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Background: Standard therapy for intermediate to high-risk acute myeloid leukemia (AML) consists of several hematopoietic cell transplantation (HCT) strategies including autologous-HCT (AUTO), allogeneic-HCT from matched-sibling donor (MSD) or well-matched unrelated donor (WM-URD). When a conventional donor is not available, HCT from partially-matched unrelated donor (PM-URD) or familial mismatched/haploidentical transplantation (FMMT) or umbilical cord blood transplantation is also considered for an alternative choice. Although HCT outcomes of those alternative strategies are advancing with optimization of pre-conditioning regimens with immunosuppressive agents, there are still subjects to debate. We tried to analyze the long-term HCT outcomes according to the donor types including FMMT and PM-URD as an alternative choice. Methods: We enrolled 561 AML patients (median 41 years old, range: 16-68) in complete remission (CR) who were transplanted in Catholic BMT Center in Korea from 2002 to 2013. Patients in at least second CR were excluded. All patients presented intermediate to high-risk karyotype according to the NCCN guidelines, and all of the patients received standard 3+7 chemotherapy followed by consolidation chemotherapy. In the absence of MSD and WM-URD, we allocated PM-URD or AUTO as an alternative choice first, and then FMMT was considered. We divided patients according to the 5 donor types (i.e. MSD (n=252), WM-URD (n=112), PM-URD (n=41), AUTO (n=104), and FMMT (n=52)), and survival outcomes with the cumulative incidence of relapse (CIR), non-relapse mortality (NRM), acute/chronic GVHD and CMV reactivation were analyzed. Results: Engraftment was successful and showed similar recovery pattern in all donor types. Our data showed mismatch in ABO, sex, and certain HLA locus was not influential, and stem cell source and conditioning-intensity were not also influential for survival outcome and incidence of GVHD. After median follow-up of 54.3 month (range: 6.6-145.6), MSD, WM-URD and FMMT showed similar 5-year OS around 62% except for AUTO at 47.4% and PM-URD at 36.7%. DFS at 5-years was 59% for MSD, 56% for WM-URD, 62% for FMMT, 44.3% for AUTO, and 33.5% for PM-URD. Five-year CIR rate was highest in AUTO (50.3%) followed by PM-URD (33.1%) and WM-URD (29.8%). Lower CIR-rate was identified in MSD (22.4%) and FMMT (21.4%), and the lowest NRM rate was identified in AUTO subgroup (5.1%) followed by WM-URD (11.4%), FMMT (15.6%) and MSD (18.0%). PM-URD showed the highest NRM rate (33.3%) with higher incidence (26.7%) of Gr°Ã3 acute GVHD compared to 9.3% of MSD. Incidence of chronic GVHD was not significantly different. In adverse-risk subgroup, 5-year OS of MSD, WM-URD, and FMMT was 46%, 47%, and 58% respectively, while AUTO and PM-URD was 11% and 0%, which was caused by significantly higher CIR rate of 79.7% and 83.5%, respectively, compared to 31.1% of MSD. In intermediate-risk subgroup, 5-year OS of AUTO (55.2%) was not inferior to that of MSD (67.2%, p =0.330) or FMMT (64.9%, p =0.451), which showed the highest CIR rate (42.8%) and the lowest NRM (5.4%). PM-URD also showed highest NRM (39.4%) with high incidence (27.3%) of Gr°Ã3 acute GVHD. Conclusions: FMMT should be considered prior to PM-URD in intermediate to adverse-risk AML and GVHD prophylaxis should be intensified when we have to use PM-URD. AUTO might be considered in intermediate-risk AML in selected patients and prospective study should validate the utility of FMMT or AUTO in addition to the conventional donor types. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Background The prognostic impact of serum ferritin level has been well established in patients with myelodysplastic syndrome and acute myeloid leukemia (AML) in the context of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, the clinical safety and efficacy of iron-chelation therapy (ICT) for adult AML with hyperferritinemia post-Allo-SCT has not been evaluated. Materials and methods We retrospectively evaluated 320 consecutive patients with de novo AML who received Allo-HSCT at complete remission in a single institution between January 2007 and February 2012. Serum ferritin levels were monitored from initial diagnosis to the several time points during the post-transplantation period in both the ICT group (n=113) and the non-treated group (NT, n=191). In the ICT group, ICT was started at least a month after transplantation when serum ferritin levels over 1,000 ng/mL, and continued to the ferritin level lower than 500 ng/ml unless serious adverse effects and/or relapse. Sixteen patients treated less than one month with ICT due to early complications, such as infection(n= 10, 62.5%), liver toxicity (n=4, 25%), and poor compliance (n=2, 12.5%) were excluded in the ICT group. The baseline characteristics between two groups were not significantly different. Results The median treatment duration in ICT group was 6.4 months (range, 1.0-49.2) with dosage of 20-40 mg/kg/day. Deferasirox treatment was discontinued at least one time in 43 patients (38%) in ICT group due to toxicities and/or poor compliance, but almost patients (n=40, 93%) could be treated again with deferasirox without further toxicities. High serum ferritin level of pre-Allo-HSCT over 1,000 ng/ml was significantly associated with poor overall survival (OS, 52.2% vs. 75.4%, HR 0.78, P Conclusion Our data demonstrate that ICT with deferasirox was well tolerable in AML with hyperferritinemia after Allo-SCT, and suggest the independent association of ICT with increased incidence of chronic GVHD and decreased relapse. Iron chelation may modulate of immunobiologic properties during the period of immune reconstitution (low level of Treg cells and higher CD16+ NK cells, 2014 ASH Abstract #2543) and/or induce direct anti-leukemia effect by iron depletion, which need to be further evaluated. Disclosures No relevant conflicts of interest to declare.

