ALBERT

Description: Abstract 4299 Background Adult T-cell leukemia/lymphoma (ATLL) has a poor prognosis because of its chemo-resistance. Many chemotherapeutic regimens have been created but none of them have shown sufficient results. We proposed allogeneic stem cell transplantation (allo-SCT) for ATLL patients and showed an improved survival rate. However, relapse or progression of ATLL is one of the major limiting factors of survival in post SCT patients. Aims In order to establish a better treatment strategy for poor responders after SCT for ATLL, we analyzed the outcome of relapse or progression cases after allo-SCT. We paid special attention to the graft versus ATLL (GvATLL) effect. Methods There were 37 ATLL patients in which allo-SCT was performed in Imamura Bun-in Hospital (IBH) from June 1998 to April 2009. Twenty-eight cases survived over 100 days after SCT. Sixteen of the 30 patients relapsed. Using data in medical records of IBH, we analyzed transplant characteristics and the outcome of these 17 patients retrospectively. Results Disease status at SCT was CR in 2 patients, 2 PR, 5 SD, and 7 PD. Eight patients received conventional stem cell transplantation (CST) and the other seven patients received reduced-intensity stem cell transplantation (RIST). Fourteen patients in 17 obtained remission (10 CR and 5 PR), but the remaining 2 did not (1 SD and 1 PD) after SCT. The sites of relapse or progression in 17 were skin in 10 patients, 8 peripheral blood, 7 lymph node, 3 central nervous system, and 1 bone. All patients discontinued immunosuppressants after relapse or progression. Eleven patients obtained remission. Especially, in 5 out of 11 patients, remission was obtained only by discontinuation of immunosuppressants (graft-versus-ATLL effect), and the time to remission after discontinuation of immunosuppressants was between 1 to 14 days. Twelve patients were complicated with acute GVHD (grade I-IV). Twelve patients died after SCT. The causes of death were disease progression of ATLL in 5 patients, 3 acute GvHD, 3 infectious complications, and 1 interstitial pneumonia. Four patients who were complicated with acute GvHD survived over 3 years. Discussions Ten patients out of 17 experienced relapse or progression as skin lesion, and 8 patients out of 10 achieved re-remission. It suggests that skin lesion can be a warning sign of ATLL relapse. Since various types of clinical entities, such as ATLL relapse, GvHD, or drug eruption, can manifest as skin lesion after SCT, we strongly recommend to do skin biopsy aggressively to clarify the diagnosis. Ten patients out of 17 achieved re-remission (5 of them achieved only after the discontinuation of immunosuppressant), and 2 patients out of 5 attained long-term survival. This fact raises the possibility that GvATLL effect play a role in controlling exacerbation of ATLL. By focusing on the 5 cases that obtained re-remission only with discontinuation of immunosuppressant, 4 cases showed GvATLL effect prior to GvHD, and one patient experienced fatal grade IV GvHD, respectively. These outcomes suggest that immunosuppressant should be resumed in response to the signs of GvHD deterioration. Relapse/progression cases shows poor survival rate compared with non-relapse ones (60% vs 20% P=0.0028). Although re-remission was highly achieved, this fact suggested that countermeasure against GvHD or re-relapse are indispensable for long-term survival. Summary/conclusions Skin was a major site of relapse or progression after SCT in ATLL patients. A certain number of patients obtained remission only by the discontinuation of immunosuppressants. Four patients survived more than 3 years with their complication of acute GVHD. These results suggest that the GvATLL effect after SCT exists and plays an important role in longer survival for poor responders of post allo-SCT in ATLL patients. Disclosures: No relevant conflicts of interest to declare.

