Donor Lymphocyte Infusion for the Treatment of Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Takami, Akiyoshi; Yano, Shingo; Yokoyama, Hiroyuki; Kuwatsuka, Yachiyo; Yamaguchi, Takuhiro; Kanda, Yoshinobu; Morishima, Yasuo; Fukuda, Takahiro; Miyazaki, Yasushi; Nakamae, Hirohisa; Tanaka, Junji; Atsuta, Yoshiko; Kanamori, Heiwa

doi:10.1016/j.bbmt.2014.07.010

Cited by 68 publications

(39 citation statements)

References 28 publications

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“…The goal of this strategy is to enhance the GVL effect through infusion of non‐tolerant donor T cells without GVHD pharmacological prophylaxis (Schmid et al , , ; Warlick et al , ; Bejanyan et al , , ; He et al , ). However, the use of DLI is associated with increased risk of acute GVHD (Mielcarek et al , ; Warlick et al , ; Takami et al , ; He et al , ). Prior reports suggest that the efficacy of the DLI in patients with relapsed AML is higher when performed after cytoreductive chemotherapy, although there is yet no uniformly accepted opinion on which chemotherapy regimens are superior (Mielcarek et al , ; Oran et al , ; Warlick et al , ; Bejanyan et al , ; He et al , ).…”

Section: Relapse After Allogeneic Haematopoietic Cell Transplantationmentioning

confidence: 99%

Treatment of relapsed/refractory acute myeloid leukaemia in adults

2018

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The prognosis of relapsed acute myeloid leukaemia (AML) is poor and treatment is challenging. While the most potent treatment modality for patients who achieve a complete remission after relapse is still allogeneic haematopoietic cell transplantation (allo-HCT), both transplant-related mortality and relapse rates are high and many patients are not candidates for this approach. After a few decades of relative stasis in this field, a large number of novel approaches have become available to tackle this highly fatal disease. This is mostly due to our improved understanding of disease pathogenesis (including targetable mutations) and the anti-leukaemia potential of the immune system. Several small-molecule inhibitors and immunotherapeutic options are being explored in clinical trials and many more are in pre-clinical phase. Future studies will focus on novel and mechanistically driven combinations, sequential treatments, and low-toxicity maintenance strategies. While cure of relapsed/refractory AML without allo-HCT is currently unlikely, treatments are becoming less toxic and remissions are lasting longer.

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Section: Relapse After Allogeneic Haematopoietic Cell Transplantationmentioning

confidence: 99%

Treatment of relapsed/refractory acute myeloid leukaemia in adults

2018

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“…DLI can be used to effectively prevent impending relapse or as salvage therapy after transplantation [17,27,28]. IFN-α also has been effective in preventing relapse [18].…”

Section: Discussionmentioning

confidence: 99%

Outcome and Minimal Residual Disease Monitoring in Patients with t(16;21) Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Qin

Yao

et al. 2018

Biology of Blood and Marrow Transplantation

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Patients with t(16;21) acute myelogenous leukemia (AML) who receive chemotherapy have poor outcomes. The treatment efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) must be identified, and the usefulness of minimal residual disease (MRD) monitoring requires evaluation. Fourteen consecutive patients with t(16;21) AML undergoing allo-HSCT at our institution were included in this study. Translocation liposarcoma- ETS-related gene (TLS-ERG) transcript levels were serially monitored for a median of 15 months (range, 3-51 months) after allo-HSCT. Eight patients relapsed, 7 patients died from relapse-related causes, and 1 patient died from a non-relapse-related cause. The 2-year cumulative incidence rates of relapse, disease-free survival, and overall survival after HSCT were 66.2%, 30.8%, and 46.2%, respectively. Of the 3 patients who received an HLA-matched sibling transplant, 2 relapsed, and 1 (33.3%) was in hematologic complete remission (CR) but died of nonrelapse mortality, whereas 5 of 11 patients (45.5%) who received haploidentical transplantation were in CR and were alive. Two of 6 patients with undetectable TLS-ERG at the time of allo-HSCT relapsed, at 14 and 15 months, and 3 of 4 PCR-positive patients relapsed, at a median of 10 months after HSCT. Four patients with continually low post-HSCT TLS-ERG levels (mostly <.01%) remained alive and in CR. The TLS-ERG levels of all 8 patients who relapsed were significantly increased before the relapse, exceeding 1.0% in all 7 patients who experienced hematologic relapse. In total, 7 patients received modified donor lymphocyte infusion (DLI), and 1 patient received IFN-α. All 7 patients with a TLS-ERG level >5.0% at the time of intervention experienced an increase or a brief decrease in TLS-ERG level, followed by an increase, and 6 relapsed, whereas the TLS-ERG level of 1 patient with a TLS-ERG level <1.0% at intervention decreased to undetectable. Therefore, t(16;21) AML is an indication for allo-HSCT. Among the HSCT recipients, 30.8% responded to treatment with CR. TLS-ERG transcript levels reflect MRD and might predict relapse and guide effective intervention.