Background: For elderly patients unfit for intensive chemotherapy in acute myeloid leukemia (AML), low-dose cytarabine (LDAC; 20 mg SQ BID for 10 days) still remains to be the standard treatment, despite its unsatisfactory complete response (CR) rate of 18% and median overall survival (OS) of < 6 months (Burnett, 2007). Recently, there have been huge efforts to develop more effective and less-toxic therapies, such as decitabine, azacitidine, clofarabine, or gemtuzumab ozogamicin, but their benefits were not concrete, even though they were compared to the classical LDAC. To improve outcomes of the classical LDAC, we modified it by giving a higher dose of cytarabine for an extended duration in combination with oral etoposide. Herein, we present the results. Methods: Between 2002 and 2014, 93 consecutive older (≥ 60 years) patients with AML, who were unfit for intensive chemotherapy, received 1st cycle of modified LDAC (mLDAC) regimen consisting of cytarabine (20 mg/m2 SQ BID) and oral etoposide (50 mg PO BID) for 14 days. Thereafter, they received additional subsequent cycles (for a maximum of 7 cycles) for 10 days every 6 to 8 weeks. We retrospectively analyzed their overall response (OR), disease-free survival (DFS), and overall survival (OS) rates. In this analysis, OR was defined as CR plus CR with incomplete platelet recovery (CRp) or blood count recovery (CRi). Results: The median age of patients in our cohort, including 69 (74.2%) with poor performance status (ECOG ≥ 2), 15 (16.1%) with AML with myelodysplastic-related changes or secondary AML, and 13 (14.0%) with poor cytogenetic risk, was 68 years (range, 60-83). The median number of mLDAC regimen cycles which they received was 2 (range, 1-8). Clinically relevant toxicities of grade III-IV including nausea/vomiting, diarrhea, hyperbilirubinemia and neutropenic fever were observed in 4 (4.3%) patients, 6 (6.5%), 3 (3.2%), and 42 (45.2%), respectively, which were comparable with those of classical LDAC (Burnett, 2007). The early mortality rates at 30 and 60 days were 11.8% and 15.0%, respectively. The OR was observed in 45 (48.4%) patients, including 34 (36.6%) CR, 7 (7.5%) CRp, and 4 (4.3%) CRi, within two cycles of mLDAC. With median follow-up duration of 26.1 months, the median DFS and OS were 6.2 and 15.8 months, respectively. For patients who achieved OR, they were 14.5 and 36.9 months, respectively. The OR of patients who had poor cytogenetic risk was not significantly different compared to others (57.1%, 46.2%, and 38.5% for favorable, intermediate, and poor cytogenetics, respectively; P=0.50). However, they showed significantly shorter median DFS (9.8, 6.6, and 5.1 months, respectively; P=0.01) and OS (NR, 1.4, and 5.1 months, respectively; P=0.01) with significantly shorter OR duration (30.6, 19.1, and 8.6 months, respectively; P=0.01). Between 2009 and 2014, among 17 patients treated with hypomethylating agents (HMA; 14 decitabine and 3 azacitidine), 1 CR and 3 partial response were achieved with a median survival of 5.5 months, and 5 patients after HMA treatment failure received subsequent mLDAC, and 3 achieved additional CR (n=2) and CRp (n=1). Conclusions: These results suggest that the outcomes of classical LDAC in elderly patients with AML can be improved by modifying it, with improved response and survival rates without increasing toxicities, even in patients with poor cytogenetics. Additionally, mLDAC could induce clinical responses in patients with HMA failure. Our mLDAC regimen may become another therapeutic option with emerging novel agents for elderly patients with AML, and these should be confirmed by large randomized trials. Disclosures No relevant conflicts of interest to declare.

