Donor Lymphocyte Infusion Group Research Articles

Randomized Trial of Prophylactic Donor Lymphocyte Infusion with Positively Selected CD4+ T Cells after HLA-Identical Allogeneic Stem Cell Transplantation

Introduction Allogeneic stem cell transplantation (alloSCT) can cure patients with hematological malignancies by T-cell mediated alloreactivity against patient hematopoiesis, the graft-versus-leukemia (GvL) effect. GvL can coincide with graft-versus-host disease (GvHD) when donor T cells target non-hematopoietic tissues. Increase of donor chimerism in bone marrow (BM) or peripheral blood (PB) after alloSCT indicates GvL response. After T-cell depleted alloSCT, donor lymphocyte infusion (DLI) can restore GvL. Dose and timing of DLI influence the degree of alloreactivity. Low dose of unmodified DLI as low as 0.3x10 6 T cells/kg 3 months after alloSCT appeared not to cause GvHD. (Zouwen et al. Ann Hematol, 2023) We hypothesized that infusion of a higher dose of purified CD4+ donor T cells would not cause GvHD, while inducing GvL by selective targeting of the MHC class II positive hematopoietic cells. Method A randomized controlled phase 2 trial was conducted in patients with hematological malignancies after HLA-identical sibling alloSCT with alemtuzumab added to the graft. Patients without GvHD or relapse were randomized at 2.5 months for prophylactic DLI with 1.0x10 6/kg CD4+ T cells (CD4+ DLI) 3 months after alloSCT or conventional care without DLI (CC). Both groups were eligible for prophylactic unmodified DLI at 6 months. Cumulative incidence (CI) of GvHD requiring immunosuppressive treatment 3 months after randomization was the primary endpoint. Changes in the trajectory of chimerism in BM and subsets in PB (CD4+ T cells, CD8+ T cells, NK cells, B cells and monocytes) were compared by means of mixed effects beta regression as secondary endpoints. Results 66 patients were included (table 1). CI of GvHD did not differ between groups (CD4+DLI: 6.1% vs CC: 9.1%, Gray's test p>0.9). Relapse was comparable (CD4+DLI: 15% vs CC: 12%), although heterogeneity of diseases prevented a formal comparison. In the CD4+ DLI group, BM chimerism was full donor (FD, >95% donor) at baseline in 23/33 patients, while 10/33 had mixed chimerism (MC, ≤95%). In the CC group, 23/33 were FD and 10/33 MC. Some patients with MC at baseline converted to FD in both groups (CD4+ DLI: 1/10 vs CC: 1/10). Changes in BM chimerism did not differ between CD4+ DLI and CC (p = 0.9). Chimerism of B cells, NK cells and monocytes in PB resembled bone marrow chimerism with most patients being FD at baseline. Changes in chimerism did not differ between CD4+ DLI and CC (p = 1.0, 0.5 and 0.9 for B cells, NK cells and monocytes respectively). In the CD4+ DLI group, 25/30 evaluable patients were MC in the CD4+ T-cell subset in PB at baseline. 3 month after randomization 7/25 had converted to FD, 17/25 remained MC and 1/25 was unevaluable. Of the 17 patient who remained MC, CD4+ donor chimerism increased (absolute increase >5%) in 13, decreased (>5%) in 2 and was stable in 2. In the CC group, 26/32 were MC in CD4+ T cells at baseline, of which 6 converted to FD, 18 remained MC and 2 were unevaluable. Of the 18 patients remaining MC, CD4+ chimerism increased in 5, decreased in 9 and remained stable in 4. The CD4+ donor chimerism increased significantly after CD4+ DLI compared to CC (p = 0.01) (Figure 1). In the CD4+ DLI group, 23/29 evaluable patients were MC in the CD8 subset at baseline. 7/23 converted to FD, 15/23 remained MC and 1 was unevaluable. Of these 15 MC patients at 3 months, 9 had increasing, 5 stable and 1 decreasing donor chimerism after 3 months. In CC, 22/31 were MC at baseline. 4/22 converted to FD at 3 months and 17/22 remained in MC. Of the 17 MC patients, 6 had increasing, 3 decreasing and 8 stable chimerism. The CD8+ donor chimerism increased significantly in the CD4+ DLI group compared to CC (p = 0.03). Conclusion CD4+ selected DLI at a dose of 1x10 6 CD4+/kg 3 months after HLA identical T-cell depleted alloSCT did not cause GvHD. Chimerism in BM leukocytes, B cells, NK cells or monocytes did not indicate GvL mediated by CD4+ DLI, possibly because most patients were already FD at baseline. CD4+ and CD8+ T-cell donor chimerism increased significantly after CD4+ DLI, suggesting a GVL-effect - earlier demonstrated in vitro for 4 selected patients. (Van Balen et al. Front Immunol, 2018) However, most patients did not convert to FD in the T-cell compartment, suggesting the GvL-effect of CD4+ DLI was limited. We considered this GvL-effect insufficient to prevent relapse and stress the importance of CD8+ donor T cells as main drivers of alloreactivity after DLI following HLA-identical alloSCT.

Donor Hematopoietic Stem Cell/Lymphocyte Maintenance Treatment After CAR T-Cell Therapy in Patients With B-Cell Acute Lymphoblastic Leukemia Relapse Following Stem Cell Transplant.

Maintaining the efficacy of anti-CD19 chimeric antigen receptor modified (CAR) T-cell therapy in patients with B-cell acute lymphoblastic leukemia (B-ALL) relapse after allogeneic hematopoietic stem cell transplant (allo-HSCT) is an urgent problem. In this study, we aimed to compare the efficacy of donor hematopoietic stem cell infusion (DSI) therapy and donor lymphocyte infusion (DLI) therapy as a maintenance therapy after R/R B-ALL patients achieved CR in anti-CD19-CAR T-cell therapy but relapsed after allo-HSCT. In total, 22 B-ALL patients who relapsed after allo-HSCT received anti-CD19-CAR T-cell therapy. Patients who responded to CAR T-cell therapy received DSI or DLI as maintenance therapy. We compared the clinical responses, acute graft versus host disease (aGVHD), expansion of CAR-T-cells, and adverse events between the two groups. In our study, 19 patients received DSI/DLI as maintenance therapy. After DSI/DLI therapy, progression-free survival and overall survival were higher in the DSI group than in the DLI group at 365 days. The grades I and II of aGVHD was observed in four patients (36.4%) in the DSI group. Only one patient developed grade II aGVHD in the DLI group. The peaks of CAR T-cells in the DSI group were higher than those in the DLI group. IL-6 and TNF-α levels increased again in nine of 11 patients after DSI but not in the DLI group. Our findings indicate that for B-ALL patients who relapse after allo-HSCT, DSI is a feasible maintenance therapy if CR is obtained with CAR-T-cell therapy.

Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long-term clinical outcomes and health-related quality of life assessment.

Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health-related quality of life (HR-QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo-HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft-versus-host disease (GvHD)-guided DLIs. Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation. A total of 105 patients were eligible. Eighty-seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2-4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%-50.6%) and 73.3% (95% CI = 67.4%-79.2%), respectively. The cumulative incidence of relapse (CIR), transplant-related mortality (TRM), and leukemia-free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%-41.1%), 22.1% (95% CI = 11.3%-32.9%), and 46.4% (95% CI = 36.8%-56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%-37.6%), 21.6% (95% CI = 11.2%-32.0%), and 50.8% (95% CI = 40.0%-61.6%), respectively. At the end of follow-up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR-QoL. Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long-term LFS, but also with satisfactory HR-QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.

Preemptive Immunotherapy for Minimal Residual Disease in Patients With t(8;21) Acute Myeloid Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation.

In patients with t(8;21) acute myeloid leukemia (AML), recurrent minimal residual disease (MRD) measured by RUNX1-RUNX1T1 transcript levels can predict relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study aimed to compare the efficacy of preemptive interferon (IFN)-α therapy and donor lymphocyte infusion (DLI) in patients with t(8;21) AML following allo-HSCT. We also evaluated the appropriate method for patients with different levels of RUNX1-RUNX1T1 transcripts. In this retrospective study, consecutive patients who had high-risk t(8;21) AML and received allo-HSCT were enrolled. The inclusion criteria were as follows: (1) age ≤65 years; (2) regained MRD positive following allo-HSCT. MRD positive was defined as the loss of a ≥4.5-log reduction and/or <4.5-log reduction in the RUNX1-RUNX1T1 transcripts, and high-level, intermediate-level, and low-level MRDs were, respectively, defined as <2.5-log, 2.5−3.5-log, and 3.5−4.5-log reductions in the transcripts compared with the pretreatment baseline level. Patients with positive RUNX1-RUNX1T1 could receive preemptive IFN-α therapy or DLI, which was primarily based on donor availability and the intentions of physicians and patients. The patients received recombinant human IFN-α-2b therapy by subcutaneous injection twice a week every 4 weeks. IFN-α therapy was scheduled for six cycles or until the RUNX1-RUNX1T1 transcripts were negative for at least two consecutive tests. The rates of MRD turning negative for patients with low-level, intermediate-level, and high-level RUNX1-RUNX1T1 receiving IFN-α were 87.5%, 58.1%, and 22.2%, respectively; meanwhile, for patients with intermediate-level and high-level RUNX1-RUNX1T1 receiving DLI, the rates were 50.0% and 14.3%, respectively. For patients with low-level and intermediate-level RUNX1-RUNX1T1, the probability of overall survival at 2 years was higher in the IFN-α group than in the DLI group (87.6% vs. 55.6%; p = 0.003). For patients with high levels of RUNX1-RUNX1T1, the probability of overall survival was comparable between the IFN-α and DLI groups (53.3% vs. 83.3%; p = 0.780). Therefore, patients with low-level and intermediate-level RUNX1-RUNX1T1 could benefit more from preemptive IFN-α therapy compared with DLI. Clinical outcomes were comparable between preemptive IFN-α therapy and DLI in patients with high-level RUNX1-RUNX1T1; however, they should be further improved.

Donor lymphocyte infusion after haploidentical hematopoietic stem cell transplantation for acute myeloid leukemia

Although haploidentical donor lymphocyte infusion (DLI) is a valid treatment option for relapsed acute myeloid leukemia (AML), the incidence and risk factors for graft-versus-host disease (GVHD) and the efficacy of haploidentical DLI have not been fully evaluated. We retrospectively analyzed the outcomes after haploidentical DLI for 84 patients with AML using a nationwide database and additional questionnaires. The median number of DLI cycles and infused CD3+ cell dose was 1 and 1.0 × 106/kg, respectively. The infused CD3+ cell count of 5.0 × 105/kg or higher was associated with acute GVHD (grade II-IV, 32.1% vs. 10.5%, p = 0.03; grade III-IV, 21.4% vs. 5.3%, p = 0.10). Patients who developed grade III-IV acute GVHD more frequently succumbed to treatment-related mortality (46.7% vs. 15.8% at 1 year, p = 0.002), although the relapse-related mortality was significantly low (40.0% vs. 72.2% at 1 year, p = 0.025). The overall response to DLI was significantly higher in the preemptive DLI group (47.4%) than in the therapeutic group (13.9%, p = 0.002). In the multivariate analysis, preemptive DLI was the predictive factor for overall response (odds ratio, 5.58; p = 0.003). Our results indicated the substantial risk of acute GVHD after haploidentical DLI with CD3+ cell count of 5.0×105/kg or higher and the favorable outcomes after preemptive DLI.

Prophylactic Modified Donor Lymphocyte Infusion after Allogeneic Peripheral Blood Stem Cell Transplantation for Very High-Risk Hematological Malignancies: Low Incidence of Relapse without Increasing the Risk of Graft-Versus-Host Disease

