Reduced Intensity Conditioning Transplantation Research Articles

TSC-100 and TSC-101, TCR-T Cell Therapies That Target Residual Recipient Cells after Reduced Intensity Conditioning Transplantation, Induce Complete Donor Chimerism with Favorable Prognosis: Early Results of a Phase 1 Trial

TSC-100 and TSC-101, TCR-T Cell Therapies That Target Residual Recipient Cells after Reduced Intensity Conditioning Transplantation, Induce Complete Donor Chimerism with Favorable Prognosis: Early Results of a Phase 1 Trial

Suitability of Hemophagocytic Syndrome who had a graft rejection for repeat transplantation

Background: Hematopoietic stem cell transplantation (HSCT) is a crucial treatment for hemophagocytic lymphohistiocytosis, with reduced-intensity conditioning transplantation (RIC) being a superior strategy. Aim: Engraftment failure is a significant challenge, necessitating additional HSCT so a case study involved ten patients who experienced engraftment failure and hemophagocytic syndrome after initial HSCT. Place & duration of study: Chughtai Institute of Pathology, Lahore from March 2018 and January2023 Results: The study found that all five subjects who underwent a second allo-HSCT achieved rapid hematopoietic restoration, with ANC levels above 0.5 108 /L for granulocytes and 20 108 /L for platelets. After transplantation, three individuals experienced acute graft-versus-host disease (aGVHD) of varying severity, with a 60% prevalence and a median onset time of 26 days. Two patients managed their conditions with methylprednisolone, while two patients underwent treatment with second-line anti-GVHD medicine. Implication: A study reveals that second allogeneic hematopoietic stem cell transplantation (allo-HSCT) can restore hematopoietic tissue in failed engraftment patients, particularly those with acute Graft-Versus-Host Disease (aGVHD). Conclusion: A trial evaluating allogeneic hematopoietic stem cell transplantation (allo-HSCT) for engraftment failure in liver and heart failure patients showed a 80% success rate. Further studies are needed to predict success factors for a second allo-HSCT treatment, but the consensus is strong for its potential in treating hemophagocytic disorders. Keywords Implantation failure, hematopoietic stem cell transplantation, Second allogeneic, Hemophagocytic syndrome

Mutation Clearance of Driver Mutations after Transplantation for Myelofibrosis Predicts Outcome

Myelofibrosis is one of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) characterized by clonal myeloproliferation. Allogeneic hematopoietic stem-cell transplantation is the only potentially curative treatment for patients with myelofibrosis. With that, it can resolve fibrosis and lead to complete loss of the clonal burden. More than 90% of myelofibrosis patients harbor driver mutations in one of the 3 genes JAK2, CALR, and MPL, with JAK2 mutations being associated with worse outcomes. We herein report a study to determine whether the persistence of cells with MPN-associated driver mutations in the early period after allogeneic hematopoietic stem-cell transplantation was associated with outcomes. Patient samples for molecular analysis were prospectively collected from peripheral blood at 5 different time points: at start of conditioning prior to stem cell infusion, at days 30, 100, 180, and 1 year after transplantation. We applied quantitative PCR technology to detect individual driver mutations in JAK2, CALR, and MPL (with a high sensitivity of 0.01%). Simulation was applied to explain variances at different time points. Multivariable modelling was employed to determine independent effects. A total of 312 patients receiving first reduced-intensity conditioning transplantation were included. Distribution of driver mutation genotype at time of transplantation was as follows: 67% with JAK2, 19% with CALR, 4% with MPL, and 8% were triple-negative. Conditioning regimen comprised busulfan and fludarabine. Donor platform for transplantation was: matched related (18%), matched unrelated (58%), haploidentical (1%), and mismatched unrelated (23%). Disease risks at time of transplantation were low (1%), intermediate-1 (22%), intermediate-2 (55%), and high (22%). Median follow-up of the total cohort was 6 years. The median allele burden at time of transplantation was significantly (P<0.001) different between driver mutations: 20% (range, 0.1-100%) for JAK2, 44% (range, 3-54%) for CALR, 60% (range, 43-99%) for MPL. CALR and MPL showed earlier mutation clearance after transplantation compared with JAK2 ( Table). Mutation clearance was achieved at day 30 after transplantation in 46% with JAK2, 67% for CALR, and 30% for MPL (P=0.02). At day 100 after transplantation, 66% of JAK2, 75% of CALR, and 100% of MPL showed complete mutation clearance (P=0.09). Complete mutation clearance at day 30 after transplantation was predictive of post-transplantation relapse at 1 year (P=0.009), showing cumulative incidence of relapse of 6% versus 16%. Similar results were seen for complete mutation clearance at day 100 after transplantation, demonstrating cumulative incidence of relapse of 4% versus 24% (P<0.001). Mutation clearance at day 30 and 100 after transplantation explained 80% and 87% of variance of later time points. The effect of mutation clearance on post-transplant relapse was irrespective of driver mutation status ( Figure). 6-year disease-free survival according to mutation type was 52% for JAK2, 63% for CALR, and 80% for MPL (P=0.045). Mutation clearance at day 30 after transplantation was associated with better disease-free survival, irrespective of driver mutation status ( Figure). Moreover, day-30 complete mutation clearance predicted disease-free survival in JAK2, showing rates of 60% for negative versus 47% in JAK2 positive patients (P=0.05). Importantly, achievement of mutation clearance at day 30 after transplantation could also distinguish different risk groups in patients with onset better prognosis harboring CALR/MPL mutations. The 6-year disease-free survival was 76% for patients with mutation clearance versus 59% for CALR/MPL-positive patients(P=0.02) . Multivariate analysis (adjusting for donor type, diagnosis of primary or secondary myelofibrosis, allele burden at time of transplantation, and age) confirmed that patients who had mutation clearance at day 30 after transplantation had lower risk of relapse, better disease-free and overall survival. In conclusion, this is the first study to show that CALR and MPL are associated with earlier mutation clearance after transplantation compared with JAK2. Mutation clearance at day 30 and 100 after transplantation was the best predictor of relapse and disease-free survival, independent of driver mutation status.

