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Background Although classic Hodgkin lymphoma (cHL) is highly curable with current treatment paradigms, there is still 20-30% of patients who will experience therapeutic failure (refractory or relapse). Tislelizumab, a monoclonal antibody targeting programmed cell death protein 1, is showing promise in the clinic with obvious response in relapsed/refractory cHL (RRcHL) patients on monotherapy. Further improvements in antitumor efficacy as salvage therapy may require exploration of a tislelizumab-based combination regimen. We conducted a phase II multi-center, open-label, non-randomized study (ChiCTR2000033441) to investigate the efficacy and safety of tislelizumab with gemcitabine plus oxaliplatin (GemOx) in patients with RRcHL. Methods Patients who had at least one previous therapy for cHL and were relapsed or refractory were eligible. Enrolled subjects received up to eight courses of gemcitabine (1g/m 2 on day 1) and oxaliplatin (100 mg/m 2 on day 1) combined with tislelizumab (200 mg on day 2) at 21-day intervals. Then, the cohort was divided into a tislelizumab maintenance group (every 2 months for 2 years) and an autologous hematopoietic stem cell transplantation group based on the choice of the investigators. The primary endpoint of this study was the best complete response rate (CRR), and secondary endpoints included overall response rate (ORR), progression-free survival (PFS) at 12 months, and safety profile. Results As of July 2021, a total of 22 patients (median age of 33 years old) were included. The predominant histologic subtype was nodular sclerosing cHL. Early-stage cHL was found in six patients and late-stage cHL in 16 (two of them with bulky disease). Correspondingly, 59.1%, 18.2%, and 22.7% of patients had 1, 2, or ≥ 3 prior therapies, respectively, and more than half of patients (59.1%) reported refractory to the latest treatment. The efficacy evaluable population comprised 20 patients. The disease control rate was 100% (95% confidence interval [95% CI]: 83-100%) and the ORR was 95% (95% CI: 75-100%). At the time of follow-up cutoff, the best CRR reached 90% (95% CI: 68-99%). Out of these, only one patient demonstrated stable disease and was switched to the other regimen. A total of 126 courses of immunochemotherapy were administered, with a median number of six courses per patient. The follow-up time averaged 191 days (range, 31-345 days), and the estimated PFS rate was 100% at 12 months. After 6-8 courses of tislelizumab plus GemOx, ten subjects received tislelizumab maintenance, and all remain in remission so far, with the longest follow-up of 345 days. Overall, the treatment was well tolerated with the majority of adverse events (AEs) being grade 1-2 in severity. Serious AEs were grade 3 anemia (n=1) and grade 3 thrombocytopenia (n=1). Conclusion Tislelizumab plus GemOx demonstrated promising antitumor activity with manageable toxicities as a salvage treatment for RRcHL. A longer follow-up is needed to demonstrate the durability of the remission after tislelizumab maintenance. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Peripheral T-cell lymphoma (PTCL) is a group of hematological malignancies originating from mature T/NK cells. Most of the subtypes are associated with aggressive clinical features and dismal outcomes. Routine first-line chemotherapy has low efficiency and a high recurrence rate, so there is an urgent need for new drugs. Monotherapy or combination therapy of epigenetic inhibitors have been shown to be effective in several hematologic malignancies. Here, we report the interim efficacy of an epigenetic priming regimen with azacytidine and chidamide prior to salvage chemotherapy for relapsed or refractory (R/R) PTCL. Methods The prospective phase II study (ChiCTR2000037232) enrolled pts were pathologically confirmed T/NK cell non-Hodgkin's lymphoma with at least one imaging measurable lesion. Pts needed to have received at least one systemic chemotherapy regimen including hematopoietic stem cell transplantation, radiotherapy, or a single epigenetic drug. Pts received AZA hypodermically at a dose of 100 mg on days 1 to 7, chidamide of 20 mg orally twice per week; the combined chemotherapy regimens included but were not limited to GemOx (gemcitabine, oxaliplatin); CPT (cyclophosphamide, prednisone, thalidomide) , etc. Treatment was performed for up to eight cycles of each 21 days. Pts who achieved partial response (PR) and better remission began maintenance therapy every two months with double epigenetic inhibitors for two years. The trial aimed to explore the efficacy and safety of AZA and chidamide combined chemotherapy in the treatment of R/R PTCL. The primary objective was investigator-assessed best overall response rate (ORR). Secondary objectives included duration of response (DOR), complete response rate (CRR), progression-free survival (PFS), overall survival (OS), and safety profiles. Results A total of 24 pts have been enrolled, baseline characteristics are shown in Table 1. Pathological subtypes included angioimmunoblastic T-cell lymphoma（AITL, n=15）, PTCL-not otherwise specified (PTCL-NOS, n=4), extranodal NK/T-cell lymphoma (ENKTCL, n=3) and mycosis fungoides(MF, n=2). The median age was 57 (range,38-72) years with male predominance. Ann Arbor Classification ≥ stage III in 20 pts. Twelve pts had B symptoms at the time of diagnosis, five pts had performance status ≥ 3 before treatment. The median number of previous systemic treatment regimens was two. Autologous hematopoietic stem cell transplantation in two pts, radiation in three pts and prior treatments containing chidamide in eight pts. At the time of data cutoff, the median number of treatments for all pts was four cycles (range,1-13). Among 16 pts evaluable for response, the best ORR was 68.8% (11/16) with five pts achieved CR, six achieved PR. In subgroup analysis, eleven AITL pts achieved an objective response. The best ORR was 72.7% (8/11) with four pts attained CR, four attained PR (Table 2). The median follow-up was 12.4 (range, 0.1-18.7) months. For all pts, the median PFS was 6.7 months (95% CI,5.8-7.6), the median OS was 8.4 months (95% CI,0.0-18.3) (Figure 1). And the median DOR was 10.2 months (95% CI,4.9-15.5). For AITL pts, the median PFS was 14.6 months (95% CI,3.6-25.6), and the median OS was not reached (Figure 2). The OS between AITL and other subtypes pts was statistically significant (1-year OS: 76.2% vs 13.9%; p=0.003, Figure 3). Almost all pts had experienced at least one adverse event (AE). The most common grade 3 or 4 AEs were anemia, leukopenia, neutropenia, thrombocytopenia, and infections. Conclusions Epigenetic priming regimen with azacitidine plus chidamide with salvage chemotherapy is effective and tolerable. The best ORR of all enrolled pts with AITL were 68.8% and 72.7%, respectively. Compare to other subtypes, patients with AITL subtype benefit more obviously from our regimen with durable remission. And further studies will focus on patients with AITL and follicular helper T-cell originated. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Background: Chidamide, as a novel subtype-selective histone deacetylase inhibitors (HDACi), can directly inhibit tumor cell cycle progression and induce tumor cell apoptosis, inhibit phenotypic transformation of tumor cells and pro-drug resistance/pro-metastasis activity of the microenvironment, induce differentiation of tumor stem cells, and reverse epithelial-mesenchymal transformation of tumor cells, thereby restoring the sensitivity of drug-resistant tumor cells to drugs and enhancing the effect of chemotherapy agents through loosening chromatin and exposing DNA. The efficacy and safety of chidamide-BEAC (carmustine, etoposide, cytarabine, and cyclophosphamide, Chi-BEAC) conditioning regimen combined with autologous stem cell transplantation (ASCT) were evaluated in a current phase II clinical trial for the treatment of high-risk and relapsed/refractory aggressive lymphoma. Methods: A total of 70 patients with high-risk diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), or mantle cell lymphoma (MCL) who had achieved complete remission (CR) or partial remission (PR) after first-line therapy or second-/third-line therapy were recruited from January 2018 to June 2021. Three of the patients were not evaluated after ASCT and two patients withdrew from the study; 65 patients were then evaluated for the effectiveness of Chi-BEAC treatment. Results: DLBCL and MCL are referred as B-cell non-Hodgkin lymphoma (B-NHL) and PTCL is referred as T and NK-cell non-Hodgkin lymphoma (T&NK-NHL) in the study. The median neutrophil engraftment time was 10 d (7-13 d) and median platelet engraftment time was 11 d (8-13 d). The CR rate at 3-6 months after transplantation was 75.4% in the 65 evaluable patients. The median progression free survival (PFS) and overall survival (OS) had not reached at the end of the follow-up period (median 18.1 month; range 1.8-42.0 months). The estimated PFS and OS at 24 months was 78.5% and 84.2%, respectively. Stratified analyses showed that in patients with B-NHL who previously received first-line treatment, the CR rate at 3-6 months after transplantation was 77.8%, and 2-year PFS was 74.8%. The survival rate might be better than previously reported for SWOG9704 (Stiff et al., 2013; PMID 24171516)-a 2-year PFS of 69%-and for DLCL04 (Chiappella et al., 2017; PMID 28668386)-a 2-year failure-free survival of 71%. In our patients with B-NHL who previously received second-/third-line treatments, the CR rate at 3-6 months after transplantation was 71.4%, and 2-year PFS was 77.1%. The survival rate might also be higher than previously reported for the CORAL trial (Gisselbrecht et al., 2010; PMID: 20660832), which showed a 2-year PFS of approximately 65%. In our patients with T&NK-NHL the CR rate at 3-6 months after transplantation was 73.3%, and 2-year PFS was 93.3%, The survival rate might be higher than previously reported for the NLG-T-01 trial (Francesco d'Amore et al., 2012; PMID: 22851556), which showed a 2-year PFS of approximately 55%. PFS stratification analysis showed that previous treatment outcomes affected the PFS: patients who had achieved CR before transplantation demonstrated better PFS than patients who had achieved PR (P = 0.199), while there was no significant difference between patients with different pathological subtypes (B or T&NK-NHL) or different risk groups. Most non-hematological adverse events (AEs) were of grade 1/2. Grade 4 AE only occurred in one patient, i.e., γ-glutamyl transpeptidase (GGT) elevation. Grade 3 AEs that occurred in ≥ 5% of the patients included febrile agranulocytosis (37.7%), hypokalemia (24.7%), hyponatremia (23.4%), GGT elevation (9.1%), and diarrhea (5.2%), which were well tolerated. Conclusions: This study showed that inclusion of the HDACi chidamide in conditioning regimen for ASCT greatly increased the PFS and OS, especially in patients with T&NK-NHL, and revealed an acceptable safety profile for refractory and relapsed lymphoma patients. Therefore, chidamide-containing conditioning regimen may be a great choice for patients with refractory and relapsed lymphoma, and awaits further confirmation by additional large-scale multi-center investigations. Disclosures No relevant conflicts of interest to declare.

Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive non-Hodgkin's lymphomas (NHL) with high heterogeneity. The first-line treatment commonly used for firstly-diagnosed PTCL is the CHOP-like regimen. However, in addition to ALK+ALCL, these regimens present poor long-term survival rate in other subtypes, mostly less than 30-40%. Even with the consolidation of autologous hematopoietic stem cell transplantation, studies have reported that the 5-year overall survival rate is barely about 50%. Therefore, for PTCL patients who have achieved remission and undergone autologous hematopoietic stem cell transplantation, there is an urgent need to explore a maintenance treatment strategy. Chidamide is an oral type of selective HDAC inhibitor with subtype specificity for HDAC 1, 2, 3, and 10. It has a regulatory effect on abnormal epigenetic functions of tumors and a novel induction and activation of cellular immune function. In China, it has been approved for relapsed or refractory PTCL at a dose of 30 mg/time, twice a week. The study of chidamide has proved its satisfactory efficacy and safety characteristics for PTCL again. This study preliminarily evaluates the near term effects of chidamide combined with chemotherapy in the first-line treatment and maintenance value of PTCL through retrospective analysis. Methods: We collect adult peripheral T-cell lymphomas inducing by CHOP-like regimen with chidamide or not. The complete response rate (CR), objective response rate (ORR), progression-free survival time (PFS) and overall survival time (OS) of patients in the combined chidamide group and non-combined group were separately analyzed and evaluated. Meanwhile, the OS in the chidamide-maintenance and non-chidamide maintenance of the PTCLs were also brought to study. Results: A total of 82 patients recruited, with a median age of 60 years (14-79 years), including 45 peripheral T-cell lymphoma (PTCL-NOS), 23 angioimmunoblastic lymphoma (AITL), 14 anaplastic large cell lymphoma (ALCL), and the follow-up time cutoff was April 30, 2021. Among 82 patients, 39 patients were treated with chidamide+CHOP-like as the first-line treatment, and 43 patients were treated with CHOP-like as the first-line treatment. The CR rate of the first-line combined chidamide group was 62%, and the ORR was 87%. The CR rate of the first-line non-combined chidamide group was 42% and the ORR was 74%. There was no significant difference in CR rate and ORR between the two groups, but the CR rate has potential clinical benefits. The median PFS of the combined chidamide group was longer than that of the non-combined group by 8 months (18.9m VS 10.9m), but there was no significant statistical difference (p=0.255). Among 82 patients, regardless of first-line treatment or salvage treatment, 42 patients in the maintenance treatment group of chidamide did not reach the median OS, and the median OS of 40 patients in the non-maintenance group was 18.9 months. The difference between the groups was statistically significant (p Conclusion: It preliminarily suggested that chidamide maintenance therapy for PTCL provided an ideal survival benefit, especially In patients with PTCL-NOS subtypes. First-line treatment combined with chidamide and chidamide maintenance therapy may improve the poor survival prognosis. Disclosures No relevant conflicts of interest to declare.

Backgroud: Waldenström macroglobulinemia (WM) is an uncommon indolent B cell non-Hodgkin lymphoma, which has heterogeneous clinical presentations and indications for treatment. Mostly the choice of first-line therapy is based on the individual patient's characteristic and indications for treatment. In China, previous studies on WM are mostly from single-center with small sample size, limiting the information available on treatment and outcome patterns. To address this knowledge gap, we present data from an analysis based on a nationwide multicenter registry with 17-years follow-up. Our study focuses on the clinical presentation, first-line therapies, as well as outcome and prognosis of WM in China. Methods: Patients diagnosed with WM between January 2003 and December 2019 at 35 academic hospitals in China, which have been entered in the database of the China Waldenström macroglobulinemia Registration (CWMG), were included in this retrospective study. Data including baseline clinical features, symptoms requiring treatment, treatment and survival were collected. The overall survival (OS) was defined as the duration from the diagnosis of WM to the date of death or last follow-up. Results: Overall 1141 patients were enrolled, 829 patients were male (72.7%), with a male-to-female ratio of 2.7:1. The median age at diagnosis was 64 years (range, 29-89 years), which 472 patients (41.4%) were older than 65 years, and 126 patients (11.0%) were older than 75 years. The patients' family histories included 6 WM and 4 other lymphoproliferative disorders. Symptoms leading to treatment initiation including anemia in 828 patients (72.6%), organomegaly in 441 patients (38.7%), thrombocytopenia in 302 (26.5%), neutropenia in 246 (21.6%), constitutional symptoms in 203 (17.8%), Bing-Neel syndrome in 13 (1.1%), IgM-related symptoms in including secondary amyloidosis in 32 (2.8%), secondary autoimmune hemolysis in 25 (2.2%), peripheral neuropathy in 23 (2.0%), secondary cold agglutinin disease in 21 (1.8%), secondary cryoglobulinemia in 11 (1.0%). At the time of diagnosis, 1125 patients had full information for IPSS-WM risk stratification. Among them, 194 patients (17.2%) were classified as low risk, 436 patients (38.8%) were intermediate risk, and 495 patients (44.0%) were high risk. Overall, 734 patients had documented treatment information. 75 patients (10.2%) received monotherapy, 264 (36.0%) received chemoimmunotherapy, and 395 (53.8%) receive other combination regimens (Figure 1). The most frequently used monotherapy was chlorambucil (3.1%), followed by ibrutinib (2.9%) and rituximab (2.5%). Rituximab, cyclophosphamide and dexamethasone or prednisone (DRC or RCP) were the most frequently used chemoimmunotherapy (10.8%). Followed by rituximab plus cyclophosphasmide, vincristine/vincristine and prednisone/prednisolone (R-COP) (6.8%), R-COP plus doxorubicin/epirubicin (R-CHOP) (6.1%), rituximab plus fludarabine, cyclophosphamide (R-FC) (4.5%), rituximab plus bortezomib based regimen (3.5%). Other combination regimens including bortezomib based regimen (18.6%), FC (10.6%), CHOP (9.3%), immunomodulatory drug based regimen (5.7%), chlorambucil plus prednisone (4.4%). After a median of 23 months (range 1-201 months) follow-up, 123 patients died. The estimated 5-year OS was 74.9%. Median OS were similar among patients who received monotherapy, chemoimmunotherapy or other combination regimens. To evaluate the prognostic factors of OS using multivariate Cox regression model, age > 65 years old (P=0.011, HR 0.622, 95% CI 0.431-0.898), platelet < 100×109/L (P=0.006, HR 0.570, 95% CI 0.381-0.853), serum albumin Conclusion: Frontline treatment choices of WM are wide heterogeneity due to various clinical presentations and the rarity of the disease. Old age, low platelet, low albumin, high β-2 microglobulin, high LDH and secondary amyloidosis indicate worse prognosis in WM. These findings may provide guidance for management of WM and better prognostic stratification of risk-adapted treatment strategies. Figure 1 Disclosures No relevant conflicts of interest to declare.

Orelabrutinib (ICP-022) is a novel and highly selective irreversible BTK inhibitor. We previously reported that orelabrutinib had high bioavailability with ~100% BTK occupancy at 24 hours at 150 mg daily dosing regimen and demonstrated excellent safety and efficacy profiles at median follow-up of 8.7 months in a Phase I/II trial of refractory/relapsed (r/r) CLL/SLL (Chronic Lymphocytic Leukemia/Small Cell Leukemia). Here we present an updated analysis of efficacy and safety results from the clinical study of Orelabrutinib in Chinese patients with r/r CLL/SLL following extended treatment. This is an open-label, multicenter, phase II study with objectives to evaluate its safety and efficacy following an oral daily administration. The primary endpoint was objective response rate (ORR). The duration of response (DOR), progression-free survival (PFS) and safety were chosen as secondary endpoints. Response was assessed per 2008 IWCLL criteria with modification for partial remission (PR) with lymphocytosis (PR-L) (Hallek 2012) or the Lugano Classification (Cheson, 2014) for CLL and SLL, respectively. Results: A total of 80 patients with r/r CLL (n=70)/SLL (n=10) were enrolled. Eligible patients had relapsed after or were refractory to ≥1 prior treatment with median age of 60.0 (range, 36.0-78.0 years). There are 70% of patients for Rai stage 3-4 disease, 22.5% for 17p13.1 deletion [del(17p)] and/or TP53 mutation, 41.3% for unmutated immunoglobulin heavy chain variable region (IGHV) and 23.8% for 11q22.3 deletion [del(11q)]. The median follow-up time was 14.3 months (range, 0.2-21.6 months), and the last patient completed a minimum of 12 cycles of orelabrutinib treatment. Efficacy: The efficacy results presented here were evaluated by IRC (Independent review committee). Following a minimum of 12 cycles treatment, the ORR (PR-L or above) was 91.3% (95% confidence interval [CI]: 82.80 ~ 96.41%) with 10.0% of patients having complete response (CR), 63.8% PR and 17.5% PR-L. Median time for achieving first response was 1.87 months (range, 1.84 - 1.94 months). The median DOR and PFS were not reached. The estimated 12-month DOR was 77.1% (95% CI: 62.50-86.60%), PFS 81.1% (95% CI: 70.53 - 88.13%) and OS 86.3% (95% CI: 76.55 - 92.14%). Patients with Del(17p) and/or TP53 mutation achieved 100% ORR. The ORR is 94.7% for Del(11q)) and 93.9% for unmutated IGHV. Comparing to the first analysis results of which the median follow-up was 8.7 months, the CR rate had increased from 3.8% to 10.0%, and 8 patients with PR-L had converted to a deeper response. So, orelabrutinib showed a significant higher CR rate comparing to other BTK inhibitors at a similar treatment period and we anticipate a further increase of CR rate with longer duration of treatment. Safety: Most adverse events (AEs) were mild to moderate, similar to the first reported safety profiles at median follow-up of 8.7 months. Extended follow-up analysis did not reveal new safety nor toxicity concerns. The most frequent adverse events (AEs) of any cause/any grade were well characterized as hematological toxicities: thrombocytopenia, neutropenia, and anemia; upper respiratory tract infection, pneumonia and hypokalemia. No case of atrial fibrillation nor secondary malignancy was reported, no patient was observed for ≥3 hypertension and only one patient had ≥3 grade diarrhea. Major hemorrhage was reported in 2 patients, one with intracranial hemorrhage (65-year-old male patient with more than 10 years hypertension) and the other with vitreous hemorrhage which were resulted from posterior vitreous detachment that was assessed as unlikely related to the treatment of orelabrutinib. Once again, it has been further confirmed that orelabrutinib has excellent safety profiles following extended treatment. Conclusion: This updated and extended study further confirms that orelabrutinib is efficacious in treating r/r CLL patients with a higher CR rate, durable response and improved safety profiles. As a highly selective BTK inhibitor with favorable pharmacokinetic and pharmacodynamic properties, orelabrutinib provides a favorable therapeutic choice for patients with r/r CLL/SLL and a potential best candidate for combination therapy. Disclosures Zhu: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhang:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Xu:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment.