Introduction The prognosis of patients with very high-risk hematologic malignancies who have relapsed/refractory diseases or carrying very poor-risk gene mutations were dismal even after allogeneic hematopoietic stem cell transplantation. Donor lymphocyte infusion (DLI) is a promising prophylactic strategy for reducing relapse after transplant. However, DLI-associated graft-versus-host disease (GVHD) and non-relapse mortality (NRM) were still concerned, especially after allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Therefore, prophylactic DLI should be safe with tolerable DLI-associated GVHD and NRM except for its anti-leukemia effect. To evaluate the safety and efficacy of prophylactic DLI for the very high-risk hematologic malignancies after allo-PBSCT, we performed a cohort study in 160 consecutive patients with hematological malignancies who received unmanipulated allo-PBSCT. DLI procedure was modified to use G-CSF mobilized peripheral progenitors instead of steady state lymphocytes and 4 to 6 weeks of immunosuppressant for prevention of DLI-associated GVHD. The outcomes of those very high-risk patients (group A: DLI group; group B: non-DLI group) and the patients without the very high-risk features (group C) who were not planned for prophylactic DLI were compared.Patients and Methods The underlying diseases consist of acute myeloid leukemia (n = 78), myelodysplastic syndrome (n = 22), acute lymphoblastic leukemia/lymphoma (n = 45), chronic myeloid leukemia (n = 7), non-Hodgkin's lymphoma (n = 7), and plasma cell leukemia (n = 1). Sixty five patients (41.2%) received allo-PBSCT from HLA-matched sibling donors, 7 patients (4.4%) from matched unrelated donors, and 87 patients (54.4%) from haploidentical donors (Table 1). The very high-risk features were defined as 1) disease in non-remission state at time of transplant; 2) acute leukemia achieving complete remission (CR1) with 3 or more cycles of induction chemotherapy; 3) leukemia in CR1/CR2 carrying TP53, TET2 or DNMT3A gene mutation. Patients in CR with FLT3/ITD or BCR/ABL T315I gene mutation were enrolled due to the unavailability of effective targeted drugs. Prophylactic modified DLI was planned at 30 to 60 days post-transplant for all very high-risk patients with the absence of GVHD. The infusion was G-CSF mobilized peripheral progenitors from cryopreserved cell aliquots of the original graft. The trough concentration of CSA was maintained at 180 to 250 ng/mL for at least 4 to 6 weeks post-DLI and then discontinued within 2 weeks when no GVHD occurred. All the patients were followed-up for a median of 11.1 (0.5 - 29.7) months after transplant.Results Prophylactic DLI was administered for 29 very high-risk patients (group A) at a median of 63 (25 - 176) days after transplant. The median numbers of mononuclear cells and CD3+ lymphocytes infused were 0.7 (0.1 - 1.4) × 108/kg and 18.5 (5.4 - 69.2) × 106/kg with a single dose. Nineteen patients (39.6%) with very high-risk features did not receive prophylactic DLI (group B) for the reasons of early relapse (n = 8), occurrence of GVHD (n = 8), and uncontrolled infections (n = 3). The cumulative incidence (CI) of grade II-IV acute GVHD at day 100 after transplant was 33.2% in group A, 38.0% in group B (p= 0.318), and 28.2% in group C (p= 0.746). The 2-year CI of chronic GVHD was 29.9% in group A, 15.8% in group B (p= 0.428), and 54.6% in group C (p= 0.255). The 2-year CI of relapse was 54.6% in group A, which was significantly lower than that in group B (68.4%, p= 0.019). The relapse-free survival in group A was superior to that in group B (37.3% vs . 24.6%, p = 0.032). In the very high-risk group of patients (group A and B), prophylactic DLI was correlated with a lower risk of relapse (p= 0.043, hazard ratio = 0.45). The 2-year CI of NRM in group A was not significantly different from that in group B (22.4% vs . 15.8%, p= 0.461) or group C (22.4% vs . 23.2%, p= 0.949). In addition, there was no significant difference in overall survival between group A and group B (48.6% vs . 35.1%, p = 0.134). The 6-month CI of CMV/EBV reactivations in group A was not significantly different from that in group B (p= 0.107 and p= 0.668) or group C (p= 0.130 and p= 0.596).Conclusions This study showed that the prophylactic DLI after unmanipulated allo-PBSCT was well tolerated and effective for the patients with very high-risk hematologic malignancies in decreasing relapse without increasing the risks of GVHD and NRM. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Outcomes after Second Allogeneic Transplantation and Donor Lymphocyte Infusion for Relapse after a First Allogeneic Transplant

Outcomes after Second Allogeneic Transplantation and Donor Lymphocyte Infusion for Relapse after a First Allogeneic Transplant

Comparison of the DONOR Lymphocyte Infusion and Second Allogeneic STEM-CELL Transplantation in the Treatment of First Hematological Relapse after Allogeneic STEM-CELL Transplantation in Adults with ACUTE Leukemia

Purpose: Relapse after allogeneic hematopoietic bone marrow transplantation (AHSCT) in acute leukemia is a poor prognosis indicator. Although there is no definite opinion about the optimal treatment chemotherapy, second allogeneic hematopoietic stem cell transplantation (AHSCT2) or donor lymphocyte infusion (DLI) are among the treatment options. Relapse after allogeneic transplantation remains unfortunately quite common and we frequently face difficult management decisions. The decision to offer either option is based on several factors, including donor availability, remission status, presence of disabling comorbidities, and center or physician preference. The aim of this study was to investigate the effect of AHBMT2 or DLI on survival in relapsed transplant patients suffers from acute leukemia. Method:We here in report a retrospective analysis of single-center experience with AHBMT2 and DLI to treat patients relapsing from acute leukemia after a first AHBMT from 2003 to 2018.We enrolled the study 20 patients who underwent DLI and 6 patients who underwent AHBMT2. Result:There was no significant difference in OS between the groups afterward intervention (p:0,9) The 2-year survival rate was 33% in the AHBMT2 group and 43% in the DLI group. After intervention, chronic GVHD was observed only in DLI group. Conclusion: DLI can be considered after relapse as a safer and less toxic method than AHBMT2. Disclosures No relevant conflicts of interest to declare.

Effect of Stem Cell Boost and Donor Lymphocyte Infusion on the Incidence of Graft-Versus-Host Disease at Emory University Hospital

