Time Of allo-SCT Research Articles

Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought?

Isolated Trisomy 11 in Patients with Myeloid Malignancies - Is the Prognosis Not As Grim As Previously Thought?

Contemporary Outcomes in HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: Single-Institution Experience

Contemporary Outcomes in HTLV-1-Associated Adult T-Cell Leukemia/Lymphoma: Single-Institution Experience

Is There Any Impact of Uric Acid Levels during the Peri-Transplant Period on Acute Graft Vs. Host Disease Incidence and Allotransplant Outcome?

Background: Damage associated molecular patterns (DAMPs) are considered important contributors to acute Graft vs Host Disease (aGvHD) pathogenesis. Uric acid (UA), a DAMPs family molecule, upon its release from damaged tissues post high dose chemo/radio therapy, triggers activation of donor derived T-cells. Currently, only two published studies evaluated the association between UA levels at day 0 and aGvHD occurrence, with totally conflicting results. Given that aGvHD is a dynamic process which takes place during the whole early post-transplant period, contrasting to previous studies, we evaluated serum UA levels not only once but in 4 different time points during the early transplant period, at days -7, 0, +7, +14, and investigated its correlation to aGvHD incidence, non-relapse mortality (NRM) and survival rates. Methods: We retrospectively evaluated 57 patients (pts), with a median age of 36.8 years (range, 17-62), who underwent allogeneic stem cell transplantation (alloSCT) from full matched sibling donors for malignant (n=48) or non-malignant (very severe aplastic anemia =9) hematological diseases. A median of 5.6 x106/kg CD34+ cells were infused after a myeloablative (n=34) or reduced intensity (n=23) regimen. At the time of alloSCT, 42 pts were in remission (CR1: 30, CR2: 10, >CR2: 2). All pts received either allopurinol or rasburicase from the day of conditioning initiation till day -1. The ROC-curve method, t-test, Kaplan-Meir method, and log-rank test were used for the univariate while the binary logistic regression method for the multivariate statistical analysis. Disease phase [early (CR1) vs. intermediate (CR2) and advanced (>CR2 or presence of residual disease)], donor gender, patient and donor age, UA levels at day -7, 0, +7, +14, type of conditioning regimens and number of infused CD34+ cells were tested as possible factors that can affect aGvHD incidence. Results: Median UA levels were 3.2, 2.4, 2.2 and 2.9 mg/dl at days -7, 0, +7 and +14 respectively; using the ROC curve method the cutoff point was determined at 4.4 mg/dl for day -7 and 2.2 mg/dl for days 0, +7 and +14. Overall, 20/57 (35%) pts developed aGvHD; 18 (31%) were assessed as gr ≥II, while 10 (17%) as gr III-IV. The incidence of the aGvHD gr ≥II was higher for pts with UA levels ≤ 4.4 mg/dl at day -7 (14 vs 4) and for pts with UA levels ≥2.2 mg/dl at days 0 (12 vs. 6 pts) and +14 (13 vs. 5 pts) however these differences did not reach statistical significance. UA levels at +7 day had no impact on aGvHD incidence. In multivariate analysis, only the number of CD34+ >6x106/kg was an adverse factor for aGVHD gr≥II (p=0.04) while intermediate & advanced disease phase along with a number of CD34+ cells >6x106/kg, proved to be significant contributors for severe aGvHD (gr III-IV) occurrence (p<0.03). We observed a better 4 years overall survival for patients with UA levels < 2.2 mg/dl at day +14 (85% vs. 55%, p=0.06). Fifteen pts succumbed to NRM causes; 8/15 deaths were attributed to aGvHD complications. The NRM was higher in patients who had UA levels ≥2.2 mg/dl at day +14 (32% vs. 15%) though this difference was not significant (p=0.2). Conclusions: The present study bears the limitations of a small series of pts and it's retrospective nature. However, it has the advantage of evaluation of UA levels, as an aGvHD mediator, at multiple time points during the peri-transplant period. Our results, though not of strong statistical significance, demonstrated that UA levels might affect aGvHD incidence as well as survival and the NRM rates post alloSCT. Definitely, well designed prospective clinical trials are warranted to clarify the role of UA on alloSCT outcome. Disclosures No relevant conflicts of interest to declare.

Allogeneic hematopoietic stem cell transplantation in patients with multiple myeloma. Impact of disease characteristics, disease status at transplant, and prior number of lines of therapy. Results of retrospective, multicentre Spanish study.

Despite several recent therapeutic advances, multiple myeloma (MM) is still considered an incurable disease. Allogenic transplantation (allo-SCT) is a potential curative treatment for these patients. However, the high morbidity and mortality associated with the procedure makes necessary to identify which are the best candidates and the most adequate timing to perform it. Aim: To analyze the impact of disease characteristics at diagnosis and at the time of allo-SCT in overall survival (OS) and progression-free survival (PFS) in patients with MM treated with proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiDs).

The Role of Anti-Thymocyte Globulin (ATG) in Patients with AML Transplanted in CR1 from Sibling and Unrelated Donors with or without Measurable Residual Disease (MRD) at the Time of Allogeneic Stem Cell Transplantation:a Study on Behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Background Measurable residual disease (MRD) status pre- transplantation (alloSCT) predicts transplant outcome. Nonetheless, the impact of MRD persistence (MRD+) might be modulated by the use of anti thymocyte globulin (ATG) to prevent graft versus host disease (GVHD). Since GVHD is usually associated with the graft versus leukemia effect (GVL), there is a concern that ATG may increase relapse incidence (RI) in patients (pts) with a higher risk of relapse. We therefore investigated whether MRD status pre-alloSCT could impact the outcome in AML patients receiving alloSCT with ATG in CR1. Methods Study included adult AML pts undergoing alloSCT in CR1 during 2005-2016 period. First, we assessed the impact of MRD status, cytogenetics, FLT3-ITD and ATG in the whole population. Then, we studied the impact of ATG in relation to the MRD status at time of alloSCT. Results 1509 pts (1083 MRD negative (MRD-) and 426 MRD+) were included. In the MRD- group, 552 (48%) pts did not receive ATG (MRD− /no ATG) and 561 (52%) received ATG (MRD−/ATG), whereas within MRD+ cohort, 187 (44%) received no ATG (MRD+/no ATG) and 239 (58%) received ATG (MRD+/ATG). Median age was 51 (range 18-73) years, 51% were females. Acute GVHD grade III-IV and cGVHD were significantly lower in pts who received ATG in comparison to those who did not, translating into better GVHD-free, relapse-free survival (GRFS). Non-relapse mortality (NRM), RI, LFS and OS did not differ statistically. Focusing on the influence of MRD status, the overall RI was higher in MRD+ patients prior to alloSCT (38.7% vs. 22.8%, p Conclusions ATG reduces acute and cGVHD incidence and severity in AML pts undergoing alloSCT in CR1, resulting in improved GRFS. AML relapse risk remained unmodified by ATG use, even in the high risk subset of MRD+ patients' pre-alloSCT. Therefore, the use of ATG is not detrimental, and can allow for a significant clinical benefit in all CR1 AML patients who are candidate for alloSCT.