Background: In spite of years of effort, Mantle Cell Lymphoma (MCL) remains a clinical challenge. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitor has been validated with the approvals by FDA for the treatment of multiple subtypes of NHL including refractory and relapse (r/r) MCL. However, some serious adverse events (AEs) due to poor target selectivity (inhibition of EGFR, TEC, BMX and others), such as diarrhea, sever bleeding and atrial fibrillation, remain as challenges in clinic. Orelabrutinib is a novel, potent irreversible BTK inhibitor with high selectivity for BTK. Results of early clinical study showed that it has excellent safety/tolerability profiles and favorable pharmacokinetic/pharmacodynamic properties. Sustained ~100% BTK occupancy at 24 hours was achieved with once daily dosing regimen of 50 mg and above. In this presentation, we will report an updated analysis of orelabrutinib in Chinese patients with r/r MCL with minimum of 12 cycles of treatment. Aims: To evaluate the sustained efficacy and long-term safety of orelabrutinib in Chinese patients with r/r MCL. Methods: This is an open-label, multicenter, two stages, phase II study. The primary endpoint was objective response rate (ORR) assessed per Lugano criteria (2014). Safety and other efficacy (DOR, PFS, OS) evaluations were chosen as secondary endpoints. Results: A Total 106 patients, were enrolled in this study with median follow up time of 15.0 months. 79.2% of the patients were male and median age of 62.0 years old. Most patients were at advanced stage (73.6% were at stage IV and 20.8% were at stage III). According to per protocol analysis, 87 (87.9%) patients achieved ORR and 93.9% patients achieved disease control. The median duration of response (DOR) was not reached, the DOR rate at 12 months was 73.7%, as expected the median PFS and OS were not reached, the PFS and OS rates at 12-month were 70.8% and 88.7% respectively. Comparing to the results of previous analysis, the CR rate, by conventional CT method, increased to 27.4% and it was expected a higher rate of in depth response may occur with prolonged treatment. Further analysis showed orelabrutinib was efficacious in all subgroups (age, gender, status, stage, prior therapy, etc.). Orelabrutinib demonstrated excellent safety profile in r/r MCL patients. The frequently reported treatment related adverse events (TRAE) were primarily hematological toxicities including thrombocytopenia, neutropenia, leukopenia, and hypertension. The frequently reported grade 3 or higher AEs of any cause was thrombocytopenia . No treatment related ≥grade 3 GI and cardio toxicity, nor severe bleeding, were observed. Of the 106 patients, 32 experienced serious AEs; and 17 of them, mainly hematological toxicities and / or infections were treatment-related. Comparing to the safety data of median follow up of 10.5 months, there was only a mild increase of adverse events rate after extended treatments; the safety profiles were essentially the same. These results suggested that safety events primarily occurred during early treatment and it appeared less eventful with orelabrutinib continue treatment. Conclusion: Orelabrutinib showed continuous efficacious in treating patients with r/r MCL. In addition, orelabrutinib is safe and well tolerated with no treatment related grade 3 or higher diarrhea, atrial fibrillation/flutter or severe bleeding in this study. Results of prolong treatment expected to produce a higher rate of in depth response without altering its safety profiles support orelabrutinib being a better selection for BTKi therapy. The improved safety as a resulting of high target selectivity, and the convenience of daily dosing regimen provides orelabrutinib as preferred therapeutic choice for B cell malignancy. Disclosures Zhang: Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment. Xu:Beijing InnoCare Pharma Tech Co., Ltd: Current Employment.

J Li, L Bao, ZJ Xia and KY Ding contributed equally to this study. Background: Based on the promising results shown in the phase 3 trial (TOURMALINE-MM1, NCT01564537) and the China Continuation Study of MM1, the oral proteasome inhibitor (PI) ixazomib (ixa) was approved in China in April of 2018, in combination with lenalidomide (len) and dexamethasone (dex) (IRd), for patients (pts) with relapsed/refractory multiple myeloma (RRMM). Data on the efficacy and safety of ixa-based therapy in Chinese pts with MM in real-life practice is rather limited. A large national, multi-center, real-world study involving 14 centers from different areas of China was performed to investigate the current status of ixa usage in China and to evaluate the efficacy and safety in routine clinical practice. A total of 246 ixa-treated MM pts was enrolled, with 163 (66.3%) RRMM, 60 (24.4%) newly diagnosed MM and 23 (9.4%) pts received ixa as maintenance. Herein, we reported the data of RRMM in this study. Methods: Medical records, including demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs) and survival, of ixa-treated (at least one cycle completed with response evaluation result) RRMM pts were analyzed. Results: A total of 149 evaluable pts (out of 163 RRMM pts) treated from April 2018, to July 2019 were included in analysis. Baseline features and prior treatment are summarized in Table 1. Patients were categorized into MM1 trial-eligible/-ineligible groups according to the inclusion and exclusion criteria of MM1 study. Median age was 62 years (range 33 - 87) with 52 (34.9%) ≥65 years. Most pts (75.2%) had ISS stage II-III disease. High-risk cytogenetic abnormalities (including del 17p, t (4;14), and/or t (14;16)) were detected in 19 patients (21.1%, among 90 patients with FISH results). Fifty-two (34.9%) pts had a ECOG PS ≥2. Overall, ixa-based regimens were used as the 2nd/3rd/4th/≥5th-line therapy in 29.7%, 33.1%, 16.2% and 17.4% of the pts, respectively. Prior treatment included bortezomib (91.9%), len (52.0%) and thalidomide (58.8%). More than half pts (54.7%) were refractory to previous bortezomib treatment, and 32.2% pts were len-refractory. MM-1 trial-ineligible pts had more advanced ISS stage, higher ECOG PS, more severe anemia, more lines of prior therapy and more refractory diseases. Treatment, outcome and survival were listed in Table 2. Ixa-based regimens included IRd in 70 (47.0%) patients, ixa-dex (Id) in 31 (20.8%) patients and Id plus chemotherapeutics/other agents (44, 29.5%; including cyclophosphamide in 14 pts, thalidomide in 12 pts, adriamycin in 6 pts, melphalan in 5 pts and daratumumab in 3 pts) in 20 (33.3%). (Table 2). One patient received stem cell transplantation (SCT) during follow-up. The best confirmed ORR (≥PR) for all 149 patients was 53.7% (80/149), including 28.2% of patients with ≥VGPR and 7.4% with a CR, with a median time to response of 41.5 days. Surprisingly, ixa-based regimens demonstrated efficacy in pts with PI/len refractory diseases, with an ORR and ≥VGPR rate of 44.4% and 19.9% for PI-refractory pts, and an ORR and ≥VGPR rate of 30.6% and 12.2% for len-refractory pts. Pts eligible for MM1 study shown comparable ORR (76.7%) with that reported in MM1 (ORR 78%). No significant difference in response between different ixa-based regimens was observed. The median PFS of the whole cohort, pts with standard/high cytogenetic risks, pts refractory to bortezomib/len and pts eligible/ineligible for MM1 trial was 8.2, 8.2, 6.8, 6.7, 5.9months, not reached and 6.6months respectively. The median overall survival (OS) of the whole cohort and every subgroup was not reached. Adverse events (AEs) of grade 3/4, reported in 40 (27.2%) patients, included 10.1% thrombocytopenia, 5.4% anemia, 3.4% diarrhea and 6.0% pneumonia. Only 3 (2.01%) pts had a grade 3/4 peripheral neuropathy during follow-up. Discussion and conclusion: Our results show that ixa-based therapy demonstrated good efficacy with limited toxicity for pts with RRMM in real-life clinical practice. Moreover, in pts with PIs- or len- refractory diseases, ixa-based therapy still showed acceptable effectiveness (ORR: 44.4% and 30.6%; mPFS: 6.7 months and 5.9 months). Although 70.5% pts in our real-life cohort were ineligible for MM1 trial, the efficacy and safety profile is similar to that reported in MM1 China Continuation Study. Ixa-based therapy is a reasonable choice for Chinese RRMM pts. Disclosures No relevant conflicts of interest to declare.

Background: Autologous hematopoietic stem cell transplantation (AHSCT) is an important therapy for non-Hodgkin's lymphoma (NHL). This study evaluated the safety and efficacy of YF-H-2015005, a new CXCR4 antagonist, when used to mobilize hematopoietic stem cells in patients with NHL eligible for treatment with AHSCT. Methods: This phase III, multicenter, randomized (1:1), double-blind, placebo-controlled study enrolled patients (age range, 18 to 65 years) with NHL, and who were in their first or second complete or partial remission. The patients received granulocyte colony-stimulating factor (G-CSF, 10 mg/kg/day) each morning for up to 8 days. Treatment with YF-H-2015005 (0.24 mg/kg/day) or placebo was initialed during the evening of the fourth day of G-CSF administration, and then continued for up to 4 days. Starting on day 5, apheresis was performed for 9 to 10 hours after each dose of YF-H-2015005 or until ≥ 5 × 106 CD34+ cells/kg had been collected. The primary endpoint was the percentage of patients who collected ≥ 5 × 106 CD34+ cells/kg during the course of 4 or fewer apheresis days. The secondary endpoints were the percentage of patients who collected ≥ 2 × 106 CD34+ cells/kg during the course of 4 or fewer apheresis days, the number of apheresis days required to reach ≥ 2 × 106 CD34+ cells/kg, the number of apheresis days required to reach ≥ 5 × 106 CD34+ cells/kg, and patient safety. Results: A total of 101 patients with NHL were randomly assigned to the YF-H-2015005 group (n = 51or placebo group (n = 50), respectively. The percentage of patients who met the primary endpoint was 57% (29/51) in the YF-H-2015005 group and 12% (6/50) in the placebo group (P < 0.001). A larger proportion of patients in the YF-H-2015005 group (86%) achieved the secondary endpoint of collecting ≥ 2 × 106 CD34+ cells/kg in 4 or fewer apheresis days when compared with the placebo group (38%, P < 0.001). Patients in the YF-H-2015005 group required shorter time periods to collect ≥ 2 × 106 CD34+ cells/kg (1 days vs. 4 days) and ≥ 5 × 106 CD34+ cells/kg (3 days vs. not reached). Treatment-related adverse event were observed in 37 patients (20 in the YF-H-2015005 group and 17 in the placebo group). The most common adverse events in the YF-H-2015005 group were diarrhea (14%), hyperhidrosis(6%), elevated alkaline phosphatase (6%). No serious treatment-related adverse event occurred. Conclusions: The combination of YF-H-2015005 and G-CSF was a tolerable regimen for use in rapidly mobilizing and collecting CD34+ cells for transplantation in patients with NHL. Disclosures Zhu: Mundipharma: Research Funding.