This paper presents the results of an investigation on the behavior of geosynthetic-reinforced segmental retaining walls in tiered arrangement. A finite element model capable of modeling the fundamental behavior of geosynthetic-reinforced segmental retaining wall was used to perform a parametric study. Primary variables considered in the parametric study include the offset distance between the tiers and the reinforcement length in the lower tier. The results of the parametric study were then used to highlight the interaction between the upper and the lowers. Practical implications of the findings from this study are discussed in great detail.

Background/Aims Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. Methods We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score ≥ 2. From 2006 to 2011, among the 150 DLBCL patients aged ≤ 60 years who were treated with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), 23 high-risk patients with a complete response (CR) were treated with auto-HSCT. For comparison, we selected 35 well-matched high-risk patients with CR who completed R-CHOP treatment alone. In addition, there were 81 low-risk patients and 11 refractory patients. Results DLBCL patients with an aaIPI score ≥ 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. Conclusions We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.

Background:Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant clonal disorder of hematopoietic stem cells characterized by a somatic mutation in the PIG-A gene, encoding the glycosyl phosphatidylinositol (GPI) moiety. PNH clones lack GPI-anchored proteins (GPI-AP) which inhibit the activation and cytolytic functions of complement. Recently, Eculizumab, humanized monoclonal antibody directed against complement component C5, has used increasingly for the patients with hemolytic PNH. However, the patients with PNH clone and bone marrow failure syndrome (i.e. aplastic anemia) should be treated as their predominant clinical manifestation. Allogeneic stem cell transplantation (SCT) can be curative treatment option especially for PNH patients with combined aplastic anemia (AA). The aim of the present study was to evaluate long-term outcome of allogeneic SCT in patients with AA/PNH. Methods: Total of 27 patients with PNH clones underwent allogeneic SCT at our institution between Jan 1998 and Mar 2014. Among them, seven patients had classic PNH and 20 patients with cytopenia had AA/PNH (with bone marrow evidence of a concomitant AA). We analyzed long-term transplant outcomes in 20 patients with AA/PNH. Results: There were 12 male and 8 female patients with a median age of 34 years (range, 13-51 years). The median interval from the diagnosis to transplantation was 8 months (range; 1-201 months). The median transfusions prior to SCT were 33 units (range; 8-208 units). Pre-transplant GPI-AP deficient neutrophils and erythrocytes were 46% (0-99) and 15.6% (0-88), respectively. Median white blood cell, absolute neutrophil count, hemoglobin, and platelet at transplant were 2.3×109/L, 0.7×109/L, 7.9 g/dL, and 21×109/L, respectively. Median LDH level was 714 U/L (range; 273-6499 U/L) and 11 (55%) patients had LDH ≥1.5x upper normal limit. PNH patients with SAA (n=14), VSAA (n=4), or non-SAA (n=2) received SCT from sibling (s) donor (n=15) or unrelated (u) donor (n=5). The conditioning regimen for s-SCT consisted of fludarabine (180 mg/m2) + cyclophosphamide (CY, 100 mg/kg) + ATG (10 mg/kg) (n=11), or busulfex (12.8 mg/kg) + CY (120mg/kg) (n=4). The conditioning regimen for u-SCT was TBI (fractionated, 800 cGy) + CY (100-120 mg/kg) ± ATG (2.5 mg/kg). GVHD prophylaxis consisted of CsA + MTX in s-SCT and FK506 + mini-MTX in u-SCT, respectively. After a median follow-up of 57 months (range 4.7-122.1), the 5-year estimated OS rates were 90.0 ± 6.7%. Two patients died of treatment-related mortality (TRM), including acute GVHD (n=1) and cerebral hemorrhage (n=1), respectively. Except one patient with early TRM, 19 patients engrafted with no secondary graft-failure. The cumulative incidence of acute GVHD (≥grade II) and chronic GVHD was 25.0 ± 1.0% and 26.3 ± 10.4%, respectively. PNH clones disappeared at median 1.8 months (range 0.9-11.9) after SCT and reemerging of PNH clone was not observed in all patients. Conclusion: This study showed that long-term transplant outcome in patients with AA/PNH were comparable to that of allogeneic SCT in SAA (the 3-year estimated OS rates were 92.7 and 89 % for s-SCT and u-SCT, respectively) at our institution (ASH Annual Meeting Abstracts 2012;120:4151). Therefore, application of allogeneic SCT should be considered in PNH patients with AA in case of availability of well matched donor. Disclosures No relevant conflicts of interest to declare.

