bluuebunny/crossref_metadata_2025_split huggingface dataset:
Yttrium-90-Ibritumomab Tiuxetan (Zevalin) in Combination with a Fludarabine-Based Reduced Conditioning Regimen (RIC) Followed by Allogenic Stem Cell Transplantation for Advanced/Aggressive Non-Hodgkin's Lymphoma (NHL): A Prospective, Multicentre, Open Phase II Study
Authors: Bouabdallah Krimo , Furst Sabine , Bouabdallah Reda , Vigouroux Stephane , Tabrizi Reza , Melot Cyril , Gouill Steven Le , Fegueux Nathalie , Tournilhac Olivier , Mohty Mohamad , Blaise Didier , Milpied noel-Jean 
Published: October 2019

Abstract
Abstract 3027
Patients (pts) with advanced/aggressive NHL who relapse after autologous stem cell transplantation (auto-sct) or who fail to respond to front-line chemotherapy have a very bad prognosis with a poor survival. We performed a prospective and multicentre study (Clinical Trials.gov, NCT 00607854) to evaluate the tolerability and the benefit of Zevalin added to a fludarabine-based RIC followed by allogenic stem cell transplantation (allo-sct) in pts with a poor prognosis lymphoma.
Between January 2008 and October 2010, 30 pts under 65 years old with NHL in relapse after at least 2 previous regimen with or without auto-sct underwent an allo-sct with this preparative regimen. The underlying disease was DLBCL (10 pts), MCL (9 pts) and low grade lymphoma (FL=9 and MZL=2). Patients had to be in CR or PR after the last salvage regimen (Cheson criteria) and to have a HLA-compatible (10/10) match-related (MRD) or unrelated (MUD) donor or 9/10 mismatched UD. GVH prophylaxis was based on CsA alone or in combination with Methotrexate in case of mismatch. The primary objective of the study was TRM at day 100.
All the pts are evaluable Twenty two were male (73%) and the median age was 57 (32–64). Twenty nine pts (97%) had prior auto-sct. Twenty pts were transplanted from a sibling donor, 8 from MUD and 2 pts had a C or DQ mismatch. At time of allo-sct, 18 pts were in CR and 12 pts in PR. Median time between diagnosis and allo-sct and between auto-sct and allo-sct was 36 mo and 18 mo respectively. Four pts died from a-GVH (n=2) at d 40 and 70, multi-organ failure (n=1) at d 117 and disease progression (n=1) at d 114 respectively. The TRM up to day 100 was 7% (n = 2). The median follow-up is 16 mo (9–40). All pts had a rapid and sustained engraftment. Twenty five pts are alive in CR. One pt died in CR (suicide) one year after transplant. The actuarial 3-year event-free and overall survival are 83% (± 6%). Estimated EFS at 2 years for the 3 different subgroups of diagnosis are 100% for FL and MZL, 89% (± 10%) for MCL and 70% (± 14%) for DLBCL.
We conclude that Yttrium-90-ibritumomab tiuxetan (Zevalin) in combination with a fludarabine-based regimen is safe with a very low TRM rate. The results we report here are in pts with a very bad prognosis are very encouraging with a very high response rate and survival.

Disclosures:
Off Label Use: Zevalin not licensed in France in this indication. Zevalin has been kindly provided by BayerHealthcare company for the study.
The Results of Patients with b Thalassemia Major Undergoing Peripheral Blood Stem Cell From Alternative Donor: New Conditioning Regimen for Thalassemia
Authors: Li Chunfu 
Published: October 2019

Abstract
Abstract 3034

Background:
Hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for thalassemia patients, However, most candidates for HSCT do not have a suitable family donor. In order to evaluate whether HSCT from an HLA–well -matched alternative donor can offer a probability of cure comparable to that of HSCT from sibling donor. The new conditioning regimen and peripheral blood stem cell transplant (PBSCT) from alternative donor (NF-08-thalassemia protocol) were used for b thalassemia patients. The improved outcome was summarized here.