ALL-RIC trial protocol: a comparison of reduced dose total body irradiation (TBI) and cyclophosphamide with fludarabine and melphalan reduced intensity conditioning in adults with acute lymphoblastic leukaemia (ALL) in complete remission

IntroductionThe usage of a T-cell depleted, reduced intensity conditioning (RIC) approach to haematopoietic cell transplantation (HCT) in adult patients with acute lymphoblastic leukaemia (ALL) over 40 years of age and...

Favorable outcomes following allogeneic transplantation in adults with hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome marked by a severe hyperinflammatory state characterized by aberrant T- and natural killer-cell activity leading to prolonged hypercytokinemia and can be rapidly fatal if not diagnosed and treated early. While upfront therapy is aimed at reducing hyperinflammation and controlling possible triggers, allogeneic hematopoietic stem cell transplantation (HSCT) is indicated for primary and relapsed/refractory cases to attain sustained remission. While this has been explored extensively in the pediatric population, there are limited data on adults undergoing HSCT for HLH. We analyzed transplant outcomes in an adult HLH population in the modern era who were transplanted at Dana-Farber Cancer Institute from 2010 onwards. Patients were uniformly transplanted on a reduced intensity platform incorporating early administration of alemtuzumab with standard infectious and graft-versus-host disease (GVHD) prophylaxis. Engraftment was documented for all patients. At 3years after transplantation, overall survival (OS) was 75% (95% confidence interval [CI], 51-89) while 3-year progression-free survival (PFS) was 71% (95% CI, 46-86). The 3-year cumulative incidence of relapse was 15% (95% CI, 3.4-33). There were no isolated HLH relapses without relapse of malignancy. The cumulative incidence of nonrelapse mortality at 3 years was 15% (95% CI, 3.5-34). Infectious complications and GVHD outcomes were comparable to standard reduced-intensity conditioning (RIC) transplantation at our institute. Mixed chimerism was common but did not correlate with transplant outcomes. Our data suggest that the immune defect in HLH can be abrogated with allogeneic transplantation using a reduced intensity regimen with early administration of alemtuzumab as preconditioning, providing a potentially curative option for this difficult disease.

Retrospective analysis of hematopoietic cell transplantation for blastic plasmacytoid dendritic cell neoplasm: conditioning intensity matters.

Blastic plasmacytoid dendritic cell neoplasia (BPDCN) is a rare myeloid malignancy with a generally poor prognosis. Although preliminary evidence suggests that hematopoietic cell transplantation (HCT) could improve outcome in patients with BPDCN, the individual contributions of conditioning and graft-versus-tumor (GVT) effects to HCT success are undefined. We present a retrospective study of 162 adult patients who underwent a first HCT (allogeneic 146, autologous 16) between 2009 and 2017, and were registered with the EBMT. Median age was 57 (range 20-73) years, and disease status at HCT was first complete remission (CR1) in 78%. Among patients receiving allogeneic HCT (alloHCT), myeloablative conditioning (MAC), reduced intensity conditioning (RIC) and in-vivo T-cell depletion (TCD) were used in 54%, 46%, and 59% respectively. Total body irradiation (TBI) was the conditioning backbone in 61% of MAC and 26% of RIC transplants. One-year overall survival (OS) and progression-free survival (PFS) rates were comparable after alloHCT and autologous HCT (autoHCT). Among alloHCT recipients, MAC with TBI significantly improved OS and PFS, independently of CR1, age, Karnofsky index and TCD. Accordingly, MAC (ideally based on TBI) should be preferred for alloHCT recipients with BPDCN. In patients who are not elegible for MAC alloHCT, autoHCT could be considered.

Multicenter Phase I Study of Post-Transplant Low-Dose Inotuzumab Ozogamicin to Prevent Relapse of Acute Lymphoblastic Leukemia

