Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Greiner, Jochen; Götz, Marlies; Bunjes, Donald; Hofmann, Susanne; Wais, Verena

doi:10.3390/jcm9010039

Cited by 26 publications

(20 citation statements)

References 117 publications

(166 reference statements)

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“…There are also developing technology to manipulate DLI to improve efficacy and limit toxicity. These are reviewed elsewhere, and studies are on-going ( 172 ).…”

Section: How Should Patients With Aml In Cr1 Be Transplanted?mentioning

confidence: 99%

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

2021

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Although the majority of patients with acute myeloid leukemia (AML) treated with intensive chemotherapy achieve a complete remission (CR), many are destined to relapse if treated with intensive chemotherapy alone. Allogeneic stem cell transplant (allo-SCT) represents a pivotally important treatment strategy in fit adults with AML because of its augmented anti-leukemic activity consequent upon dose intensification and the genesis of a potent graft-versus-leukemia effect. Increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has dramatically increased transplant access and consequently allo-SCT is now a key component of the treatment algorithm in both patients with AML in first CR (CR1) and advanced disease. Although transplant related mortality has fallen steadily over recent decades there has been no real progress in reducing the risk of disease relapse which remains the major cause of transplant failure and represents a major area of unmet need. A number of therapeutic approaches with the potential to reduce disease relapse, including advances in induction chemotherapy, the development of novel conditioning regimens and the emergence of the concept of post-transplant maintenance, are currently under development. Furthermore, the use of genetics and measurable residual disease technology in disease assessment has improved the identification of patients who are likely to benefit from an allo-SCT which now represents an increasingly personalized therapy. Future progress in optimizing transplant outcome will be dependent on the successful delivery by the international transplant community of randomized prospective clinical trials which permit examination of current and future transplant therapies with the same degree of rigor as is routinely adopted for non-transplant therapies.

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“…There are also developing technology to manipulate DLI to improve efficacy and limit toxicity. These are reviewed elsewhere, and studies are on-going ( 172 ).…”

Section: How Should Patients With Aml In Cr1 Be Transplanted?mentioning

confidence: 99%

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

2021

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“…This concept is utilized in some patients with Donor Lymphocyte Infusions (DLI). 19 , 20 Similar functional expansion of CD8+ T-cells with anti-leukemic effect has also been noted following BCG therapy. It has been proposed that BCG injection promotes anti-leukemic activity by activation of the immune system by increasing TNF-alpha, IFN-gamma, and IL-2.…”

Section: Discussionmentioning

confidence: 61%

Role of Immunomodulation of BCG Therapy on AML Remission

Kennedy¹,

Sahu²,

Černý³

2021

IMCRJ

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Bacillus Calmette–Guérin (BCG) has been studied in various cancers for its immune modulation. Although the mechanism is yet to be completely understood, we do have positive experiences in many oncological cases. Hereby, we present a case of an 82-year-old male with acute myeloid leukemia (AML) post allogeneic Stem Cell Transplants (AlloSCT) as a salvage therapy, now in remission, who presented with hematuria. Workup confirmed non-muscle invasive Bladder Cancer (NMIBC), for which he was treated with nine sessions of intravesical BCG therapy. During BCG treatment, the patient developed gradually increasing lymphocyte counts. Flowcytometry of a peripheral blood sample showed polyclonal cell lymphocytosis with CD8+ T-cell expansion. Although further work up his lymphocytosis to be polyclonal, it has persisted at follow-up for the last 4 years. Also, we did not find any evidence of leukemia recurrence at follow-up prompting us to associate the BCG use for this patient and it is role as immunomodulation to keep AML disease in remission.

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“…Of note, in analyses of stratified groups according to the presence of D816V KIT mutation and pre-transplant MRD status, Allo-HSCT and Auto-HSCT were superior to each other in MRD-negative patients with and without D816V KIT mutation, respectively. In addition, poor outcomes in pre-transplant MRD-positive patients with D816V KIT mutation due to increased post-transplant relapse suggest the necessity of pre- or post-transplant therapeutic targeting with small molecules against the RUNX1–RUNX1T1 protein, the use of tyrosine kinase inhibitors (dasatinib and FLT3 inhibitors), epigenetic modulators [ 24 ], and cellular approaches [ 25 , 26 ] for this group of patients.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the optimal time point for RUNX1–RUNX1T1 MRD monitoring might be 3 months after HSCT, which would be available to apply additional therapies in an attempt to prevent relapse because all relapse events were observed beyond 4 months after HSCT. On the other hand, earlier recognition of high-risk patients at pre-HSCT would be helpful for applying additional cellular approaches to enhance anti-leukemia effects, which needs considerable time for preparation [ 25 , 26 ]. Further studies are warranted to validate the role of risk-adapted approaches based on RUNX1–RUNX1T1 MRD monitoring as well as KIT mutations.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

Cho

Min

Park

et al. 2021

Cancers

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The prognostic significance of KIT mutations and optimal thresholds and time points of measurable residual disease (MRD) monitoring for acute myeloid leukemia (AML) with RUNX1-RUNX1T1 remain controversial in the setting of hematopoietic stem cell transplantation (HSCT). We retrospectively evaluated 166 high-risk patients who underwent allogeneic (Allo-HSCT, n = 112) or autologous HSCT (Auto-HSCT, n = 54). D816V KIT mutation, a subtype of exon 17 mutations, was significantly associated with post-transplant relapse and poor survival, while other types of mutations in exons 17 and 8 were not associated with post-transplant relapse. Pre- and post-transplant RUNX1–RUNX1T1 MRD assessments were useful for predicting post-transplant relapse and poor survival with a higher sensitivity at later time points. Survival analysis for each stratified group by D816V KIT mutation and pre-transplant RUNX1–RUNX1T1 MRD status demonstrated that Auto-HSCT was superior to Allo-HSCT in MRD-negative patients without D816V KIT mutation, while Allo-HSCT was superior to Auto-HSCT in MRD-negative patients with D816V KIT mutation. Very poor outcomes of pre-transplant MRD-positive patients with D816V KIT mutation suggested that this group should be treated in clinical trials. Risk stratification by both D816V KIT mutation and RUNX1–RUNX1T1 MRD status will provide a platform for decision-making or risk-adapted therapeutic approaches.

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Immunological and Clinical Impact of Manipulated and Unmanipulated DLI after Allogeneic Stem Cell Transplantation of AML Patients

Cited by 26 publications

References 117 publications

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

Allogeneic Stem Cell Transplantation for Acute Myeloid Leukemia: Who, When, and How?

Role of Immunomodulation of BCG Therapy on AML Remission

Prognostic Impacts of D816V KIT Mutation and Peri-Transplant RUNX1–RUNX1T1 MRD Monitoring on Acute Myeloid Leukemia with RUNX1–RUNX1T1

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