Sequential administration of low dose 5-azacytidine (AZA) and donor lymphocyte infusion (DLI) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in relapse after allogeneic stem cell transplantation (SCT): a prospective study from the Belgian Hematology Society (BHS)

Poiré, Xavier; Graux, Carlos; Ory, Aurélie; Herman, Julie; Baron, Frédéric; Schoemans, Hélène; Lewalle, Philippe; Becker, Ann De; Deeren, Dries; Berneman, Zwi; Kerre, Tessa; Zachée, Pierre; Selleslag, Dominik; Béguin, Yves

doi:10.1038/s41409-021-01464-x

Cited by 15 publications

(13 citation statements)

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“…A phase II study ( 61 ) of 30 patients demonstrated the feasibility and clinical efficacy of AZA in combination with DLI as salvage therapy for relapse after allo-HSCT. However, another recent prospective study of 49 patients showed that the administration of AZA and DLI had no significant impact on either response or survival ( 62 ). We evaluated the regimens of two different studies, and the latter administered DLI one day after AZA.…”

Section: Post-hsctmentioning

confidence: 99%

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

et al. 2022

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for patients with myeloid malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, relapse and graft-versus-host disease (GvHD) still affect the survival of patients who receive allo-HSCT, and more appropriate therapeutic strategies should be applied at all stages of transplantation to prevent these adverse events. The use of epigenetics agents, such as hypomethylating agents (HMAs), has been explored to decrease the risk of relapse by epigenetic modulation, which is especially effective among AML patients with poor mutations in epigenetic regulators. Furthermore, epigenetic agents have also been regarded as prophylactic methods for GvHD management without abrogating graft versus leukemia (GvL) effects. Therefore, the combination of epigenetic therapy and HSCT may optimize the transplantation process and prevent treatment failure. Existing studies have investigated the feasibility and effectiveness of using HMAs in the pretransplant, transplant and posttransplant stages among MDS and AML patients. This review examines the application of HMAs as a bridge treatment to reduce the tumor burden and the determine appropriate dose during allo-HSCT. Within this review, we also examine the efficacy and safety of HMAs alone or HMA-based strategies in posttransplant settings for MDS and AML. Finally, we provide an overview of other epigenetic candidates, which have been discussed in the nontransplant setting.

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Section: Post-hsctmentioning

confidence: 99%

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

et al. 2022

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“…The to be only 11%−30%. 20,21 Studies have shown that the application of pro-DLI in the haploidentical setting could help 49.1%−67.8% of the patients with MNs experience long-term survival and decrease the relapse to 14.7%−32.4%. [22][23][24] While, there is limited experience with use of pro-DLI in pediatric MN patients.…”

Section: Discussionmentioning

confidence: 99%

“…GVL effects make DLI currently one of the most common interventions used for post‐transplant relapse of hematological malignancies. However, unlike chronic myeloid leukemia, MNs recurring after allo‐HSCT do not respond well to DLI, with OS rates reported to be only 11%−30% 20,21 . Studies have shown that the application of pro‐DLI in the haploidentical setting could help 49.1%−67.8% of the patients with MNs experience long‐term survival and decrease the relapse to 14.7%−32.4% 22 – 24 .…”

Section: Discussionmentioning

confidence: 99%

Prophylactic donor lymphocyte infusion after haploidentical hematopoietic cell transplantation and post‐transplant cyclophosphamide for treatment of high‐risk myeloid neoplasms in children: A retrospective study

Qi,

Chen,

et al. 2023

Pediatric Blood & Cancer

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BackgroundPost‐transplant cyclophosphamide (PTCy) has been recommended for prevention of graft‐versus‐host disease (GvHD) following haploidentical hematopoietic cell transplantation (haplo‐HCT) for treatment of malignant blood diseases, but disease relapse remains a problem. Although donor lymphocyte infusion (DLI) is reported to be effective for treating post‐transplantation relapse, the efficacy and safety of prophylactic‐DLI (pro‐DLI) post haplo‐HCT, and PTCy in pediatric patients with hematological malignancies is unknown.MethodsWe retrospectively analyzed the outcomes of 54 pediatric patients with high‐risk myeloid neoplasms who received a PTCy regimen for GvHD prophylaxis and pro‐DLI after haploidentical peripheral blood stem cell transplantation. The high‐risk myeloid neoplasms in this cohort included acute myeloid leukemia (n = 46) and myelodysplastic syndromes (n = 8).ResultsMedian follow‐up was for 19.7 (range: 3.4–46.6) months. The cumulative incidences of grade II–IV and III–IV acute GvHD were 37.0% (95% CI: 22.7%–48.7%) and 16.7% (95% CI: 6.1%–26.0%), respectively. There were no graft‐failure events, and the 2‐year rate of moderate/severe chronic GvHD was 8.1% (95% CI: 0%–16.7%). The 2‐year non‐relapse mortality, relapse, disease‐free survival, GvHD‐free relapse‐free survival, and overall survival rates were 5.1% (95% CI: 0%–11.7%), 16.6% (95% CI: 5.3%–26.6%), 78.9% (95% CI: 68.0%–91.6%), 62.2% (95% CI: 49.4%–78.3%), and 87.3% (95% CI: 78.3%–97.4%), respectively.ConclusionsProphylactic donor lymphocyte infusion in the setting of haploidentical hematopoietic cell transplantation with post‐transplant cyclophosphamide appears to be effective and safe in pediatric patients with high‐risk myeloid neoplasms.

