Managing post allograft relapse of myeloid neoplasms: azacitidine and donor lymphocyte infusions as salvage therapy

Claiborne, John Preston; Bandyopathyay, Dipankar; Roberts, Catherine; Hawks, Kelly G.; Aziz, May; Simmons, Gary; Wiedl, Christina M.; Chung, Harold M.; Clark, William; McCarty, John M.; Toor, Amir A.

doi:10.1080/10428194.2019.1605066

Cited by 25 publications

(23 citation statements)

References 44 publications

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“…DLI could be stimulated ex vivo by TAA, which selects for an enriched, polyclonal CD4+ and CD8+ specifically directed against MDS. TTA-DLI appears to be safer, with respect to GVHD, than unselected DLI [182,183].…”

Section: Adoptive T-cell Transfer Therapymentioning

confidence: 83%

From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

2021

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The pathophysiology of myelodysplastic syndromes (MDSs) is complex and often includes immune dysregulation of both the innate and adaptive immune systems. Whereas clonal selection mainly involves smoldering inflammation, a cellular immunity dysfunction leads to increased apoptosis and blast proliferation. Addressing immune dysregulations in MDS is a recent concept that has allowed the identification of new therapeutic targets. Several approaches targeting the different actors of the immune system have therefore been developed. However, the results are very heterogeneous, indicating the need to improve our understanding of the disease and interactions between chronic inflammation, adaptive dysfunction, and somatic mutations. This review highlights current knowledge of the role of immune dysregulation in MDS pathophysiology and the field of new drugs.

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Section: Adoptive T-cell Transfer Therapymentioning

confidence: 83%

From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

2021

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“…Recently, Claiborne et al 28 reported that treatment of relapsed AML⊘MDS (n＝28) after allo-HCT with acombination of azacytidine and DLI resulted in a two-year OS rate of 35%, and noted a trend towards higher absolute CD4＋ cell count in the patient group achieving remission. Hypomethylating agents may induce synergistic effect by promoting cytotoxic effects against leukemic cells when combined with DLI 28 . Schroeder et al also reported complete and partial remission rates of 27% and 6%, respectively, which correspond to an overall response rate of 33%, following the treatment of relapsed AML⊘ MDS after allo-HCT with a combination of azacytidine and DLI.…”

Section: Discussionmentioning

confidence: 99%

Treatment of relapsed acute leukemia by Ara C plus donor lymphocyte infusion using CD34+ cells reserved at the time of allogeneic transplantation

2020

BCT

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Currently, there is no standard therapy available for relapsed acute leukemia after allogeneic hematopoietic cell transplantation(allo-HCT) . In this study, we evaluated the efficacy of cytoreduction with cytarabine followed by granulocyte colony-stimulating factor(G-CSF) -primed donor lymphocyte infusion(DLI)for patients with acute leukemia who relapsed after allo-HCT. We retrospectively reviewed 255 patients who had received allo-HCT for acute leukemia／myelodysplastic syndrome. Patients were divided into two groups based on the CD34＋ cell dose they received during the initial transplantation； patients in the lower CD34＋ group received a dose lower than 6×10 6 cells／kg and those in the higher CD34＋ group received a dose higher than 6×10 6 cells／kg. No significant differences were noted between two groups with respect to overall survival, relapse-free survival, or graft-versushost disease(GVHD) -free／relapse-free survival. Patients who relapsed after allo-HCT(n＝93)were assigned into early or late relapse groups using the median time to relapse as the threshold. Among the 93 patients with relapse, 39 received G-CSF-primed DLI. The median dose of CD3＋ cells was 2.82×10 7 cells／kg(range： 0.05-10.1) . In the late relapse group, one-year overall survival was significantly higher in patients receiving DLI than that in patients not receiving DLI (53.4% ±7.4% vs. 26.7% ±7.4%； P＝0.039) , whereas no DLI effect was detected within the early relapse group. In addition, the incidence of DLI-induced GVHD did not differ between the two groups. In conclusion, treatment with G-CSF-primed DLI after allo-HCT with a limited CD34＋ cell dose constitutes a feasible and effective option, which could replace second HCT in treatment of late-relapse patients.

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“…An analysis on 28 patients with recurrent AML/MDS after allo-SCT who received AZA-DLI showed that the likelihood of disease response was higher among those patients without an overt hematological relapse, in those who received more cycles of therapy, and in those who had chronic GVHD. Moreover, there was an association between higher CD4+ T cells and prolonged survival ( 41 ).…”

Section: Hma-based Combinationsmentioning

confidence: 99%

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

2022

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Allogeneic stem cell transplantation still represents the best curative option for most patients with acute myeloid leukemia, but relapse is still dramatically high. Due to their immunologic activity and safety profile, hypomethylating agents (HMAs) represent an interesting backbone for combination therapies. This review reports mechanism of action, safety, and efficacy data on combination strategies based on HMAs in the setting of post-allogeneic stem cell transplant relapse. Several studies highlighted how HMAs and donor lymphocyte infusion (DLI) combination may be advantageous. The combination strategy of HMA with venetoclax, possibly in association with DLI, is showing excellent results in terms of response rate, including molecular responses. Lenalidomide, despite its well-known high rates of severe graft-versus-host disease in post-transplant settings, is showing an acceptable safety profile in association with HMAs with a competitive response rate. Regarding FLT3 internal tandem duplication (ITD) mutant AML, tyrosine kinase inhibitors and particularly sorafenib have promising results as monotherapy and in combination with HMAs. Conversely, combination strategies with gemtuzumab ozogamicin or immune checkpoint inhibitors did not show competitive response rates and seem to be currently less attractive strategies. Associations with histone deacetylase inhibitors and isocitrate dehydrogenase 1 and 2 (IDH1/2) inhibitors represent new possible strategies that need to be better investigated.

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Managing post allograft relapse of myeloid neoplasms: azacitidine and donor lymphocyte infusions as salvage therapy

Cited by 25 publications

References 44 publications

From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

From Immune Dysregulations to Therapeutic Perspectives in Myelodysplastic Syndromes: A Review

Treatment of relapsed acute leukemia by Ara C plus donor lymphocyte infusion using CD34+ cells reserved at the time of allogeneic transplantation

Hypomethylating Agent-Based Combination Therapies to Treat Post-Hematopoietic Stem Cell Transplant Relapse of Acute Myeloid Leukemia

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