Bruton's Tyrosine Kinase (BTK) plays a critical role in B-cell receptor (BCR) signaling, which mediates B-cell proliferation, migration, and adhesion. As a therapeutic target, its clinical significance has been well established in multiple subtypes of non-Hodgkin's lymphoma (NHL). Orelabrutinib (ICP-022) is a novel, potent irreversible BTK inhibitor with much improved target selectivity in comparison to Ibrutinib and Acalabrunitib, which leads to improved safety profiles. With a proprietary formulation, Orelabrutinib achieves high bioavailability comparing to other BTK inhibitors. Results of Phase I study (another presentation on Orelabrutinib) demonstrated favorable pharmacokinetic and pharmacodynamic properties for Orelabrutinib. Sustained BTK occupancy at 24 hr was achieved with daily dosing regimen. In this presentation, we will report results from clinical study of Orelabrutinib in Chinese patients with r/r CLL/SLL. This is an open-label, multicenter, Phase II study with objectives to evaluate its safety, tolerability and efficacy following oral daily administration. The primary endpoint was objective response rate (ORR). The duration of response (DOR), progression-free survival (PFS) and safety were chosen as secondary endpoints. Response was assessed per 2008 IWCLL criteria with modification for PR with lymphocytosis (PR-L) (Cheson, Hallek 2012). This study is composed of two stages. The stage I was to assess the safety and tolerability of Orelabrutinib at 150 mg, QD in pts with r/r CLL/SLL, while the stage II was to evaluate its therapeutic benefits (N=80, 150 mg, QD). Total of 80 patients with r/r CLL (n=70)/SLL (n=10) were enrolled. As of 31 May 2019, 40 pts had completed six cycles of treatment (28 days/cycle). The Median follow-up was 6.3 months (range, 0.4-13.7 months). Safety: The most frequent (≥15%) any grade adverse events (AEs) of any cause were well characterized hematological toxicities: thrombocytopenia, neutropenia, and anemia; and respiratory system infections as well as purpura. No case of atrial fibrillation or secondary malignancy was reported. The most frequently (≥10%) reported ≥ Grade 3 AEs of any cause were neutropenia, thrombocytopenia, lung infection. Twenty-five pts experienced at least one serious AE. Of those, 13 were considered related to Orelabrutinib treatment, including platelet count decrease (3 pts), pneumonitis, pyrexia (2 pts each) and herpes zoster etc. (1 pt each). Efficacy: Of the 80 enrolled pts, seventy-eight pts were evaluable for response (by 31 of May 2019), the ORR was 88.5% (69/78). Among them, one patient was reported as CR, 39 pts were PR and 29 pts were PR-L. Stable disease was seen in 6/78 (7.7%). Total disease control rate is 96.2%. The median DOR was not reached, 6 months DOR rate was 89.8%. Subgroup analysis (age, disease stage, previous treatment, 17p deletion, 11q deletion, IGHV mutation) did not reveal significant differences. Conclusion: Orelabrutinib is safe and well tolerated. No significant adverse events like atrial fibrillation/flutter or secondary malignancies were reported. Orelabrutinib is efficacious to treat pts with r/r CLL/SLL. The improved safety, resulting from high target selectivity, and daily dosing regimen enable Orelabrutinib to be a valuable therapeutic choice both as monotherapy and likely in combination with other agents to treat B-cell malignancies. Disclosures Xu: Beijing InnoCare Pharma Tech Co., Ltd: Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Employment. Zhang:Beijing InnoCare Pharma Tech Co., Ltd: Employment. Zhu:Beijing InnoCare Pharma Tech Co., Ltd: Employment.

Mantle cell lymphoma (MCL), a subtype of aggressive B-cell non-Hodgkin lymphoma (NHL), remains challenging with unsatisfied outcomes from standard therapy. The clinical significance of Bruton's Tyrosine Kinase (BTK) inhibitors has been validated in multiple subtypes of NHL. Ibrutinib, the first BTK inhibitor, has been approved by FDA for the treatment of refractory and relapse (r/r) MCL. In spite of encouraging efficacy, clinically often referred adverse events such as diarrhea, bleeding and atrial fibrillation, respectively following ibrutinib treatment. It has been hypothesized that poor target selectivity (inhibitive effect on EGFR, TEC, BMX and others) may partially explain the occurrence of these adverse events. As such, there are focused efforts to develop new BTK inhibitor with high target selectivity aiming to improve the safety. Orelabrutinib (ICP-022) is a novel, potent irreversible BTK inhibitor with high selectivity for BTK vs other kinases including TEC- and EGFR-family members. Results from Phase I study demonstrated excellent safety/tolerability profiles as well as favorable pharmacokinetic and pharmacodynamic properties. Sustained BTK occupancy at 24 hr was achieved with once daily dosing regimen. In this presentation, we describe the clinical results of orelabrutinib in Chinese patients with r/r MCL. This is an open-label, multicenter, two stages, phase II study. The primary endpoint was objective response rate (ORR) and the duration of response (DOR) and safety were chosen as secondary endpoints. The stage I was designed for regimen selection (RP2D, N=20 for 100 mg, bid and 150 mg, qd each, respectively), while the stage II for efficacy at RP2D (N=86 150 mg, qd). Response was assessed per Lugano criteria (2014). Total of 106 pts with r/r MCL were enrolled. As of 31 May 2019, sixty-two pts had completed six cycles of treatment (28 days/cycle). The median duration of treatment was 197.5 days. Safety: A total of 106 pts were enrolled and treated at 22 centers in China. The most frequent (>15%) adverse events (AEs) of any cause were mostly hematological toxicities including thrombocytopenia and neutropenia; and respiratory system infections as well as rash. The frequently reported (>10%) grade 3 or higher AEs of any cause were thrombocytopenia (12.3%). No grade 2 or higher hemorrhage was reported. No treatment related grade 3 GI or cardio toxicity was observed. Of the 106 patients, twenty-five experienced serious AEs and 13 of them were treatment-related (primarily occurred as hematologic toxicities and / or infections). Efficacy: Forty patients, divided into two cohorts (n=20 each), were enrolled in stage I. The regimen, 150 mg, qd, was selected as RP2D based on a better ORR and the convenience of once daily dosing. All patients who were enrolled in the stage I continued their treatment. At the time of reporting (the 31 May 2019), 97 patients had response assessments. The response rate was assessed by traditional CT image technology. The ORR was 82.5% (80/97) for combining both regimens with the complete response rate (CR) 24.7% (24/97), partial responses 57.7% (56/97). Stable disease was seen in 9.3% (9/97). The total disease control rate is 91.8%. Six (6.2%) patients progressed by the first response assessment. The median duration of response rate (DOR) has not been reached. Conclusion: Orelabrutinib is safe and well tolerated with no reported treatment related grade 3 or higher GI toxicity, atrial fibrillation/flutter and severe bleeding in this study. Orelabrutinib is efficacious to treat patients with r/r MCL. The improved safety, resulting from high target selectivity, and the convenience of daily dosing regimen provides orelabrutinib as the potential of preferred therapeutic choice for B cell malignancy. Disclosures Lu: Beijing InnoCare Pharma Tech. Co., Ltd.: Employment. Zhang:Beijing InnoCare Pharma Tech Co., Ltd: Employment. Zhao:Beijing InnoCare Pharma Tech Co., Ltd: Employment. Xu:Beijing InnoCare Pharma Tech Co., Ltd: Employment.

Jing Li, Li Bao and Zhong-jun Xia contributed equally to this study. Background: Ixazomib (ixa) is the first oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM) in > 60 countries. In a recently reported long-term result of a phase 1/2 study (NCT01217957), the all-oral triplet regimen of ixazomib plus Rd (IRd) demonstrated favorable efficacy with acceptable toxicity in patients with newly diagnosed MM (NDMM). Meanwhile, a large phase 3 trial (TOURMALINE-MM2, NCT01850524) evaluating IRd in stem-cell transplantation (SCT) ineligible NDMM patients is ongoing. However, outcomes and toxicity profiles of novel-agent-based MM therapies in real world practice often differ from data reported in clinical trials and data of the efficacy of ixa-based treatment in NDMM in routine practice is currently missing. Aims and Methods: To assess the efficacy and safety profile of ixa-based frontline therapy in NDMM patients in routine practice, we performed a large national, multi-center, observational study enrolling ixa-treated (at least one cycle completed) NDMM patients from 14 China centers. Clinical records on demographics, disease characteristics, treatment regimen and duration, response rate, adverse events (AEs), and treatment discontinuations and survival were collected and analyzed. Results: A total of 60 NDMM patients treated with ixa-based regimens were included. Ixa-based regimens included IRd in 23 (38.3%) patients, the ixa and dexamethaxone (Id) in 17 (28.3%) patients and Id plus chemotherapeutics/other agents (Adriamycin in 12 patients, cyclophosphamide in 5 patients, and thalidomide in 3 patients) in 20 (33.3%). None of the patients included received SCT during follow-up. Median age was 69 years (range 35 - 85) with 33 (55.0%) ≥65 years. At initial diagnosis, ISS stage I/II/III disease were presented in 21.7%/28.3%/50.0% patients at initial diagnosis; high-risk cytogenetic abnormalities (including del 17p, t(4;14), and/or t(14;16) detected by fluorescence in situ hybridization) were detected in 9 patients (19.6%, among 46 patients with FISH results). Twenty-six (43.4%) patients had a ECOG PS ≥2 and 5 patients (8.3%) had extramedullary disease. Eighteen patients were not eligible for ixa phase 1/2 study (NCT01217957) according to its inclusion and exclusion criteria, and even more patients (36, 60%) were not eligible for TOURMALINE-MM2 study. (Table1). The best confirmed ORR (partial response or better) for all 60 patients was 93.3% (56/60), including 63.3% of patients with ≥VGPR and 20.0% with a CR. The median time to response was 41 days. Similar response was observed among different subgroups: the ORR in Ixa phase1/2 study-eligible/ineligible group, MM2 trial- eligible/ineligible group and patients with standard/high-risk cytogenetics was 95.2%, 88.9%, 91.7%, 94.4%, 91.9% and 100.0%, respectively. And no significant difference in response between different ixa-based regimens was observed. After a median follow-up of 137.5 days after the first dose of ixazomib treatment (range, 28 - 372), median overall survival (mOS) and progression-free survival (mPFS) were not reached. (Table2) Adverse events (AEs) of grade 3 or higher were uncommon, reported in 14 (23.3%) patients, including thrombocytopenia (4 patients, 6.7%), diarrhea (5 patients, 8.3%), pneumonia (3 patients, 5.0%) and hypokalemia (1, 1.7%). No drug-related grade 3/4 peripheral neuropathy was recorded. Median cycles of ixa received were 4 cycles (range 1-11); 50 (83.3%) were still on treatment at data cut-off; 6 (10.0%) patients discontinued ixa due to intolerable AEs and 4 (6.7%) stop treatment for other reasons (mostly economic concerns). Discussion and conclusion: Here we reported the first real world, multi-center data on the efficacy and safety profile of ixa-based frontline therapy in patients with NDMM. Our results show that the ixa-based frontline therapy in real-life clinical practice is highly effective and fast in response, with an efficacy data (ORR 93.3%, ≥VGPR rate 63.3%) even better than that reported in NCT01217957 trial (ORR 88.0%, ≥VGPR rate 58.8%). Given the fact that no patients received SCT during follow-up in our cohort, our results maybe more comparable to the ongoing MM2 trial assessing SCT-ineligible NDMM. Ixa-based frontline therapy is well tolerated in NDMM patients treated in routine clinical practice. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Ixazomib is an oral proteasome inhibitor that approved for the use in patients with relapsed/refractory multiple myeloma (RRMM). Here in this abstract, I will present data on real-life practice of the use of ixazomib in newly diagnosed multiple myeloma.