Introduction Allogeneic hematopoietic stem cell transplantation (SCT) is a widely used to treat refractory and relapsed hematological malignancies. Additional CD34+ selected cells, or stem cell boosts (SCB), and CD3+ T cells, or donor lymphocyte infusions (DLI) are often administered to treat poor hematopoietic graft function or relapse of the underlying malignancy, respectively, following SCT. Although the T cell dose in SCB and DLI vary by more than 3 logs, graft-versus-host disease (GVHD) can be a major cause of morbidity and mortality in patients who receive additional post-transplant donor T cells. The purpose of this study is to test the hypothesis that the incidence of GVHD after infusions of additional donor T cells is associated with the cumulative incidence of GVHD in patients who received DLI vs SCB. Methods A retrospective cohort study was conducted on consecutive patients at Emory University Hospital who received a DLI or CD34+ cell-selected SCB from January 2000 to September 2016. Excluding patients with incomplete records, 46 DLI and 15 SCB patients were analyzed for post-infusion GVHD and 2-year post-infusion survival. SPSS Statistics was used to conduct a binary logistic regression on DLI and SCB patients in order to determine significant variation in GVHD incidence per relevant covariates. Results The median doses of CD3+ T cells were 18 × 10E6 cells/kg and 0.054 × 10E6 cells/kg for DLI and SCB recipients, respectively. 73% of SCB patients received prophylactic immunosuppressive drug therapy versus 20% of DLI patients (Table 1). In spite of receiving less than 0.3% of the T cell dose of DLI recipients, SCB recipients had a 60% cumulative incidence of GVHD by 2-years of follow-up versus 37% in DLI patients (Figure 1; p=0.142). Binary regression models showed that GVHD incidence did not vary significantly with the dose of T cells and other covariates, except age in the DLI group (Tables 2 and 3). Overall survival at 2 years was 48% for DLI recipients and 87% for SCB recipients, with relapse of the underlying malignancy being the major cause of death among both DLI patients and SCB patients. Conclusions DLI patients had a lower incidence of GVHD compared to SCB patients, despite the former receiving higher median doses of T cells. Neither delivered T cell dose nor post-infusion immune-prophylaxis were significantly associated with the development of GVHD after post-transplant infusions of donor hematopoietic cells. These data suggest the hypothesis that failure of thymic selection of donor-stem cell derived T cells may contribute to GVHD following infusions of CD34-cell selected SCB.

Superior Salvage Treatment with Regimen Containing Sorafenib for Relapse of Acute Myeloid Leukemia with FLT3-ITD after Allo-HSCT

Background Internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3-ITD) mutation has been reported in about 25% of patients with acute myeloid leukemia (AML). In contrast to patients with FLT3-ITD wild-type, AML with FLT3-ITD mutations have an inferior survival, primarily due to shorter remission duration and higher relapse rate. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves the survival for FLT3-ITD AML, the rate of leukemia relapse remains high. Patients experiencing leukemia relapse post-transplants have a dismal prognosis. Recent studies have demonstrated that sorafenib monotherapy or in combination with other therapeutic strategies could induce sustained responses for patients with FLT3-ITD relapsed post-transplants. The aim of this study is to evaluate the efficacy of sorafenib combined with other therapeutic strategies for AML with FLT3-ITD relapsed after allo-HSCT.MethodsA total of 76 AML with FLT3-ITD relapsed after allo-HSCT from January 2012 to May 2017 were enrolled in this study. Depending on whether receiving salvage therapy containing sorafenib, patients were divided into 2 groups: sorafenib group (n=49) and non-sorafenib group (n=27). On the basis of the differences of therapeutic regimens, patients were divided into 4 subgroups, including sorafenib+ chemotherapy+donor lymphocyte infusion (DLI) (Group A, n=39), sorafenib+ chemotherapy (Group B, n=10), chemotherapy +DLI (Group C, n=15), and monochemotherapy (Group D, n=12). Outcomes of different therapeutic regimens were compared.Results Forty patients obtained complete remission (CR) and 12 partial remission after salvage therapies, with the CR and overall response (OR) rates of 52.6% and 68.4%. The CR and OR rates were 65.3% and 81.6% in the sorafenib group, compared with 29.6% and 44.4% in the non-sorafenib group (P=0.003, P=0.001). Subgroup analysis showed that the CR and OR rates in Group A were higher than that in Group D (P=0.006, P=0.001), and they were similar to that in Groups B and C (all P values >0.008). There were also no significant differences in the CR and OR rates among Groups B, C, and D (all P values >0.008). With a median follow-up of 245 (range 30-1992) days after relapse, 26 patients remained alive and 50 died. The 3-year overall survival (OS) was 33.8% (95% CI, 23.3%-44.5%). The 3-year OS in the sorafenib group was superior to that in the non-sorafenib group (42.0% vs 18.5%, P=0.002). Subgroup analysis revealed that sorafenib combined with chemotherapy followed by DLI was superior to other regimens, with 3-year OS of 47.8%, 20.0%, 20.0%, and 16.7% in Groups A, B, C, and D, respectively (P=0.007). The incidences of acute and chronic GVHD as well as the mortality of GVHD after salvage therapies were similar among the four groups (P=0.304, P=0.429, P=0.601, respectively). Multivariate analysis revealed that salvage therapy containing sorafenib was the only protective factor for OS (P=0.022, hazard ratios= 0.479).ConclusionsSalvage therapy containing sorafenib was superior to that not containing sorafenib, and sorafenib combined with chemotherapy followed by DLI revealed optimal efficacy for relapse of AML with FLT3-ITD after allo-HSCT. DisclosuresFan:National Natural Science Foundation of China (No. 81600141, No. 81770190) and Natural Science Foundation of Guangdong Province (No. 2016A030310390): Research Funding.

Abstract 598: Utility of cell therapy to control relapsed acute myeloid leukemia following allogeneic stem cell transplantation: Does cell source matter

Abstract Introduction: Although allogenic hematopoietic stem cell transplantation (Allo-SCT) is curative therapy for acute myeloid leukemia (AML), many patients experience relapse following allo-SCT. For these patients, it is well known that donor lymphocyte infusion (DLI) could rescue a certain proportion via graft versus leukemia effect. On the other hand, with the advance of abundant stem cell harvesting techniques, residual stem cell after allo-SCT is also frequently used as a rescue therapy for AML relapse. However, clinical utility of residual stem cell is not well established yet. Hence, in this study, we compare the outcome of DLI with residual stem cell infusion in relapsed AML after allo-SCT. Materials and Methods: We retrospectively reviewed the AML patients who underwent DLI or residual stem cell infusion for relapsed disease after allo-SCT from 2001 to 2017 in Seoul National University Hospital. We analyzed factors including overall survival (OS), cell counts, disease status at cell therapy, and GVHD development. Our primary outcome was to compare OS after cell therapy between DLI group and residual stem cell group. Results: A total of 81 patients were analyzed. There were 50 patients (25 males and 25 females) who received cell therapy using DLI, and 31 patients (11 males and 20 females) who received residual stem cell infusion. There was no difference in age and duration from allo-SCT to cell therapy between the two groups. Majority of patients received cell therapy for first relapse after allo-SCT (63% in DLI, 93% in residual stem cell group). Median CD3 cell count infused was not different between DLI and residual stem cell product (median value of 0.967 X 108/kg and 0.964 X 108/kg). Median CD34 cell dose was 2.34 X 106/kg in residual stem cell group. There was no difference in OS between the two groups (median OS 8.5 months for DLI and 10.2 months for residual stem cell group, p-value 0.673). GVHD occurred in 44% in DLI group and 41.9% in residual stem cell group. When multivariate analysis was performed, disease status at stem cell therapy or duration from allo-SCT to relapse did not show any significant difference. Characteristics of long-term survivors after cell therapy following relapse after allo-SCT could be summarized as whether to acquire bone marrow CR after therapy. Conclusion: This study demonstrates that clinical utility of DLI and residual stem cell infusion is similar in relapsed AML after allo-SCT. Hence, residual stem cell could be used as an alternative source for T-cell therapy following allo-SCT. Citation Format: Woochan Park, Inho Kim, Sung-soo Yoon, Seonyang Park, Youngil Koh. Utility of cell therapy to control relapsed acute myeloid leukemia following allogeneic stem cell transplantation: Does cell source matter [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 598.

Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation

ABSTRACTTo improve prognosis of post-transplant lymphoproliferative disease (PTLD), a sequential therapeutic strategy that rituximab-based treatments followed by donor lymphocyte infusion (DLI) or autologous EBV-specific cytotoxic T lymphocytes (EBV-CTL) for biopsy-proven EBV-associated PTLD in recipients of allogeneic hematopoietic stem cell transplantation was designed. 84 patients with EBV-PTLD were enrolled in this prospective study. After two cycles of the rituximab-based treatments, 68 of 84 patients (81% [95% CI 71–88]) responded and 52 (62% [51–72]) had CRs. This increased to 73 of 77 patients (95% [87–98]) with completion of sequential cell infusions, and 70 of 77 (91% [82–96]) achieved CRs after DLI or autologous EBV-CTL infusion. 22 patients experienced acute GVHD (aGVHD) (grade I in 5 and grade II in 13, grade III in 4) and 13 chronic GVHD (limited cGVHD in 7 and extensive cGVHD in 6) in 62 patients undergoing a median of three doses of DLI. The incidences of GVHD were similar between DLI and EBV-CTL group (aGVHD 35% vs. 33%, p = 0.876; cGVHD 21% vs. 13%; p = 0.503). EBV-CTL activity after the rituximab-based treatments did not change, while increased after cell infusions and reached its maximum in the 3rd or 6th month after EBV-CTL or DLI treatment, respectively. The 5-y cumulative incidence of PTLD relapse was 4.5% ± 3.3%. The 5-y overall survival (OS) and progression-free survival (PFS) after PTLD were 70.7% ± 5.2% and 68.9% ± 5.3%, respectively. Rituximab-based treatments combined with adoptive cellular immunotherapy might elevate CR rates and reduce relapse of PTLD after allo-HSCT.

Extracorporeal Photopheresis As Second Line Therapy for Steroid Refractory Acute Gvhd: Retrospective Study of Long-Term Outcomes

IntroductionUp to 50% of patients with acute GVHD (aGVHD) have a suboptimal response to first line therapy with corticosteroids. Extracorporeal photopheresis (ECP) is one of the recommended second line options. Overall response rates of 60-77% have been reported with ECP as second line therapy for aGVHD. Factors associated with lower response and survival were Grade >II at onset and number of organs involved. In a large retrospective study of ECP as second line therapy, 19.5% of patients developed chronic GVHD (cGVHD). Previous studies have included small numbers of patients with aGVHD post T cell depleted transplants or Donor Lymphocyte Infusion (DLI).MethodsWe conducted a retrospective analysis of outcomes in 40 patients treated with ECP for steroid refractory or steroid dependent aGVHD at 2 UK transplant centres. The aim was to analyse overall survival and long-term outcomes. All patients received 2-3 treatments per week for 8 weeks after which schedules differed according to centre, cessation or gradual taper.ResultsBetween 2006 and 2014, 44 patients had received ECP as second line therapy, 4 were excluded from analysis as they had received less than 4 treatments. The median age was 51years (21-67years). Table 1 illustrates details of conditioning and GVHD prophylaxis. Thirty percent of patients were post DLI: 5 (12.5%) for disease relapse and 7 (17.5%) for mixed chimerism. Transplant conditioning included T cell depletion in 24 (60%): alemtuzumab n=17, ATG n=7. The median duration of steroids pre-starting ECP was 18 days (range 5-56). Using Modified Glucksberg crtieria at the onset of ECP, 5 patients (12.5%) had Grade II, 30 (75%) Grade III (including 6 with stage 4 gut) and 5 (12.5%) Grade IV aGVHD. Nine patients (22.5%) had 1 organ involvement and 31 (77.5%) had 2 or more organs involved. The dominant organ was gut in 21 (52.5%), liver in 10 (25%)and skin in 9 (22.5%). Maximal response rates were CR 57.5%, PR 27.5% and NR 15%. A number of patients received additional immunosuppressive therapy, predominantly anti-TNF antibodies: 14 patients (35%) (etanercept n=11, infliximab n=3).Using Kaplan-Meier analysis, censoring at last follow up, the overall survival from start of ECP at 5 years was 45.1% (95% CI 31.85-63.04%) Figure 1. The median survival was 2 years (27days-7.8yrs). In the DLI group, the 5 year overall survival was 59.8%. In a subgroup log rank Mantel-Cox analysis no significant difference was observed in the 5 year overall survival according to dominant organ involved: 53% skin, 40.6% gut and 50% liver (p=0.77) Figure 2.The cumulative incidence of death was 57.5% (23patients). The leading cause of death was infection 13/23 deaths (56.5%) followed by 5 deaths due to GVHD, 4 due to relapse, 1 from unrelated causes.The incidence of chronic GVHD was 55%. Treatment for cGVHD varied with 8 patients continuing ECP >12 weeks on a tapering schedule, 2 patients restarting ECP for cGVHD and the others receiving a variety of therapies including MMF, tacrolimus, Rituximab and imatinib. At last follow up, 17 patients were alive, 9 were off immunosuppression (2 of whom had not developed cGVHD) and 8 were still on immunosuppression. The performance status in the 17 surviving patients was ECOG 0= 8, 1=8 and 2=1.DiscussionOur study shows an encouraging 5 year overall survival of 45.1% in a cohort with predominantly severe Grade III aGVHD. The 5 year survival was higher in the DLI group at 59.8%. Fifty three percent had stage 3-4 gut involvement, which is a recognised poor risk feature. Infection was the leading cause of death, which is of particular relevance in the T deplete setting. Whilst 55% developed cGVHD, over a long follow up period (median of 4years), the cGVHD resolved and performance status was preserved in most of the surviving patients. The incidence of cGVHD was higher than in other studies but the patients had higher grade of aGVHD at onset, were older and had multi-organ involvement. These findings need to be confirmed in prospective studies.Table 1Pretransplant CharacteristicsNo. of patients (%)Conditioning RegimesMyeloablative10 (25%)Non-myeloablative18 (45%)Total post DLI12 (30%)T cell depletion24 (60%)Alemtuzumab17 (42.5%)ATG7 (17.5%)GVHD prophylaxisCsA20 (50%)CsA/MTX9 (22.5%)CsA/MMF Tacro/MMF8 (20%) 3 (7.5%)Donor SourceMatched sibling Matched unrelated donor 10/10 9/10 8/10 Double Cord9 (22.5%) 21 (52.5%) 3 (7.5%) 1 (2.5%) 6 (15%) [Display omitted] [Display omitted] DisclosuresRadia:Therakos: Other: ASH travel expense, Speakers Bureau. Off Label Use: Extracorporeal Photopheresis (ECP) is not licensed for use in GVHD but is recommended in international guidelines as a therapeutic option.. McLornan:Novartis: Research Funding, Speakers Bureau. Russell:Therakos: Other: shares.

