BM donors, per 10,000; Death within 30 days = 0:1.7, SAE within 30days of post-harvest=153.0:35.5 (Definite SAE=21.5:6.8), Hematological malignancy at anytime of post donation = 3.1:2.9. On the other hand, the results obtained by EBMT, where the both surveys were retrospective, were as followings (PBSC donors: BM donors, per 10,000 ); Death within 30 days = 1.83:0.22, SAE within 30 days = 9.7:2.7, Hematological malignancy at anytime of post-donation =3.0:2.0. These results showed the followings; 1) the acute SAE might occur more frequently at PBSC donors, 2) the different frequency of acute SAE and of the mortality within 30 days of post-donation at PBSC donors between JSHCT side and EBMT side might reflect the difference of donor survey system; pre-registration with guideline for donor’s eligibility vs. retrospective survey, 3) the frequency of the occurrence of hematological malignancy was not necessarily high at PBSC donors. Although the case numbers studied at PBSC donors and BM donors in JSHCT and EBMT were different each other, no death within 30days was reported among PBSC donors of JSHCT so far and it might come from the pre-registration system of donors which made the surveillance for the safety of every donor possible and is recommended for both PBSC and BM donors at an international level in order to improve donor safety.

Description: Atherosclerosis is a major cause of various fatal diseases, such as myocardial infarction, stroke, and ischemic heart failure worldwide. The risk factors of atherosclerosis are well known, including hypertension, diabetes mellitus, dyslipidemia, smoking and obesity. Growing evidence also suggests that aging is the strongest determinant of stroke, which is less common before 40 years old (Soler and Ruiz 2010). Werner syndrome (WS) is a rare human inherited disorder characterized by the appearance of premature aging followed by early onset of aging-associated diseases including atherosclerosis. Myocardial infarction and cancer are being the most common causes of death in patients with WS (Oshima et al. 1993). However, despite being one of the most common causes of death, the etiology of atherosclerosis in WS patients have not been well documented yet. Therefore, the aim of the study was to assess in vitro model of atherosclerosis using WS patient-derived induced pluripotent stem cells (iPSC) to better understand the etiology and pathogenesis of atherosclerosis in WS patients. Atherosclerosis is a chronic inflammatory disease in which vascular endothelial cells (VEC), vascular smooth muscle cells (VSMC) and macrophages (Mφ) play interactive roles in the progression of the disease. To obtain these cells in vitro, we induced VEC, VSMC and Mφ from the progenitor cell populations, KDR+/CD34+/TRA-1-60-, KDR+/CD34-/TRA-1-60- and CD43+/CD34+ cells respectively, derived from iPSCs by the iPS-sac method we developed previously (Takayama et al. 2008, 2010). We found by co-culture with C3H10T1/2 mouse mesenchymal stromal cell line, KDR+/CD34+ and KDR+/CD34- cell populations were able to efficiently induce VEC and VSMC respectively on day 17. Especially, VEC induction efficiency was ~ 4 and ~ 21 fold as compared with the previously established method with collagen IV and laminin-411 respectively (Ohta et al. 2016; Sone et al. 2007; Taura et al. 2009). Furthermore, to induce Mφ, iPS-sac-like structures in culture were maintained for two weeks to get CD43+ hematopoietic cells. CD43+ cells were then cultured for an additional 7 days with a cytokine cocktail on C3H10T1/2 feeder layer. After 3 weeks of initiating culture, ~ 54% of CD11b+/CD33+ Mφ-like cells were obtained. To examine the responses of the induced VEC- and Mφ-like cells in atherosclerotic conditions, we applied oxidized low-density lipoprotein (Ox-LDL) at the concentration of 10, 50 and 100 μg/mL, and performed qRT-PCR analysis. It is well known that inflammatory response is triggered with the uptake of LDL both in VEC and Mφ, thereby contribute to local inflammation, cell necrosis, apoptosis, VSMC proliferation and fibrosis. Accordingly, in Ox-LDL treated iPSC-derived VEC and Mφ, mRNA expression of IL-1β, IL-6 and TNF-α were increased in a dose dependent manner. A critical event in the early stages of atherosclerosis is the internalization of lipid particles by VEC, and then, these lipids particles are oxidized to form