Role Of Donor Lymphocyte Infusion Research Articles

CD19+ lineage chimerism, an early biomarker after anti-CD19 CAR-T cell therapy in patients previously receiving a hematopoietic stem cell transplantation.

Treatment targeting CD19 by a chimeric antigen receptor expressed on T cells (anti-CD19 CAR-T) has led to a breakthrough in the management and treatment of relapsed and refractory B- cell acute lymphoblastic leukemia (B-ALL). After infusion, the efficacy of anti-CD19 CAR-T is monitored by bone marrow negative minimal residual disease and the absence of peripheral CD19+ B lymphocytes (B-cell aplasia). In patients who have received an allogenic Hematopoietic Stem Cell Transplantation (HSCT) prior to treatment with anti-CD19 CAR-T, monitoring lineage-specific chimerism could be helpful. We found that on 4 patients who received anti-CD19 CAR-T cells after HSCT and achieved early complete response, CD19+ lineage mixed chimerism but not CD3+ lineage mixed chimerism monitored by molecular techniques anticipated earlier than B-cell aplasia determined by flow cytometry, lack of effectiveness of anti-CD19 CAR-T and leukemia relapse. Donor lymphocyte infusions (DLIs) did not prevent relapse but recovered CD3+ full donor chimerism. We suggest that continuous lineage chimerism analysis should be done routinely in patients who receive anti-CD19 CAR-T cells after HSCT and achieve complete remission because it can support early treatment intervention. However, the role of DLI in this setting is unclear, so further prospective studies should be developed.

Defining the Role of Donor Lymphocyte Infusion in High-Risk Hematologic Malignancies.

The infusion of lymphocytes from the original donor (DLI) to a recipient of an allogeneic stem cell transplantation (SCT) has been the case of cellular immunotherapy. Following its introduction in the late 1980's, unmodified donor cells have been used within the treatment of post-transplant relapse in various hematological malignancies. Later on, preemptive and prophylactic strategies were introduced. Over time, clinical experience identified both the therapeutic potential and the limits of this strategy, prompting numbers of different approaches to improve efficacy and safety of unmodified DLI. Among these were activation of cell subsets by cytokines or growth factors, selection and expansion of specific T-cell subsets, and infusion of NK-cells. Later on, genetical T-cells engineering, including suicide gene technology, T-cell receptor gene transfer and most recently the CAR T-cells, entered the field to increase the allogeneic Graft-versus-Malignancy effect while reducing the risk of complications such as Graft-versus-Host disease. Similarly, synergistic effects of DLI with pharmacological approaches were discovered, leading to combined strategies. Nevertheless, standardization of the "drug" DLI and its clinical use is still challenging, and many sophisticated modifications of DLI still have to prove their suitability for a broader use. Further, increasing knowledge on escape mechanism from an allogeneic immune reaction need to be considered for the clinical application of DLI. Hence, further research requires intelligent strategies and international cooperation to fully exploit the potential of adoptive cellular immunotherapy in the context of allogeneic SCT.

The Role of Donor Lymphocyte Infusion (DLI) in Post-Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era.

Treatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n=128), (2) TKI with DLI (n=48), and (3) DLI without TKI (n=39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P=.81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.

Donor Lymphocyte Infusion Prevented Late Post-Transplant Rejection in 30 Patients with Thalassemia Major