Background: The curative potential of allogeneic transplant (alloHCT) in patients with acute lymphoblastic leukemia (ALL) is hampered by relapse, the major cause of treatment failure. Risk factors for relapse include measurable residual disease (MRD) before or after alloHCT, transplantation in second complete remission (CR) or beyond, and reduced intensity conditioning (RIC) regimens. In ALL patients, relapse rates range from 30% to 50%, with most relapses occurring within the first year after alloHCT. After relapse, options for disease control are limited, and consequently overall survival (OS) is poor. Post-alloHCT maintenance may reduce MRD, provide time for a graft-versus-leukemia effect to develop, and ultimately decrease relapse rates and prolong progression-free-survival (PFS) and overall survival (OS). Inotuzumab ozogamicin (INO) is an anti-CD22 monoclonal antibody bound to calicheamicin and approved to treat relapsed ALL. With the hypothesis that low-dose INO would be safe and reduce relapse rates, we conducted a phase I study to define INO dose in this setting. Herein we present the results of this multicenter study. Methods: Eligibility included patients aged 16-75 who underwent alloHCT for CD22+ALL and were in CR after transplant, had a high risk for relapse after alloHCT (MRD before or after alloHCT, transplantation,in second CR or beyond, RIC regimen, lymphoid blast crisis of chronic myeloid leukemia, or Ph-like ALL), had adequate graft and organ function after transplant (platelets > 50 ANC > 1000), did not have active grade III/IV aGVHD or any active liver GVHD, and had no history of hepatic VOD. Patients were consented after transplant. The primary objective was to define a post-alloHCT maximum tolerated dose (MTD) of INO. Secondary objectives included describing the safety profile of INO, determining the rate of hepatic veno-occlusive disease (VOD) in this setting, evaluating non-relapse mortality (NRM), PFS and OS at 1-year post-alloHCT, and determining if INO at these doses is effective at eradicating MRD. Pre-treatment tests included a bone marrow biopsy and aspirate to assess disease state and MRD. The trial design was a 3+3 model. The study treatment consisted of 28-day cycles (initially planned for 4 cycles, increased up to 12 cycles) of INO starting at dose level 0 (0.3mg/m2; n= 4), then 0.4 mg/m2 (n= 3), 0.5 mg/m2 (n= 6) and 0.6 mg/m2 (n= 5) given on cycle day 1. The first cycle was initiated between day 40 and 100 post-alloHCT. Pre-defined dose limiting toxicities (DLT) included VOD, prolonged cytopenia (more than 28 days), severe toxicities ascribed to INO, and death. If there were no DLTs experienced in first two cycles of a cohort, subsequent patients were enrolled in the next highest dose level. Results: We have enrolled 19 patients (18 treated, Table 1) with a median follow up of 18.1 months and a median number of 3 doses (range, 1-9). Only treated patients are included in analyses. The median time to first INO dose was 84 days (range, 47-100) after alloHCT. There was one DLT (prolonged thrombocytopenia) and the study reached the final pre-defined dose of 0.6mg/m2. No VOD was observed. The most common toxicity was thrombocytopenia (42.1% of patients; 31.6% experienced grade 3 or 4 thrombocytopenia), neutropenia (31.6% of patients, 15.8% experienced grade 3 or 4 neutropenia), and nausea/vomiting (42% of patients, all grade 1 or 2). 68% of patients received reduced intensity or non-myeloablative conditioning. OS at 1-year post-alloHCT was 94.4% and PFS was 88.9%. One-year NRM was 5.5%. One patient died of aGVHD on 0.6mg/m2 and one patient relapsed on 0.5mg/m2 at 7 months post-alloHCT. Another patient relapsed from Ph-like ALL 23 months post-alloHCT. Seven of the patients enrolled either had MRD before (n = 4) or after alloHCT (n = 3) as measured by flow cytometry, PCR, or NGS. For patients with MRD before or after alloHCT, 1-year OS and PFS are 100% (Figure 1). The 1-year PFS and OS of recipients of RIC transplants was 83.3% and 91.7%. Conclusions: We have determined that INO at doses of 0.3, 0.4, 0.5 and 0.6mg/m2 was well tolerated and that 0.6 mg/m2 is the MTD. Thrombocytopenia may be the DLT. The low observed relapse rate and favorable safety profile justify investigating low-dose INO as maintenance therapy after alloHCT in a phase II trial. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Variable impact of graft CD3+ cell content on graft versus host disease in hematopoietic stem cell transplant recipients: Is the role of donor CD3+ cells overestimated?

Graft cellular composition is considered as a significant determinant of transplant outcome. Donor CD3+ cells were shown to have a significant association with the development of graft vs host disease (GvHD). The aim of this study was to investigate the impact of graft CD3+ cell content on transplant outcome, particularly in terms of GvHD and relapse. We retrospectively analysed the records of 515 allo−HCT recipients [median age: 37(15−71) years; male/female: 323/192]. The optimal threshold of infused CD3+ cell count for acute GvHD development was estimated to be 197.5 × 106/kg (AUC: 0.572; 95 % CI: 0.513−0.631; p = 0.018) and 198.5 × 106/kg (AUC: 0.6; 95 % CI: 0.520−0.679; p = 0.019) for the general population and reduced-intensity conditioning (RIC) subgroup, respectively. Acute GvHD was more frequent in low-CD3+ group in the whole study population, particularly in RIC transplants. The incidence of cytomegalovirus reactivation was higher in low-CD3+ group and neutrophil engraftment occured earlier in the same group of patients. Overall survival and non-relapse mortality were comparable between high and low-CD3+ groups. Age, ECOG performance status, hypogammaglobulinemia, chronic GvHD and post-transplant relapse were found to predict prognosis in multivariate analysis. By focusing mainly on donor T cells, the potential role of host immune cells in the early post-transplant milieu may have been underestimated. Drawing a more detailed profile of graft and host immune cells in the joint microenvironment may elucidate our way to a better understanding of GvHD pathogenesis. By this way a comprehensive pre-transplant risk assessment could be improved to generate more personalized approaches.

Impact of donor types on reduced-intensity conditioning allogeneic stem cell transplant for mature lymphoid malignancies.

We retrospectively compared the outcomes of reduced-intensity conditioning (RIC) transplantation from matched related donors (MRD; n = 266), matched unrelated donors (MUD; n = 277), and umbilical cord blood (UCB; n = 513) for mature lymphoid malignancies. The 3-year overall survival rates for the MRD, MUD, and UCB groups were 54%, 59%, and 40%, respectively (P < 0.001). Multivariate analysis showed no differences in survival between the MRD group and the MUD or UCB group. However, survival was significantly affected by the conditioning regimen and graft-versus-host disease (GVHD) prophylaxis in the UCB group, but not in the MRD and MUD groups. Notably, multivariate analysis showed that the risk of overall mortality in the UCB recipients who received the optimal conditioning regimen and GVHD prophylaxis (n = 116) was lower than that in the MRD group (relative risk [RR], 0.69; P = 0.03) and tended to be lower than that in the MUD group (RR, 0.75; P = 0.09). Our results suggest that UCB transplantation performed with the optimal conditioning regimen and GVHD prophylaxis is highly effective. Moreover, UCB is readily available. Thus, UCB transplantation with the optimal conditioning regimen and GVHD prophylaxis is preferable to MUD transplantation when MRD are not available in the setting of RIC transplantation for mature lymphoid malignancies.