Objective:
To evaluate the overall survival (OS), thalassemia-free survival (TFS), rejection (RE) and transplant related mortality (TRM) of NF-08-thalassemia protocol.
Patients and Methods: Sixty-one thalassemia patients, 42 male and 19 female (median age, 7 years; age range, 3–15 years), were transplanted from 56 (32 patients were 8/8 and 24 patients 7/8 locus matched at HLA-A, B, Cw and DRB1) unrelated and 5 (1 patient 8/8 and 4 patients 7/8 antigen matched) parents donors from Oct.2008 to Jan.2011(median follow-up time, 14 months; range, 6–31months). NF-08-thalassemia protocol included Cyclosphosphamide (d-10 to d-9), Busulfan (d-7 to d-5), Thiotepa (d-4), Fludarabine (d-8 to d-4) and ATG (d-3 to d-1). PBSCs from unrelated (56 cases) and parents (5 cases) donor were used as only source of stem cells in all patients. GVHD prophylaxis included Cs A, MMF and sMTX.

Results:
OS, DFS and TRM in the cohort of 61 patients were 91.8%, 90.2% and 8.2%, respectively. Only one rejected his graft two months after transplantation. Acute GVHD III∼IV was 8.2% (5 patients) and none suffered from extensive chronic GVHD. Three patients died of acute GVHD and two died of the infection after transplantation.

Discussion:
In comparing this alternative donor HSCT with sibling donor HSCT (30 patients, using the same protocol, meanwhile), OS, TFS, RE and TRM were 91.8% vs. 85.9% (P=0.401), 90.2% vs. 79.2% (p=0.147), 1.6% vs. 6.9% (p=0.197) and 8.2%vs.14.1%, respectively. No significant difference was found.

Summary:
The results of alternative donor HSCT for b thalassemia patients are comparable with sibling donor transplant with using NF-08-thalassemia protocol.

Disclosures:
Li: Qi fa Liu: Workmates.
Total Therapy 6: Initial Results of Dose-Dense Strategy for Previously Treated Multiple Myeloma
Authors: Usmani Saad , Mitchell Alan , Nair Bijay , Waheed Sarah , van Rhee Frits , Alsayed Yazan , Petty Nathan M , Steward Doug , Panozzo Susan , Hoering Antje , Crowley John , Barlogie Bart 
Published: October 2019

Abstract
Abstract 3081

Background:
We have reported extensively on applying dose-intense total therapy approach in newly diagnosed multiple myeloma (MM), yielding long CR durations in ∼80% GEP-defined low-risk myeloma patients. Herein, we present for the first time the initial results of a phase II trial employing a dose-dense approach in previously treated MM. Patients & Methods: Patients received 5 cycles of combination chemotherapy (Figure 1) followed by maintenance with bortezomib, lenalidomide and dexamethasone until relapse or disease progression by IMWG 2006 criteria. Overall survival and progression free survival were estimated using the Kaplan-Meier method. Survival distributions were compared using the log-rank test. Results: 63 patients with previously treated MM were enrolled. The median follow-up from enrollment was 15.6 months. Baseline characteristics included age >=65yr in 37%, ISS stage II/III was seen in 41%/19% of patients, cytogenetic abnormalities (CA) in 37%, and GEP-70 high risk-MM (HRMM) in 26% of patients with available gene expression data. 11 patients (17%) had >2 prior lines of therapy including regimens that contained bortezomib (91%), thalidomide(45%), lenalidomide(81%), melphalan(27%) and steroids(100%). 14 patients (22%) discontinued therapy primarily due to progression, death or toxicity. Cumulative incidence of PR/VGPR/CR at 18 months was 69.4%, 54.8% and 37.0% respectively. Of the 60 patients with at least 3 months of follow-up, 33% had stable disease as the best overall response. The time to achieving PR or better at 6 months was more rapid in HR-MM vs LRMM (63.6% vs. 50%, p=0.008). Hematologic toxicities occurred in all patients (100%), whereas the most common non-hematologic toxicities counting all toxicities (>grades 3) included metabolic/electrolyte disturbances (95%) followed by infections (31%), hepatobiliary (20%) and gastrointestinal (16%) toxicities. Overall survival (OS) and progression free survival (PFS) at 12 months was 90% and 87%, respectively (Figure 2). The OS (96% vs 60%, p=0.0002) and PFS (92% vs 53%, p<0.0001) at 12 months was markedly superior in GEP-70 defined low-risk MM (LRMM) compared with high-risk MM (HRMM). ISS staging and GEP-defined p53 deletion did not impact OS/PFS at 12 months. Conclusions: Dose-dense strategy is highly effective in previously treated LRMM. Even though time to achieving best response was quicker in HRMM, response duration was shorter thus augmenting the significance of sustaining best response rather than depth of response in HR-MM.