Allogeneic Stem Cell Transplantation for Multiple Myeloma: A 34-Year Experience

Allogeneic Stem Cell Transplantation for Multiple Myeloma: A 34-Year Experience

Allogeneic Stem Cell Transplantation Provides Durable Remission in Patients with Primary Mediastinal Large B-Cell Lymphoma

Allogeneic Stem Cell Transplantation Provides Durable Remission in Patients with Primary Mediastinal Large B-Cell Lymphoma

Prospective Analysis of Bortezomib, Fludarabine and Melphalan As Conditioning Regimen Prior to Allogeneic Stem Cell Transplantation for Multiple Myeloma

Background: Despite advances in novel myeloma treatments and autologous hematopoietic stem cell transplantation (ASCT), allogeneic HSCT (alloSCT) remains the only curative option for patients (pts) with multiple myeloma (MM). Questions remain as to the timing of alloSCT, toxicity risks and optimal conditioning regimen. The addition of bortezomib (Vel) to fludarabine (Flu) and melphalan (Mel) for conditioning prior to alloSCT is based on the demonstrated safety of Vel in combination with melphalan prior to ASCT, the synergistic effect of Vel with Mel, and the ability of Vel to selectively eliminate allo-reactive T-cells. Methods: We present a prospective Phase II study using Flu/Mel/Vel (FMV) as a conditioning regimen for alloSCT. The primary endpoint is overall survival (OS), and secondary endpoints include progression free survival (PFS), incidence of graft-versus-host disease (GVHD) and transplant related mortality (TRM). For related donors, the conditioning regimen was Flu 30 mg/m2 days -5, -4, -3, -2, Vel 1.6 mg/m2 days -4, -1, Mel 140 mg/m2 day -2. For unrelated donors, rabbit ATG 4 mg/kg was given in divided doses days -3, -2, -1. GVHD prophylaxis consisted of methotrexate and tacrolimus. We compared pts receiving FMV to historical controls of pts receiving FM at the same dose and schedule without Vel. We also compared pts receiving FMV to all pts with MM treated with alloSCT including all regimens and donor types. The response criteria from the IMWG and M-Smart criteria were used to determine response and risk, respectively. Chi-square tests of association and Wilcoxon rank sum tests were performed to test for differences across groups. OS/PFS probabilities were calculated using the Kaplan-Meier product limit estimator with log rank-tests. Multivariate Cox proportional hazard models examined factors associated with OS/PFS. Results: Of the 54 pts who received FMV, 35 (65%) were male and the median age was 56 years. Twenty-seven pts had an HLA matched sibling donor and 27 had an unrelated donor. At the time of alloSCT, 5 pts were in a CR, 27 in a VGPR, 13 in a PR, 9 had Pts in the control groups had similar baseline characteristics to the FMV group. The only significant difference was 47 pts (72%) who received FM were transplanted as salvage, and 18 (28%) as consolidation after ASCT (p=0.035). The total number of pts who did not receive FMV (non FMV) was 121, with 66 pts receiving FM. Compared to pts who received FMV, there was no difference in OS for pts who received FM or the non FMV group, 35% (p=0.55) and 48% (p=0.855) respectively. There was no difference in pts who developed aGVHD, however 9 pts (13%) had ≥ grade 3 aGVHD in the FM group (p=0.004) and 15 (12%) in the non FMV group (p=0.006). The cumulative incidence of cGVHD was similar with 51% for pts receiving FM and 60% for FMV pts (p=0.32). TRM was similar to pts who had received FMV; 18% for FM and 17% for non FMV. There were no differences between the 3 groups across disease risk, donor type, or disease status at the time of alloSCT. Multivariate analysis of the 3 groups, shows achieving a CR after alloSCT (p=0.0006) or having cGVHD (p=0.0004) predicts for improved OS, while severe aGVHD (p=0.0002) predicts for decreased OS. Discussion: While FMV was associated with a lower incidence of severe aGVHD, the addition of bortezomib to the FM backbone did not improve PFS or OS. Day 100 TRM was low for all regimens, and the addition of Vel did not impact overall TRM. For all 175 pts, those who achieve a CR after alloSCT had a significantly improved OS. This prompts the question of whether strategies should be employed post alloSCT to maximize response to a CR, and the role of achieving MRD negativity after alloSCT also needs to be elucidated. Disclosures Siegel:BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Biran:Amgen: Consultancy, Speakers Bureau; BMS: Research Funding; Merck: Research Funding; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Skarbnik:Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Genentech: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead Sciences: Honoraria, Speakers Bureau; Abbvie: Honoraria, Membership on an entity9s Board of Directors or advisory committees, Speakers Bureau.

Long-Term Outcomes of Allogeneic Stem Cell Transplant in Peripheral T-Cell Lymphoma