Description: Allogeneic hematopoietic stem cell transplantation (HSCT) for advanced hematological diseases dose not reach a satisfactory result so far. Recently, umbilical cord blood transplantation (UCBT) is widely practiced for advanced hematological diseases by its tolerance of HLA matching. However, high incidence of transplant related complications such as engraftment failure, infections, pre-engraftment immune reaction (PIR) etc. are still issues to resolve. Although non-TBI regimens are easy to prepare, few reports investigated non-TBI regimens for UCBT. With respect to UCBT with non-TBI conditioning regimens, we examined efficacy and feasibility of them for high-risk hematological diseases. Non-CR hematological malignancies, and int-2/high risk MDS categorized by IPSS were defined as advanced hematological disease. From June 2011 to January 2015, 47 patients consecutively underwent UCBT at our center. Thirty-five of 47 patients (23 male, 12 female), who were suffered from advanced hematological diseases were undergone first-time UCBT with non-TBI conditioning regimens. There were five non-TBI regimens such as fludarabine (Flu) 180mg/m2 + intravenous buslufan (Bu) 12.8mg/kg + melpharan (Mel) 80mg/m2 (FB4M) and Flu 125mg/m2 + Mel 200 mg/m2 (FM200) as the myeloablative conditioning regimens (MAC) and Flu 125mg/m2 + Mel 140mg/m2 (FM140), Flu 180mg/m2 + Bu 6.4mg/kg + Mel 140mg/m2 (FB2M140) and Flu125mg/m2 + cyclophosphamide (Cy) 120mg/kg + ATG 2.5mg/m2(FCyATG) as the reduced intensity conditioning regimens (RIC) has been used at our center. We investigated patients' characteristics, engraftment, overall survival (OS), incidence of transplant related mortality (TRM) and disease related death (DRD). OS was calculated with Kaplan-Meier method and the cumulative incidence of neutrophil engraftment, TRM and DRD was calculated with Gray′s method. Statistical significance was regarded as less than 0.05 of p-value. Statistical analyses were carried out using EZR (Kanda Y. BMT 2013). Median age at UCBT was 57 years (21-70). Fourteen patients with myeloid diseases (11 AML, 3 MDS) and 21 lymphoid diseases (17 ATLL, 1 ALL, 3 NHL) were included. 25 patients used MAC, 21 patients received FB4M, 4 FM200 followed by UCBT. On the other hand, 10 patients recieved RIC, 8 patients with FM140 and 1 each FB2M140, and FCyATG. Median time to neutrophil engraftment was 23 days (14-58) and cumulative incidence of neutrophil engraftment at day100 with the competing risk as early death (14.3%; 95%CI: 0.51-28.0) was 82.9% (95%CI: 64.1-92.4). Cumulative incidence of TRM at day 100 after UCBT was 37.4% (95%CI: 21.5-53.3). Also cumulative incidence of DAD at 3 month after UCBT was 14.9% (95%CI: 5.3-29.2). These results suggested that additional use of melpharan will be contributed to high incidence of engraftment and low incidence of relapse. In patients with myeloid diseases, cumulative incidence of DAD at 6 months after UCBT was 7.9% (95%CI: 0.4-31.3). However, in the patients of lymphoid diseases, cumulative incidence of DAD at 6 months was relatively high (37.1%; 95%CI: 12.4-62.5). There was no statistical difference between myeloid diseases and lymphoid disease about the incidence of TRM at day100 after UCBT. Although a lot of problems to solve were still remained in lymphoid diseases (OS at 1 year: 21.4%; 95%CI: 9.3-66.8), UCBT with non-TBI regimens would be feasible in the aspect of neutrophil engraftment and can be a promising treatment strategy for patients who suffered from advanced myeloid diseases (OS at 1 year: 55%; 95%CI: 25.8-76.8). Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Adult T cell leukemia/lymphoma (ATL) is a poor prognostic T-cell malignancy and the median survival time of aggressive type ATL is about a year regardless of intensive chemotherapy. Since 2001, several studies mainly from Japan show that allogeneic hematopoietic stem cell transplantation (allo-HSCT) has improved overall survival (OS) of ATL. To confirm the survival of the ATL patients received treatment such as chemotherapy and allo-HSCT and the usefulness of allo-HSCT on ATL, we analyzed retrospectively the patients with ATL treated recently in our institute. Patients and methods: There were total 198 patients who were consecutively hospitalized and received treatments as ATL between July, 2006 and December, 2013 in Imamura Bun-in Hospital that located at Kagoshima, an endemic area of HTLV-1 infection in Japan. This time we studied about backgrounds (age, gender, subtypes of ATL, performance status (PS) at diagnosis and clinical stage) of the patients, content of allo-HSCT, prognostic index for acute and lymphoma type ATL (ATL-PI) and survival duration from diagnosis retrospectively. The comparisons between the mean values were performed by Student’s t test or the Mann–Whitney test. The overall survival from diagnosis (OS) was analyzed with Kaplan-Meir method and Cox regression analysis about OS was performed. Statistical significance defined P