Disclosures:
No relevant conflicts of interest to declare.
Prognostic Factors of Reducing Relapse in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation From Related Donor for Acute Myeloid Leukemia: The Japan Society for Hematopoietic Cell Transplantation (JSHCT) AML Working Group
Authors: Yano Shingo , Yokoyama Hiroki , Nishimura Rimei , Fukuda Takahiro , Ogawa Hiroyasu , Ohashi Kazuteru , Kanamori Heiwa , Tanaka Junji , Sakamaki Hisashi , Atsuta Yoshiko , Takami Akiyoshi 
Published: October 2019

Abstract
Abstract 3085

Background:
A llogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for patients with acute myeloid leukemia (AML), however a major obstacle to success is represented by the relapse of the disease. We retrospectively analyzed prognostic factors to determine whether there are clinical features that predict relapse after transplantation.

Patients and Methods:
Clinical data were collected from the Transplant Registry Unified Management Program (TRUMP) in Japan. An individual patient data-based analysis was performed on patients with AML who achieved or continued complete remission (CR) after related allo-HCT between 1991 and 2009. A logistic regression model was used to analyze associations between relapse and clinical factors. Patients with CR1 or CR2 were defined as having a standard-risk disease, and patients with ≤CR3 or non-CR were defined as having a high-risk disease. Conditioning regimens included ≤ 8Gy in fractionated doses of total body irradiation, busulfan dose < 9mg/kg, melphalan dose ≤ 140 mg/m2 defined as a reduced-intensity conditioning (RIC) regimen.

Results:
We analyzed a cohort of 1, 960 patients with AML. The median age at allo-HCT was 42 years (range, 16 to 74 years). Among the 1, 960 patients, 778 patients (38%) relapsed after allo-HCT. The probabilities of survival at 5-year for all patients, standard-risk patients, and high-risk patients were 49%, 61%, and 31%, respectively. In a multivariate analysis, significant factors for no relapse were standard-risk disease at the time of allo-HCT (HR 0.366, 95%CI 0.279–0.480, p<0.0001), presence of chronic GVHD (HR 0.442, 95%CI 0.338–0.579, p <0.0001), and CMV infection (HR 0.452, 95%CI 0.230–0.886, p =0.021). Intensity of conditioning regimen (RIC vs myeloablative), disease subtype of AML, HLA matching (matched donor vs mismatched donor), source of stem cells (peripheral blood vs bone marrow), and presence of acute GVHD did not affect relapse rates.

Conclusion:
These results indicate that in patients with standard-risk AML at the time of HCT, chronic GVHD or CMV infection after HCT were crucial for reducing relapse. Immune modulation mediated by chronic GVHD or CMV infection may have played a role in preventing disease relapse. The use of donor lymphocyte infusion before relapse may reduce the recurrence for selected patients who do not develop chronic GVHD.

Disclosures:
No relevant conflicts of interest to declare.
Elimination of Established Risk-Factors in Primary Central Nervous System Lymphoma - Impact of High-Dose Chemotherapy Followed by Autologous Stem-Cell Transplantaion - a Multicenter Retrospective Analysis
Authors: Schorb Elisabeth , Kasenda Benjamin , Atta Johannes , von Bubnoff Nikolas , Elter Thomas , Hess Georg , Krause Stefan W. , Morgner Anke , Stephan Kaun , Fritsch Kristina , Finke Jürgen , Illerhaus Gerald 
Published: October 2019

Abstract
Abstract 3089

Introduction:
High-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) demonstrated high efficacy in the treatment of newly-diagnosed primary CNS lymphoma (PCNSL) in eligible patients (pts). Prognosis of PCNSL is associated with several clinical and histopathological risk factors (RF). Early complete response (CR) during chemotherapy (CHT) was recently reported to be an additional independent prognostic factor in pts undergoing polychemotherapy without HDT+ASCT. In this analysis, we examined the extent to which known RF determined survival in pts who were treated with HDT-ASCT. We additionally investigated the impact of HDT-ASCT specific factors (e.g. conditioning regimen) on survival.

Pts. and Methods:
Retrospective multicenter (N=10) analysis of 100 pts with untreated PCNSL who underwent HCT-ASCT with or without whole brain radiotherapy (WBRT). We used univariate and multivariate Cox regression analysis to investigate the prognostic impact of the following factors on overall survival (OS): early CR, age, performance status, involvement of deep brain structures, and LDH serum level and thiotepa dose. Until now data of 82 pts have been analyzed.