Interferon-α: A Potentially Effective Treatment for Minimal Residual Disease in Acute Leukemia/Myelodysplastic Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation

In this prospective clinical study, the safety and efficacy of preemptive interferon-α (IFN-α) treatment were investigated and compared with preemptive donor lymphocyte infusion (DLI) in patients who were minimal residual disease (MRD)-positive after allogeneic hematopoietic stem cell transplantation (HSCT). Patients undergoing allogeneic HSCT were eligible if they had acute leukemia or myelodysplastic syndrome and were MRD-positive after HSCT. Patients who were able to receive DLI were assigned to a preemptive DLI group (n = 45); patients who could not or did not agree to receive DLI after HSCT received preemptive IFN-α. A total of 22 patients received preemptive IFN-α; the median treatment duration was 35 days (range, 4 to 180 days). Seven patients relapsed, and 1 patient died from severe pneumonia. The 1-year cumulative incidence of chronic graft-versus-host disease (cGVHD) after intervention was 90.9% for the IFN-α group and 62.9% for the DLI group (P < .001). MRD status after preemptive intervention was comparable in the 2 groups, and the 1-year cumulative incidence of relapse after intervention was 27.3% for the IFN-α group and 35.6% for the DLI group (P = .514). The 1-year cumulative incidence of nonrelapse mortality after intervention was 4.5% for the IFN-α group and 4.4% for the DLI group (P = .985). The 1-year probability of disease-free survival after intervention was 68.2% for the IFN-α group and 60.0% for the DLI group (P = .517). In multivariate analysis, early-onset MRD, persistent MRD after intervention, and absence of cGVHD after intervention were significantly associated with poorer clinical outcomes. Thus, preemptive IFN-α may be a potential alternative for MRD-positive patients who cannot receive preemptive DLI after HSCT.

A Comparison Of Long-Term Outcomes Of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors In CML Patients Relapsed After Allogeneic Hemopoietic Stem Cell Transplantation

Abstract 5501Relapse is a major cause of treatment failure of allogeneic hematopoietic cell transplantation (HCT) for Chronic Myeloid Leukemia (CML). DLI (Donor lymphocyte infusion) and TKI (Tyrosine Kinase inhibitors) are the two standard treatment options in this setting but reports comparing their long-term outcomes are scarce.Between 1993 and 2012, 28 patients underwent DLI and 18 patients received TKI for chronic or advanced phase relapse of CML at our institution. Chronic hematologic, cytogenetic and molecular relapses were considered as chronic phase relapses. Accelerated phase and blast crisis relapses were considered as advanced phase relapses. Overall survival (OS), failure free survival (FFS) and cumulative incidence of failure (CIF) were analyzed retrospectively and for these analyses, failure was defined as lack of response, relapse or intolerance requiring change in treatment. This study had Institutional Research Ethics Board approval.Among18 patients treated with TKI, 15 patients received imatinib, 2 received dasatinib and 1 received nilotinib as the first line treatment. In DLI group, number of infusions per patient ranged between 2 and 4. Patients in the DLI group were more likely to be transplanted during the 1st chronic phase of disease (86% vs. 56%, p=0.008), with bone marrow stem cells (100% vs. 56%, p=<0.0001) and less likely to have pre-HCT tyrosine kinase inhibitor treatment (0% vs. 33%, p=0.002). Patients in the TKI group are more likely to be treated during advance phases of relapse (39% vs. 7%, p=0.018). Type of donor, age at stem cell transplant or relapse and prior acute or chronic GVHD were not different between the groups. No patients received reduced intensity conditioning or T-cell depleted grafts.64% of patients treated with DLI and 83% treated with TKIs achieved complete molecular response (CMR). 21% of patients initially treated with DLI required further treatment with TKIs after a second relapse. In the TKI group, no patients were later treated with DLI, but one required a change from imatinib to dasatinib due to intolerance. The incidences of treatment failures in DLI and TKI groups were 43% and 28% respectively.At a median follow up of 146 (range, 40-220) and 70 (range, 9-139) months respectively, 9 (32%) in the DLI group and 6 (33%) in TKI group have died. when chronic phase relapses were analyzed separately 7 (21%) in the DLI group and none from the TKI treated group have died. Mortality was higher in advanced phase relapses with 2 (100%) patients in the DLI group having died without achieving any response, and in the TKI group; 4 (57%) patients achieved CMR but eventually 6 out of 7 (86%) patients have died at a median time of 9 (3-114) months.In multivariable analysis, advanced phase of relapse was associated with shorter OS (HR=109.7; 95% CI, 12.2-985.3; p= <0.0001), shorter FFS (HR = 82.3; 95% CI, 7.1-956.5; p =0.0004) and higher CIF (HR= 67.9; 95% CI, 6.9-669.8; p=0.0003). Comparing treatment with TKI, treatment with DLI was associated with an inferior OS (HR =37.4; 95% CI, 2.2-625.4; p=0.01), shorter FFS (HR =21.15; 95% CI, 1.8-251; p=0.02) and higher CIF (HR =19.5; 95% CI, 1.6-236.5; p=0.02). Prior acute GVHD grade 2-4 was associated with higher CIF (HR=3.3; 95% CI, 1.15-9.2; p= 0.03), but there was no effect on OS and FFS. Prior chronic GVHD, age at relapse treatment, and time from stem cell transplant to relapse treatment and year of relapse treatment were not found to be significant factors.New onset or worsening of GVHD was significantly higher in the DLI group (68% vs. 6%, p=0.001). Among the patients treated with DLI, development of post DLI GVHD was associated with better OS (HR=0.26; 95% CI, 0.07-0.99; p=0.048), FFS (HR=0.3, 95% CI, 0.11-0.88; p=0.027) and lower CIF (HR=0.32; 95% CI, 0.1-0.96; p=0.04). Prior history of chronic GVHD was associated with higher FFS in DLI treated patients (HR=0.3; 95% CI, 0.1-0.89; p= 0.03), but did not have significant effect on OS (HR=0.32, 95% CI, 0.08-1.3; p=0.1) or CIF (HR=0.43; 95% CI, 0.143-1.28; p=0.13).In conclusion, TKIs appears better than DLI in CML patients who had relapsed in chronic phase after myeloablative T-cell-replete HCT. Outcomes were poor in advanced phase relapses irrespective of modality and novel strategies need to be explored in this group of patients. Disclosures:No relevant conflicts of interest to declare.

