UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections

Dumont-Lagacé, Maude; Li, Qi; Tanguay, Mégane; Chagraoui, Jalila; Kientega, Tibila; Cardin, Guillaume B.; Brasey, Ann; Trofimov, Assya; Carli, Cédric; Ahmad, Imran; Bambace, Nadia M.; Bernard, Léa; Kiss, Thomas; Roy, Jean; Roy, Denis‐Claude; Lemieux, Sébastien; Perreault, Claude; Rodier, Françis; Dufresne, Simon F.; Busque, Lambert; Lachance, Silvy; Sauvageau, Guy; Cohen, Sandra; Delisle, Jean-Sébastien

doi:10.1016/j.bbmt.2020.09.031

Cited by 15 publications

(6 citation statements)

References 40 publications

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“…Regarding immune reconstitution, the median number of infused T cells was 2-3 times lower in UM171-expanded CB than in unmanipulated CB, even though the quantity and phenotype of T cells after transplantation were similar between the two groups 31 . T cell receptor sequencing analysis indicated that the patients who received UM171-expanded CB displayed increased T cell diversity and rapid virus-specific T cell responses at 12 months post-transplantation, leading to a significant reduction in the occurrence of severe infection.…”

Section: Clinical Applicationsmentioning

confidence: 90%

Recent advances in ex vivo expansion of human hematopoietic stem cells

2023

BCT

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Hematopoietic stem cells (HSCs) are a rare cell population present in the bone marrow. They possess self-renewal and multipotent differentiation capacities and play a crucial role in lifelong hematopoiesis and reconstitution of the hematopoietic system after hematopoietic stem cell transplantation (HSCT). HSCT remains the only curative treatment for refractory hematologic disorders. Umbilical cord blood (CB) has several advantages as an alternative donor for HSCT, including HLA flexibility and lack of donor burden. However, CB has limitations in terms of cell dose, restricted donor options, and prolonged time to engraftment. Development of techniques for expanding HSCs ex vivo , especially those contained in CB, has become a goal in the field of hematology. Attempts have been made to use various combinations of cytokines for this purpose, but these protocols showed limited expansion rates and did not progress to clinical applications. Recent advances that include the addition of small molecules to cytokines have enabled long-term and stable ex vivo expansion of human HSCs. Clinical trials have been conducted with HSCs expanded in CB using these techniques, confirming their efficacy and safety. Furthermore, we recently developed a recombinant cytokine-free, albumin-free culture system for long-term expansion of human HSCs. This approach has the potential to selectively expand human HSCs more effectively than the previous protocols. We herein present an overview of ex vivo culture protocols for expanding human HSCs together with the results of clinical trials that utilized these techniques.

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Section: Clinical Applicationsmentioning

confidence: 90%

Recent advances in ex vivo expansion of human hematopoietic stem cells

2023

BCT

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“… 22 , 23 Despite this, NRM was lower in the patients receiving UM171 CB, and a significant proportion of these patients received CBs that would be considered too small for clinical use, thus further validating the benefit of the UM171 technology. Additional reasons why outcome may be improved with a UM171-manipulated CB is the associated rapid T-cell reconstitution, greater T-cell diversity, 24 and lower risk of severe infections after transplant 24 compared with a conventional CB graft.…”

Section: Discussionmentioning

confidence: 99%

Improved outcomes of UM171–expanded cord blood transplantation compared with other graft sources: real-world evidence

et al. 2023

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Cord blood (CB) transplantation is hampered by low cell dose and high non-relapse mortality (NRM). A phase I-II trial of UM171-expanded CB transplants demonstrated safety and favourable preliminary efficacy. The aim of the current analysis was to retrospectively compare results of the phase I-II trial to those after unmanipulated CB and matched unrelated donor (MUD) transplants. Data from recipients of CB and MUD transplants were obtained from the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Patients were directly matched for the number of prior allogeneic hematopoietic stem cell transplants (alloHCT), disease and refined Disease Risk Index. Patients were further matched by propensity score for age, comorbidity index and performance status. Primary endpoints included NRM, progression-free survival (PFS), overall survival (OS) and graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) at 1- and 2-years post alloHCT. Overall, 137 CIBMTR (67 CB, 70 MUD) and 22 UM171-expanded CB patients were included. NRM at 1 and 2 years was lower, PFS and GRFS at 2 years and OS at 1 year were improved for UM171-expanded CBs compared to CB controls. Compared to MUD controls, UM171 patients had lower 1- and 2-year NRM, higher 2-year PFS, and higher 1- and 2-year GRFS. Furthermore, UM171-expanded CB recipients experienced less grades III-IV acute GVHD and chronic GVHD compared to MUD graft recipients. Compared to real-world evidence with CB and MUD alloHCT, this study suggests that UM171-expanded CB recipients may benefit from lower NRM and higher GRFS.

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“…The lack of availability of DLI with CBT has previously been seen as a disadvantage, but with newer methods of T-cell separation, cryopreservation and cord unit expansion, theoretically, cord blood T-cells could be stored for DLI in the future ( 190 , 191 ). Improvements in supportive care and utilization of targeted or less toxic conditioning regimens could dramatically reduce the burden of TRM associated with CBT.…”

Section: Future Directions To Augment Gvl Effect With Cord Blood Tran...mentioning

confidence: 99%

Immunology of cord blood T-cells favors augmented disease response during clinical pediatric stem cell transplantation for acute leukemia

Borrill,

Poulton,

Wynn

2023

Front. Pediatr.

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Allogeneic hematopoietic stem cell transplantation (HSCT) has been an important and efficacious treatment for acute leukemia in children for over 60 years. It works primarily through the graft-vs.-leukemia (GVL) effect, in which donor T-cells and other immune cells act to eliminate residual leukemia. Cord blood is an alternative source of stem cells for transplantation, with distinct biological and immunological characteristics. Retrospective clinical studies report superior relapse rates with cord blood transplantation (CBT), when compared to other stem cell sources, particularly for patients with high-risk leukemia. Xenograft models also support the superiority of cord blood T-cells in eradicating malignancy, when compared to those derived from peripheral blood. Conversely, CBT has historically been associated with an increased risk of transplant-related mortality (TRM) and morbidity, particularly from infection. Here we discuss clinical aspects of CBT, the unique immunology of cord blood T-cells, their role in the GVL effect and future methods to maximize their utility in cellular therapies for leukemia, honing and harnessing their antitumor properties whilst managing the risks of TRM.

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UM171-Expanded Cord Blood Transplants Support Robust T Cell Reconstitution with Low Rates of Severe Infections

Cited by 15 publications

References 40 publications

Recent advances in ex vivo expansion of human hematopoietic stem cells

Recent advances in ex vivo expansion of human hematopoietic stem cells

Improved outcomes of UM171–expanded cord blood transplantation compared with other graft sources: real-world evidence

Immunology of cord blood T-cells favors augmented disease response during clinical pediatric stem cell transplantation for acute leukemia

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