OBJECTIVE:To investigate the role of donor lymphocyte infusions (DLI) in preventing post-transplant graft rejection (GR) in hematopoietic stem cell transplantation (HSCT) for patients with β-thalassemia major (TM);METHODS: A total of 50 patients with TM who had mixed chimerism (MC) after HSCT from June 2011 to June 2016 was divided into 4 groups. The group 1 included the patients with grade I MC ratio of 90%-95% (n=20) but not DLI; Group 2 patients had same grade I MC ratio as Group 1 and received DLI (n=11); Group 3 had grade II MC ratio of 75%-90% (n=13); Group 4 had grade III MC of <75% (n=6). Group 1 received gradually reduced immunosuppressive agents; Groups 2 to 4 received DLIs of gradually increasing dose after reduction of immunosuppressive agents;RESULTS: (1) Full donor chimerism (FDC) conversion rates in the groups 1 to 4 were 100%, 100%, 85%, and 66.7%, respectively; The incidence of graft versus host disease (GVHD) in groups 1 to 4 was 15%, 27.3%, 46.2%, and 33.3%, respectively; (2) There was no significant differeces as comparing incidence of GVHD in group 1 and in group 2 (15% vs. 27.3%, P = 0.638); (3) A significant difference was found in comparing patients receiving initial DLI at ≤180 and > 180 days and the incidence of GVHD was 50% vs 10% (P=0.049); (4) Comparing the accumulated doses of DLI >1×107/kg with ≤1×107/kg, the incidence of GVHD was 50% vs. 27.3% (P=0.142);CONCLUSION: 1. The optimal choice for post-transplant MC grade 1 patient is only observation and decreasing the immunosuppressive drugs; 2. For grade 2-3 patients with high risk of rejection, the fractional increasing dose DLI can effectively reverse the unstable chimera to FDC; 3. Post-DLI GVHD was associated with DLI timing, and the incidence of GVHD was higher in patients who received DLI at ≤180 days after transplantation. DisclosuresNo relevant conflicts of interest to declare.

Donor Lymphocyte Infusion in Patients with Thalassemia Major Who Have Mixed Chimerism Following Allogeneic Stem Cell Transplant

▪Allogeneic stem cell transplantation (HSCT) is the only curative option for patients with thalassemia major (BTM). HSCT in BTM is associated with increased risk of graft rejection. Some patients do not achieve full donor chimerism after transplant despite hematopoietic engraftment. Early post transplant mixed chimerism (MC) is a known predictor of secondary graft rejection. Data is limited on the role of donor lymphocyte infusion (DLI) to prevent secondary graft rejection following detection of early MC in BTM. We report our experience with DLI in BTM patients who had developed progressive worsening early MC after HSCT.All patients with BTM who underwent HSCT at our centre between September 1994 and December 2013 were included in the analysis. During this period, 406 patients underwent HSCT for BTM. Median age was 8 years (range: 1 - 25) and 247 were males (60.8 %). Conditioning regimen was busulphan based in 274 (67.5%) or treosulfan based in 132 (32.5%). The graft source was BM in 305 (75.1%) and PBSC in 101 (24.9%) etc. Median CD34 stem cell dose was 9.24x106/kg (range: 2.1- 33). GVHD prophylaxis consisted of CSA and short course MTX.Patients who engrafted underwent chimerism analysis of peripheral blood at day 28 and between days 60-90. Subsequently chimerism analysis was done at the discretion of the treating physician. Chimerism analysis was done by qualitative and quantitative methods up to 2007 and by quantitative method from 2007.MC was defined by >5% recipient cells at any time point post transplant. The severity of MC was determined as per previously published criteria (level I= < 10%, level II = 10-25 %, level III = >25 %). In patients who developed MC, immunosuppression was tapered and stopped and chimerism monitored. Cyclosporine was tapered by approximately 30% every 2 weeks until there was stable MC or complete donor chimerism. If progressive loss of donor chimerism leading to level II or III MC occured on two consecutive occasions with a concurrent drop in hemoglobin despite stopping immunosuppression and in the absence of GVHD, DLI was given. Patients should have had at least 10% donor chimerism in order to have a DLI.There were 109 (41.6 %, out of 262 patients in whom chimerism was done) patients who developed MC. Of these, 35 (32.1%) developed progressively worsening MC and drop in hemoglobin despite tapering of immunosuppression (91% of these were within day 60). Of these 35 patients, 23 (65.7%) received DLI while 12 developed anemia requiring transfusion (4continued to be on blood transfusion and 8 underwent a second transplant).Among 23 patients who received DLI, 9 (39.1%) showed response (rise in Hb with CC or stable MC) while 14 (60.9%) failed to show any response. The median time to show response was 28 (8-192) days and the median time to peak response was 44 (23-442) days. The 14 patients who did not show any response developed anemia requiring transfusion (11 continued to be on blood transfusion while 3 underwent a second transplant). While 80% of those with level II chimerism responded to DLI, only 31.2% of those with level III chimerism showed a response (summarized in Table 1).DLI was well tolerated by the majority of the patients. However, 7 (30.4%) patients developed cytopenia. While 6 of these had level III chimerism at the time of DLI, 1 had level II chimerism. Two patients developed Grade IV cytopenia. Grade 2 acute GVHD developed in 3 (13%; liver=2, gut=1) which responded to immunosuppressive treatment. Chronic GVHD developed in 2 (8.7%: extensive=1). There was no mortality related to DLI.DLI helped close to 40% patients achieve either complete donor chimerism or stable MC who otherwise might have required a second stem cell transplant with minimal risk. There was a trend to suggest that early administration of DLI at level II MC was superior to DLI administered at level III.Table 1Factors affecting the response to DLIn(%)Effect of DLIResponse(CC+Stable MC)No responsepChimerism levelI 000II 54(80%)1III 165(31.2%)110.07MC 202Lucarelli classI 11(100%)0II 83(37.5%)5III 145(35.7% )90.4ConditioningBu-Cy-ATG/ALG 124(33.3%)8Thio-Treo-Flu 115(45.5%)60.7GraftBM 175(29.4%)12PB 64(66.7%)20.1Time of 1st DLI<180 days 187(38.9%)11>180 days 52(40%)31.0Total239(39.1%)14 DisclosuresNo relevant conflicts of interest to declare.