Reduced Intensity Stem Cell Transplantation Followed By Adjunctive Lenalidomide Is Tolerable and Safe and Improves Complete Response Rate in Multiple Myeloma:a UK NCRI Phase 2 Feasibility Study (LenaRIC)

BackgroundThe role of allogeneic stem cell transplantation in the management of myeloma remains uncertain as it is a procedure with significant mortality and low long term rates of disease control. We sought to evaluate the feasibility of using adjunctive Lenalidomide (Revlimid®) to augment long term myeloma response following Reduced-Intensity Conditioned (RIC) allograft in the UK NCRI trial LenaRIC (Lenalidomide in Reduced Intensity Conditioned Transplant)-ISRCTN:16228367.Material & MethodsForty (40) patients were recruited in this single arm phase II trial at ten UK stem cell transplant centres from June 2011-June 2015. All patients were in CR/VGPR 1 or 2 and had undergone a Melphalan conditioned autologous transplant in the previous 6 months. They then underwent a RIC allograft using Fludarabine & 2Gy TBI with ATG (Fresenius) as in vivo T-cell depletion (planned tandem SCT programme). Patients were scheduled to receive Lenalidomide (10mg until 2013, reduced to 5mg thereafter on DMEC advice) from day +35 if stable donor engraftment was present in the absence of GvHD. Lenalidomide was planned to be discontinued 12 months post-transplant with donor lymphocyte infusions given to patients with evidence of residual disease, relapse or mixed chimerism.ResultsOf the thirty nine(39) patients transplanted within 42 days of study entry, 8 were in CR1, 16 in VGPR1, 7 in CR2 and 8 in VGPR2. The median age was 49 years (range 35-65) with peripheral blood as the graft source in the 39 patients, from either sibling (n=16) or 10/10 matched unrelated donor (n=23). 1 patient failed to proceed to transplant. Of thirty four (34) evaluable patients, 28 (82.4%) achieved full donor T-cell chimerism and 32 (94.1%) full donor in whole blood. 34 patients completed at least one cycle of Lenalidomide. Mean number of cycles received was 7.4 (range 1-12, median 9.0). Mean dose was 5.2mg, median 5mg. 16 patients completed at least 10 cycles and 5 patients completed 12 cycles as per protocol treatment; of those completing >= 10 cycles, 5/16 received DLI.Safety dataThere were eight (8) patients who had biopsy-proven aGVHD (4 of grade 1-2 and 4 of grade 3- all 4 within 3 cycles of Lenalidomide) and 3 patients with cGVHD (2 extensive and 1 limited). No Grade 3/4 aGVHD was seen following DMEC advice to reduce the Lenalidomide dose to 5mg daily. 8 patients experienced grade 3 or 4 non-Haem toxicity. The majority of AEs were grade 1-2. Significant (Grade 3/4) non-Haem SAEs in this transplant population included Gastro-intestinal (4 patients), metabolism (4 patients), infection (13 patients) and vascular (4 patients). One year relapse-free survival was 84.3%.Clinical OutcomesEfficacy was assessed at a median follow-up of 445 days. The pre-transplant CR rate of 38.4% was improved to 67.6% at best response post-transplant. PFS at 2 years was 43.1% (figure 1a), OS at years 75.7% with a 2 year disease-free survival of 59.1% (figure 1b). Of the 10 patients who have died, 6 have been recorded as disease-related.Conclusions1) Based on the pre-defined safety stopping rules, the LenaRIC study shows that post-graft Lenalidomide is safe and tolerated in a T-depleted RIC setting at a dose of 5mg daily- this results in a tolerable AE profile with an acceptable GVHD rate.2) Acute GVHD only occurred in the first 3 cycles of exposure to Lenalidomide- consideration should be given to examining the longer term use of Lenalidomide beyond 12 months following a T-depleted RIC allograft to augment long term outcomes3) CR rates were nearly doubled by this approach4) Further work correlating Lenalidomide exposure with clinical events and immune reconstitution is ongoing.An unrestricted educational grant was provided to support the trial & adjunctive science by Cancer Research UK and by Celgene. Lenalidomide provided free of charge by Celgene. Lenograstim provided free of charge by Chugai. The support and time of participating patients and their families is gratefully acknowledged. [Display omitted] DisclosuresCook:Janssen: Honoraria, Other: Travel support, Research Funding; Amgen: Honoraria, Other: Travel support; Takeda: Honoraria; Myeloma UK: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Travel support, Research Funding; Jazz Pharmaceuticals: Honoraria. Brock:Merck: Other: travel expenses; Roche: Honoraria, Other: travel expenses; GlaxoSmithKline: Equity Ownership; Astra-Zeneca: Equity Ownership. Snowden:Sanofi: Honoraria. Hunter:Celgene: Other: Travel Support. Cavenagh:Takeda: Consultancy; Novartis: Consultancy; Janssen: Honoraria; Celgene: Consultancy. Cook:BMS: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Use of Busulfan in Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation in Adults: A Survey By the Complications and Quality of Life Working Party of the EBMT