Abstract Introduction: Peripheral T-cell Lymphoma represents a heterogeneous group of lymphoid malignancies characterized by poor prognosis with 5-year overall survival (OS) about 25% with conventional chemotherapy. Autologous stem cell transplant (Auto-SCT), as consolidation, is often considered in first complete remission (CR), providing between 30 to 40% long term disease-free survival. However, patients receiving Auto-SCT in second CR or with refractory disease have poor outcomes with progression-free survival ranging from 15-20% to 0%, respectively. In such cases, allogeneic stem cell transplant (Allo-SCT) may provide long term disease control. We intended to study outcomes of Allo-SCT in peripheral T-cell lymphoma patients. Methods: We have retrospectively evaluated long-term outcomes of adult peripheral T-cell lymphoma patients at Karmanos Cancer Institute. The objectives were to determine GVHD rate, overall survival (OS), relapse rate, progression-free survival (PFS) and non-relapse mortality (NRM) following Allo-SCT. Results: Between January 2005 and December 2017, 39 patients underwent Allo-SCT. The different diagnoses included peripheral T-cell lymphoma, not-otherwise-specified (n=16), angioimmunoblastic T-cell lymphoma (n=8), anaplastic T-cell lymphoma (n=8), hepatosplenic T-cell lymphoma (n=2), cutaneous T-cell (n=3) and NK cell lymphoma (n=2). The median age at transplant was 50 years (range, 21-67). The median number of prior therapies was 2 (range, 1-5) and 12 patients (31%) had failed prior Auto-SCT. Sixteen patients (41%) were in CR and 2 (5%) were in partial remission at the time of Allo-SCT, whereas 12 (31%) patients had relapsed disease and 9 (23%) had refractory disease. Twenty-one patients (54%) received matched related and 18 patients (46%) had unrelated Allo-SCT. Myeloablative conditioning regimen was used in 22 patients (56%), whereas reduced intensity regimen was used in 17 (44%) patients. Grade III-IV acute GVHD occurred in 25.6% (95% CI, 13.2-40.1%) and chronic GVHD occurred in 41% (95% CI, 25.1-56.3%). After a median follow-up of 3.08 years (95% CI, 2.49-7.28) among surviving patients, the estimated probabilities of 3-year OS and PFS were 35.9% (95% CI, 22.4-57.6%) and 32.5% (95% CI, 19.9-53%), respectively. The 3-year relapse rate was 23.9% (95% CI, 11.5-38.7%), whereas NRM was 35.9% (95% CI, 21.1-50.9%). No difference in OS and PFS was noticed in patients receiving Allo-SCT in first CR compared with patients receiving Allo-SCT beyond first CR (p=0.81; p=0.94). Similarly, no difference in OS and PFS was noted in patients with Allo-SCT followed by failed prior Auto-SCT compared with patients with upfront Allo-SCT (p=0.31; p=0.47). Seventeen of 39 patients were alive and 22 were deceased (n=7 disease relapse; n=15 NRM). Out of 39 patients, 13 (33%) alive patients are free of relapse and GVHD as of data analysis. Conclusion: Our study suggests that Allo-SCT is a viable treatment option for peripheral T-cell lymphoma and appears to provide cure in these highly selected patients. The survival advantage was noted in patients beyond first remission; therefore, it should be considered in all transplant eligible patients. In addition, certain proportion of patients who failed prior Auto-SCT benefited from Allo-SCT, which points towards potential role of graft-versus-lymphoma effect. Disclosures Deol: Novartis: Consultancy; Kite Pharmaceuticals: Consultancy.

Long-Term Survival and Absence of Late Relapses in Patients Who Underwent Allogeneic Stem Cell Transplantation for Advanced Cutaneous T-Cell Lymphoma

Long-Term Survival and Absence of Late Relapses in Patients Who Underwent Allogeneic Stem Cell Transplantation for Advanced Cutaneous T-Cell Lymphoma

Engraftment of Donor Cells after Allogeneic Stem Cell Transplantation: Comparison and Impact of Chimerism in Whole Blood and Peripheral CD3+ T-Cells

Introduction: After allogeneic stem cell transplantation (allo-SCT), engraftment can be assessed by quantitative polymerase chain reaction (qPCR) using differing donor/recipient markers (Alizadeh et al. Blood, 2002), identified in peripheral blood DNA cells before transplant. We report here on the concomitant examination of the proportions of donor and recipient DNA in peripheral whole blood (WB) and sorted CD3+ T-cells on days +60 and +90, looking at their impact on survival.Patients, material and methods: This monocentric study evaluated the impact on outcomes of early WB and sorted CD3+ T cells chimerism independently and of the four possible combinations of chimerism between WB and sorted CD3+ T-cells. All follow-up chimerism samples from allo-SCT patients performed in adults at Nantes University Hospital between October 2009 and October 2016 were reviewed, focusing on those where both PB and/or CD3+ T-cells were evaluated on days +60 (45-75) and/or +90 (75-120) after allo-SCT. A global cohort of 229 patients (239 grafts) was retrieved, which includes 52 patients evaluable on day +60 only, 67 evaluable on day +90 only and 120 evaluable on both days +60 and +90. A threshold of >95% donor DNA was considered for complete chimerism. Disease free survival (DFS) was calculated from the date of graft until relapse, death or last follow-up. Overall survival (OS) was calculated from the date of graft until death or last follow-up. Chi square tests were used to compare incidences. Log rang test and Kaplan Meier were used to evaluate DFS and OS.Results: The whole cohort comprised 62% males and had a median age of 58 years old (20-74) at the time of allo-SCT. Patients were treated for myeloid-lineage disease in 59% of the cases. Reduced-intensity conditioning was used in 89% (n=212), donors were familial in 45% (n=107), registry in 48% (n=114). Unrelated cord blood units were used in 8% of the cases (n=18). Post-transplant cyclophosphamide (PTCY) was performed in 48 procedures including 33 and 15 with haplo (HG) and matched donors respectively. Considering the 239 allograft procedures, the median follow-up was 5.8 years (95% CI: 3.1-5.8), the rate of relapse 27% and the rate of death 31%.Complete WB chimerism was observed for 80% and 71% of the cases on day +60 and day +90 respectively. Complete CD3+ chimerism was present for 53% and 51% of the grafts at days +30 and +90 respectively. Thus, cases displaying both complete WB and CD3+ chimerism on days +60 and +90 were 53% and 51% respectively, while 27% and 20% were documented with full WB and mixed CD3+ chimerism on days +60 and +90. Mixed chimerism was observed in both WB and CD3+ cells in 14% of the cases on day +60 and 22% on day +90. Finally, a small proportion of patients (6% and 7% at days +60 and +90) displayed an intriguing complete chimerism in CD3+ cells yet mixed WB chimerism. None of these features appeared associated to disease lineage (lymphoid or myeloid) nor cord blood allo-SCT. Interestingly, of the 27 grafts with myeloablative conditioning, only 14 had full WB/CD3+ engraftment on day +60 or +90, and thus all 27 were retained for the study.None of the four WB/CD3 chimerism combinations at the two times considered had an impact on DFS in this cohort. Surprisingly, although full or mixed WB chimerism had no impact on DFS and OS at days +60 and +90, the presence of a mixed CD3+ chimerism (vs full) at day+90 was associated with a significantly better OS (median: 5.8 months years [95%CI: -not reached] versus 3.1 years [95%CI: 2.2- 3.1]; p=0.025). CD3+ chimerism at day+60 has no impact on OS.All HG resulted in full CD3+ chimerism at both time points compared to non HG (100% vs 52%, p<0.0001). The same was almost true when considering PTCY procedures: 90% at day+60 and 92% at day +90. Of note, there was no influence on DFS nor OS of WB or CD3+ chimerism status when considering only HG or PTCY grafts vs others in this series.Discussion: In this large series, early WB chimerism status did not predict outcome. Surprisingly, mixed CD3+ chimerism at day+90 appears to be significantly associated with a longer OS, suggesting that remaining recipient memory lymphocytes could be beneficial. This result has to be confirmed prospectively. It remains also to define the place of donor lymphocyte infusions (DLI) to prevent relapse in patients with full or mixed CD3+ chimerism post-transplant (analyses of DLI received in our patients are on-going). DisclosuresMoreau:Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria.