Maximizing GVL in allogeneic transplantation: role of donor lymphocyte infusions.

Donor lymphocyte infusions (DLIs) can induce complete and durable remissions in some patients with hematologic malignancies who have relapsed after allogeneic transplantation, providing definitive evidence of a GVL effect. Despite the great promise initially envisioned for DLI as a method to augment GVL after transplantation, it utility is limited by low response rates in diseases other than chronic myelogenous leukemia and by the development of GVHD, the principal complication of DLI. To maximize GVL potency while minimizing toxicity, cellular effectors active in GVL need to be elucidated. Insight into mechanisms of GVL, such as reversal of in situ T-cell exhaustion, may allow identification of patients who will respond to DLI based on the presence of tumor-infiltrating lymphocytes in the BM. Understanding the clinical factors that influence the effectiveness and abrogate the toxicity of DLI, such as cell dose and timing of DLI after transplantation, will allow further optimization of DLI. This chapter reviews novel strategies that maximize the GVL effect of DLI by enhancing activity while limiting toxicity.

Durable responses after donor lymphocyte infusion for patients with residual multiple myeloma following non-myeloablative allogeneic stem cell transplant

The role of donor lymphocyte infusion (DLI) in mediating the graft-versus-myeloma (GvM) effect after allogeneic hematopoietic stem cell transplant (allo-HCT) is not clearly defined. We evaluated the safety and utility of DLI in patients with either persistent or recurrent multiple myeloma (MM) after allo-HCT. Twenty-three patients with MM received DLI after allo-HCT at the University of Texas M. D. Anderson Cancer Center between July 1996 and June 2008. Eight patients received preemptive DLI for residual disease (RD) while 15 patients received DLI for the treatment of recurrent or progressive disease (PD). We evaluated the response to DLI and the factors that may predict a response. Median DLI dose was 3.3 × 107 CD3 + cells (range 0.5–14.8 × 107). Grade II–IV acute graft-versus-host disease (GvHD) was seen in five patients (22%). Median follow-up in surviving patients was 24 months. Five of 23 patients (22%) achieved a complete or a very good partial response (two CR, three VGPR), while eight patients (34%) had stable disease (SD) after the DLI. Patients who received DLI for RD had a higher response rate (≥ VGPR 50% vs. 7%, p = 0.03), a longer overall survival (28.3 vs. 7.6 months, p = 0.03) and a trend toward longer progression-free survival (11.9 vs. 5.2 months, p = 0.1). In this largest single institution study, we conclude that the use of preemptive, non-manipulated DLI for RD after reduced-intensity conditioning allo-HCT is encouraging, and it was associated with a higher response rate and a longer overall survival when given preemptively. The role of DLI needs to be further explored in prospective clinical trials.