Background : With the introduction of an intravenous formulation, options for the administration of busulfan in conditioning for allogeneic hematopoietic stem cell transplantation have increased. Practical issues in which the policies of transplant centers are likely to vary include the route of administration, number of daily doses, and the use of pharmacokinetic (PK) measurements for dose adjustment. Following the general policy of the European Society for Blood and Marrow Transplantation (EBMT) to aim at standardizing transplantation procedures, the Complications and Quality of Life Working Party has carried out a survey among EBMT centers about their practice in the use of busulfan for conditioning in allogeneic transplantation.Results : All allogeneic transplant centers reporting to the EBMT and treating adult patients were invited to participate. One hundred and nine centers (28 %) sent their report. One hundred and five of these centers used busulfan for conditioning, 4 did not. One hundred and one centers used it in full conventional doses, 92 centers in lower doses for reduced intensity conditioning (RIC). The oral dose in conventional conditioning was 16 mg/kg, the intravenous dose usually 12.8 mg/kg. Six centers determined the dose according to body surface area. The most common indications for conventional dose myeloablative conditioning were AML (99 centers), MDS (87), CML (75), ALL (56), lymphoma (26), thalassemia and other hemoglobinopathies (22), CLL (17), and myeloproliferative disorders (MPD, 6 centers). Lower doses of busulfan (RIC) were most commonly used for MDS (69 centers), AML (66), CML (49), ALL (37), lymphoma (36), CLL (31), and MPD (11 centers). The busulfan dose in RIC conditioning was usually 8 mg/kg in oral administration, in i.v. administration most often (66% of the centers) 6.4 mg/kg. Four centers determined the dose according to body surface area. Eleven centers gave full conventional dose busulfan orally and 94 i.v., while in RIC transplantations the drug was given orally in 10 and i.v. in 77 centers. Overall, 17 of the 105 centers used PK measurements to adjust busulfan doses. Busulfan concentration was measured using liquid chromatography (+ mass spectrometry in 8 centers). With one exception, the parameter used for dose adjustment was AUC. The details of the sampling for PK measurements as well as the method of AUC calculation varied. There was no difference between centers giving oral and those giving i.v. busulfan in the use of PK for dose adjustment, in full dose conditioning 2/11 vs. 14/94 centers, respectively. In RIC transplantations, PK-based dose adjustment was used in 1/10 centers giving oral busulfan and 8/77 using i.v. busulfan. The centers using oral busulfan or those adjusting the doses according to PK did not differ significantly from the rest of the centers in center experience, transplant numbers, JACIE accreditation, or gross national income of their country.Full conventional doses were always given in 4 days. Oral busulfan was given in 4 daily doses with one exception (2 doses). In i.v. administration, the number of daily doses was one in 46 centers, four in 42 centers, and two in 4 centers. In RIC conditioning, busulfan was in most cases given in 2 days, i.v. busulfan usually in one (35 centers) or four (28 centers) daily doses. Twenty-seven centers reported having alternative busulfan administration schedules depending on the disease, 20 centers depending on other components of the conditioning regimen. In myeloablative conditioning, 73 centers adjusted the dose of busulfan in obese patients, whereas 25 centers did not. Thirty-two centers reported defining obesity based on body mass index, whereas 28 centers used actual body weight in relation to ideal body weight. In obese patients, the busulfan dose was determined according to actual body weight (12 centers), ideal body weight (15), AIBW-25 (ideal body weight + 0.25 x (actual body weight - ideal body weight)) (46), AIBW-40 (10), or other (11 centers). In RIC, busulfan doses were adjusted because of obesity in 52 centers but not in 32 centers.Conclusions : There is marked variation between centers in the details of busulfan administration for conditioning in allogeneic transplantation. The clinical impact of this variation remains uncertain. The present results are useful in the production of recommendations toward a more standardized use of busulfan in the conditioning. DisclosuresMohty:Sanofi: Honoraria, Speakers Bureau.

3 - A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

3 - A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

A Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplantation to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Advanced Myelodysplastic Syndrome: Blood and Marrow Transplant Clinical Trials Network Study 1102

Reduced-intensity single-unit unrelated cord blood transplant with optional immune boost for nonmalignant disorders

AbstractChildren with many inherited nonmalignant disorders can be cured or their condition alleviated by hematopoietic stem cell transplantation (HSCT). Umbilical cord blood (UCB) units are a rapidly available stem cell source and offer great flexibility in HLA matching, allowing nearly uniform access to HSCT. Although reduced-intensity conditioning (RIC) regimens promise decreased treatment-related morbidity and mortality, graft failure and infections have limited their use in chemotherapy-naive patients. We prospectively evaluated a novel RIC regimen of alemtuzumab, hydroxyurea, fludarabine, melphalan, and thiotepa with a single-unit UCB graft in 44 consecutive patients with inborn errors of metabolism, immunity, or hematopoiesis. In addition, 5% of the UCB graft was re-cryopreserved and reserved for cord donor leukocyte infusion (cDLI) posttransplant. All patients engrafted at a median of 15 days posttransplant, and chimerism was >90% donor in the majority of patients at 1-year posttransplant with only 1 secondary graft failure. The incidence of grade II to IV graft-versus-host disease (GVHD) was 27% (95% confidence interval [CI], 17-43) with no extensive chronic GVHD. Overall survival was 95% (95% CI, 83-99) and 85% (95% CI, 64-93) at 1 and 5 years posttransplant, respectively. No significant end-organ toxicities were observed. The use of cDLI did not affect GVHD and showed signals of efficacy for infection control or donor chimerism. This RIC transplant regimen using single-unit UCB graft resulted in outstanding survival and remarkably low rates of graft failure. Implementation of the protocol not requiring pharmacokinetic monitoring would be feasible and applicable worldwide for children with inherited disorders of metabolism, immunity, or hematopoiesis. This trial was registered at www.clinicaltrials.gov as #NCT01962415.

Absence of influence of peripheral blood CD34+ and CD3+ graft cell counts on outcomes after reduced-intensity conditioning transplantation using post-transplant cyclophosphamide

The influence of peripheral blood stem cell (PBSC) graft cell contents after transplant with post-transplant cyclophosphamide (PTCY) remains unclear. Here, we retrospectively report on a cohort of 77 adults who received a Baltimore-based reduced-intensity conditioning regimen either with fludarabine (n = 40) or clofarabine (n = 37) and PTCY. With a median follow-up of 29.2months, [2-]year overall (OS), disease-free (DFS), and GVHD/relapse-free survival (GRFS) rates were 62.8%, 51%, and 36.7%, respectively. The incidence of grades [2-]4 acute GVHD was significantly higher in patients transplanted with a haplodonor (n = 56), at 57.1% vs 19% (p = 0.006). PBSC graft cell contents (CD45+, CD34+, and CD3+ cells) had no impact on any outcome. Considering immune reconstitution until 1year, only monocytes were above the normal range (as early as day + 30) during the first year post-transplant. In multivariate analysis, an older donor (> 45years) and a high/very high disease risk index were independently associated with lower OS. A higher monocyte count (> median) at day + 90 was also associated with better OS, DFS, and GRFS. Donor/recipient CMV status matching was independently associated with GRFS. In conclusion, our data support the fact that there is no need to manipulate the graft before infusion in the particular context of PBSC/PTCY Baltimore-based allotransplant.