Background: Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder. Immunosuppressive therapy or allogeneic stem cell transplantation (SCT) are recommended depending on severity of the disease, patient's age and availability of donor. In addition, many patients require blood transfusions as supportive management, which lead to the development of iron overload. Previous studies have shown a negative impact of pretransplant iron overload on overall survival (OS), mortality, and infection in patients undergoing allogeneic stem cell transplantation (SCT). Although the use of oral iron-chelating agent, deferasirox, has been increased, the impact of pretransplant iron chelating therapy (ICT) on the transplant outcomes in patients with SAA was uncertain. Methods: This study included 109 iron overloaded patients with SAA who underwent allogeneic SCT between March 2002 and December 2012. All patients had available pretransplant serum ferritin data. Among them, 50 patients were received pretransplant ICT with deferasorox, when their serum ferritin was more than 1000 ¥ìg/L, whereas 59 patients had more than 1000 ¥ìg/L of serum ferritin but did not received ICT (era before availability of deferasirox). Results: Fifty-five men and 54 women were assessed. Their median age was 34 years (range, 15-59 years). The patients received grafts from either a HLA identical sibling (N=55) or an unrelated donor (N=54). Primary engraftment was achieved in all, but 5 patients developed secondary graft failure. After a median follow-up of 38.3 (range, 6.1-124.9) months for survivors, there was not statistical difference of overall survival (OS) between the patients with ICT and those without ICT (82.3% vs 89.9%, P=0.455). Of note, the possible survival benefit of pretransplant ICT was observed in unrelated transplant setting (93.5% vs. 78.3%, P=0.090). Pretransplant ICT group showed a lower infection rate after SCT compared to those without ICT (34% vs. 59%, P=0.008). For 50 patients receiving pretransplant ICT with deferasirox, median serum ferritin levels decreased from 1995 ¥ìg/L at the initiation of ICT to 1240 ¥ìg/L before SCT. Median duration of ICT before SCT was 3.6 months (range, 0.3-44.2 months), and mean daily dose was 14.8 mg/kg per day. The patients who achieved more than 650 ¥ìg/L decrement of serum ferritin levels from ICT initiation to SCT had a higher OS than the patients with less than 650 ¥ìg/L (96.7% vs. 80.0%, P=0.044). Conclusion: These results indicate that iron overload was associated with a negative impact on outcome after SCT in SAA. Pre-SCT ICT can reduce the incidence of infection after SCT and the possible survival benefit of Pre-SCT ICT was present especially in unrelated donor SCT. Among the patients receiving pretransplant ICT, significant decrement of serum ferritin is a favorable prognostic factor after allogeneic SCT in iron-overloaded patients with SAA Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

[Graphic][1] Background: To explore a real incidence of dasatinib-induced pulmonary arterial hypertension (D-PAH) in clinical practice, we investigated 82 imatinib or other 2G tyrosine kinase inhibitor (TKI)-failed chronic myeloid leukemia (CML) patients who received dasatinib as a second-line therapy. Methods: Routine chest X-ray and Doppler echocardiography were regularly evaluated in all patients and additional tests were performed if dyspnea developed on treatment. Results: Median age at the time of starting dasatinib was 48 (16-82) years. Of 82 patients, 8 patients (9.8%) showed an elevation of right ventricular systolic pressure (RVSP>35mmHg) by Doppler echocardiography. Among them, 7 patients (8.5%) were considered D-PAH with a median dasatinib treatment duration of 32.6 (10.3-108.7) months. They underwent follow-up Doppler echocardiography median 5 (2-9) times. Five patients showed severe D-PAH (RVSP >70mmHg), 1 was moderate (RVSP 46mmHg), and 1 was mild (RVSP 41mmHg). Advanced studies such as pulmonary angiographic catheterization (patient 1 and 2) or pulmonary arterial computed tomography (patient 3 and 4) were performed for confirming D-PAH or ruling out PAH due to pulmonary vascular abnormality. Six patients had bilateral pleural effusion and 1 had unilateral pleural effusion. With sildenafil (n=5) + dose reduction (n=1) + switch to other TKI (n=6), all of patients improved dyspnea, and RVSP level was completely resolved in 3 patients. In addition, previous nilotinib therapy and concomitant pleural effusion were significant contributing factors for D-PAH. Conclusion: Regardless of complete resolution of pleural effusion, a patient with sustained dyspnea on dasatinib treatment should be carefully evaluated by Doppler echocardiography and a regular monitoring will be needed for early intervention. | Cohort | Age at PAH diagnosis (year) | Sex | Treatment duration before dasatinib (month) | Previous therapy for CML | Duration between initiation of dasatinib and diagnosis of PAH (month) | Daily mean dose of dasatinib (mg/d) | Duration between diagnosis of D-PAH and last follow up (month) | Treatment of D-PAH | Switch to other TKI | Outcome | | ------ | --------------------------- | --- | ------------------------------------------- | ------------------------------------------------------- | --------------------------------------------------------------------- | ----------------------------------- | -------------------------------------------------------------- | ------------------------------------ | ----------------------- | -------- | | 1 | 53 | M | 54.4 | Interferon, Hydroxyurea, Imatinib, nilotinib | 26.4 | 123 | 73.5 | Sildenafil | nilotinib and ponatinib | partial | | 2 | 50 | M | 36.6 | Interferon, Hydroxyurea, Imatinib, dasatinib, nilotinib | 50.3 | 112 | 55.2 | Sildenafil | nilotinib and radotinib | partial | | 3 | 37 | F | 31.7 | Imatinib, nilotinib | 21.7 | 88 | 39.7 | Sildenafil Dose de-escalation | radotinib | partial | | 4 | 45 | M | 70.9 | Hydroxyurea, Imatinib | 69.8 | 101 | 35.2 | Sildenafil Dose de-escalation | ponatinib | complete | | 5 | 59 | F | 107.4 | Interferon, Hydroxyurea, Imatinib | 83.6 | 92 | 14.3 | none | radotinib | partial | | 6 | 46 | F | 12.6 | Imatinib | 29.1 | 76 | 13.0 | Steroid, Sildenafil | radotinib | complete | | 7 | 38 | F | 30.2 | Imatinib | 33.1 | 98 | 10.2 | Dose reduction | NA | complete | Abstract 5535. Table 1. Characteristics of patients with dasatinib-induced PAH Disclosures No relevant conflicts of interest to declare. [1]: /embed/inline-graphic-2.gif