Prevention of relapse using granulocyte CSF-primed PBPCs following HLA-mismatched/haploidentical, T-cell-replete hematopoietic SCT in patients with advanced-stage acute leukemia: a retrospective risk-factor analysis

The role of donor lymphocyte infusion (DLI) in the prophylaxis of relapse has not been defined. We retrospectively analyzed the data from 88 patients with advanced-stage acute leukemia after HLA-mismatched/haploidentical hematopoietic SCT (HSCT) whose treatment did (n=61) or did not (n=27) include granulocyte CSF (GCSF)-primed PBPCs infusion (GPBPCI). The two groups were compared with respect to relapse and OS. Further, a detailed analysis of risk factors was performed. The 2-year cumulative incidence of relapse in patients receiving prophylactic GPBPCI and not receiving prophylactic GPBPCI were 36% and 55% (P=0.017), respectively. Estimated survival at 3 years was 31% for patients receiving prophylactic GPBPCI and 11% for patients not receiving prophylactic GPBPCI (P=0.001). The three-year probability of leukemia-free survival was also higher in patients who received prophylactic GPBPCI (22%) compared with patients who did not (11%) (P=0.003). Multivariate analysis for relapse showed that use of prophylactic GPBPCI after transplantation was an independent prognostic factor (P=0.025). Higher OS was associated with use of prophylactic GPBPCI (P=0.002), AML (P=0.027) and female sex (P=0.023). Our results suggest that use of prophylactic GPBPCI may increase survival of patients with advanced-stage acute leukemia who receive HLA-mismatched/haploidentical HSCT.

High Response Rate to Donor Lymphocyte Infusion after Allogeneic Stem Cell Transplantation for Indolent Non-Hodgkin Lymphoma

The role of donor lymphocyte infusion (DLI) in the management of lymphoid malignancies after allogeneic stem cell transplantation (SCT) has not been clearly characterized. There is emerging evidence pointing to the effectiveness of this approach, particularly in patients with low-grade disease, although to date this has been reported only in small numbers of patients, and thus the utility of this treatment remains uncertain. A total of 28 patients with low-grade lymphoid malignancies previously treated with allogeneic SCT received a total of 68 infusions of donor lymphocytes. The diagnoses were indolent non-Hodgkin lymphoma (NHL; n = 23) and transformed NHL (n = 5), and the indications for DLI were progressive disease with or without mixed chimerism (MC) (n = 17) and persistent MC alone (n = 11). Escalating doses of cells were administered in the absence of graft-versus-host disease (GVHD) or continued disease progression, until stable full donor chimerism or disease response were achieved. The cumulative response rates after DLI to treat progressive disease and persistent MC were 76.5% and 91.6%, respectively. The major toxicity resulting from the use of donor lymphocytes was GVHD. The cumulative incidence of acute grade II-IV disease was 15%, and that of extensive chronic disease was 31%; there were no deaths resulting from GVHD. Seven patients had graft-versus-lymphoma responses without significant GVHD. These data support the existence of a clinically significant graft-versus-tumor effect in indolent NHL and suggest that this is an effective treatment for progressive disease after allogeneic SCT.

Nonmyeloablative stem cell transplantation in follicular B-cell lymphoma

Myeloablative allogeneic stem cell transplantation carries the promise of long-term disease control by graft-versus-lymphoma (GVL) immunity but is associated with a 30% to 40% risk of transplant-related mortality. Nonmyeloablative stem cell transplantation (NST) aims to exploit the GVL effect without the attendant toxicity of myeloablative conditioning. At the M.D. Anderson Cancer Center, the standard NST conditioning regimen for patients with follicular lymphoma is fludarabine, cyclophosphamide, and rituximab (FCR). Using this regimen, transplant-related mortality is currently 10%, and 85% of patients remain alive without disease at 3 to 4 years. This review discusses the current issues in NST for follicular lymphomas, including the optimization of conditioning intensity, the use of rituximab in immunomodulation, and the role of donor lymphocyte infusion.