Description: Adult T-cell leukemia/lymphoma (ATLL), which is a peripheral T-cell lymphoma related to human T-lymphotropic virus type I (HTLV-1), is known as a poor prognostic disease and its median age of onset is late 60s. Allogeneic hematopoietic stem cell transplantation is considered a treatment modality to contribute prolonging the survival in some population of patients. Although cord blood transplantation (CBT) widely practiced for hematological malignancies, a Japanese registry data suggested that 1 yr and 2 yrs overall survival (OS) after CBT in ATLL patients was only about 30% and 20%, respectively (Kato K, et al. 2014 BBMT). On the other hand, promising results were reported in the patients who were received CBT during their disease was controlled (Fukushima T, et al. 2013 IJH). Since it would be considered that CBT with non-TBI regimens, especially using reduced intensity conditioning (RIC), have a potential of engraftment failure compared to TBI regimen, it is less common conditioning regimen for CBT. Here we report a safety and an efficacy of CBT with non-TBI-RIC regimen using fludarabine (Flu) and melphalan (Mel) in 34 ATLL patients. We analyzed days from the beginning of systemic chemotherapy to transplantation, engraftment of neutrophil (EN), overall survival (OS), incidence of GVHD, non-relapse mortality (NRM) and disease-mortality (DRM), respectively. OS was defined as survival days from transplantation. OS were analyzed with logrank test. Cumulative incidence of EN and GVHD was considered with early death and NRM was considered with DRM as a competing risk. Incidence of GVHD, EN, NRM, and DRM was analyzed with Gray's method. Statistical significance defined P

Description: Background Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus which is known as the cause of adult T-cell leukemia/lymphoma (ATLL). Some reports indicated that HTLV-1 carriers were immunologically compromised host. Although there were several reports about the survival impact of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ATLL, no large study concerning HSCT for the HTLV-1 carrier with the diseases other than ATLL has been reported. Japan is one of endemic countries of HTLV-1, and the prevalence of HTLV-1 infection was reported to be almost 1% of Japanese population. On behalf of the Japan Society for Hematopoietic Cell Transplantation (JSHCT) Complication Working Group, we here report the impact of HTLV-1 serological status on survival in those with HSCT for the diseases other than ATLL by using the Transplant Registry Unified Management Program (TRUMP) which is the nationwide survey database of the Japanese Data Center for Hematopoietic Cell Transplantation. Patients and Method There were 25840 patients (24400 adult and 1440 child), who had the information about the pretransplant serological status of HTLV-1, received their first HSCT between Jan 2007 and Dec 2015 in TRUMP database. We analyzed an overall survival (OS) and non-relapse mortality (NRM) after HSCT in relation to HTLV-1 serological status using Kaplan-Meir method, Gray's test. A Gray test for NRM calculated considering with disease related death as the competing risk. In multivariate analyses using Cox proportional hazard model for OS and Fine-Gray proportional hazards models for competing risk of NRM. And a p-value of less than 0.05 was considered as statistically significant. A statistical analysis was performed with 'EZR'. Results Median age of HTLV-1 carrier and non-carrier in adult patients were 57 years (17-76) and 53 years (16-88) and in pediatric patients were 11 years (0-15) and 8 years (0-15), respectively. The number of HTLV-1 carrier/non-carrier in adult patients in each disease were 80/7511 in AML, 133/6673 in malignant lymphoma, 34/3265 in plasma cell neoplasm, 30/2885 in ALL, 31/2178 in MDS, 8/446 in CML, 5/539 in aplastic anemia, and 11/570 in others, respectively. The number of HTLV-1 carrier/non-carrier in pediatric patients in each disease were 3/684 in ALL, 6/394 in AML, 2/170 in MDS, 2/76 in congenital metabolic disease, and 3/100 in others. The number of HTLV-1 carrier/non-carrier in adult patients who received allo-HSCT or auto-HSCT were 