Ox-LDL in the endothelium, leading to an increase in inflammatory cell adhesion molecules (ICAM-1 and VCAM-1) on the endothelium. Subsequently, monocytes are then recruited and differentiated into Mφ and start to uptake Ox-LDL particles ultimately forming foam-cells (Wu et al. 2017). Next, we were enthusiastic to compare the effect of Ox-LDL for inflammatory response in WS iPSC-derived VEC and Mφ with healthy iPSC-derived VEC and Mφ. Although no differences were observed in the induction efficiency, cell proliferation and mean fluorescent intensity of Ox-LDL uptake between WS- and healthy-iPSC-derived VEC and Mφ, qRT-PCR analysis revealed that, VEC derived from WS-iPSC shows much higher mRNA expression of cell adhesion molecule gene (ICAM-1; 2.5 fold and VCAM-1; 3.6 fold), inflammatory cytokine gene (IL-6; 12.5 fold and TGF-β; 4.3 fold) and endothelial dysfunction related gene (ET-1; 5.9 fold and PAI-1; 25.2 fold) compared with healthy-iPSC-derived VEC. Consequently, our results suggest that the higher risk of atherosclerosis in WS patients might be due to excessive inflammation response against Ox-LDL in WS-iPSC-derived cells, which is independent of other risk factors frequently observed in WS, such as diabetes and hyperlipidemia, and might be implicated to understand the pathogenesis and therapeutic strategy against WS and general atherosclerosis. Disclosures Eto: Megakaryon Co. Ltd.: Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Description: Key Points In Cebpb−/− mice, the number of Ly6C− monocytes was specifically decreased in a cell-intrinsic manner due to their accelerated death. C/EBPβ supports the survival of Ly6C− monocytes, at least in part through direct upregulation of Csf1r.

Description: Modern clinical treatments of childhood acute lymphoblastic leukemia (ALL) employ enzyme-based methods for depletion of blood asparagine in combination with standard chemotherapeutic agents. L-asparaginase (L-asp) therapy causes depletion of plasma asparagine followed by the loss of intracellular asparagine. Due to the lack of a rapid up-regulation of asparagine synthetase (ASNS) protein content in ALL cells, they are preferentially killed by L-asp. Elevated expression of ASNS within the leukemia cells causes decreased sensitivity to L-asp. The proof of ASNS deficiency in leukemia cells is considered to predictive for effectiveness of L-asp even in acute myeloid leukemia (AML) other than ALL patients. The establishment of quantitative estimation of ASNS protein content would be useful for the L-asp treatment in leukemia therapy. Objective: Our aim was to set up a flow cytometry system to check ASNS deficiency in leukemia cells and to investigate the sensitivity to L-Asp and the ASNS expression in AML leukemia cells. Methods: AML (KG-1, HL-60, U937) and ALL (MOLT-4, RS4;11) and CML (K562) cell lines were grown in RPMI1640 medium with 10% FCS. Primary leukemic cells from the peripheral blood or bone marrow of 20 AML patients were harvested on EDTA and isolated by Ficoll density gradient within 72h. ASNS expression was evaluated by cytosolic flow cytometry with Z5808 McAb (Hybridoma 31: 325-332.2012) and expressed as a ΔMFI(Difference of Mean Fluorescence Intensity(MFI) between by Z5808 and isotypic control) or MFI ratio(MFI by Z5808/MFI by isotypic control). When a sufficient amount of leukemic cells was available, sensitivity to L-asp (expressed as an IC50 - concentration inhibiting 50% of cell viability) was evaluated in vitro by incubating various concentrations of E. coliL-asp with the cells and by measuring the cell viability with a counting kit (WST1 viability assay) at day 3. Results: Determination of IC50 for the HL-60 (⊿MFI 48 ± 8.01, MFI ratio 1.77 ± 0.03) and U937 (⊿MFI 16.7 ± 0.47, MFI ratio 1.19 ± 0.02) demonstrated that these cells were equally sensitive to L-asp than the ALL cell line MOLT-4 in vitro (0.37 and 0.02IU/mL versus 0.15 IU/mL, respectively). K562 and KG-1 (⊿MFI 135.7 ± 5.66, MFI ratio 2.48 ± 0.09) cells with the highest ASNS expression exhibited resistance to L-asp (〉10 IU/ml). Both of ASNS Expression by ⊿MFI and MFI ratio was inversely correlated with L-asp sensitivity judging from cell line studies. Judging from cell line study, the threshold for ASNS protein expression effective for L-asp treatment was considered to be

