CD34+ Stem Cell Selection and CD3+ T Cell Add-Back from Matched Unrelated Adult Donors in Children with Primary Immunodeficiencies and Hematological Diseases

Porta, Fulvio; Comini, Marta; Soncini, Elena; Carracchia, Giulia; Maffeis, Marianna; Pintabona, Vincenzo; Bolda, Federica; Beghin, Alessandra; Schumacher, Richard Fabian; Lanfranchi, Arnalda

doi:10.1016/j.jtct.2021.01.020

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Comparative statistical analysis showed significant difference (P= .0008) and validation of the method. The AmpFLSTR ® Identifiler ® Plus PCR Amplification Kit (Life Technologies Inc., Foster City, CA) containing 15 polymorphic STR (short tandem repeat) loci and the amelogenin marker was used to evaluate chimerism status in patients post transplant ( 20 ). Genomic DNA obtained after CD34+ selection (Automacs System -Miltenyi) from bone marrow samples was extracted using mini blood kit (QIAGEN, Valencia, CA), following the manufacturer instructions.…”

Section: Methodsmentioning

confidence: 99%

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

Malagola

Polverelli²,

Beghin³

et al. 2023

Front. Oncol.

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BackgroundMinimal residual disease (MRD) monitoring is an important tool to optimally address post-transplant management of acute myeloid leukemia (AML) patients.MethodsWe retrospectively analyzed the impact of bone marrow CD34+ molecular chimerism and WT1 on the outcome of a consecutive series of 168 AML patients submitted to allogeneic stem cell transplantation.ResultsThe cumulative incidence of relapse (CIR) was significantly lower in patients with donor chimerism on CD34+ cells ≥ 97.5% and WT1 < 213 copies/ABL x 10^4 both at 1st month (p=0.008 and p<0.001) and at 3rd month (p<0.001 for both). By combining chimerism and WT1 at 3rd month, 13 patients with chimerism < 97.5% or WT1 > 213 showed intermediate prognosis. 12 of these patients fell in this category because of molecular chimerism < 97.5% at a time-point in which WT1 was < 213.ConclusionsOur results confirm that lineage-specific molecular chimerism and WT1 after allo-SCT (1st and 3rd month) are useful MRD markers. When considered together at 3rd month, CD34+ molecular chimerism could represent an earlier predictor of relapse compared to WT1. Further studies are necessary to confirm this preliminary observation.

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Section: Methodsmentioning

confidence: 99%

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

Malagola

Polverelli²,

Beghin³

et al. 2023

Front. Oncol.

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“…Moving forward, ex vivo application of novel gene editing strategies like CRISPR-Cas9 could be employed for the rapid generation of AMPK-deficient T cells for use in both analytical purposes and clinical administration, for example, as an add-back therapy in conjunction with transplantation of CD34 + selected grafts [ 54 , 55 ] . Additionally, use of pharmacologic AMPK inhibitors during the cell manufacturing process [ 56 ] may confer similar GVHD-mitigating effects without the potential risks associated with genome engineering [ 57 ] .…”

Section: Ampk As a Therapeutic Target For Gvhdmentioning

confidence: 99%

The role of AMP-activated protein kinase in GVHD-causing T cells

2022

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Allogeneic stem cell transplantation is a curative therapy for multiple hematologic disorders. However, this life-saving procedure is often complicated by acute graft-versus-host disease (GVHD), where donor T cells attack tissues in the recipient’s skin, liver, and gastrointestinal tract. Previous research has demonstrated that GVHD-causing T cells undergo significant metabolic reprogramming during disease pathogenesis, with an increased reliance on oxidative metabolism. This dependence makes metabolic modulation a potential approach to treat and/or prevent GVHD. Here, we provide an overview on the metabolic changes adopted by allogeneic T cells during disease initiation, highlighting the role played by AMP-activated protein kinase (AMPK) and identifying ways in which these insights might be leveraged to therapeutic advantage clinically.

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CD34+ Stem Cell Selection and CD3+ T Cell Add-Back from Matched Unrelated Adult Donors in Children with Primary Immunodeficiencies and Hematological Diseases

Cited by 2 publications

References 27 publications

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

Bone marrow CD34+ molecular chimerism as an early predictor of relapse after allogeneic stem cell transplantation in patients with acute myeloid leukemia

The role of AMP-activated protein kinase in GVHD-causing T cells

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