Follow Up On CD8-Depleted Donor-Lymphocyte Infusions After T-Cell Depleted Allogeneic Hemopoietic Stem Cell Transplantation

We applied prophylactic CD8-depleted (CD8depl) donor lymphocyte infusions (DLI) in the setting of T-cell depleted reduced-intensity allogeneic hematopoietic stem cell transplantation (HSCT) in a phase I/II trial. T-cell depletion was carried out by the use of high-dose Alemtuzumab (100 mg or 60 mg for unrelated or sibling donor transplantation, respectively). We have demonstrated the feasibility of this approach after having treated 23 patients in this protocol (Meyer et al. Blood 2007). From 2004 to 2011, 134 patients with different hematologic diseases were included and followed for a median observation time of 1.5 years after transplantation (range, 1.5-9 years). Median age was 56 years (range, 19-71). Stem cell source was peripheral blood from either matched siblings (n=23), matched unrelated (n=62), or donors with single HLA mismatches (unrelated n=48, related n=1). Tapering of cyclosporine A was started in the 6th week after transplantation. Subsequently, CD8depl DLI were administered prophylactically in escalating doses starting with 1x106 CD4 T cells/kg bodyweight. 53 patients received at least one dose of DLI. Among 81 patients who did not qualify for DLI, 60 patients had primary mild GVHD. Following DLI, acute GVHD was the major reason for withholding subsequent DLI-doses (66%), mainly because of acute GVHD ≤ 2°. Extensive chronic GVHD was diagnosed in 9.4% of the patients. Overall survival after 1 and 3 years was 60% and 43%, respectively. Survival significantly differed between the DLI and non DLI group after 3 years (63.8% vs. 30.1%, p=0.002). The inferior outcome of the non DLI group was confirmed when only those patients who did not receive DLI for other reasons than GVHD were considered (28.6%). The largest patient cohort in our trial were patients with AML and MDS (n=21 with and n=33 without DLI). In these patients, the survival benefit for the DLI group after 3 years was significant (75.8% vs 28.9%, p=0.0012). Interestingly, the relapse rate did not differ between DLI and non-DLI patients but the non-relapse mortality. The presence of GVHD at any time was associated with a reduced relapse rate (57.9% vs. 31.4%, p=0.0015), independent of DLI-application. However, GVHD had no impact on overall survival. Decreasing donor T-cell chimerism (TCC) was found in 34 patients who subsequently received DLI and 13 who did not. Following CD8depl DLI, 31 patients (88%) converted to full donor. In contrast, only 2 of the patients with decreasing TCC in the non-DLI group (15.3%) converted spontaneously. In summary, we observed that the application of prophylactic CD8depl DLI was associated with a survival benefit and the re-establishment of full donor T-cell chimerism. In AML/MDS patients the improved survival was associated with lower treatment-related mortality rather than a reduced relapse-rate. Our data strongly suggest randomized trials comparing prophylactic application of CD8depl DLI vs. no DLI as well as CD8depl vs. non-manipulated DLI in a preemptive setting. Disclosures: Off Label Use: MabCampath has been used for T-cell depletion.

A Comparison of Long-Term Outcomes of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors in Patients With Relapsed CML After Allogeneic Hematopoietic Cell Transplantation

Donor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare. A total of 46 patients were treated with either DLI (n = 28) or TKIs (n = 18) during a first relapse of CML after HCT between 1993 and 2012. The stage of relapse was the chronic phase in 37 patients and the advanced phase in 9 patients. All patients had myeloablative conditioning without T-cell depletion during HCT. The median interval between HCT and treatment for relapse was 34 (range, 2-197) months. At a median follow-up of 146 and 70 months, respectively, 32% of the DLI group and 33% of the TKI group had died. Six (21%) patients initially treated with DLI received TKIs during a second relapse. In multivariable analyses, DLI was associated with inferior overall survival (OS) (hazard ratio [HR], 37.4; 95% confidence interval [CI], 2.2-625.4; P = .01), shorter failure-free survival (FFS) (HR, 21.15; 95% CI, 1.8-251; P = .02), higher cumulative incidence of failure (CIF) (HR, 19.5; 95% CI, 1.6-236.5; P = .02), and increased incidence of treatment-induced graft vs. host disease (GVHD) (68% vs. 6%; P = .001). TKIs appear better than DLI in chronic-phase relapses after myeloablative non-T-cell-depleted HCT. Outcomes were poor in advanced-phase relapses irrespective of treatment modality.