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder that leads to mucocutaneous telangiectasias, epistaxis, and gastrointestinal bleeding. Depending on the severity and manifestation of the disease, various therapeutic modalities have been used, from local bleeding control to surgery or concomitant drug therapy. Several articles under review have presented guidelines for treatment of HHT with bevacizumab as a direct anti-angiogenesis strategy. Still, neither the exact optimal dose nor the minimum effective dose of intravenous bevacizumab in patients with severe HHT has been reported. A 55-year-old man presented with long-standing epistaxis, recent melena, dizziness, and a three-generation family history of chronic epistaxis, anemia, and regular blood transfusions. Treatment with argon plasma coagulation (APC) for the gastrointestinal bleeding failed to raise hemoglobin levels, we considered using the bevacizumab. We report a patient with severe HHT, who was treated with low-dose bevacizumab (2 mg/kg) and improved substantially.

In western countries, several studies have reported that CMV seronegative acute leukemia (AL) patients might have a beneficial effect from CMV seropositive donor for reduction of relapse. These observations resulted from subclinical CMV viremia with delayed initiation of antiviral therapy which showed a stimulatory effect on natural-killer cells and cytotoxic T-cells that may enhance graft-versus-leukemia (GVL) effect. We tried to evaluate the relationship between CMV reactivation and relapse of AL in Korean population, in which CMV serostatus is mostly positive for both donors and recipients. Three hundred eighty-nine AL patients with AML (n=197), ALL (n=192) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first remission between 2007 and 2011 were retrospectively analyzed. Most of the donors (95.1%) and recipients (98.7%) were CMV seropositive. After engraftment, we serially measured CMV RQ-PCR once a week for surveillance of CMV reactivation and generally initiated preemptive ganciclovir (GCV) therapy when the titer reaches over 15,000copies/mL. Below 15,000, patients without GVHD were observed with tapering immunosuppressive agents. To evaluate the anti-leukemic activity of CMV viremia, patients with early death ( In the entire group, CMV viremia was an adverse factor for OS (p Our data showed the possible GVL effect associated with CMV reactivation measured by RQ-PCR. This finding should be evaluated by larger validated studies to disclose the role of CMV reactivation in AL in the CMV seropositive population. Disclosures: No relevant conflicts of interest to declare.