Donor Lymphocyte Infusion in the Treatment of First Hematological Relapse After Allogeneic Stem-Cell Transplantation in Adults With Acute Myeloid Leukemia: A Retrospective Risk Factors Analysis and Comparison With Other Strategies by the EBMT Acute Leukemia Working Party

To evaluate the role of donor lymphocyte infusion (DLI) in the treatment of relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the data of 399 patients with AML in first hematological relapse after HSCT whose treatment did (n = 171) or did not (n = 228) include DLI. After correction for imbalances and established risk factors, the two groups were compared with respect to overall survival. Further, a detailed analysis of risk factors for survival among DLI recipients was performed. Median follow-up was 27 and 40 months, respectively. Estimated survival at 2 years (+/- standard deviation) was 21% +/- 3% for patients receiving DLI and 9% +/- 2% for patients not receiving DLI. After adjustment for differences between the groups, better outcome was associated with age younger than 37 years (P = .008), relapse occurring more than 5 months after HSCT (P < .0001), and use of DLI (P = .04). Among DLI recipients, a lower tumor burden at relapse (< 35% of bone marrow blasts; P = .006), female sex (P = .02), favorable cytogenetics (P = .004), and remission at time of DLI (P < .0001) were predictive for survival in a multivariate analysis. Two-year survival was 56% +/- 10%, if DLI was performed in remission or with favorable karyotype, and 15% +/- 3% if DLI was given in aplasia or with active disease. Although further evidence for a graft-versus-leukemia effect by DLI is provided, our results confirm, that the clinical benefit is limited to a minority of patients. Strategies to reduce tumor burden before DLI, as well as alternative treatment options should be investigated in adults with relapsed AML after HSCT.

Results of donor lymphocyte infusions for relapsed myelodysplastic syndrome after hematopoietic cell transplantation

Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative approach for patients with myelodysplastic syndromes (MDSs). While a large proportion of HCT recipients become long-term disease-free survivors, recurrence of MDS remains the leading cause of mortality after HCT. The role of donor lymphocyte infusion (DLI) in patients with relapsed MDS after HCT is unclear. We report results among 16 patients treated with DLI for relapsed MDS after HCT at a single institution between March 1993 and February 2004. The cohort contained 10 men and 6 women with a median age of 49 (range, 22-67) years. CR with resolution of cytopenias and prior disease markers occurred in 3 of 14 patients who could be evaluated. Two patients survived without MDS for 68 and 65 months after DLI, respectively, but died with pneumonia. Grades II-IV acute GVHD and chronic GVHD occurred after DLI in 6 (43%) and 5 (36%) patients, respectively. All three responders developed grades III-IV acute GVHD and extensive chronic GVHD after DLI. Our results confirm prior reports that DLI can result in CR in some patients with recurrent MDS after transplant, but long-term survival is infrequent.

The Role of Donor Lymphocyte Infusion (DLI) and Imatinib Mesylate in the Treatment of Relapse after Allogenic Stem Cell Transplant for Chronic Myeloid Leukemia.

