Infusion of a non-HLA-matched ex-vivo expanded cord blood progenitor cell product after intensive acute myeloid leukaemia chemotherapy: a phase 1 trial

Delaney, Colleen; Milano, Filippo; Cicconi, Laura; Othus, Megan; Becker, Pamela S.; Sandhu, Vicky; Nicoud, Ian B.; Dahlberg, Ann; Bernstein, Irwin D.; Appelbaum, Frederick R.; Estey, Elihu H.

doi:10.1016/s2352-3026(16)30023-0

Cited by 30 publications

(37 citation statements)

References 19 publications

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“…Initial laboratory studies demonstrated the role of Notch signalling pathway in controlling the fate of CD34 ＋ HSPC, for example, the overexpression of Notch-1 gene in CD34 ＋ cells allowed enhanced selfrenewal capacity 84 . The NLA-101 expansion process by NOHLA Therapeutics (CA, USA) requires up to 16 days where purified UCB CD34 ＋ cells(from frozen or fresh grafts)are cultured in serum-free expansion medium supplemented with 300 ng⊘mL of SCF, 300 ng⊘mL of FLT-3L, 100 ng⊘mL of TPO, 100 ng⊘mL of IL-6, 10 ng⊘ mL of IL-3, and the required density of Delta 1(Ext-IgG) 56,85 . The CD34fraction containing the lymphoid cells is discarded and not infused into the patient unlike Omidubicel, MGTA-456, and ECT-001 [66][67][68][69] .…”

Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

“…Based on the outcomes of the pilot clinical study, the clinical use of NLA-101 was repurposed as an off-the-shelf(i.e. no matching on HLA is required)cellular therapy product to overcome neutropenia and reduce infections in patients receiving high-intensity chemotherapy 56 . Twenty-nine patients suffering from AML were recruited for a phaseⅠ study(ClinicalTrials.gov identifier: NCT01031368) as infection is a major cause of posttreatment mortality and morbidity 56 .…”

Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

“…no matching on HLA is required)cellular therapy product to overcome neutropenia and reduce infections in patients receiving high-intensity chemotherapy 56 . Twenty-nine patients suffering from AML were recruited for a phaseⅠ study(ClinicalTrials.gov identifier: NCT01031368) as infection is a major cause of posttreatment mortality and morbidity 56 . The UCB grafts that underwent expansion resulted in a median expansion of 129-and 973-fold for CD34 ＋ cells and TNC, respectively 56 .…”

Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

See 2 more Smart Citations

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next- Generation Haematopoietic Stem Cell Transplantation

2019

BCT

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Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

Section: Nla101-notch Ligand-based Expansion Of Late Hpc By Nohla Thementioning

confidence: 99%

See 1 more Smart Citation

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next- Generation Haematopoietic Stem Cell Transplantation

2019

BCT

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“…Based on the very encouraging observed in the UCBT setting, Delaney et al conducted a phase I trial investigating the administration of non-HLA-matched ex vivo expanded UCB to accelerate hematopoietic recovery after intensive AML chemotherapy [17]. Twenty-nine patients were included.…”

Section: Infusion Of a Non-hla-matched Ex Vivo Expanded Ucbmentioning

confidence: 99%

“…In this article, after briefly discussing the potential role of hematopoietic growth factors, we review recent approaches that are currently assessed for hasting hematologic recovery after allo-HCT or after intensive chemotherapy for AML [17].…”

Section: Introductionmentioning

confidence: 99%

Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy

Baron

Nagler

2016

Expert Opinion on Biological Therapy

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Introduction: High-dose conditioning regimens for allogeneic hematopoietic cell transplantation (allo-HCT) as well as intensive poly-chemotherapy for acute myeloid leukemia (AML) induce prolonged periods of neutropenia. The duration of the neutropenia is particularly long following umbilical cord blood transplantation (UCBT). Areas covered: After briefly reviewing the impact of hematopoietic growth factors administration to hasten hematologic reconstitution after allo-HCT or intensive AML chemotherapy, this article summarizes recent approaches that have been investigated to prompt hematologic reconstruction after UCBT or intensive AML chemotherapy. Expert opinion: In the allo-HCT setting, administration of G-CSF or GM-CSF shortened the duration of the neutropenia but failed to decrease infection-related mortality or to improve survival. Novel approaches to hasten hematological reconstruction after UCBT such as double UCBT with expansion of one of the 2 UCB units with Notch ligand, mesenchymal stromal cells, nicotinamide, or StemRegenin 1, co-transplanting a single UCB unit with HLA-haploidentical CD34+ cells, or increasing UCB HSC homing to marrow niches via direct intra bone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation are promising and deserve further investigations in prospective phase III studies. In the AML setting, G-CSF or GM-CSF administration after intensive chemotherapy decreased the duration of the neutropenia without improving survival. ARTICLE HISTORY

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The potential of cord blood to replenish young immune cells against cancer

Cheng

et al. 2021

Aging and Cancer

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The immune system of elderly individuals behaves differently from young adults, leading to a general assumption that the decline of immune system function increases the susceptibility to infectious and noninfectious diseases. This agerelated internal immune function failure, termed "immune senescence," contributes to the increment of morbidity and mortality associated with diseases in elderly populations. Cord blood is considered as a source of "young" immune cells for anti-infectious immunity and adoptive cancer immunotherapy. In this review, we describe immune aging and the application of cord blood for replenishing aging immune cells against neoplastic diseases.

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Infusion of a non-HLA-matched ex-vivo expanded cord blood progenitor cell product after intensive acute myeloid leukaemia chemotherapy: a phase 1 trial

Cited by 30 publications

References 19 publications

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next- Generation Haematopoietic Stem Cell Transplantation

Expansion of Haematopoietic Stem and Progenitor Cells: Paving the Way for Next- Generation Haematopoietic Stem Cell Transplantation

Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy

The potential of cord blood to replenish young immune cells against cancer

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