Backgroud and Purpose: Extranodal natural killer/T-cell lymphoma (ENKTL) is an uncommon, aggressive form of non-Hodgkin's lymphoma. Optimal therapeutic strategies have not been fully defined yet. We reported the outcome of P-Gemox for the treatment of chemotherapy-naïve, refractory ENKTL in 2013 ASH meeting at the first time. Although several clinical trials have demonstrated the efficacy and tolerability of P-Gemox, we collected and anlyzed the real-world data of P-Gemox in Chinese patients with ENKTL. Patients and methods All cases with ENKTL from 2008 to 2017 were analyzed retrospectively P-Gemox were as follows: gemcitabine 1000 mg/m2; day 1,8; oxaliplatin 130 mg/m2 day 1, pegaspargase 2000-2500 U/m2 im day1. The regimen was repeated every 3 weeks. For newly diagnosed stage I/II patients, P-Gemox regimen was administered as induction chemotherapy for 4-6cycles and followed by involved-field radiotherapy or with"sandwiched" radiotherapy/chemotherapy. Furthermore autologous haematopoietic stem cell transplantation (ASCT) was recommended to chemo-sensitive refractory/relapsed patients as consolidation. All patients come to hospital regularly. Results: 267 patients with ENKTL were treated at the 10 institutions, in the department of Oncology or hematology in China between 2008 and 2017. Patient characteristics are summarized in Table 1. All patients received P-Gemox regimen, 209 patients (78.2%) as first-line therapy and 46 patients (22.0%) as second-line therapy. The median number of treatment cycles was 4.6(1-8) in the first line, 3.3 (2-6) in the second line, 243 patients were evaluable for response. The overall response (OR) rate was 84.8% (206/243), with a complete remission (CR) rate of 59.3% (144/243) (Table2). After the median follow-up time was 43.5 months (range, 1.5-101 months). The median OS of whole group was not reached, the median PFS was 61.0 months. The OS and PFS of the newly diagnosed patients is superior to refractory and relapsed patients (Fig1 A, B, P50%) of rates of grade 1 and 2 adverse events were as follows: hypoproteinemia, 74.1%, neutropenia, 64.4%, fibrinogenopenia 56.2%, transaminase elevated, 52.8%. Grade 3 and 4 adverse reactions (>10%) were thrombocytopenia, 29.2%, neutropenia, 27.7%(Table 3) . Conclusion: P-Gemox regimen followed by EIFRT yielded promising results for patients with stage I/II ENKTL. While for advanced or refractory/relapsed patients, P-Gemox was still unsatisfied . ASCT consolidation for good responders may improve the longterm outcom. Toxicity was moderate and tolerable. Disclosures No relevant conflicts of interest to declare.

Intravenous busulfan (IV-Bu) or total body irradiation (TBI) based regimens are currently the most widely used myeloablative conditioning regimens for patients with hematologic malignancies undergoing allogeneic stem-cell transplantation(allo-SCT). Numerous trials have been undertaken on the clinical outcomes between IV Bu and TBI, but there are no comparative data for cord blood transplantation(CBT). We conducted a prospective registry-based study to analysis the outcomes of IV Bu and TBI in CBT patients with hematologic malignancies. From May 1, 2008 to Mar 31, 2016, a total of 331 consecutive patients with hematologic malignancies recieved singe unrelated CBT were involved in the study. Eligibility criteria for this analysis included:(1)Weigh ≧35 kilograms and age ≦ 60 years; (2)All patients recieved a single unit CBT but not a double units CBT; (3)Consensus criteria preparative regimens were based on full dose IV Bu(total 12.8 mg/kg, 0.8mg/kg every 6 h for 4 days) or TBI(total 12 Gy, 4 fractions) combined with Cy(60mg/kg × 2d); (4)GVHD prophylaxis regimens include cyclosporine(CSA) and mycophenolate mofetil(MMF) without Antithymocyte Globulin(ATG). Patients who has recieved a previous autologous or allogeneic transplantation was excluded in the study. The cumulative incidence of neutrophil engraftment were 91.6% in IV Bu/Cy cohort and 98.0% in Cy/TBI cohort(P < .001), respectively. The median follow-up time in IV Bu/Cy and Cy/TBI cohorts was 28.7(range, 12.2 to 91.3) months and 55.5(range, 13.1 to 117.1) months, respectively(P Our resluts demonstrates that, compared with TBI, IV Bu regimen was associated with a higher incidence of graft rejection in CBT. But there was no difference in survival with no increased risk for NRM or relapse between two regimens. For those centers lack of radiation facilities, IV Bu may be a valid and efficient alternative to TBI. With the restriction of a retrospective registry analysis and limited patient munbers, rigorously designed prospective randomized controlled trials are needed to further investigated the availability of IV Bu and TBI for CBT. Disclosures No relevant conflicts of interest to declare.

Aim The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes following allogeneic haematopoietic stem cell transplantation (allo-HSCT). However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). The aim of this study was to assess the capacity of the EBMT risk score in predicting the outcomes of patients with leukaemia receiving sUCBT. Methods We retrospectively analysed 218 consecutive patients with leukaemia who received sUCBT at our centre between February 2011 and December 2015. Sixty-eight of the 218 patients had AML, 137 had ALL, 10 had CML, 2 had mixed phenotype AL, and only one patient had plasma cell leukaemia. The median age was 12 years (range, 1-46 years), and the median weight was 40 kg (range, 10-100 kg). All of the patients received an intensified myeloablative conditioning regimen with cyclosporine A (CsA) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis. All of the patients were followed until 31 March 2016, with a median follow-up of 10.7 months (range, 0.5-58.9 months). Results The overall survival (OS) and leukaemia-free survival (LFS) of the entire cohort were 66.8% and 55.4%, respectively, whereas the cumulative incidences of relapse rate and non-relapse mortality (NRM) were 22.4% and 18.0%, respectively. In the univariate analysis, a higher EBMT risk score was associated with worse OS, worse LFS, lower NRM and higher relapse rate, ranging from 80.2%, 74.5%,7.5% and 18.0%, respectively, for patients with a score of 1 to 21.8%, 17.0%, 27.3% and 55.7%, respectively, for patients with a score of 5/6. Hazard ratios of the four indexes all steadily increased for each additional score point. Importantly, the prognostic value of the EBMT risk score on OS, LFS, NRM and relapse was maintained in the multivariate analysis. Moreover, considering the importance of allele-level HLA matching, we developed a modified sUCBT-EBMT risk score using HLA matching situations instead of donor type and found that the modified score could also be used as a predictor for patient outcomes following sUCBT. Conclusions The EBMT risk score is a good predictor of outcomes of patients with leukaemia following sUCBT. The modified sUCBT-EBMT risk score can also be used as a pretransplant risk assessment, but this metric still requires further evaluation with a larger cohort. Disclosures No relevant conflicts of interest to declare.

Few reports have focused on the impact of ABO incompatibility on the clinical outcomes, after unrelated cord blood transplantation (UCBT). Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 177 patients with hematologic malignancies, which underwent single UCBT in Anhui Provincial Hospital from May 2008 to April 2014. The study patients included 86 ABO-identical, 52 minor, 32 major, and 11 bidirectional ABO-incompatible recipients. All of them received a homogeneous intensified myeloablative pre-transplantation conditioning regimen of total body irradiation (TBI)cyclophosphamide (CY) [TBI (total,12 Gy; four fractions) and CY (60 mg/kg daily for 2 days)] (age≥14 years) or BuCY2 [busulfan (0.8 mg/kg every 6 h for 4 days) and CY]. Medians of 3.85×107/kg (range, 1.03-10.43) total nucleated cell (TNC) and 2.0×105/kg (range, 0.45-6.88) CD34+cells were transfused. Of the 177 patients who underwent UCBT, 169 achieved successful neutrophil engraftment. In patients receiving ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the cumulative incidences of neutrophil engraftment were 92.7%, 100%, 96.9% and 90.9%, respectively (P=0.509). The median days to achieve neutrophil engraftment were 17, 18, 17, and 20, respectively (P=0.409). The cumulative incidences of platelet engraftment were 81.7%, 86.5% , 87.5% and 63.6%, respectively(P=0.436) .And the median days to achieve platelet engraftment for the 4 groups were 36, 40, 36, and 38, respectively; (P=0.545). All of the data did not show any significant difference among the 4 groups. Neutrophil engraftment(cumulative incidence, 95.5% versus 95.3% , P=0.861; median day, 17 versus 18, P=0.717) also did not differ significantly between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients (HR1.08, P=0.680). And platelet engraftment (83.6% versus 81.4%, P=0.964; median day, 38 versus 37, P=0.699) reached the similar result (HR1.104, P=0.621). We investigated the results from a 169-patient population with neutrophil engraftment, the average units of platelets (Plts) and red blood cells (RBCs) transfused during the hospitalization after the UCBT were 0.204 units/kg(range, 0.03-1.45)and 0.159 units/kg (range, 0-1.56).In patients with ABO-identical, minor, major, and bidirectional ABO-incompatible UCBT, the average units of Plts transfused after UCBT were 0.221, 0.202, 0.169, and 0.195 units/kg(P=0.53), respectively, and the average units of RBCs transfused were 0.151, 0.156, 0.163, and 0.221 units/kg (P=0.847), respectively. No significant differences in the transfusion requirements among the 4 groups were noted, so did the comparison between the ABO-identical/minor ABO-incompatible and major/bidirectional ABO-incompatible recipients. With a median follow-up of 12 months (range, 3-74 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 67.1%, 57.7%, 62.5 % and 54.5%, respectively (P=0.804), and the overall survival (OS) also did not differ significantly among the four groups (68.3%, 61.5%, 65.6%, and 63.6%, respectively; P=0.929). When it came to the comparison between the ABO identical/minor incompatible group and the ABO major/bidirectional incompatible group, the DFS (63.4% versus 60.5%; P=0.995) and OS estimates (65.7% versus 65.1%; P=0.820) were not significantly different, either. What’s more, none of the patients clinical developed severe immune hemolysis or pure red-cell aplasia after transplantation. In summary, the results above indicated that :1) ABO incompatibility did not seem to have a significant impact on clinical outcomes after UCBT, such as engraftment, transfusion requirements and survival. 2) No patients developed pure red-cell aplasia after UCBT. 3) In addition, we also compared the outcomes between the ABO-identical and bidirectional ABO-incompatible groups, even it did not show any significant difference, the former did better on platelet engraftment (81.7% versus 63.6%) and DFS (67.1 versus 54.5%). The reason led to this result may be the lack of bidirectional ABO-incompatible recipients. Therefore, we’d better avoid selecting bidirectional ABO-incompatible in UCBT to improve the patients’ recovery and survival time. Disclosures No relevant conflicts of interest to declare.