237/15777 and 95/8920, and in pediatric patients who received allo-HSCT was 16/1424, respectively. No HTLV-1 carrier child recipients who recieved auto-HSCT were identified in TRUMP database. There were no significant differences about stem cell sources, disease risk, and HCT-CI score before HSCT between HTLV-1 carriers and non-carriers. The OS rates at 3yr after allo-HSCT in adult and pediatric HTLV-1 carrier vs non-carrier were 40.7% vs. 50.2% (P=0.003) and 49.1% vs. 67.1% (P=0.318), and NRM rates at 1yr after allo-HSCT were 46.9% vs 23.6% (P=0.001) and 18.8% vs 11.7% (P=0.05), respectively. In multivariate analyses in terms of OS and NRM, HTLV-1 carrier was a significant prognostic factor in adult patients (HR 1.23, 95% CI 1.03-1.47, P‹0.001 for OS, and HR 1.27, 95% CI 1.05-1.61, P‹0.001 for NRM) and in pediatric patients (no statistical significance was seen on OS, and HR 2.58, 95% CI 1.17-5.70, P‹0.001 for NRM). The incidence of non-infectious NRM, such as pulmonary complications (IPS/DAH, ARDS), acute and chronic GVHD, MOF, and VOD/SOS was significantly higher in adult HTLV-1 carriers who received allo-HSCT when compared with that in HTLV-1 non-carriers. On the other hand, Infectious NRM was significantly higher incidence in child HTLV-1 carrier. With respect to disease related death, there were no differences between HTLV-1 carrier and non-carrier both in adult and pediatric patients. Among the adult patients who received auto-HSCT, there was no statistically significant difference in terms of OS, NRM, and disease related death between HTLV-1 carrier and non-carrier. Conclusion This is the first large study showing the survival impact of HTLV-1 serological status in patients with diseases other than ATLL who received HSCT. It demonstrated that HTLV-1 antibody-positivity was the poor prognostic factor in terms of OS and NRM after allo-HSCT in adult patients and NRM after allo-HSCT in pediatric patients. Disclosures Nakasone: Phizer: Honoraria; Novartis: Honoraria; Kyowa Hakko Kirin: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Suzuki:Kyowa-Hakko Kirin: Honoraria; Chugai Pharmaceutical: Honoraria; Mochida Pharmaceutical: Honoraria; Novartis: Honoraria; Shionogi: Honoraria; Takeda Pharmaceuticals: Honoraria; Meiji Seika Pharma: Honoraria; MSD: Research Funding; Ohtsuka: Honoraria; Sawai Pharmaceutical: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Gilead Sciences: Consultancy; MundiPharma: Consultancy; Jazz Pharmaceuticals: Consultancy.

Description: Abstract 4477 Cytomegalovirus (CMV) infection is one of significant factors contribute to morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplantation (SCT). Prevention and treatment of active CMV infection based on monitoring CMV-pp65 antigenemia test or CMV-DNA PCR assay have been done in this field. As the limitation of insurance, only CMV-pp65 antigenemia test can be clinically carried out in Japan. Adult T-cell leukemia/lymphoma (ATL), HTLV-1 related hematological malignancy, is known as poor prognostic disease and only allogeneic SCT had been prolonged survival outcomes. ATL cells are morphologically characterized as having complicated nuclei and their surface markers are usually shown as CD3+CD4+CD25+. Some reports suggested that ATL patients have tendency to be in immune compromised status. However, in our knowledge, there was no report about incidence of CMV-replication in ATL patients following allgeneic SCT so far. Here we analyze the incidence of CMV-pp65 antigenemia and related clinical issues in 85 allogeneic SCT recipients of single center located in HTLV-1 endemic area. There were consecutively 97 patients (106 times) undergone allogeneic SCT from November 2006 to May 2012 in Imamura Bun-in Hospital, Kagoshima, Japan. Totally, 12 patients (21 times), 9 times of deaths earlier than 30 days after SCT, 3 times of deaths earlier than engraftment, 9 times of second or more chances of SCTs, were excluded from this study. Rest of 85 (male: 52, female: 33) patients (85 times) were analyzed. We have first picked up patients' clinical data from medical charts including result of CMV-pp65 antigenemia tests and related data. Statistical analysis had carried out using SPSS 11.0J (SPSS Japan Inc., Japan). Cumulative incidences of CMV-pp65 antigenemia were analyzed by Kaplan-Meir method in total 85 patients. Statistical significance defined P