Introduction Recent randomized trial (DASISION trial), compared clinical outcomes between dasatinib and imatinib in newly diagnosed (chronic myeloid leukemia) CML patients. Results showed that dasatinib had faster and deeper responses compared with imatinib, and thus dasatinib became to be considered as a first-line therapy in CML patients. However, the long-term administration of dasatinib has been reported to have a risk of pleural effusion and dasatinib-related (pulmonary arterial hypertension) PAH. So, we have prospectively evaluated for emergence of PAH in all CML patients treated with dasatinib in our institute. Materials and methods Between May 2005 and July 2013, a total of 89 CP CML patients on dasatinib treatment were tested with laboratory studies, Brain natriuretic peptide (BNP), echocardiography (echo) in the Catholic University of Korea, Seoul, and baseline functional capacity (NYHA or WHO functional class) was assessed. PAH was defined as mean pulmonary artery pressure (mPAP) of >25mmHg at rest, with wedge pressure < 15mmHg, or Rt. Ventricular systolic pressure (RVSP) of 40 mmHg on echocardiography. And patients who had abnormal RVSP and/or symptoms (New York heart association-NYHA class 3, 4) were performed with additional studies such as pulmonary angiographic catheterization or pulmonary arterial computed tomography. Results So far, 62 patients (70%) of total 89 were evaluated with echocardiography (46 male, 16 female). The median age was 48 year old (range, 22∼72). The median duration of disease was 8.5 years (range, 0.8∼16.1). The median mean daily dosage of dasatinib was 102mg (range, 73∼140mg). The duration of dasatinib treatment was 34.6 months (range, 0.5∼99.6). 8 of 66 patients (12.1%) showed abnormal echocardiographic findings as increased right ventricular systolic pressure or symptom. All of 8 patients had treated with dasatinib as second line, and had exertional dyspnea (2 patients on class 2, and 5 patients on class 3 of NYHA). 5 patients of these showed abnormal BNP levels. The mean RVSP in screened patients was 65.2 mmHg (range, 40∼108mmHg), 2 of 8 patients were confirmed diagnosis with overt PAH on as pulmonary angiographic catheterization, and right ventricular hypertrophy on pulmonary angiographic computed tomography. Clinical, functional, or hemodynamic improvements were observed within 5 months of dasatinib discontinuation and then, in 5 patients the treatment was switched to radotinib, and another 3 patients received reduced dosage of dasatinib. Conclusion Although the lowest estimate of incident PAH occurring in patients exposed to dasatinib was 0.45% in France group. our preliminary data show more higher incidence rates (8 of 66 patients, 12.1%) in Korea. So, we suggest that the long-term dasatinib treatment for CML requires careful attention to cardiopulmonary adverse effects. and routine cardiovascular and pulmonary evaluation on regular basis is strongly recommended before and during treatment with dasatinib. Disclosures: No relevant conflicts of interest to declare.

Background Allogeneic stem cell transplantation (SCT) from matched-sibling donor (MSD) and immunosuppressive treatment (IST) are the most widely used first-line treatments for patients with severe aplastic anemia (SAA). Overall long-term survival rates are comparable between the two groups. However, patients with age of over 40 have not been generally considered as candidates of SCT from MSD (MSD-SCT) due to higher transplant-related mortality. Recent improvements in MSD-SCT such as less intensive fludarabine-based conditioning, and use of rabbit anti-thymocyte globuline (ATG) instead of horse ATG as first-line IST may change these results. Therefore, we compared the clinical outcomes between MSD-SCT with fludarabine-based conditioning and IST with rabbit ATG and cyclosporine A (CsA). Methods We analyzed the clinical results of 54 adult SAA patients who were treated with MSD-SCT and 93 with IST as a first-line treatment from March 2006 to May 2012 at Seoul St. Mary’s Hospital, Seoul, Korea. The patients who were treated with MSD-SCT received conditioning with fludarabine (30 mg/m2/day × 6 days), cyclophosphamide (50 mg/kg/day × 2 days), and rabbit ATG (Thymoglobulin®, 2.5 mg/kg/day × 4 days). Those who were treated with IST received rabbit ATG (2.5 mg/kg/day × 5 days) with CsA. Results The median ages were not significantly different between the MSD-SCT group and IST group (38.5 years vs. 43.0 years; P=0.103). Other baseline characteristics were comparable except the interval from diagnosis to treatment (100 days vs. 40 days; P=0.013), absolute lymphocyte count (0.68 × 109/L vs. 0.93 × 109/L; P=0.013), and platelet count (10.0 × 109/L vs. 11.0 × 109/L; P=0.035). In the IST group, overall response and complete response rates at 1 year were 44.1% (95% CI, 33.8-54.8) and 10.8% (95% CI, 5.3-18.9). Treatment failure developed in 55 (59.1%) patients due to non-response in 34 (36.6%), relapse in 5 (5.4%), clonal evolution in 3 (3.2%), and treatment-related mortality in 13 (14.0%) patients. After treatment failure, 17 (18.3%) patients received SCT from MSD or unrelated donor. In the MSD-SCT group, 10 (18.5%) patients experienced treatment failure due to secondary graft failure in 5 (9.3%), clonal evolution in 1 (1.9%), and treatment-related mortality in 4 (7.4%) patients. Among the patients who experienced secondary graft failure, 4 (7.4%) patients received secondary SCT, which resulted in sustained graft function. Consequently, overall survival (OS) at 3 years in the MSD-SCT group was not significantly different compared to that in the IST group (90.7% vs. 81.0%; P=0.139). However, the MSD-SCT group showed significantly higher failure-free survival (FFS) at 3 years compared to the IST group (80.2% vs. 46.6%; P Conclusions Our data suggest that MSD-SCT is more favorable than IST as a first-line treatment, considering the curative nature of MSD-SCT even in patients over 40 years of age. Disclosures: No relevant conflicts of interest to declare.