Introduction : Unrelated cord blood transplantation (CBT) is one of the most promising curative treatment modalities for hematological malignancies. But the data was limited in China. This retrospective study evaluated the clinical outcomes of intensified myeloablative unrelated CBT for high-risk or advanced hematological malignancies in our single center. Patients and Methods: From September 2006 to December 2013, Total of 187 high-risk or advanced hematologic malignancies underwent intensified myeloablative unrelated CBT. All CBT patients received a myeloablative conditioning regimen of TBI/Ara-C/CY [total body irradiation (TBI, total 12 Gy, 4 fractions) (d-7, d-6) arabinoside cytarabine (Ara-C) (2.0g/m2 every 12h for 2 days) (d-5, d-4) and cyclophosphamide (CY, 60 mg/kg daily for 2 days) (d-3, d-2)] (age≥14 years or primary induction failure or no remission after relapse), or Fludarabine/BU/CY2 [fludarabine (Flu, 30mg/m2 daily for 4 days) (d-8~ -5), busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)] (For lymphoid malignancies patients with age ＜14 years or prior radiotherapy which would presuppose a high risk of toxicity), or Ara-C/BU/CY2 [ Ara C (2.0g/m2 every 12h for 2 days) (d-9, d-8), (busulfan (0.8mg/kg every 6h for 4 days) (d-7~ -4) and CY (60 mg/kg daily for 2 days) (d-3, d-2)](for myeloid malignancies patients with age < 14 years or prior radiotherapy which would presuppose a high risk of toxicity), and G-CSF was given with 5 ug/kg daily by subcutaneous injection one day prior to Ara-C with 3 days. For GVHD prophylaxis, all patients were given a combination of cyclosporine and short-course mycophenolate mofetil, and no patient received antithymocyte globulin (ATG). Results: Total of 181 patients (97.3%) achieved neutrophil engraftment and platelet engraftment, and the median number of days was 18 days (range 12~37 days) and 37.5days (range 15~112 days), respectively. Total nucleated-cell dose (≥5.2×107 / kg) and total CD34+ cell dose (≥3.8×105 / kg) were the favorable factors predicting for a higher probability of neutrophil engraftment (p =0.012, 0.025). The cumulative incidence of pre-engraftment syndrome (PES) and day-100 grade Ⅱ-Ⅳ acute GVHD was 75.4% (95% CI, 65.2-84.2%) and 28.34% (95% CI, 28.13~28.55%), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute GVHD 100 days after transplantation was 32.6% (95% CI, 42.3-22.8%)in the PES group and 15.2% (95% CI, 8.3-22.6%) in the non-PES group (р=0.016). Multivariate analysis showed that BU/CY2 based conditioning and without PES were significant risk factors for graft failure [RR=2.34 (95% CI, 1.32- 6.12), p =0.015; RR=2.89 (95% CI, 1.25- 6.82), p =0.009]. The median follow-up time was 27（7~89）months. Transplant-related mortality at 180 days and relapse at 3 years after CBT was 24.9% (24.7~25.2%) and 14.7% (14.6~14.9%). Probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 61.2% (95% CI, 51.3%- 72.3%) and 58.6% (95% CI, 49.5%- 67.9%), respectively. For pediatric patients, 3-year OS and DFS were 66.2% (95% CI, 56.4%- 75.8%) and 64.8% (95% CI, 54.6%- 74.2%); for adult patients, 3-year OS and DFS were 54.5% (95% CI, 45.8%- 63.7%) and 50.3% (95% CI, 41.5%- 60.1%), respectively. Conclusions: To the best of our knowledge, this is the largest clinical study of unrelated CBT reported in China. This retrospective study indicates that intensified myeloablative CBT procedures are associated with significant favorable outcomes in survival advantage in high-risk or advanced hematological malignancies. Disclosures No relevant conflicts of interest to declare.

Objective Analysis and discuss the time of cytomegalovirus (CMV) preemptive therapy after umbilical cord blood transplantation (UCBT). Analysis the risk factors of CMV infection and the effect on survival of CMV infection after UCBT. Method From April 2000 to March 2013, 176 cases of patients undergo UCBT who were detected plasma CMV-DNA twice a week routinely. Preemptive antiviral therapy was initiated with ganciclovir or foscarnet for positive PCR of 103 DNA copies or more per ml. Results 125 of 176 patients developed CMV infection (71%) at a median of 32d (range 19 to 98) post-transplant and only 4 patients developed CMV disease (2.3%). The 5-year overall (OS) was 59.4% in the patients with CMV infection and 64.9% in patients without CMV infection (P=0.193). The study identified that younger age, high-risk disease, infused little CD34 positive cells, developed III-IV degree acute graft-versus-host disease (GVHD), high-dose methylprednisolone, and treated with basiliximab and other strong immunosuppressive agent as significant risk factors for developing CMV infection. It had nothing to do with the gender of patients, transplantation of UCB units, the conditioning regime, the day of neutrophil recovery and chronic GVHD. Preemptive therapy when the CMV-DNA copies are greater than 103 does not increase the incidence of CMV disease, and the survival has not been impacted. Conclusion Preemptive therapy can be initiated when CMV-DNA copies are greater than 103 which can achieve the same effects in UCBT. Disclosures: No relevant conflicts of interest to declare.

Few clinical studies have investigated the role of salvaged unrelated cord blood transplantation (CBT) for progressive hematologic malignancies. The aim of this report is to identify the potential benefits of unrelated CBT in progressive hematologic malignancies.19 consecutive patients with progressive myeloid and lymphoid malignancies who received salvaged CBT following myeloablative conditioning regimens (12 TBI/CY/Ara-C, 6 Bu / CY / Ara-C, and 1 Bu /CY) from July 2005 to December 2012 were analyzed retrospectively. Of the 19 patients, 6 suffered from acute myeloid leukemia(AML), 5 acute lymphoid leukemia(ALL),：1 acute mixed lineage leukemia (AMLL), 1 myelodysplastic syndrome-refractory anemia with excess blasts(MDS-RAEB), 2 acute myeloid leukemia transformed from myelodysplastic syndrome, and 4 lymphoma, all of them in non-remission (NR) before transplantation. Median age of them were 13（range 6-32）years and median body weight were 45 (range 18–73 ) kg. All patients received 1 CBT unit ≤2 loci HLA-mismatched with the recipient. Infused TNC was 4.07（range 2.76-6.02）×107/kg and CD34+ stem cell 2.08（range 0.99-8.65）×105/kg. All patients were engrafted with neutrophil exceeded 0.5×109/L on median day +17（range 14-37d）and plt counts of＞20×109/L on median day +35 (range 17-70d). 10 patients (52.6%) experienced pre-engraftment syndrome (PES) and 3 (15.8%) patients progressed to acute GVHD. The incidence of Ⅱ-Ⅳ aGVHD and cGVHD were 10.5% and 21.1%. With a median follow up of 10(range 1-58) months，10 cases survived and 2 relapsed．The estimated 2 year overall survival (OS), disease-free survival (DFS) and non-relapse mortality (NRM) rate was 45.6%, 34.2% and 39.8%. Salvaged CBT might be a promising modality for treatment of progressive hematologic malignancies, even with high leukemia burden. Disclosures: No relevant conflicts of interest to declare.

Umbilical cord blood transplantation (UCBT) has now become a more common treatment for patients with hematologic malignancies who lack matched related or unrelated donors. However, few reports have addressed the impact of ABO incompatibility on the clinical outcomes, such as engraftment, transfusion requirements and survival after UCBT. Therefore, we retrospectively analyzed the impact of ABO mismatching on the clinical outcomes of 121 patients, including 51 ABO-identical, 23 minor, 39 major, and 8 bidirectional ABO-incompatible recipients after UCBT. With a median follow-up of 11 months (range, 5-151 months), the disease-free survival (DFS) rates among the ABO-identical, minor, major, and bidirectional ABO-incompatible groups were 71.7%, 60.0%, 37.1%, and 71.4%, respectively (P=0.014), whereas the OS did not differ significantly among the four groups (76.1%, 65.0%, 48.6%, and 71.4%, respectively; P=0.078). The DFS (68.2%, 42.9%; P=0.009) and OS estimates (72.7%, 52.4%; P=0.031) of the ABO identical/minor incompatible group also differed significantly from the ABO major/bidirectional incompatible group. These results were confirmed in the multivariate analysis. No significant differences in the engraftment times, transfusion requirements, graft-versus-host disease (GVHD), relapse, and non-relapse mortality (NRM) were noted among the groups. Severe immune hemolysis or pure red cell aplasia did not occur among these patients. These results indicate that ABO incompatibility somewhat affects the DFS and OS in UCBT, but further studies are still required. Disclosures: No relevant conflicts of interest to declare.

Objectives We retrospectively analyzed the safety and efficacy of a myeloablative conditioning regimen without anti-thymocyte globulin (ATG) or total body irradiation (TBI) but with fludarabine (FLU) in unrelated cord blood transplantation (UCBT) for 30 patients with hematologic malignancies. Methods The myeloablative conditioning regimen consisted of FLU, busulfan (BU) and cyclophosphamide (CY). All of the patients received Cyclosporine (CSA) and mycophenolate mofetil (MMF) as graft versus host disease (GVHD) prophylaxis. Results With this conditioning regimen, we achieved high engraftment rates (96.7%) and rapid hematopoietic reconstitution. Acute GVHD occurred in 12 cases of the 29 engraftment patients (41.4%), and 6 cases (20.7%) were of grade III-IV. Chronic GVHD only occurred in 1 of 28 evaluable patients (3.6%). Twenty-three patients (76.7%) became infected, and 3 cases (10.0%) died of severe infections. Cytomegalovirus (CMV) reactivation occurred in 70.0% of the patients, but no CMV diseases were observed, nor did any patients die of CMV infection. The cumulative incidence of relapse (6.7%) was significantly reduced, and none of the acute lymphoblastic leukemia (ALL) patients relapsed. The 3-year overall survival (OS) and event-free survival (EFS) rates were 73.3% and 70.0%, respectively, representing satisfactory survival. The 3-year OS and EFS of the ALL patients was 75.0%. Discussion This conditioning regimen resulted in a high engraftment rate, rapid myeloid reconstruction and a low incidence of infection. Although there were many patients with high-risk disease and disease progression, the regimen resulted in low relapse rates and good survival. None of the ALL patients relapsed after UCBT, indicating that this conditioning regimen could be applied to more patients with ALL. Disclosures: No relevant conflicts of interest to declare.