Allogeneic Stem Cell Transplantation for Multiple Myeloma: a Single Center Experience

IntroductionThe use of allogeneic stem cell transplantation (Allo-SCT) in patients with multiple myeloma (MM) remains controversial, but it offers prolonged disease free survival in some patients. It is unclear which patients should undergo Allo-SCT, what conditioning regimen should be used, and what the timing of the transplant should be in the course of the disease. Therefore, we sought to contribute our center's experience to the growing body of literature.MethodsWe performed a retrospective observational cohort study of all patients who underwent Allo-SCT for multiple myeloma at our center between January 1, 1992 and May 31, 2016. Categorical variables were compared using Pearson's chi-square test and the Kaplan-Meier method was used for the overall survival curves.ResultsThirty-four patients underwent Allo-SCT for multiple myeloma and were included in this analysis. The median age was 40 years and 21 (62%) were male. Nineteen patients (56%) underwent Allo-SCT as upfront therapy, 1 (3%) underwent tandem autologous stem cell transplant (auto-SCT) followed by Allo-SCT, and 14 (41%) had salvage Allo-SCT at the time of relapse. Twenty-four (70.5%) patients had a matched related donor, 1 (3%) had a mis-matched related donor, 8 (23.5%) had matched unrelated donor and matching in 1 (3%) was not available. Myeloablative conditioning was given in 18 patients (52.9%) and non-myeloablative conditioning in 13 (38.2%) with 3 (8.8%) missing. The conditioning regimens included: 5 (15%) Flu-Mel, 7(20.6%) Flu-Bu, 13 (38%) Bu-Cy ± TBI, 6 (17.6%) MelVPTBI, and 3 (8.8%) were missing. Median overall survival (OS) for all patients was 72.5 months from diagnosis (figure 1) and 26.5 months from the time of Allo-SCT. For the 19 patients who had upfront Allo-SCT, median OS from diagnosis was 7.4 years compared to 5.3 years for those having salvage Allo-SCT (figure 2). However, in the upfront group 6 (32%) were alive 10 years post Allo-SCT and the survival curve reaches plateau, whereas in the salvage group, no patient was alive after 8 years post Allo-SCT. There was no difference in median survival between myeloablative and non myeloablative conditioning (2.9 versus 1.33 years, p=0.925). There have been 20 deaths in our cohort (59%); 5 (14.7%) from transplant related mortality within 1 year, 9 (26.5%) from disease progression, and 6 (17.6%) transplanted remotely whose cause of death is unknown.ConclusionsOur data suggest that Allo-SCT offers prolonged disease free survival in some patients. In our small cohort, a greater proportion of patients undergoing upfront Allo-SCT achieved long term survival, raising the possibility that this group of patients may benefit more from Allo-SCT. Further prospective studies are needed to clarify the role of Allo-SCT in MM. [Display omitted] [Display omitted] DisclosuresKew:Celgene: Honoraria. McCurdy:Celgene: Honoraria.

Efficacy of Adoptive Immunotherapy By Donor Lymphocyte Infusions after Allogeneic Stem Cell Transplantation from Related an Unrelated Donors: A Single Center Retrospective Analysis

Introduction: Allogeneic stem cell transplantation (alloSCT) has become an integral part in the therapy of patients with malignancies of the lympho-hematopoietic system. One of the main reasons for treatment failure after alloSCT is relapse of the underlying disease, which, in the majority of cases, is associated with a poor prognosis. Adoptive immunotherapy by the use of donor lymphocyte infusions (DLI) was shown to be effective in this setting. However, the conditions and the optimal timing of DLI administration for prophylaxis or treatment of (impending) relapse remains controversial.Patients and Methods: We retrospectively analyzed 160 consecutive patients (median age: 48 (range: 17-69) years) who received DLI after previous alloSCT performed at our center between 1998 and 2014. Indications for alloSCT were: acute myeloid leukemia (AML) (N=68), acute lymphoblastic leukemia (ALL) (N=49), myelodysplastic syndrome/myeloproliferative neoplasia (MDS/MPN) (N=26), or myeloma/lymphoma (N=17). The disease risk index (DRI) was low (N=1), intermediate (N=101), high (N=43), or very high (N=6) (unknown: N=9). Comorbidities, as specified by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), were low (N=38), intermediate (N=79), or high (N=38) (unknown: N=5). In N=71 patients a 10/10 human leukocyte antigen (HLA) matched-related donor was chosen, whereas N=89 patients were transplanted from an unrelated donor, either matched (N=73) or mismatched (N=16). Conditioning was either myeloablative (MAC) (N=71) or reduced-intensity (RIC) (N=89). The median interval from alloSCT to first DLI was 7.1 (range: 1.0-93.2) months. Indication for DLI was prophylactic (e.g. high-risk of relapse or active disease at the time of alloSCT) (N=28), pre-emptive (e.g. persistent or increasing mixed chimerism/molecular relapse) (N=86), or hematologic relapse (N=46). Pre-treatment before DLI was none/cessation of immunosuppression (N=129), lymphodepleting chemotherapy (N=16), or other (N=15). The median number of DLI units given was 2 (range: 1 - 6) and the median cumulative CD3+ cell dose/kg body weight given was 1.1 x 10E7 (range: 5.0 - 16.0 x 10E7).Results: The median follow-up of all patients from day of alloSCT was 37.3 (range: 3.0 - 202.6) months, whereas the median follow-up from day of first DLI administration was 21.2 (range: 0.3 - 200.5) months. Overall survival (OS) of the entire cohort at 1, 3, and 5 years after alloSCT was 80.5%, 63.8%, and 57.7%. Calculated from the day of first DLI OS at the same time points was 68.8%, 61.0%, and 55.8%. At five years after alloSCT OS in the group of patients with AML or ALL was significantly lower as compared to patients with MDS/MPN or myeloma/lymphoma, i.e. 52.0% versus 66.2% (p=0.043). Furthermore, OS in the group of patients receiving pre-emptive DLI was virtually identical to patients who received prophylactic DLI, i.e. 70.4% versus 69.8% at 5 years. In contrast, patients with hematologic relapse prior to DLI had an inferior outcome, i.e. an OS of 23.3% at 5 years. In addition to indication for DLI administration, i.e. prophylactic or pre-emptive versus therapeutic, the occurrence of chronic graft-versus-host disease (cGvHD) was the strongest predictor for outcome, i.e. long-term survival.Conclusions: Taken together, our data indicate that adoptive immunotherapy by the use of DLI is capable of inducing long-term remissions in patients after alloSCT. As pre-emptive and prophylactic treatment yielded virtually identical results, latter may be reserved for selected patients with (very) unfavorable disease characteristics, e.g. AML or ALL with active disease at the time of transplant. The optimal type of pre-treatment needs to be determined by investigating larger patient cohorts. DisclosuresNo relevant conflicts of interest to declare.