Results:
Median age at diagnosis was 53 years (range 23–69), the majority was male (67%). After a median follow-up of 58 months median OS was reached after 121 mo (range 3–149 mo). Before HDT+ASCT, 48/82 pts (58%) did not achieve CR (35 PR, 3 SD, 10 PD). After HDT+ASCT, 54/82 pts (66%) were in CR and altogether 39% of the pts were irradiated after HDT+ASCT. Of note, of those pts with PD before HDT+ASCT, 5/10 achieved CR after HDT+ASCT without WBRT. Overall, at the time of last follow-up, 24 pts have died. Of the surviving pts, 50 were in CR (86%), 2 in PR (3%), 2 in SD, and 2 developed progression /relapse. None of the established RF (age, performance status, involvement of deep brain structures, and LDH serum level) significantly distinguished outcome with regard to OS in uni and multivariate analysis. Additionally, neither CR before HDT-ASCT, nor sex nor the dose of thiotepa (10mg versu 20mg/m2) was associated with decreased OS.

Conclusion:
We conclude that HCT+ASCT is able to neutralize established RF in PCNSL. HDT+ASCT is a high-efficient treatment option independently of remission rate before entering HDT. New prognostic factors for pts eligible for HCT-ASCT have to be identified to guide therapy and care for PCNSL pts and to define stratification criteria for future trials. Most recent follow up will be presented.

Disclosures:
No relevant conflicts of interest to declare.
Autologous Stem Cell Transplantation (ASCT) for Enteropathy-Associated T-Cell Lymphoma (EATCL): A Retrospective Study of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Jantunen Esa , Boumendil Ariane , Rambaldi Alessandro , Schapira Marc , Luan Jian Jian , Gramatzki Martin , Lenhoff Stig , Oberg Gunnar J. , Dreger Peter , Sureda Anna ,   on behalf of the Lymphoma WP of the EBMT
Published: October 2019

Abstract
Abstract 3115

Background:
EATCL is a rare subtype of peripheral T-cell lymphoma frequently observed in patients with a history of celiac disease. EATCL is characterized by poor prognosis when treated with conventional chemotherapy with only 10–20 % of long-term survivors. Limited data are available on feasibility and efficacy of stem cell transplantation in this lymphoma entity.
Patients and methods: The database of the EBMT was used to identify patients with EATCL who had received autologous and/or allogeneic stem cell transplantation in 2000–2007. All centres reporting these patients were contacted to receive confirmation to histopathology report/pathology review and to obtain information in regard to treatment prior to stem cell transplantation and more recent follow-up data.

Results:
Altogether 85 patients with EATCL were identified. Seventy-three patients had received ASCT and 12 patients allogeneic SCT. Histological report/review with additional follow-up data was available from 22 ASCT treated patients which are reported here. There were 14 females (64 %) and eight males with a median age of 55 years at the time of transplant. Half of the patients had a history of coeliac disease. The median number of treatment lines before ASCT was 1 and 50 % of the patients were in the first remission at the time of ASCT. BEAM was the most commonly used high-dose regimen (17 pts, 77 %) and all patents received blood stem cell grafts. The median time from the diagnosis to ASCT was 6 months. The median follow-up time for living patients was 45 months from ASCT. During the follow-up relapse has been observed in 13 patients (59 %), the median time was only four months from ASCT. The median disease-free survival and overall survival were nine months and 15 months, respectively. Two-year overall survival, disease-free survival, cumulative incidence of relapse and non-relase mortality (NRM) was 45%, 40%, 55% and 4%, respectively.

Conclusions:
ASCT is feasible in selected patients with EATCL with a low NRM. Of transplanted patients 40 % remained disease-free beyond 2 years. This seems to be superior when compared to historical experiences although selection factors should be taken into account. ASCT is a treatment option in transplant eligible EATCL patients who respond to initial therapy.

Disclosures:
No relevant conflicts of interest to declare.
Is There a Difference in Treatment Patterns Among Follicular Lymphoma Patients Receiving Care in the Outpatient Hospital Versus the Community Clinic Setting?
Authors: Satram-Hoang Sacha , Reyes Carolina 
Published: October 2019

Abstract
Abstract 3134

Introduction:
No studies have addressed whether the site of care involved in the treatment of patients with follicular lymphoma (FL) affects the delivery of appropriate treatment for this condition. We investigated the differences in treatment patterns between two sites of care: the outpatient hospital (OH) and the community clinic (CC) setting.