Abstract 4525 To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) using total body irradiation (TBI)-based myeloablative conditioning regimen without antithymocyte globulin (TBI/Ara-c/CY w/o ATG) in adolescent and adult patients with high-risk hematological malignancies. Outcomes of forty-five consecutive adolescent and adult patients with high-risk hematological malignancies treated with TBI-based myeloablative UCBT without ATG in a single center between September 2006 and February 2012 were retrospectively analyzed. The conditioning regimen included TBI/Ara-c/CY:TBI 12GY (four fractionated) + Ara-C 8g/m2 (two days fractionated) + CY 120mg/kg (two days fractionated), and rhG-CSF was administered for myeloid leukemia by continuous infusion at a dose of 5μg·kg−1·d−1. Infusion of G-CSF was started 24 hours before the first dose of Ara-C and stopped at the completion of the last dose. The patients included 31 males and 14 females, with a median age of 21 years (range: 14–40) and a median weight of 58 kg (range: 42–76). Of those, 17 patients (37.8%) had advanced disease. Double UCB grafts were used for 16 patients, while single UCB graft was used for 29 patients. The median number of nucleated cells infused was 3.57 (1.94∼6.76)×107/kg and the median CD34+cells infused was 2.11 (0.71∼4.95)×105/kg. All patients received a combination of cyclosporine (CSA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients successfully engrafted. The median times to neutrophil (ANC≥0.5×109/L) and platelet (PLT PLT≥20×109/L) recovery were 19 days (range: 13–35 days) and 36 days (range: 24–90 days) respectively after transplantation in 40 evaluable patients. Acute GVHD occurred in 21 patients and the cumulative incidences of gradeII-‡W and grade III-‡W acute GVHD were 24.4% and 11.1%, respectively. Chronic GVHD occurred in five of 40 evaluable patients (12.5%). Of the 45 patients, 9 (20%) had relapse. After a median follow-up of 25.1 months (range: 6–65.1) among survivors, treatment-related mortality (TRM) within 100 days and within one year was 8.9% and 24.4%, respectively. The main causes of death were pneumonia and severe acute GVHD. The probability of three-year disease-free survival and overall survival (OS) was 53.3% and 57.8%, respectively. The TBI/Ara-c/CY myeloablative conditioning regimen has been well tolerated by patients at our institution and seems to be able to establish sustained donor cell engraftment and decrease the risk of transplant-related death. For high risk patients and patients with advanced disease, this conditioning regimen could reduce relapse and chronic GVHD, indicating the feasibility of TBI/Ara-c/CY as a conditioning regimen for CBT in adolescent and adult patients with hematologic malignancies. Disclosures: Sun: Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding.

Abstract 3134 HLA-identical sibling allogeneic hematopoietic stem cell transplantation (HSCT) is the best therapeutic option for high-risk hematological disease, but it is limited by lack of availability of a suitable donor for most candidate patients. At our institution our center, unrelated cord blood transplantation (UCBT) was used as the first alternative option for patients who lack an HLA-matched related donor in the last decade. We retrospectively analyzed the clinical outcomes of UCBT versus HLA-identical sibling HSCT for adult patients with hematologic malignancies. Between April 2000 and May 2012, 194 consecutive adult patients with malignant hematological diseases received UCBT (77 patients; median age 21y, r 14–46; male 49) and related bone marrow transplantation (BMT) and/or peripheral blood stem cells transplantation (PBSCT) (117 patients; median age 30y, r 14–53; male 75). Diagnoses in two groups (UCBT/Sibling) included de novo AML (n = 23/32), ALL (n = 30/26), CML (n = 17/47), MDS/AML (n = 3/8), mixed phenotype acute leukemia (MPAL) (n = 3/1), NHL (n = 1/2), and MM (n = 0/1)). Overall rates of high-risk patients were 84.4% for UCBT recipients and 50.4% for BMT/PBSCT recipients(P The median number of nucleated cells and CD34+ cells infused were 0.36 (r 0.19–0.69)×108 and 0.21(r 0.06–0.52)×106 per kilogram of the recipient's body weight for UCBT recipients, and 5.68 (r 2.02–12)×108 and 3.63(r 0.67∼14.99)×106 per kilogram for BMT/PBSCT recipients (P=0.000). The primary engraftment rate was 96.1% (UCBT) and 100% (BMT/PBSCT). The median time to 0.5×109/L ANC was 19 days (r 12–35) and 12 days(r 10–18)(P = 0.000) and the median time to 20×109/L platelets was 36 days(r 14–90)and 15 days(r 11–17)(P = 0.001); hematopoietic recovery was significantly delayed after UCBT. The cumulative incidence of total acute GVHD (47.3% vs.22.2%, P = 0.001), early transplantation-related mortality (TRM) before day +100 (13.0% vs.3.4%, P Our data shows similar survival, but better quality of life after myeloablative transplantation using UCB versus identical sibling hematopoietic cells in adults with hematologic malignancies. HLA-mismatched cord blood should be considered an acceptable source of hematopoietic stem-cell grafts for adults in the absence of an HLA-matched adult donor. Disclosures: Sun: Anhui Provincial “115” Industrial Innovation Program (2009): Research Funding; the Fund of the Key Medical Project of Anhui Provincial Healthy Department (2010A005): Research Funding; Key Scientific and Technological Project of Anhui province “Twelfth Five-Year Plan” (11010402164): Research Funding.

Abstract 2368 We report a single center experience in treating 16 consecutive patients (nine male and seven female) with severe aplastic anemia (AA) who received unrelated cord blood transplantation (UCBT) between 2006 and 2010. The main outcomes of interest were the tolerability and toxicity of UCBT, hematopoietic reconstitution and survival. The first two patients using a conditioning regimen consisting of cyclophosphamide (total dose 120°< Disclosures: Sun: Fund of 11th Five-Year Science and Technology Key Project of Anhui Province (06013128B): Research Funding; Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.

Abstract 4583 We retrospectively analyzed of the engraftment, Transplant-related complications and survival after unrelated cord blood transplantation (UCBT) using irradiation-based myeloablative conditioning in adult with hematologic malignancies. Between September 2006 and June 2010, 29 consecutive adult patients with hematological malignancies were treated with UCBT, Thirteen of them were advanced-stage disease and 11 of them were high risk or refractory disease. All patients received four fractionated 12 Gy TBI, total dose 12 g/m2 cytarabine and total dose 120 mg/kg cyclophosphamide as myeloablative conditioning. The median age was 21 years; the median weight was 57 kg. Double or multiple UCB grafts were used for 17 patients, while single UCB graft for 12 patients. the median number of nucleated cells was 3.83×107/kg and 5.25×107/kg. All patients were given a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. All patients obtained engraftment. Median time to neutrophil≥0.5×109/L was 20 days (range 14–37) and platelet engraftment in 25 patients (≥20×109/L) was 35 days (range 25–49). Chimerism was assessed by PCR analysis of short tandem repeat (STR) sequences on whole blood or bone marrow weekly in cases who were fully donor chimeric from 7 days to 21 days after transplantation. 16 cases developed acute GVHD, more than grade II in three cases. Six of twenty-four patients who survived more than 100 days developed limited chronic GVHD.17 cases were alive and in hematologic remission at a median follow-up of 504 days (range 49 ~ 1245). The probability of over survival at 3 years was 58.6%. Five cases relapsed. Nine of twelve cases died of transplant related complications and infection. These results suggest that UCBT after TBI-based myeloablative conditioning could be safely and effectively used for adult patients with hematologic malignancies. Disclosures: Sun: the Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; the Clinical Technology foundation of Anhui Provincial healthy department (2008A011): Research Funding; the Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.

Abstract 4570 We compared the clinical outcomes of allogeneic hematopoietic stem-cell transplantation among 126 adults with hematologic malignancies: 40 received unrelated cord blood transplantation (CBT) and 86 received related bone marrow transplantation (BMT) and/or peripheral blood stem cells transplantation (PBSCT). All patients received myeloablative transplantations which performed from 2001 through 2010.Recipients of unrelated CBT were younger (median, 23.5 vs. 30 years of age; P Disclosures: Sun: International Cooperation Research Fund of Anhui Provincial Scientific and Technologic Committee (08080703026): Research Funding; Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program: Research Funding.

Abstract 4649 Objective This study was aimed to investigate the expression levels and significance of CCAAT/enhancer binding protein alpha gene and transcription factor PU.1 gene in myelodysplasyic syndromes (MDS). Methods A real time quantitative reverse transcriptase polymerase chain reaction (Real-time PCR) method was used to detect the expression levels of C/EBPα mRNA in bone marrow mononuclear cells (BMMNCs) of 33 patients with MDS and 14 normal controls, Reverse transcription polymerase chain reaction (RT-PCR) was established for detecting PU.1 mRNA expression levels in BMMNCs of above-mentioned samples. Results The expression of C/EBPα was significantly lower in low-risk and high-risk MDS than those of normal controls (P0.05). Conclusion reduced C/EBPα and PU.1 expression level have closely associated with the pathogenesis of MDS, they may be important molecular biological markers of MDS; The degree of down-regulated C/EBPα has closely related to the progression of MDS, the detection of C/EBPα gene expression level may be useful for assessing disease progress and prognostic of patients with MDS. Disclosures: Ding: Anhui Provincial Natural Science Foundation (070413257X): Research Funding; Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding.

Abstract 1267 Pre-engraftment syndrome (PES) has been described in patients receiving umbilical cord blood transplantation (CBT). However, PES remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcome of PES in CBT recipients treated for hematological malignancies at our transplantation center. A total of 60 patients (median 20 years, range 3–48) received either myeloablative (n=52) or reduced-intensity (n=8) conditioning. 28 patients received double unit grafts to augment engraftment. Cyclosporine-A and mycophenolate mofetil were used as GVHD prophylaxis, and all patients received post-transplant granulocyte colony-stimulating factor. In this study, PES was defined as noninfectious fever (>38.3°C) and/or unexplained rash occurring before neutrophil engraftment. 38 patients (63.3%) fulfilled PES criteria: 33 with fever and 36 with rash. The median onset was 8 days (range 3–15) post-transplant (a median of 12 days before neutrophil recovery). 34 patients received IV methylprednisolone (MP) (0.5-2 mg/kg/d) with 27/34 (79.4%) having fever and/or rash resolution in We conclude that PES is common following CB transplant (CBT), predicts for aGVHD, and responds promptly to corticosteroids. Disclosures: Wang: Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Clinical Technology foundation of Anhui Provincial healthy department (2008A011): Research Funding; Fund of Anhui Provincial “115” Industrial Innovation Program: Research Funding; Anhui Provincial Outstanding Young Investigator Program (08040106810): Research Funding.