Description: Background: Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can provide sustained remission for adult T-cell leukemia/lymphoma (ATL), its prognosis is still unsatisfactory. Alternative donor sources are often utilized in allo-HSCT for ATL, but advantages and disadvantages of each donor source have not been fully elucidated. Graft-versus-host disease (GVHD) -free, relapse-free survival (GRFS) has been proposed as a novel and clinically meaningful endpoint of allo-HSCT. Whereas GVHD has been relatively accepted in ATL to induce substantial graft-versus-tumor (GVT) effects, severe GVHD is associated with non-relapse mortality and disturbs quality of patients' life. Analyses of GRFS may illustrate important aspects to optimize the balance between regulating GVHD and enhancing GVT effects in ATL patients. Patients and methods: We retrospectively analyzed the data of 1363 patients with ATL who received first allo-HSCT from 2006 through 2015 in Japan. Data were collected from the nationwide database maintained by the Japan Society of Hematopoietic Cell Transplantation. The probability of OS and GRFS was estimated according to the Kaplan-Meier method, and univariate comparisons among the groups were performed using the log-rank test. The Cox proportional hazard model was used for the multivariate analysis of OS and GRFS. Results: Median age was 57 years-old (range: 20-78) and median observation period of survivors was 3.1 years (range: 0.0-10.5). One-year OS and GRFS were 45% and 24%, respectively. OS of cord blood transplantation (CB) (37% at 1 year, n = 359) was worse than those of related bone marrow transplantation (R-BM) (48%, n = 121), related peripheral blood stem cell transplantation (R-PB) (50%, n = 264) and unrelated bone marrow transplantation (UR-BM) (47%, n = 619) (p 〈 0.001). However, in the cases of complete remission (CR) at allo-HSCT, OS of CB (n = 132) was 52% at 1 year and not inferior to those of R-BM (54%, n = 52), R-PB (57%, n = 88) and UR-BM (58%, n = 280) (p = 0.14). The cumulative incidence of relapse in CB was 47% at 1 year and higher than those of R-BM (40%), R-PB (43%) and UR-BM (35%) (p = 0.002). However, in CR cases, the cumulative incidences of relapse were lower in UR-BM (21% at 1 year) and CB (26%) than those in R-BM (31%) and R-PB (31%), though not significant (p = 0.21). Notably, there were no significant differences in GRFS of CB, R-BM, R-PB and UR-BM (21%, 25%, 21% and 26% at 1 year, p = 0.08, Figure 1A). It was attributed to low incidence of chronic GVHD which needed systemic therapy in CB (9% at 1 year, R-BM: 22%, R-PB: 28% and UR-BM: 18%, p 〈 0.001, Figure 1B) and low incidence of non-GVHD/relapse mortality in R-PB (9% at 1 year, CB: 20%, R-BM: 13% and UR-BM: 16%, p 〈 0.001, Figure 1C). In R-BM and UR-BM, there were no significant differences as for OS and GRFS between HLA-matched and HLA-mismatched transplantations. In R-PB, OS of HLA haploidentical transplantation (Haplo, n = 36) was 39% at 1 year and tended to be inferior to those of HLA 6/6-matched (53%, n = 183) and HLA 5/6-matched transplantation (49%, n = 45) (p = 0.11). There was no significant difference as for GRFS among these 3 groups (Haplo: 22%, 6/6-matched: 20%, 5/6-matched: 27% at 1 year, p = 0.69). Finally, multivariate analysis revealed that male sex, higher age (〉 50 years), worse PS (〉 1) and non-CR at allo-HSCT were associated with lower OS and GRFS. Importantly, donor sources and HLA mismatch were not associated with OS and GRFS. Conclusions: Our results imply that all donor sources are feasible for CR cases and can be selected depending on their clinical characteristics such as frailty and history of infection. While the main issue of CB is high non-GVHD/relapse mortality, it is warranted to suppress severe GVHD in R-PB. Thus, GRFS provides important clues to improve the outcome of allo-HSCT for ATL. Figure Disclosures Shindo: Novartis: Research Funding. Nakano:Novartis: Honoraria. Ichinohe:Astellas Pharma: Research Funding; Chugai Pharmaceutical Co.: Research Funding; CSL Behring: Research Funding; Eisai Co.: Research Funding; Kyowa Hakko Kirin Co.: Research Funding; Ono Pharmaceutical Co.: Research Funding; Pfizer: Research Funding; Nippon Shinyaku Co.: Research Funding; MSD: Research Funding; Otsuka Pharmaceutical Co.: Research Funding; Repertoire Genesis Inc.: Research Funding; Sumitomo Dainippon Pharma Co.: Research Funding; Taiho Pharmaceutical Co.: Research Funding; Takeda Pharmaceutical Co.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Alexion Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; JCR Pharmaceuticals: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Mundipharma: Honoraria; Novartis: Honoraria. Atsuta:CHUGAI PHARMACEUTICAL CO., LTD.: Honoraria; Kyowa Kirin Co., Ltd: Honoraria.

