Risk stratification–directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation

Yan, Chen‐Hua; Liu, Dai‐Hong; Liu, Kai-Yan; Xu, Lei; Liu, Yanrong; Chen, Huan; Wang, Han; Wang, Yu; Qin, Ya‐Zhen; Huang, Xiao‐Jun

doi:10.1182/blood-2011-09-380386

Cited by 246 publications

(252 citation statements)

References 32 publications

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“…10,15,21,22 Interventions based on minimal residual disease detection are promising. Yan et al 23 recently published a study on a large cohort of standard-risk AML patients showing improved outcome of minimal residual disease-positive patients after treatment with modified donor lymphocytes. In our study, one patient with detectable minimal residual disease became negative after DLT and remained in complete hematological and molecular remission.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

Jedlickova

Schmid

Koenecke

et al. 2015

Bone Marrow Transplant

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Adjuvant transfusion of donor lymphocytes (aDLT) may reduce the risk of relapse after allogeneic stem cell transplantation in high-risk AML. We performed a retrospective analysis on the safety and efficacy of aDLT in a cohort of 46 patients. To be eligible for aDLT, patients had to be in CR for at least 120 days from transplantation, off immunosuppression for ⩾ 30 days and free of GvHD. Thirty-four patients with similar disease characteristics and fulfilling the same selection criteria served as controls. Median follow-up among aDLT recipients was 7.2 years. Ten patients (22%) relapsed inspite of aDLT, as compared with 53% in the control group. Induction of GvHD was the main complication. However, non-relapse mortality was low with patients dying from infection (n = 2), severe chronic GvHD (n = 1) and secondary malignancy (n = 2). At the time of analysis, 31/46 aDLT recipients were alive in CR at a median of 5.7 years after first aDLT. Overall survival at 7 years after transplant was 67% as compared with 31% in the control group (P o 0.001). In conclusion, aDLT is safe, when given in escalating doses to a well predefined group of patients. Long-term survival can be achieved. INTRODUCTIONDespite advances in allogeneic transplantation (allogeneic stem cell transplantation; alloSCT), high-risk AML remains a disease with poor outcome, lacking optimal therapeutic strategy. In particular, patients with refractory disease or early relapse still have a poor prognosis. High-risk disease can further be defined by delayed response to chemotherapy, unfavorable karyotype or molecular genetics 1 and by a history of preceding neoplasia and/or chemotherapy.In the era of reduced intensity conditioning (RIC), high rates and a poor outcome of relapse after alloSCT (2 years overall survival (OS) 20%) 2,3 are the main causes for treatment failure in high-risk AML. Thus, effective strategies for preventing post-transplant relapse are urgently needed. As donor lymphocyte transfusion (DLT) enhances the graft-versus-leukemia (GVL) effect, it offers an attractive therapeutic option to decrease relapse-related mortality rates. The GVL potential of donor T-lymphocytes has been described in several preclinical 4,5 and clinical studies. [6][7][8] In particular, their use in the management of post-transplant relapses of chronic myeloid leukemia has been a story of success. However, despite of its desirable GVL effects, DLT may also increase the incidence and severity of GvHD. Thus, DLT protocols have to be optimized to minimize the risk of severe GvHD and maximize the benefit of the GVL effect.The establishment of RIC provided a basis for the employment of DLT in the post-transplantation period of AML therapy. There are several clinical studies supporting the positive role of DLT in the prophylaxis 9 and treatment of post-transplant relapse in AML. 2,10 Despite these encouraging data, the efficacy and the toxicity of DLT in the management of AML is still poorly assessed,

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Section: Discussionmentioning

confidence: 99%

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

Jedlickova

Schmid

Koenecke

et al. 2015

Bone Marrow Transplant

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“…26,32,33 At Peking University, modified donor lymphocyte infusion (DLI) was administered before hematologic relapse as an interventional therapy (preemptive DLI) 3 mo post-HSCT following a trial of immunosuppressant withdrawal. The detailed criteria for preemptive DLI administration included the following: (1) an MRDC score in patients within 1 y after transplantation, which is defined as having either two consecutive positive results using either flow cytometry or Wilms' tumor gene 1 or positive for both flow cytometry and Wilms' tumor gene 1 in a single sample; (2) no uncontrolled GVHD or life-threatening infections; and (3) donor availability and willingness.…”