Description: Background: Hematopoietic stem cell transplantation (HSCT) recipients carry a high risk of primary varicella and varicella-zoster virus (VZV) reactivation. VZV infections can be fatal, and VZV reactivation can be complicated by postherpetic neuralgia, which worsens the recipients’ post-HSCT quality of life. VZV vaccines may prevent such infections; however, international vaccination guidelines do not recommend VZV vaccination of HSCT recipients because few data regarding safety among HSCT recipients are available. In Japan, we use a high-titer Oka stain vaccine for varicella vaccination and zoster prevention in the elderly; the plaque forming unit (PFU) value of this vaccine is as high as the zoster vaccine used in the U.S. Data regarding the safety of zoster vaccine in HSCT recipients is limited; therefore, we report our experience with this high-titer zoster-equivalent varicella vaccine in pediatric allogeneic HSCT recipients. Patients and Methods: Forty-seven pediatric allogeneic HSCT recipients who underwent transplantation at the Saitama Children’s Medical Center from 2000-2011 were vaccinated with live vaccines and their antibody titers were evaluated after vaccination. Among the 47 recipients, the Japanese high-titer varicella vaccine was administered to 32 recipients. Since establishing the live vaccine initiation criteria in 2009, allogeneic HSCT recipients were considered as recipients for live vaccines, including the varicella vaccine, if 24 months had passed after HSCT without active chronic GVHD or required immunosuppression. In addition, recipients were required to have a lymphocyte count 〉1500/μl or CD4 cell count 〉700/μl if they were 1000/μl or CD4 cell count 〉500/μl if they were 〉6 years, normal phytohemagglutinin response, and serum IgG level 〉500 mg/dL. Before 2009, time for vaccination depended on each doctor’s judgment. Patients were given a single dose of the Biken varicella vaccine containing a minimum of 23,000 PFUs. We use EIA to measure the antibody titer and defined seropositivity as a titer 〉6.0. The time to evaluate the antibody titer was not fixed. We retrospectively collected the clinical data of recipients and laboratory data by reviewing the medical records. Results: The 32 recipients, who received the Japanese varicella vaccine, underwent HSCT at a median age of 5.15 years (range: 0.5-16.4 years) and were vaccinated at a median of 20.65 months (range: 4.8-112.1 months) after HSCT. Twenty and 11 patients had received myeloablative and nonmyeloablative conditioning, respectively. Nine patients received related-donor transplant, of which eight were bone marrow and one was peripheral blood. Twenty-three patients received unrelated-donor transplant, of which 14 were bone marrow and nine were cord blood. Antithymocyte globulin was administered to four patients. Eighteen of the 32 patients (56.3%) were seropositive after vaccination. Of the 26 patients, whose vaccination histories and pre-transplantation histories were available, eight were affected by natural disease, six had been immunized, and 12 had not been immunized. At vaccination, the median lymphocyte count was 3201/μl (range: 817-6630/μl) and the median IgG value was 880 mg/dL (range: 233-1461 mg/dL). There was no significant risk factor associated with vaccine failure. We experienced one case of varicella because of wild type VZV and no cases of zoster after vaccination during a median follow-up period of 4.8 years (range: 0.4-11.3 years); the single patient developed varicella 13 days after vaccination, immediately after an influenza virus infection. Whereas, two cases of varicella and one case of zoster developed before vaccination. Of the other 15 recipients, who did not receive varicella vaccine, three varicella and two zoster developed in three recipients. Conclusion: We safely vaccinated pediatric allogeneic HSCT recipients with the Japanese high-titer varicella vaccine. This finding could encourage the use in the U.S. of zoster vaccines such as Zostavax@, which contains similarly high PFUs, and low-titer varicella vaccines such as Varivax@. However, the efficacy of high-titer varicella vaccines for preventing VZV reactivation in this population remains unclear. Further studies are warranted to elucidate the efficacy and difference between low-titer and high-titer varicella and zoster vaccines. Disclosures No relevant conflicts of interest to declare.