Description: Abstract 1260 Although the efficacy of cord blood transplantation (CBT) from unrelated donors as viable alternative for patients in need of hemtopoietic stem cell transplantation (HSCT) is supported by growing evidences, viral infections related to delayed immune reconstitution remains important problems for further improvement of clinical outcomes. To evaluate incidences and outcomes of late viral infections after CBT by comparison with those after unrelated bone marrow transplantation (uBMT), we retrospectively analyzed the records of 281 Japanese adult patients who underwent allogeneic unrelated HSCT for the first time at the Toranomon Hospital between January, 2002 and March, 2010, and who survived more than 100 days after HSCT without the lost-to-follow-up or retransplantation before day 100. Between 50 days and 5 years after HSCT, 116 patients had at least one late infectious episode with a cumulative incidence of 52.2%, at a median of 157 (50-1597) days after HSCT. The 5-year cumulative incidence of any late viral infections was greater in CBT versus uBMT recipients (60.7% vs. 42.2%, respectively; P=0.039, Figure 1). Thirty-three patients (28.4%) had 2 or more episodes caused by different viruses, and a total of 152 late infectious episodes were documented. The median onset of the episodes was similar between the both groups (median onset 226 days vs 222 days, P=0.89). The most common late viral infection is varicella-zoster virus (VZV) reactivation, accounting for 28.8% (disseminated 10, localized 34), followed by hemorrhagic cystitis associated with adeno- and/or BK viruria (28.2%), cytomegalovirus (CMV) diseases (16.4%; gastrointestinal diseases 23, retinitis 1, pneumonia 1), and respiratory tract infections caused by influenza virus, parainfluenza virus or respiratory syncytial virus (15.8%; upper 26, lower 8), and Epstein-barr virus lymphoproliferative diseases (4.6%). The remaining 10 infectious episodes were caused by relatively rare type of viruses including herpes simplex virus, JC virus, measles virus, mumps virus, norovirus and parvovirus, all of which occurred only in CBT recipients. Of all these viral infections, only VZV reactivation developed significantly more frequent in CBT than in uBMT recipients (P=34.0% vs 17.0%, P=0.023). There was no difference of dissemination rate between the both groups, and all the patients responded well to treatment with antiviral agents. The late viral infection was a primary cause of death in 3 episodes, all of which were pneumonia caused by CMV, influenza virus and parainfluenza virus. The 5-year incidence of infection-related mortality did not differ between CBT and uBMT recipients (0.7% vs 3.1%, P=0.46). Non-relapse mortality occurred in 11.8 % and 16.4 % patients in the CBT and uBMT groups (P=0.71). These findings suggested that cord blood might be as an acceptable and useful stem-cell source as bone marrow from unrelated donors in terms of risks of viral infection in the late posttransplant period. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2295 Poster Board II-272 Introduction: Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning has been widely applied to those who have advanced hematologic diseases and are not eligible for conventional conditioning. Although bone marrow or peripheral blood from related donors (rBM/PB) have been the first choice of graft when available, followed by unrelated adult donor or cord blood (CB), true superiority of rBM/PB over others can still be controversial. Elderly patients have difficulty finding related donors since their siblings are also in their elderly who have higher chance of having co-morbidity relative to younger patients. Rapid availability is the advantage of rBM/PB and CB share over unrelated adult donor, which enabled adapting similar policy of performing transplant possible, especially for elderly patients, given the significantly higher treatment-related mortality for elderly. Design and Methods: We retrospectively reviewed patients aged 55 and older who underwent reduced intensity allogeneic stem-cell transplantation using CB or rBM/PB at our institute from Jan. 2004 to Dec. 2008 consecutively. Patients who were considered for allogeneic transplant and had available 6/6 or 5/6 HLA-matched relatives performed rBM/PB transplants, whereas those who lacked rBM/PB donors underwent CB transplants. Patients who had prior history of transplantation, were in poor performance status (ECOG PS 2 and greater), had active bacterial or fungal infections at the time of conditioning, had diagnosed as multiple myeloma, adult T-cell leukemia, non-malignant diseases were excluded. Results: Two-hundred and