Double umbilical cord blood transplant is effective therapy for relapsed or refractory Hodgkin lymphoma

A sub-group of patients with Hodgkin Lymphoma (HL) who relapse after autologous stem cell transplant can achieve long-term disease-free-survival after allogeneic stem cell transplant (alloSCT). There is limited information regarding the tolerability and efficacy of double umbilical cord blood transplant (dUCBT) for relapsed/refractory HL. We analyzed 27 consecutive, heavily pre-treated patients receiving dUCBT for relapsed/refractory HL at two centers from 2003–2014. The majority of patients relapsed <6 months after autologous stem cell transplant. A total of 15 patients received myeloablative (most commonly melphalan, fludarabine, thiotepa and anti-thymocyte globulin [ATG]) and 12 non-myeloablative conditioning regimens (fludarabine, cyclophosphamide, 200cGy total body irradiation +/- ATG). All patients engrafted; median time to neutrophil and platelet engraftment was 17 and 37 days, respectively. Overall response rate was 68%; 58% achieved complete remission. Median progression-free survival (PFS) was 12.2 months; median overall survival was 27 months. Cumulative incidences of relapse and of non-relapse mortality at 5 years were 30% and 37.9%, respectively; 5-year PFS was 31.3% (95%CI 10.1–52.5). There was a trend toward inferior PFS in patients with lymph node size ≥2 cm at the time of alloSCT (p = 0.07) and toward inferior survival in patients with chemorefractory disease pre-alloSCT (p = 0.12). dUCBT is feasible in patients with heavily pre-treated HL and can achieve long-term disease-free survival in approximately 30% of patients.

Association Between Uric Acid Levels and Severe Acute Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation

Introduction and objectives: There is increasing knowledge on the relevance of danger signals activating the innate immune system in the pathogenesis of graft-versus-host disease (GvHD). Uric acid (UA) is a known danger signal that is released from injured cells during conditioning for allogeneic stem cell transplantation (alloSCT). UA has been identified to enhance dendritic cells maturation and to amplify T-cell responses. Previous reports analyzing the relationship between UA and acute GvHD (aGvHD) have shown controversial results (Ann Hematol 2015; 94: 139; Biol Blood Marrow Transplant 2014; 20: 730).The objective of this study is to investigate the association between UA levels pre-alloSCT and aGvHD.Patients and methods: We retrospectively analyzed data from 548consecutive patients who received an alloSCT from January 2007 to December 2014 on four institutions. The cumulative incidence of aGvHD over the first 100 days post-alloSCT was estimated in the framework of competing risks by taking relapse or death without relapse as competing events. The association between pre-alloSCT UA levels (measured between day -7 and day 0), dichotomized at the median value, and the incidence of aGvHD was investigated by calculating the subhazard rate (SHR) according to Fine & Gray (J Am Stat Assoc 1999; 94: 496).Results: Patients (median age 46y, range 16-67; 66% male) were transplanted for acute leukemia (51%), lymphoproliferative syndrome (22%), myelodysplastic syndrome (12%), multiple myeloma (8%), and other causes (7%). Disease status at the time of alloSCT was 49% complete remission, 17% partial response and 31% active disease. Fifty-one percent patients received alloSCT from related donors, 41% from unrelated donors, and 8% from alternative donors (cord blood units or haploidentical donors). The source of stem cells was peripheral blood in 84% patients. Fludarabine-based reduced intensity conditioning (RIC) regimens were used in 54% of transplants and myeloablative (MAC) in 46%. Most patients received immunosuppression with calcineurin inhibitors in combination with methotrexate (MAC) or mycophenolate mofetil (RIC). Sixteen percent also received ATG. Most patients (82%) received allopurinol 300 mg/day through conditioning regimen until day 0 of transplant. The median serum UA level prior to stem cells infusion was 3.7 mg/dL (range 0.7-8.8). Serum levels of UA (mg/dl) were higher in males than in females (4 vs. 3, p=0.0001), in patients submitted to RIC as compared with MAC alloSCT (4 vs 3.3, p=0.0001), in those not receiving ATG for GvHD prophylaxis (3.8 vs. 2.9, p=0.0002) and in the minority of patients not treated with allopurinol (4.7 vs. 3.3, p=0.0001). By day +100 post-alloSCT, 222 patients had been diagnosed of aGvHD II-IV, 79 had relapsed and 72 had died from causes unrelated to relapse or GvHD. The cumulative incidence of aGvHD II-IV was 40% (95% CI: 35%-44%) whereas the incidence of competing events (death or relapse) amounted to 11% (95% CI: 8%-13%). Patients with levels of UA above the median had an increased incidence of aGvHD II-IV (SHR: 1.4, 95% CI: 1.1-1.8; p=0.015) at the univariate analysis. However, such relationship vanished after multivariate adjustment for other factors associated with the peri-alloSCT UA levels and/or the risk of aGvHD (e.g. age, sex, type of donor, type of alloSCT, GvHD prophylaxis). Additional exploratory and subgroup analyses did not find any relationship between UA levels neither severe aGvHD (grades III/IV), early aGvHD (before day +60) nor type of conditioning regimen (RIC vs. MAC).Conclusions: There is a weak association between higher peri-alloSCT levels of uric acid and increased incidence of aGvHD. Nevertheless, our results suggest that such associations reflect confounding effects rather than causal factors and, therefore, they do not support interventions aimed at preventing aGvHD by reducing uric acid levels. DisclosuresNo relevant conflicts of interest to declare.