Background In the setting of unrelated donor stem cell transplantation (URD-SCT), several data showed that peripheral blood stem cells (PBSC) resulted in faster engraftment but increased the risk of acute or chronic graft-versus-host disease (GVHD), while other transplant outcomes were comparable. However, there are some limitations in these data due to heterogeneous diseases or registry data characterized by various other treatment strategies. Notably, we have added low-dose rabbit anti-thymocyte globuline (ATG) only to the patients who received URD-SCT with PBSC because of their higher risk of developing GVHD. In this setting, we compared the long-term outcomes of URD-SCT using PBSC and bone marrow (BM) and studied the role of low-dose rabbit ATG in the prophylaxis of GVHD. Methods Between March 2004 and April 2012, 115 adult patients with AML underwent myeloablative (n=87) or reduced-intensity (n=28) conditioning HLA-matched URD-SCT with PBSC (n=70) or BM (n=45) grafts. All patients received tacrolimus and short-course methotrexate for GVHD prophylaxis. Low-dose rabbit ATG (Thymoglobuline®, 1.25 mg/kg for 2 days) was added only to the patients who received URD-SCT with PBSC grafts. The median follow-up of survivors was 44 months (range, 2-100) for PBSC transplants and 54 months (range, 8-105) for BM transplants (P=0.01). Results Baseline characteristics were not significantly different between the two groups except for total-body irradiation conditioning regimen (72.9% vs. 91.1%; P=0.02). PBSC transplants showed faster recovery of neutrophil (11 days vs. 13 days; P=0.03) and platelet (12 days vs. 18 days; P=0.01) counts than BM transplants. No difference was observed in the cumulative incidence of acute GVHD (grade ≥2) at 100 days (54.3% vs. 64.4%; P=0.38) and chronic GVHD at 4 years (61.4% vs. 60.0%; P=0.88) between the two groups. In spite of adding low-dose rabbit ATG, PBSC transplants did not show higher incidence of relapse compared to that of BM transplants (30.8% vs. 31.2%; P=0.53). Other transplant outcomes including non-relapse mortality (13.5% vs. 6.9%; P=0.24), disease-free survival (55.7% vs. 61.9%; P=0.80), and overall survival (63.3% vs. 63.2%; P=0.59) were comparable between the two groups. In multivariate analysis, graft source had no impact on transplantation outcomes. Regardless of graft source, transplants in ≥CR2 had higher relapse risk (hazard ratio, 2.45; 95 % CI, 1.04-5.76; P=0.04), poorer disease-free survival (hazard ratio, 2.68, 95% CI, 1.29-5.56; P=0.01) and overall survival (hazard ratio, 2.59; 95% CI, 1.20-5.59; P=0.02). Conclusion Adding low-dose rabbit ATG to the patients who received URD-SCT with PBSC may lower the incidence of acute and chronic GVHD comparably to that of URD-SCT with BM without increasing the incidence of relapse. Disclosures: No relevant conflicts of interest to declare.

Core-binding factor (CBF)-positive acute myeloid leukemia (AML) is regarded as a favorable group with good complete remission (CR) rate after induction chemotherapy and is generally treated by repeated high-dose cytarabine consolidation or autologous hematopoietic stem cell transplantation (auto-HSCT). However, emerging molecular studies have recently identified the unfavorable CBF-AML subgroup which should be treated by further intensified treatments. This single center retrospective study enrolled 264 adult CBF-AML patients from 2002 to 2011. Except 15 patients, 217 patients were treated by intensive induction chemotherapy and 32 were treated by reduced intensity treatment. After CR achievement, patients with available donor were treated by allogeneic (allo)-HSCT and the rest were treated by auto-HSCT or chemotherapy alone. We evaluated 206 patients who achieved CR after intensive chemotherapy regarding survival outcomes according to post-remission therapies and prognostic factors which affected the outcomes. The factors included cytogenetic study and subgroup analysis with additional chromosomes and normal karyotype (NK) mosaicism, c-kit mutation, minimal residual disease (MRD) qPCR level, BAALC and WT1 expression. We achieved CR in 94.9% with intensive chemotherapy and 115 patients went on allo-HSCT and 72 were treated by auto-HSCT. There were no significant OS differences between CBF¥â/MYH11 and RUNX1/RUNX1T1 (p=0.173), and auto-HSCT showed favorable EFS (p=0.038) compared to allo-HSCT and chemotherapy alone. For cytogenetic analysis, inv(16) or t(16;16) with NK mosaicism showed the most favorable OS compared to t(8;21) with additional chromosome (¡Ã2) which showed the worst OS. c-kit mutation was a poor prognostic factor with lower reduction rate of post-induction MRD qPCR, however the effect was not definite after HSCT. For HSCT patients, we analyzed post-HSCT MRD qPCR and WT1 expression level. We found that undetected level of post-HSCT MRD qPCR and lower level of WT1 expression ( For CBF-AML, the role of auto-HSCT and allo-HSCT for selected patients should be re-evaluated by large prospective studies and the values like post-treatment MRD qPCR and WT1 expression level can be used for prediction of patients who might relapse with higher probability. Disclosures: No relevant conflicts of interest to declare.