Comparison of Myeloablative (CyTBI, BuCy) Versus Reduced-Intensity (FluBu2TBI400) Peripheral Blood Stem Cell Transplantation in Acute Myeloid Leukemia Patients with Low WT1 Expression Level at Transplant

Introduction: Recent data emerges that transplantation with reduced intensity conditioning (RIC) seems to be effective as myeloablative conditioning (MAC). However, relapse is a major concern with RIC, and identification of patients at equivalent probability of relapse irrespective of conditioning intensity is needed. Method: A total of 567 AML patients underwent allogeneic hematopoietic stem cell transplantation (HSCT) betwene June 2012 and Jan 2018. For this study, we selected 287 patients who fulfilled i) intermediate or poor risk group by NCCN (2017.Version 3), ii) CR or CRi at HSCT, iii) received either MAC (BuCy or CyTBI) or RIC (FluBu2TBI400) peripheral blood stem cell transplant from 8/8 matched sibling donor (MSD) or matched unrelated donor (MUD), and iv) having bone marrow Wilms tumor gene 1 (WT1) expression results before transplant. The association between conditioning intensity, WT1 level at HSCT and post-transplant clinical outcomes involving overall survival (OS), disease free survival (DFS), cumulative incidence of relapse (CIR) and nonrelapse mortality (NRM) were evaluated first. And then we attempted to compare post-tranpslant outcomes between MAC and RIC groups in pre-transplant WT1low patients only. Results: Among the total 287 patients, 232 (80.8%) and 55 (19.2%) patients received MAC and RIC transplant. The median WT1 gene expression level at diagnosis (assessable in 255 patients) was 2310.0 copies/104ABL. When ≥ 250 copies/104ABL were classified as high expression of WT1 (WT1high), 77.3% (n=197) showed WT1high at AML diagnosis. In multivariate analysis, older age and WT1high before HSCT were designated as independent prognostic factor for inferior OS, DFS and higher CIR, and NCCN risk group at diagnosis was significantly associated with incidence of relapse; whereas, conditioning intensity or WT1 level at diagnosis were not prognostic for post transplant outcomes. After excluding patients without available information on initial WT1 level (n=32), whose WT1 levels were not overexpressed at diagnosis (n=58), and whose WT1 level ≥ 250 copies before transplant (n=45), we finally selected 152 pre-trasnplant WT1low patients for further analysis. Older age was still a significant independent factor for poor OS, DFS and higher NRM, whereas NCCN risk stratification at diagnosis was no longer prognostic for post-transplant outcomes in pre-trasnplant WT1low patients only. There was no significant difference in these outcomes between MAC (n=123) and RIC (n=29) patients, and pre-HSCT WT1 level as continuous variable remain significant for predicting relapse even if the level was below 250 copies. Conclusion: Post-transplant survival or relapse did not differ by conditioning intensity in AML CR1 patients whose WT1 level was below 250 copies per 104 ABL at transplant. Figure Disclosures Kim: BMS: Research Funding; Pfizer: Research Funding; Il-Yang co.: Research Funding; Novartis: Research Funding; Takeda: Research Funding. Lee:Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Achillion: Research Funding. Kim:Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL &amp; H: Research Funding.

Non-Myeloablative Allogeneic Stem Cell Transplant in Acute Myeloid Leukemia: Graft-Versus-Host Disease Potentiates Graft-Versus-Leukemia Effect and Improves Overall Survival

Introduction: Non-myeloablative conditioning regimens enable elderly and younger patients with significant comorbidities to undergo allogenic stem cell transplant (allo SCT). These regimens allow for the benefit of graft-versus-leukemia (GVL) effect with reduced toxicity. A retrospective analysis of 94 patients with acute myeloid leukemia (AML) who received a non-myeloablative transplant with fludarabine (25 mg/m2 days -7 through -3)/cyclophosphamide (1000 mg/m2 days -7 and -6) (Flu/Cy) conditioning was conducted to evaluate patient outcomes. Methods: Ninety-four patients with AML underwent non-myeloablative allo SCT with Flu/Cy conditioning at Penn State Cancer Institute between 2007 and 2015 were retrospectively analyzed. The patients were deemed ineligible for myeloablative or reduced intensity conditioning transplants due to advanced age or significant comorbidities. Most unrelated donor patients (n=69) received tacrolimus/sirolimus/methotrexate as graft-versus-host disease (GVHD) prophylaxis. Overall survival (OS) and disease-free survival (DFS) were assessed with Kaplan-Meier survival curves and log rank tests, and non-relapse mortality (NRM) and relapse rates (RR) were assessed with cumulative incidence of competing events and Gray test. Cox proportional hazard regression with stepwise selection was used for multivariate analysis. Results: Patients with AML underwent Flu/Cy conditioning for allo SCT from either a matched related donor (MRD) (n =16), matched unrelated donor (MUD) (n=54), or mismatched unrelated donor (MMUD) (n=24). Evaluation of AML status immediately prior to allo SCT identified 79 patients in complete remission, 10 patients with non-remission, and 5 patients with primary induction failure. There were 11 patients with hematopoietic cell transplantation specific comorbidity index (HCT-CI): 0, 14 patients with HCT-CI: 1-2, and 69 patients with HCT-CI: ≥3. Post-transplant analysis identified: 48 patients with grade 0, 31 patients with grade I, and 15 patients with grade II-IV acute graft-versus-host disease (aGVHD). Furthermore, 52 patients were without chronic GVHD (cGVHD), 15 experienced limited cGVHD, and 13 experienced extensive cGVHD. One-year OS and DFS were 41.3% (95% CI: 31.3-51%) and 27.7% (95% CI: 18.7-37.4%), respectively. One-year NRM and RR were 12.9% (95% CI: 0.68-21%) and 59.5% (95% CI: 48.2-69.1%). There were no statistically significant differences in NRM between patients with varying comorbidity indices. One-year OS for patients in complete remission versus non-remission prior to transplant was 45.3% versus 20.0% (p&lt;0.01), and was significantly greater in patients with grade I versus grade II-IV aGVHD (45.2% versus 17.8%, p&lt;0.05). Patients with cGVHD showed a lower RR compared to patients without cGVHD (1-year RR 20.4% vs 48.5%, p&lt;0.05). Patients who achieve a chimerism ≥90% within 100 days of transplant achieved a better OS and lower RR compared to patients with a chimerism &lt;90% (1-year OS 51.3% versus 21.4%, p&lt;0.01; 1-year RR 44.0% vs 89.3%, p&lt;0.01, respectively). Multivariate analysis identified grade I aGVHD (versus grade II-IV, p&lt;0.01), cGVHD (versus no cGVHD, p&lt;0.05), and chimerism ≥90% (versus &lt;90%, p&lt;0.05) as independent factors for improved OS. Conclusions: The primary endpoint for this retrospective analysis was OS following non-myeloablative allo SCT for AML utilizing Flu/Cy conditioning. Although RR was high (59.5%), this conditioning regimen resulted in rapid stem cell recovery and low NRM. There were no significant differences in NRM between patients with lower (0, or 1-2) and higher (≥3) HCT-CI and patients receiving MRD, MUD or MMUD. This confirms that Flu/Cy conditioning is safe, especially for patients with multiple comorbidities and receiving MMUD. This analysis also identified a significant improvement in OS for patients with grade I as compared to grade II-IV aGVHD. Also, patients with cGVHD showed a significantly reduced RR. Collectively, the improved survival for patients with grade I aGVHD and cGVHD may be associated with a more robust GVL effect. Additionally, patients who achieve a higher chimerism showed a reduced RR. This study highlights the tolerability of Flu/Cy and the importance of balancing GVHD and GVL effects; future studies are needed to evaluate the addition of maintenance therapies to overcome higher RR occurring with this regimen. Disclosures Naik: Celgene: Other: Advisory board. Zheng:Pfizer: Research Funding. Claxton:Daiichi Sankyo Co. and Ambit Biosciences Corp, Astellas Pharma, Novartis Pharmaceuticals, Incyte Corporation, Cyclacel Pharmaceuticals, Inc, Celegene Corporation, Medimmune, Inc, Merck Sharp &amp; Dohme Corp., Gilead Sciences, Inc.: Research Funding.