Abstract 4687 Given the tremendous need for and potential of umbilical cord blood (UCB) to be utilized as a donor source for hematopoietic stem cell (HSC) transplantation in adults, there is a strong push to overcome the constraints created by the limited volumes and subsequent limited HSC and hematopoietic progenitor cell (HPC) numbers available for HSC transplantation from a single collection. Hematopoietic stem cell homing is believed to be critical for the development of methodologies to improve transplant efficiency and subsequently immune reconstitution during hematopoietic stem cell transplantation in clinical setting. We have previously described the functional defect of partial homing receptor in cord blood stem cell (the higher activity of CD26 and the lower expression of P/E-selectin ligand) in vitro. Respectively, we had confirmed that using of glycosylation engineering and CD26 inhibitor can fix the defect of stem cell homing. However, there is no evidence can prove whether the combination would improve the ability of homing. In present study, to explore the use of glycosylation combined with CD26 inhibitor as a method of improving the transplant efficiency of CB CD34+ hematopoietic stem cells (expressing CD45), we utilized the xenotransplanted nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model in vivo. 6–8 weeks age of NOD/SCID mice were divided into 5 groups (8 mice per group): blank control group (without stem cells infusion); control group (CD34+ cells infusion alone); glycosylation engineering group; CD26 inhibitor group and combination group (glycosylation engineering combined CD26 inhibitor group). Purified CD34+ stem cells (5×105 per mice) derived from fresh UCB by immunomagnetic beads were injected into lethally irradiated NOD/SCID mice intravenously. To investigate the effect of early engraftment in vivo, we monitored the expression of CD45 in peripheral blood and the overall viability rate weekly until the fourth week by flow cytometry. One week after transplantation, there is no expression of CD45 in peripheral blood in any group, but we observed 2.52±1.41% and 4.8% expression in bone marrow of recipient mice respectively in control and glycosylation engineering groups. All mice in the blank control group were dead and overall viability rate were almost the same for the other four groups (80% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group). The second week, there is only expression of CD45 in recipient mice for combination group 0.63±0.37%. The overall survival rate among control were significantly lower than the other four groups (40% in control group,80% in glycosylation engineering group, 100% in CD26 inhibitor group and 100% in combination group, P Disclosures: Sun: International Cooperation Research Fund of Anhui Provincial Scientific and Technologic Committee (08080703026): Research Funding; Fund of the Key Medical Project of Anhui Provincial healthy department (2010A005): Research Funding; Anhui Provincial “115” Industrial Innovation Program: Research Funding.

Acute lymphocytic leukemia (ALL) is a life threatening disease with high rate of relapse. To date, there is no ideal treatment for ALL. Recently, stem cell transplantation has been used as a potential therapy. However, it is unclear what the best source of donor stem cells is and whether it is safe or effective to use these regimens in human patients. In this study, we evaluated the safety and outcomes of 22 patients with ALL after umbilical cord blood transplantation (UCBT) or bone-marrow from related donors (RD). Eleven patients received stem cells from HLA 0–2 (A,B,DRB1) mismatched UCBT (median infused dose, 3.77×107 nucleated cell NC/kg; range, 3.40– 7.49 ×107 NC/kg). The other 11 patients received stem cells from bone marrow from RD (median infused dose, 4.08×108 NC/kg; range, 1.86–9.82×107 NC/kg). All patients in both groups were comparable, as shown in Table 1. All patients received myeloablative conditioning (busulfanum/cyclophosphamide was used for the RD transplantation and anti-thymus globulin 7.5 mg/kg was used for the UCB transplantation) followed by infusion of allogenetic hematopoietc stem cells from either bone marrow or cord blood. Cyclosporine A (CsA) and mycophenolate mofetil (MMF) were administered for the prophylaxis of graft-versus-host disease (GVHD). Overall survival (OS), leukemia-free survival (LFS), transplantation-related mortality (TRM) and relapse rate between RD and UCB were shown in Table 2. The results demonstrated that despite the higher HLA mismatch rate and lower number of infused hematopietic stem cells, OS, LFS, TRM and relapse rate in UCB group were 81.8%, 81.8%, 0% and 18.2% which were significantly better than in the RD group. These data strongly suggest that UCBT could be a safe and effective therapy for patients with ALL. Table 1 The Profiles of Patients RD UCBT High Risk ALL 7/11 7/11 HLA 0/6 Mismatched (%) 72.7 9.1 HLA 1/6 Mismatched (%) 27.3 81.8 HLA 2/6 Mismatched (%) 0 9.1 Median Age (years, range) 30 (8–63) 25 (3–38) Median Body Weight (kg, range) 51 (26–70) 40 (13–84) Table 2 Outcomes of ALL patients after UCB transplantation RD UCB P value Number of patients 11 11 Median follow up (years) 2.0 2.0 OS 2 yr % (95% CI) 36.4 81.8

Vascular endothelial growth factor (VEGF) is a crucial mediator of angiogenesis, and plays an important role in pathogenesis of leukemia. However, the importance of VEGF in differentiation or apoptosis of leukemic cells remains to be evaluated. A competitor DNA fragment template of VEGF gene mimic was constructed with the method of gene recombinant technologies, and a competitive quantitative reverse transcriptase-polymerase chain reaction (cQRT-PCR) for analyzing VEGF gene expression was performed to assess the regulation of VEGF gene expression in the process of all-trans retinoic acid (ATRA)-induced differentiation of an acute promyelocytic leukemia cell line NB4. In construction of a standard curve from which the amount of target cDNA was derived, serial dilutions of the target were co-amplified with a constant amount of mimic, and the intensities of bands corresponding to the target and the mimic were measured. CD11b antigen and nitroblue tetrazolium (NBT) reduction rate of NB4 cells were also assayed at different time points. cQRT-PCR was a sensitive and reliable tool for analysis of VEGF gene expression, with a detectable range from 1 to 2 times 10 the fifth power molecules. The number of VEGF gene transcripts detected by means of cQRT-PCR assay was 42.3, 12.6, 3.6, and less than 1.0 times 10 the fifth powder per microgram of NB4 total RNA at 0, 12, 24 and 48 hours after ATRA treatment, respectively. The rapid down-regulation of VEGF gene expression during ATRA-induced NB4 cell differentiation was accompanied by an upregulation of CD11b expression and an increased NBT reduction rate. In conclusion, cQRT-PCR could be used as an efficient method of qualitative analysis of VEGF gene expression. ATRA significantly depresses VEGF expression and its antileukemic effect can be brought through the two ways of differentiation induction and angiogenesis inhibition.

VEGF-C secreted by kinds of tumor cells play the key role in lymphangiogenesis via activating tyrosine kinase of VEGFR-3, which is one of most important pathway of infiltration and metastasis of tumor cells. In recent years, the effects of VEGF-C on hematological malignant cells are paid attention. In the current study, the recombinant eukaryotic expression plasmid (pcDNA3.1-VEGF-C) and the vacant pcDNA3.1 vector were introduced into the acute promyelocytic leukemia cell line- NB4 cells (VEGFR-3+/VEGFR-2−) by lipofectamine mediation and positive clones were screened by G418. The stable expression of VEGF-C was detected by reverse transcriptase-PCR and Western blotting. The proliferation ability of NB4/VEGF-C cells is analysed by MTT assay. After NB4/VEGF-C cells were induced by ATRA (1μmol/L), the expression levels of C/EBPα gene which can promote myelocytes differentiation and maturation, CD11b on cells surface and morphological variation were analysed by real-time quantitative PCR (RT-QPCR), flow cytometry analysis (FCM), Wright-Giemsa staining respectively. Furthermore, after the NB4/VEGF-C cells were cultured together with Etoposide (200ng/ml) for 48 hours, the numbers of AnnexinV+/PI−cells (apoptotic cells) were determined by FCM to investigate the effect of VEGF-C on the cells apoptosis and expression levels of antiapoptotic bcl-2 gene in these cells were analysed by RT-QPCR. The NB4/pcDNA3.1 cells was used as control during the experiments. From these experiments, NB4/VEGF-C cells can stably secret active protein VEGF-C in the cell supernatants. The cell growth curve shows that the proliferation ability of NB4/VEGF-C cells is stronger compared with NB4/pcDNA3.1cells. The expression levels of C/EBPα gene of NB4/VEGF-C cells after induced by ATRA is only 1/32 that of NB4/pcDNA3.1 cells. Morphological analysis shows that the degree of promyelocytes gradually maturing into myelocytes among NB4/VEGF-C cells is weaker compared with the controls after induced by ATRA. After induced by Etoposide, the percent of apoptotic cells of NB4/VEGF-C cells (7.20±2.52%) is significantly lower than that of NB4/pcDNA3.1 cells (16.07±3.58%)( P=0.005) and the bcl-2 gene expression level of NB4/VEGF-C cells is 2.28 times more than that of NB4/pcDNA3.1 cells. The results implied that the VEGF-C via VEGFR-3 signaling pathway could promote the proliferation of NB4 cells by autocrine pathway and inhibit the NB4cells differentiation and maturation and chemotherapy-induced apoptosis via upregulating bcl-2 gene expression. Thus, VEGF-C/VEGFR-3 signaling loops might play an important role in disease progression and be potential therapeutic target for the treatment of leukemias.

Disintegrin is a kind of small native peptides derived from the snake venom, containing RGD sequences. Its interaction with integrins, such as aIIbb3, anb3 and a5b1, can inhibit platelet aggregation. hinder the process of angiogenesis and tumor metastasis. In order to further investigate the function of disintegrin in platelet aggregation, cell adhesion and angiogenesis, the sequence encoding the disintegrin domain of agacutin was fused with enhanced green fluorencent protein(eGFP) and inserted in plasmid pQE-30. The recombinant protein was expressed in E.Coli M15 after induction by IPTG, amounting to 38% of the total bacterial protein. The cells expressing integrin such as breast cancer cell line MDA-MB-231 and endothelial cell line EA.hy926 can specifically bind to the recombinant GFP-disintegrin. Flow cytometry showed that the recombinant protein could bind to platelet specfically and could compete with anti-b3 integrin monoclonal antibody CD61. Moreover, the recombinant protein could inhibit platelet aggregation induced by collagen and ADP in a dose-dependent manner, but had no ability to impede the platelet aggregation induced by Ristocetin. Meanwhile, it could inhibit cell (MDA-MB-231 and EA.hy926) adhesion to fibronectin with inhibition rate of 69% and 48%, respectively. Finally, it could induce apoptosis of EA.hy926 endothelial cells and inhibit the angiogenesis on chicken chorioallantoic membrane mode. As a result, it is demonstrated that GFP-disintegrin has the combined quality of its disparate components and can serve as a novel tool for study of tumor and angiogenesis. In addition, the recombinant protein can efficiently inhibit platelet aggregation and angiogenesis, which will be useful for designing the potential drug for anti-thrombosis and anti-tumor metastasis.