Background/Aims The pathogenesis of bone loss in patients with inflammatory bowel disease (IBD) is complex, multifactorial, and only partly understood. We aimed to examine the extent and risk factors of bone mass reduction and to analyze the impact of early onset of a disease before attaining peak bone mass in IBD patients. Methods We compared the risk factors for osteoporosis and BMD at the lumbar spine and the hip bone in IBD patients. Results A total of 44 patients with IBD were enrolled. Twenty-one and 23 patients were diagnosed as IBD before and after the age of 30 and designated as group A and group B, respectively. Group A had significant bone mass reduction at the lumbar spine than group B (BMD, 1.01±0.10 vs. 1.14±0.17, p

Abstract 4800 Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) with distinctive biologic and clinical features that is now highly curable. Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (As2O3, ATO). Emerging evidence has implicated Src family kinases (SFKs) as regulators of proliferation and survival of myeloid lineage cells. Recent studies showed that inhibition of SFKs resulted in enhancement of retinoic acid-induced myeloid differentiation. In this study, we demonstrated that the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well when combined with as all-trans-retinoic acid (ATRA) and the difference in the retinoic acid-induced gene expression between the cells treated with PP2 in combination with ATRA and the cells treated with PP2 in combination with ATO. SFK inhibitor PP2 significantly enhanced ATRA- or ATO-induced differentiation of NB4 cells. The synergistic effect was significantly stronger when PP2 was combined with ATRA than when PP2 was combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by morphologic analysis using Wright stain and NBT staining. These effects were not related to apoptosis. Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. ICAM-1 expression was significantly increased in the cells treated with PP2 in combination with ATRA whereas cathepsin D expression was significantly increased in the cells treated with PP2 in combination with ATO. These findings suggested that the synergistic effect of SFK inhibitor PP2 in combination with ATRA was significantly stronger than that of PP2 in combination with ATO on NB4 myeloid leukemia cell differentiation and this difference was related to the disparate activation of retinoic acid-induced genes. Disclosures: No relevant conflicts of interest to declare.

e19554 Background: Palonosetron(PAL) is a 5-HT3 antagonist with an approximately 100-fold higher binding affinity for the 5-HT3 receptor compared to the other serotonic antagonists(i.e., ondansetron, granisetron, and dolasetron). Several large phase III trials have demonstrated the superiority of palonosetron compared with other 5-HT3 antagonists in preventing emesis associated with both moderate and high emetic risk chemotherapy regimens. But, these studies carried out in the pre-aprepitant era. We assessed that PAL is still preferred over the other serotonin inhibitors for high emetic risk chemotherapy in the post-aprepitant era. Methods: A retrospective analysis was made of all patients who underwent serotonin inhibitor, aprepitant and dexamethaxone for high emetic risk chemotherapy between 2009 and 2011. Group A received PAL, aprepitant and dexamethaxone. Group B received first-generation serotonin inhibitors(ondansetron, granisetron or dolasetron), aprepitant and dexamethaxone. Results: Four hundred fourty patients were included in the analyses: 331 patients in the Group A and 109 patients in the Group B. No case of grade 3-4 nausea/vomiting was noted. There were no significant differences between Group A and Group B for both acute and delayed CINV. The proportion of patients with a emesis-free during the acute phase(0-24 h) was similar in both groups: 275 of 331 patients(83%) in the Group A vs 88 of 109 patients(81%) in the Group B. The proportion of patients with a emesis-free during the delayed phase(24-120h) was similar in both groups: 255 of 331(77%) vs 76 of 109 (70%). Conclusions: In aprepitant era, all of the serotonin inhibitors seems to be equally effective for high emetic risk chemotherapy.

The degradation of amorphous indium–gallium–zinc–oxide (a-IGZO) thin film transistor (TFT) inverter operation is investigated under AC pulse stresses. From the extraction of subgap density of states (DOSs), the dominant mechanism of the pulse stress-induced degradation of driver TFT is considered as the increase of acceptor-like deep states, while that of the load TFT is attributed to the increased number of electrons trapped into the interface and/or a-IGZO thin films. We also observe that the rising and falling time of the induced pulse affects each TFT of the inverter in a different manner, and discuss the related mechanism of this phenomenon.