During the period 1988 to 2004, 89 patients underwent allogeneic stem cell transplantation for chronic myeloid leukemia (CML). At the time of transplant 63 were in chronic phase (CP) 1, 3 in CP-2, 6 in accelerated phase and 11 in blast transformation. Eighty six patients who survived more than 2 weeks were evaluable for relapse of which 15 (17.4%) had a relapse. Of these 10 had a molecular relapse (defined by real-time quantitative reverse transcriptase-polymerase chain reaction [RQ-PCR]) while 5 had a hematological relapse. At the time of relapse, 9 patients (60%) were complete chimeras with no detectable recipient band on VNTR analysis, while 3 (20%) were mixed chimeras and 3 (20%) had no donor DNA. Two of this cohort of 15 patients was free of disease after reduction of immunosuppression. Escalating doses of DLI was given to 10 patients while 3 patients were primarily treated with Imatinib. Among the patients receiving DLI, 2 patients (20%) achieved molecular remission, 2 patients underwent a second BMT and one these two one is presently in molecular remission. Six patients did not respond to DLI and were started on Imatinib and 2 (33%) of these have achieved hematological and molecular remission and have only donor cells on VNTR analysis. Three patients were primarily treated with Imatinib and at a median duration of six months of treatment, 2 are in molecular remission while one patient has not shown a molecular response while continuing to remain in hematological remission. Imatinib was well tolerated in these patients at a dose of 400 mg/day with no significant side effects. The overall remission rates with DLI alone was 20% while the use of Imatinib either alone or after DLI failed, achieved remission in 4 out of 9 patients (44%) Two out of 3 patients with a mixed chimerism achieved complete donor chimerism after Imatinib therapy while 2 patients reverted from their mixed status to full donor chimerism after DLI. Some of the patients in relapse were still complete chimeras and remained so after achieving CR with Imatinib. This may be related to the fact that RQ-PCR is one log more sensitive than the Genescan used for chimerism analysis. Analysis of this small cohort of patients suggests that imatinib is superior to DLI for achieveing molecular remission in patients with CML who relapse after stem cell transplant. The role and sequence of treatment with imatinib mesylate or DLI in the management of relapse after allogeneic stem cell transplantation for CML needs to be defined with a randomized trial.Response to DLI/Imatinib following relapse post BMTTotal no. of Allogenic Transplants for CML89Evaluable for relapse86Total no. of Relapsed patients15Patients with DLI alone and in CR2/10(20%)Patients with imatinib alone with CR2/3 (66%)Patients with DLI failure and response with Imatinib2/6 (33%)Overall response with DLI/Imatinib6/15 (40%)

Cellular adoptive immunotherapy after allogeneic stem cell transplantation

This review presents the role of donor lymphocyte infusion, natural killer cells, and dendritic cells in cellular immunotherapy after allogeneic stem cell transplantation. It becomes increasingly possible to infuse more specialized subsets of lymphocyte cells after transplantation. The infusion of natural killer cells, especially in non human leukocyte antigen-identical transplantation, may become an important tool in enhancing the graft-versus-tumor effect. Vaccination of patients after stem cell transplantation with autologous-derived dendritic cells merits further investigation. Stem cell transplantation has evolved to a specialized form of immunotherapy.

Donor T-lymphocyte infusion for unrelated allogeneic bone marrow transplantation with CD3+ T-cell-depleted graft.

In T-cell-depleted allogeneic bone marrow transplantation (TCD-BMT) using unrelated donors, the role of donor lymphocyte infusion (DLI) for survival and disease control has not been defined. In a study of 116 patients (92 matched, 24 mismatched) who received CD3+ T-cell-depleted marrow graft, sequential infusions of escalated doses of donor T lymphocytes up to 1 x 10(6) CD3+ cells/kg were prospectively investigated. T cells were administered while patients were on cyclosporine, provided >or=grade II acute graft-versus-host-disease (GVHD) had not occurred. Acute GVHD of >or=grade II occurred in 27 of 110 (25%) patients before DLI and in 39 of 79 (49%) patients after DLI. In total, 12 of 27 (44%) patients without DLI and 44 of 72 (61%) patients who received DLI developed chronic GVHD. A total of 19 patients died of GVHD, with 17 of acute and two of chronic GVHD. Overall survival (OS) and event-free survival (EFS) at 5 years were 27 and 21%, respectively. The 2-year incidence of relapse was 14%. In multivariate analysis, only chronic GVHD was a good prognostic factor for both OS: hazard ratio (HR) 1.4, P=0.04, and EFS: HR 1.6, P=0.01. Both acute and chronic GVHD were favorable prognostic factors for relapse probability: HR 1.9 for both, P=0.02, 0.01, respectively. The 1-year cumulative incidence of transplant-related mortality (TRM), excluding cases of GVHD, was 42%. The two most common causes of 1-year non-GVHD death were viral infection (9%) and idiopathic pneumonia syndrome (12%). Although the incidence of relapse was low, the study suggests that the current scheme of DLI in unrelated TCD-BMT would not improve survival unless TRM decreases significantly.