Grouping of Genetic Risk By the European Leukemia Net Classification Predicts Overall Survival and Relapse Incidence in Patients with Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation

Introduction: In acute myeloid leukemia (AML) genetic risk factors are among the strongest predictors for overall outcome. Recently, the European Leukemia Net (ELN) proposed a revised classification based on the presence or absence of specific cytogenetic and/or molecular aberrations. Here, we evaluated the prognostic significance of this system in patients with AML undergoing allogeneic stem cell transplantation (alloSCT).Patients and Methods: A total of 363 patients transplanted at our center between 2004 and 2014 was retrospectively evaluated. According to the ELN classification genetic risk was favorable (N=51), intermediate-1 (N=120), intermediate-2 (N=98), or adverse (N=94). Remission status at the time of alloSCT was first complete remission (CR1) (N=204), CR>1 (N=61), or refractory (N=98). In 107 patients standard myeloablative conditioning (MAC) was used, whereas reduced intensity conditioning (RIC) was applied in 256 patients. Grafts were from either related (N=103) or unrelated (matched: N=191, mismatched: N=69) donors. The median age was 52 (range: 18-75) years.Results: For the surviving patients the median follow-up was 30 (range: 3-129) months. Whereas in the subgroup of patients aged ≥60 years (N=98) no significant differences in disease-free survival (DFS) or cumulative incidence of relapse (CI-R) between the 4 ELN subgroups were found, the ELN classification was highly predictive for in the subgroups aged <60 years. Patients with an adverse risk karyotype had significantly lower DFS as compared to patients with a favorable or an intermediate risk profile, i.e. 30% versus 56% for favorable, 52% for intermediate-1, or 59% for intermediate-2 (p=0.0064). Correspondingly, the CI-R was highest in patients with an adverse risk profile, i.e. 53% at 5 years. In turn, patients with favorable, intermediate-1, or intermediate-2 risk disease had a CI-R of 15%, 40%, or 21% (p<0.001). In the intermediate-1 subgroup, adverse outcome, i.e. relapse, was predominant in the group of FLT3-ITD positive patients, whereas the CI-R in patients lacking a FLT3-ITD was similar to what was observed in the intermediate-2 subgroup.Conclusions: Taken together, our data suggest that the ELN classification of genetic risk is suitable for predicting relapse and overall survival of patients with AML aged <60 years undergoing alloSCT. The adverse outcome of patients in the intermediate-2 subgroup may be related to presence of a FLT3-ITD. Therefore, further efforts are needed to improve the clinical results in this particular group. DisclosuresNo relevant conflicts of interest to declare.

Treatment with Hypomethylating Agents before Allogeneic Stem Cell Transplant Improves Survival for Patients with Chronic Myelomonocytic Leukemia

▪IntroductionAllogeneic hematopoietic stem cell transplant (allo-SCT) is the only curative treatment modality for patients with CMML. Here we retrospectively reviewed the data for patients with CMML who received an all-SCT at our institution to identify factors associated with improved survival and determine whether treatment with hypomethylating agents (HMA) before transplant improves survival for these patients.MethodsAll 83 patients 18 years of age or older with a diagnosis of CMML confirmed at The University of Texas MD Anderson Cancer Center who underwent allo-SCT between April 1991 and December 2013 were identified through review of the institutionÕs medical records and included in this analysis. Forty, 7, and 36 patients had CMML-1, CMML-2 and CMML that had progressed to AML (CMML/AML) respectively.The median age was 57 years. CMML specific cytogenetic risk at diagnosis (Such E, hematologica, 2011) was good, intermediate, and high risk in 46, 19, and 18 patients respectively. Seventy-eight patients received induction treatment before transplant, 37 receiving HMA (either 5-azacytidine or decitabine) for at least 3 courses and 41 receiving 1-2 courses of cytotoxic chemotherapy. Among the patients who received induction therapy, 15 patients in HMA group and 9 patients in convention chemotherapy group achieved a complete remission before transplant.Thirty, 47 and 6 patients received transplants from matched related donors (MRD), matched unrelated donors (MUD), and mismatched related or unrelated donors (MMD), respectively. The sources of hematopoietic stem cells were peripheral blood for 48 patients (57.8%) and bone marrow for 35 patients (42.2%). Conditioning regimens varied; most patients received either fludarabine in combination with busulfan or fludarabine combined with melphalan. Sixty-four patients received myeloablative and 19 patients received reduced intensity conditioning regimens. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and methotrexate.Patient and transplant characteristics did not significantly differ between the patients treated with HMA and the patients treated with conventional chemotherapy or given supportive care alone.The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), Treatment related mortality (TRM), relapse incidence through last follow-up and incidences of acute GVHD and chronic GVHD. All of these outcomes were measured from the time of allo-SCT.ResultsMedian follow up duration for 29 survivors was 48 months. Seventy-five patients engrafted (90.4%) with median time to neutrophil and platelet engraftment of 13 and 15 days respectively.Patients treated with a HMA had a significantly lower cumulative incidence (CI) of relapse at 3 years post-transplant (22%) than those treated with other agents (35%; p=0.03), whereas TRM at 1 year post-transplantdid not significantly differ between the groups (27% and 30%, respectively; p=0.84). Acute GVHD all grades and grade 2-4 were seen in 28.2% versus 35.8% (p=0.05) and 12.8% versus 11.3% (p=0.72) in patients who received a HMA compared to those who treated with other agents respectively. CI of chronic GVHD was 35% in patients treated with a HMA versus 19.2% in those treated with other agents (p=0.36) while CI of chronic extensive GVHD was seen in only 26.7% versus 19.2% respectively (p=0.64).The lower relapse rate resulted in a significantly higher 3-year PFS rate in patients treated with a HMA (43%) than in those who received other treatments (27%; p=0.04) (Figure 1). However, therapy with HMA before transplant did not significantly influence the 3-year OS rate (45% in those treated with HMA and 39% in those treated with other agents; p=0.22).The independent prognostic factors for PFS were a blast count of < 5% before transplant (HR 0.36, 95%CI 0.14-0.78), treatment with a HMA (HR 0.44, 95% CI 0.23-0.86), a transplant from an MRD (HR 0.41, 95% CI 0.22-0.94), development of grade 2-4 acute GVHD (HR 2.7, 95% CI 1.27-5.77), and development of chronic GVHD (HR 0.15, 95% CI 0.05-0.45).ConclusionWe conclude that treatment with hypomethylating agents before allo-SCT may improve survival in patients with CMML. [Display omitted] DisclosuresAlousi:Therakos, Inc: Research Funding. Andersson:Otsuka Research and Development, Inc.: Consultancy.