thirty-two (171 CB and 60 rBM/PB) RI transplantation were performed from Jan. 2004 to Dec. 2008 at our institute, and 82 (61 CB and 21 rBM/PB) were eventually subjected to the analysis after excluding those who were ineligible according to the above mentioned criteria. The diagnoses included were AML (n=51), MDS (n=9), ALL (n=9) CML/MPD (n=4), and ML (n=9). Fifty-eight (71%) had high risk diseases, and 24 (29%) were in ECOG PS 2. Recipients of CB and rBM/PB were comparable in terms of diagnosis, disease risk (standard vs high), ECOG PS (0-1 vs 2), and year of transplant (2004-2005 vs 2006-2008). The median age for rBM/PB recipients was slightly younger (median 60, range 55-66) than that for CB (median 62, range 55-69, P 〈 .03). CB recipients received more serologically HLA-mismatched grafts (98% vs. 3%, P

Description: Abstract 1153 Poster Board I-175 Introduction Systemic corticosteroid has been used as initial treatment for gastrointestinal tract acute graft-versus-host disease (GI-aGVHD) following allogeneic hematopoietic stem cell transplantation (HSCT). However, the response remains far from satisfactory, and adverse events caused by prolonged immunosuppression are significant problem. Oral beclomethasone dipropionate (BDP) is a topically active corticosteroid with low bioavailability. Although several studies demonstrated that BDP as monotherapy or in combination with systemic corticosteroid is safe and effective for treatment of GI-aGVHD, there has been not much data available regarding this issue in unrelated cord transplantation (UCBT). Design and Methods This study was approved by the institutional review board and started since January 2006. BDP was administered as a single agent in patients who developed stage 1-2 GI-aGVHD following UCBT, were able to swallow the drug, and gave written informed consent. BDP was administered orally as one enteric-coated cellulose capsule and an aqueous suspension every 6h for a total daily dose of 8mg. Response was evaluated on days 3, 7, 14, 21, and 28 after the beginning of BDP treatment. Patients who had worsening GI symptoms at day 3, or who had no improvement at day 7 were classified as nonresponders, and systemic corticosteroid was started. Results Forty patients were included in this analysis from Jan 2006 through April 2009. Median age was 53.5 years (range 22-82). Twenty-eight (70%) had advanced disease (relapse or refractory disease), and 12 (30%) had history of prior transplantation. All but one patient received fludarabine-based preparative regimen. GVHD prophylaxis consisted of tacrolimus plus mycophenolate mofetil in 27, and tacrolimus alone in 13. Single cord blood units, matched at 4/6 in 35, 5/6 in 3, and 6/6 in 2, were infused. GI-aGVHD developed at a median of 32.5 days (range, 8-80 days) post-transplant. Twenty-five (62.5%) had stage 1 and 15 had stage 2 GI-aGVHD. Twenty (50%) had only GI involvement and the others had mild skin involvement. BDP was started at a median of 36 days (range, 8-86 days) post-transplant. Thirty-three (82.5%) responded to BDP treatment. Response occurred at a median of 4 days (range, 2-7 days) after BDP treatment. Response rate was suggestively higher in patients with stage 1 GI-aGVHD (88%) compared with those with stage 2 (73%), although not statistically significant (P=0.1). The median duration of BDP treatment was for 51 days (range, 7-343 days). Three patients progressed and 4 patients did not respond. Twenty-seven (67.5%) developed infectious episodes during BDP treatment; bacterial sepsis in 9, CMV reactivation in 10, CMV gastroenteritis in 2, Fungal pneumonia in 3, and others in 3 patients. Two patients developed symptomatic adrenal insufficiency during BDP treatment, and required systemic steroid hormone replacement. Transplant-related mortality was 15% at 100 days post-transplant. Three patients died due to sepsis associated with GVHD, 2 died from idiopathic pneumonia syndrome, and 1 died from invasive fungal infection. At median follow-up of 475 days (range, 132-1368 days), overall survival at 2 years was 35.7%. Conclusions: In this study, we evaluated the efficacy and safety of BDP as a single agent in a series of patients with stage 1-2 GI-aGVHD following UCBT. The response rate was 82.5%, which compares favorably with previously reported response rate using BDP as monotherapy or in combination with systemic corticosteroid after allogeneic HSCT. Furthermore, BDP treatment was not associated with the increased risk of severe opportunistic infections. We conclude that BDP as a single agent could become an ideal therapeutic approach for stage 1-2 GI-aGVHD following UCBT Disclosures No relevant conflicts of interest to declare.