PB2331 IMPACT OF PRETRANSPLANT CHEMOTHERAPY, GRAFT VERSUS HOST DISEASE PROPHYLAXIS, GENDER AND RISK GROUP ON ALLOGENEIC REDUCED INTENSITY CONDITIONING TRANSPLANTS FOR ELDERLY ACUTE MYELOID LEUKEMIA PATIENTS

Background:Allogeneic reduced intensity conditioning transplant (RICT) has become an accepted treatment modality for patients (pts) age ≥50 years with acute myeloid leukemia (AML). Reports on patient and transplant related factors that may influence outcome in this population are rare.Aims:To analyze the possible impact of number of chemotherapy courses, recipient gender, choice of graft versus host disease (GVHD) prophylaxis and disease risk on the outcome of elderly pts with AML in CR1 receiving an allogeneic RICT.Methods:Patients were allografted from a matched sibling donor (MSD) as part of a multinational, prospective, controlled study (NCT00342316) which aimed to compare RICT and chemotherapy in an elderly population. Patients with a median age of 63 years (yrs) (52‐70) were transplanted between 2004 and 2015. Fifty‐eight pts (29 females, 29 males) were allografted using a RICT regimen: fludarabine (150‐180 mg/m2) and busulfan (8 mg/kg orally or 6.4 mg/kg iv.) in 93%. Peripheral blood stem cells were given in 54 pts (93%). Median follow up was 36 months (2‐149). Prespecified high risk criteria were poor risk cytogenetics, secondary or therapy related AML, or blasts ≥15% after induction 1.Results:Overall survival (OS) at study termination was 36%. Twenty‐four (41%) pts relapsed. Acute GVHD grade 2 to 4 was noted in 28%, chronic extensive GVHD in 36%.Twenty‐one pts (36%) received up to 2 chemotherapy courses prior to transplant and 36 (62%) received more than 2 courses. Data was missing in 1 patient. These groups were well balanced with respect to age (63 years in both groups), gender and risk category. Neither OS, 38% versus 36%, nor relapse rate (RR), 38% versus 42% were significantly different.Data on GVHD prophylaxis was available on 57 pts, the two main immunosuppressive treatments were cyclosporine/methotrexate given to 29 pts, whereas 20 pts received cyclosporine/MMF based regimens. Age, gender, risk group distribution, number of chemotherapy regimens and performance status prior to transplant were not different in these two groups. OS was 38% versus 40% (not significant). There was no difference in either RR or acute or chronic GVHD between these two groups.Twenty‐nine of 58 (50%) pts were female. Median age of females was 62 yrs, of males 63 yrs (p = 0.275). There were no differences regarding disease risk between female and male groups, or between numbers of chemotherapy regimens. OS of female patients was 45% versus 28% in male patients (p = 0.17).Thirty‐eight pts were considered intermediate and 20 high risk. Median age was slightly higher in the high risk group, 64 vs 61 yrs (p = 0.042), and high‐risk pts received a higher number of chemotherapy courses. There was a trend to better OS in the intermediate risk group compared with the high risk group, 45% versus 20%, respectively (p = 0.087). RR was 34 versus 55%, which did not reach statistical significance.Summary/Conclusion:In our cohort of elderly patients with AML in CR1 receiving a RICT transplant from related donors, the number of pretransplant chemotherapy regimens, choice of graft versus host disease prophylaxis, patients gender, and comparison of high versus intermediate risk groups did not appear to impact on OS. Relapse rates in all patient groups were high, possibly masking any survival difference between the groups.