Treatment of leukemia with immunized donor cell infusion after nonmyeloablative haploidentical bone marrow transplantation

This study was purposed to investigate the therapeutic effects of early transfusion of immunized donor lymphocytes after haploidentical transplantation by means of mouse model of nonmyeloablative haploidentical bone marrow transplantation. CB6F1 female mouse was served as recipient and C57BL/6 male mouse was served as donor. Each CB6F1 female mouse was subjected to intravenous transfusion with 1×10(6) erythroleukemia (EL9611) cells at day 4 before transplantation, followed with intraperitoneal injection of Ara-C (0.015 g) respectively at day 2 and day 1, then conditioned for BMT with TBI (450 cGy) at day 1 before transplantation. After conditioning (day 0), each of recipients was transplanted with 6×10(7) mixture of bone marrow and spleen cells from the C57BL/6 mice, and was infused with 6 × 10(7) immunized donor lymphocytes at day 15 after transplantation. All treated animals were evaluated for survival, development of leukemia and aGVHD. The donor CD3(+) cell chimerism and sex determining region Y gene (SRY)in recipients were monitored periodically after transplantation. The results showed tht all mice with only inoculation of 10(6) EL9611 cells survived for 15 ± 1 days (n = 4); all mice of other groups obtained the varying degrees of implantation. SRY could be detected at day 30 and 60 after transplantation. The chimerism of donor CD3(+) cells in mixed bone marrow transplantation (MT) group at day 14, 30 and 60 respectively reached 17.95% ± 12.03%, 37.34% ± 2.78% and 47.06% ± 6.1%. In donor lymphocyte infusion (DLI) group it reached 69.78% ± 12.62%, 75% ± 15.97%, 83.41% ± 16.07% at day 30, 45 and 60 after transplantation. The mice of MT and DLI group survived for 66.66 ± 1.47 days and 78.2 ± 7.82 days. It is concluded that the high tumor burden before transplantation can affect donor cell engraftment and prognosis.Early post-transplanted infusion of immunized lymphocytes from donor can help to improve the therapeutic efficacy and survival.

CD4+ T Cell–Depleted Lymphocyte Infusion Impairs Neither the Recovery of Recipient Thymus nor the Development of Transplanted Thymus

Thymus transplantation, in conjunction with bone marrow transplantation (BMT), has been attracting attention for the treatment of various diseases. Recently, donor lymphocyte infusion (DLI) has been used as a helpful tool for establishing donor chimerism and preventing a relapse of leukemia/lymphoma. However, the effects of DLI on transplanted and recipient thymuses have not been explored. We therefore performed DLI in the intrabone marrow-BMT + thymus transplantation setting. We have found that DLI leads to derangements in both recipient thymuses and transplanted thymuses; by 2 wk after BMT, we saw a decrease in total cell number, a lower percentage of CD4(+)CD8(+) cells, and the obliteration of the thymic corticomedullary junction. Four weeks later, the thymic impairment became more serious. However, when we depleted the CD4(+) T cells (CD4(-)-DLI), the recipient thymic recovery and transplanted thymic development were significantly restored by the treatment. In addition, there were much greater levels of TNF-α and Fas ligand, and a lower percentage of regulatory T cells in the DLI group than in the CD4(-)-DLI group. These findings indicate that inflammation induced by DLI, especially by CD4(+) T cells, plays a crucial role in the thymic impairment.

Impact of Prophylactic CD8-Depleted Donor-Lymphocyte Infusions After Allogeneic Hematopoietic Stem Cell Transplantation and Alemtuzumab Mediated T-Cell Depletion,

Abstract 4109We have previously demonstrated that the application of CD8-depleted donor-lymphocyte infusions (DLI) is feasible after reduced-intensity conditioning and in vivo T-cell depletion by alemtuzumab. DLI overcome slow lymphocyte recovery associated with alemtuzumab-administration and improve anti-infectious immunity and reliably convert a decreasing T-cell chimerism (Meyer et al. Blood 2007 & BMT 2010).Here we provide clinical follow up data of 117 patients with different hematological diseases and a median observation time of 1 year (range, 1–86 months) post hematopoietic stem cell transplantation (HSCT). The majority of patients either suffered from an acute leukemia / MDS (n=54), lymphoma (n=32), myeloma (n=17), or myeloproliferative neoplasms (n=12). Two patients suffered from non-malignant diseases. The median age of the patients was 56 years (range, 19–71) and none of them qualified for a conventional conditioning regimen. 50 patients had undergone previous transplantations (autologous: n=47, allogeneic: n=3). Donors were matched siblings (n=20), matched unrelated donors (n=55), or unrelated donors with a single HLA mismatch (n=42). Between days 60 and 120 after HSCT, without calcineurin-inhibitors and in the absence of graft-versus-host disease (GVHD), 1×106 CD8-depleted DLI per kg bodyweight were administered. Up to three further DLI were given in escalating doses in 60 to 90 day intervals. Following this procedure, 45 patients received at least one dose of DLI. Among those patients who did not qualify for DLI, 50 patients had primary GVHD. In 22 patients DLI were not administered for other reasons (donor unavailable, infections, relapse). In 64% of DLI induced acute GVHD, which was the major reason for withholding the next DLI-dose step. The rate of acute GVHD > grade 2 was 30%. 10% suffered from extensive chronic GVHD. The 1 and 3 year overall survival was 63% and 43%, respectively. Survival significantly differed between the DLI and the non DLI group after 3 years (63% vs. 27%, p=0.002). Since this trial was not randomized, we also compared the DLI group to only those patients who did not receive DLI for other reasons than primary GVHD and found similar results (62% vs. 28%, p=0.01). As expected, the presence of GVHD at any time was associated with a reduced relapse rate in all patients (55.8% vs 30.8%, p=0.013). Although DLI was associated with a survival benefit, the relapse rate did not differ from that of the no-DLI cohort. AML/MDS patients represented the largest group of patients included in our study (n= 48). Among these, 41 patients achieved the time point for DLI administration, 16 of them received at least one dose of prophylactic DLI. 9 patients developed GVHD after DLI application. 20 patients had primary GVHD as major cause for not receiving DLI. The survival curves differed significantly between the DLI and non DLI group after 1 and 3 years (91.7% vs. 54%, and 82.5% vs 24% p=0.004). The estimated 5 year overall survival for all AML patients was 50.4%. There was no significant difference analyzing the relapse rate (20% vs 18.8%).In summary, the prophylactic application of CD8-depleted DLI in the absence of GVHD was associated with a survival benefit. However, we were not able to relate this benefit to a decreased relapse rate, and we assume a better control of infections. Our data strongly support a randomized trial, comparing prophylactic vs. preemptive / therapeutic DLI application in the context of T-cell depleted HSCT. Disclosures:Meyer:BMS: Membership on an entity's Board of Directors or advisory committees.