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“…In a retrospective Japanese study [57], including 143 adult AML patients who received DLI for treatment of first hematological relapse after HSCT, the OS rates at 1 year, 2 years and 5 years were 32, 17 and 7%, respectively. Complete remission at the time of DLI, only achieved in 8% of cases, was the strongest p redictive factor for better survival after DLI.…”

Section: • • Aml and Mdsmentioning

confidence: 99%

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

Pereira

Danby

Rocha

2015

Int. J. Hematol. Oncol.

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Donor lymphocyte infusion, a rescue therapy after hematopoietic stem cell transplantation, has been increasingly adopted, as modalities of stem cell transplantation have widened. First described as donor lymphocyte transfusion or cell therapy, it consists of infusion of donor lymphocytes, collected in steady state or after growth factor enhancement. As in literature the most used name is donor lymphocyte infusion, we'll adopt it here. Its most striking efficacy is observed in patients with chronic myelogenous leukemia, who relapsed after allogeneic stem cells transplantation. However, graft-versus-host disease, its main complication, may still hamper its feasibility. KEYWORDSAllogeneic hematopoietic stem cell transplantation (HSCT) has become an attractive approach for the treatment of many patients with hematological diseases, including malignant and nonmalignant disorders. Importantly, in the last 15 years, with the advent of reduced intensity conditioning (RIC) regimens, many older adult patients, initially excluded from this therapy approach, became eligible for HSCT. This approach decreased the transplant-related mortality, still maintaining T-cell immune response from the graft against the host tumor cells, also known as the graft-versus tumor or graft Practice points• Donor lymphocyte infusion (DLI) is an alternative strategy to reverse mixed chimerism, treat relapse and reconstitute immunity against infections after hematopoietic stem cell transplantation.• Responses to DLI are disease-dependent.• As main side effect, DLI can promote graft-versus-host disease (GVHD) in the range of 40-60% of patients.• The incidence of GVHD after unrelated DLI is similar to the incidence after related DLI, both presenting same pattern of presentation.• Although GVHD and graft versus leukemia (GVL) after DLI are highly correlated, some patients experience remission (GVL) without expressing GVHD.• Escalating doses for DLI is preferable, as it induces less GVHD. There is no clear association, yet confirmed, between T-cell dose and incidence of neither GVHD nor GVL after DLI.• The further DLI is made from transplantation, the better outcome.• Preadjuvant treatment before DLI is preferable as DLI effect is enhanced with low tumor burden.• Some strategies still under investigation are focused on separating GVHD and GVL, including graft engineering and gene therapy, to improve clinical outcome.For reprint orders, please contact: reprints@futuremedicine.com

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Donor Lymphocyte Infusion for the Treatment of Relapsed Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation

Cited by 68 publications

References 28 publications

Treatment of relapsed/refractory acute myeloid leukaemia in adults

Treatment of relapsed/refractory acute myeloid leukaemia in adults

Outcome and Minimal Residual Disease Monitoring in Patients with t(16;21) Acute Myelogenous Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Donor Lymphocyte Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

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