Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study

Ghorashian, Sara; Jacoby, Elad; Moerloose, Barbara De; Rives, Susana; Bonney, Denise; Shenton, Geoff; Bader, Peter; Bodmer, Nicole; Quintana, Águeda Molinos; Herrero, Blanca; Algeri, Mattia; Locatelli, Franco; Vettenranta, Kim; González, Berta; Attarbaschi, Andishe; Harris, S. E.; Bourquin, Jean Pierre; Baruchel, André

doi:10.1016/s2352-3026(22)00225-3

Cited by 26 publications

(17 citation statements)

References 21 publications

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“…In our cohort, one patient underwent CAR-T-cell therapy in 2020. This patient received CAR-T cells after a post-HSCT relapse; however, 9 months after administering the CAR-T cells, the patient experienced an isolated extramedullary relapse and underwent a second HSCT using a haploidentical donor, after which the patient remained in complete remission ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center

et al. 2023

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ObjectivesThis study aimed to evaluate the characteristics and outcomes of infant patients with leukemia.MethodsA retrospective analysis was conducted in a cohort of 39 patients diagnosed with infant leukemia from 1990 to 2020 who underwent treatment at the pediatric hemato-oncology department of a tertiary hospital in Madrid, Spain.ResultsOf the 588 diagnosed cases of childhood leukemia, 39 (6.6%) cases were infant leukemia. The 5-year event-free survival and the 5-year overall survival were 43.6% (SE 4.1) and 46.5% (SD 24.08), respectively. In a univariate analysis, a younger age at diagnosis was associated with poorer outcomes (p = 0.027), as was induction failure (p = 0.0024). Patients treated with hematopoietic stem cell transplantation had better outcomes than non-transplanted patients (p = 0.001); however, the group comparisons that exclude patients who were unable to undergo transplantation due to refractoriness/relapse or death during treatment showed no significant differences.ConclusionsThe main risk factors that affected survival in our study were an age younger than 6 months and a poor response to induction therapy. It is important to identify poor prognostic factors in this population in order to seek different approaches that could improve outcomes.

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Section: Discussionmentioning

confidence: 99%

Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center

et al. 2023

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“…During plateletpheresis, the LRSC reduces the leukocyte amount within the subsequent platelet concentrate by using saturated, fluidized, particle bed filtration technology [5]. As adoptive cell therapies have gained significant importance in the past decades, and chimeric antigen receptor (CAR) T-cell therapy has proven successful in treating certain relapsed and refractory hematological malignancies [6,7], exploration of new targets, improvement of manufacturing, and novel model systems have become a main area of research. Here, we isolated human T cells from the usually discarded LRSCs with the aim of manufacturing functional human CAR T cells.…”

Section: Introductionmentioning

confidence: 99%

Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets

Xhaxho,

Chen-Wichmann,

Kreissig

et al. 2023

Transfus Med Hemother

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Introduction: Primary human blood cells represent an essential model system to study physiology and disease. However, human blood is a limited resource. During healthy donor plateletpheresis, the leukoreduction system chamber (LRSC) reduces the leukocyte amount within the subsequent platelet concentrate through saturated, fluidized, particle bed filtration technology. Normally, the LRSC is discarded after apheresis is completed. Compared to peripheral blood, LRSC yields 10-fold mononuclear cell concentration. Methods: To explore if those retained leukocytes are attractive for research purposes, we isolated CD3+ T cells from the usually discarded LRSCs via density gradient centrifugation in order to manufacture CD19-targeted chimeric antigen receptor (CAR) T cells. Results: Immunophenotypic characterization revealed viable and normal CD4+ and CD8+ T-cell populations within LRSC, with low CD19+ B cell counts. Magnetic-activated cell sorting (MACS) purified CD3+ T cells were transduced with CD19 CAR-encoding lentiviral self-inactivating vectors using concentrated viral supernatants. Robust CD19 CAR cell surface expression on transduced T cells was confirmed by flow cytometry. CD19 CAR T cells were further enriched through anti-CAR MACS, yielding 80% CAR+ T-cell populations. In vitro CAR T cell expansion to clinically relevant numbers was achieved. To prove functionality, CAR T cells were co-incubated with the human CD19+ B cell precursor leukemia cell line Nalm6. Compared to unmodified T cells, CD19 CAR T cells effectively eradicated Nalm6 cells. Conclusion: Taken together, we can show that lymphocytes isolated from LRSCs of plateletpheresis sets can be efficiently used for the generation of functional CAR T cells for experimental purposes.

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“…Acknowledgment of the potential of cell and immune therapies to advance medicine has led an increasing number of academic institutions in Europe and beyond to acquire the necessary infrastructure and expertise to act as manufacturing sites for ATMPs. 41,[46][47][48] a proof-of-concept study for ALL and then adopting this for solid tumors in children and adolescents. Overall, this will enable productive cooperation between industry, academia, and regulators to overcome current roadblocks in the development of CAR T-cell therapeutics for children and adolescents and ultimately save lives.…”

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confidence: 99%

“…Acknowledgment of the potential of cell and immune therapies to advance medicine has led an increasing number of academic institutions in Europe and beyond to acquire the necessary infrastructure and expertise to act as manufacturing sites for ATMPs. 41,46-48 A European network of academic ATMP manufacturing centers could overcome limitations of cross-border trafficking of products over long distances and close the current gap between needs and availability (Fig 1). In close cooperation between biomedical/pharmaceutical industry and academia, we are currently establishing the infrastructure of this network, starting with a proof-of-concept study for ALL and then adopting this for solid tumors in children and adolescents.…”

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confidence: 99%

Chimeric Antigen Receptor (CAR) T-Cell Products for Pediatric Cancers: Why Alternative Development Paths Are Needed

Rossig,

Pearson,

Vassal

et al. 2024

JCO

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Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study

Cited by 26 publications

References 21 publications

Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center

Younger age and induction failure predict outcomes in infant leukemia: 30 years of experience in a tertiary center

Efficient Chimeric Antigen Receptor T-Cell Generation Starting with Leukoreduction System Chambers of Thrombocyte Apheresis Sets

Chimeric Antigen Receptor (CAR) T-Cell Products for Pediatric Cancers: Why Alternative Development Paths Are Needed

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