Methods:
Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort analysis of 4225 FL patients diagnosed between January 1, 1998 to December 31, 2007, >66 years, enrolled in Medicare Part A and B, and received initial treatment with rituximab (R), chemotherapy (CT), or R+CT. Chi-square test for categorical variables and ANOVA or t-test for continuous variables were used to assess differences in patient and disease related characteristics by site of care. Kaplan-Meier curves and corresponding log-rank test were used to compare time to initial treatment by site of care.

Results:
There were 3149 CC patients and 541 OH patients. The mean age was 75 years, 55% were female, and 92% were white. In general, the demographic and clinical characteristics were balanced between both sites of care, with the exception of disease stage at diagnosis where patients treated in the OH setting were more likely to be diagnosed with stage IV disease (39% vs. 34%; p<.05). Overall, 29% of patients received CT, 25% received R and 45% received R+CT. The mean time to treatment initiation was generally shorter in the CC (10 months versus 11 months) across all treatment categories (log rank p=0.1961). In the CC, the mean time to treatment initiation was 10 months for CT, 14 months for R, and 8 months for R+CT. In the OH, the mean time to treatment initiation was 12 months for CT, 16 months for R and 9 months for R+CT. Duration of treatment was similar in the CC and OH for CT and R+CT, but R had a slightly longer duration in the CC (median = 66 days) compared to the OH (median =59 days). There were more treatment cycles delivered in the CC compared to the OH. In the CC, 61% of patients received <6 cycles, 21% received 6–8 cycles and 18% received >8 cycles. In the OH, 77% received <6 cycles, 12% received 6–8 cycles and 11% received >8 cycles. Compliance with the R+CT dosing schedule (once every 3 weeks for up to 8 cycles) was higher in the CC (54%) compared to the OH (34%) cohorts (p<.0001).

Conclusions:
This observational study showed that patients treated in the OH setting tend to have longer time to treatment initiation, less cycles across all regimens, and were less likely to receive a compliant R+CT dosing schedule for FL compared to patients in the CC. These results suggest an opportunity to improve delivery of treatment to optimize outcomes in different treatment settings.

Disclosures:
Satram-Hoang: Genentech, Inc: Consultancy. Reyes:Genentech, Inc: Employment.
Anemia of Chronic Kidney Disease – Hepcidin Is a Predictor,
Authors: Gopal Srila , Madhumathi Rao , Ashby Damien R 
Published: October 2019

Abstract
Abstract 3182

Methods:
We carried out a prospective study of 167 patients with CKD stages 1 to 4 followed over a two year period. Using a competitive radioimmunoassay, we measured plasma hepcidin at baseline and studied its association to baseline clinical parameters, as well as the development of anemia and need for ESA over a two year follow up period. Exclusion criteria included any erythropoietin stimulating agent (ESA) therapy at baseline. Variables were log transformed to satisfy normality assumptions.

Results:
Median (P5-P95) Glomerular filtration rate (GFR) was 42 (20–109) ml/min and 45% were anemic at the time of enrollment by KDOQI criteria, 11 % (18/167) having severe anemia. In patients with CKD, Hepcidin was positively correlated with serum iron (Spearmans rho,p:serum iron,0.22,0.005) and negatively correlated to EPO levels (Spearmans rho,p:-0.23,0.003 vss.-0.55,0.002). Hepcidin levels at baseline were not significantly associated with GFR, hemoglobin or CRP, and did not differ according to diabetes or ethnicity. Though Hepcidin levels did not differ by the presence of anemia at baseline, they were significantly higher among patients who developed severe anemia (n=23) at the end of the first year (40 ng/mL vs. 25 ng/mL, p<0.01). A total of 13 patients initiated ESA during follow up; a 2-fold higher hepcidin was associated with a hazard ratio of 2.25 (95% CI 0.89 to 5.62) for the need to initiate ESA therapy (Fig 1), adjusted for GFR.

Conclusion:
High hepcidin, unrelated to inflammation, is a predictor for the development of anemia and the need for initiation of ESA therapy in CKD patients. The role of Hepcidin as a therapeutic target in the anemia of CKD needs further study.

Disclosures:
No relevant conflicts of interest to declare.