Low Vitamin D Levels Are Associated with Inferior Survival Following Azacitidine Treatment in Patients with Myelodysplastic Syndrome

▪Introduction: Azacitidine (AZA) therapy has become the recommended first-line treatment for patients with high-risk myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML; bone marrow blasts <30%). However, only around 50% of patients achieve objective responses with AZA therapy and the vast majority of responding patients have disease progression within 2 years resulting in dismal survival rates.Vitamin D (VitD) is a central regulator of calcium and bone homeostasis and affects multiple signaling pathways controlling proliferation, apoptosis and differentiation. More than 30 years ago, VitD was demonstrated to induce in vitro differentiation of AML blast cells. Consequently, VitD alone or in combination with other differentiating agents has been used for treatment of MDS patients showing inconsistent and rather limited efficacy. We retrospectively tested the hypothesis that VitD levels prior to start of treatment are predictive of overall survival (OS) in newly diagnosed MDS and oligoblastic AML patients receiving upfront AZA therapy. In addition, the antiproliferative effects of AZA in combination with different VitD derivatives were investigated in vitro.Patients, materials and methods: A total of 58 patients treated at our center between 2006 and 2014 had serum samples available for assessment of VitD status. Serum samples were collected at a median of 18 days prior to start of AZA treatment and cryopreserved at -80°C. VitD status was assessed by measurement of circulating 25-hydroxyvitamin D levels applying a standard chemiluminescent immunoassay (DiaSorin Deutschland GmbH, Dietzenbach, Germany). Overall survival (OS) was estimated using the method of Kaplan and Meier. Survival times were measured from the date of AZA treatment start. Comparison of OS between the VitD groups was done using the logrank test and by cox regression adjusting for known confounders.For in vitro analyses, a tetrazolium based MTT assay was used for assessment of growth inhibition of two different AML cell lines (HL60 and MOLM13) after exposure to AZA alone or in combination with VitD (1alpha,25-dihydroxyvitamin D and 25-hydroxyvitamin D; both from Cayman Chemical, Ann Arbor, MI, USA) or the VitD antagonist TEI-9647 (kindly provided by Teijin Pharma Ltd., Tokyo, Japan). Drug interactions were analyzed using the median-effect method of Chou and Talalay and combination index (CI) values were calculated according to the classic isobologramm equation with CI<1, CI=1 or CI>1 corresponding to synergism, additivity or antagonism, respectively. In cases where no antiproliferative activity upon single-agent treatment was assessable (low-dose VitD and TEI-9647), an analysis in terms of sensitization (potentiation) or inhibition of AZA activity was performed instead.Results: Estimated median follow-up time was 14.2 months. Median serum VitD level prior to AZA treatment was 33 nM (range 11-102 nM). A total of 18 patients underwent allogeneic stem cell transplantation (alloSCT) following AZA therapy and follow-up was censored at the time of alloSCT. Patient, disease and treatment characteristics did not differ significantly between the low (≤33 nM; n=29) and high (>33 nM; n=29) VitD group. Estimated one-year survival was 72% (95% CI 54-90%) in the high VitD group, which was significantly longer as compared to the low VitD group (41%, 95% CI 20-62%, p<0.05; Figure 1). In multivariate analysis with OS as endpoint, VitD (per 10 nM decrease, HR 1.83 95% CI 1.06-3.16, p=0.03) and adverse cytogenetics (HR 2.58 95% CI 1.10-6.06, p=0.03) were independent predictors of shorter survival. In vitro treatment of HL60 and MOLM13 cells with AZA in combination with VitD produced synergistic and additive antiproliferative effects. Addition of nanomolar concentrations of VitD to AZA resulted in potentiation of AZA activity. Conversely, combination with TEI-9647 resulted in inhibition of AZA activity.Conclusions: Our study suggests that higher VitD levels were associated with a survival advantage following upfront AZA therapy. As compared to AZA monotherapy combination treatment with VitD resulted in enhanced cytotoxic effects in vitro. VitD repletion/supplementation during AZA treatment should therefore be explored. [Display omitted] DisclosuresLuft:Immundiagnostik AG: Research Funding.

Stabilization of Myelodysplastic Syndromes (MDS) Following Hypomethylating Agent (HMAs) Failure Using the Immune Checkpoint Inhibitor Ipilimumab: A Phase I Trial

Background: Patients (pts) with higher-risk (HR)-MDS in whom HMAs fail have a dismal prognosis with a median overall survival (OS) of <6 months. Immune tolerance and evasion by malignant cells have been recognized as important mechanisms of progression in cancers including MDS. Immune checkpoint inhibition with the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab improved outcomes in pts with solid tumors by overcoming this resistance mechanism. We hypothesized that CTLA-4 blockade in pts with HR-MDS post HMAs failure would be tolerable and lead to meaningful clinical responses.Methods: In an investigator-initiated, CTEP-sponsored phase 1b study, eligible pts with HR-MDS (defined by Intermediate-2 or high IPSS score, or intermediate-1 with ≥5% blasts in bone marrow [BM] or transfusion needs) who had primary or secondary failure of HMAs (≥4 cycles) received ipilimumab monotherapy at 2 dose levels (DL); DL1 used 3mg/kg and DL2 used 10mg/kg. In the induction phase [Figure 1], 4 doses were administered at 3-week intervals. Responding Pts and those with stable disease (SD) at end of induction received a maintenance phase with 4 more doses of ipilimumab administered at 3-month intervals (study total is 8 doses). BM biopsies were obtained at baseline, post cycles 2, 4, and before each maintenance dose. The primary objectives were to determine the tolerability of ipilimumab and identify the optimal dose for dose expansion. Toxicities were graded according to CTCAE 4.0 criteria. Responses were evaluated using International Working Group 2006 criteria at end of induction and before each maintenance dose. Overall survival (OS) was calculated from first dose of ipilimumab until death using Kaplan-Meier methods with censoring at time of allogeneic stem cell transplantation (alloSCT) or cutoff date for data collection on 6/30/2015.Results: Eleven pts were enrolled on the dose-escalation part of the study; 6 on DL1 and 5 on DL2. Median age was 63 years (range, 50-79). Five pts had received 2 prior lines of therapy (including HMAs) while 6 pts had received only HMAs; median number of HMAs cycles 5; range, 4-18. Five pts had a normal karyotype while each of the following categories were present in one pt: del5q, del7q, complex, trisomy 8 (2 pts unsuccessful karyotyping). At baseline, 4 pts were platelet transfusion-dependent and 5 were red blood cell transfusion-dependent. Median platelet count was 25×10⁹/L (range, 12-61×10⁹/L), median white blood cell count was 1.5×10⁹/L (range, 1.05-7.6×10⁹/L), median absolute neutrophil count was 0.28×10⁹/L (range, 0.06-4.7×10⁹/L), median hemoglobin was 9.4 gm/dL (range 7.6-10.8 gm/dL), and median BM blast percentage was 9% (range, 2-30%). All pts in DL1 received ≥2 ipilimumab doses; 2 received 6 or 8 doses. Three of 6 pts in DL1 developed grade 3 immune-related adverse events (IRAEs) while 4 of 5 pts at DL2 developed grade 3 IRAEs. Four pts (36%) experienced no IRAEs (3 at DL1 and 1 at DL2). All IRAEs were reversible with stopping ipilimumab +/- initiation of systemic steroids. No pt died due to an IRAE and all patients were successfully weaned from steroids. The spectrum of IRAEs was similar to that of ipilimumab use in pts with solid malignancies (rash, hepatitis, and diarrhea/colitis). Overall no pts had objective responses. Three pts (27.3%) had SD for >6 months; one had a prolonged SD after an IRAE, and one experienced an ongoing SD for >16 months. Three pts underwent alloSCT post ipilimumab without any additional toxicities and remain in complete remission at 2, 12 and 18 months post alloSCT, respectively. Median and mean OS for entire cohort (censoring at time of alloSCT) was 368 and 352 days, respectively (95%CI for mean OS, 264-440 days) [Figure 2]. Correlative studies evaluating dynamic changes in T-cell subsets, myeloid derived suppressor cells, cytokine levels, and T-cell receptor repertoire are in progress.Conclusions: Monotherapy withanti-CTLA-4 antibody ipilimumabat 3mg/kg is tolerable and can lead to prolonged disease stabilization. This dose is currently being evaluated further in a dose-expansion multi-center study. AlloSCT appears feasible post ipilimumab use but further data are needed. These results provide rationale for further exploration of immune checkpoint inhibition therapy in pts with MDS. [Display omitted] [Display omitted] DisclosuresOff Label Use: Ipilimumab for MDS. Gore:Celgene: Consultancy, Honoraria, Research Funding.