Section: Mrd and Relapse Monitoring And Interventionmentioning

confidence: 99%

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study

Zhao

Wang

et al. 2016

OncoImmunology

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Leukemia relapse and chronic graft-versus-host disease (cGVHD) are still major obstacles of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The numbers and activity of natural killer (NK) and Tregulatory cells can be increased post-transplantation by exposure to interleukin-2 (IL-2). We tested whether administering low-dose IL-2 would decrease leukemia relapse while reducing cGVHD after allotransplantation. This controlled, open-label randomized trial included 90 recipients of allotransplants. Subjects were randomized in a 1:1 ratio to either receive or not receive low-dose IL-2 during the early post-transplantation period. Patients in the IL-2 arm received a subcutaneous injection of low-dose IL-2 (1£10 6 U/d) on day 60 after allo-HSCT. IL-2 was administered daily for 14 d followed by a 14-d hiatus. The primary endpoint was the cumulative incidence of leukemia relapse (CIR). Three-year CIRs for the IL-2 arm and control arm were 23% (range 16-30%) and 11% (range 6-15%; p D 0.20), respectively. Minimal residual disease-positive (MRDC) tests were more common in the IL-2 arm compared to the control arm (36% [range 29-44%] vs. 15% [range 10-20%], p D 0.03). The cumulative incidence of moderate-to-severe chronic GVHD (cGVHD) was lower in the IL-2 arm compared to the control arm (33% [range 26-39%] vs. 57% [range 49-64%), p D 0.02). Therefore, the 3-y GVHD-free and GVHD progression-free survival (GPFS) rates were significantly higher in the IL-2 arm compared to the control arm (47% [range 39-55%] vs. 31% [range 25-38%], p D 0.048). Blood Tregs, NK cells, and NK-cell cytotoxicity were increased in subjects in the IL-2 arm between 3 mo and 6 mo post-transplantation. Administration of low-dose IL-2 during the immediate post-transplantation period was associated with a higher GPFS but did not decrease the CIR.

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“…The number of patients was limited in the MRD group; nevertheless, observation of high effectiveness and low toxicity of DLI in patients with persistent residual disease is well confirmed. [24][25][26] The time of DLI infusion for NA and RIC indications was similar, and showed a small divergence in individual cases in comparison with the application time for MRD and REL indications. In the former case, this time was determined by the approximate course of HSCT and engraftment, whereas, in the latter, such a large dispersion was caused by the variability of disease nature after HSCT.…”

Section: Discussionmentioning

confidence: 92%

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients

Goździk

Rewucka

Krasowska-Kwiecień

et al. 2014

Bone Marrow Transplant

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The aim of this study was to analyse the experience of Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in respect to donor lymphocyte infusion procedure. The study included 51 pediatric patients with malignant (45) and non-malignant (6) diseases treated with DLI in the period 1993-2012. The indications for DLI were as follows: (1) increasing recipient chimerism after non-ablative hematopoietic SCT (18 patients); (2) immunomodulation after a reduced intensity conditioning regimen (2 patients); (3) increase in minimal residual disease detection (3 patients); and (4) relapse (28 patients). DLI was carried out at a median of 6 (0.5-79) months after SCT. DLI was administered as either a single-dose (in 19 cases) or in escalating-dose regimens (in 32 cases). The median total dose of CD3-positive T cells was 28.0 (0.1-730.0) × 10 6 /kg body weight. The time for assessment of DLI efficacy ranged from 0 to 70 (median 3) months. At evaluation, 18 patients experienced CR, 3 achieved PR, 19 showed relapse and 11 rejected the graft. DLI was found to be effective in 39% of cases. Complications of the procedure occurred in 18 patients; of these, 2 died. To sum up DLI shows efficacy in a significant percentage of children. Mortality related to the therapy adverse effects is low. However, this method requires standardization.

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Risk stratification–directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation

Cited by 246 publications

References 32 publications

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

Prophylactic use of low-dose interleukin-2 and the clinical outcomes of hematopoietic stem cell transplantation: A randomized study

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients

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