Description: B-cell lymphopoiesis is critically dependent on the bone marrow microenvironment. Early B-cell lymphopoiesis is regulated by direct interaction with bone marrow stromal cells (BM-MSCs) and by soluble factors produced by BM-MSCs. The roles of transcription factors expressed by hematopoietic cells that involve early B-cell lymphopoiesis have been well investigated; those include PU.1, Ikaros, E2A, early B-cell factor, and paired box protein 5. By contrast, transcriptional factors expressed by BM-MSCs that are important for early B-cell lymphopoiesis remain unknown. We show that CCAAT-enhancer binding protein (C/EBP) β expressed by BM-MSCs contributes to the early B-cell lymphopoiesis. In addition, the proliferation of precursor B-cell acute lymphoblastic leukemia (B-ALL) cells is also associated with BM-MSCs, in which C/EBPβ is one of the regulatory transcription factors. When c-kit+ Sca-1+ lineage- (KSL) HSCs from Wild-type (WT) mice were co-cultured with C/EBPβ-deficient BM-MSCs in the presence of stem cell factor (SCF), Flt3-L, and interleukin (IL)-7 (Figure A), the generation of hematopoietic cells from KSL cells was significantly lower than when they were co-cultured with WT BM-MSCs. In addition, the generation of B220+ B-cells from KSL cells was also significantly lower when they were co-cultured with C/EBPβ-deficient BM-MSCs than when co-cultured with WT BM-MSCs. Detailed analysis of the generated B-cell subsets showed that differentiation of KSL cells into precursor B-cells was reduced and differentiation from pre-pro-B-cells to pro-B-cells/pre-BI cells was suppressed when cells were co-cultured with C/EBPβ-deficient BM-MSCs (Figure B). Therefore, C/EBPβ was an indispensable transcriptional factor expressed by BM-MSCs for supporting the differentiation of HSCs into precursor B-cells. We next examined the expression of B-cell lymphopoiesis-associated molecules in C/EBPβ-deficient BM-MSCs by quantitative real-time PCR analysis. Levels of IL-7 and SCF mRNA tended to be lower in C/EBPβ-deficient BM-MSCs than in WT BM-MSCs, although the difference was not statistically significant in our analysis. Levels of CXCL12/SDF-1 and Flt3-L mRNA were significantly lower in C/EBPβ-deficient BM-MSCs than in WT BM-MSCs. In addition, the protein concentration of CXCL12/SDF-1 was significantly lower in the culture supernatant of C/EBPβ-deficient BM-MSCs than that of WT BM-MSCs. The concentration of CXCL12/SDF-1 in the supernatant of BM-MSC co-cultures strongly correlated with the number of B220+ B-cells that differentiated from KSL cells. Thus, the impaired differentiation of HSCs into B-cells is associated, at least in part, with reduced production of CXCL12/SDF-1 by C/EBPβ-deficient BM-MSCs. Precursor B-ALL is a hematological disease characterized by malignant transformation of precursor B-cells. We examined whether C/EBPβ expressed by BM-MSCs has effects on the precursor B-ALL cells. When the precursor B-ALL cell line BaF3/Bcr-Abl cells was co-cultured with WT BM-MSCs, the number of BaF3/Bcr-Abl cells was significantly increased than when they were cultured alone. Interestingly, when the precursor B-ALL cell line BaF3/Bcr-Abl cells was co-cultured with C/EBPβ-deficient BM-MSCs, the number of BaF3/Bcr-Abl cells was reduced to the level similar to when they were cultured alone. This was true in co-cultures with BM-MSCs that were