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“…Mice were treated with a single dose of 2.5 mg/kg body weight azacytidine (on day 9), five doses of 0.2 mg/mouse anti-PD-1 (on days 10,13,16,19,22), a combination of both or an equal volume of PBS. Flow cytometry analysis of the spleen cells was carried out on day 23 with BMDM media (Figure 5G, "exhausted T cells + BMDM media" vs. "exhausted T cells"). Our results indicate that a pro-inflammatory myeloid population might boost the T cell immune response.…”

Section: Single-cell Protein-and Rna-based Analyses Indicate That a P...mentioning

confidence: 99%

“…3,12,13 Donor lymphocyte infusions (DLI) for AML relapse result in remission rates of about 20%. [14][15][16] Other approaches to prevent or treat AML relapse after allo-HCT comprise a second allo-HCT, [17][18][19] FLT3-kinase inhibitors, 20,21 hypomethylating agents, 22,23 BCL-2 inhibitors, [24][25][26] immune checkpoint inhibitors 27,28 and others. 29 Despite the availability of these treatment options, the long-term prognosis of patients with AML relapse post-allo-HCT remains dismal.…”

Section: Introductionmentioning

confidence: 99%

Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response

Apostolova,

Kreutmair,

Toffalori

et al. 2023

Br J Haematol

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SummaryAcute myeloid leukaemia (AML) relapse after allogeneic haematopoietic cell transplantation (allo‐HCT) is often driven by immune‐related mechanisms and associated with poor prognosis. Immune checkpoint inhibitors combined with hypomethylating agents (HMA) may restore or enhance the graft‐versus‐leukaemia effect. Still, data about using this combination regimen after allo‐HCT are limited. We conducted a prospective, phase II, open‐label, single‐arm study in which we treated patients with haematological AML relapse after allo‐HCT with HMA plus the anti‐PD‐1 antibody nivolumab. The response was correlated with DNA‐, RNA‐ and protein‐based single‐cell technology assessments to identify biomarkers associated with therapeutic efficacy. Sixteen patients received a median number of 2 (range 1–7) nivolumab applications. The overall response rate (CR/PR) at day 42 was 25%, and another 25% of the patients achieved stable disease. The median overall survival was 15.6 months. High‐parametric cytometry documented a higher frequency of activated (ICOS+, HLA‐DR+), low senescence (KLRG1−, CD57−) CD8+ effector T cells in responders. We confirmed these findings in a preclinical model. Single‐cell transcriptomics revealed a pro‐inflammatory rewiring of the expression profile of T and myeloid cells in responders. In summary, the study indicates that the post‐allo‐HCT HMA/nivolumab combination induces anti‐AML immune responses in selected patients and could be considered as a bridging approach to a second allo‐HCT.Trial‐registration: EudraCT‐No. 2017‐002194‐18.

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Sequential administration of low dose 5-azacytidine (AZA) and donor lymphocyte infusion (DLI) for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in relapse after allogeneic stem cell transplantation (SCT): a prospective study from the Belgian Hematology Society (BHS)

Cited by 15 publications

References 11 publications

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

Generalist in allogeneic hematopoietic stem cell transplantation for MDS or AML: Epigenetic therapy

Prophylactic donor lymphocyte infusion after haploidentical hematopoietic cell transplantation and post‐transplant cyclophosphamide for treatment of high‐risk myeloid neoplasms in children: A retrospective study

Phase II trial of hypomethylating agent combined with nivolumab for acute myeloid leukaemia relapse after allogeneic haematopoietic cell transplantation—Immune signature correlates with response

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