Efficacy, Safety and Long Term Results of Prophylactic and Preemptive Donor Lymphocyte Infusion after Allogeneic Stem Cell Transplantation for Acute Leukemia: A Registry-Based Evaluation on 343 Patients By the Acute Leukemia Working Party of EBMT

Background: Relapse is the most frequent cause of failure after alloSCT for acute leukemia (AL). Unlike in CML, infusion of donor lymphocytes (DLI) is of limited efficacy in overt hematological relapse. Hence, it may be preferable to give DLI in complete hematological remission (CHR) after alloSCT, to exploit the allogeneic graft-versus-leukemia (GvL) effect either as maintenance in high risk patients (prophylactic DLI, proDLI), or as early intervention to prevent hematological recurrence in case of decreasing donor chimerism or minimal residual disease (preemptive DLI, preDLI). However, no systematic analysis of this strategy is available so far, neither concerning the optimal way of application, nor with respect to safety and clinical efficacy. Here, the Acute Leukemia Working Party of the EBMT presents results from a registry-based survey on 343 patients with AML (n=266) or ALL (n=77), who received DLI in CHR after alloSCT. Patients: Median age was 48y, 64% of patients had received alloSCT from a matched sibling, 36% from an 8/8 matched unrelated donor. Disease status at time of alloSCT was CR1/CR2/advanced in 68%/14%/17% of cases, respectively. Patients had received standard/reduced intensity conditioning in 53%/47% of cases. Before alloSCT, 55% had received in vivo T-cell depletion (TCD), 16% ex vivo TCD, 10% in vivo plus ex vivo, and 19% no TCD. Reasons for preDLI were persisting mixed or decreasing donor cells chimerism (n=167, 49%) and persisting or recurrent minimal residual disease (MRD; n=32, 9%). ProDLI without any sign of leukemia was given to 144 patients (42%) with high risk disease Results: Median follow up from DLI1 was 6.5 years (range, 1.1-14.5). Median interval from alloSCT to first DLI (DLI1) was 180 days (range, 15-1178). Patients received a median of 2 infusions with the median CD3+ cell dose at DLI1 being 1x106/kg (range, 0.1-163). Reasons to discontinue DLI were: number of planned infusions reached (56%), GvHD (17%), disease progression (13%), and documented improvement of donor chimerism (6%). At 5y from DLI1, cumulative incidence of leukemia relapse was 43% and 28% in patients receiving preDLI for MRD and mixed chimerism, and 28% among recipients of proDLI given for maintenance in high risk disease. The corresponding 5y OS rates were 55%, 66% and 64%, 5y-LFS rates were 52%, 57% and 58%. Efficacy of preDLI could be directly demonstrated by decreasing MRD in 71% (15/21) and by improvement of donor chimerism in 68% (110/163) of informative patients. Furthermore, hematologic improvement was observed in 13 patients following proDLI. Cumulative incidences of acute GvHD grade II-IV and chronic GvHD after DLI were 13% and 32%, respectively. A multivariate model identified a history of aGvHD ≥grade II after alloSCT (p=0.009, HR 2.1, 95% CI 1.2-3.7), an interval from alloSCT to DLI &lt;6 months (p=0.003, HR 0.997, 95% CI 0.006-0.999), and a CD3+ cell count &gt;1 x 106/kg at DLI1 (p=0.024, HR 1.011, 95% CI 1.001-1.021) as risk factors for induction of GvHD after DLI in CHR. One hundred and thirty three patients (39%) had died at last follow-up, with relapse still being the most frequent cause of death (n=87). Sixteen patients (5% of the entire cohort) died from DLI-induced GvHD, and 29 patients died from other courses. In summary, in this large cohort of patients receiving DLI for AL in CHR after alloSCT, efficacy of preemptive DLI cells could be demonstrated in 69% of patients. About half of patients with MRD, and &gt;70% of patients with mixed chimerism did not experience hematological relapse during a follow up period of &gt;5 years, suggesting a clinically meaningful effect of preDLI in AL. GvHD was the most devastating complication, leading to death in 5% of patients. The identification of risk factors for GvHD may influence the selection of candidates for prophylactic and preemptive DLI in general, and may help to refine the use of DLI in this context with respect to cell dose and timing. Disclosures Schmid: Neovii: Consultancy; Janssen Cilag: Other: Travel grand. Bug:Celgene, Novartis: Research Funding; NordMedica, Boehringer Ingelheim, Gilead: Membership on an entity's Board of Directors or advisory committees; TEVA Oncology, Astellas: Other: Travel Grant. Tischer:Sanofi-Aventis: Other: advisory board. Esteve:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.