pharmacologically treated to down-regulate the C/EBPβ expression. As well as the correlation of SDF-1 concentration in co-cultures with precursor B-cell differentiation, the proliferation of BaF3/Bcr-Abl cells was associated with the correlation of SDF-1 concentration in co-cultures. In conclusion, this work demonstrates that C/EBPβ expressed by BM-MSCs is a critical transcriptional factor for both the differentiation of physiological precursor B-cells and pathological proliferation of leukemic precursor B-cells. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 1976 Background: Heme oxygenase-1 (HO-1) is the rate-limiting enzyme in the first step of heme degradation to biliverdin, free iron, and carbon monoxide. Aside from heme degradation, HO-1 has been attributed several regulatory functions in tissue inflammation and protection against stress-induced apoptosis. Inducibility of HO-1 is moderated by a single nucleotide polymorphism (SNP) A -413 T in the promoter. It has been reported that the A-allele of this SNP is associated with higher promoter activity than T-allele. Additionally, there have been several reports on the involvement of polymorphism within the promoter region of the human HO-1 gene in various diseases of the vascular systems. Recently, the polymorphism in the HO-1 gene has been reportedly associated with the graft survival after liver transplantation. In this study we analyzed the impact of HO-1 polymorphism on transplant outcomes in patients undergoing unrelated HLA-fully-matched bone marrow transplantation (BMT) through the Japan Marrow Donation Program. Methods and Results: The SNP A -413 T was analyzed using the TaqMan system (Applied Biosystems). The HO-1 polymorphisms were retrospectively analyzed in a cohort of 259 pairs of patients with hematologic malignancies and their unrelated donors. The genotype frequencies of A/A, A/T and T/T were 22%, 48% and 38% in recipients and 20%, 53% and 27% in donors (P=0.41). The donor A/A or A/T genotype, a genotype expected to induce higher activity of the HO-1 gene, was associated with a better overall survival (OS) than the donor T/T genotype (55% vs. 38% @5-yr, P=0.002; Fig 1A) as well as trend toward reduced transplant-related mortality (TRM; 18% vs. 27% @5-yr, P=0.08; Fig 1B), while no significant differences between the A/A genotype and A/T genotype were noted. The beneficial effects of the donor A/A or A/T genotype were also found to be consistent on the multivariate analysis for OS (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.44 to 0.93; P=0.02) and TRM (HR, 0.59; 95% CI, 0.32 to 1.06; P=0.08). Furthermore, in the multivariate analysis the donor A/A or A/T genotype showed a tendency to a lower incidence of grades II-IV acute graft-versus-host disease (GVHD; HR, 0.68; 95% CI, 0.43 to 1.06; P=0.09). The recipient HO-1 genotypes did not significantly influence the transplant outcomes. Conclusions: These results suggest an association of the donor HO-1 genotype with overall survival after unrelated BMT, and may substantiate that the higher HO-1 activity by donors with the HO-1 A allele likely accounts for a reduced risk for TRM and acute GVHD in their recipients. These could therefore be useful in selecting the donor and creating therapeutic strategies for improving the final outcome of allogeneic BMT. Disclosures: No relevant conflicts of interest to declare.