PTCy-based haploidentical vs matched related or unrelated donor reduced-intensity conditioning transplant for DLBCL

AbstractThis study retrospectively compared long-term outcomes of nonmyeloablative/reduced intensity conditioning (NMC/RIC) allogeneic hematopoietic cell transplantation (allo-HCT) from a haploidentical family donor (haplo-HCT) using posttransplant cyclophosphamide (PTCy) with those of matched sibling donor (MSD) and matched unrelated donor (MUD) with or without T-cell depletion (TCD+/TCD−) in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Adult patients with DLBCL who had undergone their first NMC/RIC allo-HCT between 2008 and 2015 were included. Recipients of haplo-HCT were limited to those receiving graft-versus-host disease (GVHD) prophylaxis with PTCy. GVHD prophylaxis in MSD was limited to calcineurin inhibitor (CNI)–based approaches without in vivo TCD, while MUD recipients received CNI-based prophylaxis with or without TCD. Outcome analyses for overall survival (OS) and progression-free survival (PFS), nonrelapse mortality (NRM), and disease relapse/progression were calculated. A total of 1438 patients (haplo, 132; MSD, 525; MUD TCD+, 403; and MUD TCD−, 378) were included. Patients with haplo donors were significantly older, had a better performance status and had more frequently received total body irradiation-based conditioning regimens and bone marrow grafts than MSD and MUD TCD+ or TCD−. 3-year OS, PFS, NRM and relapse/progression incidence after haplo-HCT was 46%, 38%, 22%, and 41%, respectively, and not significantly different from outcomes of matched donor transplants on multivariate analyses. Haplo-HCT was associated with a lower cumulative incidence of chronic GVHD compared with MSD, MUD TCD+/TCD−. NMC/RIC haplo-HCT with PTCy seems to be a valuable alternative for patients with DLBCL considered for allo-HCT but lacking a matched donor.

Reduced Intensity Conditioned Sibling Transplantation Versus No Transplant in Intermediate or High Risk Acute Myeloid Leukemia: A Prospective Multi-Center Study in Patients 50-70 Years in First Complete Remission and with at Least One Potential Sibling Donor (ClinTrialGov 00342316)

▪Background and study design. Reduced intensity conditioning transplantation (RICT) is a commonly applied treatment option for AML patients >50 years of age. Prospective, controlled studies comparing RICT with standard chemotherapy are warranted. In this study, we aimed to prevent selection biases. Thus, patients were included prior to HLA typing of potential sibling donors, and statistical analyses were based on an intention-to-transplant, donor versus no-donor approach. Hence, the analyses also include events occurring during the donor search period and also the transplantation procedures along with post-transplant events.Patients and procedures. Between 2003 and 2016, 163 patients with AML in CR1 were included in Canada (n=69), Sweden (n=63), and Germany/Finland/Norway/New Zealand (n=31). Eighteen patients were excluded due to enrolment after the start of donor typing (n=14), lack of data (n=1), low-risk AML (n=2) or withdrawn consent (n=1). Thus, results from 145 patients with high (n=48) or intermediate (n=97) risk disease were available for analysis. Included patients were a median of 63 (50-70) years old, deemed fit for RICT and had at least one willing and healthy but not yet HLA typed sibling. The ensuing HLA typings thus yielded one RICT group including patients with ≥1 confirmed matched sibling donor (MSD), and one control group with no MSD. Date of inclusion was defined as date of HLA typing of the first potential MSD. The protocol-specified conditioning regimen for RICT was fludarabine (150-180 mg/m2) and busulfan (8 mg/kg orally or 6.4 mg/kg i.v., used in 95% of patients). Immunosuppression was ciclosporin alone (9%), with methotrexate (53%) or with MMF (35%). Peripheral blood stem cells were used in 95% of transplantations. Control patients received consolidation chemotherapy as per local routines.Statistics. Baseline factors were compared between study groups using Fisher´s exact test and rank sum tests. The primary endpoint was overall survival (OS) with secondary endpoints of relapse-free survival (RFS), relapse incidence (RI) and non-relapse mortality (NRM). Kaplan-Meier curves were used to estimate OS and RFS and cumulative incidence functions were used to estimate NRM and RI considering competing risks. The logrank test was employed for group comparisons of event rates with time censored at 5 yrs post inclusion.Results. The median follow-up time of surviving patients was 7.9 (0.24-14) yrs. Age, AML risk group and time from CR to inclusion did not differ between the study groups.Time lag from diagnosis to study inclusion was 65 (32-256) days (Controls) and 64 (29-319) days (RICT), P=0.74, Mann-Whitney test. Time from CR1 to inclusion was 22 (0-218) days (Controls) and 19 (0-131) (RICT).Excluding conditioning, patients in the RICT group received fewer chemotherapy cycles than controls. The time from start of last chemotherapy to transplant was median 63 (36-212) days. The incidence of acute (grade 2-4) and chronic extensive GvHD in transplanted patients was 25% and 39%, respectively.The non-relapse mortality at 3 years post inclusion (Table) was 12% (RICT group) and 4% (Controls). Causes of death was primarily AML, accounting for 73% and 88% of all deaths in the RICT and control groups, respectively. Twenty pts with an identified donor did not reach RICT due to relapse (n=12), co-morbidities (n=5), death (n=2), other (n=1).Total mortality at time of analysis was slightly lower in the RICT group (66% vs 75%). Overall survival (primary endpoint) at 3 years was 45% (CI 33-56) and 48% (36-60), in RICT and control groups, respectively. At 10 years after inclusion, OS in study groups were similar; RICT 27% (CI 15-41), Control 25% (CI 15-36). There were no significant differences between study groups with respect to primary or secondary endpoints (OS: P=0.27, RFS:P=0.98, RI: P=0.50, NRM: P=0.10, logrank tests. Figure).Conclusions. Applying an intention-to-treat analysis we did not demonstrate clinical benefit of sibling donor search and stem cell transplantation after a reduced intensity busulfan/fludarabine based regimen in AML patients ≥50 years in CR1. Early relapse was the main reason for preventing transplants in patients with an identified donor.Support from study groups: Canadian BMT Group, Australasian Leukaemia and Lymphoma Group, Norwegian/Swedish BMT Group, Swedish AML group [Display omitted] DisclosuresKiss:Alexion: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Wallhult:Jazz Pharmaceuticals: Speakers Bureau; Amgen: Speakers Bureau; Daichii-Sankyo: Speakers Bureau. Finke:Riemser: Consultancy, Honoraria, Research Funding; Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding. Sabloff:Celgene: Membership on an entity's Board of Directors or advisory committees.